Primary mucoepidermoid carcinoma of the external auditory canal with a CRTC1::MAML2 fusion: A case report and a review of literature.

Mucoepidermoid carcinoma is a malignant neoplasm of exocrine glands that arises predominantly in salivary glands. It is seldom encountered as a primary cutaneous neoplasm, and in those patients, it often involves the external auditory canal. Given their rarity, they can pose a diagnostic challenge and prompt extensive workup. In salivary glands, mucoepidermoid carcinomas commonly harbor CRTC1/3::MAML2 fusions; however, genetic alterations of primary cutaneous neoplasms are less characterized, with previous studies reporting CRTC1 rearrangements in the absence of MAML2 aberrations. Herein, we report a case of a primary cutaneous mucoepidermoid carcinoma of the external auditory canal with a CRTC1::MAML2 rearrangement. We also review the clinical, morphologic, and molecular features of this neoplasm and compare them to those reported in the literature and to histopathologic mimics.

Ulcerative erythematous papules and plaques on the face and lower legs of a man living with HIV: a clinicopathological challenge.

A 44-year-old male presented with a 2-month history of erythematous ulcerative papules and plaques on the scalp, face, and bilateral lower legs. He had a 5-year history of well-controlled HIV on antiretroviral therapy and recurrent syphilis infections. His face had violaceous plaques, while bilateral ankles and calves had ulcerative lesions with necrotic centers and purple borders. The morphologies clinically mimicked pyoderma gangrenosum on the lower extremities and cutaneous lymphoma on the face. Biopsy and reactive rapid plasma reagin confirmed a diagnosis of lues maligna, and the patient was successfully treated with penicillin G benzathine.

Artificial intelligence reveals features associated with breast cancer neoadjuvant chemotherapy responses from multi-stain histopathologic images.

Advances in computational algorithms and tools have made the prediction of cancer patient outcomes using computational pathology feasible. However, predicting clinical outcomes from pre-treatment histopathologic images remains a challenging task, limited by the poor understanding of tumor immune micro-environments. In this study, an automatic, accurate, comprehensive, interpretable, and reproducible whole slide image (WSI) feature extraction pipeline known as, IMage-based Pathological REgistration and Segmentation Statistics (IMPRESS), is described. We used both H&E and multiplex IHC (PD-L1, CD8+, and CD163+) images, investigated whether artificial intelligence (AI)-based algorithms using automatic feature extraction methods can predict neoadjuvant chemotherapy (NAC) outcomes in HER2-positive (HER2+) and triple-negative breast cancer (TNBC) patients. Features are derived from tumor immune micro-environment and clinical data and used to train machine learning models to accurately predict the response to NAC in breast cancer patients (HER2+ AUC = 0.8975; TNBC AUC = 0.7674). The results demonstrate that this method outperforms the results trained from features that were manually generated by pathologists. The developed image features and algorithms were further externally validated by independent cohorts, yielding encouraging results, especially for the HER2+ subtype.

Genetic Alterations in Invasive Breast Carcinoma with a Glycogen-Rich Clear Cell Pattern: A Case Report.

Invasive carcinoma with a glycogen-rich clear cell pattern (IC-GRCCP) is a rare and understudied subtype of invasive breast carcinoma of no special type (IBC-NST). Here we report the molecular characteristics of a mammary IC-GRCCP diagnosed in a 69-year-old woman. Next-generation sequencing of the tumor revealed an inv(1)(p36.12,q32.1) leading to loss-of-function of ARID1A gene, a MAP2K4 truncating mutation (p.E376), MYC amplification, a variant of uncertain significance of PTPRB gene (p.D1848N) and deep deletions of NCKAP5, CCNT2, MAP3K19, LRP1B, and KMT2A. The analysis of the involved pathways shows close resemblance to the ovarian clear cell carcinoma and indicates similarities in the molecular mechanisms of development of glycogen-rich clear cell carcinomas in different organs. Our findings and the literature review suggest new potential strategies for treatment of mammary IC-GRCCP, including epigenetic therapies, checkpoint inhibitors, radiation, or other double-strand DNA breaks-inducing agents. Nevertheless, larger studies are needed to substantiate those ideas.

