Immunohistochemical Surrogates for Molecular Stratification in Medulloblastoma.

BACKGROUND: The WHO classification of central nervous system neoplasms (2016) recognized 4 histologic variants and genetically defined molecular subgroups within medulloblastoma (MB). Further, in the 2021 classification, new subtypes have been provisionally added within the existing subgroups reflecting the biological diversity. YAP1, GAB1, and ß-catenin were conventionally accepted as surrogate markers to identify these genetic subgroups. OBJECTIVES: We aimed to stratify MB into molecular subgroups using 3 immunohistochemical markers. TP53 mutation was also assessed in Wingless (WNT), and Sonic Hedgehog (SHH) subgroups. Demographic profiles, imaging details, and survival outcomes were compared within these molecular subgroups. PATIENTS AND METHODS: Our cohort included 164 MB cases diagnosed over the last 10 years. The histologic variants were identified on histology, and tumors were molecularly stratified using YAP1, GAB1, and ß-catenin. Further, TP53 mutation was assessed using immunohistochemical in WNT and SHH subgroups. The clinical details and survival outcomes were retrieved from the records, and the mentioned correlates were evaluated statistically. RESULTS: The age ranged from 1 to 52 years with M:F ratio of 2:1. Group 3/group 4 constituted the majority (48.4%), followed by SHH (45.9%) and WNT subgroups (5.7%). Desmoplastic/nodular and MB with extensive nodularity had the best survival, whereas large cell/anaplastic had the worst. The follow-up period ranged from 1 to 129 months. The best outcome was observed for the WNT subgroup, followed by the SHH subgroup; group 3/group 4 had the worst. Among the SHH subgroup, TP53 mutant tumors had a significantly poorer outcome compared with SHH-TP53 wildtype. CONCLUSIONS: Molecular stratification significantly contributes to prognostication, and a panel of 3 antibodies is helpful in stratifying MB into its subgroups in centers where access to advanced molecular testing is limited. Our study reinforces the efficacy of incorporating this cost-effective, minimal panel into routine practice for stratification. Further, we propose a 3-risk stratification grouping, incorporating morphology and molecular markers.

Cytologic diagnosis of small cell carcinoma of the ovary: A case report with review of the literature.

Small cell carcinoma of the ovary (SCCO) is an exceedingly rare malignant neoplasm. It has been classified into two types: hypercalcemic and pulmonary type, the former being relatively more common. These are highly aggressive neoplasms with rapid down-hill course and poor disease-outcome. A high index of clinical suspicion, systematic radiological evaluation, and an early tissue diagnosis are a must for timely patient management and a better outcome. A definitive diagnosis can be established by demonstration of the characteristic morphologic and immunochemical features. We report a case of SCCO of pulmonary type in a peri-menopausal female, presenting with a large abdomino-pelvic mass, which was diagnosed by fine needle aspiration cytology (FNAC), by immunocytochemistry on cell-block. In addition, cytological features of metastatic SCCO, pulmonary type, in the Papanicolaou stained liquid-based cytology (SurePath) preparation are also presented. The current report highlights the diagnostic utility of FNAC in the diagnosis of such rare gynecological malignancies.

Medulloblastoma with myogenic and/or melanotic differentiation does not align immunohistochemically with the genetically defined molecular subgroups.

The World Health Organization classification of central nervous system neoplasms (2016 update) recognizes 4 histological variants and genetically defined molecular subgroups within medulloblastoma (MB). MB with myogenic differentiation is one of the rare variants, which is usually recognized as a pattern alongside the known histological variants. Because of its rarity, less is known about its molecular landscape and importantly about its placement in the current molecular schema. We aimed to analyze this rare variant for expression of 3 immunohistochemical markers conventionally used in molecular stratification of MB. Demographic profile and imaging details with survival outcome were also analyzed. Sixty-five MB cases were molecularly stratified using immunohistochemical markers (YAP1, GAB1, ß-catenin). MB with myogenic differentiation and MB cases showing variable immunoreactivity with the above 3 antibodies were further evaluated for smooth muscle actin, desmin, myogenin, and HMB45. Seven cases were categorized as MB with myogenic and/or melanotic differentiation. Age ranged from 2 to 40 years with a male-to-female ratio of 1:1.3. In 4 cases, myogenic or melanotic differentiation was evident on histology, whereas in 3, differentiation was highlighted only with muscle markers. Interestingly, all 7 cases showed variable immunoreactivity with 3 molecular markers and did not follow the conventionally accepted algorithm used for molecular stratification. Follow-up period ranged from 9 to 57 months. Overall survival revealed a varied pattern, with 3 deaths and 4 patients being alive with no evidence of disease at last follow-up. Our results provide evidence that these variants are distinct and do not align immunohistochemically with the currently recognized genetic subgroups.