|Year : 2020 | Volume
| Issue : 3 | Page : 427-434
|Evaluation of cell blocks from effusion specimens in Gynecologic Oncopathology: An experience of 220 cases, diagnosed at a Tertiary Cancer Referral Center
Bharat Rekhi1, Srushti Karmarkar2, Chhavi Gupta2, Kedar K Deodhar1, Santosh Menon1, Saleem Pathuthara3, Amita Maheshwari4, TS Shylasree4, Sudeep Gupta5
1 Department of Surgical Pathology; Division of Cytopathology, Tata Memorial Center, HBNI University, Mumbai, Maharashtra, India
2 Department of Surgical Pathology, Tata Memorial Center, HBNI University, Mumbai, Maharashtra, India
3 Division of Cytopathology, Tata Memorial Center, HBNI University, Mumbai, Maharashtra, India
4 Department of Surgical Oncology, Tata Memorial Center, HBNI University, Mumbai, Maharashtra, India
5 Department of Medical Oncology, Gynecology Disease Management Group, Tata Memorial Center, HBNI University, Mumbai, Maharashtra, India
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|Date of Submission||02-Nov-2019|
|Date of Decision||12-Dec-2019|
|Date of Acceptance||09-Feb-2020|
|Date of Web Publication||7-Aug-2020|
| Abstract|| |
One of the common indications of ascitic fluid examination in gynecological oncopathology is the detection and classification of malignant cells, especially in cases of clinically suspicious tubo-ovarian masses. The present study was undertaken to assess and validate the diagnostic utility of cell blocks (CBs) and compare its results with the corresponding conventional smears, prepared from effusion samples. CBs were prepared by thromboplastin technique in 220 cases. In 208 cases, diagnostic concordance between results obtained from smears and corresponding CBs was evaluated. Various antibody markers were tested, as per individual case. The average age of patients was 52.2 years. Positive immunohistochemical (IHC) staining for various markers was observed in 182 cases (82.7%) The most frequently positive antibody marker was PAX8 (101/134), followed by p53 (85/92) [mutation type (either diffusely positive or completely negative)], WT1 (tumor cells) (80/112), calretinin (2/87) (diffuse), BerEP4 (21/49), CA125 (21/24), CK7 (31/39) and CK20 and CDX2, together (5/16). Various other IHC markers utilized, including their positive expression, were TTF1 (1/10), p40 (3/3), p63 (2/4), ER (21/29), HBME1 (1/7), GATA3 (1/4), and MIC2 (1/1). Complete diagnostic concordance between CBs and smears was observed in 170/208 cases (81.7%). There were 20 major discordances, 10 minor and 8 cases with sampling errors. IHC was useful in classifying 158/182 (86.8%) cases, including serous or Müllerian adenocarcinoma (n = 123), mostly high-grade (121); metastatic squamous carcinoma (3); gastrointestinal-type adenocarcinoma (8); pulmonary adenocarcinoma (1); breast adenocarcinoma (1); Ewing sarcoma (1); and mesothelioma (2). CBs are complementary to smears in the detection of gynecological malignancies, mostly high-grade serous adenocarcinomas. These provide an opportunity for testing several IHC markers, for a precise diagnosis, including in various uncommon case scenarios, associated with significant therapeutic implications.
