Accepted Manuscript Lymphoepithelial carcinoma of the sublingual gland: Case Report and Review of Literature Laurence Roy, Bsc, Medical Student, Sami P. Moubayed, MD (Resident), Tareck Ayad, MD, FRCSC (Professor) PII:
S0278-2391(15)00490-5
DOI:
10.1016/j.joms.2015.04.030
Reference:
YJOMS 56795
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 18 March 2015 Revised Date:
15 April 2015
Accepted Date: 21 April 2015
Please cite this article as: Roy L, Moubayed SP, Ayad T, Lymphoepithelial carcinoma of the sublingual gland: Case Report and Review of Literature, Journal of Oral and Maxillofacial Surgery (2015), doi: 10.1016/j.joms.2015.04.030. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: Lymphoepithelial carcinoma of the sublingual
gland: Case Report and Review of
Literature
RI PT
Authors: Laurence Roy (Bsc, Medical Student), Sami P. Moubayed MD (Resident), Tareck Ayad MD, FRCSC (Professor)
SC
Institutions: Otolaryngology-Head and Neck Surgery Service, Université de Montréal Hospital
Corresponding author: Tareck Ayad MD Hôpital Notre-Dame
Montréal, Canada H2L4M1
EP
[email protected]
TE D
5415 boul. De l’Assomption
M AN U
Center and Maisonneuve-Rosemont Hospital, Montreal, Canada
AC C
Sources of support: none
Key words: lymphoepithelial carcinoma, sublingual gland, treatment
ACCEPTED MANUSCRIPT
Abstract Lymphoepithelial carcinoma represents only 0.4% of salivary gland neoplasms. Generally affecting the parotid gland, it has been only reported twice in the sublingual gland. Controversies
RI PT
concerning the treatment of lymphoepithelial carcinoma exist. Although the literature generally agrees that primary surgery and adjuvant radiotherapy is part of the treatment, the benefit of adjuvant chemotherapy is not well described. In this paper, we present the case of a 55 year-old
SC
man diagnosed with a lymphoepithelial carcinoma of the sublingual gland. The patient was admitted for progressive pain in the floor of mouth associated with trismus. A biopsy confirmed
M AN U
the diagnosis of lymphoepithelial carcinoma of the sublingual gland and magnetic resonance imaging showed multiple left lymphadenopathies. Surgery consisted of a radical neck dissection type III, surgical resection of the floor of mouth, and reconstruction with a left facial artery musculomucosal flap. The patient received adjuvant radiotherapy (60 Gy) and adjuvant
TE D
chemotherapy (three cycles of cisplatinum 100 mg/m2). The patient was disease-free at 36 months of follow-up. The evidence base for administering adjuvant chemotherapy in this
AC C
EP
situation is discussed.
ACCEPTED MANUSCRIPT
Introduction Lymphoepithelial carcinoma (LEC) is a rare undifferentiated carcinoma of the salivary glands, along with small-cell undifferentiated carcinoma, and large-cell undifferentiated carcinoma1. It is
RI PT
considered a high-grade malignancy. It represents 0.4% of salivary gland neoplasms, and predominates in the parotid gland in 83.5% of cases, and in the submandibular gland in 15% of cases. There are about 100 cases previously described in the literature1. This type of tumor has
SC
been described in the sublingual gland only twice before this report1,2. We present the first NorthAmerican case of LEC of the sublingual gland, successfully treated with surgery and adjuvant
M AN U
radiochemotherapy.
Report of a case
A 55 year-old male presented for a progressive pain in the floor of mouth over the past five
TE D
months, associated with trismus. His past medical history was significant for diabetes, hypertension, and dyslipidemia, with a family history of lymphoma and stomach cancer in his mother, and colorectal and bladder cancer in his father. He was a Caucasian, nonsmoker, an
EP
occasional drinker, and did not use drugs. On examination, a mobile, firm and non-tender 2 cm mass was palpable on the left sublingual area, without transgressing the midline, with normal
AC C
overlying mucosa. The nasopharynx was free of disease. No lymphadenopathy was noted. Magnetic resonance imaging revealed a 15 x 19 x 29 mm mass in the left sublingual gland, causing a mass effect on the genioglossus muscle and invading the sublingual space (Figure 1). Multiple left lymphadenopathies were found in zones IIA, IV, and VA, the largest one measuring 16 mm in zone IV. Distant metastatic workup with positron emission tomography/computed tomography was negative. Incisional biopsy revealed an undifferentiated lymphoepithelial
ACCEPTED MANUSCRIPT
carcinoma of the sublingual gland with lymphocytic and plasmocytic infiltration (Figure 2). EBER in situ hybridization was positive for EBV (Figure 3). Clinical staging was T2N2bM0.
