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Primary typical carcinoid tumour in the retromolar region with prominent squamous differentiation: a case report
Primary typical carcinoid tumour in the retromolar region
991
Case Report Head and Neck Oncology
Primary typical carcinoid tumour in the retromolar region with prominent squamous differentiation: a case report S. Yang, S. Chen, X. Chen, X. Long: Primary typical carcinoid tumour in the retromolar region with prominent squamous differentiation: a case report. Int. J. Oral Maxillofac. Surg. 2011; 40: 991–994. # 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Primary carcinoid tumours of the oral cavity are rare, with only one case of atypical carcinoid tumour reported in the literature. In this article, a case of primary typical carcinoid tumour in the retromolar region in a 46-year-old woman is described. Histologically, the tumour was characterized by submucosal proliferation of medium-sized monomorphous epithelioid cells with an organoid and nesting pattern of growth. Mitoses and necrosis were not found. Prominent squamous differentiation was present. Immunohistochemically, the tumour was diffuse positive for cytokeratin (CK) (AE1/AE3), CK7, p63, neurone-specific enolase, synaptophysin, and chromogranin. To the authors’ knowledge, this is the first report of primary typical carcinoid tumour in the oral cavity.
Neuroendocrine carcinomas are a heterogeneous family of neoplasms that can occur widely in various organs and tissues. The majority of neuroendocrine carcinomas in the head and neck region arise in the larynx and salivary glands6,7. Their occurrence in intraoral mucosal sites is rare, and only 15 cases of oral neuroendocrine carcinomas have been reported as Merkel cell carcinoma (7 cases), small cell neuroendocrine carcinoma (5 cases), large cell neuroendocrine carcinoma (1 case), atypical carcinoid (1 case) and moderately differentiated neuroendocrine carcinoma (1 case)1,5,6,9. According to the World Health Organization classification, laryngeal neuroendocrine carcinomas are subclassified into typical carcinoid, atypical carcinoid, and small cell carcinoma, corresponding to well, moderately, and poorly differentiated neuroendocrine carcinomas, respectively2,7. Owing to their rarity, neuroendocrine carcinomas of the
oral cavity were not incorporated into the classification of neuroendocrine neoplasms of the head and neck. In a recent review, MAHOMED6 proposed classifying oral neuroendocrine carcinomas into typical carcinoid, atypical carcinoid, small cell neuroendocrine carcinoma (including the Merkel cell type and the pulmonary type), and large cell neuroendocrine carcinoma. To the authors’ knowledge, the existence of primary typical carcinoid tumour in the oral cavity has not been published before. The authors present the first case of oral typical carcinoid tumour in the retromolar region in a 46year-old woman. Unusual prominent squamous differentiation was noted. Case report
A 46-year-old woman presented with a 5year history of a painless swelling in the retromolar region. Intraoral examination
S. Yang1,2,1, S. Chen1,4,1, X. Chen3, X. Long4 1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China; 2Department of Oral Histopathology, Faculty of Stomatology, Hainan Medical College, Haikou, Hainan, China; 3Department of Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China; 4Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
Keywords: carcinoid tumour; neuroendocrine carcinoma; oral cavity; retromolar region. Accepted for publication 9 March 2011 Available online 14 April 2011
showed a relatively well-defined, elastic, and immobile mass that measured about 1.5 cm 2 cm. It was covered with normal, healthy, non-ulcerated mucosa. A panoramic radiograph showed no bony involvement. There was no palpable cervical lymphadenopathy. A detailed general physical examination, chest X-ray, and abdominal ultrasound scan showed no evidence of distant metastasis. The patients’ laboratory findings were within normal limits, including complete blood count, blood biochemistry, and urine analysis. The clinical differential diagnosis included benign minor salivary gland neoplasm, benign mesenchymal neoplasm, and low-grade malignant tumour of minor salivary gland or mesenchymal origin. The lesion was excised completely with free margins under general anaesthesia. 1
Equal contribution.
992 [()TD$FIG]
Yang et al.
