Tag: Histopathology

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Study of Ovarian Tumours: Histomorphological Types

 *Ansari M,1  Khan AH,2 Hossain S,3 Khanom F4

  1. *Dr. MAS Ansari, Associate Professor of Pathology, Sylhet Women’s Medical College, Sylhet. drmasansari@gmail.com
  2. Professor Dr. Amjad Hossain Khan, Professor of Pathology, Sylhet Women’s Medical College, Sylhet.
  3. Sabbir Hossain, Associate Professor of Pathology, North East Medical College, North East Medical College, Sylhet.
  4. Farida Khanom, Medical Officer of Gynae & Obs, Jalalabad Ragib-Rabeya Medical Colleg, Sylhet.

 *For correspondence

 Abstract

Background: Ovarian tumour accounts for 3% of total cancer in females and is the 5th most common form of cancer related death in females with a varied clinical, morphological and histological features.

Objectives: The present  study was carreid out with an aim to find out  the frequency, age distribution and the histopathological  patterns of ovarian tumours.
Methods: Retrospective  study was done during the period  of 3 years comprised of 125 ovarian tumours diagnosed in the Department of Pathology, Sylhet Women’s Medical College, Sylhet. After thorough gross examination, representative bits were routinely processed and stained with H & E. Tumours were classified as per WHO classification.
Results: Out of 125 cases studied, majority were benign tumours (88%), followed by malignant (10.4%) and borderline tumour (1.6%). Age ranged from 11-70 years. Epithelial tumours were most common (76%), followed by germ cell tumours (16%), sex cord stromal tumours (7.2%) and metastatic ovarian tumours (0.8%). Serous cystadenoma was the commonest benign tumour and serous cyst adenocarcinoma was the commonest malignant ovarian tumour.
Conclusion: The prognosis and varying therapeutic strategies of ovarian tumours necessitate an accurate pathological evaluation. Although newer techniques like IHC and molecular analysis have made the diagnosis easier and more precise, in the institutes with provision of limited resources, histopathological study is still the gold standard in diagnosing most of these tumours.

 [Journal of Histopathology and Cytopathology, 2019 Jul; 3 (2):125-133]

Key words: Ovarian tumour, Histopathology

 Introduction

Ovarian tumours include complex, wide spectrum of neoplasms involving a variety of histological patterns ranging from epithelial tissues, connective tissues, specialized hormone secreting germinal and embryonal cells.1

The poor survival is due to the fact that they do not clinically manifest early and approximately 60-70% of the neoplasms present as either stage III or stage IV.1,3,4 Benign ovarian cysts are the commonest constituting about 80% of ovarian tumours and mostly occur in young women between the ages of 20-40 years. Borderline tumours occur at slightly older ages whereas the malignant tumours are common in older women between the ages of 40-65 years.1,4 Metastatic tumours subsequently involve the ovaries and mimic primary ovarian neoplasia. Approximately, 7% of lesions presenting clinically as primary ovarian tumours are of metastatic origin.5, 6 It is important to determine the histological pattern of ovarian tumour to achieve the optimum treatment response as prognosis depends on the degree of differentiation.2,3,7

Thus present study was undertaken to analyse the frequency of various histological subtypes, age distribution pattern and the  histopathological pattern of ovarian tumours.

 Methods

This retrospective  study was conducted for a period of 3 years (January2015 – December 2018) at Sylhet women’s Medical College, Sylhet.

Specimens sent in 10% formalin were routinely processed with paraffin embedding after adequate fixation. Paraffin sections and slides from fresh blocks and the retrieved blocks were stained with H & E. The slides were then reviewed microscopically in detail and tumours were classified according to the WHO classification of ovarian tumours.

Inclusion criteria

All histologically proven both primary and secondary ovarian tumours.

Exclusion criteria

Non- neoplastic ovarian lesions of study period.

Results

A total number of 125 cases were studied. Among these, majority were primary ovarian tumours (124; 99.2%), while one was metastatic ovarian tumours (1; 0.8 %). Of them 69 cases were benign (88%), 15 cases were malignant (10.4%) and rest 2 cases (1.6%) were borderline. Epithelial tumours (ET) were the most common histological type (95;76%), followed by Germ cell tumours (GCT) (20;16%) and sex cord stromal tumour (SST 9;7.2%; Table I).

Age Distribution

Majority of the tumours occurred in the reproductive age group (57; 45.6%) followed by 41-50 years of age group (26; 20.8%).Youngest patient was 13 years of age and older patient was about 68 years. Epithelial tumours and Sex cord stromal tumours had its peak between 31 to 40 years, whereas Germ cell tumours showed a peak in 21 to 30 years. Metastatic tumoursshowed  distribution between 61-70 years of age group.

 Gross Features

Most of the cases in this study were unilateral (117; 93.6%) and few were bilateral (8; 6.4%). Out of the total 95 Epithelial tumours, 76 were cystic in nature (80%), followed by those with cystic to solid in consistency (18; 18.9%) and solid (1; 1.05%), whereas most of Germ cell tumours were cystic in nature (16; 72.7%), followed by solid in consistency (5; 22.7%). Majority of sex cord stromal tumours (5; 71.4%) and all of the metastatic tumours were partly solid to cystic in consistency.

 Microscopy

The most common benign tumour was Serous cystadenoma (54; 43.2%), followed by Mucinous cystadenoma (14; 11.2%) and Mature cystic teratoma (16; 12.8%). Serous cyst adenocarcinoma was the most common malignant tumour (6; 4.8%), followed by Adult granulosa cell tumour (3; 2.4%). Borderline serous tumour were two in numbers. There was one case of metastatic ovarian tumours, was Krukenbergtumour. (Table II).

Discussion

Ovarian tumours are one of the major health problems and their diagnosis can be difficult due to variety of pathologic conditions affecting the ovaries. Thus knowledge of morphology and age-specific characteristics can help refine the diagnosis.8, 9

In the present study of 125 ovarian tumours, Primary ovarian neoplasms (99.2%) were the most common tumours of all ovarian tumours. Similar observations were made by Bhagyalakshmi A et al.10 (98.5%) and Vaddatti T et al.3 (98.9%). Most of the tumours belonged to Epithelial tumour category (76%) which was comparable to the results seen by Singh S et al.11 (69.17%), Krishna M & Maurya G12 (77.7%) and Badge S et al.13 (77%). GCT and SST accounted for 16% and 7.2%, respectively in our study compared to 42.2% and 3.1% reported in the others.14

In the present study, majority of the tumours were benign (88%) followed by malignant tumours (10.4%) and rest was borderline (1.6%). Findings of the present study correlated well with the studies of various authors.However, in this study the frequency of malignant tumours (10.4%) was little less than the study of Couto F et al.15 (40%).

In the present study, the patient’s age ranged from 11 years to 70 years and this was supported by the study done by Swamy GGEt al.16 where the youngest patient was 13 years old and the oldest was 68 years old. The majority of ovarian tumours (60.7%) were seen in the age group of 21-40 years, which was consistent with the study done by Kuladeepa A VK et al.17 (58.9%) and Pilli GS et al.18 (58.3%) .

In our study, majority of the tumours were unilateral (97.1%) and least were bilateral (2.9%) which were consistent with the findings of  VaddattiT et al.3, Jindal U8 and Prabhakar BR and Maingi K.19

In the present study, majority of the tumours were cystic (72%), followed by partly cystic & solid (18.4%) and few were solid (9.6%). These findings were comparable with the findings of Misra RK et al.20 where most of the tumours were cystic (78.2%) and few were solid (4.1%), whereas Couto F et al.15 have found 10.2% solid tumours which was close to our findings. Benign epithelial tumors were the commonest type (88.4%), followed by malignant epithelial tumors (9.47%) and the rest was borderline (2.10%). These findings were almost similar as observed in the study conducted by Kuladeepa A VK et al.17) Sharma I et al.21

In this study, maximum number of epithelial tumors (78%) were noted in 31-50 years age group. All malignant tumours were seen in the cases above 50 years of age. The results corroborated with the various studies done by Tushar K et al. (2005),22 Jha R & Karki S14 and Jindal U.8 Among the histomorphological types of epithelial tumors, Seroustumours (73.6%) were the most common, followed by Mucinous tumours (16.8%), Seromucinoustumours (8.42%) and least common were endometrioid tumours (1.05%). Similar results were seen by Krishna M & Maurya G12 andSarkar R.23 Serous cystadenoma was the commonest ET (53.3%) followed by Mucinous cystadenoma (21.7%) and serous cyst adenocarcinoma (8.4%). Similar results were reported by various authors in their studies.

In the present study, majority of the  germ cell tumours were benign (81.8%) and include mature cystic teratoma and Struma ovarii. These results were closer to the findings of Agrawal P et al.24 and Verma K & Bhatia A25 with 77.7% and 83.5% respectively. Malignant tumours include Dysgerminoma and Embryonal carcinoma. Germ cell tumours showed maximum cases below 35 years of age, with a gradual decline in 31-40 years age group and they were found to be uncommon after the age of 60 years. These findings were consistent with the studies of Jha R & Karki S14 and Agrawal P et al.24

In this study, majority of the sex cord stromal tumours were benign (57.1%) and the results were not similar to the findings of Rao KN et al.26 (55.6%) and were lower when compared to the findings of Jindal U8 (75%). On the contrary study of Badge SAEt al.13 (66.7%) showed mostly benign sex cord stromal tumours against malignant. The age range of sex cord stromal  tumours in our study was 41-70 years whereas Bhagyalakshmi A Et al.10 recorded age range of 21-70 years in their study. Adult granulosa cell tumour which is potentially malignant tumour occurred in 2.4% of all ovarian tumours. The frequency was consistent with the findings of Gupta SC et al.27 and Pilli GS et al.18 who recorded it as 4.4% and 3.54% respectively.

Our study showed one case of secondary tumours and constituted 0.8% of all ovarian tumours. This was lower when compared to the findings of Badge SA Et al.13  (10.9%) but was almost similar to the studies of Gupta N et al.28 (2%), Jha R & Karki S14 (2.4%) and Bhagyalakshmi A Et al.10 (1.5%). The former when compared with the studies of Misra RK et al.20 (1.07%), Prabhakar BR and Maingi K19 (1.57%) and Couto F et al.15 (1.46%) showed a good correlation.

 Conclusion

Ovarian tumour is a silent menace that presents as a tremendous clinical challenge to gynaecologist, medical oncologist and radiotherapists. Emergence of borderline tumours with prognostic difference from the benign and malignant counterparts, has added a wing to research in the field of ovarian tumours. Accurate diagnosis of ovarian tumours can be rendered in almost all of cases by correlating the clinical presentation, radiographic appearance and histomorphological features, which remains the gold standard. Even then, in the modern era by the application of specialised methods like special stains, IHC markers, ultrastructural studies and cytogenetics, there is a vast scope for reaching specific & reliable diagnosis of difficult dilemmatic cases of ovarian tumours, by which the therapeutic and prognostic implications could be modified.