RI PT
The patient was treated surgically with a left modified radical neck dissection type III (zones Iab, IIa-b, III, IV, V), elective tracheostomy, surgical resection of the floor of mouth, and reconstruction with a left facial artery musculomucosal (FAMM) flap (Figure 4). Pathology
SC
revealed negative margins, lymphovascular invasion, no perineural invasion, three positive lymph nodes out of 16 without extracapsular spread, and an independent 2x2 cm mass on the internal
M AN U
aspect of the mandible that is either a metastatic lymph node or a second focus of LEC. Definitive pathologic staging was T2N2bM0. Adjuvant radiation therapy was administered as 60 Gy to the primary tumor bed and neck basins using tomotherapy. The patient also received three cycles of cisplatinum 100 mg/m2. The patient tolerated treatment very well. He was free of
Discussion
TE D
disease after 36 months of postoperative follow-up.
EP
LEC represents only 0.4% of salivary gland neoplasms, with the parotid gland involved in the majority of cases and the submandibular gland in a minority of cases1. Only two cases in the
AC C
literature reports LEC in the sublingual gland1,2. The incidence of LEC is higher in Arctic native Inuits and Asian patients1. In these endemic areas, Epstein-Barr virus (EBV) is almost invariably associated with LEC and the relation between EBV and LEC has been well established1. However, the association between EBV and LEC is less frequent in Caucasian patients3, and Caucasians are less frequently affected by this type of salivary gland tumor1. The first paper describing a case of sublingual LEC originated from the Middle East and was treated with primary surgical resection, neck dissection, and adjuvant radiotherapy, without chemotherapy1.
ACCEPTED MANUSCRIPT
Radiation dose was not reported. The second article mentioning LEC in sublingual gland is a retrospective study where neither the case or the treatment are described2.
RI PT
Knowing that 80-90% of sublingual lesions are malignant tumors, any lesion of the sublingual gland should be considered malignant until proven otherwise4. Adenoid cystic carcinoma and mucoepidermoid carcinoma are the most common malignant tumors of the sublingual gland4.
SC
LEC only accounts for a minority of the sublingual neoplasms. Specific differential diagnoses of LEC are discussed later. Benign lesions of the sublingual gland include ranula, sialolithiasis, and
M AN U
sialadenits.
Investigation of the sublingual mass should include imaging and fine needle aspiration biopsy5. A cervical node involvement rate of up to 40% has been reported in LEC in major glands, and 20%
TE D
of patients develop distant metastases within three years of being treated6. Therefore, a standard metastsatic workup is warranted. However, no specific symptoms or images are distinctive of LEC. Definitive diagnosis is based on histopathology5. LEC is a tumor made of irregular islands
EP
of cohesive atypical epithelial cells surrounded by mixed reactive lymphoid cells7. Benign lymphoepithelial lesions, malignant lymphoma and metastatic undifferentiated carcinoma are part
AC C
of differential diagnosis of LEC1. Benign lymphoepithelial lesion and malignant lymphoma can be distinguished from LEC by microscopic examination and immunostaining for cytokeratin1,7. Ruling out metastatic undifferentiated nasopharyngeal carcinoma is necessary because the salivary glands are adjacent to the lymphatic drainage pathway of the tumors5. This is made by careful examination of the upper respiratory and digestive system1,7. Biopsies of any suspicious tissue from the nasopharynx must be performed1,7.
ACCEPTED MANUSCRIPT
Treatment of LEC is based on limited case series, most of the larger ones originating from Chinese centers due to the rarity of the disease in the Western world. The mainstay of treatment for salivary gland tumors is surgical resection, with adjuvant radiotherapy for unfavorable
RI PT
prognostic features (close or positive surgical margins, high-grade malignancy, perineural invasion, tumor infiltration of adjacent organs, recurrent disease, and locoregional metastasis8).Most series agree on primary surgical therapy with adjuvant radiation therapy, as
SC
LEC is considered a high-grade malignancy5,9,10, with 5-year survival ranging from 50 to 90%.Postoperative irradiation is delivered to the tumor bed and involved nodes at a dose of 60
M AN U
Gy and to the cervical lymph node drainage basins at a dose of 56 Gy9.
