Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant syndrome wherein affected individuals are at risk for the development of cutaneous leiomyomas, early-onset multiple uterine leiomyomas, and an aggressive subtype of renal cell cancer. HLRCC is caused by germline mutations in the fumarate hydratase (FH) gene, which inactivates the enzyme and alters the function of the tricarboxylic acid/Krebs cycle. This article reviews the hitherto described morphologic features of HLRCC-associated renal cell carcinoma (RCC) and outlines the differential diagnosis and ancillary use of immunohistochemistry and molecular diagnostics for these tumors. The morphologic spectrum of HLRCC-associated RCC is wide and histologic features, including tumor cells with prominent nucleoli, perinucleolar halos, and multiple architectural patterns within the same tumor, which are suggestive of this diagnosis. FH immunohistochemistry in conjunction with genetic counseling and germline FH testing are the important parameters for detection of this entity. These kidney tumors warrant prompt treatment as even smaller sized lesions can demonstrate aggressive behavior and systemic oncologic treatment in metastatic disease should, if possible, be part of a clinical trial. Screening procedures in HLRCC families should preferably be evaluated in large cohorts.

Context: The diagnosis of prostatic adenocarcinoma on histopathology depends on architectural and cytomorphological features supported by immunohistochemistry (IHC). Though all the prostate markers show excellent specificity, the sensitivity and percentage positivity vary. Aims: In this study, we aim to study the expression of prostein in normal, benign, and malignant (primary and metastatic) lesions with particular emphasis on its utility in the differential diagnosis of poorly differentiated and metastatic prostatic adenocarcinoma along with a standard panel of IHC markers. Settings and Design: This was both a prospective and retrospective as well as descriptive and observational study. Subjects and Methods: All samples from patients with clinically suspected carcinoma prostate from both primary and metastatic sites from June 2015 to May 2016 were included in the study. Samples with difficulty in diagnosis on hematoxylin and eosin staining were subjected to a panel of IHC markers along with prostein. Statistical Analysis Used: Receiver operating curve analysis and Chi-square test. Results: Prostein showed a 100% sensitivity and specificity to identify normal prostatic epithelium, benign and premalignant lesions, and prostatic adenocarcinoma. Prostein showed a specificity of 100% in differentiating prostatic carcinoma from poorly differentiated urothelial carcinoma and in differentiating metastatic prostatic carcinoma from adenocarcinoma of nonprostatic origin. Conclusions: Prostein is a new and promising prostate-specific marker that showed slightly more sensitivity and specificity than prostate-specific antigen. Thus, adding prostein to the IHC panel will greatly improve the detection of poorly differentiated primary and metastatic lesions of the prostate.

Objective: Gleason scoring is the grading system which strongly predicts the prognosis of prostate cancer. However, even being one of the most commonly used systems, the presence of different interobserver agreement rates push the uropathologists update the definitons of the Gleason patterns. In this study, we aimed to determine the interobserver agreement variability among 7 general pathologists, and one expert uropathologist from 6 different centers. Methods: A set of 50 Hematoxylin & Eosin stained slides from 41 patients diagnosed as prostate cancer were revised by 8 different pathologists. The pathologists were also grouped according to having their residency at the same institute or working at the same center. All pathologists' and the subgroups' Gleason scores were then compared for interobserver variability by Fleiss' and Cohen's kappa tests using R v3.2.4. Results: There were about 8 pathologists from 6 different centers revised all the slides. One of them was an expert uropathologist with experience of 18 years. Among 7 general pathologists 4 had surgical pathology experience for over 5 years whilst 3 had under 5 years. The Fleiss' kappa was found as 0.54 for primary Gleason pattern, and 0.44 for total Gleason score (moderate agreement). The Fleiss' kappa was 0.45 for grade grouping system. Conclusion: Assigning a Gleason score for a patient can be problematic because of different interobserver agreement rates among pathologists even though the patterns were accepted as well-defined.

