Fine-needle aspiration cytology of myoepithelial carcinoma of salivary gland: Diagnostic challenge to cytopathologist.

Myoepithelial carcinoma (MC) is rare malignant salivary gland neoplasm and its cytologic features have been rarely described in the literature. Furthermore, MC shows varied cell types and patterns leading to the wide range of differential diagnosis on cytology. Histopathology and immunohistochemistry (IHC) are necessary to make a definite diagnosis. A 37-year-old female presented with painless, progressive swelling in the infra-auricular region since 2 years. Fine-needle aspiration cytology was performed and cytological possibilities of cellular pleomorphic adenoma and myoepithelial cell neoplasm were rendered and patient was advised excision and histopathologic examination for final diagnosis and subtyping. Final diagnosis of MC was made on hematoxylin and eosin sections and IHC. MC is rare malignant salivary gland tumor showing a clinic-pathologic diversity. The cytological features of MC are diverse and may lack overt feature of malignancy. Pathologists should be aware of this entity while evaluating cytological smears of salivary gland mass.

Introduction

Myoepithelial carcinoma (MC), also known as malignant myoepithelioma, is a rare salivary gland malignancy. Until date, the cytomorphological features of MC have not been explicitly discussed in the literature. Potential diagnostic problems may arise due to morphologic heterogeneity of MC and difficulty in predicting malignancy in fine-needle aspiration (FNA) specimens. The authors, thus, in the current case have described the cytological features of MC with discussion of its cyto-differentials.

Case Report

A 37-year-old female patient presented with painless, progressive swelling in the infra-auricular area since 2 years. Examination with palpation revealed a smooth surfaced, mobile swelling measuring approximately 3 cm × 2.5 cm. There was no evidence of facial nerve involvement. FNA cytology was performed with 23G needle. The aspirate was stained with May-Grünwald-Giemsa stain. On examining cytological smears, possibilities of cellular pleomorphic adenoma and myoepithelial cell neoplasm were rendered and the patient was advised complete excision. A left superficial parotidectomy with preservation of facial nerve was performed and tumor sent for histopathological examination. Final diagnosis of MC was made on H and E stained section and on immunohistochemistry (IHC). No local recurrence or distant metastasis was found 6 months after surgery.

Pathological findings

Cytological smears were highly cellular with the neoplastic cells arranged singly, small groups and as large cohesive fragments [Figure 1a]. The large fragments appeared 3D with the high cellularity and nuclear overlapping [Figure 1b]. At places, these large fragments showed pseudopapillary appearance with well-defined borders. The tumor cells had epithelioid appearance with a moderate amount of dense, non-granular cytoplasm [Figure 1c]. Metachromatic stromal fragments were seen intermixed with neoplastic cells. The nuclei were round to oval, at places eccentrically located with mild nuclear pleomorphism. Background showed numerous naked nuclei and stromal fragments. Two cytological possibilities were forwarded — one of cellular pleomorphic adenoma and second of myoepithelial cell neoplasm. Patient was advised complete excision and histopathological examination for final diagnosis and subtyping.

Figure 1

(a) Cytosmears showing tumor cells in small groups and scattered singly (MGG, ×100), (b) Cytosmear showing 3-dimensional tumor fragment with high cellularity, nuclear crowding and overlapping (MGG, ×400), (c) Cytosmears showing tumor cells in clusters with interspersed stromal fragment (MGG, ×400)

Subsequently, we received grey yellow soft-tissue mass measuring 3 cm × 2.5 cm × 2 cm. Cut surface was solid, grey brown with grey white nodules. H and E sections showed a tumor with multinodular growth pattern [Figure 2] and infiltrative borders. The tumor nodules were composed of epithelioid cells arranged in diffuse sheets, nests and cords. Tumor cells had round to oval nuclei, vesicular chromatin, prominent nucleoli and a moderate amount of eosinophilic cytoplasm [Figure 2 inset]. Mitotic rate ranged from 5 to 15/10 HPF. No area of necrosis was identified. A panel of IHC comprising of cytokeratin (CK), S-100, smooth muscle antibody (SMA), epithelial membrane antigen (EMA) and glial fibrillary acidic protein (GFAP) was applied. Tumor cells were positive for S-100, SMA and negative for CK, EMA and GFAP. Based on the histopathology and IHC findings, final diagnosis of MC was rendered and patient was kept on follow-up.

