Carcinoma Cuniculatum of the Esophagus and Tongue: Report of Two Cases, Including TP53 Mutational Analysis

Abstract

Carcinoma cuniculatum (CC) is a rare variant of extremely well differentiated squamous cell carcinoma. We present the clinicopathological features of two cases of CC; one lingual and one esophageal case with a molecular genetic study regarding the TP53 gene mutational status. Case 1 was a 62 year old male with enlarging chronic ulcer in the tongue. Case 2 was a 77 year old male with progressive dysphagia and odynophagia. Both patients were treated surgically. Both tumors showed deeply invaginating, keratin-filled, burrowing crypts lined by very well differentiated squamous epithelium. The esophageal tumor showed varying degrees of reactive nuclear atypia largely limited to the areas with dense intratumoral infiltration of neutrophils. No mutation of TP53 was identified in the esophageal case. Cytologic atypia limited to areas of significant acute inflammation may occur in CC and should, in the absence of aggressive stromal invasion, not preclude a diagnosis of CC.

Extensive carcinoma cuniculatum of the mandible

“…The crypts are filled with keratin and contain neutrophil microabscesses. The network of crypts infiltrates adjacent tissues, but often maintains a clear tumorstroma interface [7,22]. These crypts were characteristically found in the present pathology (Fig.…”

“…However, studies examining p53 protein expression in carcinoma cuniculatum have largely been inconclusive. Thavaraj et al found over-expression of p53 in greater than 90% of suprabasal and basal cells in a case of tongue carcinoma cuniculatum [19], while a recent study from Goh et al found minimal p53 expression on immunohistochemistry and no mutations of TP53 on sequence analysis in the case of esophageal carcinoma cuniculatum [22]. This discrepancy is likely attributed to both methodological variation between studies and differing extents of cytologic atypia between tumor samples [23].…”

“…Morbidity and mortality from carcinoma cuniculatum are from locally destructive growth, rather than metastasis [8,10,22]. Oral carcinoma cuniculatum is typically slow growing but locally aggressive, often documented to invade adjacent connective tissue and bone with or without leukoplakia [7,9,16].…”

A Rare Case of Carcinoma Cuniculatum Involving the Larynx in Association with a Saccular Cyst

“…Additionally, an increasing number of reports describe CC involving head and neck sites, predominantly the oral cavity [2,4,[9][10][11][13][14][15][16][17][18][19][20][21][22]. Table 1 summarizes all reports of CC occurring in the head and neck which could be identified.…”

Endoscopic submucosal dissection in a rare case of carcinoma cuniculatum of the esophagus initially misdiagnosed as benign squamous papilloma

“…Carcinoma cuniculatum of the esophagus is a very rare and extremely well differentiated variant of squamous cell carcinoma, first described in 2005 [1]. Since then, it has been reported in less than 15 cases [2,3]. The etiology is unknown but there have been reported associations with chronic esophageal irritation, achalasia, diverticulum, and prior caustic injury [1,4].…”