Abstract
Carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma first described in 1954. Cases of CC in the head and neck are exceedingly rare, with 66 cases reported since 1977. These tumors are generally low-grade, well-differentiated and locally aggressive malignancies. Patients are often subjected to a long period of misdiagnoses given the clinical similarity of these entities to odontogenic cysts and abscesses. We report a case of a carcinoma cuniculatum of the mandible with very advanced local involvement of disease, highlighting the unusual characteristics of this rare tumor that are important for clinicians to recognize. Clinical presentation, histology, risk factors, treatment options, and prognosis are also reviewed.
1
Introduction
Carcinoma cuniculatum (CC), originally known as epithelioma carcinoma, is a rare well-differentiated, low-grade variant of squamous cell carcinoma initially described by Aird et al. in 1954 . The term “cuniculatum” refers to the characteristic histopathological features of complex crypts and channels filled with keratin and lined with well-differentiated squamous epithelium which resemble “rabbit burrows.” Other terms including oral florid papillomatosis, Buschke–Lowenstein tumor, giant condyloma acuminatum of the genitalia, and verrucous carcinoma have also been used to describe this neoplasm . In 2005, the World Health Organization included oral carcinoma cuniculatum as a new variant within head and neck tumors . The distinction of carcinoma cuniculatum from verrucous carcinoma remains controversial, with some suggesting that it should be considered a variant of verrucous carcinoma, while others believe that carcinoma cuniculatum should be considered a separate neoplasm for its local aggressiveness and rapid growth . Histologic diagnosis of carcinoma cuniculatum remains challenging, as it bears a significant resemblance to benign cysts and abscesses .
Initially thought to be limited to cutaneous sites, most commonly the plantar surface of the feet, this neoplasm has since been described in several noncutaneous sites, including the penis, esophagus, larynx, and oral mucosa . To our knowledge, only 66 cases of the head and neck have been reported since Flieger and Owinski first described a case involving the mandible in 1977, with very limited data in English literature involving the oral cavity .
2
Case reports
A 58 year-old male was referred for a three-year history of recurrent oral and facial abscesses requiring multiple hospitalizations and the use of broad-spectrum intravenous antibiotics in conjunction with extensive infectious disease workups. In the months prior to referral, the patient underwent multiple tooth extractions, incision and drainages, and mandibular curettage procedures with a presumed diagnosis of superinfected odontogenic keratocyst of the left mandible. Multiple biopsies taken from two prior dental procedures were consistent with “odontogenic keratocyst”. The final biopsy taken prior to referral revealed epithelial proliferation with mild atypia, and was notable for extensive crypts of squamous-lined epithelium, consistent with carcinoma cuniculatum. This diagnosis was the result of detailed inspection and review by our oral pathology team.
Physical examination was notable for marked asymmetric swelling and tender induration of the left mandible extending superiorly to the maxilla and zygomatic arch and inferiorly to level II of the neck. Intraorally, this swelling extended from tooth #21 along the left mandible to the left retromolar trigone. Two cutaneous fistulae near the left angle of the mandible were noted with active, yellow purulent drainage; no intraoral connection of these fistulae was noted. The patient also had several missing teeth on the left, consistent with prior tooth extractions, and moderate trismus. Floor of mouth and base of tongue were soft. Facial nerve (cranial nerve VII) was intact bilaterally. Aside from the large induration of the primary tumor, no discrete lymphadenopathy was found. The patient reported no significant history of tobacco or alcohol use, and also denied any history of oral or head/neck trauma.
MRI ( Fig. 1 ) and CT scans demonstrated a very large, destructive heterogenous mass centered in the left mandible, obliterating the masticator space, involving the left parotid gland, and extending to the deep parapharyngeal muscles. The tumor was also noted to have extensive surrounding inflammation and phlegmon, abutting the internal carotid artery just below the skull base and obliterating the infratemporal fossa. There was no evidence of distant metastases on preoperative evaluation.