References

  1. Pradhan A, Sinha AK, Upreti D. Histopathological patterns of ovarian tumors at BPKIHS. Health Renaissance. 2012; 10(2):87-97.
  2. Malli M, Vyash B, Gupta S, Desai H. A Histological study of ovarian tumors in different age groups.Int J Med Sci Public Health. 2014; 3(3):338-341.
  3. Vaddatti T, Reddy ES, Vahini G. Study of morphological patterns of ovarian neoplasms. IOSR Journal of Dental and Medical Sciences. 2013; 10(6):11-16.
  4. Ellenson LH, Piorg EC. The Female Genital Tract.Kumar V, Abbas AK, Aster JC. In: Robbins and Cotran Pathological Basis of Diseases. 9th edn: Elseiver, 2014; 2:1022-1034.
  5. Prat J, Morice P. Secondary tumours of ovary. Tavassoli FA, Devilee P. In: WHO classifications of tumours: Pathology of the breast and female genital organs. 3th edn. IARC Press: Lycon, 2003, 193.
  6. Rosai J. Female reproductive system- Ovary. In: Rosai and Ackerman’s Surgical Pathology. 10th edn. Missouri: Elsevier, 2012; 2:1553-1609.
  7. Sohail I, Hayat Z, Saeed S. A comparative analysis of frequency and patterns of ovarian tumours at a tertiary care hospital between two different study periods 2002-2009. J Postgrad Med Inst. 2012; 26(2):196-200.
  8. Jindal U. Pattern of ovarian neoplasm in rural population: A five year study from tertiary care hospital. Journal of evolution of medical and dental sciences. 2014; 3(8):2033-2039.
  9. Mondal SK, Banyopadhya R, Nag DR, Roychowdhury S, Mondal PK, Sinha SK. Et al. Histologic 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(4):433-437.
  10. Bhagyalakshmi A, Sreelekha A, Sridevi S, Chandralekha J, Parvathi G, Vekatalakshmi A. Et al. Prospective study of histopathological patterns of ovarian tumours in a tertiary care centre. Int J Res Med Sci. 2014; 2(2):448-456.
  11. Singh S, Saxena V, Khatri SL, Gupta S, Garewal J, Dubey K. Et al. Histopathological evaluation of ovarian tumors. Imperial Journal of Interdisciplinary Research. 2016; 2(4):435-439.
  12. Krsihna M, Maurya G. Pattern of ovarian tumors and their age distribution in Kangra Valley Himachal Pradesh. Journal of Evolution of Medical and Dental Sciences. 2015; 4(61):10602-10608.
  13. Badge SA, Gosavi AV, Sulhyan KR. Histopathological study of ovarian tumors. Indian Medical Gazette, 2013; 345-351.
  14. Jha R, Karki S. Histological pattern of ovarian tumors and their age distribution. Nepal Med Coll J. 2008; 10(2):81-85.
  15. Couto F, Naolkarni NS, Rebello MJ. Ovarian tumours in Goa: A clinic pathological study of ovarian tumours. J ObstetGynaecol of India. 1993; 43(3):408-12.
  16. Swamy GG, Saryanarayan N. Clinico pathological analysis of ovarian tumors – A study on five years samples. Nepal Med Coll J. 2010; 12(4):221-223.
  17. Kuladeepa AVK, Muddegowda PH, Lingegowda JB, Doddikoppad MM, Basavaraja PK, Hiremath SS Et al. Histomorphological study of 134 primary ovarian tumors.Adv Lab Med Int. 2011; 1(4):69- 82.
  18. Pilli GS, Suneeta KP, Dhaded AV, Yenni VV. Ovarian tumours: A study of 282 cases. J Indian Med Assoc, 2002; 100:423-424.
  19. Prabhakar BR, Maingi K. Ovarian tumors – prevalence in Punjab. Indian J PatholMicrobiol, 1989; 32:276-81.
  20. Misra RK, Sharma SP, Gupta V, Gaur R, Mishra SD. International Journal of Medical and Health Research ,Pattern of ovarian neoplasm in eastern UP. J ObstetGnecol. 1991; 41(2):242-6.
  21. Sharma I, Sarma U, Dutta UC. Pathology of ovarian tumour- A hospital based study. International Journal of Medical science and Clinical Invention. 2014; 1(6):284-286.
  22. Tushar K, Asaranti K, C MP. Intra-operative cytology of ovarian tumours.J ObstetGynecol India. 2005; 55(4):345-349.
  23. Sarkar R. Ovarian neoplasms – A 14 years study. J ObstetGynecol India, 1996; 46:156-160.
  24. Agrawal P, Kulkarni DG, Chakrabati PR, Chourasia S, Dixit M, Gupta K Et al. Clinico pathological spectrum of ovarian tumors: a 5 year experience in a tertiary health care center. Journal of Basic and Clinical Reproductive Sciences. 2015; 4(2):90-96.
  25. Verma K, Bhatia A. Ovarian neoplasms: A study of 403 tumors. J ObstGynecol India.1981; 31:406-411.
  26. Rao KN, Koteswari M, Devi CP, Sailabala G, Katta R. Morphological study of ovarian tumors with special reference to germ cell tumors. IOSR Journal of Dental and Medical Sciences. 2015; 14(1):55-60.
  27. Gupta SC, Singh PA, Mehrotra TN, Agarwal R, A clinic pathological study of ovarian tumours: Indian J PatholMicrobiol. 1986; 29(4):354-62.

28. Gupta N, Bisht D, Agarwal AK, Sharma VK. Retrospective and prospective study of ovarian tumours and tumour-like lesions.Indian J PatholMicrobiol. 2007; 50(3):525-7.

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Ultrasound Guided Fine Needle Aspiration Cytology and Histopathology in the Diagnosis of Ovarian Mass

 *Ahmed NU,1 Saha NK,2 Bhowmik DK,3 Mazumder AR,4 Shariar S,5 Hira AD,6 Keya SA7

  1. *Dr. Nasir Uddin Ahmed, Assistant Professor, Department of Pathology, Faridpur Medical College. nasirdr32@yahoo.com
  2. Naba Kumar Saha, Professor, Department of Pathology, Sylhet MAG Osmani Medical College.
  3. Dilip Kumar Bhowmik, Professor, Department of Gynaecology & Obstetrics, Sylhet MAG Osmani Medical College.
  4. Ashikur Rahman Mazumder, Professor, Department of Radiology & Imaging, Sylhet MAG Osmani Medical College.
  5. Sakib Shariar, Pathologist, Railway General Hospital, Dhaka.
  6. Ananda Dyuti Hira, Pathologist, Department of Pathology, Khulna Medical College.
  7. Shamim Ara Keya, Lecturer, Department of Pathology, Shaheed Suhrawardy Medical College, Dhaka.

* For correspondence

 Abstract

Objective: The study was designed to evaluate the efficacy of ultrasound guided fine needle aspiration cytology in the diagnosis of ovarian mass and to correlate with histopathological diagnosis.
Methods: This  cross sectional study was done on 60 patients. FNA smears were prepared before surgical procedure. Histopathological examination was done by collection of surgical specimens. Cytomorphological findings were noted and correlated with histomorphological diagnoses.
Results: The age of patients ranged from 16 to 70 years with a mean of 36 years. Study showed 59 (98.33%) were unilateral and 1(1.67%) tumor was bilateral. Among 60 histopathologically diagnosed cases, 7(11.67%) were non-neoplastic cysts, 40 (66.67%) were benign tumors, 2(3.33%) were borderline tumors, 10(16.67%) were malignant tumors and 1 (1.66 %) was inflammatory lesion. All hemorrhagic cysts and cystic lesions were considered benign because they were cytologically negative for malignancy. Concordant diagnosis between cytology and histopathology was in 57 (95%) cases.
Conclusion: USG guided FNAC showed a relatively safe, quick, cost effective and patient compliant procedure with minimal morbidity.

[Journal of Histopathology and Cytopathology, 2019 Jul; 3 (2):117-124]

 Key words: Ultrasound Guidance, Fine Needle Aspiration Cytology, Histopathology, Ovarian Mass.

 Introduction

Tumors of the ovary are incredibly varied. This multiplicity is due to the presence of three cell types in the normal ovary: the multipotent surface (coelomic) epithelium, the totipotent germ cells, and the sex cord–stromal cells, each of which gives rise to a number of different tumors.1 The clinicopathological evaluation of ovarian masses is a challenging field. Difficulty in gaining access to the tumor site is itself a major obstacle and the wide spectrum of lesions present an enigmatic picture to the pathologist. Although histopathology remains the gold standard, in recent times image guided aspiration is being increasingly used as a rapid, inexpensive and efficient method for the pre-surgical diagnosis of ovarian masses as well as planning and evaluation of treatment.2 Historically, gynaecologists are hesitant to aspirate ovarian masses in view of the possibility of seeding of an early stage ovarian cancer. The magnitude of risk of such a procedure is unknown and not substantiated by convincing evidence. It is rather overestimated and has not been pathologically confirmed.3

 However, a lot of studies have clearly documented that risk of tumor spreading by needle tract is negligible in comparison to the potential benefits of this simple, quick and effective modality of diagnosis.4 With sonographic support, any structure visualized radiologically can usually be reached precisely in any desired plane, thus increasing the cytological yield. Nevertheless, as with any technique, image-guided FNAC has its short comings; false-negative results are usually due to failure of the needle to enter the mass and failure to sample representative areas.5 In the preoperative diagnosis of ovarian masses, acellular fluid should not be considered non-diagnostic, because it represents benign cysts in a majority of the cases. Literature search failed to trace any study to see the effectiveness of USG guided FNAC in comparison with histopathology in the diagnosis of ovarian masses in our country. With this background, the study was designed to evaluate the efficacy of ultrasound guided fine needle aspiration cytology in the diagnosis of ovarian mass and to correlate with histopathological diagnosis.

 Methods

The cross sectional study was carried out in the Department of Pathology, Sylhet MAG Osmani Medical College, Sylhet in collaboration with the Department of Obstetrics and Gynaecology and Department of Radiology and Imaging, Sylhet MAG Osmani Medical College Hospital, Sylhet from 1st July 2014 to 30th June 2015. All patients with ovarian masses attended the inpatient department of Obstetrics & Gynaecology were considered as the target population and those who fulfilled the inclusion and exclusion criteria were considered as study population. Patient of all ages with ovarian mass were included in this study and patients with hemorrhagic diathesis, those who refused to undergo  USG guided FNAC and surgery, diagnosed cases under treatment and ovarian mass with pregnancy were excluded from this study. Aspirations were done by expert radiologist in radiology and imaging department. The tumors were located by USG and needle was inserted into the lesion without negative pressure. The content of the needle was expelled on to a glass slide and then allowed the aspirated material to spread by gently pulling apart two slides in opposite direction. The smeared slides were promptly dropped in 95% ethyl alcohol for fixation and kept for at least 30 minutes. This smears were then stained according to Papanicolaou method. The cytopathological examination of the stained slides was carried out on the same day or following day. Surgical specimens were collected from all patients in whom USG guided FNAC were done. All the specimens were preserved in 10% formalin. Routine tissue processing with paraffin impregnation was done and stained with hematoxylin and eosin. The diagnoses of ovarian tumors were done according to the cytopathological and histopathological findings and then cytopathological diagnoses were compared with the histopathological diagnoses.

After meticulous checking, all the relevant collected data were compiled first on a master table. Then the data were organized by using scientific calculator and standard computer based statistical software SPSS-21. Percentages were calculated to find out the proportion of the findings. The results were presented in tables, graphs and diagrams. The efficacy of USG guided FNA cytology for the diagnosis of ovarian mass was determined by calculating sensitivity, specificity, positive predictive values, negative predictive values and accuracy.

 Results

Total 62 cases were selected considering inclusion and exclusion criteria. Tissue for histopathological examination was available in 60 cases for comparison with cytopathological diagnosis. The age of patients ranged from 16 to 70 years with a mean of 36 years. Highest frequency 18 (29.03%) was found in 21- 30 age group (Table-I).

Categorization of neoplastic ovarian masses according to cell of origin

 Of the 60 histopathologically diagnosed cases, benign, borderline and malignant tumors were 40, 2 and 10 respectively. Among the benign tumors, surface epithelial tumors, germ cell tumors and sex cord-stromal tumor were 30, 9 and 1 respectively. All the malignant and borderline tumors were surface epithelial in origin. Table II shows categorization of neoplastic ovarian masses according to cell of origin.

