Abstract
Introduction
Neuroendocrine tumours of the larynx are extremely rare, though they make up only 1% of tumours in this region with the most common site being the supraglottis. On exhaustive research on PubMed, there are only a few prior cases of neuroendocrine carcinoma of subglottis published in the literature.
Case Report
A 56-year-old male presented to our center with complaints of hoarseness and dyspnoea for 1 month which was insidious in onset and gradually progressive. The patient was evaluated and diagnosed with as subglottic mass. He underwent tracheostomy followed by Micro laryngoscopy and Biopsy under GA. Post-op HPE report s/o Neuroendocrine carcinoma- small cell type. On evaluation no second primary or distant metastatic site was identified.
Conclusion
Small cell neuroendocrine carcinoma of the subglottic larynx is an exceptionally rare and aggressive malignancy. Its presentation can be atypical, such as with symptoms of stridor, necessitating a high index of clinical suspicion. Early diagnosis and prompt, aggressive management are critical for improving outcomes. Despite the limited prognosis associated with this type of cancer, the patient in this case has shown a favourable response to chemoradiotherapy. Continued monitoring is essential due to the high risk of recurrence and metastasis associated with this malignancy.
Keywords: Neuroendocrine tumors, Laryngeal malignancies, Small cell neuroendocrine neoplasm, Subglottis
Introduction
Neuroendocrine tumors are primary tumors of the gastrointestinal tract (about 70% of cases) followed by the respiratory tract (about 25%) [1].
Neuroendocrine tumors of larynx are rare with only 0.3% of laryngeal malignancies being of a non-squamous cell cancer origin. According to the degree of differentiation, neuroendocrine tumors are classified into well, moderate, and poorly differentiated. Latter consists of small cell and large cell NEC. Small cell neuroendocrine carcinoma is an extremely rare histopathological diagnosis and supraglottic airway is the leading subsite of larynx [2]. We present a rarest of rare presentation in the form of primary subglottic involvement.
We present a case of a 56-year-old male with a poorly differentiated subglottic laryngeal small cell neuroendocrine carcinoma and its management.
Case Presentation
A 56-year-old male presented with a 1-month history of hoarseness and dyspnoea, both of which developed insidiously and progressively. Over the course of next 01 week, he experienced worsening dyspnoea.
On further evaluating the patient, video laryngoscopy revealed a fleshy mass in the subglottic region extending to the inferior margin of the right true vocal cord. Both true vocal cords were mobile.
Contrast-Enhanced CT (CECT) Neck
Showed a heterogeneously enhancing endoluminal lesion in the subglottic space, inferior to the right true vocal cord, measuring 18 × 15.5 × 24 mm, causing near-total obliteration of the airway (2.2 mm) (Fig. 1).
Fig. 1.
CECT findings; coronal section
CT Angiogram of the Neck
Demonstrated a faint contrast blush along the superior aspect of the lesion.
Due to impending stridor, the patient underwent a tracheostomy followed by microlaryngoscopy and biopsy under general anaesthesia (Fig. 2).
Fig. 2.
Intra-op cranial and caudal view
Histopathological Examination
The biopsy revealed pleomorphic round to oval nuclei, hyperchromatic salt-and-pepper chromatin, and scant cytoplasm. Immunohistochemistry was positive for Pan CK, Synaptophysin, Chromogranin, CD56, and TTF1. The proliferative index by Ki67 was > 90% (Fig. 3), indicating a neuroendocrine carcinoma, small cell type.
Fig. 3.
HPE findings
In view of diagnosis of neuroendocrine carcinoma, the patient underwent additional Imaging:
Whole Body Positron Emission Tomography and Computed Tomography (WB PET-CT)
Revealed a focal hypermetabolic ill-defined enhancing endoluminal nodular lesion arising from the right lateral wall of the subglottic larynx, measuring 1.7 × 0.8 × 1.6 cm, with an SUV max of 10.5, likely representing primary neoplastic pathology (Fig. 4). No FDG-avid lesions were observed elsewhere in the body.
Fig. 4.
WB PET CT axial section
Treatment
The case was discussed in the tumour board, and the patient underwent 4 cycles of chemotherapy with Cisplatin (100 mg) and Etoposide (150 mg) along with 66 Gy/33# of radiotherapy.