Fig. 1. (a) Low power showing a circumscribed submucosal proliferation covered by normal surface epithelium. Tumour cells arranged in organoid and nesting pattern. Prominent squamous differentiation was noted. Haematoxylin–eosin stain (H–E stain): 40. (b) High power showing the relatively uniform tumour cells with round or oval, centrally placed nuclei and granular eosinophilic cytoplasm. H–E stain: 400.
The patient is being followed up and showed no evidence of disease 11 months postoperatively. Histopathological examination revealed that the resected tumour was 2 cm in diameter, whitish in colour and relatively hard in consistency. There was a circumscribed, but not encapsulated, submucosal tumour covered by normal surface epithelium. The tumour was composed of medium-sized monomorphous epithelioid cells, arranged in nests, trabeculae, and cords surrounded by thin to thick fibrovascular septa (Fig. 1a). The cytoplasm of the tumour cells varied from eosinophilic to pale. The nuclei were central, round with finely granular chromatin and inconspicuous nucleoli. Mitoses and necrosis were not found (Fig. 1b). Extensive squamous differentiation was noted. Prominent thin, elongated blood vessels were seen. Immunohistochemically, the tumour was diffuse positive for cytokeratin (CK) AE1/AE3 (Fig. 2a), CK7, neuronespecific enolase (Fig. 2b), synaptophysin (Fig. 2c), chromogranin, and p63 (Fig. 2d); focal positive for S100, vimentin, and CD57; negative for CD56, thyroid transcription factor 1 (TTF-1), and CK20. The components of squamous differentiation were positive for CKAE1/AE3 and CK7. The association of the immunoprofile with the microscopic morphology confirmed the diagnosis of typical carcinoid tumour. Discussion
Carcinoid tumour is the most common of the neuroendocrine tumours. It is usually found in the gastrointestinal tract (55%) and in the bronchopulmonary tract (30%)10. Occurrence of carcinoid tumour
in the head and neck area mainly involves the larynx, followed by the middle ear7. Primary carcinoid tumours of the oral cavity are rare, with only one case of atypical carcinoid tumour reported in the literature1. The present case is the first report of typical carcinoid tumour in the oral cavity. The clinical presentation of carcinoid tumours varies depending on the site of origin. In general, they are slow-growing tumours that pose a diagnostic challenge because they are often innocuous at the time of presentation10. In accordance with the observation that the present case was a small, slow-growing lesion without osseous erosion, it was thought most likely to represent a benign or low-grade malignant process. Neuroendocrine tumours were not included in the clinical differential diagnosis. Not surprisingly the patient did not complain of carcinoid syndrome; less than 10% of patients with carcinoid tumour have the classical carcinoid syndrome10. The diagnosis of carcinoid tumour is initially based on histology with confirmation by immunohistochemistry and/or electron microscopy3,4,10. The histological features of carcinoid tumours consist of an organoid and nesting growth pattern with uniform cytological features consisting of a moderate amount of eosinophilic cytoplasm. The nuclear chromatin is finely granular. The cells are separated by a fibrovascular or hyalinized stroma. Oncocytic, oncocytoid, mucinous and amyloid changes, focal ‘zellballen’, squamous differentiation and rosettes may be seen. Typical carcinoid tumours show no necrosis and are characterized by a mitotic rate of less than 2/10 high-power fields (HPFs). Atypical carcinoid tumours exhibit punctuate
areas of necrosis and a mitotic rate higher than 2/10 HPFs but less than 11/ 10 HPFs. Immunohistochemically, carcinoid tumours are positive for the most sensitive and specific neuroendocrine markers, in particular for synaptophysin, chromogranin, and CD56, and almost always for low-molecular-weight cytokeratins as well as other epithelial markers (carcinoembryonic antigen and epithelial membrane antigen). The neoplastic cells are also variably positive for S-100 protein and for a variety of neuropeptides, including adrenocorticotropic hormone, calcitonin, bombesin, serotonin, somatostatin3,4. On electron microscopy, tumour cells contain abundant membrane-bound, electron-dense neurosecretory granules. Complex intercellular digitation, tight intercellular junctions and mitochondria are variably present3,4. The histopathological and immunohistochemical features seen in the present case are consistent with typical carcinoid tumour. In particular, unusual prominent squamous differentiation was present. The differential diagnosis for the present case includes any primary or secondary tumour with neuroendocrine differentiation3,4,6. Atypical carcinoid tumours are distinguished from typical carcinoid tumours by increased nuclear atypia, a higher mitotic activity that ranges from 2 to 10 mitoses/10 HPFs and punctate foci of necrosis that may be seen. The high-grade neuroendocrine carcinoma, including small cell neuroendocrine carcinoma, Merkel cell carcinoma and large cell neuroendocrine carcinoma, can be distinguished from carcinoid tumours easily by their high mitotic rate and frequent necrosis in addition to characteristic morphology. Rare cases of paragangliomas arising in the oral cavity have been
Primary typical carcinoid tumour in the retromolar region
993
Fig. 2. (a) Tumour cells were strongly immunostained with CKAE1/AE3: 200. (b) Tumour cells were strongly positive for neurone-specific enolase whilst the squamous components were negative: 200. (c) Tumour cells were positive for synaptophysin: 200. (d) Tumour cells were positive for p63: 200.