Authors generally agree on cervical lymphadenectomy for the clinically involved neck1. Elective neck dissection is not routinely performed by all authors5,9. A larger series showed 26.1% of
TE D
occult neck metastases in 23 patients undergoing elective neck dissection for clinically negative necks, although stage distribution was not available10. However, elective neck dissection in
EP
advanced stages resulted in a more favorable overall survival10.
In contrast to other high-grade salivary carcinomas, LEC is radiosensitive. Some authors suggest
AC C
radiotherapy alone as an appropriate therapy for salivary LEC8,11.A review by Dubey et al.11 showed that in 34 patients with LEC originating from the salivary glands, there were no statistically significant differences in 5-year local and regional control rates between patients treated with radiotherapy only and patients treated with surgical resection and adjuvant radiotherapy. For patients who received radiotherapy, the median radiation dose given to the primary tumor was 65 Gy. However, this series is limited by the small number of patients reported.
ACCEPTED MANUSCRIPT
Chemotherapy in treatment of LEC is not well described in literature due to the paucity of cases described. Because of the similar histology of salivary gland LEC and non-keratinizing
RI PT
nasopharyngeal carcinoma, we opted for a chemotherapy regimen commonly used for NPC12. A series of 52 patients with pulmonary lymphoepithelioma showed that patients with stage III disease receiving chemotherapy had a better prognosis in terms of overall survival13. The most used
regimens
were
pemetrexed+cisplatin;gemcitabine+cisplatin,
paclitaxel/docetaxel,cisplatin/carboplatin,
SC
commonly
paclitaxel/docetaxel+cisplatin+5-FU,
and
M AN U
gencitabime+vinorelbine, in that order of frequency. However, a study of 69 patients with salivary LEC did not show a survival advantage when chemotherapy was added to the treatment protocol. This study is limited by the small number of patients (n=8) who received postoperative chemotherapy. Due to the rarity of the disease, the potential benefit described in the literature, the
TE D
possible multifocal disease in our patient, and the standard use of chemotherapy in nasopharyngeal carcinoma, chemotherapy was administered to our patient.
EP
In conclusion, we have shown that LEC may arise in the sublingual gland. Proper diagnosis is paramount, and treatment is based on the small number of previously published cases. We agree
AC C
on primary surgery with neck dissection, and adjuvant radiotherapy. Adjuvant chemotherapy may also be administered, although larger case series may be of interest to determine the optimal treatment as the increasing number of treatment modalities may result in an increased number of side effects, and affect quality of life.
ACCEPTED MANUSCRIPT
References 1.
Leiser Y, Peled M, Wolff A, El-Naaj IA. Lymphoepithelial carcinoma--review of the treatment modalities and report of a rare case in the sublingual gland. Journal of oral and
Maxillofacial Surgeons. 2014;72(4):823-828. 2.
RI PT
maxillofacial surgery : official journal of the American Association of Oral and
Ban X, Wu J, Mo Y, et al. Lymphoepithelial carcinoma of the salivary gland:
neuroradiology. 2014;35(9):1813-1819.
Manganaris A, Patakiouta F, Xirou P, Manganaris T. Lymphoepithelial carcinoma of the
M AN U
3.
SC
morphologic patterns and imaging features on CT and MRI. AJNR. American journal of
parotid gland: is an association with Epstein-Barr virus possible in non-endemic areas? International journal of oral and maxillofacial surgery. 2007;36(6):556-559. 4.
Rinaldo A, Shaha AR, Pellitteri PK, Bradley PJ, Ferlito A. Management of malignant
5.
TE D
sublingual salivary gland tumors. Oral oncology. 2004;40(1):2-5. Li F, Zhu G, Wang Y, Wang Y, Chen T, Ji Q. A clinical analysis of 37 cases with lymphoepithelial carcinoma of the major salivary gland treated by surgical resection and
6.