All the smears obtained from USG guided FNA of ovarian masses were satisfactory for cytological evaluation and cytological diagnosis was made in most of the smears. Among 62 cases, 31(50%) were diagnosed as benign tumors, 7 (11.29%) were borderline tumors, 4 (6.45%) were malignant tumors, 1(1.61%) was inflammatory lesion and 19 (30.65%) were benign cystic lesions. Cytopathological diagnoses of ovarian masses are shown in Table III.

 Histopathological diagnoses of ovarian masses

Among 60 histopathologically diagnosed cases, 7(11.67%) were non-neoplastic cysts, 40 (66.67%) were benign tumors, 2(3.33%) were borderline tumors,10(16.67%) were malignant tumors and 1 (1.66 %) was inflammatory lesion.  Histopathological diagnoses of ovarian masses are shown in Table IV.  

Histopathological examination of 60 ovarian masses was performed and comparison between cytological and histopathological diagnoses of ovarian masses is shown in Table V.

Discussion

In present study, age of the patients ranged from 16 to 70 years. The maximum number of cases 18 (29.03%) were seen in third decade which is  similar to the studies done by Sengupta et al & Agarwal et al.4,6 Ellenson and Pirog found maximum number of cases in  third & fourth decades.7  Among the 40 benign tumors, 39 (97.50%) cases were found unilateral and 1 (2.50%) case was bilateral. All the malignant, borderline and non-neoplastic lesions were found unilateral in this study. Ray S  reported that 76.56% of non-neoplastic lesions and benign tumors were unilateral and 23.44% were bilateral, 35.71% malignant tumors were unilateral and 64.29% malignant tumors were bilateral.8 This discrepancy is probably due to small sample size in the current study. On gross evaluation of the 60 ovarian masses, 46 (76.67%) were cystic, 2(3.33%) were solid and 12 (20%) were partly solid and partly cystic (mixed). Ray S  reported 64 benign tumors, of which 51(79.69%) were cystic, 7(10.94%) were solid and 6(9.37%) were mixed. Of the 14 malignant tumors, 2(14.28%) were cystic, 7(50%) were solid and 5(35.72%) were mixed in consistancy.8 These findings are  almost similar to the findings of this study. In the present study, among the 52 neoplastic ovarian masses, 42 (80.77%) were surface epithelial, 9 (17.30%) were germ cell and 1(1.93%) was sex- cord stromal origin. Out of 40 benign tumors, 30(75%) were surface epithelial, 9(22.5%) were germ cell and 1(2.5%) was sex- cord stromal origin. All borderline and malignant tumors were found surface epithelial in origin. Similar findings were found in study by Tushar, Asaranti and Mohapatra.9 They showed out of67 ovarian tumors, 53(79.10%) were surface epithelial, 11(16.41%) were germ cell, 1(1.50%) was sex-cord stromal origin and 2 (2.98%) cases were metastatic tumors. In the present study, out of 62 USG guided FNA of ovarian masses, 31(50%) were benign tumors, 7(11.29%) were borderline tumors, 4(6.45%) were malignant tumors, 1(1.61%) was inflammatory lesion and 19(30.65%) were benign cystic lesions.

Agarwal et al. reported 110 USG guided FNA diagnoses of ovarian masses. Out of 110 ovarian masses, 17 (15.50%) were non-neoplastic, 50 (45.5%) were benign and 43 (39%) were malignant tumors.6 In the present study, cytologically mucinous cystadenoma was the most common benign tumor accounting for 12 (19.35%) and mucinous cystadenocarcinoma was the most common malignant tumor accounting for 2(3.23%). Most of the internationally published journal shows, cytologically most common benign tumor is serous cystadenoma and most common malignant tumor is serous cystadenocarcinoma.3,5,6,10 The findings of present study differ from the findings of internationally published journal which may be due to small sample size. If large sample size was taken, the findings of our study might coincide with the findings of international journals. In histopathological diagnosis of 60 cases, 7(11.67%) were non-neoplastic cysts, 40 (66.67%) were benign tumors, 2(3.33%) were borderline tumors, 10(16.67%) were malignant tumors and 1 (1.66 %) was inflammatory lesion. Similar findings were found in study of 77 cases by Ray et al.3  Out of 77 cases, 43 (55.84%) were benign, 22 (28.57%) were malignant and 12 (15.59%) were non-neoplastic lesions. In the present study, histopathologically most common benign tumor was serous cystadenoma accounting for 16 (26.66%) and most common malignant tumor was mucinous cystadenocarcinoma accounting for 6(10%). Agarwal et al. reported that the most common benign tumor was serous cystadenoma accounting for 17 (24.63%) and most common malignant tumor was serous cystadenocarcinoma accounting 10 (14.50%).6 These findings are partially consistent with the current study. Among the 31 cytologically diagnosed benign tumors, 29 cases were diagnosed correctly in histopathology and 2 cases were diagnosed as malignant tumor. Cytologically diagnosed 4 malignant tumors were also diagnosed as malignant in histopathology. In cytologically diagnosed 7 borderline tumors, histopathologically 04 were malignant, 2 were borderline and 1 was benign tumor. One inflammatory lesion diagnosed correctly both in cytology and histopathology. All 17 benign cystic lesions diagnosed cytologically, were also benign in histopathology. Concordant diagnosis between cytology and histopathology was in 57 (95%) cases.

 Conclusion

USG guided FNAC is a relatively safe, quick, cost effective and patient compliant procedure with minimal morbidity and fair diagnostic accuracy. In the preoperative diagnosis of ovarian masses, acellular fluid should not be considered non-diagnostic, because it represents benign cysts in a majority of the cases. False negative results are due to paucicellularity and secondary degenerative changes of epithelial cells. Most of the hospitals in our country are not equiped with frozen section facilities.  USG guided FNAC has particular value as a preoperative diagnostic procedure where frozen section facilities are not available. USG guided FNAC in the diagnosis of ovarian masses can be practised in any centre where the help of sonologist and cytopathologist is available.

 References

  1. Sattar HA. Female Genital System and Breast. In: Kumar V, Abbas AK, and Aster JC, eds. Robbins Basic Pathology, 9th ed. Philadelphia, USA: Elsevier Saunders 2013: pp.681-714.
  2. Afzal S, Ansari H, Ansari M, Maheshwari V, Mehdi G. Image- guided fine-needle aspiration cytology of ovarian tumors: An assesment of diagnostic efficacy. Journal of Cytology 2010; 27(3): 91-95.
  3. Ray S, Gangopadhyay M, Bandyopadhyay A, Majumdar K, Chaudhury N. USG guided FNAC of ovarian mass lesions: A cyto-histopathological correlation, with emphasis on its role in pre-operative management guidelines. Journal of the Turkish German Gynecological Association 2014; 15: 6-12.
  4. Sengupta S, Mondal R, Bose K, Ray R, Jana S, Deoghoria D. Evaluation of role of ultra sound guided fine needle aspiration cytology for diagnosis of ovarian lesions with particular references to diagnostic pitfalls. Bangladesh Journal of Medical Science 2014; 13(2):158-162.
  5. Goel S, Agarwal D, Goel N, Naim M, Khan T, Ekrammulah. Ultrasound guided fine-needle aspiration cytology in ovarian neoplasms: An assesment of diagnostic accuracy and efficacy and role in clinical management. The Internet Journal of Pathology 2010; 11(2): 1-10.
  6. Agarwal N, Garg S, Aggarwal N, Santwani PM. Ovarian Neoplasm: Diagnostic accuracy of ultrasound guided fine needle aspiration cytology with histopathological correlation. IOSR Journal of Dental and Medical Sciences 2014; 13(7): 24-28.
  7. Ellenson LH, Pirog EC. The Female Genital Tract, In: Kumar V, Abbas AK, Fausto N, Aster, JC, eds. Robbins and Cotran Pathologic Basis of Disease, Philadelphia, USA: Elsevier Saunders 2010: pp.1039 -1052.
  8. Ray S. The role of imprint cytology in the diagnosis of ovarian lessions [ M. Phil thesis]. Sylhet MAG Osmani Medical College 2008,
  9. Tushar K, Asaranti K, Mohapatra PC. Intra-operative cytology of ovarian tumors. The Journal of Obstetrics and Gynaecology of India 2005; 55(4): 345-349.
  10. Khan N, Afroz N, Aqil B, Khan T, Ahmad I. Neoplastic and non-neoplastic ovarian masses: Diagnosis on cytology. Journal of Cytology 2009; 26(4):129-133.
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Concurrent Core Needle Biopsy with Fine Needle Aspiration Biopsy in The Diagnosis of Palpable and Clinically Suspicious Breast Lesions

 *Sharmin S,1 Dewan MR,2 Jinnah SA,3 Sharmin R,4 Runa NJ,5 Ambiya AS,6 Rahman N,7 Afrin SS,8 Hussain M9

 

  1. *Dr. Shegufta Sharmin, Assistant Professor, Department of Pathology, US Bangla Medical College, Dhaka. sheguftasharmin1982@gmail.com
  2. Md. Rezaul Karim Dewan, Professor & Head, Department of Pathology, Dhaka Medical College, Dhaka.
  3. Shahed Ali Jinnah, Associate Professor, Department of Pathology, Dhaka Medical College, Dhaka.
  4. Rumana Sharmin, Lecturer, Department of Pathology, Dhaka Medical College, Dhaka.
  5. Nusrat Jahan Runa, Assistant Professor, Department of Pathology, Dhaka Central Inrernational Medical College, Dhaka.
  6. Ahmed Shahed e Ambiya, Resident Medical Officer, Department of Medicine, Holy Family Red Crescent Medical College Hospital, Dhaka.
  7. Najibur Rahman, Assistant Professor (Rtd), Department of Pathology, Dhaka Medical College Hospital, Dhaka.
  8. Syeda Sadia Afrin, Resident, Department of Pathology, Dhaka Medical College Hospital, Dhaka.
  9. Maleeha Hussain, Professor of Pathology Department, Dhaka Medical College Hospital, Dhaka.

 *For correspondence

Abstract

Background: Breast lump is one of the most common surgical problem in female patients. Though excision biopsy of palpable breast lump is considered to be the gold standard method for diagnosis, there should be an improved and definitive method for establishing an accurate diagnosis of breast masses prior to surgery.
Objectives: The aim of this study was to determine the diagnostic accuracy of concurrent fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) in cases of suspicious breast lesions and to study the discordance between them.
Methods: This descriptive cross sectional study included 72 female patients with breast lumps, presented to Dhaka Medical College Hospital over a period of two years and subsequently underwent concurrent FNAB and CNB in the same sitting. The results were then compared with final histopathological findings and the correlations between FNAB and CNB were determined.
Results: Out of 72 cases included in the study, histopathological diagnosis was available in 42 cases. There were four false negative cases in FNAB (14.28%) and two false negative cases (7.14%) in CNB.  The false negative rate in the combined approach was 3.57% which is lower than the rate in individual tests. The sensitivity of combined approach was 96.5%, where FNAB and CNB had 85.71% and 92.85% respectively. The specificity and positive predictive value of both FNAB and CNB were individually 100%, so the concurrent result was also the same. The diagnostic accuracy of combined FNAB and CNB was higher than individual results, which was statistically significant (p<0.05).
Conclusion: Concurrent FNAB and CNB can provide accurate preoperative diagnosis of breast lesions and provide important information for appropriate treatment. Identification of discordant results and, therefore, careful correlation can reduce false negative rate.