reported8. These are composed of chief cells and sustentacular cells in a nesting or zellballen pattern. The chief cells are immunoreactive for neuroendocrine markers and the sustentacular cells are S100 positive. Positivity for cytokeratin, carcinoembryonic antigen and epithelial membrane antigen are all findings that are incompatible with a diagnosis of paraganglioma. The possibility of a metastatic typical carcinoid tumour should be excluded by extensive clinical investigation. In the present case, a detailed metastatic workup, including computed tomography of the patient’s head and neck, chest and abdomen, and PET scan was not performed because of the patient’s poor economic condition, but the chest Xray and abdominal ultrasonograph revealed no abnormalities. Together with the medical history, physical examination and TTF-1 negativity, the authors think the present case represents a primary tumour rather than a metastatic tumour. The treatment for typical carcinoid tumour of the oral cavity has not been
established, therefore a treatment similar to that of a typical carcinoid tumour of the larynx was used. Complete local excision is the treatment of choice. Neck dissection is not indicated in view of the usual absence of lymph node metastases. Chemotherapy and radiotherapy appear to be ineffectual3,4. The clinical nature and prognosis of carcinoid tumours vary widely depending on the location of the primary tumour10. For laryngeal typical carcinoid tumours, the clinical course is not indolent as was thought. About onethird of cases developed metastases and the 5-year survival rate was reported to be 49%3,4. It is possible that the low survival rate may be due to the erroneous inclusion of several cases of atypical carcinoids as typical carcinoids. The prognosis of typical carcinoid tumour of the oral cavity remains unknown. 11 months after surgery, the present patient is tumour free. The histogenesis of oral neuroendocrine carcinomas remains unclear. In the oral mucosa, the Merkel cells are the most authenticated neuroendocrine cell with
diverse subpopulations and elusive biologic roles. The Merkel cells show a preferential distribution along the basal layer of the keratinized epithelium of the hard palate and gingiva where they are present as widely scattered clear cells occurring singly or in clusters6. The presence of a novel cluster of neuroendocrine cells with a non-Merkel cell phenotype has been recently described in the squamous epithelium of the human tongue base5. These neuroendocrine cells normally found in the oral cavity are thought by some authors to be the cells of origin of neuroendocrine carcinomas3,5,6. Another hypothesis is that neuroendocrine carcinomas derive from pluripotential indifferent cells of either the squamous epithelium or the minor salivary gland3. The present case showed an abrupt transition from neuroendocrine differentiation to well differentiated squamous areas, favouring this hypothesis. In conclusion, a rare case of typical carcinoid tumour of the retromolar region is presented. Although intraoral occurrences are rare, the surgeon and pathologist should
994
Yang et al.
be aware of this possibility. The correct diagnosis is ascertained by combining morphologic and immunohistochemical evaluations. A thorough clinical evaluation of the patient is necessary to exclude a metastatic tumour. Conservative surgical resection without elective neck dissection is the recommended treatment for typical carcinoid tumour of the oral cavity. Competing interests
None declared. Funding
None. Ethical approval
Not required. References 1. Abiko Y, Ogawa I, Hattori Y, Kusano K, Nishimura M, Ohuchi T, Abe U, Shibata T, Matsuda S, Takata T, Kaku T. Atypical carcinoid (neuroendocrine carcinoma) of the gingiva: counterpart of a laryngeal tumor. Pathol Int 2004: 54: 97– 100.