EP
postoperative radiotherapy: a single institution study. Medical oncology. 2014;31(5):957. Schneider M, Rizzardi C. Lymphoepithelial carcinoma of the parotid glands and its
AC C
relationship with benign lymphoepithelial lesions. Archives of pathology & laboratory medicine. 2008;132(2):278-282.
7.
Abdulla AK, Mian MY. Lymphoepithelial carcinoma of salivary glands. Head & neck.
1996;18(6):577-581.
8.
Kaidar-Person O, Kuten A, Billan S. Lymphoepithelioma-like carcinoma of the salivary gland: is radiotherapy alone adequate? Case reports in otolaryngology. 2011;2011:618650.
ACCEPTED MANUSCRIPT
9.
Wang CP, Chang YL, Ko JY, Lou PJ, Yeh CF, Sheen TS. Lymphoepithelial carcinoma versus large cell undifferentiated carcinoma of the major salivary glands. Cancer. 2004;101(9):2020-2027. Ma H, Lin Y, Wang L, et al. Primary lymphoepithelioma-like carcinoma of salivary
RI PT
10.
gland: sixty-nine cases with long-term follow-up. Head & neck. 2014;36(9):1305-1312. 11.
Dubey P, Ha CS, Ang KK, et al. Nonnasopharyngeal lymphoepithelioma of the head and
12.
SC
neck. Cancer. 1998;82(8):1556-1562.
Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in
M AN U
patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998;16(4):1310-1317.
Liang Y, Wang L, Zhu Y, et al. Primary pulmonary lymphoepithelioma-like carcinoma:
EP
TE D
fifty-two patients with long-term follow-up. Cancer. 2012;118(19):4748-4758.
AC C
13.
ACCEPTED MANUSCRIPT
Figure legends Figure 1 – T2 Magnetic resonance imaging in axial (a) and coronal (b) views showing the size of
sublingual space.
RI PT
the left sublingual lesion, its mass effect on the genioglossus muscle and the invasion of the
Figure 2–Hematoxylin eosin histological preparation showing diffuse lymphocytic and plasmocytic infiltration of the stroma
SC
Figure 3 - EBER in situ hybridization showing positivity for EBV
M AN U
Figure 4 – Intraoperative photographs showing the resected tumor (a), the floor of mouth defect
AC C
EP
TE D
(b), and the harvested facial artery musculomucosal flap from the left cheek (c)
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
S0278-2391(15)00490-5
DOI:
10.1016/j.joms.2015.04.030
Reference:
YJOMS 56795
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 18 March 2015 Revised Date:
15 April 2015
Accepted Date: 21 April 2015
Please cite this article as: Roy L, Moubayed SP, Ayad T, Lymphoepithelial carcinoma of the sublingual gland: Case Report and Review of Literature, Journal of Oral and Maxillofacial Surgery (2015), doi: 10.1016/j.joms.2015.04.030. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: Lymphoepithelial carcinoma of the sublingual
gland: Case Report and Review of
Literature
RI PT
Authors: Laurence Roy (Bsc, Medical Student), Sami P. Moubayed MD (Resident), Tareck Ayad MD, FRCSC (Professor)
SC
Institutions: Otolaryngology-Head and Neck Surgery Service, Université de Montréal Hospital
Corresponding author: Tareck Ayad MD Hôpital Notre-Dame
Montréal, Canada H2L4M1
EP
[email protected]
TE D
5415 boul. De l’Assomption
M AN U
Center and Maisonneuve-Rosemont Hospital, Montreal, Canada
AC C
Sources of support: none
Key words: lymphoepithelial carcinoma, sublingual gland, treatment
ACCEPTED MANUSCRIPT
Abstract Lymphoepithelial carcinoma represents only 0.4% of salivary gland neoplasms. Generally affecting the parotid gland, it has been only reported twice in the sublingual gland. Controversies
RI PT
concerning the treatment of lymphoepithelial carcinoma exist. Although the literature generally agrees that primary surgery and adjuvant radiotherapy is part of the treatment, the benefit of adjuvant chemotherapy is not well described. In this paper, we present the case of a 55 year-old
SC
man diagnosed with a lymphoepithelial carcinoma of the sublingual gland. The patient was admitted for progressive pain in the floor of mouth associated with trismus. A biopsy confirmed
M AN U
the diagnosis of lymphoepithelial carcinoma of the sublingual gland and magnetic resonance imaging showed multiple left lymphadenopathies. Surgery consisted of a radical neck dissection type III, surgical resection of the floor of mouth, and reconstruction with a left facial artery musculomucosal flap. The patient received adjuvant radiotherapy (60 Gy) and adjuvant
TE D
chemotherapy (three cycles of cisplatinum 100 mg/m2). The patient was disease-free at 36 months of follow-up. The evidence base for administering adjuvant chemotherapy in this
AC C
EP
situation is discussed.
