Primary Epstein–Barr virus-negative lymphoepithelioma-like carcinoma of the supraglottic larynx mimicking nasopharyngeal carcinoma: a case report

Abstract

Lymphoepithelioma-like carcinoma (LELC) of the larynx is exceptionally rare and can closely mimic undifferentiated nasopharyngeal carcinoma. A 78-year-old man presented with progressive dysphonia and dysphagia. Endoscopy and computed tomography showed a supraglottic lesion with bilateral cervical lymphadenopathy (cT2N2M0). Biopsy demonstrated poorly differentiated non-keratinizing carcinoma with dense lymphoid stroma and a Schmincke-type pattern. Tumor cells were positive for p40, p63, and pancytokeratins; Epstein–Barr virus testing was negative. After exclusion of a nasopharyngeal primary, the diagnosis of primary laryngeal LELC was established. Definitive cisplatin-based chemoradiotherapy with intensity-modulated radiotherapy (70 Gy in 35 fractions) achieved complete clinical and radiological response at 12 months with preserved swallowing and phonatory function.

Introduction

Lymphoepithelial carcinoma is a poorly differentiated epithelial malignancy accompanied by a prominent lymphoid stroma. It most commonly arises in the nasopharynx, where Epstein–Barr virus (EBV) has a well-established pathogenetic role [1]. Primary laryngeal involvement accounts for ~0.2% of laryngeal malignancies and predominantly affects the supraglottis [2]. Its morphological similarity to nasopharyngeal carcinoma creates a relevant diagnostic challenge, while its rarity limits evidence regarding optimal treatment [1–3]. We report an EBV-negative supraglottic lymphoepithelioma-like carcinoma (LELC) with bilateral cervical nodal disease, initially interpreted as nasopharyngeal-type undifferentiated carcinoma, successfully treated with organ-preserving chemoradiotherapy.

Case report

A 78-year-old man was referred for progressive dysphonia and dysphagia. Flexible videolaryngoscopy demonstrated an expansive lesion involving the right false vocal cord, Morgagni’s ventricle, and right true vocal cord, with preserved laryngeal mobility (Fig. 1). Bilateral laterocervical lymphadenopathy was present clinically.

Figure 1.

Pre-treatment flexible videolaryngoscopy showing an expansive lesion involving the right false vocal cord, Morgagni’s ventricle, and right true vocal cord.

Contrast-enhanced neck computed tomography (CT) showed a supraglottic mass with multiple bilateral cervical lymphadenopathies (Fig. 2). The largest nodes measured ~3.5 cm in the left middle jugular region (level III) and 3.2 cm in the right upper jugular region (level IIa). The disease was staged cT2N2cM0 according to the eighth edition of the American Joint Committee on Cancer staging system.

Figure 2.

Contrast-enhanced neck CT showing the supraglottic laryngeal mass and bilateral cervical lymphadenopathy.

Microlaryngoscopic biopsy demonstrated a poorly differentiated non-keratinizing carcinoma with dense lymphoid stroma and a diffuse Schmincke-type growth pattern (Fig. 3), initially raising the possibility of nasopharyngeal-type undifferentiated carcinoma. Immunohistochemistry showed tumor-cell positivity for p40, p63, and pancytokeratins; the lymphoid component was positive for cluster of differentiation 20 (CD20), whereas CD30 and CD56 were negative. The Ki-67 proliferation index was ~70% (Fig. 4). Immunohistochemical testing for EBV was negative.

Figure 3.

Hematoxylin–eosin staining showing poorly differentiated non-keratinizing carcinoma with dense lymphoid stroma and a Schmincke-type growth pattern.

Figure 4.

Immunohistochemical assessment showing epithelial-marker expression and high proliferative activity, with a Ki-67 index of ~70%.

Multidisciplinary pathological review classified the lesion as poorly differentiated squamous cell carcinoma with lymphoepithelioma-like features. Flexible endoscopic examination of the nasopharynx showed no suspicious lesion, and contrast-enhanced CT demonstrated no evidence of a nasopharyngeal primary. These findings, together with the pathological assessment, supported a diagnosis of primary EBV-negative laryngeal LELC.