Context: The roles of estrogen and progesterone in human prostate carcinogenesis have been only recently recognized. Aims: This study was conducted to evaluate the expressions of esterone receptor-beta (ER-β), progesterone receptor (PR), and Ki-67 in benign and malignant lesions of the prostate. Settings and Design: The study was conducted at a tertiary care hospital. It was an analytical cross-sectional study. Materials and Methods: We selected a total of 39 cases including 26 cases of benign prostatic hyperplasia and 13 cases of adenocarcinoma prostate. The proportion of cases showing expression for ER-β, PR, and Ki-67 was noted for both groups. A difference in immunoexpression between benign and malignant cases was evaluated. Association between receptor expression and Gleason grade was evaluated for malignant cases. Statistical Analysis Used: To compare the difference in expressions of ER-β, PR, and Ki-67 Mann–Whitney U test was used. Association between ER-β, PR, and Ki-67 expression and Gleason grade was analyzed using the Chi-square test. Results: ER-β expression was seen in all benign and malignant cases, whereas the majority of the malignant cases (61.54%) were negative for progesterone expression. Epithelial expressions of ER-β and PR were significantly higher in benign as compared with malignant lesions. Malignant cases showed a significantly higher expression of Ki-67. However, we did not find any association between the expressions of these markers with Gleason grade. Conclusions: The expressions of ER-β and PR were significantly higher in the epithelium in benign cases as compared with malignant cases. Ki-67 expression was significantly higher in the malignant group as compared with the benign group.

Background: Recently, we publish two case reports about association of nonspecific granulomatous prostatitis (NSGP) and eosinophilic metaplasia (EM) in benign prostatic epithelium. There is no investigation of large series of this association in medical literature. Aim of the current study is to investigate the frequency of association of NSGP and prostatic EM in a large series of cases and their relationship with the basic prostate pathology: benign prostatic hyperplasia (BPH), National Institutes of Health-category IV prostatitis (so-called histologic prostatitis (HP)), and prostatic adenocarcinoma (PCa). Materials and Methods: A retrospective record review for NSGP was performed on a total of 2366 prostatic specimens of all types of material. All cases of NSGP were reviewed for the presence of EM, BPH, and HP. NSGP with EM-cases and control cases with high grade PCa with endocrine differentiation (so-called Paneth cell-like changes) were evaluated immunohistochemically. Results: NSGP was found in nine cases (0.38%). EM was detected in benign perigranulomatous secretory epithelial cells in 100% of cases with NSGP and were closely associated with BPH and HP. Immunohistochemically, in 55.5% of cases with EM, there was weak focal apical false-positive staining for p504s. Conclusion: EM is a very common lesion in NSGP and reflects histologically a nonspecific cellular response, connected with repeated inflammation, in close relation with BPH and HP. We speculate that EM might serve as a morphological precursor of the immunologic phase of NSGP. This constant morphological finding could facilitate the histopathological differential diagnosis of NSGP with other types of granulomatous prostatitis and high grade PCa with or without endocrine differentiation.

Paraganglioma is a rare neuroendocrine tumor arising from undifferentiated cells of the primitive neural crest. We report a case of renal paraganglioma in a 67-year-old patient. Computed tomography demonstrated a solid mass in the middle and lower pole of the right kidney. Sonography revealed an enlarged right kidney with an irregular shape but distinct border. Renal cell carcinoma was diagnosed provisionally; the tumor was completely resected and submitted for pathological examination. Unexpectedly, histopathology and immunohistochemistry confirmed paraganglioma arising from the renal parenchyma. In this study, we report the exceptional occurrence of Paired box gene 8 (PAX-8) expression in a renal paraganglioma. In addition, we demonstrated diffuse cytokeratin positivity in this renal paraganglioma. Although our report of a paraganglioma originating from the kidney is not unique, our finding expands the known immunophenotypic spectrum of this tumor. The awareness of the possible occurrence of cytokeratin diffuse positivity in paraganglioma is relevant to avoiding misdiagnosis of paraganglioma.

Primary renal angiosarcomas (AS) are uncommon tumors with poor prognosis. Aetiology is unknown but some unproven risk factors have been described. It is difficult to discriminate these masses from renal cell carcinomas or other renal masses with imaging modalities. Immunohistochemistry plays an important role in the diagnosis. Main treatment protocol for primary renal AS is still controversial and nephrectomy with chemotherapy and/or radiotherapy seems the only treatment option. We state a primary renal angiosarcoma case for its rareness and contribution to literature.

