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Oat-Cell Carcinoma of the Tongue
Acta Otorrinolaringol Esp. 2016;67(5):297---299
www.elsevier.es/otorrino
CASE STUDY
Oat-Cell Carcinoma of the Tongue夽 Carcinoma neuroendocrino de célula peque˜ na de la lengua Francina Aguilar,a,∗ Miguel Cuadrado,b Jordi Serra,a Xana Bernal-Escotéc a
Servicio de Otorrinolaringología, Hospital General de Granollers, Granollers, Barcelona, Spain Servicio de Radiología, Hospital General de Granollers, Granollers, Barcelona, Spain c Servicio de Anatomía Patológica, Hospital General de Granollers, Granollers, Barcelona, Spain b
Received 22 September 2015; accepted 22 October 2015
A 55-year-old woman, smoker, referred from the rapid diagnosis unit with right lateral cervical enlarged level II lymph node, 3×2 cm, diagnosed by fine needle punction-aspiration biopsy (FNPA), by cytology and positive immunocytochemical staining for CD56 as undifferentiated oat cell carcinoma, (Fig. 1). The patient presented with a 2-month history of mild odynodysphagia. Examination revealed a mass at the base of the tongue and right vallecula affecting the laryngeal side of the epiglottis. Computerized tomography (Fig. 2) revealed a nodular lesion 24×24 mm at the base of the tongue and right vallecula, reaching the right edge of the epiglottis, with fatty involvement at the base of the tongue cranial to the hyoid bone, and preepiglottic fat involvement posterior to the hyoid bone, together with bilateral pathologically enlarged (level II and III) lateral cervical lymph nodes. The PET scan did not detect further lesions, therefore the tongue mass was biopsied, and the definitive diagnosis was undifferentiated oat cell carcinoma of the base of the tongue, T3N2cM0, stage IVa. The patient received 3 cycles of chemotherapy (cisplatin, 80 mg/m2 /d for one day, plus Etoposide, 100 mg/m2 /d for 3 days) and a fourth cycle of chemotherapy (Cisplatin, 60 mg/m2 /d for one day, 夽 Please cite this article as: Aguilar F, Cuadrado M, Serra J, na de Bernal-Escoté X. Carcinoma neuroendocrino de célula peque˜ la lengua. Acta Otorrinolaringol Esp. 2016;67:297---299. ∗ Corresponding author. E-mail address: [email protected] (F. Aguilar).
plus Etoposide, 120 mg/m2 /d for 3 days), with concomitant intensity modulated radiation therapy (IMRT), followed subsequently with radiotherapy alone until reaching a dose of 70 Gy divided into 33 fractions (2.12 Gy/fraction). Followup computerized tomography, 3 months after treatment, showed the disappearance of the primary and lymph node lesion, but revealed cerebral, cerebellar and liver metastases. The patient died 7 months after the diagnosis.
Discussion Oat cell (neuroendocrine) carcinoma, or poorly differentiated neuroendocrine carcinoma, is a neuroendocrine tumor deriving from the amine precursor uptake and decarboxylation (APUD) system.1,2 It is most commonly located in the lung, only 4% of cases are outside the lung, and in this case the most common site is the larynx (the larynx was the first extrapulmonary location described for this type of tumor in 1972 by Oloffson and von Nostrand3 ). The rarest sites are the paranasal sinuses, oral cavity and pharynx.2,4 There are 2 published cases of this type of tumor in the oropharynx: the first case in the lingual body, was published in 1984,5 the second, at the base of the tongue, was published in this journal in 2001.6 The case that we present is the third to be described originating in the oropharynx, and the second at the base of the tongue. Associated paraneoplastic syndromes are described in none of the cases, and all of them died within less than a year after diagnosis. Metastatic
2173-5735/© 2016 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Otorrinolaringolog´ıa y Cirug´ıa de Cabeza y Cuello. All rights reserved.
298
F. Aguilar et al.
Figure 1 Giemsa stain (×10). Cytological extension from fine needle punction-aspiration biopsy (FNPA), of right lateral cervical lymph node. The base of the lymphatic node is shown, with abundant atypical cellularity arranged, loose or in three-dimensional clusters, comprising small to medium-sized cells. With higher magnification (×40, upper left box) cells can be observed with very scanty cytoplasm, irregular and hyperchromatic nuclei, granular chromatin, nuclear molding and the presence of mitosis. Immunocytochemical staining with CD56 (lower left box) showing the characteristic positivity of membrane-bound cytoplasmatic granules of neuroendocrine cells.
