Clear cell carcinoma is a rare type of salivary gland carcinoma. It has a low degree of malignancy and long-term prognosis is favourable after surgical removal. The authors describe the case of a human immunodeficiency virus (HIV) infected 43-year-old woman who presented with a tumour on the floor of the mouth. After biopsy, left suprahyoid lymph node dissection and removal of the submandibular and sublingual glands was performed, followed by radiotherapy. Histologically, the tumour presented the characteristic features of hyalinizing clear cell carcinoma, defined as a variant of clear cell carcinoma by the latest World Health Organization classification. Hyalinizing clear cell carcinoma has a characteristic histological pattern and, to date, there is insufficient information to determine whether both forms behave similarly or differently. The present case illustrates a highly uncommon tumour variant occurring in a HIV-infected patient. To date, this association has not been described in the medical literature. The low grade of malignancy reported for this tumour demands a precise diagnosis and complete tumoral excision.
Human immunodeficiency virus (HIV) infected patients often experience an increase in the size of the salivary glands, due to a wide range of conditions, including inflammatory processes, infections and neoplasms. In some patients, it is the first sign of disease. An understanding of the underlying salivary pathology is necessary to guarantee correct treatment . HIV patients have approximately a 40% chance of developing a malignant disease, a rate that is expected to rise due to their increased survival . The most frequent head and neck tumours in HIV-infected patients are Kaposi’s sarcoma (over 15%) and non-Hodgkin’s lymphoma (3–10%) . During the last few years, the risk of developing oral squamous cell carcinoma has increased .
Clear cell carcinoma (CCC) is a rare salivary gland tumour that shows a low grade of malignancy . It has a certain potential for recurrence and metastasis, but long-term prognosis is favourable after removal, with or without radiotherapy . It most often affects minor salivary glands and occurs predominantly in women as a painless, submucosal mass . The latest WHO classification has defined it as a malignant epithelial neoplasm composed of a population of monomorphic cells having clear cytoplasm . Many types of salivary gland neoplasms may contain a component of clear cells, but CCC is distinguished by the absence of the typical characteristics of other neoplasms and its monomorphic population of clear cells .
Hyalinizing CCC (HCCC) is considered a variant of CCC, distinguished by a densely hyalinized stroma. Both tumours have similar clinical characteristics .
The authors describe the case of a HIV-positive female patient who developed HCCC in a sublingual location. It is interesting not only because of the relation between HIV infection and the tumour but also because it concerns a rare morphological variant and a major salivary gland.
A 43-year-old woman was referred by her dentist for the evaluation of a painless tumour on the floor of the mouth. In 1995, during a laboratory analysis she was diagnosed HIV-positive, and since then she has been receiving antiretroviral therapy (didanosine, lamivudine and efavirenz). She has been asymptomatic with no AIDS-related disorders. The tumour was detected 1 month before surgery. Laboratory analysis confirmed the HIV positivity and showed a normal CD4 count. Complementary studies included orthopantomography, which ruled out bone involvement, and MRI, which showed a tumour on the left side of the floor of the mouth ( Fig. 1 ). No local or regional adenopathies were present. A diagnostic biopsy was carried out and a diagnosis of CCC of salivary gland was obtained. It was decided to perform a left suprahyoid lymph node dissection and to remove the submandibular and sublingual glands. The surgical sample had two nodular areas (of 3.5 and 3.9 cm) attached by a thin fibrous band ( Fig. 2 ). The smallest had a firm, irregular, solid aspect with intermixed adipose tissue whilst the largest one corresponded to the submandibular salivary gland.
Microscopically, the tumoral nodule showed salivary gland parenchyma (sublingual) extensively infiltrated by a neoplastic epithelial growth. It showed a greatest dimension of 2.7 cm. Tumoral cells formed variably sized solid nests and irregular cords. Characteristically, the stroma was dense and fibrous consisting of wide areas of hyalinizing connective fibrous tissue with few fibroblasts and lymphocytes ( Fig. 3 ). The tumoral cells were large, polygonal and the majority showed clear, empty cytoplasm with well defined cytoplasmic membranes ( Fig. 4 ). The cells were moderately pleomorphic with occasional nucleoli and mitotic figures. In addition to clear cells, a few nests showed a population of peripherically distributed, smaller cells with slightly eosinophilic cytoplasm. No squamous, acinar or mucinous differentiation was seen. There was no necrosis, vascular or neural invasion. The neoplasia was not encapsulated and showed an infiltrative growth pattern with focal, microscopic involvement of the surgical limits. The submandibular gland showed no abnormalities. The surgical specimen included two small periglandular lymph nodes that showed no metastases. Tumoral cells showed a positive reaction with PAS staining and immunohistochemical expression of cytokeratins (AE1/AE3). There was no expression of S-100 protein, smooth muscle actin, muscle-specific actin, carcinoembrionic antigen or calponin. Isolated cells expressed epithelial membrane antigen. Histology and immunohistochemistry were characteristic of HCCC involving the sublingual gland. After surgery, the patient received radiotherapy with an external radiation cycle over 6 weeks. She was given 5040 cGY in 28 fractions to the submandibular, cervical and supraclavicular lymph nodes, bilaterally, and 6120 cGY in 34 fractions to the floor of the mouth. There has been no recurrence or metastasis in the 24 months since the first operation.