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Comparison between Bethesda System and Conventional System for Standardization of Reporting Thyroid Cytopathology

Comparison between Bethesda System and Conventional System for Standardization of Reporting Thyroid Cytopathology

 *Saleheen S,1 Rahman DA,2 Chowdury MA,3 Haque MM,4 Habib S,5 Khan KH6

 

  1. * Saied Saleheen, Assistant Professor, Department of Pathology, Sheikh Hasina Medical College, Tangail. saleheen44@gmail.com
  2. DM. Arifur Rahman, Assistant Professor, Department of Pathology, TMSS Medical College, Gokul, Bogura,
  3. Mehdi Ashik Chowdury, Assistant Professor, Department of Pathology, Jahurul Islam Medical College, Bajitpur, Kishoreganj.
  4. Mohammad Mahbubul Hoque, Lecturer, Department of Pathology, Sheikh Sayera Khatun Medical College, Gopalganj.
  5. Saequa Habib, Associate Professor, Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka.
  6. Kamrul Hasan Khan, Professor, Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka.

 *For correspondence

Abstract

Background: Fine-needle aspiration cytology (FNAC) is considered as an effective test to screen and diagnose patients with thyroid swelling for surgical management. But FNAC still suffers because of its inherent limitations as well as variability in its diagnostic terminology.The Bethesda System of Reporting Thyroid Cytopathology (TBSRTC) may improve the state. This study was to report the experience in using this reporting system to redistribute the cytological diagnoses made by conventional system and also to evaluate the specificity, sensitivity, accuracy and predictive values as a tool to compare both the methods based on the correlation between cytopathology and histopathology.

Methods: A total of 73 patients presenting with thyroid swelling were subjected to FNAC and reporting was done according to the conventional system and TBSRTC. The cytological diagnosis was correlated with the histopathological diagnosis. The sensitivity, specificity, predictive values were calculated considering cytology as screening test.

Results: In this study, TBSRTC was found superior because of higher sensitivity (91.66%) and specificity (97.77%) as compared to conventional system (80.76% and 87.23% respectively). Positive predictive value, negative predictive value and diagnostic accuracy of Bethesda system were 95.65%, 95.65% and 90.41% respectively which were also significantly higher as compared to those of conventional system (77.78%, 89.13% and 84.93% respectively).

Conclusions: TBSRTC may improve the efficacy of thyroid FNAC as a screening test.

 [Journal of Histopathology and Cytopathology, 2020 Jan; 4 (1):38-47]

 Keywords: Comparison, Thyroid FNAC, Bethesda system (TBSRTC), Conventional system, Histopathology, Standardization

Introduction

Fine Needle Aspiration Cytology (FNAC) is a quick, cost-effective and minimally invasive outpatient procedure used worldwide in the initial diagnosis of thyroid swellings. As it can distinguish between benign and malignant lesions quite effectively, it is the preoperative screening method of choice worldwide.1 Before the routine use of thyroid Fine Needle Aspiration (FNA), the percentage of surgically resected thyroid nodules that were malignant was 14%.2 With current thyroid FNA practice, the percentage of resected nodules that are malignant surpasses 50%.3

However, due to the lack of a standardized system of reporting, pathologists have been using different terminologies and diagnostic criteria, leading to confusion amongst clinicians in the interpretation of the cytopathology report and ultimately hindering a definitive clinical management.4 It has also hindered the sharing of clinically meaningful data among multiple institutions.5 To mitigate this confusion all the pathologists need to use the same diagnostic criteria and terminology.6

Various reporting formats of thyroid FNAs have been suggested in the literature since the 1970s when thyroid FNAs began to be the subject of publications, and new formats continued to emerge.7 Several classification schemes have been suggested by various authors based on personal/institutional experiences but there is general support for the utilization of a tiered classification system.5 With this background, the National Cancer Institute (NCI), Bethesda, Maryland, United States, published an atlas and guidelines using standardized nomenclature for the interpretation of thyroid FNAC known as The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).4 It categorized the thyroid FNAC diagnoses into six groups with well-defined cancer risk and clear indications for further clinical management.8 It has also increased the interobserver reproducibility of cytopathological diagnoses of thyroid lesions.9-12

TBSRTC has been well received by both pathologists and clinicians and has been widely implemented by pathology laboratories in USA and in several European countries.13 Following publication of TBSRTC, the reporting system used in the United Kingdom since 2002, was updated by a working group of The Royal College of Pathologists and is now quite similar to TBSRTC.14 But TBSRTC still has to go a long way in getting acceptability in many countries of Asia and Africa.10

A good number of studies have been carried on in several countries in Asia (India, Pakistan, Iran, Korea and KSA) regarding usefulness of TBSRTC and it has been proved useful for management of patients with thyroid swelling in these countries.9,11,15-20 But this relatively recent six category scheme still needs to be validated by more prospective studies with histopathological correlation.16

In Bangladesh, there is no known reporting scheme using tiered classification system. The utility of thyroid cytopathology reporting according to TBSRTC in context of Bangladesh is also unexplored. Standardization of the reporting system by TBSRTC may result in improvement of the quality, homogenization and also reduce interobserver variability of thyroid cytopathology reports. In this context, this study was performed to assess the predictive values, sensitivity and specificity and accuracy of the TBSRTC in comparison with that of the conventional system used in the BSMMU, Dhaka, Bangladesh with histopathological correlation. The view was to observe the usefulness of Bethesda system for standardization of thyroid cytopathology reporting in the context of this country (Bangladesh).

 Methods

This is a cross sectional study carried out at the Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka during the period from March 2015 to February 2017. A total of 73 patients presenting with thyroid swelling were included in this study, who has undergone FNA followed by the biopsy of the thyroid lesions. Patients presenting with thyroid swelling in any lobe of thyroid detected by clinical palpation (multinodular, solitary nodule, diffuse goiter etc) were included except those unwilling to be involved into the study.

All clinical information were recorded in a pre-designed proforma including demographic features, address and telephone contacts (for histological follow up). Results of all the routine investigations with special attention to ultrasonography of neck, serum T3, T4, and TSH levels and thyroid scintigraphy were noted where available.     

FNA of all patients was performed at the Department of Pathology, BSMMU.  Smears were stained with Papaniculaou (PAP) and Hematoxylin and Eosin (H&E) stains. Cytological findings were recorded and diagnoses were made according to both conventional and TBSRTC for each cases. For the TBSRTC reporting the Atlas10was used as manual (Table I). Reports were issued according to conventional method.

Koss’ Diagnostic Cytology and its histopathologic bases21 was followed conventionally as reference book in this department. The diagnoses made by conventional system are mostly based on its reference. The diagnoses were: Non-neoplastic lesions: Nodular goiters (NG) including cystic degeneration (CD), Lymphocytic thyroiditis (LT), Hashimoto thyroiditis (HT), Nodular goiter with co-existent thyroiditis, Multinodular goiter (MNG).

 Cellular follicular lesion (CFL): Cellular smears on cytology that included goiters with adenomatous changes, follicular adenomas and carcinomas, as well as the follicular variant of papillary carcinomas. In BSMMU suspicious cytology, atypia of undetermined significance and other gray zone cytology are also included within this diagnosis.

 Neoplastic lesions: Papillary thyroid carcinoma (PTC), suggestive of papillary carcinoma, medullary thyroid carcinoma (MTC) etc.

Biopsy specimens or histopathological reports of the patients undergoing surgery following the FNA interpretation under this study were collected. The histopathological findings were correlated with cytopathological findings and were recorded accordingly.

Descriptive analytical statistics was calculated. Thyroid FNA was considered as a ‘screening test’ and histopathology as gold standard. FNA benign was considered to be negative and the remaining categories were considered to be positive because they indicated significant risk of malignancy and led to a recommendation of surgery.8 Sensitivity, specificity, accuracy, the positive predictive value (PPV) and negative predictive value (NPV) were calculated from the available data by statistical formulae. In this study, Thyroid FNA has been considered as a screening method as TBSRTC is formed by NCI as a screening method to triage the patients effectively into groups that need surgery and the other that do not.5

For calculating statistical parameters nondiagnostic (ND) and AUS/FLUS cases were excluded as non-definitive diagnoses and categories, SFM and malignant were put together in most of the studies.15,16,22-24 In this study, the inadequate/ND cases were reaspirated and have been included rationally in other categories. Those which were still inadequate, had been excluded from statistical analysis.

 Results                                                                                                                          

Out of the 73 cases 62(84.9%) were female and 11(15%) were male. The age of the patients ranged from 16 to 70 years with average age around 40 years.

According to the conventional system forty five (61.64%) cases were diagnosed nodular goiter. Five (11.11%) of these lesions were found to be neoplastic (one benign and 4 malignant) on histopathology. Although all PTC and suggestive of PTC categories were found neoplastic and also malignant, 60% of the cellular follicular lesions (9 out of 15) were neoplastic (one benign and 8 malignant) and the rest were benign on final histological diagnosis.

The lesions when redistributed according to the Bethesda system: 46 (63%), 04 (5.4%), 03 (4.1%), 08 (10.95%), 12(16.4%) of the lesions were diagnosed as Cat-II, Cat-III, Cat-IV, Cat-V and Cat-VI respectively. The redistribution of the lesions after application of Bethesda system is shown in Table-II.

Out of 73 cases, 64 (22 neoplastic and 42 non-neoplastic) cytological diagnoses were concordant on both the conventional and Bethesda systems. One lesion was non-neoplastic on conventional but diagnosed neoplastic on Bethesda system while 04 neoplastic lesions by conventional system were categorized as non-neoplastic by Bethesda system. Three non-neoplastic and one neoplastic case according to conventional system were categorized as Cat- III (AUS) by Bethesda system. The CFL on conventional system were distributed by the Bethesda system into various categories that matched well (Table-III) with final histological diagnoses.

All the neoplastic lesions irrespective of benign and malignant neoplasm were considered positive for both the histological and cytological diagnoses, as they recommend for surgical excision. The concordances of the cytological diagnoses made by two methods with the final histological diagnoses are shown in Table IV.

Granulomatous thyroiditis: GT, Follicular adenoma: FA, Follicular carcinoma: FC, FVPTC: Follicular Variant of PTC, WDTUMP: Well differentiated tumor of uncertain malignant potential.

Diagnoses made according to TBSRTC shows increased overall concordance with hisotoathological diagnosis than that of the conventional system.

FNA interpretation by conventional method yielded significant false positive (6) and false negative (5) diagnoses. While analyzing the smears by the Bethesda system had decreased both the false positive (1) and false negative (2) interpretations. The sensitivity, specificity, accuracy and predictive values calculated for both the methods by using the statistical formulas are compared to each other in the Table V.

Sensitivity and positive predictive value (PPV) of the Bethesda system were found better (91.66% and 95.65% respectively) when compared to that the conventional system (80.76% and 77.78% respectively). The specificity and negative predictive values (NPV) were also found higher for Bethesda system (97.77% and 95.65%) in comparison to that of the conventional system (87.23% and 89.13% respectively). Diagnoses according to the Bethesda categories were 90.41% accurate where accuracy for the conventional system was 84.93%.

 Discussion

Reporting according to the conventional system included 41 (about 56.16%) patients into benign category, while category-II (Benign) in the Bethesda system included 44 (60.27%) patients. All (12) the suspicious for malignancy and malignant diagnoses on conventional system corresponded to category V and VI of Bethesda system. It reflects that there was actually no significant change in diagnosis of unequivocally benign and malignant cases according to the two systems of reporting.

15 (20.54%) CFL diagnosed by conventional system was the major field where the Bethesda system varied markedly. So, CFL was a “gray zone” diagnosis that included some benign (26.67%) and malignant (53.33%) cases.25 These cases when reclassified by the Bethesda system yielded more specific results with good histological correlation (Table IV). This difference can be explained by- i) Subjective underscoring of some neoplastic cytologies which are of SFM category in more objective Bethesda system and  ii) Assigning the follicular lesion diagnosis for some hyper cellular smears of goiter arranged in folded sheet appearance.

The 06 false-positive FNA diagnoses in conventional system included cellular smears of histologically nodular goiters that were interpreted as CFLs. Four of these cases were interpreted benign (category-II) by Bethesda system and 01 case was designated category-IV (suspicious for Hurthle cell neoplasm) because of relative abundance of Hurthle cells showing pleomorphism. Five cases were false negative for conventional method, 04 of which were due to compromised cytology samples. The rest one case diagnosed conventionally as nodular goiter that was histologically follicular adenoma and Category-IV (SFM) in Bethesda system.

When compared with other studies using TBSRTC with histological follow up, sensitivity and NPV of the present study were consistent with most of the studies (Table VI). The specificity and PPV were higher than most of the other studies, which may be due to small sample size in this present study.

Conclusion

By dint of its higher sensitivity, specificity, predictive values and accuracy TBSRTC has been proved to be better than  conventional system for reporting thyroid cytopathology. So, it should be useful for standardization of thyroid cytopathology reporting. However, studies needed to explore its effect in reducing inter-observer variation of reporting thyroid cytopathology as well as its usefulness to the clinicians in decision making.