After multidisciplinary tumor-board discussion, the patient received definitive concurrent cisplatin-based chemoradiotherapy with intensity-modulated radiotherapy delivering 70 Gy in 35 fractions to the primary tumor and involved nodal regions. The choice of definitive chemoradiotherapy was based on the bilateral clinically positive cervical nodal disease (cN2c), the reported radiosensitivity of LELC, and the aim of achieving organ preservation while providing concurrent treatment of the primary tumor and regional nodal disease. Treatment was completed without major complications.

At 12-month follow-up, flexible videolaryngoscopy showed a complete regression with no residual or recurrent disease (Fig. 5), and contrast-enhanced CT showed no macroscopic recurrence (Fig. 6). Swallowing was preserved and phonatory performance remained acceptable. Written informed consent for publication of the clinical information and images was obtained from the patient.

Figure 5.

Follow-up flexible videolaryngoscopy showing complete regression of the lesion with preservation of laryngeal anatomy.

Figure 6.

Contrast-enhanced neck CT at 12 months after treatment showing no macroscopic evidence of recurrent disease.

Discussion

Laryngeal LELC is among the rarest epithelial malignancies of the upper aerodigestive tract; fewer than 50 laryngeal and hypopharyngeal cases have been described, with the supraglottis representing the most frequent site [1, 2, 4]. Histologically, these tumors may show Regaud or Schmincke patterns. The latter, characterized by diffuse malignant epithelial cells within abundant lymphoid stroma, was present in this patient and explains the initial resemblance to nasopharyngeal carcinoma [1, 5].

A crucial diagnostic step is the exclusion of a nasopharyngeal primary or secondary involvement. In the present case, direct flexible endoscopic assessment of the nasopharynx and contrast-enhanced CT showed no nasopharyngeal lesion. Pathologically, the differential diagnosis includes nasopharyngeal-type carcinoma involving the larynx and other poorly differentiated laryngeal malignancies. The diffuse Schmincke-type architecture with abundant lymphoid stroma, together with epithelial differentiation demonstrated by p40, p63, and pancytokeratin expression and the absence of CD30 and CD56 expression, supported a LELC. Immunohistochemical testing for EBV was negative. In contrast to nasopharyngeal carcinoma, the association between EBV and laryngeal LELC is inconsistent, and many Western cases are EBV negative, suggesting EBV-independent pathways [1, 3, 5, 6]. Rare head and neck histotypes can present substantial diagnostic difficulties and may benefit from expert pathological review. Filippini et al. recently highlighted the role of second-opinion pathology and dedicated diagnostic networks in this setting [7].

No standardized treatment algorithm exists. Surgery, radiotherapy, chemoradiotherapy, and multimodal approaches have all been reported [1–4, 8]. Lymph-node metastases are relatively frequent at presentation, particularly for supraglottic tumors, reflecting the rich regional lymphatic drainage [1, 2]. Contemporary evidence emphasizes the prognostic relevance of cervical nodal disease and the need to tailor neck treatment to nodal risk and clinical nodal status [9]. In the present patient, multiple bilateral metastatic-appearing cervical nodes, including a 3.5-cm left level III node and a 3.2-cm right level IIa node, supported the cN2c classification and favored comprehensive treatment of both the primary tumor and involved nodal regions. Given the reported radiosensitivity of LELC, the bilateral cN2c disease and the objective of laryngeal preservation, definitive cisplatin-based chemoradiotherapy was selected after multidisciplinary discussion and achieved a complete response at 1 year with preserved swallowing and phonatory function. The 12-month follow-up is a relevant limitation of this report and is insufficient to establish durable oncological control; longer surveillance is therefore required.

Acknowledgements

During manuscript preparation, the authors used OpenAI ChatGPT to assist with English-language editing and formatting to the target journal’s requirements. All authors critically reviewed, revised, and approved the final text and take full responsibility for its content.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Funding

No funding was received for this study.

Data availability

All relevant data supporting this case report are included in the article.

Ethics

According to institutional policy, ethical approval was not required for this single case report.

Patient consent

Written informed consent for publication of the clinical information and images was obtained from the patient.