Primary Lymphoepithelial Carcinoma of the Submandibular Gland in A Young Patient: A Case Report

Abstract

Lymphoepithelial carcinoma (LEC) is a rare entity of malignancy. It has been associated with Epstein-Barr virus (EBV), and in regions where it is endemic, such as Southeast Asia, EBV is typically associated with nasopharyngeal carcinoma. The incidence of such malignancies in the young population is unusual. Here we report a 17-year-old with a 5-year history of a painless right submandibular mass presenting with a sudden increase in size for one month before surgery. Neck examination revealed a firm right submandibular gland measuring five by five cm, with an irregular surface, non-tender with normal overlying skin. We performed a fine needle aspiration cytology (FNAC), and he underwent computed tomography (CT) scan of the neck. He underwent a right submandibulectomy. Lymph nodes from levels I and II were also removed. The final histopathology was reported as LEC. Following this tissue diagnosis, another follow-up surgery, a modified radical neck dissection, was carried out for locoregional clearance. Postoperatively, he completed chemoradiotherapy treatment and is now on regular follow-up.

Case Report

A 17-year-old boy presented with a 5-year history of right submandibular mass. Since it was initially small and painless, it did not bother him or his parents to seek medical advice. However, the mass then progressed to a significant size within a month, which prompted the family to seek medical attention. The mass, however, was still painless, and the size did not change with food intake. There were no other palpable masses in the neck. Fine-needle aspiration cytology (FNAC) was arranged, and he was also scheduled for computed tomography (CT) scan of the neck. The FNAC reported moderately cellular smears composed of a heterogeneous population of lymphoid cells consisting of small and large lymphocytes mixed with some germinal centre cells accompanied by scattered neutrophils and tingible body macrophages. No granuloma, Reed Sternberg cells or malignancy was identified. These features are consistent with a lymphoproliferative process.

The CT scan of the neck reported a right submandibular region mass measuring 3.5 × 2.5 × 3.7 cm in the widest dimension with multiple enlarged and enhancing right cervical lymph nodes at levels I and II. Based on these initial FNAC and CT findings, he underwent a right submandibulectomy with excision of the surrounding lymph nodes. Intraoperatively, a multilobulated, smooth and well-encapsulated tumour was found (Fig. 1).

Fig. 1.

Descriptions: The tumour’s cross-section reveals multifocal solid tan-greyish nodules surrounded by haemorrhagic areas

The histopathology examination (HPE) revealed a solid tumour of multifocal tan-greyish nodules with foci of haemorrhages. The neoplastic epithelial cells formed syncytial sheets. Intratumoral lymphoid cell infiltrates and dense peritumoral lymphoid cells forming into prominent germinal centres were seen. The residual salivary gland showed chronic inflammation (Fig. 2). The tumour cells were stained positively for cytokeratin AE1/AE3, EMA and EBER in situ hybridisation. One lymph node was positive for metastasis. The patient was diagnosed with lymphoepithelial carcinoma (LEC) of the submandibular gland, TNM8 stage pT3 N1, with underlying characteristics indicative of chronic sialadenitis.

Fig. 2.

Descriptions: A microscopic examination reveals tumour cells in syncytial sheets and small clusters. The tumour cells have round to oval nuclei, vesicular chromatin, prominent nucleoli, and a scant to moderate cytoplasm. Intratumoral lymphoid cell infiltrates and dense peritumoral lymphoid infiltrates are observed. Residual salivary glands are noted at the specimen edge (arrowhead)

Based on this HPE report, a PET CT scan of the neck found evidence of F-fluorodeoxyglucose (FDG) avid metastases to the right-sided level II, III and IV cervical nodes with no evidence of avid distant metastases. An endoscopy of the nasopharynx showed enlarged adenoid tissue with normal Fossa of Rossenmuller on both sides. We did a punch biopsy of the mucosa of the nasopharynx, and HPE revealed no malignancy. Following this latest report and findings, we performed a right-modified radical neck dissection type 3. HPE of the cervical nodes’ specimen showed evidence of metastatic carcinoma in 2 out of 13 lymph nodes at levels I to IV. He was then sent to the oncology department for postoperative chemoradiotherapy, receiving 33 cycles of radiotherapy and six cycles of chemotherapy. The patient remained well six months post-treatment and is currently in regular follow-up.

Discussion

Lymphoepithelial carcinoma (LEC) of the submandibular gland is a scarce and distinct type of salivary gland malignancy. It is well established that the major salivary glands, particularly the parotid gland, are affected in a 4 to 1 submandibular gland ratio. The age representation usually refers to the adult population aged 30 to 60 years. Currently, there is little available literature on LEC among the younger population. However, there is one reported case of an 18-year-old with LEC of the submandibular gland [1]. Other than the salivary glands, lymphoepithelial-like carcinoma (LELC), analogous to LEC, has also been seen within the head and neck region, particularly in tissues within the soft palate, tonsils, larynx, and thymus [2].

