CYLD-mutant cylindroma-like basaloid carcinoma of the anus: a genetically and morphologically distinct class of HPV-related anal carcinoma.

Rare reports of anal carcinoma (AC) describe histologic resemblance to cutaneous cylindroma, but mutations in the tumor suppressor CYLD, the gene responsible for familial and sporadic cylindromas, have not been systematically investigated in AC. Here, we investigate CYLD-mutant AC, focusing on molecular correlates of distinct histopathology. Comprehensive genomic profiling (hybrid-capture-based DNA sequencing) was performed on 574 ACs, of which 75 unique cases (13%) harbored a CYLD mutation. Clinical data, pathology reports, and histopathology were reviewed for each CYLD-mutant case. The spectrum of CYLD mutations included truncating (n = 50; 67%), homozygous deletion (n = 10; 13%), missense (n = 16; 21%), and splice-site (n = 3; 4%) events. Compared with CYLD-wildtype AC (n = 499), CYLD-mutant ACs were significantly enriched for females (88% vs. 67%, p = 0.0001), slightly younger (median age 59 vs. 61 years, p = 0.047), and included near-universal detection of high-risk HPV sequences (97% vs. 88%, p = 0.014), predominantly HPV16 (96%). The CYLD-mutant cohort also showed significantly lower tumor mutational burden (TMB; median 2.6 vs. 5.2 mut/Mb, p < 0.00001) and less frequent alterations in PIK3CA (13% vs. 31%, p = 0.0015). On histopathologic examination, 73% of CYLD-mutant AC (55/75 cases) showed a striking cylindroma-like histomorphology, composed of aggregates of basaloid cells surrounded by thickened basement membranes and containing characteristic hyaline globules, while only 8% of CYLD-wildtype tumors (n = 34/409) contained cylindroma-like hyaline globules (p < 0.0001). CYLD-mutant carcinomas with cylindroma-like histomorphology (n = 55) showed significantly lower TMB compared with CYLD-mutant cases showing basaloid histology without the distinctive hyaline globules (n = 14) (median 1.7 vs. 4.4 mut/Mb, p = 0.0058). Only five CYLD-mutant cases (7%) showed nonbasaloid conventional squamous cell carcinoma histology (median TMB = 5.2 mut/Mb), and a single CYLD-mutant case showed transitional cell carcinoma-like histology. Within our cohort of ACs, CYLD mutations characterize a surprisingly large subset (13%), with distinct clinical and genomic features and, predominantly, a striking cylindroma-like histopathology, representing a genotype-phenotype correlation which may assist in classification of AC.

Electrocorticographic functional mapping identifies human cortex critical for auditory and visual naming.

More comprehensive, and efficient, mapping strategies are needed to avoid post-operative language impairments in patients undergoing epilepsy surgery. Conservative resection of dominant anterior frontal or temporal cortex frequently results in post-operative naming deficits despite standard pre-operative electrocortical stimulation mapping of visual object (picture) naming. Naming to auditory description may better simulate word retrieval in human conversation but is not typically tested, in part due to the time demands of electrocortical stimulation mapping. Electrocorticographic high gamma (60-150 Hz) activity, recorded simultaneously through the same electrodes used for stimulation mapping, has recently been used to map brain function more efficiently, and has at times predicted deficits not anticipated based on stimulation mapping alone. The present study investigated electrocorticographic mapping of visual object naming and auditory descriptive naming within conservative dominant temporal or frontal lobe resection boundaries in 16 patients with 933 subdural electrodes implanted for epilepsy surgery planning. A logistic regression model showed that electrodes within traditional conservative dominant frontal or temporal lobe resection boundaries were significantly more likely to record high gamma activity during auditory descriptive naming than during visual object naming. Eleven patients ultimately underwent resection and 7 demonstrated post-operative language deficits not anticipated based on electrocortical stimulation mapping alone. Four patients with post-operative deficits underwent a resection that included sites where high gamma activity was observed during naming. These findings indicate that electrocorticographic mapping of auditory descriptive naming may reduce the risk of permanent post-operative language deficits following dominant temporal or frontal resection.

Glycogenic Hepatopathy Masquerading as Acute Pancreatitis.

Glycogenic hepatopathy (GH), defined histologically by hepatocytic glycogen accumulation without fatty change or fibrosis, is a benign reversible condition. It presents clinically as hepatomegaly with elevated liver enzymes in young diabetic (type 1) patients with poor glycemic control. We report a case of a 20-year-old female with a history of poorly controlled type 1 diabetes mellitus (T1DM) and prior pancreatitis who presented with sharp epigastric pain and hepatomegaly. She was found to have diabetic ketoacidosis with elevated lipase and amylase. Though at first her symptoms were erroneously attributed to pancreatitis, a liver biopsy showing glycogenated nuclei led to a diagnosis of GH.

Primary Neuroendocrine Tumor of the Scrotum: An Uncommon Site for a Rare Tumor.

Neuroendocrine tumors (NETs) are a heterogeneous group of tumors developing from neural crest cells, with numerous sites of origin, commonly the gastrointestinal and genitourinary tracts. NETs of the genitourinary tract are more common in women. Small cell carcinoma of the prostate or testicular carcinoid are the NETs in male. In this article, we present a rare case of NET of the scrotum. Our patient was a 47-year-old male with a history of complicated pilonidal cysts resulting in chronic scrotal wounds. Biopsy of a large nonhealing scrotal wound revealed a high-grade neuroendocrine carcinoma with features most suggestive of small cell carcinoma. Presenting with advanced disease at diagnosis, he was started on systemic therapy and unfortunately progressed through multiple lines of treatment, including CAPTEM (capecitabine and temozolomide). Unfortunately, due to multiple logistical reasons, the patient was unable to receive the then off-label immunotherapy based on DART (Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors) trial. He, unfortunately, succumbed to his disease within months of diagnosis.