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ABSTRACT Background: Urothelial carcinomas (UC) account for 6 and 2% of all cancers in men and women, respectively. Human papillomavirus (HPV) is one of the causative agents in cancers of the uterine cervix and head and neck. The role of HPV is also being studied in cancers of the urinary bladder, penis, and prostate. As p16-INK4a is a surrogate marker for high-risk HPVE7 oncoprotein, this study aims to highlight the utility of p16 immunohistochemistry (IHC) in the evaluation of HPV-associated UC. Materials and Methods: A retrospective study was conducted on UC of the bladder received in the Pathology department between January 2013 and December 2018. Bladder biopsies from non-neoplastic lesions served as controls. IHC was done for the detection of the p16 antigen. The p16 staining was recorded as positive, when there was strong staining in >50% of tumor nuclei. The p16 positive and negative tumors were compared based on age, gender, tumor size, grade, and muscle invasion. P value <0.05 was considered statistically significant. Results: The expression of p16 was analyzed in 72 UC and compared with 20 non-neoplastic cases, of which 26.4% of the cases showed p16 expression. The p16 expression was absent in the non-neoplastic lesions. While the majority (87.5%) of the low-grade tumors were negative for p16 expression, 43.8% high-grade tumors were positive. Similarly, a larger proportion of invasive carcinomas (38.8%) expressed p16 as compared to non-invasive carcinomas (13.8%). Thus, p16 expression showed a significant association with grade and stage in these malignancies (P < 0.05). Conclusion: The p16 expression was associated with high-grade and muscle-invasive UC. The p16 was absent in all non-neoplastic and precursor lesions. Thus, it can provide essential information not only about HPV association but also on the prognostic implications for the patients.

Diogenes syndrome is characterized by extreme self-neglect, social withdrawal, and poor personal and domestic hygiene. We report a case of Diogenes syndrome presenting with dermatitis passivata. An unusual \"mask\" of dirt resembling a carapace, onset of neglect after awareness of a breast lump and resumption of personal grooming and social activities after removal of the lump and counseling were seen.

Background Plasma cell disorders are a rare group of hematological malignancies that accounts for 10% of all hematological neoplasms. Solitary plasmacytomas are rarer entities accounting for less than 5% of all the plasma cell dyscrasias. They encompass three subtypes - Solitary Plasmacytoma of Bone (SPB) and Solitary Extramedullary Plasmacytoma (SEP) and multiple solitary plasmacytomas (MSP). In this study, we discuss the clinical, histopathological and immunohistochemical characteristics of solitary plasmacytomas. Methods A 13 year retrospective analysis of solitary plasmacytomas was performed from a single tertiary care center. Bone marrow evaluation was done concurrently at the time of diagnosis to rule out the presence of multiple myeloma. Results A total of 29 cases fulfilled the diagnostic criteria for SP during the study period. SPB accounted for 55.2%, SEP for 44.4% and MSP for 3.4% of the cases. The most common sites involved were the paranasal sinuses and vertebrae. Other infrequent sites included lymph node, tonsil and lungs. The mean age of presentation of SPB was a decade later than SEP. A male preponderance was observed in both subtypes. Conclusion Solitary plasmacytoma is a rare entity, the diagnosis of which requires a systematic approach. There is limited data available in the literature on the clinico-pathological characteristics of SP from India.

The surgeon needs to assess clinically significant thyroid nodules as they may represent aggressive forms of thyroid cancer or ectopic parathyroid glands. We discuss one such unusual nodule in the thyroid.

Key Clinical Message This case report highlights the importance of recognizing and accurately diagnosing ganglioneuroblastoma, an uncommon variant of neuroblastic tumors in children. Ganglioneuroblastomas have diverse clinical and morphological presentations, and histopathological examination is paramount in guiding treatment decisions, especially in cases with ambiguous symptoms. Early detection is crucial, as the prognosis varies significantly based on the subtype and the presence of metastatic disease. Clinicians should maintain a high index of suspicion and utilize radiological examinations to promptly identify and treat these tumors. Children are frequently affected by neuroblastic tumors, which grow from the sympathoadrenal lineage of the neural crest during its development. However, intermixed ganglioneuroblastomas are far less common within the same tumor spectrum, the diagnosis of which could become challenging amidst an unusual presentation. In our case report, we present a 4‐year‐old boy who had complaints of fever and difficulty in walking, with a supra‐renal mass on ultrasound, which was diagnosed as ganglioneuroblastoma‐intermixed type on histopathological examination. This report aims to contribute to the understanding of the diverse clinical and morphological spectrum of ganglioneuroblastomas and the importance of multidisciplinary collaboration and histopathological examination to enhance decision‐making in such ambiguous scenarios. Microscopy and immunohistochemical findings suggestive of Ganglioneuroblastoma Schwannian stroma rich type.

