Identifying cellular markers of focal cortical dysplasia type II with cell-type deconvolution and single-cell signatures.

Focal cortical dysplasia (FCD) is a brain malformation that causes medically refractory epilepsy. FCD is classified into three categories based on structural and cellular abnormalities, with FCD type II being the most common and characterized by disrupted organization of the cortex and abnormal neuronal development. In this study, we employed cell-type deconvolution and single-cell signatures to analyze bulk RNA-seq from multiple transcriptomic studies, aiming to characterize the cellular composition of brain lesions in patients with FCD IIa and IIb subtypes. Our deconvolution analyses revealed specific cellular changes in FCD IIb, including neuronal loss and an increase in reactive astrocytes (astrogliosis) when compared to FCD IIa. Astrogliosis in FCD IIb was further supported by a gene signature analysis and histologically confirmed by glial fibrillary acidic protein (GFAP) immunostaining. Overall, our findings demonstrate that FCD II subtypes exhibit differential neuronal and glial compositions, with astrogliosis emerging as a hallmark of FCD IIb. These observations, validated in independent patient cohorts and confirmed using immunohistochemistry, offer novel insights into the involvement of glial cells in FCD type II pathophysiology and may contribute to the development of targeted therapies for this condition.

Fumarate hydratase-deficient renal cell carcinoma: A tumor with diverse morphology including cannibalism, lymphocytic emperipolesis, and defective autophagy.

We report the clinicopathological findings of the first series of 3 patients from Brazil with fumarate hydratase-deficient renal cell carcinoma. The clinicopathological findings disclosed a very aggressive tumor. All 3 patients had solitary tumor at the left side, metastasis and advanced stage at the time of diagnosis; were females with a median age of 40 years; had a history of uterine leiomyomas; and, at follow-up two patients are deceased and one patient alive. The microscopic findings of these 3 patients are in accordance with the literature disclosing a variety of morphologic features being papillary arrangement, eosinophilic cytoplasm, and prominent nucleoli surrounded by clear halo the constant and most frequent findings. Previously not reported in this tumor, we describe presence of cannibalism, lymphocytic emperipolesis, and cytoplasmic vacuoles with eosinophilic inclusions associated with overexpression of p62 in immunohistochemistry which is considered to be evidence of defective autophagy. Lymphocytic emperipolesis was a more frequent finding than cannibalism and immunohistochemistry for p62 was overexpressed only in the 2 patients disclosing cytoplasmic vacuoles with eosinophilic inclusions. The presence, frequency and significance of these novel findings should be checked in large series of this rare and aggressive tumor aiming to associate with clinical behavior and eventually influence the strategy of treatment.