Collagenofibrotic glomerulopathy (CFG) is a rare idiopathic kidney disease characterized by abnormal deposition of atypical Type III collagen fibers in the glomerulus causing subendothelial and mesangial expansion, manifesting as progressive renal dysfunction accompanied by proteinuria. The majority of CFG cases reported in literature are from Japan where this disease entity was initially recognized. There is an increased awareness and diagnosis of this rare renal disease in India with the recent increase in utilization of electron microscopy (EM) in clinical diagnostic settings. We describe a 28-year-old Bangladeshi woman who presented with hypertension and nephrotic range proteinuria not amenable to treatment with steroids and cyclophosphamide, whose renal biopsy demonstrated diagnostic ultrastructural features of CFG. This illustrative case is presented to highlight the role of EM analysis for diagnostic accuracy in renal biopsy evaluation in addition to demonstrating the unusual renal biopsy findings of this rare entity.

Malignant phyllodes tumor of the prostate is a very rare entity. Here, we describe a 51-year-old patient with a malignant phyllodes tumor of the prostate with a poor prognosis and normal prostate-specific antigen levels. Digital rectal examination revealed a hard, nodular mass in the prostate, and magnetic resonance imaging exhibited a cystic mass measuring 8.7 cm × 7.0 cm × 6.7 cm. Immunohistochemical staining showed that the epithelial components were positive for CK8/18 and cytokeratin AE1/AE3; the atypical stromal cells were positive for CD34 and vimentin. Histological analysis resulted in a diagnosis of malignant phyllodes tumor of the prostate. Radical surgery was the treatment of choice. However, tumor recurrence was identified 6 months after the surgery, and the patient died 10 months after the surgery.

Paratesticular tumours are relatively rare and mostly of the mesenchymal origin. Due to its rarity, general surgical pathologists might have limited experience on the diagnostic entities and relevant differential diagnoses related to mesenchymal paratesticular tumours. This may likely cause diagnostic difficulties in a daily pathology practice. Paratesticular liposarcoma is a highly heterogeneous tumour and may be misdiagnosed as a benign fibromatous lesion. Herein we present a case of well-differentiated paratesticular liposarcoma of the sclerosing type initially diagnosed as a fibrous pseudotumour. Main differential diagnostic considerations are highlighted.

In spite of the advent of many high throughput technologies, tumor tissue biomarkers are still the gold standard for diagnosis and prognosis of different malignancies including epithelial ovarian cancer (EOC). EOC is a heterogeneous disease comprised of five major subtypes which show distinct clinicopathological features and therapy response. Acquirement of chemoresistance toward therapy is a major challenge for successful treatment outcome in EOC patients. Several markers have been tested by immunohistochemical method to evaluate their prognostic merit to predict clinical outcome. However, a vast majority of such markers have been assessed for high-grade serous and clear cell ovarian cancer, among all subtypes of EOC. The current review elaborates upon those biomarkers that can potentially predict chemoresistance with subtype specificity.

Over the years, immunohistochemistry has emerged as a powerful tool for a more precise diagnosis of certain tumors in gynecologic oncopathology and resolving certain diagnostic dilemmas with significant treatment implications. Certain specific immunohistochemical (IHC) markers have been useful in the more correct identification of rare tumors, characterized by specific molecular signatures. Immunohistochemistry has also been useful in the identification of underlying genetic events, characterizing various tumors, as well as precancerous lesions. This review will focus upon the judicious application of various IHC antibody markers in gynec oncopathology, including authors' experience during “sign-outs” and especially during interaction with other oncology colleagues within the institutional disease management group. The updated references were retrieved from PubMed.

