Background

Carcinoma cuniculatum (CC), called cuniculate carcinoma, is a rare low-grade carcinoma [1]. Arid et al. reported a case series of CC on the plantar surface of the foot for the first time [2]. CC has been recorded in other sites including the abdominal wall, skin and, genital region [3,4,5,6]. However, in the oral cavity CC was first identified by Flieger and Owinski [7]. A plethora of synonyms were used in the past denoting this entity such as epithelioma cuniculatum, Buschke–Lowenstein tumor, and inverted verrucous carcinoma (VC) [1, 2, 5].

In terms of its unique clinical and pathological aspects, the World Health Organization (WHO) declared CC of the oral cavity, called oral carcinoma cuniculatum (OCC), as a separate well-differentiated subtype of oral squamous cell carcinoma (OSCC) in 2005 and 2017. Also, OCC and VC were considered as different subtypes, although of being confused in the past [1, 8]. OCC remains a rare entity that has diagnostic challenges, with a total of about 75 cases between 1977 and May 2021 were described in the literature [9]. Herein, we present a new case of OCC in the gingiva of an elderly female.

Case presentation

An 86-year-old female patient presented with a 6 months history of non-painful lesion involved her left lower gingiva. A thorough medical history and clinical data were obtained. On intra-oral examination, a firm mandibular gingival swelling with blunt, pebbly “cobble-stone” surface was developed on both the buccal and lingual aspects of the premolar-molar region. The color of the lesion was similar to the surrounding normal mucosa intermixed with red-white areas (Fig. 1). No palpable draining lymph nodes were noted. Upon preoperative radiographic evaluation, no evidence of bone involvement was noted.

Fig. 1
figure 1

Clinical presentation of a pinkish and red-white colored lesion with an exophytic “cobble-stone” surface

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An incisional biopsy specimen (measuring 1.5 × 1 cm down to bone) was obtained for histopathological examination. Microscopically, the lesion showed proliferation of the well-differentiated stratified squamous epithelium, forming endophytic complex branching networks interconnected with multiple deep keratin-filled clefts and crypts. Such characteristic “burrowing” architecture was evident, which resembles rabbit burrows; the hallmark of OCC (Fig. 2A–C). Besides, the neoplastic cells displayed tortuous cyst-like sinuses (Fig. 2D, E), and neoplastic islands of well-differentiated squamous cells showing minimal cellular atypia and mitosis, with stromal reaction. Notably, there was a close similarity of this field to the well-differentiated conventional OSCC (Fig. 2F).

Fig. 2
figure 2

Photomicrographs, hematoxylin and eosin (H&E) staining, showing A, B endophytic deep “burrowing” growth of neoplastic epithelium with keratin-filled crypts (× 100). C A higher magnification (× 200). D, E Neoplastic cells forming cyst-like sinuses and tracts filled with keratin debris (× 100). F Neoplastic islands. Arrow points to the tumor nest and * indicates the keratin pearls (× 100)

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Based on the previously mentioned clinicopathological features, a diagnosis of a separate variant of OSCC named OCC was made. The surgical decision was a wide excision as the case showed no bone invasion. Neck dissection was not carried out as there was no clinical indication. Of note, management was hard because of the patient’s age.

Discussion

OCC is a unique variant of OSCC that shows distinct clinicopathological features [1, 8]. Intraorally, OCC occurs most commonly on mucoperiosteum, with a predilection for mandibular gingiva, as with our patient. Also, it can frequently affect the tongue. This tumor displays variable clinical presentations with/without bone involvement [10]. Unlike conventional OSCC, OCC differs mainly in that it has (1) a locally aggressive behavior with predominantly endophytic “burrowing” growth pattern, including branched sinuses and deep extending keratin-filled crypts and tracts that resemble rabbit burrows. Hence, the term “cuniculatum” derivates from the Latin meaning rabbit burrow crypts (rabbit-hole like) [11, 12], (2) a well-differentiated squamous epithelium with absent or minimal cellular atypia, and (3) a low-grade malignancy that has a better prognosis than conventional OSCC with a lesser tendency to metastasize. Nevertheless, it is crucial to note that the early diagnoses included metastases to local lymph nodes [13].

Unfortunately, its diagnosis is still challenging because OCC is frequently either missed or misdiagnosed and subsequently undertreated. The diagnostic dilemma of this lesion might return to the following factors:

  • being unacquainted due to its low incidence in addition to insufficient knowledge about this entity, with consequent under-reporting [14].

  • improper biopsy taking (fragmented, limited, or inadequate depth) which may omit the histopathological parameters necessary for reliable diagnosis [10].

To avoid underdiagnosis of OCC and its confusion with other tumors, a diagnostic process is necessary which entails proper knowledge of its entity and diagnostic criteria, an extended clinical evaluation of the suspected cases, following by performance of proper biopsies, appropriate thorough specimen sectioning of these biopsies, and then careful histopathological assessment which is crucial to reveal the endophytic ‘burrowing pattern’, the hallmark of this lesion. Eventually, proper correlation of clinicopathological findings is essential for confident differentiation of OCC from other confusing lesions and in turn for its final diagnosis with the consequent establishment of the proper treatment plan (Fig. 3).

Fig. 3
figure 3

Basis for a proper approach to diagnose OCC

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Wide surgical excision for cases with no bone invasion

The differential diagnosis list of OCC includes lesions of the oral mucosa with exophytic surface and well-differentiated dysplastic epithelial component: VC, papillary squamous cell carcinoma (PSCC), and well-differentiated conventional OSCC. All of these lesions can be distinguished when biopsied, as each variant has a unique histopathological appearance. Consequently, a precise histological diagnosis can assist the clinician in planning accurate treatment, because the prognosis of each varies significantly. The distinctive properties of OCC and other similar lesions to differentiate between them are declared in Table 1.

Table 1 Differential diagnosis of oral carcinoma cuniculatum, verrucous carcinoma, papillary SCC, and well-differentiated conventional OSCC, respectively
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OCC managed for cases associated with bone involvement is subtotal maxillectomy or mandibulectomy with a safety margin. Meanwhile, wide surgical excision is the treatment of choice for cases with no bone invasion. This tumor is of low risk of metastasis. Neck dissection is only required if lymph node enlargement is clinically evident. The role of radiotherapy and chemotherapy remain questionable in the treatment of OCC [10].

Conclusions

In conclusion, diagnosis of OCC requires familiarity with the entity, awareness of clinical and additional parameters, passing through obtaining abundant tissues, and ending with proper knowledge of the histopathological evidence that leads to an accurate diagnosis.