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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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jhc-2019-jul-v-3-n-2-analysis-ray-s

Analysis of the Diagnostic Value of Cytological Smear Method Versus Cell Block Method in Pleural Effusion Fluid of Suspected Lung Cancer Patients

 *Ray S,1 Zinnah SA,2 Awal N,3 Hassan I,4 Dewan RK,5 Jeba R,6 Hussain M7

 *Dr. Subrata Ray, Assistant Professor, Department of Pathology, Jashore Medical College. subrataray29@gmail.com

  1. Shahed Ali Zinnah, Associate Professor, Department of Pathology, Dhaka Medical College.
  2. Dr . Naila Awal , Assistant Professor, Department of Pathology, Greenlife Medical College.
  3. Imran Hassan, Assistant Professor(CC), Department of Pathology, (Col) Malek Medical College, Manikgonj.
  4. Rezaul Karim Dewan, Professor and Head, Department of Pathology, Dhaka Medical College
  5. Dr . Ruksana Jeba, Associate Professor, Department of Pathology, Dhaka Medical College.
  6. Dr Maleeha Hussain, Professor, OSD, DGHS.

 *For correspondence

 Abstract

Background: For any kind of lungs pathology accompanying pleural effusion pleural biopsy guided with thoracoscopy, of course, may provide important results. Since biopsy is an invasive procedure, the priority is to do,  a cytological examination of pleural fluid obtained with thoracentesis, which  is very crucial for the disease staging and treatment strategy. In this purpose, even though conventional cytosmear techniques have been used generally till this day, cell block technique is also being used recently.
Methods: In our study, 100 pleural effusion fluid sample were included. All the fluid specimen was subjected to cytosmear (CS) and cytoblock (CB).
Results: By using conventional CS method, 85 fluid specimens were diagnosed as negative for malignancy (85%), 5 cases were diagnosed as positive for malignancy (5%) and the remaining 10 cases were diagnosed as suspicious for malignancy (10%). On the contrary by using CB, complimented by combined PAS-Alcian blue stain where required, 90 cases were diagnosed as negative for malignancy (90%) and 10 cases were diagnosed as positive for malignancy. Thus, by the CB method, an additional 5 more cases were diagnosed as positive for malignancy, that is, 5% more diagnostic yield for malignancy.
 Conclusion: CB technique could be considered as a useful adjunct in evaluating malignant cells in MPE for a final cytodiagnosis, along with the routine CS method.

[Journal of Histopathology and Cytopathology, 2019 Jul; 3 (2):99-106]

 Key Wards: Cell block , Pleural effusion , Lung cancer 

Introduction

Development of pleural effusion is a common complication in patients with lung cancer either primary or secondary. There may be presence of neoplastic cells in the pleural effusion which is called malignant effusion (MPE) or it may be a para-malignant effusion, which is  pleural effusion with absence of cytological evidence of tumor cells in a known setting of malignancy. In UK, 40000 people per year are affected by MPE and it is estimated that up to 50% of the patients  with metastatic malignancy  develop a pleural effusion – either at the time of diagnosis or during the evaluation of cancer.1,2,3  The common etiologies of MPE are lung cancer, breast cancer, lymphoma, ovarian cancer and gastric cancer in order of decreasing percentage.

For any kind of lung lesion accompanying pleural effusion, pleural biopsy guided with thoracoscopy, of course, may provide important results, but has the risk of being an invasive procedure and it depends on the experience and efficiency of the surgeon. So, in a country with poor resource settings, the priority should be a cytologic examination of pleural fluid obtained by thoracentesis. It not only helps in diagnosis but also can help in disease staging and treatment strategy.4

In conventional cytological smear (CS), discrimination of the reactive mesothelial cells and malignant cells is the most important diagnostic problem. Distinguishing benign from malignant cellular changes may require meticulous screening, careful scrutiny of cellular features and an understanding of the range of reactive changes. Since the introduction of cell block (CB) technique by Bahernburg nearly a century ago,  it has been used routinely for processing fluid.5 CB has the advantage of recognition of the histological pattern of disease, possibility of study multiple sections by routine staining, special staining and immunological procedures.

In this study, we assessed the utility of CB and CS techniques and evaluated whether the CB, when it complements conventional CS, can increase the diagnostic yield.

Methods

This is an analytic study, carried out at the Department of Pathology, Dhaka Medical College, Dhaka from  July 2015 to  June 2017, over 100 pleural effusion fluid specimen of suspected lung cancer patients.

 10 ml of fresh pleural fluid sample was obtained by thoracentesis from each patient during clinical evaluation. Each sample was divided into two equal parts.