small cell/neuroendocrine carcinomas of the tongue have also been described.7,8 A histological differential diagnosis with undifferentiated carcinoma, rhabdomyiosarcoma and primitive neuroectodermal tumor (much more common) is very important. In terms of cytological differences, we would point out that oat cell (neuroendocrine) carcinoma presents with molding and granular chromatin. CD56 confirms its neuroendocrine origin. Oat cell (neuroendocrine) carcinoma should be considered a systemic disease; therefore, extension studies at the time of diagnosis are necessary to rule out metastasis. It
Figure 2
always behaves aggressively, with early lymph node involvement and rapid systemic extension. Therefore the treatment of choice is chemotherapy and concomitant radiotherapy, from the second cycle, if possible. The indicated chemotherapy is, by extrapolation, that which is indicated for oat cell (neuroendocrine) tumors of the lung, Cisplatin plus Etoposide or VP16. The Cisplatin dose is 80 mg/m2 /d for one day, when not given together with radiotherapy, and 60 mg/m2 /d for one day, when it is combined with radiotherapy. The dose of Etoposide is 100 mg/m2 /d for 3 days, when not given in combination with radiotherapy, and 120 mg/m2 /d for 3 days, when combined. The total radiotherapy dose, if there are no
Sagittal and axial slice computed tomography showing the lesion and its origin at the base of the tongue.
Oat-Cell Carcinoma of the Tongue contraindications, is 70 Gy, intensity modulated when necessary due to the location and for organ preservation. Surgery is not indicated for these tumors.
Conflict of Interests The authors have no conflict of interests to declare.
References 1. Williams ED, Sandlers M. The classification of carcinoid tumors. Lancet. 1963;1:238---9. 2. Ibrahim NBN, Briggs JC, Corbishley CM. Extrapulmonary oat cell carcinoma. Cancer. 1984;54:1645---61.
299 3. Olofsson J, von Nostrand AW. Anaplastic small cell carcinoid of the larynx. Case report. Am Otol Rhinol Laryngol. 1972;81:284---7. 4. Ferlito A. Oat cell carcinoma of the larynx. Ann Otol Rhinol Laryngol. 1974;83:254---6. 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. 6. Benito JR, Mier M, Morote F, Poras E, García N, Pérez-Requena J. Carcinoma microcítico de lengua. A propósito de un caso. Acta Otorrinolaringol Esp. 2001;52:438---41. 7. Mitchell RB, Stedeford J, Buchanan G. Oat cell carcinoma of the tongue from an unknown primary. Ear Nose Throat J. 1998;77:221---3. 8. Sridhar KS, Chaninian AP, Schwartz IS. Tongue metastasis from undifferentiated small cell (oat cell) lung cancer. J Fla Med Assoc. 1985;72:428---30.
www.elsevier.es/otorrino
CASE STUDY
Oat-Cell Carcinoma of the Tongue夽 Carcinoma neuroendocrino de célula peque˜ na de la lengua Francina Aguilar,a,∗ Miguel Cuadrado,b Jordi Serra,a Xana Bernal-Escotéc a
Servicio de Otorrinolaringología, Hospital General de Granollers, Granollers, Barcelona, Spain Servicio de Radiología, Hospital General de Granollers, Granollers, Barcelona, Spain c Servicio de Anatomía Patológica, Hospital General de Granollers, Granollers, Barcelona, Spain b
Received 22 September 2015; accepted 22 October 2015
A 55-year-old woman, smoker, referred from the rapid diagnosis unit with right lateral cervical enlarged level II lymph node, 3×2 cm, diagnosed by fine needle punction-aspiration biopsy (FNPA), by cytology and positive immunocytochemical staining for CD56 as undifferentiated oat cell carcinoma, (Fig. 1). The patient presented with a 2-month history of mild odynodysphagia. Examination revealed a mass at the base of the tongue and right vallecula affecting the laryngeal side of the epiglottis. Computerized tomography (Fig. 2) revealed a nodular lesion 24×24 mm at the base of the tongue and right vallecula, reaching the right edge of the epiglottis, with fatty involvement at the base of the tongue cranial to the hyoid bone, and preepiglottic fat involvement posterior to the hyoid bone, together with bilateral pathologically enlarged (level II and III) lateral cervical lymph nodes. The PET scan did not detect further lesions, therefore the tongue mass was biopsied, and the definitive diagnosis was undifferentiated oat cell carcinoma of the base of the tongue, T3N2cM0, stage IVa. The patient received 3 cycles of chemotherapy (cisplatin, 80 mg/m2 /d for one day, plus Etoposide, 100 mg/m2 /d for 3 days) and a fourth cycle of chemotherapy (Cisplatin, 60 mg/m2 /d for one day, 夽 Please cite this article as: Aguilar F, Cuadrado M, Serra J, na de Bernal-Escoté X. Carcinoma neuroendocrino de célula peque˜ la lengua. Acta Otorrinolaringol Esp. 2016;67:297---299. ∗ Corresponding author. E-mail address: [email protected] (F. Aguilar).
plus Etoposide, 120 mg/m2 /d for 3 days), with concomitant intensity modulated radiation therapy (IMRT), followed subsequently with radiotherapy alone until reaching a dose of 70 Gy divided into 33 fractions (2.12 Gy/fraction). Followup computerized tomography, 3 months after treatment, showed the disappearance of the primary and lymph node lesion, but revealed cerebral, cerebellar and liver metastases. The patient died 7 months after the diagnosis.