Response
Post-CCRT, the patient responded well. No residual lesions were observed on fibre-optic laryngoscopy (Fig. 5) and the patient was decannulated 01 month after completion of therapy. Currently, the patient is asymptomatic with no swallowing or breathing difficulty at nine months of follow up.
Fig. 5.
Cranial view showing no growth; only tracheostomy tube cuff is visualise
Discussion
Neuroendocrine tumors of the larynx are not only rare but also have a myriad of subsets. An accurate histologic diagnosis is essential because the treatment and prognosis depend on the type of neuroendocrine tumor. Small cell neuroendocrine neoplasm of the larynx has the worst prognosis, with a five-year survival rate of 5% [3, 4]. Small cell neuroendocrine carcinomas usually arise sub-mucosal in the supraglottic region and it is rare for them to originate in the subglottic larynx. Our case involved a neuroendocrine carcinoma of the subglottic region, which as a primary presentation is exceptionally rare. Small cell neuroendocrine carcinomas are very aggressive neoplasms characterized by diffuse early metastasis. The aggressive nature of small cell neuroendocrine carcinoma of the larynx presents a challenge to the oncologist [4, 5]. Reports of improved survival with systemic chemotherapy combined with radiation therapy had been suggested as a primary treatment modality [5–9].
Conclusion
Small cell neuroendocrine carcinoma of the subglottic larynx is an exceptionally rare and aggressive malignancy. Its presentation can be atypical, such as with symptoms of stridor, necessitating a high index of clinical suspicion. Early diagnosis and prompt, aggressive management are critical for improving outcomes. Despite the limited prognosis associated with this type of cancer, the patient in this case has shown a favourable response to chemoradiotherapy. Continued monitoring is essential due to the high risk of recurrence and metastasis associated with this malignancy.
Declarations
Ethical Approval
Ethical approval was not taken in view of the treatment being offered were part of the routine care in the tertiary care institute.
No identification of any patients done in the paper. Appropriate sections covered to hide identity.
Informed Consent
Consent from patient taken.
Conflict of Interest
The authors have no relevant financial or non-financial interests to disclose.
The authors have no competing interests to declare that are relevant to the content of this article.
All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.
The authors have no financial or proprietary interests in any material discussed in this article.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Mikić A, Zvrko E, Trivić A, Stefanović D, Golubović M (2012) Small cell neuroendocrine tumor of the larynx–a small case series. Coll Antropol 36(2):201–204 Browne JD [PubMed] [Google Scholar]
- 2.Browne JD (1997) Management of nonepidermoid cancer of the larynx. Otolaryngol Clin North Am 30(2):215–29. PMID: 9052666 [PubMed] [Google Scholar]
- 3.Ferlito A, Silver CE, Bradford CR, Rinaldo A (2009) Neuroendocrine neoplasms of the larynx: an overview. Head Neck: J Sci Specialties Head Neck 31(12):1634–1646 [DOI] [PubMed] [Google Scholar]
- 4.Giddings NA, Kennedy TL, Vrabec DP (1987) Primary small cell carcinoma of the larynx: analysis of treatment. The J Otolaryngology 16(3):157–166 [PubMed] [Google Scholar]
- 5.Monroe AT, Morris CG, Lee E, Mendenhall WM (2005) Small cell carcinoma of the head and neck: the University of Florida experience. Journal-Hong Kong College Of Radiologists 8(2):83.
- 6.Arensman AF, Pingnet L, Lammens M, Nicolay S, Vanderveken OM (2023) A rare laryngeal tumor: poorly differentiated primary small cell neuroendocrine carcinoma. B-ENT 19(3):188–191 [Google Scholar]
- 7.Zhu Y, Gao L, Meng Y, Diao W, Zhu X, Li G, Gao Z, Chen X (2015) Laryngeal neuroendocrine carcinomas: a retrospective study of 14 cases. BioMed research international 2015 [DOI] [PMC free article] [PubMed]
- 8.Becht R, Kiełbowski K, Żychowska J, Dembowska W, Król M, Birkenfeld B, Owsiak M, Lewandowska M, Kubrak J, Amernik K (2023) Small cell carcinoma with neuroendocrine differentiation of subglottic larynx-a case report. Front Oncol 13:1222418 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Singh H, Chauhan A (2011) Primary small cell carcinoma of the larynx: report of a rare tumor. Case Reports in Oncological Medicine 2011 [DOI] [PMC free article] [PubMed]