CASE REPORT |
https://doi.org/10.5005/jp-journals-11010-1105 |
Neuroendocrine Tumor of Larynx—A Rare Entity: A Case Report
1–3Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
Corresponding Author: Sufian Zaheer, Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India, Phone: +919650594818, e-mail: sufianzaheer@gmail.com
Received: 04 November 2023; Accepted: 23 April 2023; Published on: 18 June 2024
ABSTRACT
Neuroendocrine laryngeal neoplasms are uncommon and comprise only 1% of all laryngeal neoplasms. These tumors are characterized by cells showing various degrees of pleomorphism that are arranged in nests and trabeculae containing neurosecretory granules, which show immunohistochemical positivity for synaptophysin, chromogranin, and neuron-specific enolase (NSE). Here, we present a rare case of neuroendocrine tumor (NET) grade III of the supraglottic region. The patient presented with a change in voice for 3 years and difficulty in swallowing solid and liquid both for the last 4 months. Histopathological examination showed a lobular architecture with cells exhibiting moderate pleomorphism and finely stippled chromatin. In immunohistochemistry (IHC), these cells showed positivity for synaptophysin and chromogranin with a Ki-67 index of 25%, thus confirming the diagnosis of NET, grade III.
How to cite this article: Jain S, Ahuja S, Zaheer S. Neuroendocrine Tumor of Larynx—A Rare Entity: A Case Report. Indian J Respir Care 2024;13(2):117–120.
Source of support: Nil
Conflict of interest: None
Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.
Keywords: Case report, Grade, Larynx, Neuroendocrine carcinoma, Neuroendocrine tumor, Supraglottis, Synaptophysin
INTRODUCTION
Neuroendocrine laryngeal neoplasms are uncommon and account for only 1% of all laryngeal neoplasms.1 The first incidence of neuroendocrine tumor (NET) was described in 1969, and since then, the terminology of laryngeal neuroendocrine neoplasm (NENs) has improved significantly.2 NENs are categorized into three broad types based on histology and clinical behavior—(1) well-differentiated NETs; (2) neuroendocrine carcinoma (NEC), with two different types: (a) small cell carcinoma, and (b) large cell NEC; (3) mixed neuroendocrine nonneuroendocrine neoplasms.3 The genesis of these tumors is unknown, with several ideas proposed; the most widely accepted theory is that they are derived from neuroendocrine precursor cells. Smoking is the most significant predisposing factor. The present case report offers a distinctive perspective on the clinical presentation, diagnostic challenges, and treatment considerations of neuroendocrine grade III tumor, which is a rare tumor in comparison to the typical/atypical carcinoids and NECs. By highlighting the specific classification of the tumor as a grade III NET, we contribute to the broader understanding of this rare entity and emphasize the importance of accurate histopathological characterization. Additionally, the specific location and extent of the tumor, as well as the detailed histopathological and immunohistochemical findings, provide valuable insights into the varied manifestations and characteristics of neuroendocrine laryngeal neoplasms. Here, we report a case of a supraglottic grade III NET in a 52-year-old reformed smoker.
CASE DESCRIPTION
A 52-year-old male presented with a change in voice for 3 years and difficulty in swallowing solid and liquid both for the last 4 months. General physical examination was within normal limits. Bilateral air entry was equal on respiratory examination.
He was a reformed smoker, had a known case of diabetes mellitus for 10 years, and was on oral hypoglycemic drugs. There was no history of hypertension, pulmonary tuberculosis, or head/neck malignancy in his family. Indirect laryngoscopy revealed globular growth arising from the right arytenoid and aryepiglottic fold. Bilateral vocal cords were not visible. His other biochemical investigations were within normal limits. A computed tomography scan of the neck showed a lobulated heterogeneously enhancing, soft tissue lesion involving the right aryepiglottic fold, posterior pharyngeal wall, and anterior aspect of true vocal cord on the right side with partial effacement of the right pyriform fossa (Fig. 1).