 References

  1. Bagga PK, Mahajan NC. Fine needle aspiration cytology of thyroid swellings: How useful and accurate is it? Indian Journal of cancer, 2010 Oct 1;47(4):437.
  2. Hamberger B, Gharib H, Melton LJ, Goellner JR, Zinsmeister AR. Fine-needle aspiration biopsy of thyroid nodules: impact on thyroid practice and cost of care. The American journal of medicine. 1982 Sep 1;73(3):381-4.
  3. Yassa L, Cibas ES, Benson CB, Frates MC, Doubilet PM, Gawande AA et al. Long‐term assessment of a multidisciplinary approach to thyroid nodule diagnostic evaluation. Cancer Cytopathology: Interdisciplinary International Journal of the American Cancer Society. 2007 Dec 25;111(6):508-16.
  4. Mondal SK, Sinha S, Basak B, Roy DN, Sinha SK. The Bethesda system for reporting thyroid fine needle aspirates: a cytologic study with histologic follow-up.Journal of Cytology. 2013; 30(2):94.
  5. Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Thyroid. 2009 Nov 1;19(11):1159-65.
  6. Schinstine M. Pathology Hawaii Hotline: A Brief Description of the Bethesda System for Reporting Thyroid Fine Needle Aspirates. Hawaii medical journal. 2010 Jul; 69(7):176.
  7. Wang HH. Reporting thyroid fine‐needle aspiration: literature review and a proposal. Diagnostic cytopathology. 2006 Jan; 34(1):67-76.
  8. Ali SZ and Cibas ESThe Bethesda system for reporting thyroid cytopathology: definitions, criteria and explanatory notes. Springer Science & Business Media.2010
  9. Ahmed S, Ahmad M, Khan MA, Kazi F, Noreen F, Nawaz S, Sohail I. The interobserver reproducibility of thyroid cytopathology using Bethesda Reporting System: Analysis of 200 cases. J Pak Med Assoc. 2013 Oct 1;63(10):1252-5.
  10. Bhasin TS, Mannan R, Manjari M, Mehra M, Sekhon AK, Chandey M, Sharma S, Kaur P. Reproducibility of ‘The Bethesda System for reporting Thyroid Cytopathology’: a multicenter study with review of the literature. Journal of clinical and diagnostic research: JCDR. 2013 Jun; 7(6):1051.
  11. Mufti ST, Molah R. The Bethesda system for reporting thyroid cytopathology: a five-year retrospective review of one center experience. International journal of health sciences. 2012 Jun; 6(2):159.
  12. Pathak P, Srivastava R, Singh N, Arora VK, Bhatia A. Implementation of the Bethesda System for Reporting Thyroid Cytopathology: interobserver concordance and reclassification of previously inconclusive aspirates. Diagnostic cytopathology. 2014 Nov; 42(11):944-9.
  13. Auger M, Nayar R, Khalbuss WE, Barkan GA, Benedict CC, Tambouret R et al. Implementation of the Bethesda System for Reporting Thyroid Cytopathology: observations from the 2011 thyroid supplemental questionnaire of the College of American Pathologists. Archives of Pathology and Laboratory Medicine. 2013 Nov; 137(11):1555-9.
  14. Crippa S, Dina R. Interobserver reproducibility of thyroid fine-needle aspiration using the UK Royal College of Pathologists’ classification system. American journal of clinical pathology. 2012 May 1;137(5):833-5.
  15. Mamatha M, Sekhar SC, Rani HS, Anil SS and Vandana G. A comparative study between conventional system and the Bethesda system applied for reporting thyroid cytopathology. International Archives of Integrated Medicine.2015; 2(3):87 – 95
  16. Mehra P, Verma AK. Thyroid cytopathology reporting by the Bethesda system: a two-year prospective study in an academic institution. Pathology research international. 2015;2015. 240505.doi: 1155/2015/240505
  17. Ahmed S, Ahmad M, Khan MA, Kazi F, Noreen F, Nawaz S, Sohail I. The interobserver reproducibility of thyroid cytopathology using Bethesda Reporting System: Analysis of 200 cases. J Pak Med Assoc. 2013 Oct 1; 63(10):1252-5.
  18. Bukhari MH, Khan AA, Niazi S, Arshad M, Akhtar ZM, Al-Sindi KA. Better thyroid cytopathology reporting system may increase the clinical management and patients outcome. J Cytol Histol. 2012;3(6):1000158.
  19. Hajmanoochehri F, Rabiee E. FNAC accuracy in diagnosis of thyroid neoplasms considering all diagnostic categories of the Bethesda reporting system: A single-institute experience. Journal of Cytology/Indian Academy of Cytologists. 2015 Oct; 32(4):238.
  20. Jo VY, Stelow EB, Dustin SM, Hanley KZ. Malignancy risk for fine-needle aspiration of thyroid lesions according to the Bethesda System for Reporting Thyroid Cytopathology. American journal of clinical pathology. 2010 Sep 1;134(3):450-6.
  21. Sanchez AM and Stahl RE.The Thyroid, Parathyroid, and Neck Masses Other Than Lymph Nodes.in: Koss LG, Melamed MR, editors. Koss’ diagnostic cytology and its histopathologic bases. Lippincott Williams & Wilkins; 2006.pp1148-1173.
  22. Joshi D and Jesalpura NS. Comparision Between Bethesda System and Conventional System in Thyroid Cytopathology: International Journal of Scientific Research, 2015;4(9).
  23. Naz S, Hashmi AA, Faridi N, Edhi MM, Kamal A and Khan M. Diagnostic accuracy of Bethesda system for reporting thyroid cytopathology: an institutional perspective.International archives of medicine, 2014; 7(1):46..
  24. Theoharis CG, Schofield KM, Hammers L, Udelsman R, Chhieng DC. The Bethesda thyroid fine-needle aspiration classification system: year 1 at an academic institution. Thyroid. 2009 Nov 1;19(11):1215-23.
  25. Bonzanini M, Amadori P, Morelli L, Fasanella S, Pertile R, Mattiuzzi A et al. Subclassification of the “grey zone” of thyroid cytology; a retrospective descriptive study with clinical, cytological, and histological correlation. Journal of thyroid research. 2011:251680.doi:10.4061/2011/251680.
  26. Gupta M, Gupta S, Gupta VB. Correlation of fine needle aspiration cytology with histopathology in the diagnosis of solitary thyroid nodule. Journal of thyroid research. 2010 Apr 18;2010:379051.
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Histopathological Spectrum of Prostatic Lesions Evaluated in a Tertiary Hospital

Histopathological Spectrum of Prostatic Lesions Evaluated in a Tertiary Hospital

 *Sultana SS,1 Hossain S,2 Rahman A3

 

  1. *Dr. Sk Salowa Sultana, Assistant Professor, Department of Pathology, Ad-Din Women’s Medical College. salowasultana257@gmail.com
  2. Shahadat Hossain, Associate Professor, Department of Pathology, Ad-Din Women’s Medical College.
  3. Afiqur Rahman, Professor of Urology, Department of Urology, Ad-Din Women’s Medical College.

*For correspondence

 Abstract

Objective: To determine the age distribution of various prostatic lesions, to evaluate histopathological  pattern  of prostatic lesions  and  to analyze adenocarcinoma  of prostate according to Gleason  system.

Methods: This was a retrospective study comprising of 178 cases, carried out at the department of Pathology, Ad-din Women´s  Medical College Hospital during the  period of January 2017 to December 2019.

Results: Out of 178 cases, 159(89.32%) were diagnosed as benign lesion, nodular hyperplasia being the commonest one. Prostatic adenocarcinoma was found in 16(9%) cases, majority of which belonged to Gleasons score 7.

Conclusion: Histopathological examination of prostatic biopsy specimen is essential for diagnosis of benign and malignant lesions, to rule out the incidental carcinoma and HGPIN.

 [Journal of Histopathology and Cytopathology, 2020 Jan; 4 (1):33-37]

 Keywords: Nodular hyperplasia of prostate, prostatic carcinoma, HGPIN

Introduction

The  prostate that weights up to 20 gm in normal adult depends for its subsequent growth and differentiation on androgenic hormones.1,2  Lesions of prostate are extremely common over the age of 50 years and important cause of morbidity and mortality in male in advance age. Pathological processes affecting this organ include inflammation, benign nodular enlargement and tumor.1 The clinical incidence of the diseases is only 8% during the 4th decade  but it reaches 50% in the 5th decade and 75% in the 8th decade.2 Benign prostatic  hyperplasia(BPH) and carcinoma are increasingly frequent with advancing age.3  BPH results from hyperplasia of both stromal and epithelial cells, gradually being enlarged, compress and narrow the urethral canal and often leads to urinary obstruction. Inflammation of prostate is known as prostatitis and divided into acute, chronic and granulomatous prostatitis. Prostatic carcinoma is one of the most common malignancies affecting men, also it is the sixth leading cause of cancer death in male.4 Among the prostatic malignancies 95% is adenocarcinoma. premalignant lesion of prostatic adenocarcinoma  is known as high grade intraepithelial neoplasia (HGPIN). The objective of this study was to determine the age distribution of various prostatic lesions, to evaluate histopathological  pattern  of prostatic lesions  and  to analyze adenocarcinoma  of prostate according to Gleason  system.

Methods

The study was conducted in the Department  of Pathology, Ad-din Women´s Medical College Hospital – a  tertiary level hospital of Dhaka, Bangladesh. The study period was from January 2017 to December 2019. The data were collected retrospectively from histopathology register. A  total of 178 TURP (Transurethral resection of prostate) were evaluated. The received specimen were fixed in 10% formalin and routine paraffin processing followed by hematoxylin and eosin staining was done and the slides were examined under light microscope. The specimens were ananlyzed as type of specimen, age of the patient, histopathological  pattern and final diagnosis. The tumour were classified according to 2016 WHO classification and histological grading was done using modified Gleason´s system. Data  were analyzed using tables, figures and percentage.

 Results

A total of 178 cases were included in our study, all of which (100%) were TURP specimen.  In the present study, most of the prostatic lesions were benign(89.32%) followed by malignant (9.6%) and HPIN (1.12%) and ratio of benign and malignant lesions is 1:9, approximately.

In the present study, benign lesions were mostly found (45%) in the age group of 61-70 years  and 34% in the age group of 51-60 years,  whereas malignant lesions were common  41% in the age group of 71-80 years and 29% in the age group of 61-70 years of age. In our study, benign lesions(159) were nodular hyperplasia of prostate 130(73.03%) and nodular hyperplasia of prostate with co-existing prostatitis 29(16.3%). Out of 29 cases of prostatitis, 24 cases were chronic non specific prostatitis, 2 cases were granulomatous prostatitis and 3 cases were acute prostatitis.  In our study, 2(1.12%) cases were diagnosed as HGPIN and 17(9.6%) cases were diagnosed as malignant. Most of the malignant cases 16(9%)  were prostatic adenocarcinoma and 1(0.56%) was metastatic adenocarcinoma. In this study, 41% cases of malignant belong to 71-80 years age group and 29% cases belong to 61-70 years age group. According to Gleason score, most commonly (81.25%) found grade was grade 7, in this study.

Discussion

We enrolled a total of 178 cases in our study, all of which (100%) were TURP specimen. Bhatta S et al5 have found 88.54% specimen of TURP in their study. Screening procedure like trans-rectal ultrasound, prostate specific antigen (PSA) are still used, but biopsy remains the gold standard for final diagnosis.6 In the present study, most of the prostatic lesions were benign (89.32%) followed by malignant (9.6%) and HPIN (1.12%). These findings are similar to the studies done by Bhatta S et al,5 Bal et al,7 Jehoram  et al,8 and Bhat S et al.9 They found (89.58%), (87%), (93%) and (92.4%) cases of BPH in their study, respectively. In our study, ratio of benign and malignant lesions is 1:9, approximately.

In the present study, benign lesions were mostly found 45% in the age group of 61-70  years  and 34% in the age group of 51-60 years,  whereas malignant lesions were common  41% in the age group of 71-80 years and 29% in the age group of 61-70 years of age. These findings are in concordance with other studies.10,11,12

In our study, benign lesions(159) were nodular hyperplasia of prostate 130(73.03%) and nodular hyperplasia of prostate with co-existing prostatitis 29(16.3%). Out of 29 cases of prostatitis, 24 cases were chronic non specific prostatitis, 2 cases were granulomatous prostatitis and 3 cases were acute prostatitis.  Bhatta S et al found 24(25%) cases of prostatitis associated with nodular hyperplasia of prostate, out of which 22 cases were chronic non specific prostatis and two cases were acuteprostatis.5 Prostatic carcinoma is one of the most common malignancies affecting men. In our study, 2(1.12%) cases were diagnosed as HGPIN and 17(9.6%) cases were diagnosed as malignant. Most of the malignant cases 16(9%)  were prostatic adenocarcinoma and 1(0.56%) was metastatic adenocarcinoma. Bhatta S et. al5found 2.08% of HGPIN and 8.34% of prostatic carcinoma. Also Deshmukh BD et. al11 and Bhat S et. al9 found similar observation. In this study, 41% cases of malignant  belong to 71-80 years age group and 29% cases belong to 61-70 years age group. Bhat S et. al12  found 75% cases of malignancy diagnosed after 60 years. All the cases of prostatic adenocarcinoma were graded according to Gleason score which determine the tumour aggressiveness.1  In this study, most commonly 13(81.25%) found grade was grade 7. Albasri et al.13 found Gleasons score 5-7 as the commonest among 71 cases of prostatic adenocarcinoma. Bhat S et. al9 found 56.16% of adenocarcinoma with Gleason score 8-9.

 Conclusion

Histopathological  examination of prostatic lesions is essential for diagnosis and management. Prostatic lesions are common in the age group of 60-70 years. All the specimen received were TURP. Benign prostatic hyperplasia (BPH) was predominant type among all the lesions. Majority of the malignant lesions were incidental diagnosis and most of the malignant lesions were prostatic adenocarcinoma. Emphasis should be  given to identify premalignant lesions.