2. Barnes L, Eveson JW, Reichart P, Sidransky D. World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. Lyon: IARC Press 2005. 3. Ferlito A, Devaney KO, Rinaldo A. Neuroendocrine neoplasms of the larynx: advances in identification, understanding, and management. Oral Oncol 2006: 42: 770–788. 4. Ferlito A, Silver CE, Bradford CR, Rinaldo A. Neuroendocrine neoplasms of the larynx: an overview. Head Neck 2009: 31: 1634–1646. 5. Kusafuka K, Asano R, Kamijo T, Iida Y, Onitsuka T, Kameya T, Nakajima T. Large cell neuroendocrine carcinoma of the tongue base: case report of an unusual location with immunohistochemical analysis. Int J Oral Maxillofac Surg 2009: 38: 296–299. 6. Mahomed F. Neuroendocrine cells and associated malignancies of the oral. Mucosa: a review. J Oral Pathol Med 2010: 39: 121–127. 7. Mills SE. Neuroectodermal neoplasms of the head and neck with emphasis on neuroendocrine carcinomas. Mod Pathol 2002: 15: 264–278. 8. Nielsen TO, Se´jean G, Onerheim RM. Paraganglioma of the tongue. Arch Pathol Lab Med 2000: 124: 877–879. 9. Nishihara K, Nozoe E, Hirayama Y, Miyawaki A, Semba I, Nakamura N.
A case of small cell carcinoma in the buccal region. Int J Oral Maxillofac Surg 2009: 38: 1000–1003. 10. Pinchot SN, Holen K, Sippel RS, Chen H. Carcinoid tumors. Oncologist 2008: 13: 1255–1269. Addresses: Xinming Chen Department of Pathology School and Hospital of Stomatology Wuhan University Wuhan 430079 Hubei China Tel.: +86 27 87646341 fax: +86 27 87686229 E–mail: [email protected] Xing Long Department of Oral and Maxillofacial Surgery School and Hospital of Stomatology Wuhan University Wuhan 430079 Hubei China Tel.: +86 27 87686328 fax: +86 27 87873260 E-mail: [email protected] doi:10.1016/j.ijom.2011.03.008
Case Report Head and Neck Oncology
Oral squamous cell carcinoma in a 7-year-old Brazilian boy C. M. B. Ribeiro, L. A. M. Gueiros, J. E. Leon, M. do Carmo Abreu e Lima, O. P. de Almeida, J. C. Lea˜o: Oral squamous cell carcinoma in a 7-year-old Brazilian boy. Int. J. Oral Maxillofac. Surg. 2011; 40: 994–997. # 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Squamous cell carcinomas (SCCs) are amongst the commonest malignancies in adults but in paediatric patients are exceptionally rare, particularly those involving the oral mucosa. The aim of the present report is to describe the features of a gingival well-differentiated SCC in a 7-year-old Brazilian boy. Immunostaining for p53, Ki-67 and Mcm2 showed increased cellular proliferation compared with normal epithelium. In situ hybridization failed to identify human papilloma virus infection. Correct diagnosis of well-differentiated squamous carcinoma can be difficult in children and differentiation from pseudoepitheliomatous hyperplasia is essential to establish proper treatment.