Figure 2

Section showing a nodular tumor in salivary parenchyma (H and E, ×100) and inset showing round to oval tumor cells with vesicular chromatin and clear to eosinophilic cytoplasm (H and E, ×400)

Discussion

MC is a rare salivary gland malignancy representing lesser than 1% of all salivary gland tumors. Most occur in the parotid gland.[1] Over half of cases develop within pre-existing pleomorphic adenomas or myoepitheliomas.[12] The entity was first described by Stromeyer et al.[3] in 1975. However, the tumor was included in World Health Organisation classification of salivary gland neoplasms in 1991. These tumors are considered extremely rare and our current knowledge of MC is limited. Only in recent times, few case series have reasonably discussed the clinicopathological features of MC with particular emphasis on histomorphological spectrum.[245] The currently accepted diagnostic criteria for MC are exclusive myoepithelial differentiation (morphologic and IHC) and clear cut tumor infiltration into adjacent salivary gland or other tissue.[1]

The cytological features of MC are diverse and may lack overt features of malignancy. Few case reports describing cytomorphology of MC have documented presence of epithelioid, spindle and even clear cells in FNA smears.[267] In the current case report, we observed predominant population of epithelioid cells admixed with few spindle cells. Scant to abundant fragments of metachromatic stroma intermixed with neoplastic cells have been observed in cytological smears of MC. In our case also, these stromal fragments were abundant and conspicuous. We found highly cellular smears with considerable nuclear crowding and overlapping, but other features of malignancy including prominent pleomorphism, coarse chromatin, prominent nucleoli, mitotic figures, necrosis was not seen in our smears, making the diagnosis of malignancy unlikely on cytological smears. Similar difficulties have also been encountered by Chhieng and Paulino[1] and DiPalma et al.[8] on FNA smears. Tumor infiltration into adjacent normal tissue is thus, the most important histological feature that distinguishes malignant from benign myoepithelial neoplasms. Hence, histopathology is mandatory to reach the correct diagnosis.

In view of its diverse cytological presentations, MC raises a variety of neoplasm in the differential diagnosis [Table 1]. Benign mixed tumor should be included in the differential diagnosis of MC, particular when the stromal component of MC is conspicuous. Amelonotic melanoma and oncocytic adenoma might also be confused with a myoepithelial neoplasm displaying a plasmacytoid cell appearance. Another great mimicker of MC with clear cell morphology is acinic cell carcinoma. Another differential is epithelial-MC, which shows characteristic bimodal population.[910] In cases where MC have spindle cell morphology, the important differentials are sarcomatoid squamous carcinoma, spindle cell melanoma and schwannoma.

Table 1

Cytological differential diagnosis of myoepithelial carcinoma

IHC further aids in ruling out other differentials and establishing the myoepithelial nature of the neoplasm. In most of MC, calponin and S-100 were consistently positive.[12] CK and SMA reactivity was seen in 70% and 35% of tumors respectively.[1] EMA was found positive only in 27% cases.[1] In our case, tumor cells were positive for S-100 and SMA but showed negativity for CK, EMA and vimentin.

The clinical behavior of MC is variable. Most tumors that display marked cytological atypia, high mitotic activity and necrosis tend to behave aggressively. Because of its rarity, there is a limited experience on treatment of MC. Complete surgical resection is often the treatment of choice.[2]

Conclusion

MC is a rare malignant salivary gland tumor showing the clinicopathological diversity and present with various stages of myoepithelial differentiation. The cytological features of MC are diverse and may lack overt feature of malignancy. Pathologists should be aware of this entity while evaluating cytological specimen of salivary gland mass.