References

  1. Epstein JI. The lower urinary tract and male genital system. 8th rev ed. Kumar V, Abbas AK, Fausto N, Aster JC, editors. Robbins and Cotran. New Delhi: Elsevier Pathologic Basis of Disease, 2010. p993-1002.
  2. Rosai J. Male reproductive system. In: Rosai J, editor. Rosai and Ackerman’s Surgical Pathology. 10thed. New Delhi: Elsevier, 2011:1287-1333.
  3. A Josephin-2014, clinicopathological study of prostatic biopsy, ©2014journal of Clinical and Diagnostic 2014 Sep; 8(9): FC04-FC06.
  4. Chandanwale S, Jadhav PS, Anwekar SC, Kumar H, Buch AC, Chaudhari US, et al. Clinico-pathological study of benign and malignant lesions of prostate. IJPBS. 2013;3:162-178.
  5. Bhatta S, Hirachan S. Prostatic lesions: Histopathological Study in a Tertiary Care Hospital. JMMIHS. 2018;4(1):12-19.
  6. Garg M, Kaur G, Malhotra V, Garg R. Histopathological spectrum of 364 prostatic specimens including immunohistochemistry with special reference to grey zone lesions. Prostate Intl. 2013;1:146-151.
  7. Bal MS, Kanwal S, Goyal  AK, Singla N, Prostatic lesions in surgical biopsyspecimen. JK Pract 2011;16:33-4.
  8. Jehoram TA, Sitara AS, Mohammed EB. Hyperplastic , premalignant and malignant lesions of the prostate gland. Hum Pathol. 2005;36:480-5.
  9. Bhat S, Chaudhri S, Bhat P, Hatwal D. Histopathological study of prostatic Diseases in Garhwal Region. Int  J Sci stud. 2015: 3(8):136-140.
  10. Shakya G, Malla S, Shakya KN. Salient and co-morbid features in benign prostatic hyperplasia: A histopathological study of the prostate. Kathmandu Univ Med J. 2003;2:104-109.
  11. Deshmukh BD, Ramteerthakar NA, Sulhyan KR. Histopathological study of lesions of prostate- A five year study. Int J Health Sci Res. 2014;4:1-9.
  12. Yadav M, Desai H, Goswami H. Study of Various Histopathological Patterns in Prostate Biopsy. IJCRR. 2017;9(21):59-63.
  13. Albasri A, EL-Sidding A, Hussainy A, Mahrous M, Alhosaini AA, Alhujaily A. Histopathologic characterization of prostatic diseases in Madinah, Saudi Arabia. Asian Pac J Cancer prev. 2014;15:4175-9.
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Histopathological Patterns of Ovarian Tumours and HER2 Expression in Epithelial Ovarian Carcinoma

Histopathological Patterns of Ovarian Tumours and HER2 Expression in Epithelial Ovarian Carcinoma

*Barua M,1  Hossain MI,2  Bini UH,3 Nasreen S,4 Ahamad MU,5 Bhattecharjee P,6 RahmanM Z7

 

 

  1. * Mitasree Barua, Lecturer, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh. mitakmc12@gmail.com
  2. Mohammad Ismail Hossain, Lecturer, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh
  3. Umme Habiba Bini, Assistant Professor, Department of Pathology, Pabna Medical College, Pabna, Bangladesh.
  4. Sayeeda Nasreen, Assistant Professor, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh.
  5. M. Sahab Uddin Ahamad, Associate Professor, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh.
  6. Pradip Bhattacharjee, Associate Professor, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh.
  7. Md. Zillur Rahman, Professor & Head, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh.

 *For correspondence

 Abstract

Background: Ovarian tumours are a heterogenous group of neoplasm of epithelial, stromal and germ cell origin. The management of which depends on the histological type of the tumour. Neoadjuvant chemotherapy is limited by toxicity and resistance. Hence targeted therapy is now being proposed to overcome these hurdle.

Objectives: To find out the histopathological patterns of ovarian tumours and to evaluate HER2 overexpression in epithelial ovarian carcinoma.

Methods: This study was carried out in the Department of Pathology, Chittagong Medical College, Chattogram, received from Department of Gynaecology and Obstetrics, Chittagong Medical College Hospital, Chattogram during the period from January 2016 to December 2016. A total of 92 cases of ovarian tumours were selected consecutively. The age range was 12-80 years. Histopathological sections were stained with Hematoxylin and Eosin stain and epithelial ovarian carcinoma were subjected to HER2/neu immunohistochemical stain. Histopathological patterns of ovarian neoplasm, histopathological subtyping and grading of epithelial ovarian tumours and the expression of HER2/neu among epithelial ovarian carcinomas on immunohistochemistry was analyzed.

Results: Out of total 92 cases, histopathological diagnosis showed 65 (70.7%) were benign tumours and 27 (29.3%) were malignant tumours. Histologically, surface epithelial tumours were the most common (74%) followed by germ cell tumours (21.7%) and sex cord stromal tumours (4.3%). Age incidence of benign tumour was age group of 21-40 yrs and malignant 41-60 years. One in 23 epithelial ovarian carcinoma cases (4.3%) exhibits HER2 overexpression. Only one HER2 positive case was mucinous cystadenocarcinoma grade II.

Conclusion: Surface epithelial tumours were most common followed by germ cell tumours. Serous cystadenocarcinoma were most common epithelial ovarian carcinoma.

 

[Journal of Histopathology and Cytopathology, 2020 Jan; 4 (1):23-32]

 Keywords: Ovarian tumour, Epithelial Carcinoma, HER2/neu.

 

Introduction

Ovarian tumours account for 3% of all cancers in females, being the second most common cancer of the female genital tract, next only to uterine cancer.1 Ovarian cancer, traditionally known as the silent killer, is a dreaded disease because of its vague, nonspecific symptoms and late presentation. Worldwide, it is the seventh most common cause of cancer and eighth most common cause of cancer-related death among women.2 It is be a disease of developed and industrialized countries where parity of women is low. As the standard of living increases and resources for a medical infrastructure improve in Bangladesh, there will be an increased need to address less common but highly lethal cancers such as ovarian cancer. Globocan predicts a change in the reported incidence of ovarian cancer from 2912 in year 2012 to 3132 in year 2015.3

Risk factors for ovarian cancer are not well defined. However, there is general agreement on two: nulliparity and family history. Women 40 to 59 years of age who have taken oral contraceptives or undergone tubal ligation have a reduced risk of developing ovarian cancer.4 Two treatment options, available for ovarian cancers in advanced stage, are either a primary surgical cytoreduction/debulking or chemotherapy in an attempt to downstage the tumor followed by surgery. Though platinum-based therapy has produced an impressive result, chemoresistance and toxicity are creating hurdles. To overcome this, monoclonal antibodies targeting HER2/neu, a transmembrane protein homologous to epidermal growth factor receptor, has been introduced recently that might bring a new era of management.5

HER2/neu protein expression is commonly measured using immunohistochemistry (IHC).6 Overexpression of HER2/neu is seen in 20–30% patients with ovarian cancer. Some of these differences are likely to be attributable to the diagnostic technique used to measure HER2 expression. HER2/neu overexpression in epithelial ovarian carcinomas has not been studied as extensively as it has been studied in case of breast carcinomas, especially in Bangladesh scenario.

The aim of my study was to determine histopathological patterns of ovarian tumor and to evaluate the frequency of the expression of HER2 among epithelial ovarian carcinomas.

 Methods

It was a cross-sectional descriptive study carried out in the Department of Pathology of Chittagong Medical College, Chattogram, Bangladesh. Study period was for one year from 1st January, 2016 to 31st December, 2016. All female patients clinically diagnosed as ovarian neoplasm received at the Department of Pathology of Chittagong Medical College, Chattogram referred from Department of Gynaecology and Obstetrics, Chittagong Medical College Hospital (CMCH) during the specified time duration. Finally, 92 consecutive patients were selected according to time frame.

 Inclusion criteria

Patient with clinically diagnosed as ovarian tumours who underwent intervention like diagnostic laparoscopy or laparotomy; at least for biopsy in Chittagong Medical College Hospital, Chattogram.  Patient with histopathologically diagnosed ovarian tumour in the Department of Pathology, Chittagong Medical College.

 Exclusion criteria

Previously diagnosed case of ovarian tumour who already has got treatment. Patient unwilling to give written consent.

Protocol was ethically reviewed and approved by the Ethical review Committee of Chittagong Medical College, Chattogram. All the patients included in the study were informed and explained about the nature of study. Informed written consent was taken from all the subjects after full explanation of nature, purpose and potential risks of all the procedures.

A brief clinical history was taken from each patient with particular reference to the age, occupation, marital history, parity, menstrual history, family history, history of breast feeding, use of contraceptives etc. Clinical history, questionnaire, thorough physical examination, and relevant investigations were recorded in details in all cases.Routine histopathology with H & E stain and Immunohistochemistry for ovarian carcinoma were done.

H&E stained slides were examined under light microscope to get a definitive diagnosis of the ovarian tumour and its type. Histological classification was based on the 2003 World Health Organization classification of ovarian tumours. The Shimizu-Silverberg three-grade histological grading system was used in epithelial ovarian carcinoma (EOC).

The most representative tumor tissue was chosen from each epithelial ovarian carcinoma case and 4 μm sections were taken to poly-L-lysine coated slides for immunohistochemical staining. For immunohistochemistry, epitope retrieval was done with a polymer-based detection system (Envision; Dako) using a Herceptin kit (HercepTest; Dako) according to the manufacturer’s instructions.Antigen retrieval for HER2 using Hercep Test was performed by immersing and incubating the slides in 10 mmol/L citrate buffer in calibrated water bath (95- 99°C) for 40 minutes. After decanting the epitope-retrieval solution, the sections was rinsed in the wash buffer and later, soaked in the buffer for 5 to 20 minutes before staining. Then the slides were rinsed, placed in 200 μL peroxidase-blocking reagent for 5 minutes, rinsed, placed in 200 μL primary anti-HER2 protein (or negative control reagent) for 30 minutes, rinsed twice, and finally immersed in 200 μL substrate chromogen solution (3,3´-diaminobenzidinetetrahydrochloride, DAB) for 10 minutes. The slides were counter stained with hematoxylin and finally were cover slipped.

 Results

In this study the age range of 92 ovarian tumours was 12-80 years, were divided into seven age groups and it was observed that maximum number of benign lesions 19 (20.6%) were in age groups 21-30 years. Maximum number of malignant tumours were found 9 (9.8%) in age group 41-50 years. Among 92 ovarian lesions, 68 (74%) were surface epithelial tumour, 20 (21.7%) were germ cell tumour, 4 (4.3%) were sex cord stromal tumours .

Discussion 

Current study was carried out in Departmant of pathology, Chittagong Medical College to see the histopathological patterns of ovarian tumours and HER2 expression in epithelial ovarian carcinoma (EOC).Total number of the patients in this study was 92. The age range was 12-80 years. The mean age was 34.64 years. Patients were divided into seven groups consisting of each decade as a single group and maximum number patients 23 (25%) were in 21 – 30 years group, followed by 21 (22.8%) were in 41-50 years age group. Study done in Nepal by Vaidya et al.(2014) showed highest number of patients (58%) were in 21-40 years age group which is similar to present study.7 In this study in 21-40 years age group total number of patients were 42 (45.65%). Study done in India by Bhagyalakshmi et al (2014)) patients age ranged from 11-70 years, majority of benign cases and malignant cases were between 21 to 40 years and 41 to 60 years respectively.8 Agrawal et al. (2015) also showed age ranged from 12 to 80 years with most common benign and malignant lesions cases were 21 to 40 years and 41 to 60 years respectively which was consistent with this study.9

In this study, among 92 cases, 72 (78.3%) were married and 20 (21.7%) cases were unmarried women. This is probably due to more married women presented to the outpatient department than unmarried ones. Among 72 married women 08 (11.1%) were nulliparous, 03(4.2%) were primiparous and 64 (84.7%) were multiparous.Study done in Dhaka by Dhar et al (2015) showed 8% were unmarried and 92% were married, of whom 12% were nulliparous and 80% was parous.10

Regarding socio-economic status 68 (73.9%) cases were from average socioeconomic condition, 23 (25%) were from poor and only 1 (1.1%) cases from high socioeconomic family. Among the malignant cases maximum 13 (48.1%) cases were from average socioeconomic condition. This is similar to the finding of  Dhar et al (2015).10This may be due to the fact that patients attended at a government hospital and most of the people of average and poor socioeconomic conditions usually come here to get treatment.

