Basaloid squamous cell carcinoma (BSCC) is considered a rare variant of squamous cell carcinoma (SCC).¹ It was first described by Wain et al. in 1986.² In 1991, it was included in the revised edition of the World Health Organization (WHO) classification³,⁴ and was considered as a distinct variant of SCC due to its more aggressive nature and morphological features.⁵ BSCC arises preferentially in the upper aerodigestive tract. Dimorphic pattern is the histological hallmark BSCC of with a characteristic feature of basal cells showing nuclear pleomorphism, hyperchromatic, and indistinct cytoplasm associated with squamous portion. Overlying epithelium showing carcinomatous changes and areas of comedo-necrosis are other common histological features.¹,⁶,⁷ In the oral cavity, the tongue is the most common site of occurrence. However, it is also found in other sites such as floor of the mouth, palate, retromolar area, buccal mucosa, and the gingiva.⁴,⁵,⁶ BSCC on gingiva is very rare, and only a few reported cases are seen in the literature. This study reports and reviews a rare BSCC case involving the gingiva.

A 60-year-old male patient reported to the outpatient department of the authors' institution with the complaint of pain and swelling in the lower front tooth region for 15 days. The patient gave a history of extraction 1 month back due to loosened teeth following which he noticed a soft-tissue overgrowth in his mandibular anterior tooth region. The patient had the habit of bidi smoking for 30 years. Extraoral examination did not reveal any significant findings. He also experienced dull pain associated with this overgrowth. The submandibular and submental lymph nodes on the ipsilateral side were palpable.

On inspection, a soft nodular growth measuring about approximately 5 cm × 3 cm × 2 cm was seen on the mandibular anterior region. The lesion was pinkish white in color and ulceroproliferative in nature. The lesion was extending labiolingually from labial attached gingiva to lingual attached gingiva and mesiodistally from mandibular left canine to mandibular right first premolar region Figure 1. The growth was tender and firm in consistency. Based on clinical findings, a provisional diagnosis of aggressive inflammatory lesion with a differential diagnosis of granulomatous lesion and carcinoma of gingiva was made. No significant findings were noticed in an orthopantomogram. After routine hematological investigations, an incisional biopsy was performed. The tissue specimen was routinely fixed and processed. The H- and E-stained sections showed dysplastic epithelium invading into the connective tissue stroma. Invaded epithelial cells were in the form of nests, islands, and sheets composed of basaloid cells showing hyperchromatic large nuclei and indistinct cytoplasm Figure 2 and Figure 3. Areas of comedonecrosis were seen in between the sheets of cells Figure 4. Frequent mitotic figures were also evident. The stroma also showed numerous blood vessels with areas of hemorrhage. Based on the histopathological findings, a diagnosis of BSCC with differential diagnosis of adenoid cystic carcinoma (ACC) (solid variant) was made. To differentiate between the two tumors, periodic acid–Schiff (PAS) stain and immunohistochemical staining for pan-cytokeratin were done. The negative results of PAS and positive for pan-cytokeratin Figure 5 lead to the final diagnosis of BSCC. The patient did not comply with any further treatment and succumbed to the disease within 1 month.Figure 1

Photograph showing the ulceroproliferative lesion with indurated margins in the mandibular anterior gingiva.

BSCC is a rare variant of SCC with a frequency of >1% of all SCCs.⁴ According to the WHO, it is defined as “an aggressive and distinct variant of SCC, which is composed of basaloid and squamous components.”⁷

BSCC is a particularly rare tumor of the oral cavity having predilection to occur in the base of the tongue (61%) and the floor of the mouth (30%).⁷,⁸ Its occurrence in the gingiva is very rare.⁷,⁹ BSCCs are often diagnosed at advanced clinical stages and their prognosis is unfavorable due to the overall poor patient survival rates.⁴

The etiopathogenesis of BSCC is similar to conventional SCC. Most of the patients will have a long history of tobacco smoking and consumption of alcohol. In the pathogenesis of BSCC, risk factors such as smokeless tobacco and other exogenous carcinogens such as occupational, environmental, and nutritional factors also play a role.⁷

