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Primary Neuroendocrine Small Cell Carcinoma in Larynx

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Primary Neuroendocrine Small Cell Carcinoma in Larynx Romanian Journal of Rhinology, Vol. 7, No. 27, July - September 2017 DOI: 10.1515/rjr-2017-0021 CASE REPORT Primary neuroendocrine small cell carcinoma in larynx: case report and literature review Anca Evsei1,2 , Cristina Iosif2, Simona Enache2,3, Claudiu Manea1,4, Codrut Sarafoleanu1,4 1CESITO Center, “Sfanta Maria” Clinical Hospital, Bucharest, Romania 2Department of Pathology, “Sfanta Maria” Clinical Hospital, Bucharest, Romania 3“Victor Babes” National Institute of Research – Development in the Pathology Domain and Biomedical Sciences, Bucharest, Romania 4ENT&HNS Department, “Sfanta Maria” Clinical Hospital, Bucharest, Romania ABSTRACT BACKGROUND. Neuroendocrine tumors of the larynx represent a rare group of neoplasms characterized by pathological and biological heterogeneity. The histological and immunohistochemical diagnosis is the most important step in the appropri- ate management of these tumors and the prognosis varies according to histological types. Conventional anatomical and func- tional imaging can be complementary for diagnosis, staging and monitoring of treatment response. MATERIAL AND METHODS. Here we report on a case of a laryngeal neuroendocrine small cell carcinoma occurring in a 67-year-old man who was referred to our clinic for clinical reevaluation, diagnosis and treatment. The clinical presentation, the histopathological and immunohistochemical examination and management of this kind of tumor are highlighted. CONCLUSION. Small cell neuroendocrine carcinomas are very aggressive neoplasms. Patients could benefit from surgery, but radiotherapy and chemotherapy remain the treatment of choice. Very low incidence of neuroendocrine tumors in the larynx and specifically very poor prognosis of neuroendocrine small cell carcinoma encouraged an extensive literature review. KEYWORDS: small cell carcinoma, laryngeal, neuroendocrine, prognosis. INTRODUCTION group of neoplasms, which share specific pathological and immunohistochemical features, with prognosis Neuroendocrine neoplasms of the larynx are a het- dependent on the tumor type. They have received in- erogeneous group of tumors and the most common creasing attention in recent years because of a contro- nonsquamous types arising in this region. The origin versial terminology that was in need of standardiza- of these tumors has not been clearly identified but pa- tion4. thologists believe that precursor cells belong to the Small cell carcinoma neuroendocrine type (SCC- diffuse neuroendocrine system1. The recent World NET) is a rare tumor (2.5-4% of all small cell carcino- Health Organization book simplified former classifica- mas) and, according to one study, during the past 30 tions dividing neuroendocrine tumors in 3 subtypes: years only 160 cases of primary small cell carcinoma of well-differentiated neuroendocrine carcinoma (typi- the larynx have been published worldwide2. Most of cal carcinoid, neuroendocrine carcinoma grade I), the patients are between 60 to 70 years of age, with the moderately-differentiated neuroendocrine carcinoma male population being more commonly affected5. (atypical carcinoid tumor, neuroendocrine carcinoma Heavy smoking is the most important risk factor in- grade II) and poorly-differentiated neuroendocrine volved in tumor etiology6. Clinical presentation is non- carcinoma (small cell neuroendocrine carcinoma and specific, sharing similar features to other types of la- large cell neuroendocrine carcinoma)1. The most fre- ryngeal carcinomas. In consequence, diagnosing small quent type is the atypical carcinoid, while the typical cell carcinoma of the larynx relies strictly on histo- carcinoid is a very rare tumor2,3. Laryngeal tumors with pathological examination and immunohistochemical neuroendocrine morphology are a rare and diverse testing7. Primary small cell carcinoma of the larynx Corresponding author: Anca Evsei email: [email protected] 186 Romanian Journal of Rhinology, Vol. 7, No. 27, July - Septembe 2017 continues to challenge oncologists in treatment op- cardiology consult that revealed grade I/II arterial hy- tions. This is one of the most lethal of neoplasms as- pertension and a short PR interval on the electrocar- sociated with early widespread metastases and poor diogram and an additional upper gastrointestinal se- prognosis. Some studies reported a two- and five-year ries (barium meal) that showed no lesions. survival of 16% and 5% respectively8. Presence of me- In addition to a complete ENT examination, we tastases at the initial clinical presentation and treat- performed an indirect laryngoscopy and nasopharyn- ment options are probably the most important fea- golaryngeal fibroscopy that showed an ulcerated exo- tures to