Oral Carcinoma Cuniculatum: A Variant of Squamous cell Carcinoma with Unique Histological Characteristics and a Diagnostic Challenge

Abstract

Oral carcinoma cuniculatum (OCC) is a rare squamous cell carcinoma (SCC) variant with low incidence often due to misdiagnosis. This report aims to highlight this unique variant of SCC which is suggested to have a better prognosis with a focus on its histopathological features in comparison with similar clinical entities.

Introduction

Oral carcinoma cuniculatum (OCC) was classified by WHO in 2005 as a variant of oral squamous cell carcinoma (SCC) due to its unique histological characteristics which include unique architecture and the presence of well-differentiated cells unlike OSCC [1, 2]. First described in 1954 by Arid et al. over the foot, followed by various other sites of the body like the face, palm, abdomen, esophagus, and cervix. Oral carcinoma cuniculatum was first described in 1977 by Flieger and Owinski [3, 4]. Its low incidence is mainly attributed to under reporting of it which is mainly due to challenges in its diagnosis, and lack of awareness of its unique histological characteristics like keratin-filled branching crypts and keratin cores which give the appearance of rabbit burrows (cuniculatum architecture)[2, 5]. Differential diagnosis includes verrucous carcinoma, differentiated SCC, and papillary SCC which need to be correlated clinically, radiological and histologically to come to the diagnosis of carcinoma cuniculatum (CC)[1, 2, 5–7].

Case Report

A 47-year-old male patient with no comorbidities and no history of consumption of tobacco or alcohol, presented with a slow growing lesion in the left side of cheek since the last 7 years. He gave a history of a similar lesion 8 years ago for which he underwent surgical excision, details of which were not available.

On clinical examination, a proliferative verrucous lesion was seen in the left buccal mucosa of 4 × 3 cm in size extending upto the retromolar trigone area posteriorly and the angle of mouth anteriorly. There were no palpable neck nodes. Biopsy from the lesion at another centre was reported to be verrucous carcinoma, however, well-differentiated squamous cell carcinoma cannot be ruled out. On reviewing, at our centre a diagnosis of SCC carcinoma cuniculatum was made. On CT scan a 3.3 cm x 2.4 cm x 1.7 cm lesion was seen in the left buccal mucosa and lower gingivobuccal sulcus region. It was found to be extending into the masticator space with the involvement of the masseter muscle, while it did not extend beyond the sigmoid notch of the mandible superiorly. Externally it was seen to be involving the skin and subcutaneous tissue. The patient underwent wide local excision of the lesion with left hemi-mandulectomy, left upper alveolectomy, and neck dissection. Final histopathology was reported to be pT4aN0 with free margins and no poor prognostic markers. The patient is 18 months post-surgery and has no local recurrence (Fig. 1).

Fig. 1.

: Clockwise from top right : (A) Low power view of H&E stained slide shows nests of squamous cells invading in a bulbous expansile pattern with few nests showing a central lumina with keratin material. (B) Photo prior to resection (C)Specimen (D) 18 months post op

Discussion

Carcinoma cuniculatum is a relatively rare and unacquainted variant of SCC which according to sun et al. showed an incidence of 2.7% in a review of 540 cases of oral SCC [1]. It is a disease mainly seen in the sixth and seventh decades of life and it is unclear regarding genetic predisposition as several studies report its predominance in either [1, 6]^,. The mandibular and alveolar mucosa are the most common sites [7, 8] while Sun et al. reported a higher incidence in tongue [1] but other sites are also involved like the floor of mouth, buccal mucosa, and tongue. Etiological factors are no different from regular SCC which include tobacco, alcohol, and poor oral hygiene [9]^,.

Histopathologically it has 3 unique entities which include [6], a complex architecture resembling a rabbit’s burrow consisting of branching sinuses and keratin cysts, a minimal or lack of cellular atypia, and lastly broad rete pegs. Although it exhibits both endophytic as well as exophytic growth patterns, it is the former pattern that dominates which makes it locally invasive. Chen et al. [10] proposed a scoring system based on its histological features which help in accurately diagnosing OCC and helps differentiation from other similar clinical entities such as verrucous carcinoma (VC) and papillary SCC. Table 1 provides a detailed comparison between these entities. Verrucous carcinoma although similar to OCC, does not show a branching pattern and sinuses filled with keratin debris histologically while radiologically mandibular erosion produces bony resorption/ destruction in VC while it produces radiolucency in OCC [6]. As per thavaraj et al. [7], there can be foci of SCC in verrucous carcinoma but not in OCC while lymph node metastasis is not seen in VC but can be seen in OCC. Treatment of OCC includes a complete resection with clear margins along with nodal dissection with or without post-op radiotherapy. Its prognosis is better than other variants of squamous cell carcinoma.

Table 1.

Distinguishing features between carcinoma cuniculatum and other mimickers [9]

Features	Carcinoma Cuniculatum	Verrucous carcinoma	Conventional SCC	Papillary squamous carcinoma
Clinically	Broad based; pink, red or white; cobblestone mucosa, nodular lesion	White, warty, cauliflower-like	Ulceroproliferative growth	Soft, finger-like projections
Endophytic and exophytic Components	Predominantly endophytic with variable exophytic component	Broad endophytic and exophytic component	Exophytic component dominantly	Variety of patterns; commonly ulcero-infiltrative
Defining feature	Deeply invasive, branching, keratin-filled large cavities and elongated tunnels	‘Bulldozing’ type, pushing pattern of invasion	Infiltrative, ‘disruptive rather than pushing’ type squamous proliferation with variable cytologic anaplasia	Exophytic papillary tumor lined by dysplastic squamous epithelial covering
Branching keratin-filled cysts	Present	Absent	Absent	Absent
Invasive front	Broad pushing	Broad pushing	Infiltrative; frequently as small irregular destructive islands	Infiltrative
Cytologic anaplasia	Absent; if present, restricted to the basal cells of advancing edges	Absent to minimal; intracytoplasmic dyskeratosis is present	Present; ranging from mild to severe	Present- variable

Conclusion

OCC is a rare variant of SCC, often underreported due to its diagnostic challenges. It demonstrates unique histological characteristic findings, local aggressiveness and has a low risk of distant metastasis which needs awareness among clinical pathologists for appropriate diagnosis and optimal treatment.

Funding

This research did not receive any grant from public, commercial, or not-for-profit funding agencies.

Declarations

Consent

Written informed consent was obtained from all patients regarding publishing data.

Conflict of interest

All authors declare no conflict of interest.

Ethics Approval

Taken from the institutional review committee.