Molecular and immunophenotypic characterization of anal squamous cell carcinoma reveals distinct clinicopathologic groups associated with HPV and TP53 mutation status.

Squamous cell carcinoma (SqCC) is the most common malignancy of the anal canal, where it is strongly associated with HPV infection. Characteristic genomic alterations have been identified in anal SqCC, but their clinical significance and correlation with HPV status, pathologic features, and immunohistochemical markers are not well established. We examined the molecular and clinicopathologic features of 96 HPV-positive and 20 HPV-negative anal SqCC. HPV types included 89 with HPV16, 2 combined HPV16/HPV18, and 5 HPV33. HPV-positive cases demonstrated frequent mutations or amplifications in PIK3CA (30%; p = 0.027) or FBXW7 mutations (10%). HPV-negativity was associated with frequent TP53 (53%; p = 0.00001) and CDKN2A (21%; p = 0.0045) mutations. P16 immunohistochemistry was positive in all HPV-positive cases and 3/20 HPV-negative cases (p < 0.0001; sensitivity: 100%; specificity: 85%) and was associated with basaloid morphology (p = 0.0031). Aberrant p53 immunohistochemical staining was 100% sensitive and specific for TP53 mutation (p < 0.0001). By the Kaplan-Meier method, HPV-negativity, aberrant p53 staining, and TP53 mutation were associated with inferior overall survival (OS) (p < 0.0001, p = 0.0103, p = 0.0103, respectively) and inferior recurrence-free survival (p = 0.133, p = 0.0064, and p = 0.0064, respectively). TP53/p53 status stratified survival probability by HPV status (p = 0.013), with HPV-negative/aberrant p53 staining associated with the worst OS, HPV-positive/wild-type p53 with best OS, and HPV-positive/aberrant p53 or HPV-negative/wild-type p53 with intermediate OS. On multivariate analysis HPV status (p = 0.0063), patient age (p = 0.0054), T stage (p = 0.039), and lymph node involvement (p = 0.044) were independently associated with OS. PD-L1 expression (CPS ≥ 1) was seen in 30% of HPV-positive and 40% of HPV-negative cases, and PD-L1 positivity was associated with a trend toward inferior OS within the HPV-negative group (p = 0.064). Our findings suggest that anal SqCC can be subclassified into clinically, pathologically, and molecularly distinct groups based on HPV and TP53 mutation status, and p16 and p53 immunohistochemistry represent a clinically useful method of predicting these prognostic groups.

Benign Breast Cyst in a Young Male.

Simple benign breast cysts are commonly diagnosed in female breasts and may present as palpable masses. However, they are extremely uncommon in the male breast and are rarely reported in the literature. Here, we report a case of a simple benign cyst of the breast in a relatively healthy 37-year-old man. The patient initially presented with a palpable 2-3 mm tender left breast lump. Further evaluation with mammography and ultrasound revealed a mass most consistent with a simple benign cyst. However, considering the rarity of breast cysts in males, the lesion was biopsied to rule out malignancy. Pathology results from ultrasound-guided core needle biopsy demonstrated fibro-adipose tissue with a benign cyst lined by foamy cells with apocrine features, consistent with a diagnosis of a benign epithelial cyst and concordant with the radiological findings. To our knowledge, this is the youngest case of a benign breast cyst in a male that has been reported in the literature. In this case report, we discuss the typical features and presentation of breast cysts in males, associated imaging findings on mammography and ultrasound, and the necessity for pathological confirmation with biopsy in this population.

Cystic adenomatoid tumor of the uterus.

We present a case of a cystic adenomatoid tumor in a 40-year-old woman. The tumor was an intramural multicystic mass, histologically similar to a multicystic mesothelioma. Cystic adenomatoid tumors of the uterus are extremely rare. They present with a wide differential diagnosis in radiology. The tumors are known to be benign and awareness of this rare entity is the key to its diagnosis for a pathologist.