The patient was seen and cared for at our Head and Neck Multi-Disciplinary Conference, and after a careful discussion with the patient and his family, the patient underwent a composite mandibulectomy, radical parotidectomy, left modified radical neck dissection, and left fibular free flap for mandibular reconstruction. Final pathology ( Fig. 2 ) revealed T4aN0M0 carcinoma cuniculatum of the left mandible, with invasion and cortical destruction of the left mandible and maxilla, as well as involvement of the extrinsic tongue muscles, left maxillary sinus, and left facial skin. Primary tumor size was a 3.5 × 3.5 × 3 cm round to oval soft white to red variegated mass infiltrating the parenchyma and the adjacent bone tissue with a large region of surrounding inflammation and keratin debris. All surgical margins were uninvolved by tumor.
The patient has been seen for follow up for 5 months post operatively, and to date, the patient is doing well with no evidence of recurrent malignancy.
2
Case reports
A 58 year-old male was referred for a three-year history of recurrent oral and facial abscesses requiring multiple hospitalizations and the use of broad-spectrum intravenous antibiotics in conjunction with extensive infectious disease workups. In the months prior to referral, the patient underwent multiple tooth extractions, incision and drainages, and mandibular curettage procedures with a presumed diagnosis of superinfected odontogenic keratocyst of the left mandible. Multiple biopsies taken from two prior dental procedures were consistent with “odontogenic keratocyst”. The final biopsy taken prior to referral revealed epithelial proliferation with mild atypia, and was notable for extensive crypts of squamous-lined epithelium, consistent with carcinoma cuniculatum. This diagnosis was the result of detailed inspection and review by our oral pathology team.
Physical examination was notable for marked asymmetric swelling and tender induration of the left mandible extending superiorly to the maxilla and zygomatic arch and inferiorly to level II of the neck. Intraorally, this swelling extended from tooth #21 along the left mandible to the left retromolar trigone. Two cutaneous fistulae near the left angle of the mandible were noted with active, yellow purulent drainage; no intraoral connection of these fistulae was noted. The patient also had several missing teeth on the left, consistent with prior tooth extractions, and moderate trismus. Floor of mouth and base of tongue were soft. Facial nerve (cranial nerve VII) was intact bilaterally. Aside from the large induration of the primary tumor, no discrete lymphadenopathy was found. The patient reported no significant history of tobacco or alcohol use, and also denied any history of oral or head/neck trauma.
MRI ( Fig. 1 ) and CT scans demonstrated a very large, destructive heterogenous mass centered in the left mandible, obliterating the masticator space, involving the left parotid gland, and extending to the deep parapharyngeal muscles. The tumor was also noted to have extensive surrounding inflammation and phlegmon, abutting the internal carotid artery just below the skull base and obliterating the infratemporal fossa. There was no evidence of distant metastases on preoperative evaluation.
The patient was seen and cared for at our Head and Neck Multi-Disciplinary Conference, and after a careful discussion with the patient and his family, the patient underwent a composite mandibulectomy, radical parotidectomy, left modified radical neck dissection, and left fibular free flap for mandibular reconstruction. Final pathology ( Fig. 2 ) revealed T4aN0M0 carcinoma cuniculatum of the left mandible, with invasion and cortical destruction of the left mandible and maxilla, as well as involvement of the extrinsic tongue muscles, left maxillary sinus, and left facial skin. Primary tumor size was a 3.5 × 3.5 × 3 cm round to oval soft white to red variegated mass infiltrating the parenchyma and the adjacent bone tissue with a large region of surrounding inflammation and keratin debris. All surgical margins were uninvolved by tumor.
The patient has been seen for follow up for 5 months post operatively, and to date, the patient is doing well with no evidence of recurrent malignancy.
3
Discussion
In 1977, Flieger and Owinski were the first to describe non-cutaneous carcinoma cuniculatum within the head and neck with a case involving the oral cavity . To date, only 26 cases involving the oral mucosa have been previously published in the English literature ( Table 1 ), with a previously reported incidence of 2.7% amongst all oral cavity squamous cell carcinoma . Other head and neck cases of carcinoma cuniculatum have been found esophagus and larynx, with predominantly more cases reported in the esophagus . Carcinoma cuniculatum most commonly occurs in the sixth and seventh decades of life, with a mean age of 60. However, a significant age range in this limited literature exists; Hutton et al. reported a 7-year old patient with carcinoma cuniculatum of the anterior maxilla, while the retrospective series reported by Sun et al. included a 92 year old patient . Including the present study, our current review shows an essentially equivalent gender distribution (14 males, 13 females), although previous literature suggests a slight male predominance .
