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Clinical Review Neuroendocrine Neoplasms of the Larynx: an Overview

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CLINICAL REVIEW David W. Eisele, MD, Section Editor NEUROENDOCRINE NEOPLASMS OF THE LARYNX: AN OVERVIEW Alfio Ferlito, MD, DLO, DPath, FRCS, FRCSEd, FRCSGlasg, FRCSI, FHKCORL, FDSRCS, FRCPath, FASCP, IFCAP,1 Carl E. Silver, MD,2 Carol R. Bradford, MD,3 Alessandra Rinaldo, MD, FRCSI1 1 Department of Surgical Sciences, ENT Clinic, University of Udine, Udine, Italy. E-mail: [email protected] 2 Departments of Surgery and Otolaryngology–Head and Neck Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York 3 Department of Otolaryngology–Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan Accepted 24 March 2009 Published online 17 June 2009 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.21162 proven to be of a little benefit. Paragangliomas are treated by Abstract: Neuroendocrine neoplasms of the larynx are local excision or partial laryngectomy. rare but are the most common nonsquamous tumors of this It is difficult to determine the valid survival statistics for typical organ. In the past, there has been considerable confusion carcinoids because of their rarity and confusion in the literature about the nature and classification of these neoplasms, but the with their atypical counterparts. They have a greater tendency to current consensus is that there are 4 different types of laryn- metastasize, and thus a worse prognosis than was previously geal neuroendocrine tumors composed of paraganglioma, typi- believed. Atypical carcinoid tumors have a 5-year survival rate of cal carcinoid, atypical carcinoid tumor, and small cell approximately 50%, which decreases with time. The prognosis of neuroendocrine carcinoma. Carcinoids and small cell neuroen- small cell neuroendocrine carcinoma of the larynx is dismal, with 5- docrine carcinomas are epithelial neoplasms, whereas para- year survival rates of 5%. The biological behavior of laryngeal gangliomas are of neural origin. Diagnosis is based primarily paraganglioma is generally benign and the prognosis is on light microscopy and confirmed by immunohistochemistry excellent. VC 2009 Wiley Periodicals, Inc. Head Neck 31: 1634– and electron microscopy. Precise diagnosis is essential 1646, 2009 because the natural history, treatment, and prognosis vary widely for the different neoplastic categories. Keywords: neuroendocrine neoplasms; larynx; terminology; Typical carcinoids are very rare and are treated by wide pathology; treatment; prognosis local excision, usually partial laryngectomy, without elective neck dissection. Atypical carcinoid tumors are more common and more aggressive. They are treated by partial or total laryn- gectomy with elective or therapeutic neck dissection. Adjuvant TERMINOLOGY AND CLASSIFICATION chemo/radiotherapy may be of benefit in some cases. Small cell neuroendocrine carcinomas are highly aggressive and The larynx is the most common site of cancer should be considered disseminated at initial diagnosis. The in the head and neck. However, laryngeal can- treatment is by irradiation and chemotherapy as surgery has cer is listed as a ‘‘rare disease’’ by the Office of Rare Diseases of the National Institutes of Correspondence to: A. Ferlito Health. This means that laryngeal cancer VC 2009 Wiley Periodicals, Inc. affects fewer to 200,000 people in the United 1634 Neuroendocrine Neoplasms of the Larynx HEAD & NECK—DOI 10.1002/hed December 2009 Table 1. Various terms to indicate laryngeal neuroendocrine neoplasms. Aggressive carcinoid Moderately differentiated neuroendocrine carcinoma Anaplastic cell carcinoma Mucinous carcinoid tumor Anaplastic small cell carcinoma Neuroendocrine adenocarcinoma Apudoma Neuroendocrine APUD neoplasm Argentaffinoma Neuroendocrine carcinoma Argyrophilic cell carcinoma Neuroendocrine carcinoma of combined cell type Atypical carcinoid Neuroendocrine carcinoma of intermediate-cell type Atypical carcinoid tumor Neuroendocrine carcinoma of small-cell type Atypical endocrine carcinoma Neuroendocrine carcinoma with exocrine differentiation Atypical endocrine tumor Neuroendocrine tumor Carcinoid Nonchromaffin paraganglioma Carcinoid carcinoma Oat cell carcinoma Carcinoid tumor Oncocytic carcinoid Carcinoma with amine-precursor uptake decarboxylase cell differentiation Oncocytic carcinoid tumor Chemodectoma Oncocytic carcinoma Combined neuroendocrine carcinoma Oncocytic neuroendocrine carcinoma Combined small cell carcinoma, neuroendocrine type Oncocytoid carcinoid tumor Composite neuroendocrine carcinoma Paraganglioma Composite small cell carcinoma Pheochromocytoma Endocrine carcinoma Poorly differentiated neuroendocrine carcinoma Endocrinocarcinoma Reserve cell carcinoma Endocrinoma Small cell carcinoma Glomus tumor Small cell carcinoma, neuroendocrine