Objectives Data on Papanicolaou (Pap) tests with atypical glandular cells (AGCs) with concurrent squamous cell abnormalities (AGC + Sq) are limited. We evaluated histologic outcomes and the role of high-risk human papillomavirus (HR-HPV) testing in this setting compared with AGCs without concurrent squamous cell abnormalities (AGC-alone). Methods This study used a retrospective cohort of patients with Pap test diagnoses of AGC + Sq and AGC-alone between October 2013 and August 2021. Results We included 287 Pap tests from 278 patients. The HR-HPV test was positive in 55% of AGC + Sq cases and 14% of AGC-alone cases (P < .0001). Most AGC + Sq cases displayed squamous lesions (41.5%) or were benign (41.5%) on histology, whereas AGC-alone cases were predominantly benign (72%) or extracervical neoplasms (18%). AGC + Sq cases showed higher rates of significant histologic lesions (P = .0001), which were associated with positive HR-HPV status (P = .0012). In AGC-alone cases, HR-HPV status was associated with significant histology only in patients 50 years of age or younger. In both groups, 20% or more of HR-HPV–negative patients harbored significant lesions. Conclusions AGC + Sq represents a distinct group of patients. HR-HPV testing and patient age provide useful information in the evaluation of AGC, but triage based on HR-HPV testing is not recommended because of the potential for missing significant lesions.

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Introduction Sclerosing variant of pancreatic neuroendocrine tumor (PanNET) is a rare variant of PanNET characterized by decreased tumor cellularity and prominent stromal fibrosis, and it is considered associated with serotonin expression. We herein present an unusual case of a sclerosing PanNET expressing glucagon. Methods The patient, a 75-year-old woman with refractory diabetes, scaly erythematous skin plaques in the eyelid, bilateral elbows and scalp, and episodes of nausea and poor appetite, presented to emergency department for acute abdominal pain. Abdominal computed tomography showed a 17-mm pancreatic head mass. Endoscopic ultrasound with fine-needle biopsy was performed for histopathological examination, followed by pancreaticoduodenectomy. Results Biopsy showed a background of predominantly blood and benign strips of pancreatic parenchyma and scanty fragments of fibrotic hyalinized stroma containing medium-sized atypical monotonous cells with round-to-ovoid nuclei, smooth borders, and inconspicuous nucleoli. These cells were difficult to characterize morphologically due to the scanty sampling. Immunohistochemical stains revealed the atypical cells were positive for AE1/AE2, synaptophysin, chromogranin, and glucagon and negative for insulin, serotonin, and pancreatic polypeptide. The lack of heterogeneous peptide cell composition supported a neoplastic proliferation of neuroendocrine cells. The pancreaticoduodenectomy specimen showed a 1.2-cm white firm mass in the pancreatic head. Histopathological study showed that, in a sclerotic background, the tumor cells grew mostly in trabecular patterns and occasionally in single cells, infiltrating into adjacent pancreatic parenchyma, and showed the same immunoprofile features as in the biopsy specimen. The proliferative index was <3%, supporting the diagnosis of low-grade sclerosing PanNET. The patient recovered well postsurgery. Moreover, the episodes of nausea and loss of appetite improved postsurgery. Patient did not show up for follow-up appointments in the dermatology clinic. Conclusion Sclerosing PanNET is challenging for diagnosis, especially on small biopsy specimens. Immunohistochemistry helps establish the diagnosis. Our case demonstrates a rare presentation of sclerosing PanNET expressing glucagon.