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LETTER TO THE EDITOR - DOCUMENTING A CASE
Year : 2011  |  Volume : 7  |  Issue : 3  |  Page : 343-346

Large cell neuroendocrine carcinoma of the retromolar trigone


1 Department of Surgical Oncology, Division of Pathology, Cancer Institute (WIA), Adyar, Chennai, India
2 Department of Pathology, Cancer Institute (WIA), Adyar, Chennai, India

Date of Web Publication2-Nov-2011

Correspondence Address:
Arvind Krishnamurthy
Department of Surgical Oncology, Cancer Institute (WIA), 36, Sardar Patel Road, Adyar, Chennai - 600 020
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.87002

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How to cite this article:
Krishnamurthy A, Vaidhyanathan A, Majhi U. Large cell neuroendocrine carcinoma of the retromolar trigone. J Can Res Ther 2011;7:343-6

How to cite this URL:
Krishnamurthy A, Vaidhyanathan A, Majhi U. Large cell neuroendocrine carcinoma of the retromolar trigone. J Can Res Ther [serial online] 2011 [cited 2020 Jun 4];7:343-6. Available from: http://www.cancerjournal.net/text.asp?2011/7/3/343/87002

Sir,

Large cell neuroendocrine carcinoma (LCNEC) is a poorly differentiated and high-grade neuroendocrine neoplasm that has several morphological and biologic features between atypical carcinoid and small cell carcinoma (SCC). [1] Since recognition of LCNEC as pulmonary pathology, several authors describe the incidence of pulmonary LCNEC to range between 2 and 3% of patients diagnosed with lung cancer, with an overall 5-year survival as low as 15%. [1],[2]

There are reports of these tumors arising in head and neck subsites, the commonest being the larynx. The salivary glands are perhaps the second most commonest site, the intraoral mucosa is one of the rarest sites for a primary NECs. [3],[4],[5],[6],[7]

To the best of our knowledge, this is perhaps the second reported case of a LCNEC with a primary in an intraoral location and the first to manifest with distant metastases and bone marrow infiltration.

A 34-year-old lady presented with an ulcer in the right retromolar trigone (RMT), which developed following an extraction of a mobile right lower molar 2 months prior and multiple lymph nodal swellings on the right side of her neck.

Physical examination confirmed the ulcer overlying the vertical ramus of mandible and also the multiple significant cervical lymphadenopathy along neck node levels I-III. Her hemogram, chest skiagram and serum biochemistry including alkaline phosphatase levels were normal. Computerized tomography of the head and neck identified the primary 2 × 1.5 cm ulcer in the right RMT with multiple enlarged lymph nodes in the right submandibular, upper and midjugular regions, with the largest right upper jugular node measuring 3.6 × 2.7 × 2.6 cm [Figure 1]a-c. There was no evidence of involvement of the mandible.
Figure 1: (a-c) CT scan showing the tumor and multiple neck adenopathy

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A punch biopsy from the tumor was suggestive of a poorly differentiated carcinoma. FNAC from the node demonstrated metastatic deposits from a poorly differentiated carcinoma. She underwent right RMT composite resection and reconstruction with a pectoralis major flap [Figure 2]a and b.
Figure 2: (a) Intra op photograph following composite resection and neck dissection. (b) Specimen photograph

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Postoperative microscopy of the specimen revealed ulcerated squamous epithelium with an underlying tumor composed of solid groups of large nest of atypical polygonal cells divided by fibrous septae, with pleomorphic vesicular nuclei, prominent nucleoli and moderate amounts of eosinophilic to clear cytoplasm [Figure 3]. Scattered tumor giant cells were seen. Mitosis was observed in 1-3/high-power field, some of the atypical cells showed droplet positivity to mucin. Three out of 16 nodes were positive for tumor with extra capsular spread.
Figure 3: H and E, ×10 - Microscopy showing tumor composed of large nest of atypical polygonal cells divided by fi brous septae, with pleomorphic vesicular nuclei, prominent nucleoli and moderate amounts
of eosinophilic to clear cytoplasm. Scattered tumor giant cells were seen. Mitosis was observed in 1-3/high-power fi eld


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Immunohistochemical staining was strongly positive for epithelial membrane antigen, keratin, chromogranin, S100P CD56 and CD57 [Figure 4]a. The tumor cells displayed a negative reaction whereas the lymphoid tissue displayed a positive reaction to leukocyte common antigen, CD43 and CD68. The Ki67-labeling index was 50%. Taking histology and immunohistochemistry into consideration, the diagnosis was in favor of LCNEC-high grade.
Figure 4: (a) IHC, ×20 - CD 57 positivity in the tumor cells. (b) H and E, ×20 bone marrow infiltration by malignant cells

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She was planned for adjuvant chemotherapy and radiation which was started a month after surgery. While on radiotherapy, she developed generalized weakness and bone pains. A bone marrow biopsy revealed atypical cells suggestive of metastatic deposits [Figure 4]b. A bone scan revealed lesions suspicious for metastatic deposits in the ribs, dorsal and lumbar vertebrae [Figure 5]. The patient offered to be on supportive care after one cycle of cisplatin and etoposide chemotherapy. At 9 months follow-up, she continues to live with disease.
Figure 5: Bone scan showing multiple hot spots

