Epithelial-myoepithelial carcinoma (EMC) is a rare low-grade salivary gland malignancy of presumed intercalated duct origin comprising 1% of all salivary gland tumours. High grade transformation (HGT) in EMC is a recently recognised entity with only a few cases reported in the literature. The authors report an additional case of EMC with HGT involving the submandibular gland. The patient was a 60-year-old woman who requested examination of the rapid growth of a mass in the left submandibular area, which she had first noticed 20 years previously. Histologically, the tumour had two distinct carcinomatous components. One component had features of a low grade EMC. The second component consisted of polygonal cells, arranged in a solid and nested pattern, with marked nuclear pleomorphism, brisk mitotic activity, and frequent necrosis. The Ki-67 labelling index of the EMC component was 9%, and that of the high grade component was 40%. The patient developed multiple pulmonary metastases 15 months after surgery. The aggressive behaviour of EMC with HGT suggests that it is important to recognise this variant of EMC to avoid misdiagnosis and inappropriate treatment.
Tumour development or progression is a multistep process, often involving sequential accumulation of genetic changes. The progression of salivary gland tumours has two major pathways: malignant transformation of a benign tumour and progression from low-grade to high-grade carcinoma (high-grade transformation, HGT) . HGT, previously referred to as dedifferentiation, is defined as the histological progression of a low-grade malignant neoplasm to a high-grade one, within which the original line of differentiation is lost. HGT of salivary gland carcinomas is a rare event, but has been recognised in a variety of salivary gland carcinomas, including epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma, adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, mucoepidermoid carcinoma, and myoepithelial carcinoma . High-grade transformed salivary gland carcinomas are generally associated with an aggressive clinical course despite the histological types of the original tumour. Failure to recognise areas of HGT results in the therapeutic mismanagement of patients.
EMC is a rare low-grade salivary gland malignancy of presumed intercalated duct origin comprising 1% of all salivary gland tumors . EMC with HGT is extremely rare with only a few cases reported in the literature . The clinicopathologic features of this entity are not well characterised. In this paper, the authors present an additional case of EMC with HGT arising in the submandibular gland.
A 60-year-old female patient presented with a non-tender left submandibular mass. The lesion had been present for about 20 years with a recent rapid increase in size. An extraoral physical examination revealed an elastic–firm, relatively well-defined, and moderately mobile mass with a maximum diameter of 3 cm, in the left submandibular area. No lymphadenopathy was palpable and no palsy involved the left marginal mandibular branch of the facial nerve. Routine hematologic and biochemical examination, chest radiograph, and abdomen ultrasound appeared normal. Computed tomography (CT) revealed an irregular-shaped mass measuring 3.4 cm × 3.0 cm in the left submandibular gland ( Fig. 1 ). The mass was heterogeneous with scattered calcifications. Total excision of the left submandibular gland was performed under a diagnosis of a submandibular tumour, probably a pleomorphic adenoma or carcinoma ex pleomorphic adenoma. At surgery, it was found that the tumour was not fixed to adjacent structures and was contained within the submandibular salivary gland capsule. The pathological diagnosis was ‘salivary duct carcinoma’, made by a general pathologist at that time. Further neck dissection and adjuvant radiotherapy and chemotherapy were suggested but refused by the patient because of her poor economic condition. The postoperative course was uneventful. 15 months after surgery, the patient presented with cough and moderate dyspnoea for several weeks. The chest X-ray indicated the presence of patchy opacities in her left middle lung field. Subsequent CT of the lung demonstrated multiple nodular lesions involving both lungs. The patient declined further therapies and was lost to follow up.
In a retrospective study, the present case was re-evaluated by the authors and selected immunohistochemical stains were performed. After a review of the literature, the diagnosis of EMC with HGT was finally established.
Examination of the haematoxylin–eosin (H–E) stained sections revealed an incompletely encapsulated tumour, consisting of two different components, including approximately 80% EMC and 20% high-grade carcinoma of the whole tumour. Both components were well delineated, but there were areas where they merged imperceptibly with each other ( Fig. 2 a ). No area of pleomorphic adenoma was seen in any section. The EMC component was composed of islands, large nests, or cords of tumour cells frequently forming ductules within a prominently hyalinised background ( Fig. 2 b). The inner layer of ductules consisted of cuboidal eosinophilic cells and the outer layer consisted of clear cells. The clear cells were the predominant component, characterised by their large size, polygonal shape and clear cytoplasm, with hyperchromatic nuclei and inconspicuous nucleoli. Focal luminal calcifications, as well as foci of stromal calcification, were noted. There was mild to moderate cytologic atypia and the number of mitoses was low (3 per 10 high power fields). The high-grade component consisted of solid and nested growth patterns with marked central necrosis, similar to comedonecrosis. The tumour cells were polygonal with abundant clear or pale eosinophilic cytoplasm, and had large pleomorphic nuclei and frequent mitosis (15 per 10 high power fields) ( Fig. 2 c). Spindle-shaped cells were focally present. There was no evidence of glandular or squamous differentiation. The high-grade component infiltrated into the adjacent submandibular gland tissue with perineural and vascular invasion. These findings were consistent with an undifferentiated carcinoma.