BACKGROUND: Intraductal carcinoma of the salivary gland (IDC) is a rare cancer with potential actionable targets, including RET fusions. Histologic and molecular features of IDC were recently reported, but cytomorphologic data are limited. In the largest multi-institutional fine-needle aspiration (FNA) series, the authors describe the cytomorphologic features of 13 IDC cases with available clinical, radiologic, histopathologic, and molecular data. METHODS: The cases included 13 FNAs for 9 low-grade (LG) IDCs and 4 high-grade (HG) IDCs with corresponding histopathology and available molecular, imaging, and clinical data. Smears and liquid-based preparations available for 12 FNAs were semiquantitatively scored for key cytomorphologic findings and correlated with the corresponding resection. RESULTS: LG IDC FNAs showed a cellular, biphasic population of large, atypical ductal cells with mildly pleomorphic nuclei in a clean background and a minor population of small, uniform myoepithelial cells. In contrast, all HG IDC FNAs showed predominantly ductal cells with marked nuclear pleomorphism, coarse chromatin, and necrosis. With the Milan system, most LG and HG IDC FNAs were classified as either salivary gland neoplasms of uncertain malignant potential (54%) or malignant (31%). Immunohistochemistry showed ductal epithelial reactivity with mammaglobin, androgen receptor, and S100, whereas myoepithelial cells were positive for p63 and/ or calponin. Among cases with next-generation sequencing, 4 LG IDCs showed NCOA4-RET gene fusions, whereas an HG IDC showed HRAS and PIK3CA mutations. CONCLUSIONS: The cytomorphology of IDC overlaps with other benign and malignant salivary gland neoplasms. Immunohistochemistry limits the differential diagnosis, but definitive classification requires molecular analysis. A diagnosis of IDC has potential implications for patient management. Cancer Cytopathol 2021;129: 928-946.

Oncogenic (tumor-induced) osteomalacia is a rare paraneoplastic syndrome of phosphate wasting that is frequently associated with phosphaturic mesenchymal tumor (PMT). As the cytologic features of this tumor apparently have not been reported, we describe the fine-needle aspiration (FNA) findings for PMT that arose from the gluteal soft tissue in a patient with hypophosphatemia and multiple fractures secondary to osteomalacia. Smears from the computerized tomography (CT)-guided FNA showed groups of spindle cells having elongated nuclei, fine to moderately coarsely granular chromatin, inconspicuous nucleoli, and delicate cytoplasm. Marked nuclear atypia, mitotic figures, and necrosis were absent. The differential diagnosis included a variety of benign and malignant spindle cell neoplasms such as monophasic synovial sarcoma, leiomyoma, peripheral nerve sheath tumor, fibrosarcoma, and, less likely, metastatic melanoma and sarcomatoid carcinoma. The bland-appearing cytologic features of a spindle cell tumor in a patient with osteomalacia should suggest the diagnosis of PMT.

Cytology frequently has some role in preoperatively distinguishing pancreatic mucus-producing neoplasia (intraductal papillary mucinous neoplasms [IPMNs] and mucinous cystic neoplasms [MCNs]) from other pancreatic cysts. We evaluated all cytologic specimens at our institutions from resected pancreatic cystic lesions for lesional extracellular and cellular material. Lesional extracellular material was identified in 32 of 38 of the cytologic samples from cystic pancreatic mucus-producing neoplasms (28 of 31 IPMNs and 4 of 7 MCNs). Lesional cellular material was seen in 22 of 38 cases (17 of 31 IPMNs and 5 of 7 MCNs). Lesional material was more commonly identified in higher grade and invasive lesions. Lesional extracellular material was seen in 3 of 14 samples of other pancreatic cysts, and lesional cellular material was seen in 6 of 14 cases.

Transgender women who have not undergone orchiectomy remain at risk for the development of testicular cancer. Unfortunately, many physicians self-report a weak fund of knowledge around transgender health issues and some are uncomfortable performing proper exams or advising patients on self-exams. Here we report the first case of a testicular mixed germ cell tumor that developed in a transgender woman and discuss the salient points of caring for transgender patients.