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Neuroendocrine tumors are a heterogeneous family of neoplasms with differences in histomorphology, tissue origin, clinical behavior and therapeutic implications. Yao identified 35,618 patients with NECs from The Surveillance Epidemiology and End Results database. They document a significant increase in reported annual age-adjusted incidence from 1973 (1.09/100,000) to 2004 (5.25/100,000). As a result of increased incidence, these tumors represent a substantial clinical problem as they are known to be clinically aggressive and largely resistant to therapy. [8]

A recent classification produced by the World Health Organization (2005) comprises of four subtypes of tumors: the low-grade typical carcinoid, the intermediate-grade atypical carcinoid and the two high-grade i.e., LCNEC and small-cell lung carcinoma. [9]

It is a characteristic feature that these tumors at their primary site are small and often go unnoticed and are devoid of clinical symptoms till the tumor has metastasized. Our patient presented with a small 2 × 1.5 cm ulceroproliferative lesion at the retromolar trigone and massive metastases to the neck.

Iyoda [2] discusses that the final diagnosis of most cases of LCNEC have been accomplished on resected post operative specimens, thereby enabling only retrospective studies on initial presentation and clinical behavior. Similarly, in our case, while FNAC and incisional biopsy were helpful in acquiring a pre operative diagnosis of a poorly differentiated malignancy, both modalities failed to recognize its epithelial neuroendocrine character. While the various subtypes of neuroendocrine neoplasms are marked by different light microscopic appearances, the use of a range of immunohistochemical stains is essential to determine if a neuroendocrine phenotype exists. Neuroendocrine markers such as chromogranin, synaptophysin, S100 and neural cell adhesion molecule (CD56, CD57) are reliable markers and are considered essential to its diagnosis and to distinguish NEC from other tumors [Table 1]. Aggressive behavior with early dissemination to neighboring organs and lymph nodes is usually expected in such tumors. [1],[10]
Table 1: Immunohistochemical profile of neuroendocrine tumors

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The occurrence of marrow infiltrates appears to be a rare complication of certain types of NECs. [11] Tritz in their review of 129 patients with SCC of the lung document an incidence of 30% with bone marrow involvement. [11] Thus, while SCC possesses the capacity to metastasize to bone marrow- numerous studies on its counterpart large cell carcinoma variant do not document bone marrow infiltration. [1],[2]

Management for oral cavity sub sites of large cell NEC still remains a controversial subject. Surgery is accepted as the primary treatment modality and can be supplemented with postoperative radiotherapy and chemotherapy. To the best of our knowledge, within the category of NECs as primary oral cavity tumors, there exist only one case of LCNEC and three cases of SCCs in the English language literature. [4],[5],[6],[7]

Unfortunately due to the rarity of this neoplasm, there is no specific recommendation on management guidelines, treatment options are generally extrapolated from similar tumors of pulmonary origin. It is the author's opinion that it is important to report single institution experiences of poorly differentiated NECs of the oral cavity, to perhaps aid in forming a consensus on the treatment and its outcomes.

 
 > References Top

1.Travis WD, Linnoila RI, Tsokos MG, Hitchcock CL, Cutler GB Jr, Nieman L, et al. Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. Am J Surg Pathol 1991;15:529-53.  Back to cited text no. 1
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2.Iyoda A, Hiroshima K, Nakatani Y, Fujisawa T. Pulmonary Large Cell Neuroendocrine Carcinoma: Its Place in the Spectrum of Pulmonary Carcinoma. Ann Thorac Surg 2007;84:702-7.  Back to cited text no. 2
[PUBMED]  [FULLTEXT]  
3.Baker P, Alguacil-Garcia A. Moderately differentiated neuroendocrine carcinoma in the floor of the mouth: A case report. J Oral Maxillofac Surg 1999;57:1143-7.  Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.Benning TL, Vollmer RT, Crain BJ, Shelburne JD. Neuroendocrine carcinoma of the oral cavity. Mod Pathol 1990;3:631-4.  Back to cited text no. 4
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5.Hull MT, Eble JN, Warfel KA. Extrapulmonary oat-cell carcinoma of the tongue: An electron-microscopic study. J Oral Pathol 1984;13:489-96.  Back to cited text no. 5
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6.Kusafuka K, Asano R, Kamijo T, IidaY, Onitsuka T, Kameya T, et al. Large cell neuroendocrine carcinoma of the tongue base: Case report of an unusual location with immunohistochemical analysis. Int J Oral Maxillofac Surg 2009;38:296-9.  Back to cited text no. 6
    
7.Yoshida H, Onizawa K, Hirohata H. Neuroendocrine carcinoma of the tongue: Report of a case. J Oral Maxillofac Surg 1995;53:823-7.  Back to cited text no. 7
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8.Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One Hundred Years After "Carcinoid": Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008;26:3063-72.   Back to cited text no. 8
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9. Barnes EL, Eveson JW, Reichart P, Sidransky D. Pathology and genetics of head and neck tumours. Kleihues P, Sobin LH, editors. World Health Organization classification of tumours. Lyon: IARC Press; 2005.  Back to cited text no. 9
    
10.Mills SE. Neuroectodermal neoplasms of the head and neck with emphasis on neuroendocrine carcinomas. Mod Pathol 2002;15:264-78.  Back to cited text no. 10
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11.Tritz DB, Doll DC, Ringenberg QS, Anderson S, Madsen R, Perry MC, et al. Bone marrow involvement in small cell lung cancer. Clinical significance and correlation with routine laboratory variables. Cancer 1989;63:763-6 .  Back to cited text no. 11
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1]


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