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Surgical palliation in poorly differentiated neuroendocrine carcinoma of the hypopharynx: Case report

Abstract Background Primary neuroendocrine carcinomas (NECs) are very rare entities accounting for 0.49% of all malignancies. Within the head and neck, the most common sites are the larynx and paranasal sinuses, while the hypopharynx is seldom described. Case We present a patient with a poorly differentiated metastatic NEC of the hypopharynx treated palliatively with organ‐preserving surgery and post‐operative chemotherapy, and literature review for well‐documented pure hypopharyngeal NECs. Our patient died of chest infection during chemotherapy, 4 months after surgery. Conclusion Chemotherapy remains the mainstay of treatment in the presence of metastases with 2‐year overall survival of 15.7%. Due to the aggressive nature of poorly differentiated metastatic NECs, surgical management is seldom considered. We report and advocate the successful palliative role of organ‐preserving, minimally invasive trans‐oral LASER micro‐surgery and neck dissection to control loco‐regional head and neck disease, safe‐guarding better quality of home life, despite limited life expectancy for this condition.

In the present article, we describe a case of small cell poorly differentiated metastatic NEC of the hypopharynx. We underline the practical benefits of a non-radical, palliative surgical approach to ensure a better quality of home and family life in a disease with a very poor prognosis. A literature review is also presented. Clinical examination showed a large, expanding conglomerate nodal mass at right neck level II to IV with palpable contralateral cervical disease. Fiberoptic laryngeal examination showed an exophytic lesion obliterating the whole right pyriform fossa, spilling over marginally onto the right aryepiglottic fold and laryngeal vestibule; although reduced right vocal cord motility, the airway was uncompromised.

