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Lymphoepithelial carcinoma in the submandibular salivary gland: A rare case report
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
Contents lists available at ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Case Report
Lymphoepithelial carcinoma in the submandibular salivary gland: A rare case report Shiori Kuwasakia, Shogo Kikutaa,*,1, Joe Iwanagaa,b, Jingo Kusukawaa a b
Dental and Oral Medical Center, Kurume University School of Medicine, Fukuoka, Japan Seattle Science Foundation, Seattle, WA 98122, USA
A R T I C LE I N FO
A B S T R A C T
Keywords: Lymphoepithelial carcinoma Submandibular gland Chemoradiotherapy Oral cavity
Lymphoepithelial carcinoma (LEC) is a rare tumor characterized by the undifferentiated or poorly differentiated malignant epithelial cells with marked reactive lymphoplasmacytic infiltrate. In the major salivary glands, LEC commonly occurs in the parotid gland and rarely seen in the submandibular gland. We present a case of submandibular gland LEC found in a 64 years-old Japanese male with Epstein-Barr virus infection. The patient underwent radical neck dissection and postoperative chemoradiotherapy. No evidence of recurrence has been detected during the 5-year follow-up.
1. Introduction
2. Case report
Lymphoepithelial carcinoma (LEC) is a rare subtype carcinoma. LEC has been described as an undifferentiated carcinoma with lymphoid stroma, malignant lymphoepithelial lesion, malignant lymphoepithelioma, and lymphoepithelial-like carcinoma in literature [1]. The World Health Organization (WHO) defined it as “a poorly differentiated squamous cell carcinoma or histologically undifferentiated carcinoma accompanied by a prominent reactive lymphoplasmacytic infiltrate, morphologically similar to nasopharyngeal carcinoma” (WHO, 2005). LEC predominantly occurs in the nasopharynx and various organs [1–3], and the Epstein-Barr virus (EBV) is often associated with the endemic areas [4]. In 1962, Hilderman et al. first reported the LEC in the salivary gland that occupies only 0.3% of all the salivary gland cancers. LEC occurs nearly 80 % in the parotid gland in the nonendemic area and the majority (approximately 75%) are in the Mongolian population [1,5,6]. Less than 15% are in Caucasian, mostly North Americans, and the remainder includes those who are Indian, Japanese, and African-American [1,6]. Previous studies reported 24–28.5 % of LECs in the salivary glands occurred in the submandibular glands [6–8]. We report a rare case of the LEC in the submandibular gland found in a 64 years-old Japanese male with EBV infection.
A 64-year-old Japanese male was referred to our department with a chief complaint of two painless masses in the right submandibular region which had been noticed for a month. His medical history was benign prostate hyperplasia and segmental gastric resection for gastric ulcer. The patient was an occasional drinker and had no habit of smoking or drug usage. Physical examination disclosed two non-tender masses in the right submandibular region. The anterior mass was 30 × 15 mm in size and soft, and the posterior one was 15 × 15 mm and slightly hard, respectively. Both masses were movable and no adhesion. Other lymphadenopathies such as swollen nodes were not noted. On intraoral examination, the secretions of saliva from the opening of the right submandibular duct was not observed. Laboratory data were within a normal range. No malignancy was detected by the fine needle aspiration (FNA) of the right submandibular gland. Computed tomography (CT) and magnetic resonance imaging (MRI) visualized a 25 × 26 mm mass with lobulated shape and partially ill-defined margin within the right submandibular gland (Fig. 1a). The rim-enhanced swollen lymph node was observed anterior to the submandibular gland (Fig. 1b). There was no evidence of the mass invasion in the mandible. The positron emission tomography and the contrast CT showed no evidence of the distant metastasis. All modality revealed no nasopharyngeal lesion. The clinical diagnosis was the malignant tumor of the right submandibular gland (T2N2bM0).
⁎
Corresponding author at: Dental and Oral Medical Center, Kurume University School of Medicine, Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan. E-mail address: [email protected] (S. Kikuta). 1 Equally contributed. https://doi.org/10.1016/j.ajoms.2019.10.012 Received 3 September 2019; Received in revised form 1 October 2019; Accepted 25 October 2019 2212-5558/ © 2019 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd All rights reserved.