[Journal of Histopathology and Cytopathology, 2019 Jul; 3 (2):107-116]

 Key Words: Breast lesions, FNAB, CNB, Histopathology

Introduction

Breast cancer is the second most common cancer in the world and the most frequent cancer among women with an estimated 1.67 million new cancer cases diagnosed in developing countries in 2012.1 Breast cancer is the leading cause of cancer death in women in the less developed regions (324,000 deaths, 14.3% of total) and the second cause of cancer death in the more developed countries  (198,000 deaths, 15.4%) after lung cancer.2 According to the Globocan estimate, more than half of the 1.67 million new breast cancer cases were diagnosed in developing countries in 2012 which is about 52.9%, whereas the corresponding figure for 1980 was only 35%.3,4 In Bangladesh, the number of new cases of breast cancer in the year 2008 was 17,781.5

Breast cancer usually presents with a palpable breast lump. Most breast lumps are benign and of no serious consequence. Fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are both used in the evaluation of breast lesions and play an important role in the management.6 Both have their specific advantages and limitations. Recent studies have shown the high accuracy and cost effectiveness of FNAB to identify cancer in patients with palpable breast lump.7

FNAB is often used as a first priority investigation in patients with breast lump, but this technique is highly dependent on the skill and expertise of the aspirator.8 FNAB cannot confirm the presence of tumor invasion and therefore cannot be used to differentiate between invasive and in situ neoplasia. In addition, low grade breast lesions, such as atypical ductal hyperplasia, ductal carcinoma in situ and tubular carcinoma cannot be accurately diagnosed using this modality alone. Therefore, erroneous diagnosis can occur due to sampling error or due to misinterpretation.

Tru cut biopsy, also known as core needle biopsy (CNB) is now one of the most useful means of obtaining histopathological diagnosis.9 Besides, core biopsy allows the discrimination between in situ and invasive lesions and is a more accurate method to distinguish between invasive ductal and invasive lobular carcinoma.9 A well sampled CNB specimen usually has greater diagnostic efficacy and provides more tissue for ancillary studies.10 However, CNB still has some pitfalls.11 In some cases, even with image guidance, CNB can miss the lesion and yield inadequate material.12 During the procedure, blood vessels may be injured by large bore needles; in such cases the invasive biopsy procedure will only yield clotted blood on repeated puncture.13 In these instances, core biopsies cannot produce adequate samples which in turn will cause a delay in the histological interpretation.

If FNAB and CNB are used concurrently in cases of suspicious breast lesions, the sensitivity and specificity may be better than either alone.

This study was aimed to find out the diagnostic accuracy of concurrent CNB and FNAB of palpable and clinically suspicious breast lesions.

 Methods

The present cross sectional study was carried out in the Department of Pathology, Dhaka Medical College over a period of two years from January 2015 to December 2016. Female patients of any age group with clinically suspicious and palpable breast lumps who were advised for FNAB or CNB were enrolled and were subjected to concurrent FNAB and CNB in the same sitting with their informed written consent.

With proper aseptic measures, fine needle aspiration was done using a 5 cc or 10 cc disposable syringe for each puncture and for each patient and two to six smears were prepared in glass slides for each patient according to need.  The core needle biopsy was performed by an automated biopsy device equipped with a 14 gauge needle having a sample notch of 15 mm in length. Samples were obtained from different areas of the lesion, usually from the center and close to the borders at the 3, 6, 9 and 12 O’clock positions and were placed in a vial containing 10%  neutral buffered formalin. For each CNB procedure, the number of biopsies taken was recorded. The outcomes of FNAB and CNB were reported using the standard National Health Service Breast Screening Programme (NHSBSP) criteria.

In this study, histopathological examination of mastectomy or lumpectomy or excisional biopsy was considered as gold standard. Statistical analysis of the results was obtained by window based computer software devised with Statistical Packages for Social Sciences (SPSS).

 Results

A total 72 cases were included in the study in whom FNAB and CNB were performed, and subsequently lumpectomy or mastectomy specimen were available in 42 cases. Histopathological diagnosis was the gold standard of the study. Individual and combined FNAB and CNB were compared and validity test results were calculated. It was observed that the majority (44.4%) of patients belonged to the age group of 31-40 years. The mean age was found 40.94±7.9 years with range from 28 to 62 years (Table I).


More than one third (43%) of the samples were cytologically diagnosed as malignant, 07(9.72%)were diagnosed as suspicious and 09(12.5%) showed atypia. 25(34.72%) cases were cytologically diagnosed as benign(Table II). On the other hand in CNB, 34 (47.2%) cases were found to be malignant cases, 26(36.11) benign , 06 suspicious of malignancy, 05(6.94%) of uncertain malignant potential and 01 (1.38%) unsatisfactory tissue (Table III). Finally, after histopathology of the 42 cases, where surgical biopsy were available, 28(66.66%) cases were confirmed as malignant and 14(33.33%) cases were found to have benign lesions. It was observed that 25(59.52%) patients with duct cell carcinoma was the most frequent diagnosis, followed by 2(4.8%) papillary carcinoma and 1(2.3%) lobular carcinoma (Table IV)

Of the 20 malignant cases and 4 suspicious cases diagnosed by FNAB, all proved to be malignant by histopathology. Among the 05 cases presented with atypia in FNAB, 4 were diagnosed histologically as malignant and 1 was benign. None of the benign cases diagnosed by FNAB was otherwise in histology (Table V).Of the 19 patients diagnosed as malignancy by CNB, 17(79.2%) were diagnosed as duct cell carcinoma, 01(100.0%) as lobular carcinoma and 01(100.0%) as papillary carcinoma by histopathology (Table VI). All 07 suspicious cases in CNB were histologically diagnosed as malignancy and the 04 cases presented with atypia in CNB, ultimately diagnosed as benign in 03 cases and malignant in 01 case (Table VI).

ith concurrent FNAB and CNB, true positive cases were 27 in number, true negative cases were 14 and false negative cases was 1 in number. There were no false positive case (Table VII). In the present study, the sensitivity of FNAB is 85.71%, specificity 100%, PPV (positive predictive value) 100%, NPV (negative predictive value) 77.77% and accuracy 90.47%. In comparison, the sensitivity of CNB is 92.85%, specificity 100%, PPV (positive predictive value) 100%, NPV (negative predictive value) 87.5% and accuracy 95.23%. When both FNAB and CNB are combined, the sensitivity is 96.05%, specificity 100%, PPV (positive predictive value) 100%, NPV (negative predictive value) 93.33% and accuracy 97.61% (Table VIII). So the combined results are superior to FNAB or CNB alone (p<0.05) statistically significant


Discussion
Fine needle aspiration biopsy and core needle biopsy currently are the most widely used methods for pathological diagnosis of breast lumps. They have their specific advantages and limitations. To minimize the limitations of individual procedure, in the current study simultaneous FNAB and CNB was used for the diagnosis of clinically suspicious and palpable breast lumps. Results of the combined approach were compared with FNAB and CNB separately.

With a population of over 163 million, Bangladesh is one of the most densely populated countries in the world.14 Not much information on breast cancer in Bangladesh is available as there is no population based cancer registry in our country. However, the only hospital based cancer registry at the National Institute of Cancer Research and Hospital tracks new cancer cases systematically in this country. According to NICRH report, 5255 breast cancer cases were diagnosed during the period of 2005-2010.15,16 The data of NICRH states that breast cancer has overtaken cervical cancer as the most common female cancer in Bangladesh. (Breast cancer cases 26% and cervical cancer cases 21.1% during the period 2008-2010: NICRH, Cancer registry report).16

In the present study, a total of 72 cases of clinically suspicious and palpable breast lumps were included. FNAB and CNB were done in all of them but surgical biopsy was available in 42 cases only. Of these 42 cases, 28 were malignant and 14 were benign. The firm to hard consistency, irregularity and larger size of the lumps in these 14 benign cases made them to be clinically suspicious. Histopathology was the gold standard in this study and the validity test results of FNAB and CNB were evaluated and compared with it.

In this study, among the 48 cancer patients diagnosed either by core needle biopsy or fine needle aspiration biopsy, age ranged from 33 years to 62 years with a mean age of 42.5 years. In this present study, 26(54.16%) cancer patients out of 48 malignant cases were premenopausal and 22(45.83%) cases were postmenopausal.

Fine needle aspiration biopsy is a routine procedure in the diagnosis of breast lesions in our laboratories. It is a relatively rapid, inexpensive, maintains tactile sensitivity and allows multidirectional passes allowing a broader sampling of the lesions and immediate reporting where it is necessary. However, it has some limitations in the assessment of tumor invasion, tumor grade or receptor status. In this perspect, use of core needle biopsy has been shown to be an excellent tool while working with the tissue specimens because it permits the evaluation of both the architectural and cytological patterns and provides adequate material to perform diagnostic ancillary studies.

However, the performance of CNB has a few disadvantages. Missampling can occur, even with image guidance.12 Improper processing of small tissue fragments may lead to tissue distortion and challenge sample adequacy. These technical errors or missampling can lead to false negative results. The study showed that the sensitivity of FNAB was 85.71% in the diagnosis of breast cancer with a false negative rate of 14.28%. The specificity was 100%. This result is similar to other studies done by Mahmood H. Hasssan in Iraq (2014).17 Mohammed Bdour et al (2008) in Pakistan18 and Tiwarie M. in Nepal (2007).19

All four false negative cases in FNAB belonged to proliferative breast disease with atypia group. The false negative results of FNAB were mainly due to underestimation of cellular atypia.

In our study, CNB had a sensitivity of 92.85% and specificity of 100% in the diagnosis of breast cancer. The false negative rate was 7.14%. The results are comparable to others studies done by Mahmood H. Hasssan in Iraq(2014),17 Mohammed Bdour in Pakistan (2008),18 Karimian F. in Iran (2008),9 AD Baildum in UK (1989)19 and Stanley Minkowitz in USA (1986)20 which showed 95.0%, 90.0%, 98.07%, 95.0% and 89.0% sensitivity, respectively .

We found that, there were two false negative cases in CNB. Out of the two cases, one showed cystic change in ultrasonography. The repeated missing of the lesion in core biopsy may be due to this cystic change. . In this case as FNAB could cover much more area, it yielded adequate material from solid area.

Though accuracy of CNB is superior to FNAB,to minimize the limitation, the aim of pathologist should be to diagnose all the breast cancers confidently and not a single case should be missed. With this aim, the concurrent FNAB was done in this study and it showed sensitivity of 96.5%. In this present study, the number of cores taken from each patient was four or above. The combined approach of FNAB and CNB yielded better diagnostic accuracy than FNAB and CNB alone. The sensitivity of combined approach is 96.5%, where FNAB and CNB had 85.71% and 92.85% respectively. The specificity and positive predictive value of both FNAB and CNB are individually 100%, so the concurrent result is also the same. The 100% specificity of FNAB or CNB should not be generalized for all breast lesions in this study, because all the cases in the present study had breast lumps more than 2 cm in size and all were palpable.

The false negative rate in the combined approach was 3.57% which is lower than the rate in individual tests (14.28% in FNAB and 7.14% in CNB). A false negative diagnosis may delay the treatment of breast cancer. The concurrent examination of FNAB and CNB reduced the false negative rate by 50 %(7.14% to 3.57%), in comparison to CNB alone.

Conclusion
It is established that CNB is superior to FNAB regarding sensitivity and specificity. 9,10,11,13 In our country with poor resource setting, guided FNAB and CNB are not always possible. So to increase the sensitivity and to reduce the numbers of false negative cases of CNB, combined approach are helpful.

