Fine needle aspiration cytology including the analysis of human papilloma virus (HPV) DNA enhances the diagnostic workup of solitary cystic neck lesions

Sep 24, 2026

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Distinguishing branchial cleft cysts (BrCCs) from cystic metastases of human papillomavirus (HPV) positive tonsillar or base of tongue squamous cell carcinoma and cancer of unknown primary (CUP) is difficult because fine needle aspiration cytology (FNAC) may be nonrepresentative for metastasis and atypical for BrCC. Preoperative FNAC morphology and HPV-DNA were reevaluated and correlated with final diagnoses. In 304 evaluated patients, all BrCC cases were HPV-DNA negative, while HPV-DNA was present only in malignant HPV-related cystic neck masses or CUP, supporting HPV-DNA analysis to guide diagnosis and management.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Introduction

Background on solitary cystic neck lesions

HPV-related HNSCC and diagnostic challenge

Materials and Methods

Patient cohort and preoperative reassessment

Results

HPV-DNA status in BrCC, CUP, and primary sites

Interpretation

Diagnostic value of HPV-DNA in FNAC

Article history and keywords

ORIGINAL ARTICLE Fine needle aspiration cytology including the analysis of human papilloma virus (HPV) DNA enhances the diagnostic workup of solitary cystic neck lesions in a population with a high incidence of HPV positive oropharyngeal cancer Evelina Jörtsöa,b , Linda Marklunda,c,f , Martin Harper Hysekd,e , Anders Näsmand,e , LalleHammarstedt-Nordenvalla,f , Mattias von Beckeratha,f , Tina Dalianisd,f and Rusana Barka,f a Division of Ear Nose and Throat Diseases, Department of Clinical Sciences Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; bMedical Unit Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden; c Department of Surgical Sciences, Section of Otolaryngology and Head and Neck Surgery, Uppsala University, Uppsala, Sweden; dDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; e Department of Clinical Pathology, Karolinska University Hospital, Stockholm, Sweden; fMedical Unit Head, Neck, Lung, and Skin Cancer, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden ABSTRACT Background and purpose: Distinguishing branchial cleft cysts (BrCCs) from cystic metastases of human papillomavirus (HPV) positive tonsillar or base of tongue squamous cell carcinoma and cancer of unknown primary (CUP) is challenging. Fine needle aspiration cytology (FNAC) from cystic metastasis can be nonrepresentative, while reactive squamous cells from BrCC can be atypical. It is unclear whether benign characteristics and the absence of HPV-DNA in FNAC can enhance distinguishing BrCC from a cystic metastasis; therefore, we investigated here. Patients/materials and methods: Morphology and HPV-DNA in FNAC were reevaluated preoperatively and correlated to final diagnosis of 304 BrCC and CUP patients at Karolinska University Hospital during 2016-2023. Results and interpretation: All 176 cases finally diagnosed as BrCC were HPV-DNA negative in the preoperative FNAC. HPV-DNA was present in 100/128 (78.1%) of the FNAC with a solitary cystic neck metastasis and in 3/3 CUPs separately investigated on surgical specimens, which is distributed in 40/58 (69.0%) CUP, 40/41 (97.6%) tonsillar cancer, 21/22 (95.5%) base of tongue cancer, 2/2 uterine cervical cancer, and 0/5 non-HPV-related cancers. Interpretation: All cases with final BrCC diagnosis were HPV-DNA negative in FNAC. HPV-DNA was only present in FNAC of malignant cystic neck masses of HPV-related tumors or CUP. The data suggest that HPVDNA analysis in FNAC enhances the diagnostics of cystic masses of the neck. A FNAC with a benign morphology and the absence of HPV-DNA indicated a BrCC, while an HPV-DNA positive aspirate irrespective of morphology suggested an HPV-DNA positive cancer or CUP. ARTICLE HISTORY Received 26 September 2024 Accepted 29 January 2025 Published 17 February 2025 KEYWORDS FNAC; branchial cleft cyst; cystic metastasis; tonsillar cancer; base of tongue cancer; cancer of unknown primary; cervical cancer Introduction Solitary cystic masses occurring in the neck can encompass a spectrum from benign entities like branchial cleft cysts (BrCCs) to malignant conditions, including cystic metastases stemming from oropharyngeal squamous cell carcinoma (OPSCC), cancer of unknown primary (CUP), as well as papillary thyroid cancer (PTC) [1, 2]. BrCCs typically arise from congenital epithelial cysts, primarily due to the failure of second branchial cleft obliteration [3]. BrCC presents as a lateral neck mass typically situated anterior to the sternocleidomastoid muscle in the mid part of the neck. Head and neck squamous cell carcinoma (HNSCC) often present with a node metastasis in the neck, and in many cases, the metastasis is solid [4] . For human papilloma virus (HPV)-related HNSCC, typically OPSCC and CUP, the metastasis in the neck is often cystic, and because of the shared anatomical location, differentiation between BrCC, OPSCC, and CUPs poses a diagnostic challenge, especially in

FAQs

What diagnostic problem does the study address?

It addresses the difficulty of distinguishing branchial cleft cysts from cystic metastases originating from HPV-positive tonsillar/base of tongue squamous cell carcinoma and cancer of unknown primary using FNAC.

How were FNAC samples evaluated in this study?

FNAC morphology and HPV-DNA results were reevaluated preoperatively and correlated with the final diagnoses after surgery.

What key finding supports using HPV-DNA analysis in FNAC?

All cases with a final BrCC diagnosis were HPV-DNA negative in FNAC, while HPV-DNA was present in FNAC only for malignant cystic neck masses from HPV-related tumors or CUP, regardless of morphology.

Sep 24, 2026

Uploaded by Callum