Nonmeningothelial Dural-Based Lesions: A Histopathological Analysis.

Introduction We report 30 cases of nonmeningothelial dural-based lesions encountered during a 3-year study period. Materials and Methods We retrospectively reviewed pathology records of patients operated for extra-axial, dural-based lesions during the years 2016 to 2018 and included nonmeningothelial lesions as a part of this study. Results Among the 3,243 neurosurgical specimens for histopathologic examination, only 30 (0.93%) were "nonmeningothelial dural-based lesions." Six (20%) patients were in the pediatric age group. Pathologic assessment identified 13 cases of solitary fibrous tumor/hemangiopericytoma (43.3%) and 7 cases of Ewing's sarcoma/primitive neuroectodermal tumor (23.3%). Two cases (6.7%) were of metastasis. Other lesions included a single case each of non-Hodgkin's lymphoma, undifferentiated sarcoma, solitary plasmacytoma, and granulocytic sarcoma. Nonneoplastic lesions included two cases each of Rosai-Dorfman disease and nonspecific inflammatory lesions. Conclusion Nonmeningothelial dural-based lesions being rare, thorough examination of morphological features is a must by the pathologist, to arrive at the accurate diagnosis. Ancillary tests, if required, should be employed in the context of the morphologic picture.

Plasmacytoid urothelial carcinoma - A clinicopathological case series of an aggressive variant of urothelial cancer.

Background: Many new morphological variants of urothelial carcinoma of urinary bladder have been described in the literature, plasmacytoid/signet ring cell/diffuse variant being one of the rare amongst these. Till date, no case series has been reported from India, describing this variant. Materials and Methods: We retrospectively analyzed the clinicopathological data of 14 patients diagnosed at our center with plasmacytoid urothelial carcinoma. Results: Seven cases (50%) were pure forms while the remaining 50% of cases had a concurrent conventional urothelial carcinoma component. Immunohistochemistry was performed to rule out other mimickers of this variant. Treatment-related data were available for seven patients, while follow-up was available for nine cases. Conclusion: Overall, plasmacytoid variant of urothelial carcinoma is considered to be an aggressive tumor with poor prognosis.

Programmed cell death ligand - 1 expression in triple negative breast carcinoma and its prognostic significance in Indian population.

BACKGROUND: The programmed cell death protein - 1 (PD-1) - programmed cell death ligand - 1 (PD-L1) axis is emerging as a promising target for immunotherapy in triple-negative breast cancers (TNBC). AIMS: We analyzed the expression of PD-L1 in TNBC cases, with special emphasis on lymphocyte-predominant tumors along with correlation of the same with clinicopathological features and outcome. SETTINGS AND DESIGN: Tissue microarrays (TMA) were prepared from resection specimens of TNBC cases diagnosed from 2004 to 2008. SUBJECTS AND METHODS: Immunohistochemical staining was performed on the TMA using the ventana PD-L1 antibody (Clone SP 263). STATISTICAL ANALYSIS: Chi-square test was used for correlation of PD-L1 positivity in tumor and immune cells with clinicopathological features. Univariate and multivariate survival analyses were carried out using the Kaplan Meir and Cox Regression methods, respectively. RESULTS: Overall, PD-L1 staining was seen in 35.9% (66 out of 184) tumors. PD-L1 positivity of tumor cells was seen in 14.7% (27 out of 184 cases), whereas stromal immune cell expression was observed in 21.2% (39 out of 184) cases. Lymphocyte-predominant tumors showed statistically significant expression of PD-L1 in both tumor (P < 0.0001) and immune cells (P 0.036). On univariate analysis, PD-L1 in immune cells was associated with good overall survival (P 0.05) as well as disease-free survival (P 0.013). On multivariate analysis, the same was associated with a significantly decreased risk for recurrence (P 0.018). CONCLUSION: PD-L1 expression in stromal immune cells proved to be a significant prognostic factor for TNBC. This data can serve as a baseline to plan clinical trials with anti-PD-L1 drugs for TNBC in the Indian setting.

Intravascular papillary endothelial hyperplasia of the cavernous sinus-A rare occurrence.

Intravascular papillary endothelial hyperplasia (IPEH) is a benign, reactive proliferation of endothelial cells within areas of thrombus. It most commonly occurs in the skin and subcutaneous tissue, with less than 40 cases reported in intracranial location. Ours is the first case report from India of IPEH in the cavernous sinus. A 45-year-old male presented with headache and decreased visual acuity. Magnetic resonance imaging (MRI) revealed a well-defined, homogeneously contrast-enhancing mass in the cavernous sinus. Postoperatively, examination of tissue showed organizing thrombus within the vessel wall along with delicate, acellular, pseudopapillary cores. The fibrin-rich connective tissue of these showed blue staining with Masson's trichrome stain. These were lined by a single layer of endothelial cells without evidence of atypia; no nuclear pleomorphism, hyperchromasia, atypical mitosis, or areas of necrosis were seen. Hence, it was diagnosed to be IPEH. Follow-up MRI revealed no residual disease and the patient is disease-free at 8 months. Recognition of this entity by pathologic examination is important to rule out angiosarcoma. Gross total resection is curative. Residual lesions have the potential for recurrence, requiring adjuvant therapy.