In this study, it was seen that, 19 (20.7%) had history of hormonal contraceptive use and 49 (53.3%) had no history. Among 27 malignant cases 3 (11.1%) had history of contraceptive use. Ness et al (2011) had reported that oral contraceptives reduce the risk of developing ovarian cancer.11

In this study 75 (81.5%) patients presented with lower abdominal pain 74 (80.4%) with lower abdominal mass. Study done by Jaffar et al (2013) showed, abdominal pain was in 90% cases, abdominal mass was present in 24% of the patients with benign tumours and in 66% with malignant tumours.12

In the present study, among 65 benign lesions 20 (21.7%) cases had increased level of CA-125 and among 27 malignant lesions 3(3.3%) cases were found within normal level.Miralles et al. (2003) suggested that variety of malignancies and benign conditions courses with increased CA-125 level and it is observed that CA-125 is very important as tumour marker for malignancy.13

In the present study, out of 65 benign tumours 62(95.3%) were unilateral and 3(4.6%) were bilateral. Out of 27 malignant tumours 5(18.51%) were bilateral and 22(81.48%) were unilateral. Modepalli et al (2016) reported 93.8% of the neoplasms were unilateral and remaining 6.2% of the lesions were bilateral.14 Benign tumours were more unilateral than malignant tumours. In this present study, out of 92 cases, maximum number of lesions were 48 (52.2%) in the right side of abdomen which is similar to the study done by Modepalli et al (2016).14

Among 92 cases 43 (46.7%) were solid and cystic lesion, 41 (44.6%) were cystic lesions and 8 (8.7%) were solid. Similar study done by Agrawal et al (2017) showed 83.3% benign tumours were cystic whereas 65.3% malignant tumours were solid and cystic.9 Benign tumors were more often cystic in consistency in this study and malignant tumors were solid consistency which was comparable to the study of Kanthikar et al. (2014).15

In this study of the 92 cases of ovarian tumours, 67 (70.7%) were benign and 27 (29.3%) were malignant. Similar studies in India carried out by GG swamy et al. (2010) showed 86 (71.6%) benign tumours, 30 (25.1%) malignant and 4 (3.3%) borderline tumors.16 In Nepal R Jha et al reported 83.9% benign, 16.1% malignant and 2.8% borderilne ovarian tumour.17 In  Pakistan a similar study by Ahmed et al showed 59.18% benign and 40.81% malignant tumour. In this study there was no borderline malignancy which were similar to the study done by Yasmine et al. (2008).18

Among the histologic types, in the present study, surface epithelial tumours were most common 68 (74%), germ cell tumour was 20 (21.7%), and sex cord stromal tumour was 4 (4.3%).Similar observation made by Pilli et al.(2002) showed 70.9% surface epithelial tumours, 21.2% germ cell tumours and 6.7% sex cord stromal tumours.19

In this present study Among 92 cases the most common benign surface epithelial tumour was mucinous cystadenoma 26 (28.3%) followed by serous cyst adenoma 18 (19.6%) and benign brenner tumour 1(1.1%). The most common benign germ cell tumour was mature cystic teratoma 18 (19.6%).In this study benign sexcord stromal tumour was fibroma 2(2.2%). Studies done by Bhagyalakshmi et al (2014)8 and Mondol et al (2011)20 showed serous cystadenoma was the most common benign tumour. Study done by Ahmed et al (2000) however found the most common benign tumour to be benign cystic teratoma.21

The commonest malignant tumour was serous cyst adenocarcinoma 13 (14.1%), followed by mucinous cystadenocarcinoma 8 (8.7%), malignant brenner tumour 1 (1.1%) and clear cell carcinoma 1 (1.1%). Similar results were shown in studies by Mondol et al (2011) and Yogambal et al (2014).22

In this present study 23 cases of epithelial ovarian carcinoma (EOC) were evaluated for HER2/neu protein expression using immunohistochemistry.The positive expression rate of HER2/neu in this study was 1(4.3%).This is comparable to the rate of  HER2/neu positivity in EOC reported in the literature,which ranges from 7-50%Verri et al (2005),23 Berchuck et al (1990),24 Mayr et al (2006).25 The variation in HER2/neu protein expression rate in different studies may be early stage and 17% of patients with advanced stage disease in the study by Kacinsky et al (1992). However, multiple factor may be involved in producing a wide range of positivity, such as sample size, the detection technique and type of monoclonal antibody used, staining intensity and the tissue where analysis is performed. Studies with populations smaller than 100 patients reported a frequency of 1.8-76%,(Serrano-Olvera et al., 2006).26

In this study among 8 mucinous cystadenocarcinoma, HER2 expression was positive in 1 (12.5%) case and was in Grade-II. In the study done by Missaoui et al (2014),27 HER2 expression was described in 14.3% of mucinous carcinoma. Study in Nijeria done by Ajani et al.(2015) 28 observed that a higher proportion of serous carcinoma (as opposed to mucinous carcinoma) was HER2/neu positive. Sarkar et al (2015)2 also showed that HER2 expression was more intense for high grade serous carcinoma.

In this study HER2 expression is relatively common in mucinous epithelial carcinoma of the ovary and trastuzumab therapy would be an option for patients with mucinous carcinoma when the tumour has HER2 overexpression.

The study also has some limitations. This study was severely constrained by the limited duration that led to have small population size and this study was done in patient who underwent surgery and samples were collected from Chittagong Medical College and Hospital only. In spite of these reason the present study showed more or less acceptable findings with consideration of the observations by others.

 Conclusion

Ovarian cancer presents a tremendous clinical challenge to gynecologists, medical oncologists and radiotherapists. It is a silent menace and is not associated with significant symptoms. Surface Epithelial Tumours were the commonest group followed by Germ Cell Tumours. Most common Germ cell tumours were mature cystic teratoma occured in much younger women. Malignant ovarian neoplasms were more common in patients above 40 years. Sex Cord Stromal Tumours were also common with Fibroma and Granulosa cell tumour. Unilateral involvement of ovarian neoplasms was more common than bilateral and involvement of right ovary was more than the left. Mucinous cystadenoma was the commonest benign ovarian neoplasm while the commonest malignant tumour was serous cystadenocarcinoma. Mucinous epithelial carcinoma have expressed HER2.

 References

  1. Lora EH, & Edyta PC. The Female Genital Tract. 8 ed. Philadelphia; Saunders; 2010.1040p.
  2. SarkarM, JhaT, Das TK, SauV et al. Spectrum of Epithelial ovarian tumors with HER2/new expression by the carcinomas among patients admitted in a tertiary care hospital in Eastern India.J Med Sci Public Health. 2015; 4(10):1388-1392.
  3. Pervin S, Islam F, Hall T, & Goodman A. The management of ovarian cancer in Bangladesh: A report of a long-term survivor.Austin Journal of obstetrics and Gynecology. 2015;2(4):1047.
  4. Ness RB, Dodge RC, Edwards RP, et al. Contraception Methods, beyond Oral Contraceptives and Tubal. Ann Epidemiology. 2001;21(3):188–196.
  5. Ray-Coquard I, Gaustalla JP, Allouache D, Combe M, et al. HER2 Overexpression / amplification and trastuzumab treatment in advanced ovarian cancer: a GINECO Phase II study. Clin Ovarian Cancer. 2008;1(1):54-59.
  6. Wolff AC, Hammond ME, Schwartz JN. et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118–45.
  7. Vaidya S, Sharma P, KC S,Vaidya SA . Spectrum of ovarian tumour in a referral hospital in Nepal. Journal of Pathology Nepal. 2014; l4: 539-543.
  8. BhagyalakshmiA, SreelekhaA, Sridevi S, Chandralekha J, Parvathi G,Venkatalaksmi A Prospective study of histopathological patterns of ovarian tumours in a tertiary care centre. International Journal of Research in Medical Sciences. 2014;2(2):448-456.
  9. Agrawal P, Kulkarni DG, Chakrabarti PR, Chourasia S, Dixit M, Gupta K. Clinicipathological Spectrum of Ovarian Tumors: A 5 Year Experience in a Tertiary Health Care Center. Journal of Basic and Clinical Reproductive Science. 2015;4(2), 90-96.
  10. Dhar SR, Begum S, Zabin F, Akter S. Socio-demographic Characteristics of Ovarian Tumor Patients attended at a tertiary care hospital in Dhaka city. Journal of Current and Advance Medical Research. 2015;2(2):39-41.
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  12. Jaffer Y, Ehsan N, Ambreen. Clinical presentation of ovarian tumors. Journal of Surgery Pakistan (International). 2013;18(2):82-86.
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  15. Kanthikar SN,Dravid NV, DeorePN ,Nikumbh DB, Suryawanshi KH. et al.Clinico-Histopathological Analysis of Neoplastic and Non-Neoplastic Lesions of the Ovary: A 3-Year Prospective Study in Dhule, North Maharashtra, India,Journal of Clinical and Diagnostic Research. 2014;8(8):04-07.
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  20. Mondal SK, Bandopadhyay R, Nag DR, Roychowdhury S, Mondal PK, Sinha SK, Histological pattern, bilaterality and clinical evaluation of 957 ovarian neoplasms. A 10 year study in a tertiary hospital of Eastern India. J Can Res Ther.2011; 7:433-437.
  21. Ahmad Z, Kayani N, Hasan SH & Muzaffar S. Histopathological Pattern of Ovarian NeoplasmJ Pak Med Assoc. 2000;50(12):416-419.
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Correlation of Lymphovascular Density with Histological Prognostic Parameters in Gastric Carcinoma

Correlation of Lymphovascular Density with Histological Prognostic Parameters in Gastric Carcinoma

*Hassan MI,1 Kabir AN,2 Poly FH,3 Ray S,4 Munmun UK,5 Mehjabin M6

 

  1. * Mohammed Imran Hassan, Assistant Professor (CC), Department of Pathology, National Institute of Diseases of Chest and Hospital, Mohakhali, Dhaka. imran.vua@gmail.com
  2. AKM Nurul Kabir, Associate Professor, Department of Pathology, BangabandhuSheikh Mujib Medical University, Shahbag,Dhaka.
  3. Ferdousi Hossain Poly, Medical Officer, OSD, DGHS, Attached- Department of Pediatric Neurology, National Institute of Neurosciences and Hospital, Dhaka.
  4. Subrata Ray, Assistant Professor, Department of Pathology, Jashore Medical College.
  5. Umme Kulsum Munmun, Lecturer, Department of Pathology, Dhaka Medical College, Dhaka.
  6. Monika Mehjabin, Lecturer, Department of Pathology, Shahid Suhrawardy Medical College, Dhaka.

*For correspondence

 Abstract

Background: Carcinoma of the stomach is a major cause of cancer mortality worldwide. Gastric cancer is actually a curable disease if it is detected at an appropriate stage and treated adequately. It rarely disseminates widely before it has involved the lymph nodes and, therefore, there is an opportunity to cure the disease prior to dissemination. Tumor-induced lymphangiogenesis plays a crucial role in metastasis and tumor progression. However, the significance of lymph vessel density has been controversial in gastric cancer. Specific lymphatic markers are now available making possible analysis of lymphatic in cancer. The aim of this study was to investigate the relation of lymph vessel density with histological prognostic factors in gastric cancer as potential indicator.
Objectives: To estimate of the lymph vessel density using Podoplanin immunostain in gastric cancer and then to correlate lymph vessel density with histological prognostic factors.
Methods: Sections from Paraffin blocks of gastric adenocarcinoma with routine stain were assessed to detect prognostic factors and then assessed with immunostain Podoplanin to count lymph vessel density. The mean number of lymph vessels in five hot spots was calculated in both intratumoral and peritumoral areas. Finally correlation was seen between histological prognostic factors and lymph vessel density in gastric carcinoma.
Results: A positive significant correlation was found between lymph node metastasis with lymph vessel density in both intratumoral and peritumoral area. Similarly, a positive significant correlation was found between tumor stage with lymph vessel density in both intratumoral and peritumoral area.

 [Journal of Histopathology and Cytopathology, 2020 Jan; 4 (1):12-22]

 Keywords: Podoplanin, Lymphovascular density, Gastric carcinoma

 Introduction

Carcinoma of the stomach is a major cause of cancer mortality worldwide. The prognosis of gastric carcinoma is poor with cure rates little better than 5–10%, although better results are obtained in Japan where the disease is common. Gastric cancer is actually a curable disease provided that it is detected at an appropriate stage and treated adequately. It rarely disseminates widely before it has involved the lymph nodes and, therefore, there is an opportunity to cure the disease prior to dissemination.1

Worldwide gastric cancer ranks fourth in frequency and second in cancer mortality rate; with a 5-year survival rate not exceeding 30% in Western countries.2 Gastric cancer incidence varies markedly with geography. In Japan, Chile, Costa Rica, and Eastern Europe the incidence is up to 20-fold higher than in North America, northern Europe, Africa, and Southeast Asia.1 The incidence of gastric carcinoma in Bangladesh is 5.2 per 100,000.3

 

Gastric cancer is a multi-factorial disease. Epidemiological studies point to a role for Helicobacter pylori, although its importance is disputed. Helicobacter pylori seem to be principally associated with carcinoma of the body of the stomach and the distal stomach rather than the proximal stomach. As Helicobacter is associated with gastritis, gastric atrophy and intestinal metaplasia, the association with malignancy is perhaps not surprising. Patients with pernicious anemia, gastric atrophy, duodenogastric reflux and reflux gastritis, intestinal metaplasia and cigarette smoking are at increased risk, as are those with gastric polyps. Diet appears to be important factor. The ingestion of substances such as spirits may induce gastritis and, in the long term, cancer. Excessive salt intake, deficiency of antioxidants and exposure to N-nitroso compounds are also implicated.1

The most useful classification of gastric cancer is the Lauren classification.4 In this system, there are principally two forms of gastric cancer: intestinal gastric cancer and diffuse gastric cancer. In intestinal gastric cancer, the tumor resembles carcinomas found elsewhere in the tubular gastrointestinal tract and forms polypoid tumors or ulcers. It probably arises in areas of intestinal metaplasia. In contrast, diffuse gastric cancer infiltrates deeply into the stomach without forming obvious mass lesions but spreading widely in the gastric wall.1

These tumors have several prognostic and predictive factors. The depth of invasion and the nodal and distant metastasis at the time of diagnosis remain the most important prognostic indicators for gastric carcinoma. Currently tumor size, nuclear grade and patient’s age are well known prognostic factors for patients with operable gastric cancer. These prognostic factors are widely used to determine whether to apply neo-adjuvant therapy in patient with gastric cancer.  In advanced cases, gastric carcinoma may first be detected as metastases to the supraclavicular sentinel lymph nodes, also called Virchow’s node. Gastric carcinoma can also metastasize to the periumbilical region to form a subcutaneous nodule, termed as Sister Mary Joseph nodule. Local invasion into the duodenum, pancreas, and retroperitoneum is also characteristic. In such cases efforts are usually focused on chemotherapy or radiation therapy and palliative care. However, surgical resection remains the preferred treatment for gastric carcinoma.5

Lymphangiogenesis is a critical process for tumor growth, invasion and metastasis.  That is why measurement of lymph vessel density may be clinically important in gastric cancer specimens. The induction of lymphangiogenesis by a tumor is controlled process, influenced by lymphangiogenic factors, which involve a complex interaction between tumor and endothelial cells.6 The pathologic approach to assess lymphangiogenesis involves microscopic estimation of lymph vessel density by using endothelial markers in immunohistochemistry.

