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IDH wild-type (wt) grade 2/3 astrocytomas are a heterogenous group of tumors with disparate clinical and molecular profiles. cIMPACT-NOW recommendations incorporated in the new 2021 World Health Organization (WHO) Classification of Central Nervous System (CNS) Tumors urge minimal molecular criteria to identify a subset that has an aggressive clinical course similar to IDH -wt glioblastomas (GBMs). This paper describes the use of a panel of molecular markers to reclassify IDH -wt grade 2/3 diffuse astrocytic gliomas (DAGs) and study median overall survival concerning for to IDH -wt GBMs in the Indian cohort. IDH -wt astrocytic gliomas (grades 2, 3, and 4) confirmed by IDHR132H immunohistochemistry and IDH1/2 gene sequencing, 1p/19q non-codeleted with no H3F3A mutations were included. TERT promoter mutation by Sanger sequencing, epidermal growth factor receptor amplification, and whole chromosome 7 gain and chromosome 10 loss by fluorescence in situ hybridization was assessed and findings correlated with clinical and demographic profiles. The molecular profile of 53 IDH -wt DAGs (grade 2: 31, grade 3: 22) was analyzed. Eleven cases (grade 2: 8, grade 3: 3) (20.75%) were reclassified as IDH -wt GBMs, WHO grade 4 ( TERT promoter mutation in 17%, epidermal growth factor receptor amplification in 5.5%, and whole chromosome 7 gain and chromosome 10 loss in 2%). Molecular GBMs were predominantly frontal (54.5%) with a mean age of 36 years and median overall survival equivalent to IDH -wt GBMs (18 vs. 19 mo; P =0.235). Among grade 2/3 DAGs not harboring these alterations, significantly better survival was observed for grade 2 versus grade 3 DAGs (25 vs. 16 mo; P =0.002). Through the incorporation of a panel of molecular markers, a subset of IDH -wt grade 2 DAGs can be stratified into molecular grade 4 tumors with prognostic and therapeutic implications. However, IDH -wt grade 3 DAGs behave like GBMs irrespective of molecular profile.

Chordoid meningiomas have an aggressive clinical course characterized by frequent recurrences. Recent whole-genome sequencing studies demonstrated Chr22 loss in chordoid meningiomas not accounted for by NF2 mutations. SMARCB1/INI1 is a candidate gene on Chr22, which has not been analyzed extensively in meningiomas. AKT1 mutation has been recently identified to be a driver of meningiomagenesis.Cases of chordoid meningioma were retrieved along with meningiomas of other subtypes for comparison. INI1 immunohistochemistry was performed. SMARCB1 and AKT1 were analyzed by sequencing.Sixteen chordoid meningiomas were identified (1.1% of all meningiomas). Six cases (37.5%) showed loss of INI1 immunoexpression. All other meningioma subtypes (n = 16) retained INI1 immunoexpression. AKT1 E17K mutation was identified in one case (16.7%). Notably, SMARCB1 mutations were not identified in any of the chordoid meningiomas analyzed, including those showing INI1 loss immunohistochemically.This is the first study to demonstrate loss of SMARCB1/INI1 immunoexpression in chordoid meningiomas, adding to the tumors with INI1 loss. However, in absence of INI1 mutation, mechanisms for INI1 loss require further evaluation. Identification of AKT1 mutation opens up new avenues for targeted therapy in patients with such aggressive tumors.

Mucormycosis in humans has been described as early as 1885 in literature. Isolated renal mucormycosis is rare as it has been mainly described in developing countries like India and China. It is rarer still to find this entity in immunocompetent young males without any risk factors. Specific guidelines on the treatment is not yet known but combined surgical and medical therapy is considered the best modality for its management. We describe a young male who presented with bilateral hydroureteronephrosis. He was initially treated as a case renal tuberculosis which is relatively more common in TB endemic country like ours. However when he did not respond to the anti-tuberculosis drug (ATT), a biopsy revealed mucormycosis. He was treated with nephrectomy and liposomal amphotericin B and oral posaconazole. On follow up of 2 years he is healthy and leading his normal life.