Melanoma of the central nervous system: A report of three cases.

Melanomas within the Central Nervous System (CNS) are most commonly metastatic lesions, with primary melanomas comprising only 0.05-0.07% of all brain tumors. We report three cases of primary CNS melanoma. The patients were young adults. There were two females and one male. On preoperative investigations, two cases were misdiagnosed to be angiomas on Magnetic Resonance Imaging (MRI). The melanotic nature of the lesion was an intraoperative observation. Pathologic examination showed features of malignancy with invasion of tumor cells into the brain parenchyma. In two patients, presence of systemic lesions were ruled out after surgery by whole-body Positron Emission Tomography (PET) scan. These patients were subject to adjuvant radiotherapy, while one patient succumbed immediately post-surgery. Primary CNS melanomas are rare with no defined treatment protocols. Histopathology diagnosis is crucial to rule out pigmented mimics.

Glioblastoma Occurring as Second Primary in a Treated Case of Diffuse Large B-Cell Lymphoma.

Glioblastoma as second primary malignancy (SPM) has been reported after prostate cancer, meningiomas, Hodgkin's lymphoma. We report an extremely rare case of glioblastoma as SPM, occurring after remission of diffuse large B-cell lymphoma (DLBCL). Fifty-year-old male presented with loss of consciousness followed by right-sided weakness. He was treated with chemotherapy for DLBCL of the cervical lymph nodes, 5 years back. Present scans revealed well-defined intra-axial lesion in the left parietal lobe, suggestive of central nervous system (CNS) involvement by lymphoma. Left parieto-occipital craniotomy was performed and microscopic examination revealed the tumor to be Glioblastoma, WHO Grade IV. The tumor cells were positive for glial fibrillary acid protein and negative for leucocyte common antigen. He was treated by radiotherapy and temozolomide. Pathologic examination is a must for CNS lesions. Had it not been for the biopsy, the patient would have been treated as a recurrence of CNS lymphoma by chemotherapy and would have probably succumbed.

Triple Negative Breast Cancer: Expression of Folate Receptor Alpha in Indian population.

Folate Receptor Alpha (FRA) is a membrane protein expressed on the apical surface of epithelial cells. Its expression in increased in certain tumors, where it can serve as a target for therapy. Triple Negative Breast Carcinoma (TNBC) are a heterogeneous group of tumors, with limited therapy options and poor prognosis. We aimed to study the expression of FRA in TNBC. Tissue microarrays were prepared from archived paraffin blocks of 300 TNBC resection specimens. Staining for FRA immunohistochemistry was carried out using the clone 26B3.F2. Clinical and pathologic details of the patients were obtained from the electronic medical records. Chi square test was performed for correlation of clinicopathological features with FRA expression. Kaplan Meir and Cox Regression analysis were carried out to study the Disease Free Survival (DFS) and Overall Survival (OS). FRA showed positivity in 43% (129/300) of TNBCs in our study. In univariate analysis, TNBC expressing FRA had a significantly better OS compared to FRA negative tumors (p - 0.035). Also, FRA positive tumors showed a trend towards longer DFS, though this was not statistically significant. In multivariate analysis however, FRA expression did not emerge as a significant factor. To conclude, TNBCs in our study showed FRA expression and though this did not emerge as an important prognostic factor, it can represent a therapeutic target for future clinical trials.

Dual-color dual-hapten in situ hybridization (D-DISH) - Comparison with fluorescence in situ hybridization (FISH) for HER2/neu testing in breast cancer.

CONTEXT: HER2/neu testing in breast cancer is a mandate due to availability of trastuzumab, a monoclonal antibody targeted against this biomarker. Dual-color dual-hapten in situ hybridization (D-DISH) is a new test for assessment of HER2/neu gene overexpression on light microscopy. AIMS: This was a validation study for D-DISH in our laboratory and was conducted to study the concordance between fluorescence in situ hybridization (FISH) and D-DISH for HER2/neu testing in breast cancer. MATERIALS AND METHODS: In all, 150 cases of invasive breast carcinoma requested for FISH analysis were selected. Immunohistochemistry by Ventana PATHWAY anti-HER2/neu (4B5) antibody, FISH by ZytoLight SPEC ERBB2/CEN17 Dual Color Probe, and D-DISH using the Ventana INFORM HER2 Dual ISH DNA Probe Cocktail Assay was carried out. STATISTICAL ANALYSIS: Cohen's kappa coefficient was used to calculate concordance between FISH and D-DISH assays. The ratios and average number of signals were compared with Lin's concordance correlation coefficient. RESULTS: About 93.1% of the cases showed concordance between FISH and D-DISH results. Cohen's kappa correlation coefficient was 0.836, indicating almost perfect level of agreement. Lin's concordance correlation coefficient (ρc) showed moderate strength of agreement for HER2/chromosome 17 ratios between FISH and D-DISH assays (ρc 0.9452). As per the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 updated guidelines, four of the cases that were nonamplified on FISH showed low-level amplification on D-DISH due to counting errors caused by faint signals or background dust. Genomic heterogeneity and larger red chromosome 17 signals on D-DISH led to discordance of the six cases amplified by FISH. D-DISH failure rate was 3.33%. CONCLUSION: Overall, D-DISH showed good concordance with FISH but needs expertise for reporting.