On previous studies detection of lymphangiogenesis was limited due to lack of specific lymphatic endothelial markers. The recent discovery of anti-Podoplanin antibody has a major impact on lymphatic studies. Podoplanin has become a valuable marker for detecting lymph vessels and for identifying lymph vessel invasion in tumor.7

Podoplanin is a specific marker of the lymphatic endothelium and is not expressed in blood vessels. It is expressed by both developing and mature lymphatic endothelial cells and seems to be a more specific marker of lymphatic endothelial cells.  By electron microscopy and immunoelectron microscopy, it was demonstrated that Podoplanin is mainly expressed on the luminal surface of lymphatic endothelial cells.  Peritumoral (PT) lymphatic vessels are larger and more irregular than the intratumoral (IT) lymphatic’s, with a significantly lower density. Intratumoral lymphatic vessels are found in a large variety of tumors and are usually small, flattened and irregular. It was suggested that Podoplanin has potential role in invasion and metastasis of tumor. This hypothesis is mainly based on the observation that high expression of Podoplanin is consistently correlated with the presence of metastases. It was reported that Podoplanin expressing cells were found at the invasion.8 The use of an anti-Podoplanin-based therapeutic strategy could be suggested in the treatment of lymphatic metastases based on three considerations: (i) Podoplanin is a well-known marker of lymphatic endothelial cells; (ii) its expression seems to be associated with bad prognosis and high risk for lymph node metastases; (iii) it is involved in tumor invasion. In conclusion, Podoplanin is a sensitive marker of lymphatic endothelial cells and is very useful in evaluating lymphatic micro vessel density. Immunohistochemical detection of Podoplanin is helpful in the diagnosis of lymphovascular invasion.8 Some studies have suggested that lymph vessel density is associated with an increased risk of lymph node metastasis;9 however, this conclusion is not supported by all of the published studies.10

 

 

 

 

 

 

 

 

 

 

 

The study was conducted a) to investigate morphological prognostic factors of gastric adenocarcinoma, b) to estimate lymph vessel density by using immunostain Podoplanin and c) to correlate lymph vessel density with prognostic factors.

 Methods

It was a cross sectional observational study carried out from March, 2016 to July, 2018at the Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. The study population was paraffin blocks of gastric adenocarcinoma from pathological laboratory in the same Institute with consecutive convenience sampling. Inclusion Criteria was paraffin blocks of gastric samples diagnosed as gastric adenocarcinoma in pathology laboratory and Exclusion criteria were with history of treated gastric carcinoma cases like neo adjuvant therapy, blocks containing autolyzed tissue, extensive necrosis, hemorrhage and desmoplasia, blocks having no tissue or damaged blocks and blocks containing other cancers like lymphoma, carcinoid tumor, malignant GIST etc. The sample size was 53. Monoclonal Anti-Human Podoplanin antibody, clone D2-40, Ready to use (code- IR072) was used for detecting lymph vessel. In this study, sections of normal vermiform appendix were taken as positive control (as recommended by Dako). Podoplanin antigen expression was detected by immunohistochemistry in the submitted blocks (paraffin blocks with maximum tumor bulk were chosen) and were performed using DAKO Cytomation at immunohistochemistry laboratory, department Pathology, BSMMU.

Histopathological categorization of tumor and grading of all the cases were done. Lymphovascular invasion was recorded. Each lymph node was histologically examined to determine metastasis. Numbers of lymph vessels were counted by Weidner’s method in peritumoral (PT) and intratumoral (IT) areas.11

 Micro vessel Quantification

Determination of lymph vessel density (LVD) were performed according to Weidner et al.11Brown staining of cytoplasmic membrane of endothelial cells of lymph vessels were considered as positive reaction. Lymph vessel density was calculated according to Weidner’s method by Olympus microscope model BH51. The immunostained sections were scanned by light microscopy at low magnification (10x) and the areas of tissue with the greatest numbers of distinctly highlighted lymph vessels (“hot spots”) were selected. So, “hot spot” is an area with the most dense lymph vessels growth. Five hot spots were selected in intratumoral (IT) and peritumoral (PT) areas. When the hot spots were defined, lymph vessel count were performed by counting the individual stained lymph vessel (at power 20x) representing a field size of 0.74mm2 (i.e. – 20x objective lens, 10x ocular lens; equivalent to 0.7386 mm2 per 200x field).11 The mean number of lymph vessels in each case were determined and considered as the lymph vessel density.7So, at first five hot spots were chosen in intratumoral (IT) and peritumoral (PT) area. In each hot spot, lymph vessel count was performed at power x20. Finally lymph vessel density was calculated as the mean of the total number of lymph vessels in these five hot spots. Lymph vessel density (LVD) assessed in this manner may be not equivalent to LVD seen in multiple areas of multiple samples of the stomach; however, it is well accepted that these hot spots, not arbitrary areas, are representative of the entire tumor. Although there is some variability in the distribution of lymph vessels within the layers of the gastric wall, the five ‘hot spot’ areas were chosen to obtain an objective assessment and to avoid observer variation.7

Results

A total number of fifty three diagnosed cases of gastric adenocarcinoma were taken for this study. Forty six samples were partial/subtotal gastrectomy specimen and seven samples were total gastrectomy specimen. All fifty three samples contain epigastric lymph nodes ranging one to twenty five. Thirty seven cases had lymph node metastasis and the rest sixteen were free of tumor metastasis. Thirty seven cases were LVI positive in H&E routine stain and forty two cases were LVI positive with Podoplaninimmunostain.

In the group of 53 patients with gastric carcinoma, mean patients’ age was 49.87±11.38 years (range 20-70).33 patients ware male and 20 patients ware female with a male/female ratio of 1.6:1. According to Lauren’s classification, 30 cases ware diffuse type and 23 cases were intestinal type. Two third (60.4%) samples belonged to tumor size ≤ 5 cm. The mean tumor size was 5.61±1.92 cm, ranged from (3.0 – 11.0) cm. Lymph vessel density (LVD) was more frequent in cases having tumor size > 5 cm in diameter.

The histological grade was assessed according to WHO grading system. 33(62.3%) samples belonged to grade-III (poorly differentiation), followed by grade-II (moderate differentiation) (24.5%) and grade-I (well differentiation)(13.2%). Lymph vessel density (LVD) was most frequent in grade- II group.

Cases were grouped according to depth of invasion (tumor stage) as T1, T2, T3 and T4. 41.5% samples belonged to subserosal invasion (T3). T3 was followed by T2(32.1%), T4 (20.8%) and T1(5.7%). Lymph vessel density(LVD) was most frequent in T3 group.

Numbers of lymph node ranged from 1-25. Cases were grouped according to the numbers of lymph node metastasis as N0, N1, N2 and N3. 30.2% samples had no lymph node metastasis (nodal stage N0). 28.3% samples belonged to nodal stage N1, followed by nodal stage N2 (20.8%) and N3 (20.8%). Nodal stages were increasing with increase of Lymph vessel density (LVD).

Lymph vessels in intratumoral (IT) area ranged from 1-12 and peritumoral (PT) area ranged 2-11. Mean LVD in IT area was 5.93 ±2.79 cm and mean LVD in PT area was 5.50±2.38 cm.

A positive correlation was found between Lymph vessel density(LVD) and tumor stage in intratumoral (IT) area (Figure 7).

The value of Pearson’s correlation coefficient was 0.377 and it was significant (p=0.005). Therefore, there was linear association between tumor stage and lymph vessel density (LDV) in intratumoral (IT) area with Podoplanin stain.

A positive correlation was found between Lymph vessel density(LVD) and tumor stage in peritumoral (PT) area (Figure 8).  The value of Pearson’s correlation coefficient was 0.334 and it was significant (p=0.014). Therefore, there was linear association between tumor stage and lymph vessel density (LVD) in peritumoral (PT) area with Podoplanin stain.

A positive correlation was found between Lymph vessel density (LVD) and Lymph node metastases inintratumoral (IT) area (Figure 9).

The value of Pearson’s correlation coefficient was 0.855 and it was significant (p=0.000). Therefore, there was linear association between lymph node metastasis and lymph vessel density (LVD) in intratumoral (IT) area with Podoplanin stain.

A positive correlation was found between Lymph vessel density (LVD) and Lymph node metastases in peritumoral (PT) area (Figure 10).

The value of Pearson’s correlation coefficient was 0.791 and it was significant (p=0.000). Therefore, there was linear association between lymph node metastasis and lymph vessel density (LVD) in peritumoral (PT) area with Podoplanin stain.

A positive correlation was found between LVD in IT and PT.

The value of Pearson’s correlation coefficient was 0.937 and it was significant (p=0.000). Therefore, there was linear association between LVD in intratumoral (IT) and peritumoral (PT) area with Podoplanin stain.

Discussion

Gastric carcinoma is the most common leading tumor of the world. Although great efforts have been made in the field of early diagnosis and adjuvant therapy, the incidence and overall mortality of gastric carcinoma continues to increase. Since gastric tumor cells commonly infiltrate into the lymphatic system, lymph node status is routinely used to identify a patient’s prognosis, tumor stage, and treatment modality. Inhibition of tumor cells to lymph node metastasis (LNM) is a promising way to prevent distant metastasis. However, the relationship between lymphangiogenesis, lymphovascular invasion and lymph node metastasis (LNM) remains ambiguous.

This cross sectional study was carried out with an aim to estimate the density of expression of Podoplanin in lymphangiogenic vessel in gastric adenocarcinoma and to see the correlation between the percentages of area covered by lymphangiogenic vessels with prognostic factors. The present study findings were discussed and compared with previously published relevant studies.

In this study, 62.3% sample had grade-III (poorly differentiation) followed by 24.5% grade-II (moderately differentiation) and 13.2 % grade-I (well differentiation). Significant relation was found between lymph vessel density-intratumoral (LVD-IT) area (p=0.013) and lymph vessel density-peritumoral (LVD-PT) area (p= 0.006) with different histological differentiation. In their study, Pak et al., 201512 found that 53.3 % sample had grade-III and significant relation (p= 0.021) between LVD-IT area with histological differentiation, which is comparable with the current study.

 

It was observed that 41.5 % of samples belonged to T3, followed by 32.1% T2, 20.8% T4  and 5.7% T1 and significant relation found between LVD-IT area (p=0.019) and LVD-PT area (p=0.041) with different tumor stage. Gresta, Rodrigues Jr and Cabral, 201413 found 63.5% cases were T3, followed by 19.2% T2, 13.4% T1 and 3.8% T4. Pak et al., 2015 found 39.3% samples were T3 followed by 16.6 % T2 and T4. They also found significant association between LVD-IT area (p=0.024) with different tumor stage. Raica et al., 20088 found significant correlation between LVD with tumor stage (p<0.002) and Nakamura et al., 20067 found significant positive correlation between LVD with tumor stage (p=0.0008). So, present study result is consistent with previous study.

According to number of lymph node metastasis (LNM), it was observed that 30.2% sample belonged to nodal stage 0 (N0), followed by 28.3% stage-I (N1), 20.8% stage II (N2) and stage III (N3). There was significant relation was found between LVD-IT area (p<0.001) and LVD-PT area (p<0.001) with nodal status. Yan et al., 200814 reported that LVD was obviously higher in the colorectal cancer sample with metastasis (12.08 ± 4.96) than in those without (8.26 ± 4.08) (p<0.001). Schoppmann et al., 200115 demonstrated that lymph vascular invasion (LVI), assessed by anti-Podoplanin immunostain, has been strongly associated with presence of lymph node metastasis. Pak et al. 201512 found LVD-IT area was a higher than LVD-PT area (12.29± 4.36 vs. 11.01±3.62), Nodal stage N0 cases were more frequent and significant relation between LVD-PT in area (p=0.040) with nodal status. Nakamura et al., 20067 found significant positive correlation between LVD with nodal metastasis (p= 0.0094). Raica et al., 20088 found significant correlation between LVD with nodal metastasis (p<0.031) which is comparable with current study.

In this study, there was a positive significant Pearson’s correlation (r= 0.855, p= 0.000) was found between lymph node (LN) metastasis with LVD in IT area. Similarly, there was a positive significant Pearson’s correlation (r= 0.791 p= 0.000) was found between LN metastasis with LVD in PT area. Pak et al., 201512 found in their study that LVD in PT area was significantly associated with LN metastasis (p=0.040). Nakamura et al., 20067 found significant correlation between LN metastasis with LVD (p= 0.0094). Raica et al., 20088 reported that there was significant positive correlation between both LVD in IT and PT areas with LN metastasis (P<0.031). So current study result is consistent with previous study.

In this current study, there was a positive significant Pearson’s correlation (r= 0.377, p= 0.005) was found between tumor stages with LVD in IT area. Similarly, there was a positive significant Pearson’s correlation (r= 0.334, p= 0.014) was found between tumor stage with LVD in PT area. Nakamura et al., 20067 found significant positive correlation between tumor stage with LVD (p= 0.0008). Raica et al., 20088 reported that there was significant positive correlation between both LVD-IT area and LVD-PT area with tumor stage (P<0.02).