After reviewing, the English literature showed only 17 reported cases of BSCC involving the gingiva. Table 1 discusses and summarizes the clinicopathological features of BSCC cases of gingiva, including the present case. BSCCs of the gingiva have a strong predilection to males (n = 13) than females (n = 4) with 40–85 years of age range and a mean age of 62.5 years. The present case is consistent with the literature with male predilection. Most frequently, it was seen in the mandibular gingiva (n = 13) as compared to the maxillary gingiva (n = 4). Five patients were presented in Stage I, three in Stage II, four in Stage III, and two in Stage IV, according to the AJCC standard tumor-node-metastasis staging. Staging was not assessed for the other three cases. Surgery was the treatment of choice for all the cases. Six patients were treated with neck dissections and four were also given adjuvant radiotherapy. Eleven of 17 patients of BSCC had survived till 56 months of median follow-up time.{Table 1}

Wain et al. first described the BSCC in 1986,²,⁶ and BSCC was diagnosed on the basis of four principal histologic features: (a) solid groups of cells in a lobular configuration closely apposed to the surface mucosa; (b) small, closely packed cells with scant cytoplasm; (c) dark, hyperchromatic nuclei without nucleoli; and (d) small, cystic spaces containing mucin-like material.⁶,⁸ All these features were histologically consistent with the present case.

Clinically, BSCCs are similar to the conventional SCC; therefore, it becomes very difficult to differentiate it from SCC. Therefore, the diagnosis of BSCC is largely dependent on histopathological and immunohistochemical characteristics.⁸ Histopathologically, the BSSC shows that basaloid cells are usually arranged in cords, nests, islands, and lobules. The cells display an increased nuclear/cytoplasmic ratio with scant cytoplasm and oval hyperchromatic nuclei with nucleoli. The cells also show nuclear pleomorphism, and mitotic figures are often observed. The tumor islands exhibit basaloid cells with areas of comedonecrosis and focal keratinization.⁴,⁹

BSCC should be histologically differentiated from solid ACC, adenosquamous carcinoma, mucoepidermoid carcinoma, neuroendocrine carcinoma, basal cell and polymorphous low-grade adenocarcinoma, small-cell undifferentiated carcinoma, conventional SCC, basal cell carcinoma, spindle cell carcinoma, and adenoid SCC.⁷

All these tumors show overlapping histopathological features, and distinction becomes difficult. ACC is one of the minor salivary gland tumors with a palate and retromolar region as their favorite sites. Usually, the solid variant of ACC is difficult to differentiate it from BSCC.² In the present case, the basaloid pattern of ACC was ruled out because of the presence of squamous component and surface dysplastic epithelium which was close to the tumor nests. Certain features such as mitosis, nuclear pleomorphism, and comedonecrosis are common in BSCC compared with ACC, as observed in our case. The mucin positivity and true ductal-acinar differentiation in adenosquamous carcinoma differentiate it from BSCC.²¹

By immunohistochemistry, BSCC expresses cytokeratins, epithelial membrane antigen, pan-cytokeratin AE/AE3, and squamous epithelial marker 34βE12 which are the most useful marker for this tumor.⁷ The present case was immunohistochemically positive for pan-cytokeratin AE/AE3. Immunohistochemical studies have shown that the indices of AgNOR and PCNA (Proliferating Cell Nuclear Antigen) were significantly higher in BSCC than in SCC cases. Immunostaining for p53 protein showed a higher percentage of positive cells and more intense staining in the BSC tissues than in the SCC tissues. In addition, MMP-1, MMP-2, and MMP-9 expression was higher in BSC cells than in SCC cells.¹

The clinical course and the prognosis of BSCC have been considered worse than conventional SCC with an increased tendency for local invasion and distance metastasis. It commonly metastases to lymph nodes, lung, bone, skin, and brain, through lymphatics and blood vessels. Hence, BSCCs are generally been treated with intensive multimodality therapy. It includes excision by radical surgery, dissection of the neck, and radiotherapy along with chemotherapy. BSCC shows a high (60% die of the disease) mortality rate.²² Immunotherapy as adjunct treatment has shown improved treatment with a reduction rate of mortality.⁷,⁹

BSCC of mandibular gingiva is an unusual location. Here, we add an additional case of BSCC involving gingiva to the literature. BSCC is an uncommon malignant tumor and is a distinct clinicopathological entity of SCC. It has aggressive clinical course, high rate of metastasis, and poor prognosis than conventional SCC. Its diagnosis still depends on hematoxylin and eosin sections by recognizing the defined histological criteria and histopathological evaluation. Hence, awareness of BSCC's clinical and pathological characteristics is thus essential for its early diagnosis and treatment.

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Conflicts of interest

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