Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Cancer Cytopathol. 2019 Feb;127(1):26-34. doi: 10.1002/cncy.22075. Epub 2018 Nov 26.
The majority of human papillomavirus (HPV)-associated oropharyngeal carcinomas are squamous cell carcinomas; however, there are rare reports of HPV-associated neuroendocrine carcinomas (HPV-NECs) in the upper aerodigestive tract. The aim of this study was to characterize the diagnostic features of fine-needle aspiration (FNA) cases of head and neck HPV-NEC.
Cytology cases of HPV-NEC were identified over a 3-year period from 2 institutions. Clinical, cytomorphologic, and ancillary test results were evaluated.
Five FNA cases of HPV-NEC were identified from 4 patients with cervical lymph node metastases with primaries in the oropharynx (n = 2), nasopharynx (n = 1), and larynx (n = 1). Three cases showed mixed small cell and large cell neuroendocrine morphologies; 1 case was a small cell carcinoma, and the last case appeared as a large cell neuroendocrine carcinoma. All tumors were strongly positive for synaptophysin and p16 and negative for p63/p40. Two cases tested for INSM1 showed diffuse nuclear staining. HPV was confirmed by in situ hybridization in 4 cases, and HPV-18 was detected by polymerase chain reaction in the fifth case. Retinoblastoma (Rb) staining was moderate to weak (5/5), and p53 was weakly positive (5/5).
Head and neck HPV-NEC is a rare, aggressive entity that can show mixed small and large cell features and p16 upregulation; p53 and Rb are variable with limited diagnostic utility. Because p16 positivity can be nonspecific, confirmatory HPV testing is required and may be helpful in determining the primary site for neuroendocrine carcinoma of an unknown primary. The accurate diagnosis of HPV-NEC is also important because of its worse prognosis in comparison with HPV-associated squamous cell carcinoma.
大多数人乳头瘤病毒（HPV）相关的口咽癌为鳞状细胞癌；然而，在上呼吸道罕见报道 HPV 相关神经内分泌癌（HPV-NEC）。本研究旨在描述头颈部 HPV-NEC 细针抽吸（FNA）病例的诊断特征。
从 2 个机构回顾性分析 3 年内的 HPV-NEC 细胞学病例。评估临床、细胞学形态和辅助检查结果。
从 4 例有原发于口咽（n = 2）、鼻咽（n = 1）和喉（n = 1）的颈部淋巴结转移的患者中，共发现 5 例 HPV-NEC 的 FNA 病例。3 例显示混合小细胞和大细胞神经内分泌形态；1 例为小细胞癌，最后 1 例为大细胞神经内分泌癌。所有肿瘤均突触素和 p16 强阳性，p63/p40 阴性。2 例检测 INSM1 的病例显示弥漫性核染色。4 例通过原位杂交证实 HPV，第 5 例通过聚合酶链反应检测到 HPV-18。视网膜母细胞瘤（Rb）染色为中等至弱（5/5），p53 弱阳性（5/5）。
头颈部 HPV-NEC 是一种罕见的侵袭性实体瘤，可表现为混合小细胞和大细胞特征以及 p16 上调；p53 和 Rb 表现多变，诊断作用有限。由于 p16 阳性可能是非特异性的，需要进行确认性 HPV 检测，这可能有助于确定原发灶为不明原因的神经内分泌癌。HPV-NEC 的准确诊断也很重要，因为其预后比 HPV 相关的鳞状细胞癌更差。