Pilocytic astrocytomas occur rarely in adults and show aggressive tumor behavior. However, their underlying molecular‐genetic events are largely uncharacterized. Hence, 59 adult pilocytic astrocytoma (APA) cases of classical histology were studied (MIB‐1 LI: 1%–5%). Analysis of BRAF alterations using qRT‐PCR, confirmed KIAA1549‐BRAF fusion in 11 (19%) and BRAF‐gain in 2 (3.4%) cases. BRAF‐V600E mutation was noted in 1 (1.7%) case by sequencing. FGFR1‐mutation and FGFR‐TKD duplication were seen in 7/59 (11.9%) and 3/59 (5%) cases, respectively. Overall 36% of APAs harbored BRAF and/or FGFR genetic alterations. Notably, FGFR related genetic alterations were enriched in tumors of supratentorial region (8/25, 32%) as compared with other locations (P = 0.01). The difference in age of cases with FGFR1‐mutation (Mean age ± SD: 37.2 ± 15 years) vs. KIAA1549‐BRAF fusion (Mean age ± SD: 25.1 ± 4.1 years) was statistically significant (P = 0.03). Combined BRAF and FGFR alterations were identified in 3 (5%) cases. Notably, the cases with more than one genetic alteration were in higher age group (Mean age ± SD: 50 ± 12 years) as compared with cases with single genetic alteration (Mean age ± SD: 29 ± 10; P = 0.003). Immunopositivity of p‐MAPK/p‐MEK1 was found in all the cases examined. The pS6‐immunoreactivity, a marker of mTOR activation was observed in 34/39 (87%) cases. Interestingly, cases with BRAF and/or FGFR related alteration showed significantly lower pS6‐immunostatining (3/12; 25%) as compared with those with wild‐type BRAF and/or FGFR (16/27; 59%) (P = 0.04). Further, analysis of seven IDH wild‐type adult diffuse astrocytomas (DA) showed FGFR related genetic alterations in 43% cases. These and previous results suggest that APAs are genetically similar to IDH wild‐type adult DAs. APAs harbor infrequent BRAF alterations but more frequent FGFR alterations as compared with pediatric cases. KIAA1549‐BRAF fusion inversely correlates with increasing age whereas FGFR1‐mutation associates with older age. Activation of MAPK/ERK/mTOR signaling appears to be an important oncogenic event in APAs and may be underlying event of aggressive tumor behavior. The findings provided a rationale for potential therapeutic advantage of targeting MAPK/ERK/mTOR pathway in APAs.

✓Meningeal melanocytomas are uncommon intracranial tumors and their occurrence at the cerebellopontine angle (CPA) is extremely rare. The authors describe the case of a 58-year-old woman who presented with a left CPA tumor; on the basis of histopathological studies after resection, a diagnosis of meningeal melanocytoma was reached. The relevant literature is reviewed.

Parathyroid carcinoma is extremely rare. Correct preoperative and even histopathological diagnosis may be difficult owing to the deceptively bland cytoarchitectural features, especially when presenting with localized disease. Recurrence/metastases developing years later then make the malignant nature obvious.We present here an unusual case of a 32-year-old patient with carcinoma of the left upper parathyroid gland, initially diagnosed as parathyroid adenoma, treated with endoscopic left parathyroidectomy, and later developing subcutaneous metastatic nodules over the medial end of the right clavicle and right anterior chest wall, followed by a right breast deposit. The recurrences, especially subcutaneous ones, were probably secondary to tumor seeding along the track of insertion of the endoscope.Involvement of subcutaneous tissue and the breast in parathyroid carcinoma is extremely rare. The case is being reported for its uniqueness along with a discussion of possible appropriate course of management, which may have averted the aggressive clinical course of the disease.

Sebaceous carcinomas (SBCs) are aggressive tumors with the potential to cause great morbidity and mortality. Poorly-differentiated tumors may at times pose challenges for the correct diagnosis. p40, a new antibody that targets a short isoform of p63 has been shown as a promising squamous cell marker. In this study, we sought to evaluate cytomorphological features of SBC and p40 expression analysis.A total of 29 previously diagnosed cases of SBCs including fine-needle aspirates and histopathology specimens from various sites were reviewed and studied for p40 expression. p40 nuclear expression was semi-quantitatively assessed. Adequate positive and negative controls of non-small cell lung carcinoma were taken for comparison. Expression pattern of normal sebaceous glands was also analyzed.Of the 29 cases, 13 (44.8%) were from the periocular region. The most common extraocular site was parotid gland. Morphologically tumors were categorized into well- and poorly-differentiated varieties based on extent of sebaceous differentiation. p40 positivity was seen in all cases of cytology aspirates and histology sections with similar intensity. No difference in percentage positivity of cells was recorded in well- and poorly-differentiated tumors.p40 can be a valuable marker when evaluating tumors with possible sebaceous differentiation. Although p40 expression in SBCs is not as useful for the differential diagnosis that includes poorly-differentiated squamous cell carcinoma, this study, for the first time in the literature, highlights an important observation that p40 can be utilized as a marker for sebaceous lineage.