Reference
1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer, 2015;136(5):359-86.
2. Globocan, IARC 2012 IARC, 2012. Latest world cancer statistics Global cancer burden rises to 14.1 million new cases in 2012: Marked increase in breast cancers must be addressed. http://globocan.iarc.fr.
3. IARC, 2012. Latest world cancer statistics Global cancer burden rises to 14.1 million new cases in 2012: Marked increase in breast cancers must be addressed. http://globocan.iarc.fr.
4. Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ and Naghavi M, Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. The lancet, 2010; 378(9801):1461-84.
5. IARC, 2008. World cancer report 2008. International Agency for Research on Cancer. http://globocan.iarc.fr/
6. Cochrane RA, Singhal H, Monypenny IJ, Webster DJT, Lyons K and Mansel RE. Evaluation of general practitioner referrals to a specialist breast clinic according to the UK national guidelines. European Journal of Surgical Oncology (EJSO), 1997; 23(3):198-201.
7. Touhid Uddin Rupom, Tamanna Choudhury, Sultana Gulshana Banu. Study of Fine Needle Aspiration Cytology of Breast Lump:Correlation of Cytologically Malignant Cases with their Histological Findings. BSMMU J, 2011;4(2):60-64.
8. Yong WS, Chia KH, Poh WT and Wong CY. A comparison of trucut biopsy with fine needle aspiration cytology in the diagnosis of breast cancer. Singapore medical journal, 1999;40(9):587-89.
9. Karimian F, Aminian A, Hashemi E, Meysamie AP, Mirsharifi R and Alibakhshi A. Value of core needle biopsy as the first diagnostic procedure in the palpable breast masses. Shiraz E Medical Journal, 2008;9(4):188-192.
10. Pieter J, Westenend Ali R, Sever, Hannie JC., Beekman-de Volder et al. A comparison of Aspiration Cytology and Core Needle Biopsy in the evaluation of breast lesions. Cancer cytopathol 2001,93:146-150.
11. Liberman L, Dershaw DD, Rosen PP, Giess CS, Cohen MA, Abramson AF and Hann LE. Stereotaxic core biopsy of breast carcinoma: accuracy at predicting invasion. Radiology, 1995;194(2):379-81.
12. Yao-Lung Kuo, Tsai-Wang Chang. 2010, :Can concurrent core biopsy and fine needle aspiration biopsy improve the false negative rate of sonographically detectable breast lesions? BMC cancer, 2010;10(371):1-7.
13. Berner A, Davidson B, Sigstad E, Risberg B. Fine needle aspiration cytology vs. core biopsy in the diagnosis of breast lesions. Diagnostic cytopathology, 2003;; 29(6):344-8.
14. CIA. The world factbook; 2014.
15. NICRH. Cancer Registry Report National Institute of Cancer Research and Hospital 2005-07; 2009.
16. NIRCH. Cancer Registry Report National Institute of Cancer Research and Hospital 2008-2010; 2013.
17. Mahmood H. Hassan Ahmed R, HizamSafa, M. Al-Obaidi. The role of Tru-cut needle biopsy in the diagnosis of palpable breast masses. J Fac Med Baghdad, 2014;56: 292-295.
18. Mohammed Bdour, Saleh Hourani, WaseemMefleh, Ashraf Shabatat, Samer K.A. Radsheh, et al. Comparision between Fine needle aspiration cytology and Tru-cut biopsy in the diagnosis of breast cancer: Journal of surgery Pakistan international 2008: 13; 19-21.
19. Tiwari M. Role of fine needle aspiration cytology in diagnosis of breast lumps.Kathmundu University Medical Journal, 2007;5:215-17.
20. Baildam AD, Turnbull L, Howell A, Barnes DM and Sellwood RA, 1989. Extended role for needle biopsy in the management of carcinoma of the breast. British Journal of Surgery, 1989;76(6):553-58.
21. Stanley Minkowitz, Robert Moskowitz, Rene A., Khafif Martha N, Tru-cut needle biopsy of the breast and analysis of its specificity and sensitivity. Cancer 1986;15;320-323.

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Histomorphological Pattern of Radiologically Detected Osteolytic Lesions of Bone – A Study of Eighty Cases

Histomorphological Pattern of Radiologically Detected Osteolytic Lesions of Bone – A Study of Eighty Cases

*Runa NJ,1 Khan JB,2 Kaizer N,3 Dewan MR,4 Sharmin S,5 Ahmed SS,6 Hasan AM,7 Haque N,8 Hussain M9

 

Abstract:

To determine the spectrum of lesions and to correlate them with age, sex of patients and also anatomical site a histomorphological study of radiologically detected osteolytic lesions of bone was done. Eighty cases of radiologically detected lytic lesions of bone were studied over a period of two years from January 2014 to December 2015. Out of 80 cases of lytic lesion of bone, 18 cases were of inflammatory, 32 cases were of benign tumors, 20 cases of primary malignant bone tumors and 10 cases of metastatic lytic lesions were found. Most of the patients belonged to the middle age group with the age incidence varying with the type of lesion. Out of the 80 cases, 46 were males and 34 were females. Most of the bone diseases occurred more commonly around the knee joint and in the males within the age group of 11-20 years. Conclusion: Benign tumors are more common amongst all lytic lesions with giant cell tumor ranking first. Tuberculous osteomyelitis is more common in this study than pyogenic osteomyelitis. Osteosarcoma and secondary metastasis were more common among malignant bone tumors.

 [Journal of Histopathology and Cytopathology, 2017 Jul; 1 (2):83-90]

Key words: Bone, Osteolytic lesions, Histopathology, Radiology

 

 

 

  1. *Dr. Nusrat Jahan Runa, Assistant Professor, Department of Pathology, Dhaka Central International Medical College, Dhaka. njruna03@gmail.com
  2. Zubaida Bahroon Khan, Lecturer, Department of Pathology, Dhaka Medical College, Dhaka.
  3. Nahid Kaizer, Assistant Professor of Pathology, MH Samorita Medical College, Dhaka.
  4. Md. Rezaul Karim Dewan, Professor of Pathology, Dhaka Medical College, Dhaka.
  5. Shegufta Sharmin, Resident of Pathology, Dhaka Medical College, Dhaka.
  6. Syed Salauddin Ahmed, Associate Professor of Pathology, National Institute of Traumatic and Orthopedic Rehabilitation, Dhaka.
  7. AZ Mahmudul Hasan, Assistant Registrar, Department of Orthopedic Surgery, Dhaka Medical College Hospital, Dhaka
  8. Nazmul Haque, Associate Professor, Department of Pathology, Dhaka Medical College, Dhaka.
  9. Maleeha Hussain, Professor and Head, Department of Pathology, Dhaka Medical College, Dhaka.

 

*For correspondence

Introduction
 Lesion of bone is a frequently found radiological presentation of patients seen in orthopedic practice. Osteolytic lesions are evident radiologically where the destructive processes outstrip the laying down of new bone. The spectrum of pathological conditions causing osteolytic changes can be inflammatory to neoplastic lesions.1-3 Within benign lesions, the common differential diagnosis of lytic lesion includes simple bone cyst, aneurysmal bone cyst, osteochondroma (exostosis), enchondroma, non-ossifying fibroma and brown tumor of the bone. Among the malignant tumors the most common are Ewing sarcoma, osteosarcoma and multiple myeloma.4 Primary bone cancer is much rarer than bone metastasis.5,6 Bone is the third most common site of metastatic disease. Metastatic tumor that produces osteolytic lesions, detected in X-ray when the lesion is greater than 1.0 cm and 30% – 50% of the bone density have beendestroyed.4 As far as secondary tumors are concerned primary sites like lung, kidney, thyroid, breast, gastrointestinal and melanomas produce mainly lytic lesion while others elicit mixed lytic and sclerotic reaction.7 Carcinomas are much more likely to metastasize to bone than sarcomas.

It is difficult to determine radiologically with plain film imaging whether a lytic lesion is benign or malignant. It is important to remember, however that some benign processes such as osteomyelitis can mimic malignant tumors and some malignant lesions such as metastases or myeloma can mimic benign. The osteolytic lesions of tuberculosis may closely mimic those due to multiple myeloma or secondary malignant deposits.8 The histopathologist is the final person to guide an orthopedic surgeon for the treatment of patients with lytic lesions.

 Methods

This study was conducted at the Department of Pathology, Dhaka Medical College, Dhaka from January 2014 to December 2015. The criterion for the selection of the patient was radiologically detected osteolytic lesions of bone. Total 80 cases were selected. Detailed history was taken. Biopsy for histopathology was performed in all patients for the diagnosis of lytic lesions of bone. Biopsy was taken mainly by incision and excision method.

In laboratory soft tissue were fixed in 10 % formalin while for bone 3 to 5 mm thick sections were made and adequately fixed in 10% buffered formalin and then decalcification was achieved by placing the specimens in 5% nitric acid for 2 days. After that all tissue were processed by increasing concentrations of alcohol and paraffin blocks were prepared. Sectioned were stained with haematoxylin and eosin. After that all slides were examined under microscope, the final diagnosis was made into inflammatory, benign and malignant lesion accordingly.

 Results

In this study 18 cases of inflammatory, 32 cases of benign, 20 cases of primary malignant and 10 cases of secondary malignant lytic lesions were found out of total 80 cases. Benign neoplastic lesions of bone comprises the highest number (32 cases, Table I).

Table I: Distribution of frequency of study patients by histological diagnosis (n=80)

Lesions Number %
             Inflammatory 18 22.5
Neoplasm
Benign 32 22.5
Malignant primary 20 25.0
Malignant Secondary 10 12.5
Total 80 100%

From different age group, the most common age group was 11-20 years, in which total 32 cases of lytic lesion were found. Benign neoplastic lesions (18 cases) were most common in this group. In age group 21-40 years, total 25 cases of lytic lesion were found, of which benign lesion (12 cases) was most common. In age group of above 40 years, total 19 cases of lytic lesion were found, in which 12 malignant lesions were found. In below 10 year group only 4 cases were found, which were of malignant type (Table II).

Table II: Showing distribution of the study patients by age

 

 

Lesions

 Age groups (in years)
0-10 11-20 21-40 Above 40
Inflammatory Pyogenic Osteomyelitis 0 4 2 2
Tuberculous osteomyelitis 0 1 6 3
Neoplasm Benign 0 18 12 2
Malignant primary 4 9 3 4
Malignant secondary 0 0 2 8
         Total 4 32 25 19

 

Out of 80 patients, 46 (57.50%) were male and 34 (42.50%) were female. In male patients 19 cases were of benign neoplastic lesion, 8 cases were inflammatory lesion and 19 cases were malignant lesion. Where as in female, 13 cases were benign lesion, 10 cases were inflammatory lesion and 11 cases were malignant lesion. So, benign neoplastic lesions were the most common among both the sex (Table- III).

 

Table III: Types of leions with sex distribution of the study patients

 

               Lesions                    Male                Female
        Inflammatory Pyogenic osteomyelitis                     02 (2.5%)                   06 (7.5%)
Tuberculous osteomyelitis                     06 (7.5%)                   04 (5.0%)
 

 

Benign

 Giant cell tumor                     06 (7.5%)                   09 (11.25%)
Enchondroma                     04 (3.75%)                   01 (1.25%)
Simple bone cyst                     02 (2.5%)                   01 (1.25%)
Fibrous dysplasia                     02 (2.5%)                   01 (1.25%)
Aneurymal bone cyst                     03 (3.75%)                   01 (1.25%)
Hemangioma                     02 (1.25%)                   —
 

 

Malignant

      Primary
Osteosarcoma                     05 (6.25%)                  03 (3.75%)
Ewing sarcoma                     03 (3.75%)                  04 (5.0%)
Chondrosarcoma                     02 (2.5%)                  01 (1.25%)
Multiple myeloma                     01 (1.25%)                  —
          MFH                     01 (1.25%)                  —
    Secondary                     07 (8.75%)                 03 (3.75%)
                                           Total                    46 (57.50%)                 34 (42.50%)

Out of 80 cases, 24 patients had osteolytic lesion in the tibia. Among them 17 lesions were in the upper end. The second most common site of lesion was femur [Table IV].