Evidence shows a close correlation exists between the LEC of salivary glands and Epstein-Barr virus (EBV) [3]. In Southern China, Southeast Asia, and the Arctic regions (Alaska, Greenland, and Northern Canada), EBV is linked with endemic nasopharyngeal carcinoma (NPC). LEC is rare in Americans and Europeans, with Caucasians accounting for less than 15% of reported cases [4]. It is, therefore, necessary for proper management to correctly identify and diagnose these two distinct entities.

As seen in this case, there are few symptoms and signs to suggest malignancy. Most malignant salivary gland lesions cannot be distinguished from their benign counterparts when judged on clinical criteria alone. A minimally invasive investigation such as fine needle aspiration cytology (FNAC) has a role in the initial preoperative tissue diagnosis. When FNAC reports the presence of both lymphoid and epithelial components, it is safe to consider the likelihood of lesions such as sialadenitis, lymphadenoma, or other epithelial salivary gland tumours commonly associated with lymphoid proliferations, such as in Warthin’s tumour, acinic cell carcinoma, mucoepidermoid carcinoma, adenocarcinoma, and LEC [5]. In contrast to parotid tumours, tumours of the submandibular gland have an incidence of malignancy of approximately twice that of the parotid gland.

Histopathological diagnosis remained the gold standard in diagnosing LEC. The tumour expressed Epstein-Barr virus (EBV), where its presence in the specimens was examined by in situ hybridisation technique using oligonucleotide probes targeted to EBV-encoded small RNA 1 (EBER-1). Although our case showed the presence of EBV in the tumour cells, there are reported cases of EBV-negative LEC [6]. We wish to highlight that in our Southeast Asian region, EBV is commonly associated with NPC. Therefore, as illustrated in our case, any suspicious tissue found in the nasopharynx would deserve a tissue biopsy to rule out NPC.

The treatment protocol for malignant salivary glands should be surgical resection with postoperative radiotherapy. However, our first approach to treating the tumour is performing a submandibulectomy with excision of the level I and II cervical lymph nodes. This initial surgery was carried out due to the limited cytological information from the FNAC. Once a correct histopathological diagnosis has been established, treatment strategies for such malignancy should include primary resection combined with neck dissection followed by adjuvant radiotherapy and chemotherapy. Because LEC is rare, most reports agree with this treatment regimen based on the results of limited case series [7]. Since our patient is young, we had to treat this malignancy aggressively. Although some reports have shown that between 40 and 57% of LEC patients have metastatic regional lymph nodes requiring neck dissection, we did not find this in our initial patient assessment [8]. He had to undergo a second surgery to complete neck dissection after we detected suspicious metastatic nodes from the PET scans. Therefore, we strongly recommend a PET scan to look for locoregional involvement, as illustrated in our case.

Like NPC, LEC is radiosensitive; therefore, radiotherapy should be recommended as a treatment [8]. Because of the similar histological features with NPC, chemotherapy has also been recommended for treating LEC [9]. However, there are limited reports on chemotherapy for LEC. Therefore, more extensive studies are needed to see the efficacy of chemotherapy treatment in LEC.

A study by K.Y Zhan et al. concluded that surgical resection combined with postoperative radiotherapy showed significant overall survival outcomes among LEC patients as opposed to doing surgery alone [10]. Thus, a combination of treatment of surgical resection followed by postoperative radiation therapy can be considered adequate for treating the LEC of the salivary gland.

In conclusion, LEC is a rare tumour of the head and neck region, especially when it occurs in a young patient. An aggressive approach to managing such young patients by performing complete surgical resection with neck dissection and postoperative radiotherapy will provide the best outcome possible. Besides taking a good history and careful physical examination, we strongly recommend a nasopharyngeal biopsy to rule out NPC. Radiological imaging procedures such as PET-CT scans, when available, are beneficial diagnostic aids and should be obtained as part of the preoperative diagnosis and planning.

Authors’ contributions

AII performed the initial surgery and was the major contributor to writing the manuscript.

LSK performed the histological examination of the tumour and provided the final histopathological report for the manuscript.

MZAB performed the second surgery and analysed the findings of the PET scans.

MRMY proofread the manuscript and provided ideas for the literature search for the discussion.

All authors read and approved the final manuscript.

Funding

Not applicable.

Data Availability

Not applicable.

Declarations

Ethics approval and consent to participate

1. Case reporting from our institution does not require approval from our ethics committee, the JKEUPM (Ethic Committee for Research Involving Human Subjects) of Universiti Putra Malaysia

2. However, the patient has obtained informed consent before this write-up.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Verbal and written consent has been obtained from the patient.