Introduction: Uterine tumors resembling ovarian sex cord tumor (UTROSCT) are a unique group of neoplasms with diverse morphology and immunophenotypic characteristics, coexpressing sex cord, epithelial, and smooth-muscle markers. To date, less than 100 cases have been reported and there is paucity of data concerning their clinical behavior. Materials and Methods: All cases of uterine body tumors diagnosed over a period of two and a half years (2016-2018) were retrieved. Histopathological features were reviewed and extended panel of immunohistochemistry was performed to identify cases of UTROSCTs. Results: Six cases of UTROSCTs were identified with a median age of 46.5 years. Four of them presented with menorrhagia, while two with postmenopausal bleeding including one with a history of carcinoma breast. Three of these cases were initially misdiagnosed as endometrial stromal sarcoma and adenocarcinomas. They all underwent hysterectomy with bilateral salpingo-oophorectomy. Conclusion: It is considered a tumor with low malignant potential; however, one out of six cases (16.7%) in our study showed metastasis, within 1 year of diagnosis. It is important to recognize this entity as it mimics a wide range of both benign and malignant tumors. Molecular pathogenesis and exact management protocols remain elusive due to rarity,hence, multi-institutional studies are warranted.

Background: Abnormal placentations such as placenta accreta, placenta increta and placenta percreta are important causes of hemorrhage after delivery causing maternal morbidity and mortality. Risk factors for abnormal placentation are prior caesarean section, placenta previa and pre-eclampsia. There is a need for reliable antenatal diagnosis for these serious conditions. If these pregnancies can be identified, antepartum, site and time of delivery as well as the surgical approach can be planned ahead; this decreases the incidence of maternal mortality due to massive hemorrhage. Aim: (1) To study the incidence of abnormal placentation in emergency peripartum hysterectomy specimen. (2) To evaluate various risk factors associated with abnormal placentation. Materials and Method: Retrospective cross-section study done in patients with abnormal placentation leading to emergency peripartum hysterectomy during a course of eight-year period. Result: We received total of 18 emergency hysterectomy specimens during eight-year period of which placenta accreta accounts 55.5 percent (10/18), placenta increta upto 38.8 percent (7/18) and placenta percreta 5.5 percent (1/18). Analysis of result with parity shows uniparous women up to 22.2 percent (4/18), and multiparous women 77.7 percent (14/18). Risk factor analysis shows previous caesarean section in 55.5 percent (10/18), placenta previa in 33.3 percent (6/18) and pre-eclampsia in 11.1 percent (2/18). Conclusion: In our study, among abnormal placentation, incidence of placenta accreta accounts for 55.5 percent and it is more common in multiparous women than uniparous women. Among risk factors in our study, previous caesarean section is commonly associated with abnormal placentation followed by a placenta previa and pre-eclampsia.

Dedifferentiated endometrioid carcinoma or dedifferentiated endometrioid adenocarcinoma (DEAC) is defined by the presence of undifferentiated carcinoma with endometrioid carcinoma. Undifferentiated component can be misinterpreted as solid component of high-grade endometrioid carcinoma or sarcomatous component of malignant mixed mullerian tumor. We present two cases of DEAC. Two postmenopausal women underwent hysterectomy for vaginal bleeding. Microscopically, sections from the endometrial tumors showed a biphasic growth consisting of an undifferentiated component and a glandular component with sharp transition between the two components. The undifferentiated component showed focal positivity for cytokeratin and vimentin, while glandular component was diffusely positive for cytokeratin and negative for vimentin expression.

Primary uterine angiosarcoma is a very rare malignant tumor in the female genital tract and only 23 cases have been previously reported in the literature. It is often clinically misrecognized as another disease due to its low incidence. In this report, we present a new case of a 78-year-old woman diagnosed on histopathologic observation and immunohistochemical staining. Additionally, available studies are collected and reviewed to summarize the clinical and pathological characteristics of primary uterine angiosarcoma to remind gynecologists and pathologists of this rare disease when they encounter such cases.

Epithelioid trophoblastic tumor is a rare gestational trophoblastic neoplasm arising from the intermediate trophoblasts. Although usually seen in the reproductive period, it may be encountered during the postmenopausal period. A 56-year-old woman who had given her last birth 21 years ago presented to the hospital with a complaint of postmenopausal bleeding. She had a history of eight live pregnancies and had been in menopause for 4 years. With the help of typical histopathologic and immunohistochemical findings, a diagnosis of “epithelioid trophoblastic tumor” was made. The diagnosis was made at an advanced age and the case had extraordinary features such as high mitotic activity and Ki-67 proliferation index (70%). Gestational trophoblastic neoplasms are rare causes of postmenopausal bleeding which may cause differential diagnosis problem. They should be kept in mind even if the patient age does not comply with because of the differences in treatment.