Keywords: Cell blocks, gynecologic effusion, ovarian cancer, p53, PAX8, serous adenocarcinoma, immunohistochemistry
|How to cite this article:|
Rekhi B, Karmarkar S, Gupta C, Deodhar KK, Menon S, Pathuthara S, Maheshwari A, Shylasree T S, Gupta S. Evaluation of cell blocks from effusion specimens in Gynecologic Oncopathology: An experience of 220 cases, diagnosed at a Tertiary Cancer Referral Center. Indian J Pathol Microbiol 2020;63:427-34
|How to cite this URL:|
Rekhi B, Karmarkar S, Gupta C, Deodhar KK, Menon S, Pathuthara S, Maheshwari A, Shylasree T S, Gupta S. Evaluation of cell blocks from effusion specimens in Gynecologic Oncopathology: An experience of 220 cases, diagnosed at a Tertiary Cancer Referral Center. Indian J Pathol Microbiol [serial online] 2020 [cited 2020 Sep 19];63:427-34. Available from: http://www.ijpmonline.org/text.asp?2020/63/3/427/291694
| Introduction|| |
Cytological examination of serous fluids in cases of suspected ovarian cancers is crucial in their diagnosis, staging, and prognosis. An exact diagnosis, including subtype of cancer and grade (in case of serous carcinomas), has significant therapeutic implications. Diagnosis by conventional cytology smears can be challenging, especially in differentiating reactive mesothelial cells from adenocarcinoma, subtyping an adenocarcinoma, and in differentiating an adenocarcinoma from mesothelioma.,,
The cell block (CB) constitutes another technique for identifying malignant cells and can be utilized for testing immunohistochemical (IHC) stains in a relatively high throughout manner, especially in diagnostic dilemmas and in an exact subclassification of malignant cells, using various antibody markers.,,,
| Materials and Methods|| |
This was a descriptive study comprising retrospective and prospective cases, wherein smears and corresponding CBs were prepared from fluid samples in cases of clinically suspicious malignancies, presenting with effusion, referred to gynecologic oncology. Two hundred and twenty cases with CB preparations were analyzed in this study.
Smears were stained with Papanicolaou (Pap) and May Grunwald Giemsa (MGG) stain after centrifugation. CBs were prepared by plasma-thromboplastin technique. Hematoxylin and Eosin stained CBs were reviewed by two authors (B.R with S.K). IHC staining was performed in 182/220 cases (82.7%).
Diagnostic concordance between smears and CBs, with regards to malignancy, was recorded and further, discordances wherever noted were subclassified as major or minor, accordingly, as per treatment implications. Major discordances were labelled as those associated with significant treatment implications. Another objective of this study was to validate results obtained from CBs, including IHC results, with corresponding histopathological results, wherever available.
| Results|| |
The average age of patients was 52.2 years. Out of 220 cases, smears and corresponding CBs were available in 208 cases (94.5%). In the remaining 12 cases, only CBs were available. Among 220 cases, most frequently received samples were of ascitic fluid (188 cases; 85.4%), followed by pleural fluid (21 cases; 9.5%). Both, ascitic and pleural fluid were received in nine cases (5%). Pericardial fluid was submitted in two cases (0.9%).
Clinical diagnosis, including radiologic imaging, was available in 207 cases (94%). IHC staining was performed in 182/220 cases (82.7%). Most frequently tested IHC antibody marker was PAX8 (101/134), followed by p53 (85/92) [mutation type (either diffusely strongly positive, or completely negative)), WT1 (tumor cells) (80/112), calretinin (2/87) (diffuse staining), and BerEP4 (21/49). Other, less frequently tested IHC markers were CA125 (21/24), Ki67 (n = 22) (1%–2% to 60%–70%), CK7 (31/39), and CK20 and CDX2, together (5/16). In uncommon case scenarios, other IHC markers used, including their positive expression, were TTF1 (1/10), p40 (3/3), p63 (2/4), ER (21/29), HBME1 (1/7), GATA3 (1/4), MIC2 (n = 1/1), Napsin A (n = 0/5), and CEA (1/4). In a few cases, CD163 was also tested [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5].
