Answer: Squamous cell granulomas

Histology: The larynx is fibrotic and involved by a granulomatous process. The granulomas have a distinctly zonal pattern: a central core of pink laminated material is surrounded by a zone of histiocytes and foreign-body giant cells and an outer band of dense fibrosis. In some of the central cores, the pink flakey material resembles keratin; and although no viable tumor is apparent, outlines of degenerated squamous cells can still be recognized. The granulomas are scattered throughout the submucosa, soft tissues and even within the ossified thyroid cartilage.

Discussion: Squamous cell granulomas are histologically characterized by scarring, cystic degeneration and an intense foreign-body giant cell reaction to keratin debris. Evidence suggests that squamous cell granulomas represent a form of degenerated squamous cell carcinoma following chemotherapy or chemoradiation: They are almost exclusively encountered in resections from patients with head and neck squamous cell carcinomas; and the material inciting the inflammatory reaction morphologically resembles keratin and degenerated squamous cells.

The term “squamous cell granuloma” is meaningful and convenient. “Squamous cell” directly links the lesion to a primary malignancy of the head and neck, and the term “granuloma” emphasizes the predominant histologic finding. In effect, “squamous cell granulomas” is a term which effectively communicates locoregional tumor spread even when the histologic findings seemingly reflect an inflammatory reaction as opposed to a neoplastic process. For the pathologist, the term enables one to correlate the histologic and the clinical findings while avoiding erroneous phrases such as “negative for tumor” (when the process of locoregional tumor spread has clearly occurred) and “positive for tumor” (when viable tumor is not actually seen on the slides).

For patients with HNSCC treated by organ-preservation modalities, laryngeal dysfunction and/or persistent cervical adenopathy are ominous clinical findings that point to tumor persistence and progression. Paradoxically, “persistent disease” due to squamous cell granulomas may instead reflect conspicuous tumor involution and exquisite tumor sensitivity to cytotoxic agents.