Treatment of recurrent oral carcinoma cuniculatum with immune checkpoint blockade: A case report and literature review

Abstract

Background: Carcinoma cuniculatum (CC) is a rare variant of carcinoma that can arise in the oral cavity. CC can be locally aggressive but rarely metastasizes, and there are few reports of treatment with systemic therapy.

Methods: We present a case of a 44-year-old man with T4bN0 oral carcinoma cuniculatum of the retromolar trigone.

Results: Despite resection with wide margins and adjuvant radiation, the disease recurred 14 months later and was extensive. Following positive margins on a repeat resection, the patient opted for systemic therapy. Despite a PD-L1 combined positive score of 15, the patient did not respond to immunotherapy (pembrolizumab).

Conclusion: Though it has a low propensity for metastasis, oral CC is a locally aggressive variant of squamous cell carcinoma, and recurrences are difficult to treat. Although reports of systemic therapy for CC are limited, this case suggests that immunotherapy may have limited activity in this oral cancer variant.

Keywords: Carcinoma cuniculatum; Head and neck surgery; Immunotherapy; Oral cancer.

Fig. 1.

Axial CT at initial presentation showed a lesion in the retromolar trigone with erosion of the mandible (arrow, A) and multiple prominent ipsilateral lymph nodes (B).

Fig. 2.

Macroscopic features of primary resection. Cut surface of the primary resection specimen demonstrating a bulky exophytic and endophytic carcinoma with complex architecture. Redundant, interconnected cyst-like spaces (arrowheads) abut the buccal vestibule (oral mucosa, chevron) and invade the bone of the mandible (star). A prominent, mass-like fibroinflammatory response associated with tumor obscures tissue planes within the floor of the mouth.

Fig. 3.

Microscopic features of primary and recurrent oral carcinoma cuniculatum (oral CC). Microscopic appearance of oral CC demonstrating characteristic and similar architectural features within the primary resection (A, B), initial recurrence (C, D) and second local recurrence (F, G) including prominent cystic burrows (arrowheads) of neoplastic epithelium. Carcinoma demonstrates bone invasion within the primary resection (A) and in the second recurrence, a distinctive pattern of cystic tunneling adjacent to the original free-tissue surgical reconstruction is noted (f, arrow). Higher magnification of oral CC at the primary site demonstrates well-differentiated keratinizing squamous epithelium arranged as crowded cyst-like structures invading stroma (B), and central keratin accumulation within a cystic tumor island (E). Representative PD-L1 (DAKO 22C3 pharmDx) immunohistochemistry with variable reactivity in tumor cells and surrounding inflammatory cells (E). Similar to findings within the primary tumor, small microabscess formations (chevron) were identified in the second recurrence (G).