|Figure 1: (a) Cell block (CB) preparation in a case reported as “suspicious for adenocarcinoma,” on smears. CB reported as adenocarcinoma (H and E, ×200). Inset: Positive BerEP4 immunostaining (cytoplasmic membranous) highlighting adenocarcinoma (Diaminobenzidine, ×400). (b) CB preparation in a case reported as “adenocarcinoma,” on smears. CB reported as high-grade serous adenocarcinoma (H and E, ×400). Inset: Tumor cells showing distinct positivity for WT1 (Diaminobenzidine, ×400). (c) Tumor cells showing PAX8 (Mullerian differentiation) positivity (Diaminobenzidine, ×400). (d) Diffuse, strong immunostaining for p53 (mutation type) (Diaminobenzidine, ×400)|
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|Figure 2: (a) Case reported as high-grade adenocarcinoma on smears and CB (Hand E, ×400). (b) Tumor cells displaying diffuse, strong CK7 positivity (Diaminobenzidine, ×400). (c) Tumor cells showing negative expression for calretinin. Interspersed mesothelial cells, representing internal positive controls (Diaminobenzidine, ×400). (d) Tumor cells displaying WT1 positivity (Diaminobenzidine, ×400). (e) Significant ER positivity within tumor cells (Diaminobenzidine, ×400)|
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|Figure 3: (a) CB in a case reported as “mesothelial-rich” effusion, on smears (H and E, ×400). (b) Tumor cells displaying diffuse, strong CK7 positivity, (Diaminobenzidine, ×400). (c) Tumor cells displaying diffuse, strong calretinin positivity, (Diaminobenzidine, ×400). (d) Tumor cells displaying WT1 positivity, (Diaminobenzidine, ×400). (e) Tumor cells lacking desmin immunoreactivity, indicative of mesothelioma, (Diaminobenzidine, ×400)|
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|Figure 4: (a) Case of cervical carcinoma with ascitis, reported as carcinoma on smears. CB reported as metastatic squamous carcinoma (H and E, ×400). (b) Tumor cells displaying distinct p63 positivity (Diaminobenzidine, ×400). (c) P40 positivity (squamous differentiation) (Diaminobenzidine, ×400). (d) Case of adenocarcinoma (reported on smears and CB), with lung and ovarian masses. (e) Diffuse TTF1 positivity, reinforcing pulmonary adenocarcinoma. PAX8 and WT1 were negative (Diaminobenzidine, ×400). (f) Metachronous ovarian and breast carcinoma in a case with metastatic adenocarcinoma cells (H and E, ×400). (g) Diffuse GATA3 positivity and PAX8 negativity (not shown), indicating metastatic breast adenocarcinoma (Diaminobenzidine, ×400)|
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|Figure 5: (a) Case reported as adenocarcinoma on smears and metastatic colorectal-type adenocarcinoma on CB. Atypical cells, focal mucin (H and E, ×200). (b) Clusters of adenocarcinoma (H and E, ×400). (c) Adenocarcinoma cells within mucin (H and E × 400). (d) CK7 negativity with positivity in isolate mesothelial cells (Diaminobenzidine, ×400). (e) CK20 immunostaining in tumor clusters (Diaminobenzidine, ×400). (f) CK20 highlighting adenocarcinoma cells (Diaminobenzidine, ×400). (g) Distinctly positive CDX2 cells, reinforcing diagnosis of colorectal-type adenocarcinoma (Diaminobenzidine, ×400)|
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Complete concordance between CBs and smears with regards to the diagnosis of malignancy was observed in 170/208 cases (81.7%), while discordances were noted in 30/208 cases (14.4%). In eight cases (3.8%), there was sampling error, i.e. true discrepancy.
Among the 30 discordant cases, major discordances were identified in 20 cases and minor in 10 cases [Table 1], [Table 2] and [Figure 6], [Figure 7].
|Figure 6: (a) Cluster of cells amid macrophages and mesothelial cells, misinterpreted as adenocarcinoma (MGG, ×400). (b) An occasional cluster, misinterpreted as adenocarcinoma. Pap, ×400. (a-d). Major discordance. (c) Cell block section showing macrophages and mesothelial cells, forming clusters. (d) CD163 highlighting clusters of macrophages (Diaminobenzidine, ×400). (e) Focal calretinin immunoexpression, highlighting few interspersed mesothelial cells (Diaminobenzidine, ×400)|
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|Figure 7: (a) Metastatic adenocarcinoma in pleural fluid initially treated as a pulmonary adenocarcinoma. Subsequently, ascitic fluid and pleural fluid cell block (retrospective) tested. (b) PAX8 positivity in both, pleural fluid specimen and ascitic fluid (not shown) with TTF1 negativity, confirming a metastatic Müllerian adenocarcinoma (Diaminobenzidine, ×400). (c and d) Ascitic fluid smears, initially diagnosed as adenocarcinoma. Pap × 400. (e) Cell block showing squamous cell carcinoma. H and E, ×400. (f) Diffuse p40 positivity reinforcing a squamous cell carcinoma (Diaminobenzidine, ×400)|
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In 125/220 cases (56.8%), histopathologic results of the excised specimens and/or biopsy specimens were available. Out of these, 119 cases (95.2%) had a concordant diagnosis on CBs with histopathologic results of tumor excisions. In the remaining six cases, the discordance was because of fewer no abnormal cells on CBs, which were reported either as “atypical” or as negative for malignancy. Forty-two cases, including discordant and 6 cases with sampling issues, were diagnosed as “negative” on CBs. Twenty-one cases were concordantly negative for malignant cells, both on smears and CBs.