The multidisciplinary team approach has been employed internationally for decades, as an attempt to bring collaborative decision-making and concentrate clinical experience from multiple specialties on single patient cases in a systematic fashion. Adoption is not yet worldwide, but is increasing. The role of the histopathologist is central, providing vital information and context to clinical diagnosis and management. Our review summarizes some of the most relevant research on the topic of MDT usage and efficacy in relation to breast cancer, attempting to draw together its advantages and challenges. It is hoped that this review will make a contribution to the current international literature regarding multidisciplinary approaches in breast cancer care.

Aims and Objectives: We examined the prognostic value of Tumor stroma ratio (TSR) in breast tumor core biopsy (TCB) specimen to determine response to neoadjuvant therapy (NAT) prior to modified radical mastectomy (MRM). Methods: This was a retrospective analysis of patients with breast cancer who underwent TCB before NAT between August 2016 and July 2018. TSR in TCB was studied independently by 2 pathologists ( VM, VS) defined as stroma rich (TSR≤50%) or stroma poor (TSR>50%). MRM specimen of these patients were subsequently studied .Residual cancer burden (RCB) was calculated using the MD Anderson RCB calculator, categorized as complete (0), good (1) Partial (2) and no response (3). Statistical analysis was done to assess correlation of TSR to RCB. Results: A total of 62 patients were analyzed. Mean(SD) age was 48(11) years.Twenty eight (45%) and 34 (55%) patients were stroma rich and stroma poor respectively. Twenty six (42%) patients were responders and 36 (58%) non-responders to NAT. Among stroma rich patients, only 3 (10%) were responders (Class 0 &1)and 25 (90%) non-responders(Class2&3)to NAT, among stroma poor patients 23 (68%) responded well and 11 (32%) did not.TSR had a moderate negative correlation with RCB (-0.6). On univariate analysis, only TSR had a significant effect on RCB class (<0.001). Conclusions: TSR on TCB is a useful prognostic factor to determine response of breast carcinoma patients to neoadjuvant therapy.It is cost effective, simple and quick. Larger multi-centric studies would be useful to study its clinical implications.

Background: Tumor budding denotes a phenomenon in which the tumor cells, singly or in small aggregates, become detached from the neoplastic glands at the invasive front of adenocarcinoma. Tumors with budding cells have a significantly more aggressive clinical course. Significance of tumor budding has mainly been examined in the field of colorectal cancer. Aims: To document the number tumor buds at the invasive front of invasive breast cancer. To correlate the number of tumor buds with other histopathological parameters, and available clinical details. Setting and Study Design: Analytical study at a rural tertiary care referral institute. Materials and Methods: It was a retrospective study of invasive breast cancer cases from January 2012 to April 2015. Tumor buds were counted in H and E stained sections in 10 High Power Fields (HPFs). Association of tumor budding with histological parameters and available clinical details were analyzed statistically. Statistical Analysis Used: Frequencies, Chi-Square Test and Crosstabs were used for calculation. Results: 50 cases of invasive breast carcinoma were analyzed. Invasive ductal carcinoma constituted predominant histological type (92%). Low tumor budding (tumor buds ≤20/10HPFs) constituted 20 cases. High tumor budding (tumor buds >20/10HPFs) constituted 30 cases. Association of high tumor budding with lympho-vascular invasion, lymph node metastasis, primary tumor staging, regional lymph node staging, necrosis and Monckeberg medial sclerosis was statistically significant. Conclusion: Tumor budding may be incorporated as a new parameter in reporting protocols. Tumor budding serves as an indispensable touchstone in evaluating cases of invasive breast cancer.