 

Table IV: Distribution of the study patients according to anatomical site (n=80)

 

Diagnosis Femur
Upper		 Femur

Lower

 Tibia

Upper

 Tibia

Lower

 Fibula Humerus Radius Meta-carpal Phalanges Total
Tubercular osteomyelitis – 2 3 3 – – – 1 1 10
Pyogenic osteomyelitis – 2 2 2 – 1 1 – – 8
Giant cell tumour of bone – 6 3 2 1 1 1 – – 15
Enchondroma – – – – – – – 1 4 5
Hemangioma – – – – 1 1 – – – 2
Benign cystic lesion – – – – 1 1 1 – – 3
Aneurysmal bone cyst – – 1 1 – 2 – – – 4
Fibrous dysplasia – – 2 1 – – – – – 3
Ewing sarcoma 1 2 1 – 1 1 1 – – 7
Osteosarcoma 3 5 – – – – – – 8
Chondrosarcoma 1 – – – – 2 – – – 3
Multiple myeloma 1 – – – – – – – – 1
MFH – 1 – – – – – – 1
Metastatic adenocarcinoma – – 1 – 2 – – – 3
Metastatic squamous cell carcinoma 1 – – – – – – – – 1
Metastatic renal cell carcinoma 2 – – – – – – – – 2
Metastatic follicular variant of papillary carcinoma – – – – 2 1 – – 3
Metastatic Prostatic carcinoma 1 – – – – – – – – 1
Total 6 15 18 10 4 14 5 2 5 80

 

MFH – Malignant fibrous histiocytoma

Out of total 18 inflammatory lytic lesions, 8 cases were of pyogenic osteomyelitis and 10 cases were of tuberculous osteomyelitis (fig 1 and 2). So, tuberculous osteomyelitis was slightly more common than pyogenic osteomyelitis in inflammatory lytic lesions (Table V). From total 32 benign neoplastic lytic lesions, 15 cases were of giant cell tumor, 5 cases were of enchondroma. Giant cell tumour shows a higher incidence than other benign lytic lesion (Table VI).

Table V: Distribution of inflammatory lesion

 

Histologically diagnosed Inflammatory lesion   Number %
Pyogenic osteomyelitis          08 10
Tuberculous osteomyelitis          10 12.5

 

Table VI: Distribution of frequency of benign lesion by histopathological diagnosis

 

Histologically diagnosed Benign lesion No of cases %
   Giant cell tumor       15 18.75
   Enchondroma       05   6.25
   Simple bone cyst       03   3.75
   Fibrous dysplasia       03   3.75
  Aneurysmal bone cyst       04   5.0
  Hemangioma       02   2.5
            Total       32 40.0

While in 30 malignant lesions, 20 cases were primary and 10 cases were secondary malignant lesions. Primary malignant lesions were more common than metastatic lytic lesions in the present series  (Table VII).

 

Table VII: Distribution of frequency malignant lytic lesion by histological diagnosis

 

          Malignant lesion No of cases Percentage (%)
Primary Osteosarcoma 08 10
Ewing sarcoma 07 8.75
Chondrosarcoma 03 3.75
Multiple myeloma 01 1.25
Malignant fibrous histiocytoma 01 1.25
Secondary Metastatic follicular variant of papillary
carcinoma of thyroid in bone		 03 3.75
Metastatic adenocarcinoma of lung in bone 03 3.75
Metastatic renal cell carcinoma in bone 02 2.5
Metastatic adenocarcinoma of prostate in bone 01 1.25
Metastatic squamous cell carcinoma of lung in bone 01 1.25
                    Total 30 37.5

 

Osteosarcoma and metastatic tumours from lung were common in the primary and secondary malignant tumour groups (fig 3 and 4).

 

 

 

 

 

 

Fig 1. X-Ray photograph showing lytic area in the right upper tibia. Subsequent biopsy revealed tubercular osteomyelitis (case no 16)

 

 

 

 

 

 

 

Fig 2. Photomicrograph of the case in fig 1 showing epithelioid cells, lymphocytes, a giant cell and bone, consistent with tubercular osteomyelitis (ase No: 16, H & E stain ´200)

 

 

 

 

 

 

Fig 3. X-ray photograph showing lytic lesion with destruction of the overlying cortical bone with ‘sunburst’ appearance in lower end of femur (Case no. 42)

 

 

 

 

 

 

Fig 4. Photomicrograph showing Osteosarcoma (Case No: 42, H&E stain ´400)

 

 

 

 

 

Fig 5. X-ray photograph showing a lytic lesion in upper end of femur (Case no. 17)

 

 

 

 

 

 

Fig 6. Photomicrograph showing metastatic squamous cell carcinoma (Case No: 17, H&E stain´400)

Discussion

This study was carried out to determine various histomorphologic pattern of lytic lesions of bone. Of total 80 cases, 18 cases of inflammatory, 32 cases of benign neoplastic lesion, 20 cases of primary malignant bone tumors and  10 cases of secondary tumors were found. One of the important point to be considered is the age of the patient. Some of the lytic lesions are most probably confined to certain age groups such as: metastatic neuroblastoma in the infant and young child, metastasis and multiple myeloma in the middle-aged and elderly, lymphomas affecting only bone usually occur during adult life. Ewing sarcoma mostly affecting children and young teenagers while giant cell tumor in the young to middle aged adults.9,10 In our study, the most common age group of bone lesions was in second decade. Among 32 cases of benign osteolytic lesion, 18 cases were belonging to age group 11-20 years. In age group 21-40 years, total 25 cases of lytic lesion were found, in which benign (12 cases) were the commonest. In age group above 40
years, a total of 19 cases were found, in which malignant lesion was the most common diagnosis. In below 10 years age group only 4 cases were found to be Ewing’s sarcoma (Table II).In our study, osteomyelitis was found in all age groups above ten years. The diagnosis of chronic recurrent multifocal osteomyelitis is essentially one of exclusion. Infective osteomyelitis and malignancy are the main differential diagnoses.11 The osteolytic lesions of tuberculosis at multiple sites need to be differentiated from multiple myeloma, secondary metastasis and bacterial osteomyelitis.

 

In this study, more than half (57.50%) of the patients were male and  42.50% were female; male to female ratio was 1.4:1, which indicates that osteolytic lesion are predominant in male subjects, which closely agrees with available literature.12,13

 

The bone around the knee joint that is, the distal end of the femur and the proximal end of the tibia, were found to be the commonest sites for osteolytic lesions comprising 38.7% in this series. The lower end of the femur was affected in 17.5% of cases and the upper end of the tibia in 21.2% of cases that has matched with other literature.14

In our study, out of 80 cases of lytic bone lesions, most common were benign neoplastic lesions making 32 cases. Among them, 15 cases were giant cell tumour of bone having female predominance (Table III).  In present study, the most common site of giant cell tumor was lower end of femur and upper end of tibia [Table IV]. Characteristic radiologic findings demonstrate the lesion is most often eccentrically placed lytic lesion with no periosteal reaction to the long axis of the bone. Total 5 cases of enchondroma has been reported with an incidence of 6.26% of total cases and an incidence of 15% of all benign tumors, mostly seen in patients younger than age 20 years (3/5 cases) in the current study.

Osteosarcoma is the most common primary bone tumor in young and adolescents. It occurs most frequently in the second decade, occurring in the metaphysis, mostly in lower end of femur followed by upper end of tibia.15,16 In the present study, we observed a similar finding. Ewing sarcoma is a highly malignant, undifferentiated, peripheral primitive neuro-ectodermal tumor occurring most commonly at the diaphysis of long bones, in the 0-20 years age group, with female predominance.15,16 Our study has matched with the available literature. Pain, pathological fractures and hypercalcemia are the major sources of morbidity with bone metastasis. Pain is the most common symptom found in 70% patients with bone metastases.17 Pain is caused by stretching of the periosteum by the tumor as well as nerve stimulation in the endosteum. Pathological fractures are most common in breast cancer due to the lytic nature of the lesions.18 In our study ten cases of metastatic lytic lesion were found, which included Follicular Variant Of Papillary Carcinoma of thyroid metastasize to upper end of the humerus, Carcinoma of kidney with metastasis to upper end of femur, Squamous Cell Carcinoma and adenocarcinoma of Lung metastasize to upper end of femur and humerus.  In case of follicular variant of papillary carcinoma of thyroid lytic lesion over humerus was the first noticeable sign and even the patient & clinician were unaware of thyroid malignancy.

Among the various diagnoses, benign tumors form the largest group (40%) of patients presenting with a lytic lesion on radiological findings. There is a male preponderance with 57.5% of the patients being males. Also, majority of the patients fall into the second decade with 40% of the patients in the age group of 11- 20 years. The common diagnoses among the benign lesions were giant cell tumors, while there were a slightly higher number of cases of tuberculous osteomyelitis as against bacterial osteomyelitis in the inflammatory conditions. Among the malignant lesions, primary tumors were a commoner diagnosis as opposed to the secondaries. The metastatic tumors tend to occur more commonly in the elderly population. The commonest primary malignant lesion that showed up was osteosarcoma. Overall, giant cell tumor is the commonest diagnosis presenting with a lytic lesion on radiological finding. Occult malignancy can be presented as lytic lesion of bone in the form of secondary. All lyticlesions may have osteoclastic giant cells and they should not be misinterpreted as Giant cell tumor.

 Conclusion

Lytic lesion of bone is a very used to radiological finding for orthopedic surgeon in many patients. Even an orthopedic surgeon and radiologist together won’t be able to reach to the precise conclusion and further treatment. Histopathology is the gold standard for the precise diagnosis from a very large number of conditions leading to lytic lesion.