In this current study, there was a positive significant Pearson’s correlation (r= 0.937, p= 0.000) was found between LVD-IT areas with LVD-PT areas. Pak et al., 201512 found significant correlation (p=0.028) between LVD-IT area with LVD-PT area.

Conclusion

Total fifty three cases of gastric adenocarcinoma were examined for lymphangiogenic vessels in peritumoral (PT) and intratumoral (IT) areas. Thirty seven cases had lymph node metastasis and the rest sixteen were free of tumor metastasis. Both peritumoral and intratumoral lymphangiogenic vessel count (density) stained by Podoplanin antibody correlated with lymph node metastasis and tumor stage. Lymphatic vessel count is more in the intratumoral area.  The specific lymphatic endothelial marker Podoplanin proved to be a valuable tool in highlighting lymph vessel density (LVD) and lymphovascular invasion, and therefore a predictor of lymph node metastasis.

Limitation 

The study population was selected from one institute in Dhaka city, so that the results may not be reflect the exact picture of the country.  The study period was short. Sample size was small. Podoplanin was only marker used to detect lymph vessels. Sometimes differentiation between blood vessels and lymph vessels were difficult in tissue sections. Differentiation between blood vessels and lymph vessels was also a limitation of this study.  Use of blood vessel immunostain like factor VIIIa, CD31, and CD 34 etc. could have overcome the limitation and overall no control was used.

 

References

  1. Williams NS, Bulstrode CJ, O’connell PR. Bailey & Love’s short practice of surgery. Crc Press; 2008. pp.450-456.
  2. Carl-McGrath S, Ebert M, Röcken C. Gastric adenocarcinoma: epidemiology, pathology and pathogenesis. Cancer therapy. 2007; 5(2):877-94.
  3. Rahman R, Asombang AW, Ibdah JA. Characteristics of gastric cancer in Asia. World journal of gastroenterology: WJG. 2014;20(16):4483.
  4. Lauren P. The two histological main types of gastric carcinoma: diffuse and so called intestinal type carcinoma: an attempt at a histoclinical classification. Acta Pathologica Microbiologica Scandinavica. 1965; 64(1):31-49.
  5. Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran pathologic basis of disease, professional edition e-book. elsevier health sciences. 2014 Aug 27. pp.760-777.
  6. Joo YE, Sohn YH, Joo SY, Lee WS, Min SW, Park CH, Rew JS, Choi SK, Park CS, Kim YJ, Kim SJ. The role of vascular endothelial growth factor (VEGF) and p53 status for angiogenesis in gastric cancer. The Korean journal of internal medicine. 2002; 17(4):211.
  7. Nakamura Y, Yasuoka H, Tsujimoto M, Kurozumi K, Nakahara M, Nakao K, Kakudo K. Importance of lymph vessels in gastric cancer: a prognostic indicator in general and a predictor for lymph node metastasis in early stage cancer. Journal of clinical pathology. 2006; 59(1):77-82.
  8. Raica M, Ribatti D, Mogoanta L, Cimpean AM, Ioanovici S. Podoplanin expression in advanced-stage gastric carcinoma and prognostic value of lymphatic micro vessel density. Neoplasma. 2008;55(5):455-60.
  9. El-Gohary YM, Metwally G, Saad RS, Robinson MJ, Mesko T, Poppiti RJ. Prognostic significance of intratumoral and peritumoral lymphatic density and blood vessel density in invasive breast carcinomas. American journal of clinical pathology. 2008;129(4):578-86.
  10. Zhao YC, Ni XJ, Li Y, Dai M, Yuan ZX, Zhu YY, Luo CY. Peritumorallymphangiogenesis induced by vascular endothelial growth factor C and D promotes lymph node metastasis in breast cancer patients. World journal of surgical oncology. 2012;10(1):165.
  11. Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, Gasparini G. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. JNCI: Journal of the National Cancer Institute. 1992;84(24):1875-87.
  12. Pak KH, Jo A, Choi HJ, Choi Y, Kim H, Cheong JH. The different role of intratumoral and peritumoral lymphangiogenesis in gastric cancer progression and prognosis. BMC cancer. 2015; 15(1):498.
  13. Gresta LT, Júnior IA, Cabral MM. Micro vessel density quantification in gastric cancer: comparing methods for standard measures. J Cancer SciTher. 2014;6(10):401-5.
  14. Yan G, Zhou XY, Cai SJ, Zhang GH, Peng JJ, Du X. Lymphangiogenic and angiogenicmicrovessel density in human primary sporadic colorectal carcinoma. World Journal of Gastroenterology: WJG. 2008; 14(1):101.
  15. Schoppmann SF, Birner P, Studer P, Breiteneder-Geleff S. Lymphatic microvessel density and lymphovascular invasion assessed by anti-podoplanin immunostain in human breast cancer. Anticancer research. 2001; 21(4A):2351-5.
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Malignant Solid Childhood Tumors: Morphological Study in a Tertiary Hospital

Original Contribution

Malignant Solid Childhood Tumors: Morphological Study in a Tertiary Hospital

 *Rahman SS,1 Hossain MI,2 Nasreen S,3 Ahamad MU,4 Bhattecharjee P,5 Rahman Z,6 Khan MA7

 *Dr. Sharmin Sultana Rahman, Assistant Professor, Department of Pathology, Tairunnessa Memorial Medical College, Gazipur, Bangladesh. path@gmail.com

  1. Mohammad Ismail Hossain, Lecturer, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh. ismail.tushar@gmail.com.
  2. Sayeeda Nasreen, Assistant Professor, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh.
  3. M. Shahabuddin Ahamad, Associate Professor, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh.
  4. Pradip Bhattecharjee, Associate Professor, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh, 4203.
  5. Zillur Rahman, Professor, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh, 4203.
  6. Md. Morshed Alam Khan, Public Health Graduate. West Chester University of Pennsylvania, USA.

*For correspondence

Abstract

Background: Malignancy is the second most common childhood mortality in the developed world. The types of cancer that develop in children are often different  types that develop in adult with respect to incidence, type of tumor, underlying familial or genetic aberration and tendency to regress spontaneously or cytodifferentiation. In recent years, identification of specific genes, oncogenes, tumor markers and other biological and pathological factors have played an important role in staging and classifying risk categorization of specific tumors as low, intermediate and high-risk lesions.

Objectives: This study was done to evaluate the incidence and morphological patterns of solid malignant tumors in children.

Method: This hospital based cross-sectional descriptive study was conducted the Department of Pathology, Chattogram Medical College, Chattogram referred from Department of Pediatric Surgery, Chattogram Medical College Hospital, Chattogram. All the cases were subjected to examine histopathological slides with haematoxylin and eosin stain, and IHC done in malignant small round cell tumors and few tumors cases.
Results: An analysis of 43 cases of childhood solid malignant tumors, over a period of a year, was done. The study found that 28 out of 43cases of malignant tumors were seen in boys, whereas 15 casesin girls. The commonest tumor was lymphoma (11 cases) with non-hodgkin’s predominance (10 cases), followed by nephroblastoma (10 cases). In addition, the common age group was found 0-4 years (22 cases), with male predominance.
Conclusion: Histopathological diagnosis could be confirmed with IHC in cases B cell non-hodgkin lymphoma, infantile fibrosarcoma, malignant fibrous histocytoma, Ewing’s sarcoma / PNET. The frequency of tumors and their distribution was comparable to that report from other studies.

[Journal of Histopathology and Cytopathology, 2020 Jan; 4 (1):3-11]

 Keywords: Morphology, Malignant, Childhood, Solid tumour.

 

 Introduction

Malignancy is the 2nd most common cause of childhood mortality in the developing world 1st being malnutrition and infection. About 1/650 children develops malignancy before their 15thbirthday.1

In Bangladesh, there are no perfect cancer registries. Childhood cancers are expected to be high in Bangladesh because of the young population structure – about 30% (47.4 million) of the population is under 15 years old.2

Common childhood malignant tumor (almost 80%) arises from haemopoietic elements, lymphnodes, bones and soft tissues. The childhood cancer often the result of DNA changes in the cells that take places very early in life, sometimes even before birth. A few environmental factors, such as radiation exposure, have been linked with some types of childhood cancer. Some children inherit DNA mutation from parents that increases their risk of certain types of cancer. The reason for DNA changes that cause most childhood cancers are not known.3

Childhood malignancies differ biologically and histopathologically from those of adults with respect to incidence, type of tumor, underlying familial or genetic aberration and tendency to regress spontaneously or cytodifferentiate4. In recent years, identifications of specific gene, oncogenes, tumor markers and other biological and pathological factors have played an important role in staging and risk categorization of specific tumors. Hence there is a need for accurate histopathological reporting in conjugation with ancillary methods.5 Histological type is important for understanding etiology and progression of disease.

This study aims to provide a comprehensive recent overview on childhood cancers in the Department of Pathology, Chittagong Medical College, Chattogram which would contribute to the understanding of characteristics and provide a basis for the future strategies to deal with childhood cancer.

Method

It is a hospital based cross-sectional descriptive study carried out in the Department of Pathology, Chittagong Medical College, Chattogram over a one year period from 1st January 2017 to 31st December, 2017.

Children of 0-14 years old age diagnosed as malignant tumor, who had undergone operative treatment in the Department of Pediatric Surgery, were included in this study. Patients diagnosed as a case of malignant solid tumor was subjected to detail clinical history and thorough physical examination followed by relevant investigations.

All the specimens sent from Department of Pediatric Surgery were evaluated and stained by haematoxylin and eosin in all cases and immunohistochemistry (IHC) done in malignant small round cell tumors and (few tumors cases). All the necessary and relevant data regarding patients were recorded methodically in pre-designed data sheet.

 Statistical analysis

The data were collected from the filled data sheet and statistical analysis was done using the SPSS (Statistic Package for Social Science) Version-20 software package for windows.

 Result

Age incidence ranged from 0-14 years. Patients were divided into 3 age groups. The mean age was 6 years 9 months. 28 (65.1%) cases were seen in boys and 15 (34.9%) cases were seen in girls showing male preponderance. Male and female ratio: 1.87:1.

Lymphoma is the commonest malignant tumor and it constituted 25.3% of all tumors. 10 cases were Non-Hodgkin’s lymphoma and 01 case is Hodgkin lymphoma. Mean age is 8 years. Male is more prevalent than female with male female ratio 9:1, more frequently found in 0-4years age group. Immunohistochemistry CD20 and CD3 are done in selective cases. 6 cases of Non-Hodgkin’s lymphoma were B cell origin, CD20 positive and one case was T-cell origin which is CD3 positive. Hodgkin’s lymphoma was CD30 negative. 8 cases arose from lymph nodes and 2 cases were soft tissue origin. One of them was diagnosed as a case of malignant small round cell tumor.

Among the renal tumors, only Wilm’s tumor (10 cases) was found, with classical triphasic tumors were more prominent feature. The mean age was 4 years 7 months. Male to female ratio was 1:1.

Among the germ cell tumors, 4 cases were noted as immature teratoma: 3 of them arose from sacro-coccygeal region and 1 from ovary; 2 cases were dysgerminoma and 2 cases were yolk sac tumor; 1 case was extra gonadal origin. Female predominance with male female ratio 1:2.5. Mean age was 5 years 7 months.

 

In this study, four cases were diagnosed as malignant small round cell tumor. For further evaluation, CD20, Myogenin, Desmin, Neuron-specific enulose (NSE), Synaptophysin markers were done. 2 cases were diagnosed as B cell Non-Hodgkin lymphoma, 1 case is desmoplastic malignant small round cell tumor and other was neuroblastoma.

 

Soft tissue sarcoma comprised 9.3% (4 cases). Mean age was 8 years 4 months, with male female ratio 3:1. 2 cases were histologically diagnosed as infantile fibrosarcoma and malignant fibrous histocytoma. Infantile fibrosarcoma was found, six months old, male baby, arising from abdomen. Malignant fibrous histocytoma was noted in male, 14 years old. Immunohistochemically both cases showed strong positive for vimentin. A case of desmoplastic small round cell tumor also found. Histologically diagnosed as a case of malignant small round cells arising from intra abdominal cavity and confirmed by desmin. 1 case was PNET/ Ewings sarcoma family. For further evaluation CD99 was recommended.

Colorectal adenocarcinoma accounts for 7% (3 cases) of pediatric malignant tumors in the present study and commonly seen in 10-14years age group. Mean age is 11 years 7 months.

Bone tumor constituted 7% (3 cases): 1 case was metastatic osteosarcoma on the left chest wall; 1 case was Ewing’s sarcoma/PNET family; another was chondrosarcoma. Male were predominant with male female ratio 2:1. Immunophenotyping CD99 and S100 were applied for confirming the diagnosis in respectively Ewing’s sarcoma and chondrosarcoma.

 

 

 

 

 

Discussion

Most of the childhood malignant tumors occur below the age of eight years, although wide age variability exists in children.6 In present study, 14 years was considered as the pediatric age with infancy as a separate age group. The peak occurrence of tumors was found in 0-4 year’s age.

 

 

The overall incidence of malignant tumors of childhood was more in male (M: F=1.53:1) patients. This observation has been made uniformly in literature by author. Male predominance is noted in all age groups and female predominance in germ cell tumor by Lee et al10 and Miler  et al,11 In present study, male predominant in all age group of tumor except germ cell tumors. Male and female ratio: 1.86:1.

 

The commonest tumor comprised of lymphoma (11cases, 25.3%). Similar results were reported by Sharma et al,13 and Baneerjee et al.14 NHL was more frequent than Hodgkin. Non-Hodgkin lymphoma represented 23.3% whereas Hodgkin 2.3%. Non-Hodgkin lymphoma commonly expressed in 0-4 years age group in this study. Patients presented with swelling, pain, fever, and loss of weight with the duration ranging from one month to year. IHC CD20 was applied in 6 cases and revealed B cell origin Non-Hodgkin lymphoma.