Discussion Oat cell (neuroendocrine) carcinoma, or poorly differentiated neuroendocrine carcinoma, is a neuroendocrine tumor deriving from the amine precursor uptake and decarboxylation (APUD) system.1,2 It is most commonly located in the lung, only 4% of cases are outside the lung, and in this case the most common site is the larynx (the larynx was the first extrapulmonary location described for this type of tumor in 1972 by Oloffson and von Nostrand3 ). The rarest sites are the paranasal sinuses, oral cavity and pharynx.2,4 There are 2 published cases of this type of tumor in the oropharynx: the first case in the lingual body, was published in 1984,5 the second, at the base of the tongue, was published in this journal in 2001.6 The case that we present is the third to be described originating in the oropharynx, and the second at the base of the tongue. Associated paraneoplastic syndromes are described in none of the cases, and all of them died within less than a year after diagnosis. Metastatic
2173-5735/© 2016 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Otorrinolaringolog´ıa y Cirug´ıa de Cabeza y Cuello. All rights reserved.
298
F. Aguilar et al.
Figure 1 Giemsa stain (×10). Cytological extension from fine needle punction-aspiration biopsy (FNPA), of right lateral cervical lymph node. The base of the lymphatic node is shown, with abundant atypical cellularity arranged, loose or in three-dimensional clusters, comprising small to medium-sized cells. With higher magnification (×40, upper left box) cells can be observed with very scanty cytoplasm, irregular and hyperchromatic nuclei, granular chromatin, nuclear molding and the presence of mitosis. Immunocytochemical staining with CD56 (lower left box) showing the characteristic positivity of membrane-bound cytoplasmatic granules of neuroendocrine cells.
small cell/neuroendocrine carcinomas of the tongue have also been described.7,8 A histological differential diagnosis with undifferentiated carcinoma, rhabdomyiosarcoma and primitive neuroectodermal tumor (much more common) is very important. In terms of cytological differences, we would point out that oat cell (neuroendocrine) carcinoma presents with molding and granular chromatin. CD56 confirms its neuroendocrine origin. Oat cell (neuroendocrine) carcinoma should be considered a systemic disease; therefore, extension studies at the time of diagnosis are necessary to rule out metastasis. It
Figure 2
always behaves aggressively, with early lymph node involvement and rapid systemic extension. Therefore the treatment of choice is chemotherapy and concomitant radiotherapy, from the second cycle, if possible. The indicated chemotherapy is, by extrapolation, that which is indicated for oat cell (neuroendocrine) tumors of the lung, Cisplatin plus Etoposide or VP16. The Cisplatin dose is 80 mg/m2 /d for one day, when not given together with radiotherapy, and 60 mg/m2 /d for one day, when it is combined with radiotherapy. The dose of Etoposide is 100 mg/m2 /d for 3 days, when not given in combination with radiotherapy, and 120 mg/m2 /d for 3 days, when combined. The total radiotherapy dose, if there are no
Sagittal and axial slice computed tomography showing the lesion and its origin at the base of the tongue.
Oat-Cell Carcinoma of the Tongue contraindications, is 70 Gy, intensity modulated when necessary due to the location and for organ preservation. Surgery is not indicated for these tumors.
Conflict of Interests The authors have no conflict of interests to declare.
References 1. Williams ED, Sandlers M. The classification of carcinoid tumors. Lancet. 1963;1:238---9. 2. Ibrahim NBN, Briggs JC, Corbishley CM. Extrapulmonary oat cell carcinoma. Cancer. 1984;54:1645---61.
299 3. Olofsson J, von Nostrand AW. Anaplastic small cell carcinoid of the larynx. Case report. Am Otol Rhinol Laryngol. 1972;81:284---7. 4. Ferlito A. Oat cell carcinoma of the larynx. Ann Otol Rhinol Laryngol. 1974;83:254---6. 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. 6. Benito JR, Mier M, Morote F, Poras E, García N, Pérez-Requena J. Carcinoma microcítico de lengua. A propósito de un caso. Acta Otorrinolaringol Esp. 2001;52:438---41. 7. Mitchell RB, Stedeford J, Buchanan G. Oat cell carcinoma of the tongue from an unknown primary. Ear Nose Throat J. 1998;77:221---3. 8. Sridhar KS, Chaninian AP, Schwartz IS. Tongue metastasis from undifferentiated small cell (oat cell) lung cancer. J Fla Med Assoc. 1985;72:428---30.