Hypophysitis is classified into primary and secondary. Xanthomatous hypophysitis is one of the rare types of primary hypophysitis. A 55-year-old female presented with headache, vomiting, and blurring of vision. She also had endocrine dysfunction in the form of low serum T3, T4, and low cortisol levels. MRI scan showed a sellar expansile lesion suggestive of pituitary macroadenoma. Microscopy showed pituitary tissue replaced by inflammatory infiltrate made up of foamy histiocytes arranged in sheets along with lymphoplasmacytic infiltrate. Interspersed areas of fibrosis, hyalinization, few congested and sclerosed blood vessels were seen. Compressed residual pituitary tissue was identified at the periphery. Xanthomatous hypophysitis is a rare entity which can mimic as pituitary adenoma both clinically and radiologically. Accurate diagnosis at an early stage with postsurgical steroid therapy may help to prevent permanent pituitary damage.

Background The incidence of and mortality from colorectal cancers (CRC) can be reduced by early detection. Currently there is a lack of established markers to detect early neoplastic changes. We aimed to identify the copy number variations (CNVs) and the associated genes which could be potential markers for the detection of neoplasia in both ulcerative colitis-associated neoplasia (UC-CRN) and sporadic colorectal neoplasia (S-CRN). Methods We employed array comparative genome hybridization (aCGH) to identify CNVs in tissue samples of UC nonprogressor, progressor and sporadic CRC. Select genes within these CNV regions as a panel of markers were validated using quantitative real time PCR (qRT-PCR) method along with the microsatellite instability (MSI) in an independent cohort of samples. Immunohistochemistry (IHC) analysis was also performed. Results Integrated analysis showed 10 overlapping CNV regions between UC-Progressor and S-CRN, with the 8q and 12p regions showing greater overlap. The qRT-PCR based panel of MYC, MYCN, CCND1, CCND2, EGFR and FNDC3A was successful in detecting neoplasia with an overall accuracy of 54 % in S-CRN compared to that of 29 % in UC neoplastic samples. IHC study showed that p53 and CCND1 were significantly overexpressed with an increasing frequency from pre-neoplastic to neoplastic stages. EGFR and AMACR were expressed only in the neoplastic conditions. Conclusion CNVs that are common and unique to both UC-associated and sporadic colorectal neoplasm could be the key players driving carcinogenesis. Comparative analysis of CNVs provides testable driver aberrations but needs further evaluation in larger cohorts of samples. These markers may help in developing more effective neoplasia-detection strategies during screening and surveillance programs.

Abstract Introduction: Dedifferentiated liposarcoma (DDLPS) is defined as a progression of well-differentiated liposarcoma (WDLPS) to another nonlipogenic sarcoma. Since a variety of heterologous sarcomas can be encountered in dedifferentiation, clinical dilemmas arise. The present study analyzed the role of clinicopathologic and immunohistochemical (IHC) features in the diagnosis of DDLPS and its differentiation from mimics. Materials and Methods: A retrospective and prospective study was conducted wherein all cases of liposarcoma from 2012 to 2017 were reviewed. DDLPS cases were identified among pleomorphic lesions. Clinical and histopathological details for these cases were retrieved from medical records section and department archives. Histomorphology and immunohistochemistry (MDM2, S100, and Ki-67) were analyzed for these cases. Results: Among 37 cases of liposarcomas reviewed, DDLPS was diagnosed in 12 cases (32.4%). Mean age of the patients was 54.3 years with equal gender distribution (M:F =1:1.2). Two patients had recurrent tumors. Most were retroperitoneal (58.3%) with mean duration of symptoms being 8.7 months. Mean tumor dimension was 17.5 cm. High-grade dedifferentiated component was most common (83.3%) with only one case each (8.3%) of low-grade and homologous dedifferentiation. Undifferentiated pleomorphic sarcoma was the frequent nonlipogenic sarcoma. MDM2 overexpression was detected in 100%, focal S100 positivity seen in 66.6%, and mean Ki-67 labeling index was 24. Conclusion: DDLPS exhibits aggressive clinical behavior. Adequate sampling, correlation to clinical details, demonstration of transition from WDLPS to DDLPS aid in narrowing the differentials. Immunostaining with MDM2 helps in definite categorization and S100 highlights lipoblasts, when they are not easily identifiable. MDM2, CDK4, and p16 IHC panel is recommended in all cases and fluorescence in situ hybridization analysis where IHC is noncontributory.