ACCEPTED MANUSCRIPT
Introduction Lymphoepithelial carcinoma (LEC) is a rare undifferentiated carcinoma of the salivary glands, along with small-cell undifferentiated carcinoma, and large-cell undifferentiated carcinoma1. It is
RI PT
considered a high-grade malignancy. It represents 0.4% of salivary gland neoplasms, and predominates in the parotid gland in 83.5% of cases, and in the submandibular gland in 15% of cases. There are about 100 cases previously described in the literature1. This type of tumor has
SC
been described in the sublingual gland only twice before this report1,2. We present the first NorthAmerican case of LEC of the sublingual gland, successfully treated with surgery and adjuvant
M AN U
radiochemotherapy.
Report of a case
A 55 year-old male presented for a progressive pain in the floor of mouth over the past five
TE D
months, associated with trismus. His past medical history was significant for diabetes, hypertension, and dyslipidemia, with a family history of lymphoma and stomach cancer in his mother, and colorectal and bladder cancer in his father. He was a Caucasian, nonsmoker, an
EP
occasional drinker, and did not use drugs. On examination, a mobile, firm and non-tender 2 cm mass was palpable on the left sublingual area, without transgressing the midline, with normal
AC C
overlying mucosa. The nasopharynx was free of disease. No lymphadenopathy was noted. Magnetic resonance imaging revealed a 15 x 19 x 29 mm mass in the left sublingual gland, causing a mass effect on the genioglossus muscle and invading the sublingual space (Figure 1). Multiple left lymphadenopathies were found in zones IIA, IV, and VA, the largest one measuring 16 mm in zone IV. Distant metastatic workup with positron emission tomography/computed tomography was negative. Incisional biopsy revealed an undifferentiated lymphoepithelial
ACCEPTED MANUSCRIPT
carcinoma of the sublingual gland with lymphocytic and plasmocytic infiltration (Figure 2). EBER in situ hybridization was positive for EBV (Figure 3). Clinical staging was T2N2bM0.
RI PT
The patient was treated surgically with a left modified radical neck dissection type III (zones Iab, IIa-b, III, IV, V), elective tracheostomy, surgical resection of the floor of mouth, and reconstruction with a left facial artery musculomucosal (FAMM) flap (Figure 4). Pathology
SC
revealed negative margins, lymphovascular invasion, no perineural invasion, three positive lymph nodes out of 16 without extracapsular spread, and an independent 2x2 cm mass on the internal
M AN U
aspect of the mandible that is either a metastatic lymph node or a second focus of LEC. Definitive pathologic staging was T2N2bM0. Adjuvant radiation therapy was administered as 60 Gy to the primary tumor bed and neck basins using tomotherapy. The patient also received three cycles of cisplatinum 100 mg/m2. The patient tolerated treatment very well. He was free of
Discussion
TE D
disease after 36 months of postoperative follow-up.
EP
LEC represents only 0.4% of salivary gland neoplasms, with the parotid gland involved in the majority of cases and the submandibular gland in a minority of cases1. Only two cases in the
AC C
literature reports LEC in the sublingual gland1,2. The incidence of LEC is higher in Arctic native Inuits and Asian patients1. In these endemic areas, Epstein-Barr virus (EBV) is almost invariably associated with LEC and the relation between EBV and LEC has been well established1. However, the association between EBV and LEC is less frequent in Caucasian patients3, and Caucasians are less frequently affected by this type of salivary gland tumor1. The first paper describing a case of sublingual LEC originated from the Middle East and was treated with primary surgical resection, neck dissection, and adjuvant radiotherapy, without chemotherapy1.
ACCEPTED MANUSCRIPT
Radiation dose was not reported. The second article mentioning LEC in sublingual gland is a retrospective study where neither the case or the treatment are described2.
