|Year : 2015 | Volume
| Issue : 3 | Page : 659
Neuroendocrine carcinoma of the tongue
Ebrahim Esmati1, Mohammad Babaei1, Amirhassan Matini2, Monir Sadat Mirai Ashtiani1, Ehsan Akbari Hamed3, Hassan Nosrati1, Farideh Razi4, Maryam Ganjalikhani4
1 Department of Radiation Oncology, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Pathology, Beheshti Hospital, Kashan University of Medical Sciences, Kashan, Iran
3 Department of Radiation Oncology, Mahdieh Hospital, Hamedan, Iran
4 Tehran University of Medical Sciences, Tehran, Iran
|Date of Web Publication||9-Oct-2015|
Department of Radiotherapy Oncology, Cancer Institute, Tehran University of Medical Sciences, Imam Khomeini Hospital, Keshavarz Blvd., Tehran
Source of Support: None, Conflict of Interest: None
Neuroendocrine carcinoma usually originates from lung. Few data exist in the literature regarding neuroendocrine carcinoma of the tongue. Patient data including history, surgical procedure, histology, and radiology investigations were collected and summarized. A 40-year-old woman was referred after partial glossectomy. Squamous mucosa with neoplasm and cells with round nuclei and light cytoplasm was reported in the tongue biopsy. Immunohistochemistry (IHC) staining was positive for cytokeratin, neuron specific enolase, synaptophysin and chromogranin and negative for leukocyte common antigen. This case showed a high proliferative activity (Ki-67 labeling index were 60%). These IHC findings were in favor of poorly differentiated neuroendocrine carcinoma. After surgery, she received chemotherapy and chemoradiation. The diagnosis of neuroendocrine tumors in the present case is based on immunohistochemical markers and cellular shapes. Postoperative chemoradiotherapy is a critical element of therapy for head and neck high-grade neuroendocrine carcinomas, our patient received this treatment after surgery.
Keywords: Neuroendocrine carcinoma, radiotherapy, tongue
|How to cite this article:|
Esmati E, Babaei M, Matini A, Ashtiani MS, Hamed EA, Nosrati H, Razi F, Ganjalikhani M. Neuroendocrine carcinoma of the tongue. J Can Res Ther 2015;11:659
| > Introduction|| |
Neuroendocrine carcinoma is an entity with clearly defined clinicopathology characteristics. It usually originates from lung, but can arise from extrapulmonary site.  This neoplasm was first described in the lung as part of the spectrum of pulmonary neuroendocrine tumors.  It is described as a poorly differentiated and high-grade neuroendocrine tumor that morphologically and biologically is between atypical carcinoid and small-cell lung carcinoma. Large cell neuroendocrine carcinoma (LCNEC) has been reported in other organs such as stomach, thymus, ovary, ampulla of vater, urinary bladder, uterine cervix, uterine corpus, colon, and rectum. 
Neuroendocrine carcinoma of the tongue is extremely rare and one case has been reported up to now.  Therefore, the clinicopathological features, prognostic factors and optimal treatment of neuroendocrine tumors of the tongue are not well-characterized.
| > Case report|| |
The patient is a 40-year-old woman who was referred to our clinic after partial glossectomy. She had a history of a small lump in the right side of her oral tongue for 14 years, which started and become larger since November 2006 and made her to go for biopsy in August 2007. At that time, a 6 mm × 5 mm × 5 mm sample was obtained, and squamous mucosa with neoplasm and cells with round nuclei with light cytoplasm was reported on light microscope.
Immunohisochemistry (IHC) staining was positive for cytokeratin (CK), neuron specific enolase (NSE), synaptophysin and chromogranin and negative for leukocyte common antigen. This case showed a high proliferative activity (Ki-67 labeling index were 60%). These IHC findings were in favor of poorly differentiated neuroendocrine carcinoma.
In November 2007, she underwent partial glossectomy. The specimen consisted of a piece of irregular creamy-brownish elastic tissue measuring 2.5 cm × 1.5 cm × 1.5 cm. An irregular, firm, brownish tumor measuring 1.5 cm × 1 cm was seen on one side of the specimen.
The tumor invaded into skeletal muscles without evidence of vascular or perineural invasion. All surgical margins were free of tumor.