C. M. B. Ribeiro1,2, L. A. M. Gueiros1, J. E. Leon2, M. do Carmo Abreu e Lima3, O. P. de Almeida2, J. C. Lea˜o1 1 Universidade Federal de Pernambuco, Departamento de Clinica e Odontologia Preventiva, Recife, Brazil; 2Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, Departmento de Diagno´stico Oral – Patologia, Piracicaba, Brazil; 3Hospital do Caˆncer de Pernambuco, Departamento de Patologia, Recife, Brazil
Accepted for publication 10 February 2011 Available online 7 May 2011
991
Case Report Head and Neck Oncology
Primary typical carcinoid tumour in the retromolar region with prominent squamous differentiation: a case report S. Yang, S. Chen, X. Chen, X. Long: Primary typical carcinoid tumour in the retromolar region with prominent squamous differentiation: a case report. Int. J. Oral Maxillofac. Surg. 2011; 40: 991–994. # 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Primary carcinoid tumours of the oral cavity are rare, with only one case of atypical carcinoid tumour reported in the literature. In this article, a case of primary typical carcinoid tumour in the retromolar region in a 46-year-old woman is described. Histologically, the tumour was characterized by submucosal proliferation of medium-sized monomorphous epithelioid cells with an organoid and nesting pattern of growth. Mitoses and necrosis were not found. Prominent squamous differentiation was present. Immunohistochemically, the tumour was diffuse positive for cytokeratin (CK) (AE1/AE3), CK7, p63, neurone-specific enolase, synaptophysin, and chromogranin. To the authors’ knowledge, this is the first report of primary typical carcinoid tumour in the oral cavity.
Neuroendocrine carcinomas are a heterogeneous family of neoplasms that can occur widely in various organs and tissues. The majority of neuroendocrine carcinomas in the head and neck region arise in the larynx and salivary glands6,7. Their occurrence in intraoral mucosal sites is rare, and only 15 cases of oral neuroendocrine carcinomas have been reported as Merkel cell carcinoma (7 cases), small cell neuroendocrine carcinoma (5 cases), large cell neuroendocrine carcinoma (1 case), atypical carcinoid (1 case) and moderately differentiated neuroendocrine carcinoma (1 case)1,5,6,9. According to the World Health Organization classification, laryngeal neuroendocrine carcinomas are subclassified into typical carcinoid, atypical carcinoid, and small cell carcinoma, corresponding to well, moderately, and poorly differentiated neuroendocrine carcinomas, respectively2,7. Owing to their rarity, neuroendocrine carcinomas of the
oral cavity were not incorporated into the classification of neuroendocrine neoplasms of the head and neck. In a recent review, MAHOMED6 proposed classifying oral neuroendocrine carcinomas into typical carcinoid, atypical carcinoid, small cell neuroendocrine carcinoma (including the Merkel cell type and the pulmonary type), and large cell neuroendocrine carcinoma. To the authors’ knowledge, the existence of primary typical carcinoid tumour in the oral cavity has not been published before. The authors present the first case of oral typical carcinoid tumour in the retromolar region in a 46year-old woman. Unusual prominent squamous differentiation was noted. Case report
A 46-year-old woman presented with a 5year history of a painless swelling in the retromolar region. Intraoral examination
S. Yang1,2,1, S. Chen1,4,1, X. Chen3, X. Long4 1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China; 2Department of Oral Histopathology, Faculty of Stomatology, Hainan Medical College, Haikou, Hainan, China; 3Department of Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China; 4Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
Keywords: carcinoid tumour; neuroendocrine carcinoma; oral cavity; retromolar region. Accepted for publication 9 March 2011 Available online 14 April 2011
showed a relatively well-defined, elastic, and immobile mass that measured about 1.5 cm 2 cm. It was covered with normal, healthy, non-ulcerated mucosa. A panoramic radiograph showed no bony involvement. There was no palpable cervical lymphadenopathy. A detailed general physical examination, chest X-ray, and abdominal ultrasound scan showed no evidence of distant metastasis. The patients’ laboratory findings were within normal limits, including complete blood count, blood biochemistry, and urine analysis. The clinical differential diagnosis included benign minor salivary gland neoplasm, benign mesenchymal neoplasm, and low-grade malignant tumour of minor salivary gland or mesenchymal origin. The lesion was excised completely with free margins under general anaesthesia. 1
Equal contribution.
992 [()TD$FIG]
Yang et al.
