Objective:To investigate the clinicopathological and molecular characteristics of the epithelioid glioblastoma (eGBM) with BRAF V600E mutation.Methods:Sixteen cases of eGBM with BRAF V600E mutation diagnosed at the West China Hospital of Sichuan University, China from 2012 to 2019 were collected. Their clinicopathological and molecular characteristics were analyzed. Results:The range of patients′ age was from 7 to 61 years (median 31.5 years). There were 4 males and 12 females, with a male to female ratio of 1∶3. Eleven cases were newly diagnosed eGBM and five cases had a previous history of astrocytomas. Most of the tumors were located in the cerebral hemisphere, often in the frontal lobe, with an average diameter of 4.6 cm (2.0-8.0 cm). The tumors were composed of relatively uniform, closely packed epithelioid cells, some showing discohesion, with distinct cell membrane, eosinophilic cytoplasm, eccentric nuclei, distinct nucleoli and mitotic activity. Palisaded/coagulative necrosis was seen in all cases. Glomerular microvascular proliferation was seen in most of the cases, while mono-or multi-nucleated tumor giant cells were seen in some cases. Focal sarcomatoid area was seen in 2 cases, and focal pleomorphic xanthoastrocytoma (PXA)-like area was seen in 3 cases. Immunohistochemistry showed variable positivity for GFAP, Olig2 and p53. The median Ki-67 index was 30% (10%-50%). Only one case lost ATRX protein expression. Sanger sequencing identified the BRAF V600E mutation in all sixteen patients. Five cases also had mutations in the TERT gene promoter. No IDH1 (R132) or IDH2 (R172) mutation was detected. Surgical resection of the tumors was performed for all patients, and 3 patients also received adjuvant radiotherapy and chemotherapy. Follow-up data were available for 15 patients, with a follow-up time of 1-89 months (median 10 months). Among the 15 patients, 7 patients died of disease and another 5 patients had recurrences. The overall survival time of the patients under 35 years of age was significantly longer than that of the patients aged 35 years or older ( P=0.014), but their progression-free survival was not statistically different ( P=0.232). Conclusions:eGBM with BRAF V600E mutation is more commonly detected in young women than other the populations (i.e. elderly or male). The epithelioid morphology should include rhabdoid meningioma, anaplastic PXA, atypical teratoid/rhabdoid tumor, metastatic tumors, and melanoma in its differential diagnosis. PXA-like area is observed in some eGBM cases, suggesting a relationship of these two types of tumor. eGBM is a high-grade malignant tumor and most of the cases show recurrences or deaths in a short-period time. The younger patients have a relatively better prognosis than the older ones.

Objective:To study the clinicopathological features, immunophenotype, molecular genetic characteristics and prognosis of renal cell carcinoma associated with TFEB gene rearrangement (TFEBr-RCC).Methods:Eight cases of TFEBr-RCC diagnosed at the West China Hospital of Sichuan University from 2014 to 2022 were collected for clinicopathological, immunohistochemical, fluorescence in situ hybridization and RNA sequencing analyses, with review of literature.Results:Six patients were male and two were female. The patient ages ranged from 25 to 50 years (mean: 34 years, median: 32 years). The tumors were present in the right kidney (3 cases) or the left kidney (5 cases). The maximum diameters of the tumors ranged from 4.0 cm to 18.5 cm, with an average of 8.5 cm. Histologically, majority of the cases (5/8) showed typical biphasic "pseudorosette" structure, while the remaining three cases demonstrated atypical morphology that was similar to epithelioid angiomyolipoma or clear cell renal cell carcinoma. Immunohistochemical study showed positivity of TFEB (8/8), PAX8 (8/8), MART-1 (7/7), and HMB45 (5/6). Interestingly, PD-L1 was variably expressed in all five tested cases. Staining for TFE3 in all cases was negative. TFEB translocation was verified in all 8 cases using TFEB fluorescence in situ hybridization. RNA sequencing showed MALAT1-TFEB gene fusion in 4 of the 5 tested cases (two of which showing novel MALAT1-TFEB fusion sites), and one case with a novel ACTB-TFEB gene fusion. Patient follow-ups ranged from 5 to 96 months (average 47 months). All patients were alive without recurrence or metastasis.Conclusions:TFEBr-RCC tends to occur in young adults and has a good prognosis. Histologically, most of the cases show characteristic biphasic structure, and some cases show epithelioid angiomyolipoma-like or clear cell RCC-like morphology. Immunohistochemical reactivity to TFEB, melanocytic markers and PD-L1 is characteristic. MALAT1-TFEB gene fusion is the most common molecular change, with variable fusion sites.

Objective:To investigate the clinicopathological features, immunophenotype, and differential diagnosis of adenocarcinoma of the rete testis.Methods:Four adenocarcinoma cases of the rete testis diagnosed at West China Hospital, Chengdu, China (3 cases, including 2 consultation cases) and the First Affiliated Hospital of Fujian Medical University, Fuzhou, China (1 case) between January 2009 and December 2017 were included. Their clinical, morphologic and immunohistochemical features were analyzed using histological analysis and immunohistochemical staining. Related literature was reviewed to reveal the characteristics of this tumor.Results:The 4 patients′ age range was 26-64 years. The maximum diameters of the tumors were 3.0 and 4.5 cm in 2 cases, respectively. On gross examination, adenocarcinomas of the rete testis appeared as a solid, white to gray or tan to yellow mass that raised at the hilum of the testis. Microscopically, all tumors showed multiple histologic patterns, including corded/trabecular (4/4), glandular, nested, sarcomatoid (3/4), solid (2/4), papillary, cribriform, and slit-like (1/4). Three types of adenocarcinoma cells included cuboidal to columnar (4/4), polygonal (4/4) and spindle-shaped (2/4) with pale eosinophilic and clear cytoplasm. The tumor cell nuclei appeared moderately to markedly atypical and pleomorphic, with a various number of mitoses. Transition from benign to malignant rete epithelium was seen in all cases. Eosinophilic hyaloid globules were found in 1 case. On immunohistochemical study, the tumor cells were diffusely, strongly positive for CKpan (4/4), EMA (4/4), Ber-EP4 (3/3) and CAⅨ(2/2), and focally positive for CK7 (4/4), vimentin (4/4), CD10 (4/4), PAX8 (3/3), PAX2 (3/3). The Ki-67 proliferative index was all>50% (4/4). The prognosis was poor. Two of the 3 patients died within 1 year after the surgical resection.Conclusions:Adenocarcinoma of the rete testis is a rare malignant tumor with several histologic patterns. Transition from benign to malignant rete epithelium is an important diagnostic clue. Detailed clinical history, tumor growth site and immunohistochemistry are helpful for its diagnosis and differential diagnosis.