Human epidermal growth factor receptor HER2/neu status is an important prognostic factor for breast cancer as it is crucial in stimulating growth and cellular motility. Overexpression of HER2/neu is observed in 10%−35% of the human breast cancer and is associated with prognosis and response to treatment. The magnitude of amplification must be determined to facilitate better prognosis and personalized therapy in the affected patient. This study aims to investigate the HER2/neu status in breast cancer by concurrent HER2/neu protein overexpression immunohistochemically with HER2/neu DNA amplification by quantitative real-time polymerase chain reaction (PCR), allowing accurate and precise quantification of HER2/neu amplification after a follow-up period. A total of 54 paired tissue samples from formalin-fixed paraffin-embedded (FFPE) breast cancer patients enrolled in this study were collected to evaluate tumor and normal tissues. Only cases with 80% and more tumor cells were included. For confirmation of immunohistochemistry (IHC) results, qPCR was used to determine the HER2/neu amplification. The association between clinicopathological variables like age, tumor size, histological grade, stage, lymph node status, hormone receptor status, family history, recurrence rate, and vital status was evaluated. We observed that 11/54 (20.4%) of the tumor tissues are positive for HER2/neu protein overexpression by IHC. A total of 8 out of these 11 cases (72.7%), which presented a score of 3+, showed gene amplification of HER2/neu. The concordance rate between IHC and qPCR was 94.4%. HER2/neu gene amplification was found to be significantly associated with recurrence, increased risk of death, and progesterone receptor status, supporting a negative prognostic role of HER2/neu in breast cancer survival. In conclusion, IHC can be used as an initial screening test to detect HER2/neu protein overexpression, and the use of qPCR can verify the IHC results and establish HER2/neu status in routine clinical practice.

Introduction: Breast cancer is the most common cancer in women. Owning to the prominent role of biomarkers in molecular classification of breast cancer in recent years, evaluation of estrogen receptor (ER), progesterone receptor (PR), and Her2/neu seems to be required for prognosis and treatment of patients. Material and Methods: One-hundred twenty two patients with primary breast carcinoma were selected and immunohistochemistry staining for ER, PR, and Her2/neu were performed on representative paraffin blocks. ER level can be semi-quantified by immunohistochemistry using the H-score. The score, given as the sum of the percent of tumor cells staining multiplied by the intensity level, ranges from 0 to 300 as low, intermediate, and high grades. The statistical association of ER expression with the level of PR and Her2/neu, tumor size, necrosis, microscopic grade, vascular invasion, and lymph node involvement were analyzed using SPSS16 software. Results: Results showed that among 122 studied patients, 44.3% were in the low ER-positive group where most of these cases (22.1%) were Her2/neu negative. Although there was a reciprocal interplay between the expression of ER and Her2/neu, increased expression of ER had a direct relation with PR level. However, there was no statistical relation between ER level with age, tumor size, necrosis, microscopic grade, vascular invasion, and lymph node involvement. Discussion: The study clearly indicated that low ER group encompasses the high frequency of breast cancer patients. Furthermore, the most cases of low ER patients were in Her2/neu negative group.

Aims: To explore clinical, histopathological and immunohistochemistry (IHC) features of mammary analogue secretory carcinoma (MASC) with systematic literature review. Settings and Design: Hospital based cross-sectional study. Subjects and Methods: The data of all cases of MASC diagnosed over a period of 1 year i.e., from July 2017 to July 2018 were retrieved. The haematoxylin and eosin (H and E) sections, and IHC sections were studied. A strict histological and recently updated criteria were applied and patients with a confirmed diagnosis of MASC were included in the study. A systematic literature review was conducted by searching the PubMed and National Centre for Biotechnology Information database. Statistical Analysis Used: Microsoft Excel 2010. Results: The present case series is 27th in the English literature and 1stcase series describing its histopathology in the Indian literature. The mean age of presentation is 43 years. Female preponderance was found i.e., M:F ratio of 0.5. Conclusion: Histopathology and if necessary, followed by IHC is required for the confirmation of diagnosis of MASC. We should be aware about this recently described entity which is usually mistaken for other low grade salivary gland carcinomas like Acinic cell carcinoma (AciCC) and Mucoepidermoid carcinoma (MEC). The knowledge about its typical morphology, high degree of suspicion and IHC confirmation with both S-100 and Mammaglobin help in precise diagnosis.