Fig. 1. (a) Low power showing a circumscribed submucosal proliferation covered by normal surface epithelium. Tumour cells arranged in organoid and nesting pattern. Prominent squamous differentiation was noted. Haematoxylin–eosin stain (H–E stain): 40. (b) High power showing the relatively uniform tumour cells with round or oval, centrally placed nuclei and granular eosinophilic cytoplasm. H–E stain: 400.
The patient is being followed up and showed no evidence of disease 11 months postoperatively. Histopathological examination revealed that the resected tumour was 2 cm in diameter, whitish in colour and relatively hard in consistency. There was a circumscribed, but not encapsulated, submucosal tumour covered by normal surface epithelium. The tumour was composed of medium-sized monomorphous epithelioid cells, arranged in nests, trabeculae, and cords surrounded by thin to thick fibrovascular septa (Fig. 1a). The cytoplasm of the tumour cells varied from eosinophilic to pale. The nuclei were central, round with finely granular chromatin and inconspicuous nucleoli. Mitoses and necrosis were not found (Fig. 1b). Extensive squamous differentiation was noted. Prominent thin, elongated blood vessels were seen. Immunohistochemically, the tumour was diffuse positive for cytokeratin (CK) AE1/AE3 (Fig. 2a), CK7, neuronespecific enolase (Fig. 2b), synaptophysin (Fig. 2c), chromogranin, and p63 (Fig. 2d); focal positive for S100, vimentin, and CD57; negative for CD56, thyroid transcription factor 1 (TTF-1), and CK20. The components of squamous differentiation were positive for CKAE1/AE3 and CK7. The association of the immunoprofile with the microscopic morphology confirmed the diagnosis of typical carcinoid tumour. Discussion
Carcinoid tumour is the most common of the neuroendocrine tumours. It is usually found in the gastrointestinal tract (55%) and in the bronchopulmonary tract (30%)10. Occurrence of carcinoid tumour
in the head and neck area mainly involves the larynx, followed by the middle ear7. Primary carcinoid tumours of the oral cavity are rare, with only one case of atypical carcinoid tumour reported in the literature1. The present case is the first report of typical carcinoid tumour in the oral cavity. The clinical presentation of carcinoid tumours varies depending on the site of origin. In general, they are slow-growing tumours that pose a diagnostic challenge because they are often innocuous at the time of presentation10. In accordance with the observation that the present case was a small, slow-growing lesion without osseous erosion, it was thought most likely to represent a benign or low-grade malignant process. Neuroendocrine tumours were not included in the clinical differential diagnosis. Not surprisingly the patient did not complain of carcinoid syndrome; less than 10% of patients with carcinoid tumour have the classical carcinoid syndrome10. The diagnosis of carcinoid tumour is initially based on histology with confirmation by immunohistochemistry and/or electron microscopy3,4,10. The histological features of carcinoid tumours consist of an organoid and nesting growth pattern with uniform cytological features consisting of a moderate amount of eosinophilic cytoplasm. The nuclear chromatin is finely granular. The cells are separated by a fibrovascular or hyalinized stroma. Oncocytic, oncocytoid, mucinous and amyloid changes, focal ‘zellballen’, squamous differentiation and rosettes may be seen. Typical carcinoid tumours show no necrosis and are characterized by a mitotic rate of less than 2/10 high-power fields (HPFs). Atypical carcinoid tumours exhibit punctuate
areas of necrosis and a mitotic rate higher than 2/10 HPFs but less than 11/ 10 HPFs. Immunohistochemically, carcinoid tumours are positive for the most sensitive and specific neuroendocrine markers, in particular for synaptophysin, chromogranin, and CD56, and almost always for low-molecular-weight cytokeratins as well as other epithelial markers (carcinoembryonic antigen and epithelial membrane antigen). The neoplastic cells are also variably positive for S-100 protein and for a variety of neuropeptides, including adrenocorticotropic hormone, calcitonin, bombesin, serotonin, somatostatin3,4. On electron microscopy, tumour cells contain abundant membrane-bound, electron-dense neurosecretory granules. Complex intercellular digitation, tight intercellular junctions and mitochondria are variably present3,4. The histopathological and immunohistochemical features seen in the present case are consistent with typical carcinoid tumour. In particular, unusual prominent squamous differentiation was present. The differential diagnosis for the present case includes any primary or secondary tumour with neuroendocrine differentiation3,4,6. Atypical carcinoid tumours are distinguished from typical carcinoid tumours by increased nuclear atypia, a higher mitotic activity that ranges from 2 to 10 mitoses/10 HPFs and punctate foci of necrosis that may be seen. The high-grade neuroendocrine carcinoma, including small cell neuroendocrine carcinoma, Merkel cell carcinoma and large cell neuroendocrine carcinoma, can be distinguished from carcinoid tumours easily by their high mitotic rate and frequent necrosis in addition to characteristic morphology. Rare cases of paragangliomas arising in the oral cavity have been
Primary typical carcinoid tumour in the retromolar region
993
Fig. 2. (a) Tumour cells were strongly immunostained with CKAE1/AE3: 200. (b) Tumour cells were strongly positive for neurone-specific enolase whilst the squamous components were negative: 200. (c) Tumour cells were positive for synaptophysin: 200. (d) Tumour cells were positive for p63: 200.