For conventional smear technique, 5 ml fluid specimen was centrifuged at 2500 rmp for 10 min. A minimum two smears were prepared from the sediment. They were immediately fixed in 95% alcohol and stained with the Papanicoloau and Haematoxylin- Eosin stain.

 

For cell block, we used AAF (95% ethyl alcohol + acetic acid + 10% formalin). After centrifuge at 2500 rmp for 10 min, cell sediments were mixed with thrice the volume of AAF fixative and again centrifuged at 2000 rmp for 10 min. The centrifuged tube was aside undisturbed for six hours. The cell button was scraped out and wrapped in filter paper and processed in automatic tissue processor for routine histopathological sections. The cell blocks were embedded in paraffin and sectioned at 4 micro meter thickness.

 The samples were studied in detail taking into account the available clinical and radiological data and various investigation reports. Each individual slide was objectively analyzed for cellularity, background blood, nuclear and cytoplasmic details and arrangement of the cells using the point scoring system described by Mair et al., (1989).6 All these criteria were put together and each cases was categorized as Benign, Suspicious for malignancy and Malignant effusion. Special stain of cell blocks, including combined PAS-Alcian blue stain was done whenever needed. In cases, where pleural biopsy of the same patients was available, used to confirm the diagnosis.

Results

In our study, 100 pleural effusion fluid sample were included. The age-rang from 26 to 82 years. Most of the patients are between the age group 51-60 years (30%). The male female ratio was 1.8:1. All the fluid specimen was subjected to CS and CB. By using connectional CS method, 85 fluid specimens were diagnosed as negative for malignancy (85%), 5 causes were diagnosed as positive for malignancy (5%) and the remaining 10 causes were diagnosed as suspicious for malignancy (10%).On the contrary by using CB, complimented by combined PAS-Alcian blue stain where required , 90 cases were diagnosed as negative for malignancy (90%) and 10 cases were diagnosed as positive for malignancy. Thus by the CB method, an additional 5 more cases were diagnosed as positive for malignancy, that is, 5% more diagnostic yield for malignancy .

Among the 10 malignant cases, diagnosed by CB, 9 cases were subcategorized as adeno carcinoma (90%) and 1 cases was diagnosed as lymphoma.

The malignant effusion was more common in male (70%) than female (30%). The male female ratio was 7:3.

When the cytological smear and cell block techniques were studied for their quality using the point scoring system of Mair et al, (1989).6  it was noticed that 5% of the CS and 6% of the CB was inadequate and unsuitable for diagnosis. 50% of the CB and 32% of the CS showed highest cellularity. 41% of the CB and only 11% of the CS yielded highest morphological details. Wilcoxon Signed Rank test was done to measure the level of significant, which was highly significant in CB compared to CS regarding cellularity and morphological details.


Table V: Distribution of patients according to point scoring system adopted by Mair et al,(1989)6 in CS

 

 

Discussion

Lung cancer, whether primary or secondary, is invariably accompanied by pleural effusion. The cell population in sediment of pleural fluid represent much larger surface area than obtained by needle biopsy.  Malignant cells first involve the visceral pleura and tend to be focal in the parietal pleura.7 This explains why, pleural fluid cytology is a more sensitive diagnostic test than closed percutaneous pleural biopsy.8,9

Thoracentesis followed by cytological examination is the first investigation performed in a pleural effusion fluid of a suspected lung cancer patients and has been accepted as a routine laboratory procedure. The differentiation of a malignant effusion from a para-malignant effusion is extremely important, not only in the diagnosis of a malignant lesion, but also in staging, prediction of prognosis and to reform a proper treatment protocol.10

In our study, 100 pleural effusion fluid specimen of radiologically and clinically suspected lung cancer patients were examined by using conventional CS and CB techniques. In CS, of 85 patients, the fluids were diagnosed as negative for malignancy (85%).

All the 85 negative cytosmear cases were confirmed by CB. In conventional CS method 10 cases were diagnosed as suspicious for malignancy, of which 5 cases turned to be negative and another 5 cases   proved to be positive for malignancy in CB. In conventional CS method, reactive mesothelial cells, an abundance of inflammatory cell and paucity of representative cells contributed to the considerable difficulties in making conclusive diagnosis of malignancy.