 References

  1. Bommer KK, Ramzy I & Mody D. Fine needle aspiration biopsy in the diagnosis and management of bone lesions: A study of 450 cases. Cancer, 1997; 81:148-156.
  2. Kreicbergs A, Henrik C, Bauer F, Brosjo O, Lindholm J & Skoog L. Cytological Diagnosis of Bone Tumors. The Journal of Bone and Joint Surgery, 1996; 78(2):258-263.
  3. Ackerman LV & Del Regato JA 1954, Cancer: Diagnosis, Treatment, and prognosis. 2nd edition, Louis, Mosby, p. 1028.
  4. Popat V, Sata V, Vora D, Bhanvadia V, Shah M & Kanara L. Role of Histopathology In Lytic Lesions of Bone. The Internet Journal of Orothopedic surgery, 2010; 19(1):1-7.
  5. Bhattacharya P, Chowdhury AR, Bhaskar M & Biswanath P. Clinico pathological correlation of Primary Malignant Bone Tumors. Open Journal of Orthopedics, 2015; 5:100-108.
  6. Wedin R, Henrik C, Bauer F, Skoog L, Soderlund V & Tani E. Cytological diagnosis of skeletal lesions. The Journal of Bone and Joint Surgery, 2000; 82(5):673-678.
  7. Adler O & Rosenberger A. Fine Needle Aspiration Biopsy of Osteolytic Metastatic Lesions. AJR, 1979; 33:15-18.
  8. Chawla KP, Pandit, AA, Jaiswal PK & Ahuja A. 1990, ‘Ostearticular tuberculosis with involvement of multiple sites (a case report)’, J Postgrad Med,1990;36:171-72.
  9. Manaster BJ. Tumors. In: Manaster BJ, Disler DG, May DA, eds. Musculoskeletal
    Imaging: The Requisites.2nd ed. St. Louis, MO: Mosby; 2002:1-104.
  10. Resnick D. Tumors and tumor-like lesions of bone: Imaging and pathology of specific lesions. In: Resnick D, ed. Bone and Joint Imaging.2nd ed. Philadelphia, PA: W.B. Saunders; 1996:991-1063.
  11. L P Robertson, P Hickling. Chronic recurrent multifocal osteomyelitis is a differential diagnosis of juvenile idiopathic arthritis. Ann Rheum Dis 2001; 60:828-831.
  12. Chakrabarti S, Datta AS & Hira M. Critical Evaluation of Fine Needle Aspiration Cytology as a Diagnostic Tecnique in Bone Tumors and Tumor-like lesions. Asian Pac J Cancer Prev, 2012; 13: 3031-4
  13. Wahane R. Fine Needle Aspiration Cytology of Bone Tumors. ACTA, 2007; 51(%):711-720.
  14. Mahajan S, Saoji AA & Agarwal A. Utility of Fine Needle Aspiration Cytology in Diagnosis Bone Tumors. Cancer Transl Med, 2015; 1(5):166-169.
  15. Bone RJ. Ackerman’s Surgical Pathology. In: Rosai J, editor. St. Louis: Mosby; 1996. pp. 1917–2020.
  16. Rosenberg AE. Bones, joints and soft tissue tumors. In: Kumar V, Abbas AK, Fausto N, Aster JC, editors. Robbins and cotran; Pathologic Basis of disease. 8th ed. Gurgaon: Elsevier Reed Elsevier India private limited; 2010. pp. 1205–56.
  17. Vinholes J et al., Effects of Bone Metastases on Bone Metabolism: Implications for Diagnosis, Imaging and Assessment of Response to Cancer Treatment, Cancer Treatment Reviews, 1996; 22:289-331.
  18. Stoll B and Parbhoo S, Bone Metastasis, Raven Press Books, Ltd.: New York NY, 1983, p. 14. 3 Vinholes, et al. 1/14/98 8:46 AM 1.

 

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Role of Cytopathology in Eyelid Growth with Histopathological Correlation

Role of Cytopathology in Eyelid Growth with Histopathological Correlation

*Paul R,1 Kundu UK,2 Kabir E,3 Islam MN4

Abstract
The purpose of this study was to evaluate diagnostic accuracy of cytopathology in  different eyelid lesions using fine needle aspiration cytology (FNAC) & scrape cytology with histopathological correlation. Accurate diagnosis of eyelid tumors is necessary to guide ophthalmologists to design optimal management. Fine needle aspiration from 85 eyelid growth and histopathological correlation were studied. Immunohistochemical analysis were done in few cases.  A majority of the patients (43 out of 85) were in the 26-50 age group (53.49% male vs 46.51% female). Mean age was 43.22±17.42 (range 19 – 90 years) years. Of the malignant lesions, basal cell carcinoma were highest (12 in number, 36.36%) followed by sebaceous gland carcinoma and squamous cell carcinoma. Less common  malignant tumor were Non-Hodgkin’s lymphoma. Among benign neoplastic lesions, nevi were most common (14 in number, 43.75%) followed by haemangioma and squamous papilloma. Other less common  benign tumors were fibroepithelial polyp, adenoma, lipoma and neurofibroma. Most common benign cystic lesions of eyelid are cyst (10 in number, 50%) of moll/Hydrocystoma/Sudoriferous cyst, followed by Dermoid cyst, Epidermal inclusion cyst and Sebaceous cyst. Present study revealed that accuracy of cytopathological diagnosis of malignant eyelid growths were 97.65%. Cytopathology had a high diagnostic accuracy rate. Aspiration cytology was cost effective and offers rapid diagnosis with minimal discomfort to the patient.

[Journal of Histopathology and Cytopathology, 2018 Jul; 2 (2):134-144]

Key wards: Eye lid growth, Cytopathology, Histopathology, Correlation

Introduction
Eyelid growth is a common cause to be presented to ophthalmologists1 and many of them can be treated as day care service. At the same time some of the tumors demand emergency surgical intervention and thus early referral.2 Introduction of cytopathology prior to excision biopsy would contribute to early diagnosis and management plan.3 Pathologic conditions affecting the eyelid may be inflammatory or neoplastic. Neoplastic lesion may be benign or malignant.1 It becomes difficult to decide clinically either it is a true neoplasm or an inflammatory lesion. In all such cases, cytopathology (FNAC / scrape cytology) proved to be very useful in quickly determining the nature of the lesion and also deciding the mode of treatment.4 FNAC has a high diagnostic accuracy rate, if the aspirated material is sufficient for microscopical examination and if it is properly interpreted.5 Aspiration cytology is also cost effective and offers rapid diagnosis, with minimal discomfort to the patient..6

  1. *Dr. Rita Paul, Assistant Professor, Department of Pathology, Ibrahim Medical College, Dhaka. ritapaul16@gmail.com
  2. Utpal Kumar Kundu, Assistant Professor (Eye), Mugda Medical College, Dhaka.
  3. Professor Enamul Kabir, Professor, Department of Pathology, Sir Salimullah Medical College, Dhaka.
  4. Professor Md. Nasimul Islam, Professor and Head, Department of Pathology, Sir Salimullah Medical College, Dhaka.

*For correspondence

Method

This was a cross sectional study conducted at the Departmentof Pathology of Sir Salimullah Medical College, Dhaka and National Institute of Ophthalmology and Hospital, Dhaka, Bangladesh from January 2012 to December 2013. 85 adult patients with eye lid growths of both sexes were recruited. Purposive sampling technique was used. FNAC was done using 22 Guage needle without anaesthesia and smears were stained with Papanicolaou’s stain. Biopsy was taken by clinician and diagnosis was confirmed by histopathological examination. Inclusion criteria were adult patients with eyelid growth. Exclusion criteria included patients who were clinically diagnosed to  have inflammatory eyelid lesions, patients belonging to less than 18 years of age, and very tiny growth <0.5cm in diameter.

FNA Features of different Eye-lid lesions

Smears from nevus showed single and small clusters of cells with rounded or oval nuclei and indistinct cytoplasm.7 Smears from haemangioma showed only blood, with a few cases showing an occasional cluster of endothelial cells. Smears from squamous papilloma showed degenerated squamous epithelial cells along with mature superficial squamous cells. Smears from neurofibroma showed cohesive spindle-shaped cells within fibrillary mesenchymal background material. Smears from hidrocystoma / Sudoriferous cyst / Cyst of Moll showed foamy macrophages in the background of proteinecious material. Smears from epidermal inclusion cyst showed high cellularity with numerous nucleated squamous cells and anucleated squames in a background of keratinous debris.8 Smears from dermoid Cyst showed anucleated and nucleated squamous epithelium and keratin debris.9 Smears from chalazion showed a polymorphic picture with neutrophils, plasma cells and macrophages. The granulomas are more of histiocytic cells with abundant vacuolated cytoplasm; the backround is generally dirty with nuclear debris and fat spaces.10 Smears from molluscum contagiosum showed Molluscum bodies, in the enlarged superficial cells of the epidermis.11 Molluscum bodies, also called Henderson-Patterson bodies, were large, round cytoplasmic inclusions (within the enlarged cells of epidermis), which push the nucleus to the periphery.12  Smears from Rhinosporidiosis showed many scattered basophilic rhinosporidial endospores and rhinosporidial spores in a background of amorphous eosinophilic material.13 Smears from basal cell carcinoma showed tightly cohesive small clusters of uniform hyper­chromatic basaloid cells with high nuclear-cytoplasmic ratio and absence of cytoplasmic vacuolation. Peripheral palisading of nuclei may be evident in some clusters. Squamous, sebaceous and adenoid differentiation may be seen and pigmented variant may be seen.14 Smears from sebaceous gland carcinoma showed large pale cells and vacuolated cytoplasm however another type is poorly differentiated cells with dark and irregular nuclei. The smears of squamous cell carcinoma showed markedly enlarged hyper-chromatic nuclei of variable size and keratinization.10 Smear from cutaneous melanoma showed atypical dispersed population of cells with abundant cytoplasm, eccentric uniform hyperchromatic nuclei, internuclear inclusions in the background of melanin pigment.15 In Non-Hodgkin’s lymphoma, cytology smears showed a monotonous population of lymphocytes with round nuclei having coarse granular chromatin. Histopathological examination of biopsied tissue confirmed the diagnosis16 and in a few cases by the help of immuno-histochemical analysis using specific antibodies.

Results

Age distribution of the patients presented with eyelid growths showed almost half (50.59%) of the patients comprised of middle age group (26-50 years) with a little more than one-fourth (30.59%) above 50 years of age. Gender distribution of the patients presented with eyelid growths showed slightly male preponderance (50.59%) and female constituted 49.41%. Mean age was 43.22±17.42 (range 19 – 90 years) years.

Among benign neoplastic lesions, nevus was most common, followed by vascular lesion and squamous papilloma. Others were adenoma, lipoma and hamartoma. Correlation with cytopathological and histopathological examination were done. Cytopathologically diagnosed fourteen (14) cases of Nevus were confirmed by histopathological examination. Cytologically diagnosed Vascular Lesion in eight (8) cases were histologically confirmed in seven (7). The other case was histologically diagnosed as Hamartoma. Five (5) cases of squamous papilloma corresponded cytologically and histologically. One (1) case of cytologically diagnosed lipoma was also confirmed histologically. Both (2) cases of histologically diagnosed Fibroepithelial Polyp were cytologically diagnosed as benign Mesenchymal lesion. One (1) case of histologically diagnosed Neurofibroma was cytologically diagnosed as a malignant peripheral nerve sheeth tumor (False positive; Table III).

Cytologically diagnosed Cyst of Moll/ Hydrocystoma/ Sudoriferous Cyst corresponded histologically in all ten (10) cases. Five (5) cases of cytologically diagnosed Dermoid Cyst were confirmed histologically. Cytologically diagnosed three (3) cases of Epidermal Inclusion Cyst corresponded histologically. Two (2) cases of cytologically diagnosed Sebaceous Cyst were later on confirmed histologically (Table IV). Among the malignant lesions encountered during the present study, Basal cell carcinoma was the most common malignancy, followed by Sebaceous Gland Carcinoma and Squamous Cell Carcinoma. Non-Hodgkin’s lymphoma (NHL) was found to be less common. Cytological diagnosis was confirmed by histopathological examination in the present study. Eleven (11) cases of cytologically diagnosed Basal Cell Carcinoma were confirmed histologically. One (1) case of cytologically diagnosed Nevus (False negative) was histologically diagnosed as Basal Cell Carcinoma. Sebaceous Gland Carcinoma corresponded cytologically and histologically in all nine (9) cases. Nine (9) cases of cytologically diagnosed Squamous Cell Carcinoma were also confirmed histologically. Lymphoma corresponded cytologically and histologically in both (2) cases, which was later on confirmed by immuno-histochemical study as Non-Hodgkin’s lymphoma of ‘B’ cell origin. One (1) case of cytologically diagnosed Small Cell Tumor was confirmed histologically (Table V).

Comparison of diagnosis between cytopathology with histopathology among the malignant eyelid growths

Among 85 eyelid growths, 32 cases were cytopathologically and histopathologically true positive for malignant lesions. The comparison between cytopathology and histopathology were statistically highly significant (p < 0.0001; Table VI). Out of 85 (100%) patients of eyelid growths 32 (37.64%) were positive for malignancy, 51(60.00%) were negative for malignancy, 01(1.18%) was false positive(1.18%) and 1 (1.18%) was false negative (Table VII). The validity of cytopathology to diagnose malignant eyelid growths, Sensitivity, Specificity, PPV, NPV and Accuracy were 96.97%, 98.08%, 96.97%, 98.08% and 97.65% respectively (Table VIII).