Histological examinations revealed neoplastic tissue with a solid pattern that composed of rather uniform cells with eosinophilic cytoplasm and mild hyperchromatic nuclei, without keratinization pearl [Figure 1]a and b. The second IHC (on the glossectomy specimen) was diffusely positive for NSE and choromogranin [Figure 1]c and d, weekly positive for CK and negative for epithelial membrane antigen.
|Figure 1: (a) Lingual mucosa and underling tumor (H and E, low power field), (b) tumor (H and E, high power field), (c) cytokeratin immunostain showing cytoplasmic reactivity in tumor cells as well as surface epithelium, and (d) neuron specific enolase immunoreactivity in tumor cells|
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No lymphatic, distant or satellite metastases were detected in computed tomography (CT) scan images of the neck and chest. Three months after surgery, she was referred to our clinic for adjuvant treatment. First she received two cycles of EP regimen (cisplatin 25 mg/m 2 and etoposide 100 mg/m 2 for 3 consecutive days).
Three weeks after the second cycle, concurrent chemoradiotherapy was started in April 2008. She received 6000 cGy with concurrent weekly cisplatin (35 mg/m 2 ). Radiation included of two phases; first phase has been done with two lateral opposed fields of the oral cavity, upper and middle neck, up to 4600 cGy in 23 fractions, then radiotherapy continued with two (anterior and right lateral) wedge fields (second phase) to a total dose of 6000 cGy in 30 fractions. Three weeks after chemoradiation, two courses of chemotherapy the same as the previous courses, were prescribed. Treatment was completed in September 2008.
Before and after treatment CT scan of head and neck were normal.
The patient was followed every 3 months with clinical examination. She was symptom free and without evidence of local or distant recurrences on her last clinical examination in January 2, 2013.
| > Discussion|| |
Neuroendocrine carcinoma is a poorly differentiated carcinoma that usually occurs in the lung. Although rare in the head and neck, salivary and mucosal subtypes have been recognized.  Neuroendocrine tumors constitute of a group of neoplasms that are widely dispersed throughout the body. These neoplasms are characterized by the presence of secretory granules and production of peptide substances.
According to the World Health Organization, classification of neuroendocrine neoplasms of the larynx can be divided into typical carcinoid tumors, atypical carcinoid tumors, small-cell neuroendocrine carcinomas, and paragangliomas. 
Neuroendocrine carcinoma of the tongue is extremely rare and only one case has been reported before. It was reported by Kusafuka et al. which was a LCNEC of the tongue base. It was characterized by solid tumor nests with central necrosis and rosette formation resembling basaloid squamous cell carcinoma (SCC), but the immunohistochemical examination revealed its neuroendocrine differentiation. It was diagnosed as LCNEC of the tongue base. It was the first report of mucosal LCNEC in the oral cavity. Basal cells in the normal squamous epithelium around the tumor indicated positivity for neural cell adhesion molecule and N-cadherin. The authors propose that the LCNEC of the tongue base originates from some specialized cells with neuroendocrine features in the basal cell layer of the squamous epithelium. 
Neuroendocrine carcinoma presenting as a mucosal lesion of the head and neck is relatively a new entity. Furthermore, it must be differentiated from the metastases of neuroendocrine tumor of another location, especially neuroendocrine tumors of the lung. Carcinoid tumors and small-cell NE carcinoma also frequently occur in the larynx, especially in the supraglottis. ,
Neuroendocrine tumors were formally diagnosed as poorly differentiated SCCs and previous reports have pointed out that neuroendocrine tumor was often misdiagnosed as poorly differentiated SCC or poorly differentiated adenocarcinoma.  IHC staining is essential to demonstrate the neuroendocrine nature of this tumor.
The diagnosis of neuroendocrine tumors in the present case is based on immunohistochemical markers and cellular shapes. Barker et al. showed that chemotherapy is a critical element of therapy for head and neck high-grade neuroendocrine carcinomas.  In this case, chemotherapy was done with cisplatin and etoposide regiment for four cycles, two cycles before and two cycles after chemoradiotherapy. Prognosis of neuroendocrine tumors of the tongue is unknown.
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