دورية أكاديمية
Head and neck squamous cell carcinomas of unknown primary: Can ancillary studies help identify more primary tumor sites?
| العنوان: | Head and neck squamous cell carcinomas of unknown primary: Can ancillary studies help identify more primary tumor sites? |
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| المؤلفون: | Hutchens T; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, United States of America. Electronic address: troyjh@uw.edu., Thorstad W; Department of Radiation-Oncology, Washington University School of Medicine, St. Louis, MO, United States of America., Wang X; Department of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, Chicago, IL, United States of America., Li Y; Department of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, Chicago, IL, United States of America., Duncavage EJ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States of America., Sun L; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States of America., Chernock RD; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States of America; Department of Otolaryngology Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States of America. |
| المصدر: | Experimental and molecular pathology [Exp Mol Pathol] 2024 Jul 03; Vol. 138, pp. 104915. Date of Electronic Publication: 2024 Jul 03. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0370711 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0945 (Electronic) Linking ISSN: 00144800 NLM ISO Abbreviation: Exp Mol Pathol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2000- > : Amsteram : Elsevier Original Publication: New York : Academic Press |
| مستخلص: | A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as Epstein-Barr virus (EBV) testing by EBER-ISH. CD5 and c-KIT (CD117) IHC was done to evaluate for possible thymic origin in all virus-negative cases. Whole exome sequencing, followed by MSA, was used to identify UV signature mutations indicative of cutaneous origin. HPV was identified in 12 of 22 tumors (54.5%), favoring an oropharyngeal origin, and closely associated with nonkeratinizing tumor morphology (Fisher's exact test; p = 0.0002). One tumor with indeterminant morphology had discordant HPV and p16 status (p16+/HPV-). All tumors were EBV-negative. Diffuse expression of CD5 and c-KIT was identified in 1 of 10 virus-negative SCCUPs (10%), suggesting a possible ectopic thymic origin rather than a metastasis. A UV mutational signature, indicating cutaneous origin, was identified in 1 of 10 (10%) virus-negative SCCUPs. A cutaneous auricular primary emerged 3 months after treatment in this patient. Primary tumors became clinically apparent in 2 others (1 hypopharynx, 1 hypopharynx/larynx). Thus, after follow-up, 6 tumors remained unclassifiable as to the possible site of origin (27%). Most SCCUPs of the neck in our series were HPV-associated and thus likely of oropharyngeal origin. UV signature mutation analysis and additional IHC for CD5 and c-KIT for possible thymic origin may aid in further classifying virus-negative unknown primaries. Close clinical inspection of hypopharyngeal mucosa may also be helpful, as a subset of primary tumors later emerged at this site. Competing Interests: Declaration of competing interest The spouse of Wade Thorstad is an employee of Elekta, Inc. (No Elekta products were used for this study and no Electa products are currently used within the Department of Radiation-Oncology at Washington University School of Medicine). Rebecca D. Chernock is a member of Precision Oncology Alliance, Caris Life Sciences (non-financial relationship) and a Steering Committee Member for a Phase III clinical trial of neoadjuvant Pembrolizumab in surgically resectable, locally advanced head and neck squamous cell carcinomas, Merck & Co., Inc. There are no additional potential conflicts of interest relevant to this manuscript. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Epstein–Barr virus; Human papilloma virus; Mutational signature analysis; Squamous cell carcinoma; UV mutational signature; cancer of unknown primary |
| تواريخ الأحداث: | Date Created: 20240704 Latest Revision: 20240704 |
| رمز التحديث: | 20240705 |
| DOI: | 10.1016/j.yexmp.2024.104915 |
| PMID: | 38964052 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-0945 |
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| DOI: | 10.1016/j.yexmp.2024.104915 |