Oral carcinoma cuniculatum (OCC) is a rare variant of squamous cell carcinoma (SCC). It has similar characteristics to verrucous carcinoma (VC), although it is more locally aggressive and carries a rare risk of metastasis¹.

Carcinoma cuniculatum (CC) usually affects the plantar aspect of the foot, but it has been reported at other sites as well, including the oesophagus, abdomen, palm, leg, penis, and cervix^2-9. Flieger and Owiński¹⁰, who first described CC in the oral cavity in 1977, highlighted its aggressive behaviour and unique features. The incidence of OCC is very rare, with fewer than 60 cases ever reported¹¹, and it accounts for 2.7% of all oral squamous carcinomas¹². Its etiology remains unclear, although trauma, tobacco use, alcohol consumption, chronic inflammation, and human papilloma virus (HPV) have been implicated as potential risk factors^11,13,14. The most common location of OCC is the alveolar mucosa and gingiva, followed by the tongue, hard palate, mandible, and buccal mucosa¹¹. It can present with a variety of clinical manifestations such as exophytic induration, verrucous or cauliflower mass, erythroleukoplakia, or as a non-healing ulcer with or without bone exposure¹¹. Histologically, OCC is characterized by well-differentiated epithelial cells that are organized into ramified sinuses and keratin-filled crypts that resemble rabbit burrows (cuniculatum in Latin) with a notable lack of cytological atypia, unlike SCC. This may be the reason it is often not identified as a malignancy, resulting in treatment delays¹⁵. Most clinicians are unaware of its distinct existence, which makes its diagnosis challenging and potentially missed¹⁶. In this article we present a series of four OCC cases that was referred to our department. Our goal was to demonstrate its unique features and discuss its diagnosis and management.

A retrospective review of oral cancer patients treated by Department of Oral and Maxillofacial Surgery between 2009 and 2020 was performed. The inclusion criterion was an OCC diagnosis based on biopsy findings. Four cases were identified, and their characteristics were analysed. This study was approved in accordance with the Institutional Review Board standards of KAT General Hospital of Attica (IRB No. 11/05-01-2021), and the written informed consent was obtained from all patients.

OCC is a well-differentiated locally aggressive tumour that is characterized by minimal atypia but with evident ability to invade bony structures and rarely to metastasize¹⁵. Its incidence is quite rare, with fewer than 60 cases reported in the English literature^11,17. Usually, OCC affects patients older than 60 years and has a slight female predominance, although it has been reported in children as well^10,11,18. The mean age in our series was 63.5 years, and 3 of 4 patients were men. The aetiology of OCC remains unclear. Smoking and alcohol have been implicated to play a significant role, and trauma, chronic inflammation, and HPV have also been reported as potential etiologic factors^11,13,14. However, unlike oral squamous carcinoma and VC, no clear association between these risk factors and OCC has been established. Two patients in our series (Case 1 and Case 3) had a history of smoking but none reported alcohol consumption. Immunohistochemically, HPV results were negative for all our cases.

Clinically, OCC typically presents as a slow growing, painful mass with an ulcerated/cobblestone surface that most commonly affects the alveolar mucosa/gingiva, followed by the tongue^11,13. Imaging may reveal erosion and destruction of the underlying bone, indicating the aggressive behaviour of the tumor^14,15,19. Two cases in our series (Case 1 and Case 3) involved lesions at the maxillary gingivae with bone involvement. Due to its rarity, OCC is unfamiliar to many clinicians, resulting in misdiagnosis. Diagnosis is based on histopathologic examination of the lesion for characteristic features of a branching network of keratin-filled crypts resembling rabbit burrows, well-differentiated squamous epithelium lining, and little or no atypia^12,17. However, these keratin-filled burrows may not be identified in cases when the tissue sample is small or superficial, which can lead the pathologist to underdiagnose the lesion as pseudoepithelial hyperplasia²⁰. For instance, the patient in Case 2 of our series was misdiagnosed with pseudoepithelial hyperplasia based on a biopsy of her tongue lesion at another institution.

In the past, OCC was thought to be a variant of VC and has been described as an inverted VC^2,5. The World Health Organization classification of 2005 included OCC as a distinct new variant of oral squamous carcinoma^19,21. To differentiate it from OCC, VC is defined by a verrucous growth pattern with vertical fronds mimicking church spires and an intact basal membrane. VC does not usually penetrate the lamina propria, while OCC may invade bony structures. Differential diagnosis also includes papillary squamous cell carcinoma (PSCC); however, PSCC has a characteristic papillary finger-like pattern of growth with a narrow stroma and carries a high risk of regional metastasis¹².

Radical surgical excision is the treatment of choice for OCC. This may include subtotal maxillectomy or mandibulectomy because of the invasive nature of the tumour. To date, due to the low risk of metastasis of OCC, there is no clear evidence that neck dissection is required unless there is clear involvement^11,20. Farag et al.¹¹ in their systematic review found that 6.9% (3 out of 43 OCC cases) had lymph node metastasis, 2% distant metastasis, and 9.3% demonstrated local recurrence. Sun et al.¹² performed the most comprehensive retrospective case series of OCC to date, with 15 cases and a mean follow-up of 45 months; they reported 13.3% nodal involvement in the initial diagnosis. A 20% local recurrence rate was recorded, with no neck involvement¹². Nevertheless, despite its low risk of metastasis, OCC should not be disregarded as an early diagnosis because appropriate treatments can impede tumour spread. None of the cases in our series had initial cervical lymphadenopathy, and the follow-up ranged from 12 to 60 months. The role of other treatments, such as radiotherapy and/or chemotherapy, is controversial as radiotherapy may cause anaplastic transformation^12,22.

OCC has a better prognosis than SCC, as it is associated with a low local recurrence rate and rare metastasis. In cases of recurrence, the tumour appears to have a more aggressive and resistant behaviour than does SCC, and chemo/radiotherapy do not seem to be effective^12,22.

OCC is a rare entity. Although it shares some clinicopathological features with SCC, the two are distinct. Despite its locally invasive nature, OCC is associated with good prognosis after radical surgical treatment. Both clinicians and pathologists should be aware of its existence, as clinicopathologic correlation is essential to avoid misdiagnosis. It is recommended to perform multiple deep biopsies with adequate tissue sampling and to provide the pathologist with a thorough clinical description to achieve an accurate diagnosis. Long-term follow-up is mandatory to rule out recurrence.