Overall, immunostaining on CBs was performed in 182/220 cases and was useful in classifying and subclassifying malignancies in 158/182 cases (86.8%). These included 142 adenocarcinomas, which were further classified as high-grade serous adenocarcinomas (97); high-grade Mullerian-type adenocarcinomas (22), followed by gastrointestinal-type adenocarcinomas (8) (biopsy confirmation in 3 cases); low-grade serous adenocarcinomas (2); breast carcinoma (1); pulmonary adenocarcinoma (1); squamous cell carcinoma (3); mesothelioma (2); and Ewing sarcoma (1). Twenty-one cases of adenocarcinomas (not specified), including few tested for PAX8 (and negative), were treated as Müllerian adenocarcinomas, in view of clinicoradiological evidence of an adnexal mass, with increased serum CA125 levels in some of those cases. Immunoexpression of certain IHC markers was compared between CBs and corresponding histopath sections, wherever available and 100% concordance was achieved with PAX8, tested in 7 cases; p53 expression, in 5 cases; CK7 in 2 cases, along with WT1, calretinin, MIC2, ER, and CDX2 in a single case, respectively, both on CB and corresponding histopathologic section. Data regarding 220 cases is available in [Supplementary Table 1].
| Discussion|| |
One of the most common indications of ascitic fluid examination in gynecological oncopathology, including our settings, is the detection of adenocarcinoma cells in cases of tubo-ovarian masses, considering a vast majority of epithelial ovarian cancers present with ascites., Diagnosis of adenocarcinoma, including high-grade, invariably subjects the affected patient to a specific, platinum-based chemotherapy regimen, in contrast to metastatic carcinomas from the gastrointestinal tract, wherein the patients are treated with a different chemotherapy regimen. Cases of low-grade serous adenocarcinomas do not respond equally, as those of high-grade serous adenocarcinomas, to the specific chemotherapy regimen.
On conventional smears, there can be a considerable challenge in differentiating reactive mesothelial cells and macrophages from adenocarcinoma cells. Macrophages and mesothelial cells, which are common in long-standing effusions, show reactive changes in the form of cytomegaly, nucleomegaly, multinucleation, and mitotic figures, as occurred in our nine discordant (major) cases, on smears. In that way, mere conventional morphological-based assessment has less sensitivity due to features such as overcrowding of cells, cell loss, and different processing methods used. Therefore, there is a need for a more objective assessment, which is possible with the application of certain sensitive and specific immunostains, for example, BerEP4 and MOC31, which highlight adenocarcinoma cells and calretinin, which stain mesothelial cells in most cases.,,
CBs seem better in recognition of the tumor architectural patterns, when compared to smears., Moreover, these provide an opportunity for testing the samples for various antibody markers, for a more definite diagnosis, including subtyping, as noted in the present study. There is relatively lesser cellular dispersal, and the stained sections, as well as the blocks, can be stored for retrospective studies, or for testing any new predictive as well as prognostic marker in recurrent/relapsed cases. Lately, estrogen receptor (ER) testing is being performed in cases of high- and low-grade serous carcinomas for considering hormonal (tamoxifen, letrozole) chemotherapy in such cases, including at our center.
There have been earlier studies on a comparison between CBs and cytologic smears in cases' effusion specimens. Thapar et al. analyzed 190 samples and observed 13% more yield in malignant cases, after combining CBs with smears. They observed that it was better to prepare CBs in cases, where smears were negative. In another study, Shivakumaraswamy et al. studied 44 samples, obtained 13.6% more yield in malignant cases on CBs, and concluded that CBs are useful adjuvants to smears in the diagnoses of malignancy. However, none of these studies included subtyping the malignancies, as IHC markers were not performed.
In the present study, results obtained from smears were reasonably at par with CBs, in terms of diagnosis of malignant versus benign effusions, with an overall concordance of 81.7% cases, in terms of interpretation, between the two preparations.
There were 20 cases with major discordances. Among these, nine cases were over-diagnosed as adenocarcinomas and four cases were misdiagnosed as adenocarcinoma, on smears. However, these were correctly classified as squamous cell carcinomas (2 cases) and mesothelioma (2 cases), respectively, on CBs, with IHC testing. Conversely, two cases, which were underdiagnosed on smears (atypical cells), were correctly diagnosed as adenocarcinomas, on CBs.
