Basal cell adenocarcinoma of submandibular salivary gland-problems in cytologic diagnosis

Abstract

Basal-cell adenoma and basal-cell adenocarcinoma of the salivary gland are rare tumors. Fine-needle aspiration cytology of these tumors, particularly those of basal-cell adenocarcinoma, has rarely been described in the literature. In this report, we describe the clinical, cytomorphologic and histopathologic features of basal cell adenocarcinoma in a 48-year-old male patient. Fine-needle aspiration specimen showed abundant cohesive groups of basaloid cells revealing focal anisonucleosis and nuclear atypia. The tumor cells also showed rosette-like arrangement around central eosinophilic globule. Pertinent literature is reviewed and differential diagnosis are discussed.

Introduction

Basal-cell adenocarcinoma (BCAC) of salivary gland is considered to be the malignant counterpart of basal-cell adenoma (BCA). Reports of malignant basaloid salivary gland tumors are extremely rare. Very few reports describing the cytological features of BCAC are available in the literature. It is important to differentiate BCAC from other basaloid cell tumors of salivary gland tumors because of the differences in prognosis and potential differences in treatment. This case report describes the cytological features of BCAC in the sub-mandibular gland of a 48-year-old male. Further, we have discussed the differential diagnosis of these tumors with other basaloid tumors of salivary gland.

Case Report

A 48-year-old male patient presented with a tender swelling in the lower-right region of face since 6 months. On examination, swelling was present on right side of the face, in the right sub-mandibular region, measuring approximately 5 × 4 cms in size. The swelling was well defined, firm and tender and was fixed to the underlying structures. Fine needle aspiration cytology (FNAC) was done from the right sub-mandibular region. Smear showed cellular smears comprising of cohesive sheets of monomorphic, small round-to-oval cells showing mild pleomorphism and nuclear overlapping. The tumor cells were showing hyperchromatic nuclei, with inconspicuous nucleoli, scanty cytoplasm [Figure 1] and tendency towards peripheral palisading in a few clusters. Occasional clusters revealing anisonucleosis were also seen [Figure 2]. Mitotic figures and anaplasia could not be appreciated. Rosette-like pattern with central, eosinophilic globules were appreciated [Figure 1, inset]. Features were suggestive of BCA with suspicion of malignancy. However, histopathological examination was advised to confirm the diagnosis.

Figure 1.

Nests of basaloid cells containing basal lamina-like material in between the cells. Inset shows rosette-like arrangement around central eosinophilic globule (Giemsa, ×200)

Figure 2.

Occasional clusters revealed anisonucleosis and nuclear atypia (Giemsa, ×200)

Patient underwent right sub-mandibular gland extirpation. Gross examination of the specimen revealed a greyish brown partially encapsulated soft tissue mass measuring 6 × 4 × 3 cms. The outer surface was nodular and cut section was lobular with minute cystic areas. Microscopically, the section showed sheets and nests of proliferating monotonous basaloid cells having hyperchromatic nuclei. Two types of basaloid cells were observed-dark basophilic cells towards the periphery and pale basophilic cells towards the centre of the proliferation. Some of these nests revealed peripheral palisading of cells. There was deposition of PAS positive basal lamina like material within and around the nests of tumor cells [Figure 3, inset]. However, in some areas, nests of tumor cells revealed moderate pleomorphism, slightly irregular vesicular nucleus, inconspicuous nucleolus and atypical mitotic figures. There was evidence of vascular invasion by tumor cells. Some of the tumor nests showed central area of necrosis. Encapsulation could not be identified, and nests of tumor cells were invading the surrounding adipose tissue and skeletal muscles [Figure 3]. Intervening connective tissue stroma was fibrous with hemorrhagic areas. Perineural infiltration of tumor tissue was evident

Figure 3.

Nests of basaloid cells invading the surrounding skeletal muscle and adipose tissue (H and E, ×200). Inset shows PAS positive basal lamina material between tumor cells (PAS, ×400)

Discussion

BCAC, a sub-type of salivary gland carcinoma, which was included in the 1991 World Health Organization classification of salivary gland neoplasms. Although there have been occasional references in the literature over the past 30 years to malignant basaloid tumors, malignant transformation of BCA and salivary gland carcinomas associated with BCA, BCAC has only recently been characterized.[1]

The 2005 World Health Organization classification categorizes BCAC as a low-grade tumor with a favorable prognosis.[2] They comprise 1.6% of all salivary gland neoplasms and 2.9% of malignant salivary gland neoplasms.[3] Ninety percent of cases reported are in the major salivary glands, usually the parotid. Four cases have been reported in the sub-mandibular gland till 2009.[4] No further case reports could be found in the literature. This case adds up to the incidence of reported cases of BCAC of the sub-mandibular salivary gland.