Out of a total 33 histologically confirmed cases of malignant tumor, thirteen (13) cases were ulcerated. From these ulcerated lesions, samples were collected by scraping. Out of these, nine (9) cases were Basal Cell Carcinoma, three (3) cases were Squamous Cell Carcinoma and one (1) case was found to be Sebaceous (Meibomian) Gland Carcinoma.

Table I: Distribution of different eyelid lesions with Cytological and Histological Diagnosis (n=85)

Eyelid Growth Cytological Diagnosis Histological Diagnosis
Nevus 15 (17.65) 14 (16.47)
Vascular Lesion 8 (9.41) 7 (8.23)
Squamous Papilloma 5 (5.88) 5 (5.88)
Adenoma 1 (1.18) 1 (1.18)
Lipoma 1 (1.18) 1 (1.18)
Hamartoma 0 (0.00) 1 (1.18)
Benign Mesenchymal Lesion 2 (2.36) 0 (0.00)
Fibroepithelial Polyp 0 (0.00) 2 (2.36)
Neurofibroma 0 (0.00) 1 (1.18)
Cyst Of Moll/ Hydrocystoma/ Sudoriferous Cyst 10 (11.76) 10 (11.76)
Dermoid Cyst 5 (5.88) 5 (5.88)
Epidermal Inclusion Cyst 3 (3.52) 3 (3.52)
Sebaceous Cyst 2 (2.36) 2 (2.36)
Basal Cell Carcinoma 11 (12.94) 12 (14.12)
Sebaceous Gland Carcinoma 9 (10.58) 9 (10.58)
Squamous Cell Carcinoma 9 (10.58) 9 (10.58)
Lymphoma 2 (2.36) 2 (2.36)
Small Cell Tumor 1 (1.18) 1 (1.18)
Malignant Peripheral Nerve Sheath Tumor (MPNST) 1(1.18) 0 (0.00)
Total 85 (100) 85 (100)

Table II: Age distribution of the patients of all types of eyelid lesions with percentage

(n=85)

Age Frequency Percentage
Up to 25 16 18.82
26 – 50 43 50.59
Above 50 26 30.59
Total 85 100.0

Table III: Distribution of different benign neoplastic eyelid growths

Final Histological Diagnosis  

Cytological Diagnosis
Total (Final Histology) Nevus Haemangioma Squamous Papilloma Adenoma Lipoma Hamartoma Benign Mesenchymal Lesion Fibroepithelial Polyp Neurofibroma

 

 MPNST
Nevus 14 14 0 0 0 0 0 0 0 0 0
Haemangioma 7 0 7 0 0 0 0 0 0 0 0
Squamous Papilloma 5 0 0 5 0 0 0 0 0 0 0
Adenoma 1 0 0 0 1 0 0 0 0 0 0
Lipoma 1 0 0 0 0 1 0 0 0 0 0
Hamartoma 1 0 1 0 0 0 0 0 0 0 0
Fibroepithelial Polyp

 

 2 0 0 0 0 0 0 2 0 0 0
Neurofibroma 1 0 0 0 0 0 0 0 0 0 1
Total = 32 Total= 32

Table IV: Distribution of different benign cystic eyelid lesions

Final Histological

Diagnosis

 Cytological Diagnosis
Total Final Histology Cyst of Moll Dermoid Cyst Epidermal Inclusion Cyst Sebaceous Cyst
Cyst of Moll 10 10 0 0 0
Dermoid Cyst

 

 5 0 5 0 0
Epidermal Inclusion Cyst

 

 3 0 0 3 0
Sebaceous Cyst 2 0 0 0 2
Tolal 20 Total = 20

 

Table V: Distribution of malignant eyelid lesions (total of 85 cases each)

Final

Histological

Diagnosis

 Cytological Diagnosis
Total Final Histology Basal Cell Carcinoma Sebaceous Gland Carcinoma Squamous Cell Carcinoma Lymphoma Small Cell Tumor Nevus
Basal Cell Carcinoma

 

 12 11 0 0 0 0 1
Sebaceous Gland Carcinoma

 

 9 0 9 0 0 0 0
Squamous Cell Carcinoma

 

 9 0 0 9 0 0 0
Lymphoma 2 0 0 0 2 0 0
Small Cell Tumor 1 0 0 0 0 1 0
Total = 33 Total = 33

 

TableVI: Comparison of diagnosis between Cytopathology with Histopathology among the Malignant Eyelid Growths

 

Cytopathology Histopathology Total
Malignant Benign
Malignant 32 (37.64) 1 (1.18%) 33 (100.0%)
Benign 1 (1.18%)  51 (60.00%) 52 (100.0%)
Total 33 (38.82%)   52 (61.18%)  85 (100.0%)

* p value < 0.0001

 

Table VII: Assessment of diagnostic accuracy of cytopathology of eyelid growths

 

Cytopathological Diagnosis No. of cases Percentage
Positive for Malignancy 32 37.64%
Negative for Malignancy 51 60.00%
False Positive 1 1.18%
False Negative 1 1.18%
Total 85 100%

 

Table VIII: Cytopathological validity of different malignant eyelid growths

Sensitivity Specificity Positive Predictive Negative Predictive Value Accuracy
96.97% 98.08% 96.97% 98.08% 97.65%

Figure 1. (A) Case 1. Basal cell carcinoma, (B) Photomicrograph of cytology smear of basal cell carcinoma showing tightly cohesive small clusters of uniform hyper­chromatic basaloid cells (Pap’s, x200), (C) Photomicrograph of Basal cell carcinoma showing atypical basaloid cell with retraction artifact (H&E, x400)

Figure 2. (A) Case 2.  Squamous cell carcinoma, (B) Photomicrograph of cytology smear of Squamous cell carcinoma showing enlarged hyper-chromatic nuclei of variable size and keratinization (Pap’s, x400), (C) Photomicrograph of Squamous cell carcinoma (Grade-I) showing atypical squamous cell invading deeply into the dermis. It also shows squamous pearl. (H&E, x200)

Figure 3. (A) Case 3. Sebaceous (meibomian) gland carcinoma, (B) Photomicrograph of cytology smear of sebaceous (meibomian) gland carcinoma showing atypical tumor cells arranged in clusters and singly with foamy eosinophilic cytoplasm (Pap’s, x400), (C) Photomicrograph of sebaceous (meibomian) gland carcinoma showing atypical tumor cells and necrosis (H&E, X200).

Figure 4. A. Case 4. Non-Hodgkin’s Lymphoma, B. Photomicrograph of cytology smear of Non-Hodgkin’s Lymphoma showing monomorphous population of atypical lymphoid cells, scanty cytoplasm with clumped chromatin. (Pap’s x200), C. Photomicrograph of Non-Hodgkin’s Lymphoma showing  hypercellular proliferations. Most of the tumor cells are monotonous in appearance, having large nuclei with condensed chromatin. (H&E, x400), D. Photomicrograph of IHC study showing lymphoid cells with positive staining for LCA. (IHC, x400), E. Photomicrograph of IHC study showing scattered lymphoid cells with positive staining for CD3. (IHC, x400), F. Photomicrograph of IHC study showing  majority of atypical  lymphoid cells with positive staining for CD20 (IHC, x400) Conclusion: Immunostaining results favor the diagnosis of Non-Hodgkin’s Lymphoma of “ B” cell origin.

Figure 5. A. Case 5.  Hydrocystoma. B. Photomicrograph of cytology smear of benign cystic lesion showing foamy macrophages in the background of proteinecious material (Pap’s, x200), C. Photomicrograph of hydrocystoma showing cyst wall lined by a double layer of columnar cells with eosinophilic cytoplasm and prominent papillary projections. (H&E x400)

Figure 6. A. Case. Nevus, B. Photomicrograph of cytology smear of nevus showing single and small clusters cells with rounded or oval nuclei and indistinct cytoplasm (Pap’s x200). C. Photomicrograph of nevus showing nests of round cells in the underlining dermis. (H&E, x200)

Discussion

The present study was conducted with an aim to assess the cytopathological and histopathological correlation of different types of eyelid growths. It was a hospital based cross sectional study which enrolled 85 clinically suspected eyelid growths. Out of them 52 (61.18%) were benign and 33 (38.82%) were malignant. A recent study by Mondal and Dutta,8 Fine needle aspirates from 80 eyelid swellings were studied.  Forty eight cases of benign and 32 cases of malignant lesions were diagnosed by FNAC.

Mean age in the present study was 43.22 years (SD ±17.42) (range 19 – 90 years). Pombejara et al.17 reported mean age of presentation 52.4 years ± SD 21.8 years in Thailand. Most benign growths were within the age group 26-50 years and malignant eyelid lesions were in patients above 51 years of age.Mondal and Dutta8 studied 80 eyelid lesions by FNAC, in which 32 cases were malignant. In that study most common malignant lesion was basal cell carcinoma (12 cases, 15%) followed by sebaceous gland carcinoma (nine cases, 11.25%) and squamous cell carcinoma (eight cases, 10%). In the present study, malignancy were 38.82% (33 out of 85), and the most frequent malignant tumor was basal cell carcinoma (12 out of 33, 36.37%) followed by sebaceous gland carcinoma (09, 27.27%), squamous cell carcinoma (09, 27.27%), Non-Hodgkin’s lymphoma (2, 6.06%) and small cell carcinoma (1,3.03%).

Among benign lesions, in the present study, nevus was most common in 14 cases (43.75%), followed by haemangioma 7 cases (21.88%) and squamous papilloma in 5 cases (15.64%). Other less common lesions were fibroepithelial polyp, adenoma, lipoma, neurofibroma and hamartoma. In the present study, among benign cystic lesions (20 cases) of eyelid, sudoriferous cyst was most common in 10 cases (50.00%) followed by dermoid cyst in 5 cases (25.00%), epidermal inclusion cysts in 3 cases (15.00%), and sebaceous cysts in 2 cases (10.00%). In a recent study by Toshida et al.,18 the most frequent diagnosis among 106 benign lesions were nevus in 23 cases (21.7%). The second common was squamous cell papilloma in 18 cases (17.0%), followed by seborrheic keratosis in 14 cases (13.2%). Less common causes were epidermal cyst in 10 cases (9.4%) and dermoid cyst in 7 cases (6.6%).

 

Ulcerated skin of eye-lid can be scraped safely and it is recommended to combine FNAC with scrape cytology for any ulcerated lesions of eyelid skin and conjunctiva (Rai, 2007). In the present study, out of a total 33 histologically confirmed malignant tumors, thirteen (13) ulcerated cases were taken by scraping. Of these, nine (09) were Basal Cell Carcinoma, three (3) were Squamous Cell Carcinoma and one (1) was found to be Sebaceous (Meibomian) Gland Carcinoma.

In recent studies by Mondal and Dutta 8 and  Arora et al.5 showed accuracy of cytological diagnosis of eyelid growths were 83.87% and 89.4% respectively. In the present study, accuracy of cytological diagnosis of malignant eyelid growths was 97.65%. These comparisons are clearly emphasizing need for cytopathology and histopathology of all surgically removed specimens.19,20 The present study also compared cytopathological and histopathological diagnosis of all specimens.When comparing cytopathology with histopathology of the clinically suspected malignant eyelid growths, the comparison between cytopathology and histopathology was statistically highly significant (p<0.0001).In the present study, Sensitivity, Specificity and Accuracy of cytopathology to diagnose malignant eyelid growths were 96.97%, 98.08% and 97.65% respectively.

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