Metastatic HPV-Related Head and Neck Squamous Cell Carcinoma to the Lung and Mediastinal Lymph Nodes in Aspirated Cytology Material: A Diagnostic Pitfall

Background: Although HPV-related head and neck squamous cell carcinoma (HNSCC) has good prognosis, a small proportion of patients develop distant metastases and have worse outcomes. Such metastases can be particularly difficult to diagnose in the lung and mediastinum, where they show extensive morphologic overlap with primary pulmonary neoplasms. This case series discusses metastatic HPV-related HNSCC in lung and mediastinal fine needle aspiration (FNA) cytology. Methods: The cytopathology archives were searched for lung and mediastinal FNA specimens of patients with HNSCC. Specimens were included if either the index FNA or the patient's original HNSCC was positive for HPV by DNA in-situ hybridization (ISH). Ten such cases were identified. Patient demographics and primary tumor details were tabulated from the electronic medical record. All FNA slides and stains were reviewed. Results: The ten patients (mean age of 58.2 years) included 4 smokers. Smears from all cases were hypercellular and hyperchromatic, with focal keratinization in 6/10 (60%). Core biopsies and cell blocks showed basaloid morphology with variable amounts of necrosis. All ten FNAs were diffusely positive for p16 (100%) and 7/9 cases stained (77.8%) were positive for HPV DNA ISH. Conclusions: Metastatic HPV-related HNSCC to the lung and mediastinal lymph nodes share the characteristic basaloid, minimally keratinizing morphology seen in Primary HNSCC cytology. Poorly differentiated pulmonary squamous cell carcinoma and neuroendocrine carcinomas are the primary differentials. Although primary lung neoplasms are not HPV-related, p16 positivity can be seen in both squamous cell and small cell lung carcinomas. HPV ISH allows definitive diagnosis of metastatic HPV-related HNSCC. (C) 2016 Wiley Periodicals, Inc.