Figs 1A to C: Radiological findings of NET grade III: (A to C) Contrast enhanced computed tomography (CECT) neck exhibiting a heterogeneously enhancing lesion in the right supraglottic larynx involving the right aryepiglottic fold, posterior pharyngeal wall, false vocal cord, and anterior aspect of true vocal cord on the right side with partial effacement of the right pyriform fossa
Elective tracheostomy and direct laryngoscopic excisional biopsy of the mass were performed under general anesthesia. Histopathology report showed a lobular architecture separated by fibrous septa. These cells exhibited moderate pleomorphism and were medium in size, with a moderate amount of eosinophilic cytoplasm and salt pepper chromatin. Based on IHC analysis, these cells were immunopositive for synaptophysin and chromogranin and negative for thyroid transcription factor-1 (TTF-1) and p63 with a Ki-67 index of 25%, confirming the diagnosis of NET, grade III (Fig. 2).
Figs 2A to F: Microscopic and immunohistochemical findings: (A to C) Hematoxylin and eosin-stained sections exhibited a tumor arranged in lobules separated by fibrous septa (A, B); The cells exhibited moderate pleomorphism with salt pepper chromatin and a moderate amount of eosinophilic cytoplasm (C) (×4, ×10, and ×20); (D to F) IHC showed positive expression for synaptophysin (D) and chromogranin (E) with a Ki-67 proliferation index of 25% (F) (×10, ×20)
DISCUSSION
Neuroendocrine laryngeal tumors are the most frequent nonepidermoid tumors of the larynx, accounting for <1% of all laryngeal tumors.4 Small cell neuroendocrine carcinoma (SCNEC) (41%) is the most common laryngeal NEN documented, followed by NET G2 (37%) and NET G1 (5.3%).5,6 Patients with laryngeal NENs are usually middle-aged to elderly and have a history of heavy smoking.5-7 A strong predilection for the supraglottic region has been reported previously, with the aryepiglottic fold being the primary subsite, which was similar to our case. The majority of the symptoms and presentation mimic a classical laryngeal malignancy and can only be differentiated by histopathologic evaluation. NETs are characterized by cells showing various degrees of pleomorphism that are arranged in nests, cords, and trabeculae containing neurosecretory granules which show immunohistochemical positivity for synaptophysin, chromogranin, and neuron-specific enolase (NSE).8
On a small biopsy, the histological findings of laryngeal NENs might be confused for more common pathologic entities. Cellular monotony, fine-stippled nuclear chromatin, and a myriad of histomorphological patterns lying in a fibrovascular stroma were characteristics of NET G2 tumors. The peculiar ”glomeruloid structures” are a distinctive characteristic of this entity. The differential diagnoses for NET include squamous cell carcinoma (SCC), melanoma, salivary gland neoplasms, paraganglioma, medullary thyroid carcinoma, glomus tumor, and plasmacytoma. If the monotony of neoplastic cells and organoid pattern is ignored on low-power examination, they may be misdiagnosed as SCC, the most common laryngeal cancer.9 Laryngeal NEN therapy strategies are not standardized because they are uncommon, and there is little clinical experience with them. Depending on the biological characteristics of the various histological types and the stage of the disease, several therapeutic modalities are used to treat laryngeal NETs. Surgery continues to be the mainstay of NET G3 treatment, and the function of radiation and chemoradiotherapy is still unclear. However, for the majority of NEC patients, chemotherapy, with or without radiotherapy, is the main course of treatment.5,10 NETs classified as grade I or II have an average prognosis of 48% for the first 5 years and 30% for the 10th year of survival; however, grade III NETs have a worse prognosis of 29% for the first 5 years of median survival.10 However, the prognosis and 5-year survival of NET grade III is better than NEC. Hence, it is essential to differentiate between the two entities. NET grade III is relatively well differentiated, with a high Ki-67 proliferation index. On the contrary, NECs are poorly differentiated with necrosis and abundant mitosis.11 Ki-67 is the most widely utilized prognostic biomarker and serves as the foundation for NET grading. Furthermore, Yuan et al. have proposed that insulinoma associated protein 1 (INSM1) plays a critical role in the diagnosis and categorization of laryngeal NEC.12,13Table 1 summarizes the clinicopathological findings of previously reported cases of NENs of the larynx.14-19