reported8. These are composed of chief cells and sustentacular cells in a nesting or zellballen pattern. The chief cells are immunoreactive for neuroendocrine markers and the sustentacular cells are S100 positive. Positivity for cytokeratin, carcinoembryonic antigen and epithelial membrane antigen are all findings that are incompatible with a diagnosis of paraganglioma. The possibility of a metastatic typical carcinoid tumour should be excluded by extensive clinical investigation. In the present case, a detailed metastatic workup, including computed tomography of the patient’s head and neck, chest and abdomen, and PET scan was not performed because of the patient’s poor economic condition, but the chest Xray and abdominal ultrasonograph revealed no abnormalities. Together with the medical history, physical examination and TTF-1 negativity, the authors think the present case represents a primary tumour rather than a metastatic tumour. The treatment for typical carcinoid tumour of the oral cavity has not been
established, therefore a treatment similar to that of a typical carcinoid tumour of the larynx was used. Complete local excision is the treatment of choice. Neck dissection is not indicated in view of the usual absence of lymph node metastases. Chemotherapy and radiotherapy appear to be ineffectual3,4. The clinical nature and prognosis of carcinoid tumours vary widely depending on the location of the primary tumour10. For laryngeal typical carcinoid tumours, the clinical course is not indolent as was thought. About onethird of cases developed metastases and the 5-year survival rate was reported to be 49%3,4. It is possible that the low survival rate may be due to the erroneous inclusion of several cases of atypical carcinoids as typical carcinoids. The prognosis of typical carcinoid tumour of the oral cavity remains unknown. 11 months after surgery, the present patient is tumour free. The histogenesis of oral neuroendocrine carcinomas remains unclear. In the oral mucosa, the Merkel cells are the most authenticated neuroendocrine cell with
diverse subpopulations and elusive biologic roles. The Merkel cells show a preferential distribution along the basal layer of the keratinized epithelium of the hard palate and gingiva where they are present as widely scattered clear cells occurring singly or in clusters6. The presence of a novel cluster of neuroendocrine cells with a non-Merkel cell phenotype has been recently described in the squamous epithelium of the human tongue base5. These neuroendocrine cells normally found in the oral cavity are thought by some authors to be the cells of origin of neuroendocrine carcinomas3,5,6. Another hypothesis is that neuroendocrine carcinomas derive from pluripotential indifferent cells of either the squamous epithelium or the minor salivary gland3. The present case showed an abrupt transition from neuroendocrine differentiation to well differentiated squamous areas, favouring this hypothesis. In conclusion, a rare case of typical carcinoid tumour of the retromolar region is presented. Although intraoral occurrences are rare, the surgeon and pathologist should
994
Yang et al.
be aware of this possibility. The correct diagnosis is ascertained by combining morphologic and immunohistochemical evaluations. A thorough clinical evaluation of the patient is necessary to exclude a metastatic tumour. Conservative surgical resection without elective neck dissection is the recommended treatment for typical carcinoid tumour of the oral cavity. Competing interests
None declared. Funding
None. Ethical approval
Not required. References 1. Abiko Y, Ogawa I, Hattori Y, Kusano K, Nishimura M, Ohuchi T, Abe U, Shibata T, Matsuda S, Takata T, Kaku T. Atypical carcinoid (neuroendocrine carcinoma) of the gingiva: counterpart of a laryngeal tumor. Pathol Int 2004: 54: 97– 100.