Minor discordances were observed in 10 cases. These were most frequently related to the diagnosis of “atypical cells,” on smears, which turned out to be negative on CBs and “suspicious” cells, which turned out to be adenocarcinomas. In three cases, diagnosis of “suspect adenocarcinoma” was offered on the smears, whereas the CBs were useful in a confirmatory diagnosis of adenocarcinoma in those cases.
In two cases, smears were more representative of carcinoma, whereas, in view of paucity of cells, definite diagnosis of malignancy could not be achieved with the help of CBs.
Therefore, a combination of smears and CBs, including IHC makers, can lead to a correct and complete diagnosis in cases with both benign and malignant effusions. Furthermore, in cases of less number of abnormal cells in smears, CBs might not be useful, especially for immunostaining.
Very few studies have demonstrated the utility of immunohistochemistry in the diagnoses of malignancy with CBs., Arora et al. conducted a study of 100 cases, wherein they concluded calretinin and BerEP4 as highly sensitive (90% and 98%, respectively) and specific (100% and 86%, respectively) markers, proving their utility in a limited resource setting. In another study, Lucchi et al. analyzed 86 samples, including immunocytochemical markers, in combination with smears and CBs and observed that BerEP4 and calretinin were the two IHC markers with 100% sensitivity and specificity. In addition, they observed utility of a panel of immunocytochemical markers, such as Keratin, BerEP4, calretinin, and CD68, in differentiating mesothelial cells from metastatic carcinoma cells.
Similarly, we observed that CBs provide an opportunity to perform a specific panel of IHC markers in a particular case. Considering diagnosis of adenocarcinoma cells was possible on smears, in most cases, the most frequently used markers were PAX8 (positive in 101/134) and WT1 (positive in 80/112 cases, in the tumor cells). PAX8 and WT1 were useful in confirming diagnosis of Müllerian/ovarian primary in those cases. In a study, Zhao et al. studied PAX8 and WT1 immunoexpression in 68 cases with a definitive cytologic diagnosis of metastatic ovarian carcinoma in peritoneal or pleural effusion. They observed positive immunostaining for PAX8 in 58 cases (85%); for WT1 in 56 cases (82%); combined positivity for both, PAX8 and WT1 in 50 cases (74%), and positivity for either or both these markers in 64 cases (94%). They concluded that a combination of PAX8 and WT1 staining substantially increased the overall detection rate of metastatic ovarian carcinoma. In another study, Liliac et al. evaluated PAX8 and WT1 expression in 86 cases of different subtypes of ovarian cancer. They observed positive immunoexpression of PAX8 in 70 cases (81.4%) and negative expression for PAX8 in the remaining 15 cases (17.44%) suggestive of a non-Müllerian origin, in those cases. In addition to PAX8 and WT1, we observed mutation type of p53 immunostaining pattern in 92.3% cases, including a single mesothelioma. Ki-67 immunostaining ranged from 60%–70% in most cases and 20%–30% in some cases, wherever performed. The latter immunomarkers were useful in confirmation of high-grade in most cases of metastatic serous adenocarcinomas.
Exact subtyping of serous adenocarcinomas, in terms of low and high grades, is crucial, considering low-grade serous adenocarcinomas are not as chemosensitive, in contrast to high-grade subtypes., While PAX8 and WT1 were useful in identifying adenocarcinoma cells, calretinin was useful in identification of mesothelial cells and in differentiating these from adenocarcinoma cells and possibly macrophages.
One of the first extensive studies regarding the value of calretinin immunostains, in differentiating peritoneal mesotheliomas from serous carcinomas, was conducted by Ordonez. In that investigation, the author observed strong calretinin expression in all 35 peritoneal mesotheliomas, while focal positivity 4 out of the 45 cases (9%) of serous carcinomas, thereby confirming calretinin as a fairly specific mesothelial marker. Subsequently, Attanoos et al. reported calretinin immunoexpression in 88% peritoneal mesotheliomas and in none of the 23 serous carcinomas, in that study. Ordonez  investigated calretinin expression in a series of peritoneal mesotheliomas and peritoneum serous carcinomas. All 40 (100%) mesotheliomas in that study were diffusely, strongly immunopositive for calretinin and 14/45 cases (31%) of serous carcinomas were immunopositive for calretinin.