type Grade I neuroendocrine carcinoma Small cell endocrine carcinoma Grade II neuroendocrine carcinoma Small cell neuroendocrine carcinoma Grade III neuroendocrine carcinoma Small cell tumor Kultschitzky cell carcinoma Small cell undifferentiated carcinoma Large cell neuroendocrine carcinoma Spindle-cell carcinoid tumor Large cell undifferentiated neuroendocrine carcinoma Typical carcinoid Malignant carcinoid Typical carcinoid tumor Malignant nonchromaffin paraganglioma Typical endocrine tumor Malignant paraganglioma Undifferentiated carcinoma Mature carcinoid Undifferentiated small cell carcinoma Medullary type of neuroendocrine carcinoma Very well differentiated neuroendocrine carcinoma Melanotic carcinoid tumor Well differentiated neuroendocrine carcinoma Microcytoma States.1 Laryngeal cancer accounts for approxi- nology.5–14 Laryngeal neuroendocrine neoplasms mately 2% and 5% of new malignancies world- (LNN) are divided into 2 broad categories based wide every year, of which 85% to 90% are of the on their tissue of origin: epithelial and neural. squamous type.2,3 The epithelial-derived tumors, neuroendocrine Epithelial malignancies with neuroendocrine carcinomas, are subclassified into 3 subtypes: differentiation can occur in any organ of the body. typical carcinoid (well differentiated neuroendo- Laryngeal tumors with neuroendocrine morphol- crine carcinoma, grade I), atypical carcinoid tu- ogy are a distinct, uncommon, heterogeneous mor (moderately differentiated neuroendocrine group of neoplasms, which share specific morpho- carcinoma, grade II; large cell neuroendocrine logic, histochemical, immunohistochemical, and carcinoma), and small cell neuroendocrine carci- ultrastructural characteristics with prognosis de- noma (poorly differentiated neuroendocrine carci- pendent on the tumor type. They have received noma, grade III). Small cell neuroendocrine increasing attention in recent years.4 The termi- carcinoma includes oat cell, intermediate cell, nology is confusing and controversial and needs and combined variants. The oat cell carcinoma is standardizing, as a wide variety of names have composed of fusiform small cells with sparse cyto- been used to refer to these neoplasms (Table 1). plasm, whereas the cells of intermediate type ex- There is no universal agreement on which termi- hibit a more abundant cytoplasm. The combined nology should be used for the neuroendocrine or composite small cell neuroendocrine carcinoma neoplasms of the larynx. Table 2 summarizes the is a tumor in which there is a definite component most used classifications and the relevant termi- of small cell (oat cell or intermediate type) Neuroendocrine Neoplasms of the Larynx HEAD & NECK—DOI 10.1002/hed December 2009 1635 Table 2. Nomenclature for laryngeal neuroendocrine neoplasms. Ferlito and Brandwein- Classic system Gould5 Woodruff et al6 Wenig et al7 Friedmann8 Shanmugaratnam9 Wick10 Mills et al11 Mills12 Barnes13 Gensler et al14 Carcinoid Very well differ- Typical Well differenti- Typical Carcinoid tumor Grade I neuro- Carcinoid Well differenti- Typical Well differenti- entiated neu- carcinoid ated neuroen- carcinoid (typical carcinoid endocrine ated neuroen- carcinoid ated neuro- roendocrine docrine tumor) carcinoma docrine endocrine carcinoma carcinoma carcinoma carcinoma Atypical Well differenti- Large cell neu- Moderately dif- Atypical Atypical carcinoid Grade II neuro- Moderately dif- Moderately dif- Atypical Moderately dif- carcinoid ated neuro- roendocrine ferentiated carcinoid tumor endocrine ferentiated ferentiated carcinoid ferentiated endocrine carcinoma neuroendo- carcinoma neuroendo- neuroendo- neuroendo- carcinoma crine crine crine crine carcinoma carcinoma carcinoma carcinoma Small cell undif- Intermediate/ Small cell neuro- Poorly differenti- Small cell neuro- Small cell carci- Grade III neuro- Small cell neuro- Poorly differenti- Small cell carci- Poorly differenti- ferentiated poorly differ- endocrine ated neuroen- endocrine noma (small cell endocrine endocrine ated neuroen- noma, neuro- ated neuroen- carcinoma entiated neu- carcinoma docrine carcinoma neuroendocrine carcinoma carcinoma docrine carci- endocrine docrine roendocrine carcinoma carcinoma) noma (small type carcinoma carcinoma cell and large cell subtypes) Combined small cell carci- noma, neuro- endocrine type, with non-small cell carcinoma Large cell undif- ferentiated neuroendo- crine carcinoma Paraganglioma Paraganglioma Paraganglioma Paraganglioma Paraganglioma Paraganglioma Paraganglioma Paraganglioma Paraganglioma Paraganglioma Paraganglioma Reprinted as adapted, with permission from Ferlito et al, Oral Oncol, 2006;42:770–778, VC Elsevier. carcinoma together with squamous cell carci- Table 3. Spectrum of laryngeal neuroendocrine neoplasms. noma and/or adenocarcinoma.15,16
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