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Lesions with a prominent inflammatory infiltrate and reactive vessels may have a granulation tissue-like appearance, therefore being difficult to distinguish from reactive lesions, like contact ulcers, post-intubation granulomas, inflammatory pseudotumors, or benign vascular lesions. In this study, we analyzed the clinicopathological features of a series of 17 head and neck SC-SCC with granulation tissue-like appearance. All patients, but two, were males, ranging in age between 57 and 80\u00a0years. The larynx was the most frequently affected site (<jats:italic>n<\/jats:italic>\u2009=\u200912), followed by the tongue (<jats:italic>n<\/jats:italic>\u2009=\u20094). One tumor was hypopharyngeal. Most consult cases were submitted with benign suggestion or because of unexpected recurrences of granulation tissue polyps. Histologically, all lesions consisted of an ulcerated polypoid proliferation of moderately to markedly atypical spindle cells, with a minor component of conventional invasive or in situ squamous carcinoma. At least one cytokeratin cocktail was positive in 13 cases. The staining was limited to a few neoplastic cells in most cases. Positivity for p63, p40, and cytokeratins 5\/6 was detected only in the conventional squamous cell carcinoma component, when present. ALK1 was negative in all cases. Sixteen cases were tested for p53 and all showed aberrant expression (12 diffusely positive and 4 of null-phenotype). The diagnosis of granulation tissue-like SC-SCC is challenging due to the close clinical and histological overlap with several benign conditions. Since the expression of epithelial markers is limited, the use of an immunohistochemical panel including p53 is recommended.<\/jats:p>","DOI":"10.1007\/s00428-024-03770-3","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T02:02:03Z","timestamp":1708912923000},"page":"799-806","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Granulation tissue-like spindle cell (sarcomatoid) carcinoma of the head and neck: a deceptively bland-looking underdiagnosed malignancy"],"prefix":"10.1007","volume":"484","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1332-5838","authenticated-orcid":false,"given":"Alessandro","family":"Franchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas","family":"Agaimy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"3770_CR1","unstructured":"Hernandez-Prera JC, Bishop JA, Zidar N. Spindle cell carcinoma. Spindle cell squamous carcinoma. In: WHO Classification of Tumours Editorial Board. Head and neck tumours [Internet; beta version ahead of print]. Lyon (France): International Agency for Research on Cancer; 2022 [cited 2023 December]. (WHO classification of tumours series, 5th ed.; vol. 9). Available from: https:\/\/tumourclassification.iarc.who.int\/chapters\/52."},{"key":"3770_CR2","doi-asserted-by":"publisher","first-page":"E489","DOI":"10.1002\/lary.28956","volume":"131","author":"L Ding","year":"2021","unstructured":"Ding L, Bi ZF, Yuan H, Zhao XH, Guan XD, Yao HR, Liu YM (2021) Sarcomatoid carcinoma in the head and neck: a population-based analysis of outcome and survival. 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The procedures used in this study adhere to the tenets of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"No patient consent was required for this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}