BCAC is believed to arise from pluripotent ductal reserve cells. Grossly, these tumors appear solid grey-tan and can grow as large as 7 cm in diameter.[3] Histologically, BCAC is a tumor similar to BCA except that it grows in an invasive destructive fashion, often with perineural and/or vascular invasion.[1] True invasion must be distinguished from both multi-nodularity with a pushing type of growth pattern and multi-focal origin in adjacent salivary lobules, both of which are the features of BCA. Cellular atypia and mitosis may be present and variable and do not warrant the diagnosis of malignancy but may be helpful if there is a lack of surrounding tissue.

Recently, diagnostic fine-needle aspiration cytomorphology of these tumors have been described in isolated case reports. These include basaloid-cell clumps with hyperchromatic nuclei and scant cytoplasm, accompanied by characteristic peripheral features, including palisading poor cohesiveness, and/or intermingling with fat cells.[5] According to Gary et al.[6] the cytologic features of BCAC are not distinctive, but the presence of two-cell populations with moderate pleomorphism and a rosette-like pattern with central, eosinophilic globules may assist with its differentiation from other salivary gland neoplasms. Pisharodi[7] described the cytomorphological features in their two cases of BCAC. Fine-needle aspiration specimens in both cases contained cohesive, focally papillary, and filiform groups of neoplastic cells, which were highly reminiscent of BCA on low-power examination. Higher power, however, revealed significant cytologic atypia and mitotic activity.

In general, FNAC for salivary gland tumors requires expertise in interpretation. It becomes more difficult especially in cases of rare tumors where limited literature is available on their cytomorphology. When a diagnosis is not clear (despite a cellular aspirate), repeat FNAC may provide a cytological diagnosis. Cytology should be used in conjunction with other investigations of salivary tumors, including image-guided biopsy examination where appropriate.[8] In the present case also, repeat FNA and correlation with radiological findings helped in the final diagnosis.

The cytologic evaluation of salivary gland tumors, however, is limited by the wide range and heterogeneous nature of benign and malignant tumors arising in this area, many of which share similar or show overlapping cytologic features, making the diagnosis of rare tumors problematic. The sensitivity ranges from 62% to 97.6% and specificity is higher ranging from 94.3% to 100%.[9] Diagnostic criteria depend on cytological features, architectural organization and synthetic cellular products. Background of the smear is equally important. Romanowsky type of stain is a must for FNA of salivary gland lesions. Certain guidelines can be formed in order to avoid the pitfalls to a certain extent. It is prudent on occasions to limit the FNA report to differential diagnosis.[10] In this tumor, differential diagnoses includes BCA, adenoid cystic carcinoma (ACC), cellular pleomorphic adenoma with hyaline globules, epithelial myoepithelial carcinoma and basaloid squamous cell carcinoma among others. The distinction from BCA is more important and can be equally difficult. Mitotic figures, mild nuclear atypia and evidence of necrosis indicate malignancy. ACC is another most important differential diagnosis. However, the hyaline globules of BCA are smaller, are of more uniform size and with a less hyaline texture. The nuclei of tumor cells of ACC are less regular, hyperchromatic with a corsely granular chromatin and nucleoli are more prominent. Nuclear molding is a common feature in ACC, but not seen in BCAC. Distinction from cellular pleomorphic adenoma requires spindle shaped and plasmacytoid cells with well-defined cytoplasm. Epithelial myoepithelial tumors show biphasic population of tumor cells in addition to hyaline stromal globules. Differentiation of basaloid squamous cell carcinoma depends on the identification of cells with obvious squamous differentiation. Immunohistochemically, BCAC show diffuse or focal strong positivity for cytokeratin (CK) and demonstrate negative staining for CK20.[11] Positivity for carcinoembryonic antigen and epithelial membrane antigen are noted. The presence of myoepithelial cells was demonstrated by moderate to strong expression of S-100.[11] These immunohistochemical markers can be applied on cell blocks and can be of great diagnostic value in suspicious cases.

It is clear that these neoplasms do not have a malignant potential to metastasize and lead to death. At present, these are believed to be low-grade adenocarcinomas, with a relatively good prognosis. They are locally destructive with a propensity to recur. Surgical excision with a wide margin to ensure complete removal has been suggested as the primary treatment for BCAC.[10] BCAC is well controlled locally, although local recurrence was reported in 28% of the cases of Ellis and Wiscovitch.[12] The surgeon should aim for complete surgical removal of the tumor during the first surgical procedure to avoid recurrence.

Enucleation or curettage is to be avoided. Radiotherapy has been proposed for lesions in the minor salivary glands because of the higher likelihood of vascular and neural invasion.[4] Radiotherapy has also been used for tumors with a diffuse infiltrating pattern to adjacent tissue

To conclude, although the incidence of BCAC in sub-mandibular salivary gland is very low, one should consider this entity in the differential diagnosis of sub-mandibular salivary gland neoplasms. It is necessary to differentiate BCAC from other basaloid cell tumors because of the differences in prognosis and potential differences in treatment.