Neuroendocrine Carcinoma of the Hypopharynx - An Elusive Clinical Rarity

Abstract

Neuroendocrine carcinoma originating from neuroendocrine cells is typically linked to unfavourable survival rates. We are introducing an exceptional case of neuroendocrine carcinoma occurring in the hypopharynx. To date, only a handful of instances involving primary neuroendocrine carcinoma of the hypopharynx have been documented. Advanced age, being male, a history of chronic alcoholism, smoking, and previous radiation are all risk factors associated with this condition. The majority of patients present with distant metastases and are not amenable to a complete cure. As there are no guidelines for the treatment of this rare tumour, various treatment modalities have been tried. Here, we are reporting one such case which was diagnosed as small-cell neuroendocrine carcinoma of the hypopharynx on the basis of histopathological cues and received concurrent chemoradiotherapy.

Introduction

Neuroendocrine carcinoma originating from neuroendocrine cells is typically linked to unfavourable survival rates [1]. Neuroendocrine carcinomas especially small cell carcinoma is a common pulmonary tumour and its extrapulmonary components are rare. Olofsson and Van Nostrand [2] reported the first instance of EPSmCC originating in the head and neck region in 1972, specifically as a primary tumour in the larynx. Since then, EPSmCC has been observed in various locations within the upper aerodigestive tract of the head and neck, including the larynx, paranasal sinuses, and salivary glands [3]. However, the occurrence of this tumour in the hypopharynx is uncommon. Due to the scarcity of cases involving primary SmCC of the hypopharynx, there is limited information regarding their diagnosis and management.

Case Report

An elderly male in his seventh decade with no comorbidities presented to us with complaints of painful swallowing and left ear pain for five months duration. He denied any change in voice or breathing difficulty. Examination revealed a left level II non-tender, mobile lymph node measuring approximately 1*1 cm. On video laryngoscopy, an ulceroproliferative growth was noted in the left pyriform sinus with pooling of secretions (Fig. 1A). Contrast-enhanced computed tomography revealed a heterogeneously enhancing soft tissue lesion measuring 1.6*1.3*1.1 cm in the left pyriform sinus abutting the left aryepiglottic fold (Fig. 1B).

Fig. 1.

A: Video laryngoscopy image showing growth with pooling of secretions in the left pyriform sinus (*). B: CECT showing heterogeneously enhancing lesion in the left pyriform sinus (#). C: PET CT showing metabolically active lesion in left level 2 lymph node and left Pyriform fossa. D: PET CT showing sub centimetric metabolically inactive lesion in right lung

18 FDG PET CT revealed a low-grade metabolically active left pyriform fossa lesion (SUV_max 1.03), metabolically active left II and III cervical lymph nodes (SUV_max 4.16), suggestive of nodal metastases and a metabolically inactive right lung lower lobe sub centimetric solid nodule- suspicious of metastases (Fig. 1C and D) The lung lesion was biopsied which showed diffuse positivity for Synaptophysin and confirmed as a metastatic NECN lesion.

After doing baseline blood investigations a direct laryngoscopy-guided biopsy was taken from the growth in the left pyriform sinus and sent for histopathological analysis which revealed monomorphous tumour cells arranged as nests, sheets and single infiltrating cells with scant cytoplasm, hyperchromatic nuclei exhibiting nuclear moulding and extensive crushing (Fig. 2A). Immunohistochemistry showed positivity for Synaptophysin, CD56, weak positivity for PanCK and negative for p63 (Fig. 2B C). Ki67 index was 80% (Fig. 2D), in favour of Small cell Neuroendocrine carcinoma.

Fig. 2.

A: Biopsy from left pyriform fossa shows stratified squamous epithelium with monomorphous tumour cells in nests and sheets (H&E 100x); B: IHC with synaptophysin showed strong membranous positivity. C: Pan CK is negative (IHC 100x). D: Ki 67 index is 80% (IHC 200x)

We planned the patient for concurrent chemoradiotherapy keeping in view, his age and performance status. He received cisplatin and etoposide chemotherapy and 60 Gy in 30 fractions radiotherapy to the gross disease and bilateral neck. A 6th week post-treatment scan showed progressive disease and the patient was further planned for palliative care owing to his worsening performance status.

Discussion

Neuroendocrine carcinoma arises from neuroendocrine cells of the body’s endocrine system. The site of primary lesions in the order of decreasing frequency includes the gastrointestinal system (48%), lungs (25%), pancreas (9%), and liver [4]. Primary NEC of the hypopharynx are of very rare occurrence and not more than 6 cases of pure Small cell NEC have been reported so far [5–8].

As per The WHO epithelial neuroendocrine neoplasms of the upper aerodigestive tract and salivary glands classification, 2022 [9] Neuroendocrine tumours are classified as well-differentiated tumours, moderately differentiated and poorly differentiated tumours that are further divided as large cell and small cell type tumours.

As an aggressive type of tumour, patients often exhibit early and widespread metastases [1]. Consequently, it is crucial to assess for distant metastases in all individuals with neuroendocrine tumours and initiate appropriate management based on the findings.

Diagnosis of neuroendocrine tumours is based on histopathological analysis from the suspected lesion, blood or urine investigations to see for 5-hydroxy indole acetic acid (which is a breakdown product of serotonin) in case of functional tumours, endoscopy including video laryngoscopy and upper gastrointestinal endoscopy, computed tomography, nuclear imaging – positron emission tomography, where Ga DOTATE PET CT is preferred (which is a form of somatostatin receptor imaging that is sensitive for low-grade tumours), whereas 18 FDG PET CT is used for high-grade tumours. Immunohistochemical analysis shows positivity for cytokeratin, CD 56, Chromogranin A, synaptophysin and negative for p⁶³, CK7 and CD45.

The latest WHO classification advises against utilizing non-specific biomarkers like CD56, CD57, PGP9.5, and neuron-specific enolase, emphasizing the importance of employing the most dependable biomarkers for confirming a diagnosis of NEN. Synaptophysin is commonly considered the most sensitive biomarker for NENs [10]; however, relying solely on synaptophysin is insufficient to establish a diagnosis. On the other hand, chromogranin-A has been identified as the most precise diagnostic marker for NENs [11].

There are currently no guidelines regarding the treatment of neuroendocrine carcinoma of the hypopharynx, although multimodal treatment combining chemotherapy, radiotherapy and surgery is usually employed. In our case scenario, owing to the patient’s age and general patient factors, we started with combined chemotherapy and radiotherapy.

Management of neuroendocrine tumours differs with individual case scenarios. For localised cases, surgery is considered the most appropriate modality along with adjuvant chemotherapy. Even for metastatic disease, surgery is deemed appropriate if these metastatic deposits are amenable to a total resection, thereafter, adjuvant combined chemotherapy and radiotherapy can be employed. However, the expected outcomes have not been so promising in the previous reports, where the first-year survival rates were below 35% [12].

Conclusion

Neuroendocrine tumours originating in the hypopharynx are exceptionally uncommon, with only a limited number of documented cases. Once diagnosed, aggressive management is typically pursued given the aggressive behaviour of the disease. However, survival rates, even with aggressive management, tend to be low, and optimal treatment for this condition is yet to be determined.

Funding

None declared.

Data Availability

All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The data is available to anyone for review upon request.

Declarations

Ethical Approval

Our institution does not require ethical approval for reporting individual cases or case series.

Informed Consent

Written informed consent was obtained from the patient(s) for their anonymized information to be published in this article.

Conflict of Interest

The authors have no conflict of interests.

Grant Number

Not applicable.