Hepatic angiomyolipoma with predominant epithelioid component: Diagnostic clues on aspiration and core needle biopsies.

Hepatic angiomyolipoma (HAML) is a rare mesenchymal neoplasm that belongs to the perivascular epithelioid tumor family. Though it is characteristically, a triphasic tumor composed of smooth muscle, blood vessels, and adipocytes, the smooth muscle cells are often epithelioid and can represent the near-entirety of the tumor. A HAML composed predominantly of epithelioid smooth muscle cells occurring in the liver presents significant diagnostic challenges as many liver tumors are composed of large epithelioid cells. Furthermore, even if the tumor is not composed predominantly of epithelioid smooth muscle cells, this may be the only component present in a fine-needle aspiration (FNA) or core needle biopsy. A 38-year-old female with a 3 month history of abdominal pain, nausea, and diarrhea was found to have a 12 cm right hepatic lobe mass. FNA biopsy revealed a moderately cellular specimen composed of plump epithelioid cells with indistinct cell borders, low N:C ratio, round to oval nuclei, fine chromatin, occasional nucleoli, and abundant vacuolated to fibrillary cytoplasm. Rare intranuclear inclusions and occasional foamy macrophages were noted. Concurrent core biopsy revealed large polygonal cells with eccentric nuclei and clear, vacuolated to granular, eosinophilic cytoplasm that stained strongly for HMB45, confirming the diagnosis of HAML. Because HAML is a rare tumor, this diagnosis can be easily overlooked; cognizance of the typical cytologic, histologic, and immunophenotypic findings is crucial to establishing a diagnosis.

IgA Nephropathy in the Setting of Anti-TNF-α Therapy for Inflammatory Bowel Disease.

Tumor necrosis factor-α (TNF-α)-inhibiting agents are a standard therapy for moderate-to-severe inflammatory bowel disease (IBD). IgA nephropathy in the setting of prolonged exposure to TNF-α inhibitors is a rare, clinically significant adverse event often overlooked by gastroenterologists but well documented in the rheumatologic literature. We present a case series of 3 patients with IBD on TNF-α inhibitors who developed biopsy-proven IgA nephropathy. Clinicians prescribing TNF-α inhibitors to patients with IBD need to be aware of this potential side effect. Therapies with alternative mechanisms of action should instead be considered.

Risk of malignancy in "atypia of undetermined significance" category of salivary gland fine-needle aspiration: A bi-institutional experience.

BACKGROUND: Many prior institutional and multi-institutional studies have applied the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) retrospectively to their specimens to determine the risk of malignancy (ROM) of each category. Most of these studies focused on general assessment of the system and risk classification. However, there seems to be less focus on the category of atypia of undetermined significance (AUS) that could be attributed to the low number of cases that could fit into this category. Herein, we present a bi-institutional experience with this category. METHODS: A computerized search of the databases was performed to identify all salivary gland fine-needle aspiration (FNA) in two institutions over a period of 12 years. The final diagnosis of each case was reclassified based on MSRSGC, and histology follow-up was retrieved. RESULTS: Sixty AUS cases (out of 1560 salivary gland FNA) were identified with a rate of 3.8%. Forty cases (66%) had a subsequent tissue material. Correlation with histology revealed that the estimated ROM is 37.5% (15/40) and the overall ROM is 25% (15/60). Fifty percent of the cases had a prominent lymphoid component and most commonly represented lymphomas, reactive lymph node or sialadenitis. CONCLUSION: The AUS category is a heterogeneous group of lesions with predominant lymphoid-rich entities. Some variability exists between institutions with most having higher ROM than the suggested 20% by the MSRSGC atlas.