2. Barnes L, Eveson JW, Reichart P, Sidransky D. World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. Lyon: IARC Press 2005. 3. Ferlito A, Devaney KO, Rinaldo A. Neuroendocrine neoplasms of the larynx: advances in identification, understanding, and management. Oral Oncol 2006: 42: 770–788. 4. Ferlito A, Silver CE, Bradford CR, Rinaldo A. Neuroendocrine neoplasms of the larynx: an overview. Head Neck 2009: 31: 1634–1646. 5. Kusafuka K, Asano R, Kamijo T, Iida Y, Onitsuka T, Kameya T, Nakajima T. Large cell neuroendocrine carcinoma of the tongue base: case report of an unusual location with immunohistochemical analysis. Int J Oral Maxillofac Surg 2009: 38: 296–299. 6. Mahomed F. Neuroendocrine cells and associated malignancies of the oral. Mucosa: a review. J Oral Pathol Med 2010: 39: 121–127. 7. Mills SE. Neuroectodermal neoplasms of the head and neck with emphasis on neuroendocrine carcinomas. Mod Pathol 2002: 15: 264–278. 8. Nielsen TO, Se´jean G, Onerheim RM. Paraganglioma of the tongue. Arch Pathol Lab Med 2000: 124: 877–879. 9. Nishihara K, Nozoe E, Hirayama Y, Miyawaki A, Semba I, Nakamura N.
A case of small cell carcinoma in the buccal region. Int J Oral Maxillofac Surg 2009: 38: 1000–1003. 10. Pinchot SN, Holen K, Sippel RS, Chen H. Carcinoid tumors. Oncologist 2008: 13: 1255–1269. Addresses: Xinming Chen Department of Pathology School and Hospital of Stomatology Wuhan University Wuhan 430079 Hubei China Tel.: +86 27 87646341 fax: +86 27 87686229 E–mail: [email protected] Xing Long Department of Oral and Maxillofacial Surgery School and Hospital of Stomatology Wuhan University Wuhan 430079 Hubei China Tel.: +86 27 87686328 fax: +86 27 87873260 E-mail: [email protected] doi:10.1016/j.ijom.2011.03.008
Case Report Head and Neck Oncology
Oral squamous cell carcinoma in a 7-year-old Brazilian boy C. M. B. Ribeiro, L. A. M. Gueiros, J. E. Leon, M. do Carmo Abreu e Lima, O. P. de Almeida, J. C. Lea˜o: Oral squamous cell carcinoma in a 7-year-old Brazilian boy. Int. J. Oral Maxillofac. Surg. 2011; 40: 994–997. # 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Squamous cell carcinomas (SCCs) are amongst the commonest malignancies in adults but in paediatric patients are exceptionally rare, particularly those involving the oral mucosa. The aim of the present report is to describe the features of a gingival well-differentiated SCC in a 7-year-old Brazilian boy. Immunostaining for p53, Ki-67 and Mcm2 showed increased cellular proliferation compared with normal epithelium. In situ hybridization failed to identify human papilloma virus infection. Correct diagnosis of well-differentiated squamous carcinoma can be difficult in children and differentiation from pseudoepitheliomatous hyperplasia is essential to establish proper treatment.
C. M. B. Ribeiro1,2, L. A. M. Gueiros1, J. E. Leon2, M. do Carmo Abreu e Lima3, O. P. de Almeida2, J. C. Lea˜o1 1 Universidade Federal de Pernambuco, Departamento de Clinica e Odontologia Preventiva, Recife, Brazil; 2Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, Departmento de Diagno´stico Oral – Patologia, Piracicaba, Brazil; 3Hospital do Caˆncer de Pernambuco, Departamento de Patologia, Recife, Brazil
Accepted for publication 10 February 2011 Available online 7 May 2011