Lymphoepithelial Carcinoma: A Case Report of a Rare Tumour of The Vocal Cord

Priya Philip^1,*, AN. Aswin², Andrew C. Fenn², AN. Vaidhyswaran³

¹Registrar, Department of Radiation Oncology, Kauvery Hospital, Chennai, India

²Consultant, Department of Radiation Oncology, Kauvery Hospital, Chennai, India

³Senior Consultant and Director, Department of Radiation Oncology, Kauvery Hospital, Chennai, India

Abstract

Lymphoepithelial carcinoma (LEC) of the vocal cord is an extremely rare malignancy accounting for 0.2% of laryngeal cancers. It is an aggressive tumour which is rarely associated with Epstein Barr Virus (EBV) unlike LEC of nasopharynx. It should be distinguished from squamous cell carcinoma. The diagnosis often requires immunohistochemistry (IHC) or Electron Microscopy (EM) for confirmation. A 71-year old male, smoker for 40 years, presented to our department with the history of progressive hoarseness of voice of 6 months duration. Laryngoscopy revealed an ulcero-proliferative growth involving anterior two-third of left vocal extending to anterior commissure and anterior part of right vocal cord. The patient underwent micro laryngeal laser surgery and multiple punch biopsies. Microscopic analysis and IHC confirmed the diagnosis of LEC.HPV and EBV markers were negative. PET CT done showed uptake in the anterior 2/3rd of left vocal cord, extending to anterior commissure, with enlarged left level II cervical lymph node. He underwent definitive radiotherapy to a total dose of 66Gy. Chemotherapy was deferred in view of elderly age, comorbidity and poor general condition as per Multidisciplinary board’s decision. Follow-up clinical examination, endoscopy and CT scan after 6 weeks revealed a complete clinical response to treatment. The patient is coming for regular follow-up with the Disease-Free Interval (DFI) of 6 months. Although LEC is an aggressive and a rare tumour of vocal cord, a proper diagnosis and an optimal treatment strategy will enable to get a good clinical outcome as seen in our case report.

Keywords: Lymphoepithelial carcinoma, Epstein Barr Virus, Immunohistochemistry, Disease-Free Interval

Background

Lymphoepithelial carcinoma (LEC) of the vocal cord is an extremely rare malignancy accounting for 0.2% of laryngeal cancers [1]. It is an aggressive tumour which is rarely associated with Epstein Barr Virus (EBV) unlike LEC of nasopharynx [2]. It should be distinguished from squamous cell carcinoma. The diagnosis often requires immunohistochemistry (IHC) or Electron Microscopy (EM) for confirmation. LEC is characterized by nests or sheets of poorly or undifferentiated malignant epithelial cells which are surrounded by plasma cells and lymphocytes. Although the most common site for LEC is nasopharynx, it can arise in other sites such as nasolacrimal duct, sino-nasal tract, salivary glands, oral cavity, oropharynx, larynx, hypopharynx, trachea, thymus, oesophagus, stomach, lung, breast, uterine cervix, vagina, urinary bladder and skin [3]. Majority of the patients were treated surgically although LEC is a radiosensitive tumour. Radiotherapy should be considered as the primary treatment and neoadjuvant chemotherapy can be recommended in node positive patients in order to prevent distant metastases. We report an elderly gentleman diagnosed with LEC of vocal cord, who underwent LASER surgery and definitive radiotherapy to the primary and bilateral neck region. The patient had a complete clinical response post treatment as evidenced by endoscopy and he is coming for follow-up with the Disease-Free Interval (DFI) of 6 months.

Case Presentation

A 71-year old male, smoker for 40 years, presented to our department with the history of progressive hoarseness of voice of 6 months duration. Laryngoscopy revealed an ulcero-proliferative growth involving anterior two-third of left vocal cord extending to anterior commissure and anterior part of right vocal cord (Fig. 1A and B). The patient underwent micro laryngeal laser surgery and multiple punch biopsies. Histopathological examination revealed fragments of neoplastic tissue showing cells arranged in sheets and syncytial pattern showing nuclear atypia and prominent eosinophilic nucleoli admixed with lymphoid cells. By immunohistochemistry, the neoplastic cells are positive for Cytokeratin. The lymphoid cells are positive for CD45 and mixed positivity for CD3 and CD20. LMP-1 and p-16 were negative. Hence the final diagnosis is lymphoepithelial carcinoma (Fig. 2A-C).

Fig. 1A

Fig. 1B

PET CT done showed uptake in the anterior 2/3rd of left vocal cord, extending to anterior commissure, with enlarged left level II cervical lymph node (Fig. 3). He underwent definitive radiotherapy, daily dose of 200cGy to a total dose of 66Gy to the primary and involved lymph nodes with the daily dose of 180cGy to a total dose 60Gy to the bilateral neck using IMRT-SIB (Intensity Modulated Radiation Therapy – Simultaneous Integrated Boost) technique (Fig. 4A-D). Chemotherapy was deferred in view of elderly age, comorbidity and poor general condition as per Multidisciplinary board’s decision. The patient completed the treatment uneventfully. The follow-up clinical examination and endoscopy after 6 weeks revealed a complete clinical response to the treatment. CT scan of neck showed good response to the radiotherapy. The patient is coming for regular follow-up with the Disease-Free Interval (DFI) of 6 months.

Fig. 2A

Fig. 2B

Fig. 2C

Discussion

Lymphoepithelial carcinoma of the larynx is an aggressive neoplasm with high propensity to spread to cervical node and early distant metastasis. Thirty-four cases of LEC have been reported in the literature. In majority of the cases the tumour originated from supraglottic larynx, 77% had positive lymph nodes in the neck dissection specimens, 16% had cervical node involvement at the time of diagnosis and 23% had systemic metastasis [1]. In our case, the site of origin is larynx and PET CT revealed the presence of left level II cervical node.

Fig. 3

Marioni et al [1] reported that EBV plays a limited role in the etiology of LEC of the larynx which is similar to our case study. Microscopically, the neoplasm is composed of large, poorly differentiated, nonkeratinized cells with large, round or vesicular nuclei, each containing a single large centrally located prominent nucleolus. Immunohistochemical stains for keratin and epithelial membrane antigen are usually positive [4]. In our patient, the neoplastic cells are positive for Cytokeratin. The lymphoid cells are positive for CD45 and mixed positivity for CD3 and CD20. Although EBV is associated with nasopharyngeal LEC and HPV has been implicated in few cases, LMP-1 and p-16 were negative in our patient.

Fig. 4A

Fig. 4B

Fig. 4C

Fig. 4D IMRT field arrangements and Dose-volume histogram.

LEC of the larynx is a highly radiosensitive disease and excellent local control rates can be achieved with radiotherapy [5]. Chemotherapy is usually recommended in neck node positive patients in order to prevent distant metastasis [6,7]. However optimal treatment strategy is very difficult in view of its rare incidence. In our case, the patient had good response to radiotherapy. Chemotherapy deferred in view of elderly age, comorbidity and poor general condition. Our case report shows definitive radiotherapy can achieve complete response with the DFI of 6 months. Long term follow-up is needed to find out the presence of local and distant metastasis since chemotherapy is deferred in our patient.

Conclusion

Although LEC is an aggressive and a rare tumour of vocal cord, a proper diagnosis and an optimal treatment strategy will enable to get a good clinical outcome as seen in our case report.

References

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