| CASE
An magnetic resonance imaging (MRI) scan of the neck with contrast ( Figure 1) showed a 3.5 x 3.4 x 1.6 cm mass centred in the right pyriform fossa and a right level II to IV large lymph node conglomerate mass measuring up to 7.5 cm in craniocaudal diameter, encasing the common carotid artery to its bifurcation and obliterating the IJV. Separate abnormal left level II lymph and level III lymph nodes measuring 1.4 and 2.3 cm respectively were noted.
A 68 Ga-DOTATATE PET-CT showed pulmonary nodules (non-avid for tracer), highly suspicious for metastases, with primary right hypopharynx mass and bilateral cervical lymph nodes (right > left; all nonavid for tracer). The patient was radiologically staged as T4aN3bM1 (stage IVC).
We performed a panendoscopy and biopsy of the hypopharynx mass, which revealed a small cell poorly differentiated NEC. Immunostains showed patchy positivity for AE1/AE3 and widespread positivity for CAM5.2 and CD56. Very few cells expressed CK5, while they were negative for p63, thyroglobulin, synaptophysin, chromogranin, TTF1, CK7, CK20 and Napsin A. After formal Head and Neck Cancer MDT discussion (and debate on the advantages and disadvantages of radical laryngo-pharyngectomy), in agreement with patient and family, we performed a trans-oral CO 2 LASER debulking of the primary tumour along with a right radical neck dissection (sternocleidomastoid muscle, IJV and accessory nerve sacrificed, Figure 2) for loco-regional disease and symptom control, allowing chemoradiation to then be progressed at a neighbouring quaternary referral unit hosting a super-specialist NEC MDT. Nutritional support was ensured via a percutaneous endoscopic gastrostomy tube in the immediate perioperative period, however she made a good recovery and was restarted on a soft diet a few days after surgery. She was discharged home 11 days post-operatively. At her last follow-up appointment, 8 months after first GP presentation, her airway remained uncompromised despite obvious clinical F I G U R E 1 T2-weighted magnetic resonance imaging head and neck sequences (axial, coronal and sagittal in sequence) showing a 3.5 x 3.4 x 1.6 cm mass centred in the right pyriform fossa, involving the hypopharyngeal surface of the right aryepiglottic fold, extending posteriorly and inferiorly into the hypopharyngeal wall where it crossed the midline. Laryngeal cartilages and larynx itself spared from within. The right level II to IV lymph node mass measured up to 7.5 cm in craniocaudal diameter, encasing the common carotid artery to its bifurcation and obliterating the IJV; the left level III lymph node measured 2.3 cm and level II 1.4 cm disease progression (smaller volume recurrence in right neck and at primary hypopharynx site). Through trans-oral CO 2 LASER debulking, she avoided the multiple limitations associated with tracheostomy care and continued to manage a soft diet and oral liquids safely, using the gastrostomy tube feed to supplement her nutrition. Her pain was overall well controlled. The palliative radical neck dissection was associated with immediate relief of pain and discomfort caused by grossly enlarged and bulky unilateral cervical lymph nodes that limited neck movements. This nodal enlargement also threatened skin thinning and tumour ulceration, as well as provided a significant source of social embarrassment for the patient impacting her mental health, due to a grossly distorted appearance for neck and facial morphology.
Although she was offered FOLFIRI (folinic acid, fluorouracil and irinotecan) second line chemotherapy, unfortunately she developed a chest infection requiring hospitalisation. She died of presumed cardiopulmonary arrest, before receiving this, a full 4 months following palliative surgery. There was a 2 months delay from initial presentation to ENT to commencement of definitive palliative treatment due to the care pathway limitations associated with referring patients through three separate regional cancer MDTs from Watford District General Hospital. Initial discussions held at head and neck cancer MDT at London North West, then at Imperial, and then finally Royal Free Hospital NEC MDT, the three MDTs being located at separate hospitals in Northwest, West and North London.
F I G U R E 2 Intraoperative pictures: exophytic lesion in the right pyriform fossa before (A) and after (B) CO 2 LASER debulking; (C-E) right neck mass, encasement of the CCA noticeable; (f) image of the neck following RND, the mass was peeled off the CCA, which was fully preserved; (g) neck dissection specimen pinned on cork board; (h) appearance of the neck after closure of the wound. CCA, common carotid artery; IJV, internal jugular vein; RND, radical neck dissection There is a number of retrospective studies in the literature [2][3][4]8 focusing on NECs of larynx, which remains the most common site of presentation for this rare entity in the head and neck region.
In the largest meta-analysis by Van  These tumours often present as loco-regionally advanced disease, that is, with cervical lymphadenopathies and more than 90% develops distant metastases. 26 Lee et al 16   ranges between 92 and 98%. The main limitation appears lack of reproducibility due to the lack of standardisation regarding preparation, production procedure and examination protocols.
Studies have also compared 68 Ga-DOTANOC to standard imaging (CT, MRI, US, OctreoScan). 30  Where loco-regional disease bulk impacts (or may start to impact) upon mental health and basic human functions defining quality of life during palliation (ability to breathe, voice and swallow), organpreserving and minimally invasive surgical treatment provides an important treatment adjunct, necessitating key expertise of the ENT-Head and Neck surgical team.
In this case, the social embarrassment of unaesthetic, gross and asymmetrically enlarged painful neck nodes with propensity for fungation was avoided through neck dissection. Transoral CO 2 LASER debulk safeguarded the airway, avoided tracheostomy-associated limitations for patient mobility and quality of life, allowing safe and unrestricted mobility at home during remaining months of life.
Transoral LASER surgery, accompanied by neck dissection where required, can play an important role controlling local symptoms and improving quality of life, as part of an informed and considered multidisciplinary palliative care plan.

CONFLICT OF INTEREST
The authors declare there is no conflict of interest.

AUTHOR CONTRIBUTIONS
All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analy-

ETHICAL STATEMENT
We obtained Institutional Review Board approval and the next of kin consent before disclosing the patient personal information.

DATA AVAILABILITY STATEMENT
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.