The false positive diagnosis in CS was secondary to the marked atypia of the mesothelial cell which may be due to the microbiological, chemical, physical, immunological or metabolic insult to the serous membrane or due to the subtle cytomorphological features of some malignant neoplasm, particularly well differentiated adenocarcinoma.11 The problem was compounded by artifact   caused by poor fixation, preparation and staining technique. In our settings, fixation and transportation are contributory factors. Generally the reactive mesothelial cells appears rounded and have single centered or eccentric nucleus. Some of the mesothelial cells form cell ball, clusters and takes a signet-ring cells appearance, thus closely mimicking malignancy. The malignant cells have irregular nuclear membrane, nuclear molding and prominent nucleoli with absence of windows. However, these differentiating features are sometimes difficult to identify.

By using CB method, 5 more malignant cases were diagnosed, which were diagnosed as suspicious for malignancy by conventional CS, thus increasing the diagnostic yield by 5% (5/10). Further special stain (PAS-Alcian blue) supported the diagnosis of malignancy.

Another 5 cases were diagnosed as negative for malignancy by CB, which were diagnosed as suspicious for malignancy by conventional CS. The benign cells did not take PAS-Alcian blue stain.

In a parallel study on effusion fluid, Shivakumaraswamy et al, (2012)5 found   15% more diagnostic yield for malignancy on CB.   Bhanvadia et al., (2014)12 in another study observed    10% more diagnostic yield in CB. Thapar et al, (2009)4  also   showed 13% more diagnostic yield by CB.

In our study, after the final diagnosis as benign or malignant effusion, a critical evaluation was made for diagnostic yield taking a consideration on cellularity, morphology, architecture and background blood. The conventional CS and CB technique were studied for their quality by using point scoring system of Mair et al, (1989).6 In CB, 41% ensured highest morphological details where as in CS, highest morphological detail was acquired in only 11% cases. The comparative result of our point scoring system was analyzed by Wilcoxson Signed Ranks test which was highly significant in respect of cellularity and cellular morphology.

Reactive mesothelial cells have in the past been responsible for simulating malignancy in CS, largely due to the formation of rosettes, pseudo acini or acini, with or without the presence of prominent nucleoli. The CB effectively puts both the features in their proper prospective. That is, the nucleoli does not appear as prominent in CS and the pseudoaciner or acinar strictures can be better appreciated when present in the CB. Similar findings were noticed in the Dekker and Bapp (1978)(13) study. More important is, this CB is a valuable tool in the evaluation of well differentiated adenocarcinoma, where the presence of true acini is seen in the CB with mucin. Positive stain  for mucin in CB  indicated  malignancy.

In our study, we noticed a significant number of macrophages admixed with malignant cells having large pleomorphic nuclei simulating malignant cells. Multiple large PAS positive granules were identified by special stain that were diagnosed as suspicious for malignancy by CS. We also noticed pericellular lacunae in many of the cases of adenocarcinoma specially of mucin secreting type, characterized by cell clusters and Bull’s eye (Target) inclusion like finding was seen in one case of metastatic carcinoma.

There had not been yet any standard method for the preparation of CB from effusion fluid. Our study was done by using 10% alcohol formalin fixative. In our paraffin embedded CB section our attention was drawn by the presence of large clusters of cells either malignant or reactive mesothelial cells in a separate peripheral layer leaving a  thick amorphous proteinaceous material in the center. These helped in reducing background artifact and ensured more nuclear details for the distinction between reactive mesothelial cells and malignant cells. Few inflammatory cells were noticed in a less peripheral separate layers admixed with other cells in malignant cases. The other advantage of CB was concentration of cellular materials in one small area that can be evaluated at a glance with all cells lying in the same focal plane of microscope. It bridges the gap between cytology and histology

Conclusion

The cell block made by using 10% formalin-alcohol as a fixative, is a simple, inexpensive method, and does not require any special training or instrument. Multiple sections could be obtained required, for special stain. Therefore, CB technique could be considered as a useful adjunct in evaluating malignant cells in MPE for a final cytodiagnosis, along with the routine CS method.

References

  1. Kastelik JA. Management of malignant pleural effusion. Lung, 2013;191(2):165-75.
  2. Bennett R & Maskell N. Management of malignant pleural effusions. Curr Opin Pulm Med, 2005;11(4): 296-300.
  3. Maskell N, Gleeson F & Davies R. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. The Lancet, 2003;361(9366):1326-30.
  4. Thapar M et al. Critical analysis of cell block versus smear examination in effusions. Journal of Cytology, 2009;26(2):60–64.
  5. Shivakumarswamy U, Arakeri SU, Karigowdar MH & Yelikar BR. Diagnostic utility of the cell block method versus the conventional smear study in pleural fluid cytology. Journal of Cytology, 2012;29(1):11–15.
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jhc-2019-jul-v-3n-2-The-Incidental-awal

The Incidental Findings of Thyroid Neoplasms in 200 Sequential Autopsies in Dhaka Medical College

 *Awal N,1 Dewan RK,2 Ray S,3 Ferdous JN4

  1. *Dr. Naila Awal, Assistant Professor, Department of Pathology, Greenlife Medical College. nailaawal@gmail.com
  2. Rezaul Karim Dewan, Professor and Head, Department of Pathology, Dhaka Medical College.
  3. Subrata Ray, Assistant Professor, Department of Pathology, Jessore Medical College.
  4. Jesmin Naz Ferdous, Assistant Professor, Department of Pathology, Sir Salimullah Medical College.