Background: Loss of heterozygosity of p53 along with aneuploidy is deemed to be the early molecular steps in Barrett metaplasia-dysplasia-adenocarcinoma sequence. Objective biomarkers need to be used along with microscopy for risk stratification to predict the progression of Barrett esophagus (BE) to carcinoma. Aim: This study aims to study p53 protein expression in dysplasia and correlate the same with morphology in BE. Materials and Methods: A time-bound study was conducted from January 2011 to June 2015. All esophageal biopsies showing histological evidence of columnar epithelium with the presence of goblet cells were included. The cases which showed dysplasia were graded on hematoxylin and eosin stain. Evaluation of p53 immunohistochemistry staining was done on all the cases of BE. Dysplasia was correlated with the expression of p53 using Chi-square value (χ2) and Fischer's exact test wherever appropriate. P < 0.05 was considered to be statistically significant. Results: Of 829 esophageal biopsies received, 119 were endoscopically suspected to be BE, of which 85 cases were confirmed on microscopy. In our study, there were 75 cases negative for dysplasia (88.2%), 8 with low-grade dysplasia (LGD) (9.4%), and two with high-grade dysplasia (HGD) (2.4%). Three cases of BE had associated adenocarcinoma. Immunostaining with p53 done on all the 85 cases showed positive staining in all cases with LGD, one with HGD and two with adenocarcinoma. In the present study, immunostaining with p53 showed 90% sensitivity, 89.3% specificity, positive predictive value of 52.9%, and negative predictive value of 98.5%. Conclusion: The technical simplicity, easy availability, and comparatively lower cost enhance the role of p53 as a biomarker in risk stratification for patients with BE.

Introduction: Neoplastic involvement of cerebrospinal fluid (CSF) secondary to known or unknown primaries elsewhere is a poor prognostic factor and is equivalent to stage IV disease. Aim: The aim of the study is to analyse the cytological features of neoplastic meningitis in a tertiary care center. Materials and Methods: A retrospective study of 400 consecutive CSF samples was done in the cytology laboratory of our hospital. The fluid obtained by spinal tap was sent for microbiological, biochemical and cytological evaluation. Smears that showed the presence of malignant cells were included in this study. Results: Out of 400 cases, 36 (9%) showed neoplastic meningitis. Of which, 13 cases (36%) revealed leukemic infiltration, 2 (6%) lymphomatous infiltration and 21 (58%) carcinomatous meningitis. The leukemia cases included seven cases of acute lymphoblastic leukemia and six cases of acute myeloid leukemia. Among the carcinomatous meningitis cases, eight were metastasis from carcinoma breast, six from lung carcinoma and one each from malignancies of gallbladder, stomach and retinoblastoma. Four cases were metastatic adenocarcinoma from unknown primary. Pleocytosis was a significant finding seen in 58% cases (n = 21). Elevated protein and hypoglychorrhachia was noted in 68% cases (n = 18). Conclusion: A combined diagnostic approach including biochemical, microbiological and pathological evaluation was useful in eliminating infectious meningitis and confirming neoplastic meningitis in these cases. Cytology should be performed on cerebrospinal specimens from all patients with known or suspected malignancy with meningismus. Detection of malignant cells on cytological examination of CSF is the diagnostic gold standard for neoplastic meningitis.