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.

Fig. 1

a Magnetic resonance imaging (MRI) showing a well-demarcated tumor at the left posterolateral aspect of the tongue (Case 1). b Endoscopy revealed a raised irregular tumorous lesion in the distal esophagus (Case 2). c Photomicrograph from the deparaffinized surgical specimen of the tongue (sagittal plane) showing a flat, well-demarcated endophytic tumor. d Photomicrograph from the esophagus showing an area of raised thickened mucosal folds and interspersed furrow with a crypt in the esophageal wall

Fig. 2

Histological features of carcinoma cuniculatum of the tongue. a The flat tumor is composed of an endophytic proliferation of complex branching network of burrowing crypts (whole mount H&E stained section). b Pseudoepitheliomatous hyperplasia-like features of the crypts with tongue-like pseudo-invasive infiltrative growth pattern (H&E stain: original magnification ×40). c Keratin filled crypt with no acute inflammation lined by well differentiated squamous epithelium with no cytologic atypia and well delineated tumor–stromal interface (H&E stain: original magnification ×200). d Mild cytologic atypia limited to the acutely inflamed areas (H&E stain: original magnification ×400)

Fig. 3

Histological features of carcinoma cuniculatum of the esophagus. a The tumor is composed of deep branching and burrowing crypts (H&E stain: original magnification ×10). b Crypt with no acute inflammation lined by well differentiated squamous epithelium with absent to minimal cytologic atypia (H&E stain: original magnification ×100). c Acutely inflamed intact and ruptured crypts with neutrophilic microabscesses (H&E stain: original magnification ×100). d Pronounced cytologic atypia in the acutely inflamed areas. The basal epithelial cells show nuclear enlargement, nuclear hyperchromasia and conspicuous nucleoli (H&E stain: original magnification ×100). e Crypts with pseudoepitheliomatous hyperplasia display a reticulated network of tongue-like basal epithelial layer protrusions with a jagged tumor–stromal interface mimicking aggressive stromal invasion (H&E stain: original magnification ×40)