 

Wilm’s tumor is common renal tumour that is 100% as compared to the 78.4% by Louisa et al. This difference may be due to small sample size in present study. Male and female ratio is 1:1. Whereas in the study of Paul et al,6 11 infantile Wilm’s tumor found the male to female ratio was 2.3:1. Husain et al.2found that Wilm’s tumor was slightly more common in girls in whom it tends to present at an older age.

 

Malignant germ cell tumors in the ovaries of very young children are rare in condition1. Weinblatt and Ortega, 1982 noted dysgerminoma as the commonest tumor.16 In this study, 7 cases were malignant germ cell tumors. Among them 3 cases were gonadal origins. Rest of them arose from extragonadal site, and two cases of dysgerminoma in ovary were documented. It is more common in gonadal tumor in patient with gonadal dysgenesis.17 Tumors with syncytiotrophoblastic giant cells have the same prognosis as tumors in which they are absent.18 

 

In this study, two cases of yolk sac tumor was locates at testis and intra abdomen. Both of them had shown elevated level of AFP. One case of yolk sac tumor, in testicular origin, at the age of 8 years and other one of female patient with 45 days arising from intra abdomen.

 

Soft tissue sarcoma comprises 9.3% of pediatric malignancy. Two cases are histologically diagnosed as infantile fibrosarcoma and malignant fibrous histocytoma. Infantile fibrosarcoma is found, six months old, male baby, arising from abdomen. Malignant fibrous histocytoma is seen in male, 14 years old. Immunohistochemically both cases show strong positive for vimentin. A case of desmoplastic small round cell tumor is also found. Histologically it is diagnosed as a case of malignant small round cells arising from intra abdominal cavity and confirmed by desmin.

 

Bone tumor constitutes 7% of pediatric malignant tumors in this study: one case is metastatic osteosarcoma arising from the left chest wall; one case is Ewing’s sarcoma/PNET family; another is chondrosarcoma. Male are predomident, and male female ratio is 2:1. Immunophenotyping CD99 and S100 are applied for confirming the diagnosis in respectively Ewing’s sarcoma and chondrosarcoma.

In this study, colorectal adenocarcinoma account for 7% (3cases) of pediatric malignant tumor and commonly seen in 10- 14 years age group which is similar to the study of Tonbary et al. 2012.19 Among the three cases, tumor arises from appendix, descending colon and rectum, respectively.

In this study, four cases of malignant small round cell tumor are documented .Male to female ratio is 1:1. Out of four cases of small round cell tumor, three cases arose from intra abdominal mass and one case from axillary swelling. For further evaluation of immunohistochemistry of CD20, CD3, Myogenin, Desmin, Vimentin, Neuron-specific enulose (NSE), Chromogranin, Synaptophysin markers are done. Two cases were diagnosed as B cell Non- Hodgkin lymphoma as well as one case was diagnosed as desmoplastic malignant small round cell tumor and other was as neuroblastoma.

In this study, one case is noted as anaplastic astrocytoma; Pilocytic astrocytoma, the most common type of astrocytoma in children, is a low grade tumor that typically arises in the cerebellum. One case of invasive squamous cell carcinoma is documented in the study, arose from retro-molar mass, male, 10 years old patient. No predisposing factor was elicited.

 Because of unwanted technical fault like delayed cold ischemic time and fixative time, negative result of IHC was found.

 Conclusion

In this study, histopathological diagnosis could be confirmed with IHC in following cases: B cell non-hodgkin lymphoma, infantile fibrosarcoma, malignant fibrous histocytoma, Ewing’s sarcoma / PNET. The frequency of tumors and their distribution is comparable to that report from other studies. The early onset and the embryonal nature of the major pediatric tumors suggest a prenatal origin and role of genetic factors. Infection, exposure to drugs and chemicals during pregnancy are other contributory factors. Accurate incidence of data is important in the planning and evaluation of clinical trial. Documentation of cases, advanced diagnostic methods like IHC, cytogenetic studies and treatment modalities with close follow up is needed to achieve better statistical evaluation of the problem.

 Acknowledgement

We express our heartiest gratitude to the staffs of the Department of Pathology of Chittagong Medical College, Chattogram.

 References

  1. Vandana G, Maruti D. The spectrum of malignant solid childhood tumors in the age group of 0-12 Years. Pediatrics and Neonatal Nursing. 2015 Oct 29; 2(3):85-90. Available from: http://dx.doi.org/10.17140/PNNOJ-2-114
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  8. Jussawala DJ, Yeole BB. Childhood cancer in greater Bombay.1973-84. Indian J Cancer. 1988; 25:197-206.
  9. Jain KK, Mathur GP, Srivastava JR. Malignancy in childhood. A clinico-pathological study of 45 cases. Ind J Paediatrics. 1975; 42(326):61-66.
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  16. Weinblatt ME and Ortega JA. Treatment of children with dysgerminoma of the ovary.Cancer. 1982 Jun 15; 49(12):2608-2611. Available from: https://doi.org/10.1002/1097-0142(19820615)49:12<2608::AID-CNCR2820491233>3.0.CO;2-0
  17. Kota SK, Gayatri K, Pani JP, Kota SK, Meher LK, Modi KD. Dysgerminoma in a female with turner syndrome and Y chromosome material: A casebased review of literature. Indian Journal of Endocrinology and Metabolism., 2012 May-June; 16(3): 436–440. Available from: http://www.ijem.in/temp/Indian J EndocrMetab163436-1232556_032525.pdf
  18. Fletcher CD. Germ cell tumors. In Diagnostic Histopathology of Tumors. 3rd Philadelphia: Elsevier Health Sciences; 2007. 605 p.
  19. Tonbary YA, Darwish A, Hussein AE, Fouda A. Adenocarcinoma of the colon in children: Case series and mini-review of the literature. Research Gate. 2012 November 24: 6(1): 29–33. Available from: DOI: http://dx.doi.org/10.1016/j.hemonc. 2013.02.003

 

 

 

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Editorial

Editorial

Artificial Intelligence (AI) in Histopathology: An Emerging Technology in Diagnostic Fields

*Talukder SI

Microscopic examination of tissue sections on glass slides prepared from formalin fixed paraffin embedded tissue section stained with hematoxylin and eosin is histopathological  diagnostic technique. It is an old but is the gold standard diagnostic technique till now. Newer techniques, such as immunohistochemistry is used for refining the histopathological diagnosis. Both techniques are time consuming and laborious job. Artificial intelligence (AI) is a branch of computer science that deals with building smart machine capable of performing tasks that typically require human intelligence.1 AI technology of computer science and engineering has been incorporated in tissue level diagnosis.2 This technology is applied on histological glass slides. Microscopic images of glass slides are digitized by computer. These images are presented as digital matrix and is called virtual slide. A virtual slide allows calculation and related presentation of image information that otherwise can only be seen by individual pathologist. The digital world permits attachments of several (if not all) fields of view and the contemporary visualization on a screen. The presentation of all microscopic magnifications is possible if the basic pixel resolution is less than 0.25 microns. To start digital histopathological diagnosis into the daily routine practice of a histopathologist requires a new setup of workflow arrangement and procedures. The quality of digitized images is sufficient for diagnostic purposes; however, the time needed for viewing virtual slides exceeds that of viewing original glass slides by far. It is due to a slower and more difficult sampling procedure, which is the selection of information containing fields of view. By application of artificial intelligence, Kayser et al, mentioned, histopathological diagnosis in routine work can be managed automatically in steps as follows: 1. The individual image quality has to be measured, and corrected, if necessary. 2. A diagnostic algorithm has to be applied. An algorithm has be developed, that includes both object based (object features, structures) and pixel based (texture) measures. 3. These measures serve for diagnosis classification and feedback to order additional information, for example in virtual immunohistochemical slides. 4. The measures can serve for automated image classification and detection of relevant image information by themselves without any labeling. 5. The pathologists’ duty will not be released by such a system; to the contrary, it will manage and supervise the system, i.e., just working at a “higher level”.1 Virtual slides are already in use for teaching and continuous education in anatomy and pathology. Attempts to introduce them into routine histopathology laboratory work have been reported. Application of AI has been established by automated immunohistochemical measurement systems (EAMUS, www. diagnomX.eu). The performance of automated diagnosis has been reported for a broad variety of organs at sensitivity and specificity levels > 85%.

Histopathology has undergone major changes firstly with the introduction of Immunohistochemistry, and latterly with Genomic Medicine. Salto et al (2018) argued that a third revolution,  Artificial Intelligence (AI) is coming on Digital Pathology (DP).3 The introduction of AI has the potential to both challenge traditional practice and provide a totally new realm for diagnostic pathology.

Hereby, all pathologists should accept new revolutionary technique and be ready to innovate and actively engage in the creation, application and validation of technologies and oversee the safe introduction of AI into diagnostic histopathology practice.

References

  1. What is Artificial Intelligence? https://builtin.com/artificial-intelligence
  2. Klaus Kayser, JĂźrgen GĂśrtler, Milica Bogovac, Aleksandar Bogovac, Torsten Goldmann, Ekkehard Vollmer, Gian Kayser. AI (artificial intelligence) in histopathology-from image analysis to automated diagnosis. Folia histochemica et cytobiologica 2009; 47 (3), 355-361.
  3. Salto-Tellez, M., Maxwell, P., & Hamilton, P. W. (2018). Artificial Intelligence – The Third Revolution in Pathology. Histopathology. https://doi.org/10.1111/his.13760.

*Dr. Sadequel Islam Talukder, Associate Professor, Department of Pathology Mymensingh Medical College, Mymensingh. sadequel@yahoo.com

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Editorial Board

Journal of Histopathology and Cytopathology
Official Organ of Bangladesh Academy of Pathology
Vol 4 No 1, January 2020

Editorial Board
Editor in Chief : Professor Mohammed Kamal
Associate Editor
: Professor Enamul Kabir
: Professor Dr. Md. Zillur Rahman
: Dr. Md. Sadequel Islam Talukder

Advisory Board
: Professor AJE Nahar Rahman
: Professor Abdul Mannan Sikder
: Professor Fouzia Akhtar Banu
: Professor Badrul Islam
: Professor Shah Monir Hossain
: Professor Tareak Al Nasir
: Professor Kaniz Rasul
: Professor Ashim Ranjan Barua
: Professor AUM Muhsin
: Professor Farooque Ahmad
: Professor Md. Golam Mostofa
: Professor Paritosh Kumar Ghosh

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Journal of Histopathology and Cytopathology 2020 January, Vol-4 N-1

Journal of Histopathology and Cytopathology

Official Organ of Bangladesh Academy of Pathology

Vol 4, No 1, January 2020

Front Cover
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Editorial Board
Open
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Index
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Contents

Sl No Article Title Page no
Editorial
1 Artificial Intelligence (AI) in Histopathology: An Emerging Technology in Diagnostic Fields
Talukder SI
Open
PDF		 1
  Original Contributions  
2 Malignant Solid Childhood Tumors: Morphological Study in a Tertiary Hospital
Rahman SS, Hossain MI, Nasreen S, Ahamad MU, Bhattecharjee P, Rahman Z, Khan MA
Open
PDF		 3
3 Correlation of Lymphovascular Density with Histological Prognostic Parameters in Gastric Carcinoma
Hassan MI,Kabir AN, Poly FH, Ray S, Munmun UK, Mehjabin M
Open
PDF		 12
4 Histopathological Patterns of Ovarian Tumours and HER2 Expression in Epithelial Ovarian Carcinoma
Barua M,  Hossain MI,  Bini UH, Nasreen S, Ahamad MU, Bhattecharjee P, Rahman M Z
Open
PDF		 23
5 Histopathological Spectrum of Prostatic Lesions Evaluated in a Tertiary Hospital
Sultana SS, Hossain S, Rahman A
Open
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6 Comparison between Bethesda System and Conventional System for Standardization of Reporting Thyroid Cytopathology
Saleheen S, Rahman DA, Chowdury MA, Haque MM, Habib S, Khan KH
Open
PDF		 38
Review Article
7 C3 Glomerulopathy: Overview on a New Disease Entity
Rahman DA, Banu SG
Open
PDF		 48
  Case Reports  
8 Histopathological Diagnosis of Rhinofacial Entomophthoramycosis in a 16-Year-Old Girl: A Case Report
Asaduzzaman, Khandkar T, Rahman DA
Open
PDF		 55
9 Papillary Thyroid Carcinoma Arising within Mature Ovarian Teratoma: A Case Report
Sadaf A,  Hossain MI,  Sultana  N, Nasreen S, Rahman Z
Open
PDF		 60
10 Epidermal Nevus with Epidermolytic Hyperkeratosis: A Case Report
Fatima K, Banu SG, Kamal M
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PDF		 65
11 Information for Contributors
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 69

 

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jhc-2019-jul-v-3-n-2-information-contributors

Journal of Histopathology and Cytopathology

 Information for Contributors

 General Information

The Journal of Histopathology and Cytopathology (JHC) aims in our understanding of the pathophysiological and pathogenetic mechanisms of human disease by publishing  original papers, review articles, case reports and short communications related to basic and translational fields in pathology. It serves as  bridges between basic biomedical science and clinical medicine with particular emphasis on, but is not restricted to, tissue based studies only. It is published twice a year as the Journal Committee of the Bangladesh Academy of Pathology.

Manuscript Preparation.