RI PT
Knowing that 80-90% of sublingual lesions are malignant tumors, any lesion of the sublingual gland should be considered malignant until proven otherwise4. Adenoid cystic carcinoma and mucoepidermoid carcinoma are the most common malignant tumors of the sublingual gland4.
SC
LEC only accounts for a minority of the sublingual neoplasms. Specific differential diagnoses of LEC are discussed later. Benign lesions of the sublingual gland include ranula, sialolithiasis, and
M AN U
sialadenits.
Investigation of the sublingual mass should include imaging and fine needle aspiration biopsy5. A cervical node involvement rate of up to 40% has been reported in LEC in major glands, and 20%
TE D
of patients develop distant metastases within three years of being treated6. Therefore, a standard metastsatic workup is warranted. However, no specific symptoms or images are distinctive of LEC. Definitive diagnosis is based on histopathology5. LEC is a tumor made of irregular islands
EP
of cohesive atypical epithelial cells surrounded by mixed reactive lymphoid cells7. Benign lymphoepithelial lesions, malignant lymphoma and metastatic undifferentiated carcinoma are part
AC C
of differential diagnosis of LEC1. Benign lymphoepithelial lesion and malignant lymphoma can be distinguished from LEC by microscopic examination and immunostaining for cytokeratin1,7. Ruling out metastatic undifferentiated nasopharyngeal carcinoma is necessary because the salivary glands are adjacent to the lymphatic drainage pathway of the tumors5. This is made by careful examination of the upper respiratory and digestive system1,7. Biopsies of any suspicious tissue from the nasopharynx must be performed1,7.
ACCEPTED MANUSCRIPT
Treatment of LEC is based on limited case series, most of the larger ones originating from Chinese centers due to the rarity of the disease in the Western world. The mainstay of treatment for salivary gland tumors is surgical resection, with adjuvant radiotherapy for unfavorable
RI PT
prognostic features (close or positive surgical margins, high-grade malignancy, perineural invasion, tumor infiltration of adjacent organs, recurrent disease, and locoregional metastasis8).Most series agree on primary surgical therapy with adjuvant radiation therapy, as
SC
LEC is considered a high-grade malignancy5,9,10, with 5-year survival ranging from 50 to 90%.Postoperative irradiation is delivered to the tumor bed and involved nodes at a dose of 60
M AN U
Gy and to the cervical lymph node drainage basins at a dose of 56 Gy9.
Authors generally agree on cervical lymphadenectomy for the clinically involved neck1. Elective neck dissection is not routinely performed by all authors5,9. A larger series showed 26.1% of
TE D
occult neck metastases in 23 patients undergoing elective neck dissection for clinically negative necks, although stage distribution was not available10. However, elective neck dissection in
EP
advanced stages resulted in a more favorable overall survival10.
In contrast to other high-grade salivary carcinomas, LEC is radiosensitive. Some authors suggest
AC C
radiotherapy alone as an appropriate therapy for salivary LEC8,11.A review by Dubey et al.11 showed that in 34 patients with LEC originating from the salivary glands, there were no statistically significant differences in 5-year local and regional control rates between patients treated with radiotherapy only and patients treated with surgical resection and adjuvant radiotherapy. For patients who received radiotherapy, the median radiation dose given to the primary tumor was 65 Gy. However, this series is limited by the small number of patients reported.
ACCEPTED MANUSCRIPT
Chemotherapy in treatment of LEC is not well described in literature due to the paucity of cases described. Because of the similar histology of salivary gland LEC and non-keratinizing
RI PT
nasopharyngeal carcinoma, we opted for a chemotherapy regimen commonly used for NPC12. A series of 52 patients with pulmonary lymphoepithelioma showed that patients with stage III disease receiving chemotherapy had a better prognosis in terms of overall survival13. The most used
regimens
were
pemetrexed+cisplatin;gemcitabine+cisplatin,
paclitaxel/docetaxel,cisplatin/carboplatin,
SC
commonly
paclitaxel/docetaxel+cisplatin+5-FU,
and
M AN U
gencitabime+vinorelbine, in that order of frequency. However, a study of 69 patients with salivary LEC did not show a survival advantage when chemotherapy was added to the treatment protocol. This study is limited by the small number of patients (n=8) who received postoperative chemotherapy. Due to the rarity of the disease, the potential benefit described in the literature, the
TE D
possible multifocal disease in our patient, and the standard use of chemotherapy in nasopharyngeal carcinoma, chemotherapy was administered to our patient.