| Author (year) | Age/sex | Clinical presentation | Clinical diagnosis | Radiological findings | Histopathology | Treatment |
|---|---|---|---|---|---|---|
| Rai et al.(2017)14 | 50/M | Change in voice, dysphagia, and dyspnea | Ulceroproliferative growth | CECT: A soft tissue lesion with smooth outlines in the left piriform fossa with involvement of left AE fold | Atypical carcinoid | Total laryngectomy |
| Paudel et al.(2020)15 | 50/F | Throat pain, hoarseness, and dysphagia | Cystic mass | NET grade II | Complete endoscopic excision | |
| Y et al.(2021)16 | 65/M | Pharyngeal paresthesia | Hemangioma | Atypical carcinoid | Partial laryngectomy | |
| Mesolella et al. (2021)17 | 68/M | Dysphagia and dysphonia | Ulcer-vegetative growth | CT: A voluminous expansive neoformation that presented enhancement after contrast into the left lateral wall of the larynx | Small cell NEC | Total laryngectomy with radical neck dissection with neoadjuvant CT and RT |
| Zhu et al.(2015)18 | 61/F | Hoarseness, sore throat, hemoptysis, a lump sensation, and dyspnea | Typical carcinoid | Endolaryngeal microsurgery | ||
| 60/F | Typical carcinoid | Total laryngectomy with neck dissection | ||||
| 75/M | Atypical carcinoid | Partial laryngectomy with neck dissection | ||||
| 62/M | Atypical carcinoid | Partial laryngectomy with neck dissection | ||||
| 66/F | Atypical carcinoid | Partial laryngectomy and neck dissection and radiotherapy | ||||
| 30/F | Atypical carcinoid | Partial laryngectomy | ||||
| 66/M | Atypical carcinoid | Total laryngectomy and neck dissection and radiotherapy | ||||
| 53/F | Small cell NEC | Chemotherapy and radiotherapy | ||||
| 66/M | Small cell NEC | Induction chemotherapy, radiotherapy, and adjuvant chemotherapy | ||||
| 27/F | Small cell NEC | CRT and chemotherapy | ||||
| 50/M | Small cell NEC | Chemotherapy and radiotherapy | ||||
| 54/M | Small cell NEC | Induction chemotherapy, radiotherapy, and adjuvant chemotherapy | ||||
| 52/M | Small cell NEC and adenocarcinoma | Partial laryngectomy, neck dissection, chemotherapy, and radiotherapy | ||||
| 16/F | Small cell NEC | Chemotherapy and radiotherapy | ||||
| Feola et al.(2020)19 | 59/M | Dysphagia and dyspnea | CT: A vascularized lesion of the supraglottic left hemilarynx | NET grade II | Tumor debulking |
CECT, contrast enhanced computed tomography; CT, computed tomography; F, female; M, male, NEC, neuroendocrine carcinoma; NET, neuroendocrine tumor; RT, radiotherapy; CRT, chemoradiotherapy
Neuroendocrine tumors are frequently observed in the gastrointestinal and respiratory tract, rarely in the head and neck region. We would want to highlight the present case because laryngeal NETs are a very uncommon entity when compared to tumors with epidermal origin. It is critical to get an accurate diagnosis of the NET subtype because treatment and prognosis differ. Conservative surgery, such as endoscopic excision and supraglottic laryngectomy, are preferable alternatives, although larger lesions may require total laryngectomy.
CONCLUSION
Neuroendocrine tumors of the larynx are extremely rare, accounting for only 1% of all laryngeal neoplasms, and pose significant diagnostic and therapeutic challenges. This case report of a grade III neuroendocrine tumor in the supraglottic region underscores the importance of thorough diagnostic evaluations, including histopathological and immunohistochemical analysis, to accurately classify and grade the tumor. The distinctive immunohistochemical markers, such as synaptophysin, chromogranin, and Ki-67, are crucial for diagnosis and prognosis. Surgical intervention remains the primary treatment for these tumors, although the roles of chemotherapy and radiotherapy are still being defined. This case adds to the limited knowledge of laryngeal neuroendocrine tumors and highlights the need for continued research to develop standardized treatment protocols and improve patient outcomes.
ORCID
Sana Ahuja https://orcid.org/0000-0002-4630-016X
Sufian Zaheer https://orcid.org/0000-0002-8044-4327
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