 *For correspondence

 Abstract

Background: The incidental findings may contribute to identify many common latent thyroid neoplasms. The study was carried out to evaluate the frequency of undiagnosed thyroid neoplasms existing in the general population of our country.
Methods: Total 200 whole thyroid glands were collected from the deceased who had apparently normal thyroid gland. The study includes 85 male and 115 female cadavers between 14 to 65 years of age. Sections were taken from grossly identified lesions for histopathological process, and studied microscopically, other areas were collected randomly for microscopic examination.
Result: In all cases, both benign and malignant neoplasms were incidental findings, seen in 4.5% of the cases. Malignant neoplasm was found in 2% of cases and was latent.
Conclusion: Clinically normal appearing thyroid glands may contain major pathological lesions, when they are microscopically studied. Considering the high prevalence of thyroid malignancy to other parts of the world, routine systematic examination of the gland is recommended to detect unsuspected thyroid pathology mainly carcinoma.

[Journal of Histopathology and Cytopathology, 2019 Jul; 3 (2):93-98]

 Key words: Occult neoplasm, thyroid

 

Introduction

Thyroid cancer is the fifth most common cancer in women worldwide.1 In most countries, incidence have been appreciably increasing over the last few decades.2,3 If recent trend is maintained, thyroid cancer may become the fourth most common cancer by 2030 in United States.4

Small “occult” thyroid carcinomas are present in a substantial proportion of the general population. In surgical practice, biopsy of thyroid without symptom is not indicated. So, autopsy sample can be an alternative to assess the incidence of latent thyroid neoplasms.

Usually, the thyroid gland is not examined in routine autopsies in Dhaka Medical College.  When a more careful and systematic study of the thyroid is done in autopsy material, latent thyroid lesions are found in a frequency of 20 times greater than the incidence seen at routine autopsy series (0.8 %).5 Pingitore R, (1982) found 3.6 % of latent carcinomas in his autopsy specimen.6 There is no data of unsuspected thyroid neoplasm after a systematic and histologic examination of the gland during autopsy in Bangladesh.

  The present study was designed to determine the frequency and evaluation of the prevalence of incidental carcinomas in our population in autopsy specimen. It may be of interest in regard to causal or prognostic factors.

Methods

This study was initiated after receiving approval of the ethical committee of our institution. It is cross-sectional descriptive study with convenient sampling done over a period of two years (January 2016 to December 2017). The study population comprised deceased undergoing medicolegal autopsy in morgue under the Forensic Medicine Department of Dhaka Medical College. The specimen was discarded if obtained from decomposed or mutilated body or when there was injury over the neck involving thyroid gland as well as from the subject in whom there was previous hemi thyroidectomy. Enlarged thyroid beyond normal range was also discarded from this study.

After receiving the specimen, it was fixed in 10% neutral buffered formalin and dissected free from surrounding neck tissues. The thyroid glands were weighed, measured and divided into right and left lobes with isthmus attached to one of lobes.

The whole thyroid gland was divided into three parts and labeled as anterior, middle and posterior from superior pole to inferior pole. The lobes were serially sectioned at 2 mm intervals from 16 areas of both lobes and isthmus.

Figure 1. Diagram of the areas and sections of the thyroid gland to obtain fragments for further histologic examination.

All grossly visible lesions were noted and many were photographed. Histological sections were made from all grossly visible lesions. If no gross lesions was identified at least one histologic section was prepared from each lobe of the glands and were processed. All the sections were stained with hematoxylin and eosin. The prepared slides were examined and the findings were noted. Special stain was donein selected cases.

Data was collected, compiled and properly tabulated in master chart. Representative tables and graphs were made and subjected to suitable statistical analysis by using appropriate methods.

 

Result

Among 200 cases, 85 cases (42.5%) were male and 115 cases (57.5%) were female. The male female ratio was 1: 1.36. The age of the study subject was 14 to 65 years with mean age 24.48± 12.09 years. The mean weight of thyroid gland was 15.50 ± 4.43 gm.