EP
In conclusion, we have shown that LEC may arise in the sublingual gland. Proper diagnosis is paramount, and treatment is based on the small number of previously published cases. We agree
AC C
on primary surgery with neck dissection, and adjuvant radiotherapy. Adjuvant chemotherapy may also be administered, although larger case series may be of interest to determine the optimal treatment as the increasing number of treatment modalities may result in an increased number of side effects, and affect quality of life.
ACCEPTED MANUSCRIPT
References 1.
Leiser Y, Peled M, Wolff A, El-Naaj IA. Lymphoepithelial carcinoma--review of the treatment modalities and report of a rare case in the sublingual gland. Journal of oral and
Maxillofacial Surgeons. 2014;72(4):823-828. 2.
RI PT
maxillofacial surgery : official journal of the American Association of Oral and
Ban X, Wu J, Mo Y, et al. Lymphoepithelial carcinoma of the salivary gland:
neuroradiology. 2014;35(9):1813-1819.
Manganaris A, Patakiouta F, Xirou P, Manganaris T. Lymphoepithelial carcinoma of the
M AN U
3.
SC
morphologic patterns and imaging features on CT and MRI. AJNR. American journal of
parotid gland: is an association with Epstein-Barr virus possible in non-endemic areas? International journal of oral and maxillofacial surgery. 2007;36(6):556-559. 4.
Rinaldo A, Shaha AR, Pellitteri PK, Bradley PJ, Ferlito A. Management of malignant
5.
TE D
sublingual salivary gland tumors. Oral oncology. 2004;40(1):2-5. Li F, Zhu G, Wang Y, Wang Y, Chen T, Ji Q. A clinical analysis of 37 cases with lymphoepithelial carcinoma of the major salivary gland treated by surgical resection and
6.
EP
postoperative radiotherapy: a single institution study. Medical oncology. 2014;31(5):957. Schneider M, Rizzardi C. Lymphoepithelial carcinoma of the parotid glands and its
AC C
relationship with benign lymphoepithelial lesions. Archives of pathology & laboratory medicine. 2008;132(2):278-282.
7.
Abdulla AK, Mian MY. Lymphoepithelial carcinoma of salivary glands. Head & neck.
1996;18(6):577-581.
8.
Kaidar-Person O, Kuten A, Billan S. Lymphoepithelioma-like carcinoma of the salivary gland: is radiotherapy alone adequate? Case reports in otolaryngology. 2011;2011:618650.
ACCEPTED MANUSCRIPT
9.
Wang CP, Chang YL, Ko JY, Lou PJ, Yeh CF, Sheen TS. Lymphoepithelial carcinoma versus large cell undifferentiated carcinoma of the major salivary glands. Cancer. 2004;101(9):2020-2027. Ma H, Lin Y, Wang L, et al. Primary lymphoepithelioma-like carcinoma of salivary
RI PT
10.
gland: sixty-nine cases with long-term follow-up. Head & neck. 2014;36(9):1305-1312. 11.
Dubey P, Ha CS, Ang KK, et al. Nonnasopharyngeal lymphoepithelioma of the head and
12.
SC
neck. Cancer. 1998;82(8):1556-1562.
Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in
M AN U
patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998;16(4):1310-1317.
Liang Y, Wang L, Zhu Y, et al. Primary pulmonary lymphoepithelioma-like carcinoma:
EP
TE D
fifty-two patients with long-term follow-up. Cancer. 2012;118(19):4748-4758.
AC C
13.
ACCEPTED MANUSCRIPT
Figure legends Figure 1 – T2 Magnetic resonance imaging in axial (a) and coronal (b) views showing the size of
sublingual space.
RI PT
the left sublingual lesion, its mass effect on the genioglossus muscle and the invasion of the
Figure 2–Hematoxylin eosin histological preparation showing diffuse lymphocytic and plasmocytic infiltration of the stroma
SC
Figure 3 - EBER in situ hybridization showing positivity for EBV
M AN U
Figure 4 – Intraoperative photographs showing the resected tumor (a), the floor of mouth defect
AC C
EP
TE D
(b), and the harvested facial artery musculomucosal flap from the left cheek (c)
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
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