In the present study, diffuse and strong calretinin expression, coupled with lack of desmin immunoexpression in tumor cells was seen in two cases of mesothelioma. Both cases of mesotheliomas were misdiagnosed as adenocarcinomas, on smears. Lower index of suspicion and a relatively higher frequency of adenocarcinomas, referred to our Institution, are possible reasons for underdiagnoses of peritoneal mesotheliomas. Diagnostic challenges associated with primary mesotheliomas have been previously reported. IHC stains are useful in such cases. Lack of desmin in a mesothelial-rich effusion is a pointer toward the diagnosis of mesothelioma that needs to be interpreted in a clinicoradiological context, as noted in the present study. Focal immunostaining, reinforcing interspersed mesothelial cells, was noted in 53/87 cases of serous carcinomas. PAX8 was useful in highlighting adenocarcinoma cells in most cases, wherever utilized.
Various other IHC markers were tested, such as TTF-1, p40 and p63, MIC2, and CDX2, in classifying malignancies, other than ovarian adenocarcinomas. TTF-1 was positive in one out of 10 cases of a suspected lung primary, with ascites and was concordant with the histopathologic diagnosis of a poorly differentiated pulmonary adenocarcinoma on biopsy of the lung mass. That led to triaging the patient for EGFR testing and possibly a different therapy. P40 and p63 were diffusely positive in tumor cells in three out of three cases with suspected carcinoma cervix, presenting in ascitic samples. In a single case, p40 positivity helped in the confirmation of a vault recurrence in a post-treated case of squamous cell carcinoma of the cervix. A single case of squamous cell carcinoma was misinterpreted as adenocarcinoma, in view of air-dried smears (referral samples), especially when cell clusters develop rounded edges in centrifuged fluid samples. Careful assessment of individual cell morphologic features and immunostains (p40 and p63) are useful in correct identification.,
CDX2 and CK20 positivity, together, was observed in five out of the 16 cases with suspected primary in the gastrointestinal tract. Diagnosis of a gastrointestinal adenocarcinoma in ascitic smears would lead the patient to a fluorouracil-based chemotherapy regimen.,,
MIC2 was positive in a rare case of Ewing sarcoma, presenting in ascitic fluid. The patient was triaged for Ewing family of tumors (EFT) 2001 protocol.,
An overall, 95% concordance between results obtained from CBs and histopath specimens (resections and biopsies), in the present study, validates CB technique in our laboratory, as a useful diagnostic procedure, for evaluation of ascitic fluid, in suspected gynecologic malignancies. Furthermore, a complete concordance between immunoexpression of various antibody markers between CB and histopath sections provides evidence that all IHC markers can be reasonably tested on CB specimens. Lately rare cases of ovarian clear cell carcinoma in effusion samples have been objectively identified with Napsin A immunoexpression, tested on CBs.
To conclude, in most cases, smears were at par with CBs in identification of malignant cells, most frequently, adenocarcinomas. However, CBs were useful in exact subtyping of malignant cells, mostly adenocarcinomas; in identifying false positives, as well as in identifying relatively uncommon malignancies in gynec effusion specimens, with significant therapeutic implications, for example, gastrointestinal type adenocarcinomas, squamous carcinomas, along with rare cases of mesothelioma and Ewing sarcoma, which were objectively diagnosed with IHC markers. CBs are useful for testing several IC antibody markers. However, in some cases with fewer “atypical” cells on smears, CBs failed to show the respective abnormal clusters. Such samples should be ideally tested by immunocytochemical staining, which constitutes a limitation of our study. The other limitation includes a lack of a consistent panel of immunostains in a particular diagnostic scenario.
It is noteworthy that CBs are not a replacement for smears, but are complementary to the smears. IHC results need to be interpreted in a clinical and cytomorphological context. CBs can be utilized in a relatively high throughput manner. In a way, the present study is an example of capacity building in our laboratory, as it constitutes a validation for the usage of CBs for further testing of various prognostic and predictive markers in ovarian cancers.
The entire data related to 220 cases is available as [Supplementary Table 1] against the online version.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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Professor/Pathologist, Room Number: AB-818, Department of Surgical Pathology, 8th Floor, Annex Building, Tata Memorial Hospital, Dr E.B. Road, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2]