consider for patient survival. phytic mass that infiltrated the right hemilarynx with extension to the anterior commissure and into one third of the vocal cord. Imagistic studies such as com- CASE REPORT puter tomography and chest X-ray confirmed our re- sults and excluded other lesions in other organs. Total A 67-year-old male patient was referred to our laryngectomy with bilateral neck dissection was per- center with dysphonia and inspiratory dyspnea, with a formed. progressive aggravating evolution for over 7 months. Gross examination showed a 2.5/2/1.5 cm exo- The patient had a 40 pack-year history of cigarette phytic, ulcerated glottic lesion which comprised both smoking with complete cessation 3 months prior to commissures and vocal cords and extended in the sub- admission and reported daily alcohol consumption. glottic space. Specimen samples were fixed with 10% The patient reported working in a toxic environment buffered formalin and were processed by conventional for over 10 years. histopathological methods using paraffin embedding, Past medical records outlined a prior admission in sectioning and Hematoxylin–Eosin (HE) staining. Mi- another ENT center for similar symptoms 2 months croscopic examination highlighted a tumor which before he was referred to our clinic. Endoscopic biop- grew in nest, sheets or trabeculae, with diffuse, cribri- sies with subsequent histopathological examination form, ribbon-like, pseudoglandular and rosette-like performed there suggested well-differentiated invasive pattern (Figure 1A,B,C), composed of small to spin- squamous cell carcinoma. dle-shaped cells with hyperchromatic granular (or On admission, we performed a full clinical workup “salt and pepper”) chromatin, scant cytoplasm, incon- including a chest X-ray that excluded other lesions, a spicuous nucleoli, nuclear molding, high mitotic activ- B A C D Figure 1 A. 20x: Small cell carcinoma, neuroendocrine type: tumor showing a pseudoglandular/acinar pattern. B. 4x: tumor composed of sheets or ribbons of closely packed cells. C. 20x: tumor composed of closely packed cells with inconspicuous cytoplasm and oval/spindle nuclei with dense chromatin and absent nucleoli. Mitoses and apoptosis are present. D. 10x: tumor displaying a rosette architectural pattern. Evsei et al Primary neuroendocrine small cell carcinoma in larynx: case report and literature review 187 ity (more than 10 mitoses per 2 mm2 or 10 high-power dilution 1:200); Cell Marque: Synaptophysin antibody fields) and apoptosis (Figure 1D); the tumor infil- (clone: MRQ - 40, dilution 1:500); Cell Marque: Chro- trated both the surface epithelium and laryngeal skel- mogranin A (clone: LK 2H10, dilution in 1:100); etal muscle fibers (Figure 2A); extensive areas of Ventana: p16 Cintec ready-to-use. We chose to per- tumor necrosis (Figure 2B), neurotropism and an- form immunohistochemistry testing on paraffin blocks gioinvasion (Figure 2D) were present. The tumor that contained various tumor architectural patterns. stroma showed extensive hyalinization (Figure 2C). Initial hematoxylin-eosin examination showed solid, We have also performed immunohistochemical insular and pseudoglandular patterns (Figure 3A). tests. The paraffin blocks acquired by histopathologi- Synaptophysin markers (Figure 3B), chromogranin cal processing were sliced at a microtome resulting in (Figure 3C) and AE1-AE3 (Figure 3D) were positive in sections of 3-μm thickness that were mounted on tumour cells in a cytoplasmic granular pattern; Ki67 slides covered with poly-Lysine. After that, the sections was positive in 60-65% of tumor cells. We also per- were deparaffinised in toluene and alcohol successive formed TTF1 marker (Figure 4A,B) which showed dif- baths, one hour (15 minutes by bath), rehydrated fuse nuclear staining in tumor cells and p16 marker (three successive alcohol baths with decreased con- (Figure 4C,D) which showed similar intense nuclear centration: 96%, 80% and 70% (10 minutes in each staining. Metastatic carcinoma was present in 4 out of bath) and followed by a bath with distilled water, 13 lymph nodes (the largest 1.5 cm). Final histopatho- where the sections were hold for 10 minutes. Washing logical TNM classification was pT3N2c. in PBS (phosphate-buffered saline), incubation with normal serum, for 20 minutes, incubation with pri- mary antibody over-night, Dako LSAB kit, washing in DISCUSSIONS carbonate buffer and development in 3,3’-diamino- benzidine hydrochloride/ hydrogen peroxide and Neuroendocrine tumors of the larynx represent a nuclear counterstain with Mayer’s Hematoxylin were rare group of neoplasms characterized by pathological performed. We used the following antibodies from and biological heterogeneity. The histological diagno- Leica: TTF1 antibody (clone: SPT24, dilution 1:100); sis is the most important step in the appropriate man- immunologic:
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