Neoplasm was seen in 9 cases out of 200 cases (4%). The youngest cadaver was 25 years and the oldest was 65 years of age. Major incidence occurred in 3rd decade. The most common neoplasm was follicular adenoma (5 cases, 2.5 %) followed by malignant neoplasm (4 cases, 2 %). The malignant neoplasm was papillary thyroid carcinoma and medullary thyroid carcinoma (1 case, 0.5%). All neoplasm was restricted to single lobe of thyroid except in one papillary thyroid carcinoma, where tumor foci were multiple involving left lobe and isthmus of thyroid

Follicular adenoma was the most common benign neoplastic lesion of solitary thyroid nodule. A total of 5 cases (3%) was diagnosed histologically as follicular adenoma, 3 cases were male and 2 cases were female. The size of the adenoma varied from 0.2 to 1.1 cm in diameter and had single foci distributed in single lobe of thyroid. Microscopically, they showed well demarcated areas consisting of numerous small uniform follicles with scanty colloid. The neoplastic cell showed follicular morphology. No capsular and vascular invasion was identified in any of the cases.

Among the malignant neoplasm, 3 cases (1.5%) were revealed as latent papillary thyroid carcinoma based on characteristic nuclear feature. None was encapsulated. All of these lesions were within 1 cm in maximum diameter. By definition, the tumors were diagnosed as papillary microcarcinoma.7 One of them was follicular variant of papillary carcinoma presented with ground glass appearance of nucleus and formation of follicles. Some of the neoplastic cells showed intranuclear groove. Psammoma bodies were not found in any cases.

The only one case diagnosed as medullary carcinoma, composed of polygonal to spindle shaped cells forming nests. Acellular amorphous amyloid deposition was seen in stroma. Special stain Congo red was done and supported the diagnosis by green birefringence of amyloid.

 

Discussion

The incidental findings can contribute to discover many common thyroid lesions. The incidence of both benign and malignant lesions of thyroid varies widely in different geographical areas in the world.

This study was carried out with a view to evaluate the frequency of undiagnosed thyroid neoplasms existing in the general population of our country.

The incidence of thyroid carcinoma differs in different countries range from 0.5 to 10 per 105 persons.8 In most countries, papillary carcinoma was the most common histologic type, comprising approximately 40-70 % of all thyroid malignancy.8

In our study, the weight of thyroid gland with latent neoplasm (17.66 ± 4.03 gm) was similar to that of glands without neoplasm(15.39 ± 4.43 gm), because of we include apparently normal thyroid gland with normal weight. This correlates with previous study done by Ottino et al, (1989).9

 

The most common thyroid neoplasm of this study was follicular adenoma (3%, 5 cases) which is similar to the study done by Bisi, et al. (1989) which was 4.33%.10 Among the malignant neoplasms, one was medullary carcinoma and rest of three were papillary microcarcinoma. Papillary thyroid microcarcinoma is a specific subgroup of papillary thyroid carcinoma and defined by WHO on the largest dimension of 1.0 cm or less.7,11 Most of Papillary thyroid microcarcinoma are not detectable in clinical examination and are diagnosed incidentally during pathologic examination of thyroid specimens after surgery for benign thyroid diseases or in autopsies.11

The rate of malignancy in this study was 2% (4 cases) whereas in a previous study done by das et al, (2017) the rate of malignancy was 2.1% (5 out of 240 cases) which is similar to our study.12 On the other hand, study done by Bondenson and Ljungberg (1981), they estimated rate of malignancy was 8.6 %.13 The higher prevalence of their study was probably due to large number of study subject. The study done by Furmanchuk and Rusak (1992), the estimated rate of malignancy was 9.9% (11 out of 122).14 The higher prevalence of their study was probably due to radiation and other hazard.14 Following tables show the prevalence rate (%) of occult papillary carcinoma in different autopsy series

 Conclusion

Many thyroid neoplasms may remain silent and diagnosed only autopsy during histopathological examination of specimen. So routine systematic examination of the gland is recommended to detect unsuspected thyroid neoplasm mainly carcinoma.

The presence of 2 % (4 cases out of 200) of malignant thyroid neoplasm in this study speaks about the burden of this disease in our population which may be detected by thorough thyroid screening test.

The latent thyroid diseases including thyroid carcinoma is treatable and have good prognosis. So, routine evaluation of thyroid status by thyroid function tests in a reasonable time interval can be done to evaluate the latent thyroid neoplasm. Routine systematic examination of thyroid gland during autopsy not only would be useful in determining the cause of death but also contribute to the social health data by yielding the frequency of latent thyroid neoplasm.

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