Primary angiitis of the central nervous system (PACNS) is a rare form of vasculitis of unknown aetiology. Multifaceted clinical manifestations, non-specific MRI findings, a broad range of differential diagnoses and diverse pathological appearances prove to be a diagnostic challenge. However, a prompt diagnosis and aggressive treatment are crucial to avoid permanent damage. Hence, we present the clinico-pathological spectrum of this entity and highlight the limitations of currently available diagnostic modalities. We describe in detail the histopathological findings of eight cases of PACNS diagnosed at the Department of Pathology, AIIMS, over a period of eight years. Eight cases of PACNS were identified during this period. Five cases (62.5%) showed features of granulomatous vasculitis, two (25%) showed lymphocytic vasculitis and one case (12.5%) showed a predominantly necrotizing pattern of vasculitis. Diagnosis of PACNS is a challenge and requires a high index of clinical suspicion. Appropriate work-up to exclude other conditions is mandatory. Brain biopsy is useful in making the diagnosis and ruling out mimicking conditions.

Ependymomas are relatively rare glial tumours, whose pathogenesis is not well elucidated. They are enigmatic tumours that show site-specific differences in their biological behaviour. Recent studies have hypothesized that ependymoma cancer stem cells (CSCs) are derived from radial glia and express stem cell markers such as nestin, which is associated with a poor prognosis. CSCs reside in 'vascular niches', where endothelial cells and molecular signals like vascular endothelial growth factor (VEGF) play an important role in their survival. Studies analysing VEGF expression in ependymomas showed that ependymal vascular proliferation is less sensitive to induction by VEGF, questioning the possible beneficial effect of anti-VEGF therapy in ependymomas. We aimed to study nestin and VEGF immunoexpression in ependymomas, correlate them with clinicopathological parameters and reveal a role for VEGF in ependymomas that extends beyond the context of tumour angiogenesis.We analysed 126 cases of ependymomas of different grades and locations for nestin and VEGF immunoexpression. Endothelial cells were labelled with CD34. Vascular patterns and microvascular density was determined.Nestin and VEGF expression in tumour cells were more frequent in supratentorial tumours [89% (33/37) and 65% (24/37) respectively], and were associated with a significantly poor progression-free survival (PFS). VEGF expression did not reveal any correlation with necrosis or bizarre vascular patterns.Supratentorial location is an independent predictor of a poor PFS. Significant coexpression of nestin and VEGF suggests that latter possibly augments stem cell survival. Thus, anti-VEGF therapy may be a good option in future for nestin immunopositive ependymomas.

Background & objectives: Growing body of literature on sarcoidosis in India has led to an increased awareness of the disease. With the advent of better imaging tools hitherto under-recognized manifestations of sarcoidosis are likely to be better recognized. We sought to study the rare clinical and radiological manifestations (

The paranasal sinuses are an extremely unusual location for a vascular hamartoma. As far as we know, only 1 such case has been previously reported in the English-language literature. We report 3 new cases of vascular hamartoma of the paranasal sinuses, which occurred in a 20-year-old woman and in 2 men aged 36 and 45 years. Radiologically, the lesion in the woman was confined to the sinuses, while evidence of intraorbital extension was seen in the 2 men. No intracranial extension was seen in any patient. The diagnosis was confirmed by histopathologic examination of the excised lesions. All 3 patients were alive without recurrence at 12 to 24 months of follow-up.

Three unrelated patients, one girl, one boy, and an adult female, aged 14, 11 and 41 years, respectively, at the time of biopsy, revealed lysosomal glycogen storage, autophagic vacuoles and peculiar globular inclusions of distinct ultrastructure, which were reducing but did not appear like true "reducing bodies" as described in the congenital myopathy "reducing body myopathy". All three patients had residual activity of acid alpha-glucosidase in their muscle biopsy samples. Leukocytes in the girl showed normal acid alpha-glucosidase activity, but in the boy activity was reduced. Molecular genetic analysis of the GAA gene revealed disease-causing mutations in each patient: H568L/R672W, IVS1-13TG/G615F, and IVS1-13TG/IVS1-13TG. Although only one patient with such globular inclusions has been reported up to now, the three patients described here indicate that in the late-onset type of GSD II such inclusions may not be rare.