Manuscripts should be prepared in MS Word format in accordance with The Uniform Requirements for Manuscripts Submitted to Biomedical Journals

(see http://www.icmje.org). All pages of the manuscript should be double-spaced and numbered consecutively beginning with the Title page.  Each of the following sections should begin on separate pages: Title,  Name and affiliation of authors, Abstract and Keywords, Text, Acknowledgements, References, individual Tables and legends.  Reformatting of the accepted papers may be needed according to the Journal specifications.

Title Page

The title page should include (i) type of publication (original, review, case report etc.) (ii) the complete title of the article (iii) authors’ name in abbreviation  (iv) list of authors including full name, highest degree, signature, designation and institutional affiliation and (v) name, mailing address, email and telephone/mobile number of author responsible for correspondence.

Abstracts

It should begin with full title of the article. Do not write authors name in the abstract page. The abstracts should not be more than 200 words. The abstract should state the purpose of the study or investigations, basic procedures, main findings and principal conclusion. Three to ten keywords may be provided below the abstract using terms from the Medical Subject Headings (Index Medicus, NLM, USA). Abbreviations and citations should be avoided.

 Text

The text of the original articles should be divided into following sections: Introduction,

Methods, Result and Discussion.

 References

References to literature should be numbered in Arabic numerical in superscripts

consecutively in the order in which they are mentioned in the text. At the end of article the full list of references should give the name of all authors followed by the title of the article, the title of the journal abbreviated according to Index Medicus, the year of publication, volume number and first and last pages of the article. Title of the books should be followed by the edition, place of publication, the publisher, the year and the relevant pages. Examples of correct form of reference are given below: References should begin on a new page, be double-spaced and numbered in order of citation in the text, including citations in tables and figure legends. Citations that first appear in tables, figures, or supplemental data should be numbered according to the item’s first call out in the text; a separate reference list should not be prepared for supplemental data. Complete author citation is required (use of “et al” is only acceptable for sources with more than 35 authors).

References should conform to the style of the Journal.

 Examples follow:

Journals: van Riel D, Leijten LM, Kochs G, Osterhaus AD, Kuiken T: Decrease of Virus Receptors during Highly Pathogenic H5N1 Virus Infection in Humans and Other Mammals. Am J Pathol 2013, 183:1382-1389

 Electronic Journals: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group: Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 2009, 6:e1000097. http://dx.doi.org/10.1371/journal.pmed.1000097

 Books: Frosch MP: Central Nervous System. Robbins Basic Pathology, 9th Edition. Edited by Kumar V, Abbas AK, Aster JC. Philadelphia, PA, Saunders, 2012, pp. 811-850

 Product Inserts: Cite in text only: (Affymetrix technical note: Globin Reduction Protocol: A Method for Processing Whole Blood RNA Samples for Improved Array Results. Santa Clara, CA).

 

Web sites: Cite in text only. See Data Supplements and Non-Traditional Media section below for proper use of web site references. Use the doi when available. Include the name of the institution sponsoring the web site, URL address with direct linkage to the referenced information, and date of last access.

Tables

Tables should be typed written on separate numbered pages submitted after the main text on separate pages, as part of the manuscript. The preferred file format for Tables is MS Word. and should follow the reference list. All tables should be numbered consecutively using Roman numerical. Each must carry a brief descriptive heading. Tables should be planned to fit within print area. Table footnotes should use the sequential symbols: *, †, ‡, §, ¶, ∥; and abbreviations.

Illustrations

Figure file formats (including those embedded in the text) are unacceptable.

Photographs and photomicrographs should be of high resolution (minimum 5 mega pixels), in original unedited form and jpg format. These should contain a legend with magnification and stain used. Figure number and name of the first author should be mentioned in each file. Legend should be given in separate page.  Patients’ identification should be hidden.

Abbreviation

Standard abbreviation should be used whenever possible. The full term for which

the abbreviation stands followed by abbreviation in parenthesis should be proceed

the first use of the abbreviation in the text except for standard units of measurements

like 27OC and 25 mmol/L etc.

Letters to the editor

Communications with reference to an article published in the journal and current health

problems in the community will be accepted as letter to the editor.

 Electronic Copy

An electronic copy (soft copy) in the form of CD must be submitted with the printed copy of the article. Electronic copy may be send by email attachment at sadequel@yahoo.com.

Text should be processed with MS Word and pictures should be saved in JPG format.

Manuscript Submission

Electronic version of the manuscripts should be submitted through email to the Executive Editor.  Alternatively send DVD/CD to: The Executive Editor of the Journal of Histopathology and Cytopathology.  A cover letter to the editor must accompany the manuscript stating any,  (a) conflicts of interest (both financial and personal), (b) that the manuscript has not been published previously and is not being considered concurrently by another publication, and (c) all authors and acknowledged contributors have read and approved the manuscript. Submissions are not considered for review if previously published in any form (print or online) other than as an abstract. The editor reserves the customary right to style and if necessary shorten the material accepted for publication and to determine the priority and time of publication. Editor assumes that work based on honest observations. It is not the task of the editor to investigate scientific fraud paper.

Proofs

The corresponding author will be contacted by email once proofs are ready, and will be directed to download electronic proofs from a secure website. The author should check the proofs carefully, mark any printer’s errors, and answer queries as requested. Author changes should be kept to a minimum. Proof corrections and replacement figures (if any) must be returned within 48 hours to avoid any delay in publication.

The Review Strategy

On receipt, manuscripts are assessed by the Editor-in-Chief, to one Associate Editor. The Reviewers’ and Associate Editor’s views are used by the Editor-in-Chief (or a Senior Editor) in reaching a decision, usually within three weeks of submission.

 Summary of Submission, General points

Format the word processing document as double spaced A4 pages with an additional space between paragraphs and margins of at least 2 cm all round. Use a 12-pt standard font such as Times, Helvetica or Arial (with Symbol for special characters). Do not use line numbering, but include page numbers in the header or footer, aligned right. Use consistent, preferably UK English spelling.

 Manuscript title

This should be clear, simple and concise; long titles lack impact. Please remember that many readers will only scan titles, so they should reflect the message of the paper and catch the readers’ attention.

 A short running title

This must be 75 characters or less, including spaces, and reflect the main title and content of the manuscript.

 List of authors

Authorship credit should be based only on 1) substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; 2) drafting the article or revising it critically for important intellectual content; 3) final approval of the version to be published.

 A statement outlining the specific contribution of each author to the manuscript and the work reported in it must appear after the acknowledgements section (see below).

 Full affiliations of all authors:

Include the name of the department(s) and institution(s) to which the work should be attributed. Append the corresponding author(s) full postal address, phone number and email address.

 Conflict of interest statements

Authors must disclose all financial and personal relationships that might bias their work; to prevent ambiguity, a conflict of interest statement must appear on the manuscript title page, detailing any conflicts (or the absence thereof) for each author.

 Word count (from beginning of Introduction to end of Discussion)

Concise articles make a greater impact than long ones and are less likely to be delayed by editing to a suitable length. Full articles should be no more than 4000 words from the beginning of the Introduction to the end of the Discussion. Review articles and special features may occasionally exceed this limit by arrangement with the Editor-in-Chief.

 Abstract (not structured and no more than 300 words)

Following the title page(s), the next page should carry an unstructured prose abstract of 300 words or less. It should clearly convey the purposes of the study, and the main procedures, findings and conclusions. It should be understandable without reference to the rest of the paper, and contain no citation to references in the reference list. Only standard abbreviations as listed below are permitted.

 Keywords (3 to 10)

Below the abstract, authors should provide and identify as such 3 to 10 keywords or short phrases to assist indexing the article and that may be published with the abstract. MESH headings are a useful guide for authors in considering keywords.

 Manuscript structure

Research articles are divided into sections with the headings: Abstract, Introduction, Methods, Results and Discussion. Long articles may need subheadings (especially within the Results and Discussion) to clarify their content. The sections should not be numbered. Other types of articles, such as reviews and commentaries, still need a title and abstract and should adhere as closely as possible to these guidelines.

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jhc-2019-jul-v-3-n-2-mesenteric-ms

Mesenteric Cystic Lymphangioma – Case Report

 

*Nazrin MS,1 Rahman DS2

 

  1. *Dr. Mosammet Suchana Nazrin, Professor & Head, Department of Pathology, North East Medical College, Sylhet, Bangladesh. nazrinsuchana@gmail.com
  2. Dil Shakira Rahman, Lecturer, Department of Pathology, North East Medical College, Sylhet, Bangladesh.

 

*For correspondence

 

Abstract

Cystic lymphangioma is a rare tumor of lymphatic origin. Incidence of intra-abdominal lymphangioma  accounts <5%. A 4 years old boy, admitted in the North East Medical College and Hospital, Sylhet, Bangladesh with the complaints of abdominal distension,  severe pain in whole abdomen, nausea, anorexia and vomiting. CT findings were suggestive of mesenteric cyst. At laparotomy, a cystic tumor was found in the mesentery, that  was attached to bowel loops. Histopathological examination confirmed the diagnosis of cystic lymphangioma.

 

[Journal of Histopathology and Cytopathology, 2019 Jul; 3 (2):172-174]

 

Key words: Lymphangioma, Cyst, Mesentery.

 

Introduction

Lymphangioma is a rare cystic tumors of lymphatic system, characterized by proliferating lymphatic vessels, occurs most commonly in the head, neck and axilla.1 Other sites include mouth, arm, mediastinum, lung, abdomen and viscera. Intra-abdominal cystic lymphangiomas are rare and comprises less than 5% of all cystic lymphangiomas.2 Differentiating cystic lymphangioma from other cystic growths by imaging techniques alone is often inconclusive and surgery followed by histopathological examination is required for final diagnosis. We are here reporting  a rare case of mesenteric cystic lymphangioma in a 4 years old male children.

 

Case report

A 4 years old boy, admitted in the North East Medical College and Hospital with the complaints of abdominal distension and severe pain in whole abdomen for 15 days, nausea and anorexia for 15 days and vomiting for 1 day. On physical examination, abdomen was hugely distended. Tenderness was present in whole abdomen. There was no organomegaly. Umbilicus was everted and transverse slit was present. The laboratory data presented no anaemia,  CRP was 10 mg/dl, serum creatinine 0.5 mg/dl, serum electrolytes showed Na+ 141 mmol/L, K+ 4.4 mmol/L, Cl– 105 mmol/L, HCO3–18 mmol/L. However, computed tomography revealed a large cystic mass of about 16x13x10.5 cm, which extended from right side of upper abdomen to pelvic cavity and displaced adjacent gut loops towards left. No soft tissue component or calcification was seen within the cyst. There was also right sided hydronephrosis, probably due to pressure effect of the cystic mass. Patient was diagnosed clinically as a case of mesenteric cyst.  Laparotomy was done under general anaesthaesia. On laparotomy, there was a mesenteric cyst in the abdomen. Aspiration was done. The fluid color was haemorrhagic, probably due to pressure effect and congestion of the blood vessels. The cyst was clinically designated as mesenteric cyst and sent for histopathological examination.

 

 

On gross examination, there was a cystic mass measuring 7x 6 x4 cm size. The surface was smooth. On cut section, it was multiseptate and multiloculated with various sized cystic spaces. Microscopic examination showed multiple cystic spaces separated by fibrocollageous stroma. The cysts were lined by single layer of endothelium. The lumens were filled with homogenous eosinophilic material with a few clusters of macrophages. The stroma was infiltrated with lymphocytes, forming lymphoid aggregates. Histopathological examination confirmed the diagnosis of mesenteric cystic lymphangioma. The post-operative period was uncomplicated and the patient was discharged on 6th postoperative day.

Discussion

Lymphangioma, a rare cystic tumors of lymphatic system. It is  a benign, slow-growing lesions, characterized by proliferating lymphatic vessels, preferentially located in the head & neck (75%), axilla (20%). Incidence of intra-abdominal lymphangioma (accounts <5%), have been reported in the mesentery, genitourinary tract, spleen, liver & pancreas.3 Abdominal cystic lymphangiomas arises from mesentery (59% – 68%), omentum (20-27%), and retroperitonium (12-14%).4 Abdominal cystic lymphangioma is  more frequent in boyes (5:2) with mean age at 2 years.5 Intra-abdominal cystic lymphangiomas is most commonly presented with abdominal mass and distension, loss of appetite, nausea and vomiting.1,2,6 Ultrasound findings are not specific, the computed tomographic scan allows the initial diagnosis.1 The diagnosis of cystic lymphangioma can only be confirmed by histological examination.

 

Conclusion

Cystic lymphangioma is a rare benign tumor that may be arises in various sites. Confirmatory diagnosis of this lesion includes laparotomy followed by histopathology.

 

Reference

  1. Chaker K, Sellami A, Ouanes Y, et al. Retroperitoneal cystic lymphangioma in an adult: A case report. Urol Case Rep. 2018;18:33-34.
  2. Karkera PJ, Sandlas GR, Ranjan RR et al. Intra-abdominal cystic lymphangioma in children: A case series. Arch IntSurg 2012;2:91-95.
  3. Bhavsar T, Saeed-Vafa D, Harbison S etal., Retroperitoneal cystic lymphangioma in an adult: A case report and review of literature. World Journal of Gastrointestinal Pathophysiology. 2010; 1(5):171-176.
  4. Muramori K, Zaizen Y and Nogushi S. Abdominal lymphangioma in children: report of three case. Surgery today. 2009; 39: 414-417.
  5. Kati O, Gunor S, Kandur Y. Mesenteric cystic lymphangioma: Case report. Journal of Paediatric Surgery 2018;35:26-28
  6. Rami A, Mahmoudi A, EiMadi A, et al., Giant cystic lymphangioma of mesentery: varied clinical presentation of 3 cases. Pan Afr Med J. 2012; 12:7