Solitary Plasmacytoma with Amyloid - An Unusual Dural-Based Lesion.

Solitary plasmacytoma of the dura without systemic involvement are extremely rare lesions, with <15 cases reported in the literature. Among these, ours is the second case to show the presence of amyloid. Fifty-year-old male had presented with headache, sudden onset right-sided weakness, and vomiting. Magnetic resonance imaging revealed an extra-axial mass in the left fronto-parietal region measuring 10 cm × 8.7 cm × 3.9 cm, suggestive of meningioma. The left fronto-parietal craniotomy was performed and multiple tissue bits aggregating to 10 cm × 8.5 cm × 2 cm along with thinned out membrane-like bit of calvarium was sent for pathologic examination. H and E stained sections showed sheets of plasmacytoid cells along with amyloid, which showed apple-green birefringence on Congo red staining. On immunohistochemistry, tumor cells were positive for CD38, CD138, showed kappa light chain restriction and were negative for CD45, CD34. Hence, it was diagnosed as a plasma cell neoplasm. Further work-up with whole-body positron-emission tomography scan revealed no systemic involvement. Dural-based lesions can mimic meningioma radiographically as well as intraoperatively. Histopathological examination unveils the diagnosis, to guide appropriate therapeutic regimens.

Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study.

BACKGROUND: The androgen receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR's prognostic role in TNBC are putting its usefulness in question. Some studies conclude that AR positivity indicates a good prognosis in TNBC, whereas others suggest the opposite, and some show that AR status has no significant bearing on the patients' prognosis. METHODS: We evaluated the prognostic value of AR in resected primary tumors from TNBC patients from six international cohorts {US (n = 420), UK (n = 239), Norway (n = 104), Ireland (n = 222), Nigeria (n = 180), and India (n = 242); total n = 1407}. All TNBC samples were stained with the same anti-AR antibody using the same immunohistochemistry protocol, and samples with ≥1% of AR-positive nuclei were deemed AR-positive TNBCs. RESULTS: AR status shows population-specific patterns of association with patients' overall survival after controlling for age, grade, population, and chemotherapy. We found AR-positive status to be a marker of good prognosis in US and Nigerian cohorts, a marker of poor prognosis in Norway, Ireland and Indian cohorts, and neutral in UK cohort. CONCLUSION: AR status, on its own, is not a reliable prognostic marker. More research to investigate molecular subtype composition among the different cohorts is warranted.

Buccal Mucosa Exfoliative Cell Prussian Blue Stain Co-Relates with Iron Overload in ß-Thalassemia Major Patients.

Thalassemics require regular blood transfusion therapy leading to iron overload in the body tissues, which is a major cause of morbidity and mortality in these patients. We hereby attempted to measure this iron overload by means of exfoliative cytology, a non-invasive and inexpensive technique. The aims and objectives of our study were: 1. To detect iron overload by oral exfoliative cytology using Perl's Prussian blue stain in ß-thalassemia major patients. 2. To correlate staining positivity with serum ferritin levels. Smears were obtained from buccal mucosa of 50 ß-thalassemia major patients (who had taken more than 12 transfusions) and 25 healthy subjects of the same age group as controls. Smears were stained with Perl's Prussian blue. Blood samples were taken from the study group for estimation of serum ferritin levels. Grading criteria were defined for assessing the Prussian blue positivity. Perl's positivity was observed in 49 out of 50 of thalassemic patients (98%). 1 patient had Grade 0, 7 patients had Grade I, 5 had Grade II, 12 had Grade III, 14 had Grade IV while 11 patients had Grade V positivity. Spearman Rank's Correlation Co-efficient was 0.38, signifying a weak positive correlation between positivity of buccal smears for Perl's Prussian blue staining and respective serum ferritin levels. Perl's Prussian blue staining of exfoliated cells from buccal mucosa can be used to assess iron overload in ß-thalassemia major patients, as a screening as well as diagnostic tool. With the grading system we can give a semi-quantitative assessment of the same.

Fibroadenoma in Axillary Ectopic Breast Tissue Mimicking Lymphadenopathy.

Swellings in the axilla especially in women are always viewed with suspicion owing to a large number of these being associated with breast carcinoma presenting as nodal metastasis. In a country like India, tuberculous lymphadenopathy is also amongst the first differentials. We present a case of a woman with right sided axillary swelling mimicking lymphadenopathy which on Fine Needle Aspiration Cytology (FNAC) turned out to be fibroadenoma of the ectopic breast tissue. This condition is a rare occurrence in Ectopic Breast Tissue (EBT) as opposed to that in the normal breast, the most common pathology affecting ectopic breast being carcinomas.