Acantholytic squamous cell carcinoma of the oral cavity: A rare entity.

Acantholytic squamous cell carcinoma (ASCC) is an uncommon but well-recognized variant of squamous cell carcinoma that was first described by Lever in 1947. ASCC has been reported to originate in the sun-exposed skin of the head and neck and in other sites. However ASCC located in the oral cavity is extremely rare. The patient was a 50-year-old man who presented with an ulcer on the right maxillary alveolar mucosa. The biopsy was diagnosed as ASCC. Tumor resection was therefore performed. Histologically, acantholytic pattern was seen throughout the tumor.

INTRODUCTION

Acantholytic squamous cell carcinoma (ASCC) is commonly seen in the sun exposed areas of adults. Their occurrence in the oral cavity is rare and confers bad prognosis. We report one such occurrence in a 50-year-old male and review the pertinent literature.

CASE REPORT

A 50-year-old male presented with a painful bleeding ulcer in the upper right back region of oral cavity which he observed since 15 days. Patient gave history of smoking since 25 years. On examination there was a 3 × 3 cm ulcer on the right maxillary alveolar mucosa. The ulcer had irregular margins and a necrotic base covered with yellowish slough [Figure 1]. Computed tomography (CT) paranasal sinus revealed a heterogeneously enhancing mass of approximately 6.5 × 4.5 cm in the right maxillary antrum [Figure 2]. There was destruction of the antral walls and inferior floor of right orbit. The mass was also extending in to the right pterygopalatine fossa and in to subcutaneous tissue of the face. Excisional biopsy was done and histopathological examination revealed nests of malignant squamous cells revealing acantholysis in the centre and focal pearl formation giving pseudoglandular/alveolar appearance [Figures 3 and 4]. Tumor cells at the periphery of nests were showing pleomorphism, enlarged, irregular hyperchromatric nucleus, densly eosinophilic cytoplasm and frequent mitotic figures. Focal areas of typical squamous cell carcinoma was also found. The tumor cells were also negative for mucicarmine stain. The tumor was diagnosed as ASCC.

Figure 1

Patient photograph revealing the growth in the oral cavity

Figure 2

CT of paranasal sinus revealing a heterogeneously enhancing mass with destruction of the antral walls and inferior floor of right orbit

Figure 3

Nests of squamous cells showing acantholysis and pearl formation (H&E stain, ×200)

Figure 4

Acantholytic squamous cell carcinoma resulting in a pseudoglandular appearance (H&E stain, ×400)

DISCUSSION

ASCC is a histologically distinct variant of squamous cell carcinoma that arises most commonly in areas of the skin exposed to the sun. It is rare on mucosal surfaces of the upper aerodigestive tract.[1] This well-recognized variant of squamous cell carcinoma was first described by Lever in 1947. Although the World Health Organization (WHO) defined ASCC as an original entity since a long time,[23] there are less than 30 cases of ASCCs documented in the international literature so far.[4]

ASCC is also known as adenoid squamous carcinoma, pseudoglandular squamous cell carcinoma, squamous cell carcinoma with glandlike (adenoid) features, angiosarcoma-like squamous cell carcinoma, adenoacanthoma, pseudovascular adenoid squamous cell carcinoma and pseudoangiosarcomatous carcinoma. It differs from common squamous cell carcinoma in histologic features and its aggressive nature. Microscopically, the tumor shows cystic degeneration of the neoplastic epithelium, producing a prominent alveolar pattern and pseudoglandular structures with acantholytic cells. This finding is associated with loss of immunohistochemical expression of E-cadherin, causing loss of cell adhesion in the center of the tumor nests.[5] The peak incidence of the oral ASCC is in the sixth decade.[6] These tumors may have an association to previous exposure to ionizing radiation.[7] It occurs most commonly on the lips, rarely intraorally.[8]

ASCC is differentiated from adenocarcinomas particularly, adenosquamous carcinomas by absence of true glandular formations and negativity for mucin stains. ASCC can mimic adenoid cystic carcinomas due to the presence of glandular spaces and fibrin in these spaces may masquerade as mucin. However in ASCC the glandular spaces often have angular appearance and mucin stains do not show evidence of epithelial mucin. ASCC is almost always accompanied by foci of conventional SCC, suggesting the correct diagnosis. In addition adenosquamous carcinomas show only focal glandular formations, whereas ASCC show pseudoglandular formations throughout the lesion. If these lesions are perceived as glandular and a squamous component also is identified, mucoepidermoid carcinoma (MEC) may enter the differential diagnosis. Low and intermediate grades of MEC show easily definable mucin and rounded glandular spaces. High grade MEC never has abundant glandular formations.

Although angiosarcoma and ASCC are completely different tumor entities, their histological features are similar and defined by intratumoral spaces. Formation of anastomosing spaces and channels in ASCC closely mimicks angiosarcoma. Interestingly both tumor entities show comparable clinical appearance in the oral cavity. The peak incidence of angiosarcoma is the seventh decade and the peak incidence of the oral ASCC is the sixth decade. Macroscopically both entities located in the oral cavity are fast growing, eruptive lesions and have poor prognosis.[79] Like all oral squamous cell carcinomas, ASCC show male predilection of 1-3.5 whereas no sex predilection of oral angiosarcoma is known. Angiosarcoma and ASCC do not only share identical clinical features and a similar histopathological pattern in common histological staining but also show overlaps of cytokeratin-expression and of expression of vascular differential markers. Expression of Fli-1 in angiosarcoma and cytoplasmatic immunoreaction for γ2-chain of ln-5 in ASCC are worked out as distinguishing features of both entities.[4] ASCC differs from common squamous cell carcinoma not only histologically but also by its aggressive nature. When it occurs in the oral cavity, it is associated with a poor prognosis.[8]

In conclusion, ASCC is a distinct histological variant of squamous cell carcinoma, rarely seen in oral cavity and has poor prognosis. It should be differentiated from angiosarcomas and adenosquamous carcinomas.