Please cite this article as: Shiori Kuwasaki, et al., Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, https://doi.org/10.1016/j.ajoms.2019.10.012
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
S. Kuwasaki, et al.
Fig. 1. Axial contrast-enhanced CT showing a mass with a lobulated shape and partially ill-defined margin within the right submandibular gland (a; black triangles) and the rim-enhanced swelling lymph node anterior to the submandibular gland (b; white triangles).
Fig. 2. Histopathological specimens showing irregular tumor nests of atypical epithelial cells closely mixed with lymphocytes and plasma cells in the tumor of the submandibular gland (a) and metastatic lymph node (b) (Hematoxylin and Eosin stain, 400 × magnification). EBER in situ hybridization in the tumor of the submandibular gland showed strong expression of EBER signals in the neoplastic cells (c) (40 × magnification).
tumor and histologically similar to undifferentiated carcinoma of the nasopharynx. The most common site is the parotid gland and rarely seen in the submandibular gland. Compared to the undifferentiated carcinoma of the salivary gland, LEC shows a better prognosis because the lymphoid stroma limits the aggressiveness of LEC [1]. LEC develops with the EBV infection especially in the Eskimo, Chinese, and Japanese populations [5,9]. Pathological observation of the present case revealed the patient had been infected with EBV. FNA is a safe, simple, and primary diagnostic tool for detection of the salivary gland tumor. A recent study has reported that the sensitivity and specificity of FNA for salivary gland tumors are respectively 87.2% and 96.7% [8]. However, FNA occasionally aspirates only normal tissues that might have happened in the present case. In such as pleomorphic low-grade adenocarcinoma, carcinoma ex pleomorphic adenoma and cystic lesions, the accuracy is lower, and imaging examinations and intraoperative frozen sectioning is necessary for confirmation of diagnosis [8]. LEC in the submandibular gland may be indistinguishable from pleomorphic adenoma or Warthin’s tumor by imaging of the corresponding site itself when FNA aspirates normal tissues. Abdelkrim et al. [10] recommended that when clinical characteristics do not suggest malignancy, intraoperative frozen section analysis should be used to determine the appropriate treatment. The morphologic patterns of LEC are classified into three types by the margin and shape of the lesions in CT and MRI images; round or
An intraoperative excisional biopsy for the swollen lymph node showed malignancy, and right radical neck dissection with the resection of the submandibular gland was performed. Histopathological examination of the resected specimen revealed irregular tumor nests of atypical epithelial cells closely intermingled with lymphocytes and plasma cells in the tumor of the submandibular gland and metastatic lymph node. Immunohistochemically, the tumor cells were positive for P40 and p63, weakly positive for AE1/AE2, and negative for α-SMA. In situ hybridization for EBV coded RNA (EBER) returned positive results for EBV showed strong expression of EBER signals in the neoplastic cells (Fig. 2). The resected specimen showed no lymphovascular invasion and perineural invasion. The metastatic lesion was detected without extracapsular spread in 3 of 34 detected lymph nodes in level IIb. The metastatic lymph nodes showed the same histological characteristics as the mass lesion within the submandibular gland. Pathological diagnosis was the lymphoepithelial carcinoma (pT2N2bM0). Postoperatively, the patient received radiotherapy at 60 Gy to the right neck region including the primary site and three cycles of low dose 5-fluorouracil/ cisplatin therapy. No evidence of recurrence has been observed for 5 years. 3. Discussion Lymphoepithelial carcinoma (LEC) of salivary glands is a very rare 2
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
S. Kuwasaki, et al.
References
oval mass with a well-defined margin (type 1), lobulated or plaque-like shape mass with a partially or ill-defined margin (type 2), and irregularshaped mass with an ill-defined margin and diffuse invasive growth (type 3) [7]. Since the present case showed the lobulated shape with partially ill-defined margin, it could have been diagnosed as type 2. In general, initial treatment of LEC of salivary glands is surgical resection and followed by adjuvant radiotherapy. In contrast to other high-grade salivary carcinomas, LEC is more radiosensitive. Chemotherapy for LEC has not been well described in the literature due to a small number of reported cases. In the previous case report, a chemotherapy regimen for the nasopharyngeal cancer was applied for the treatment of LEC of salivary gland because of the similar histological characteristics of LEC of salivary glands and nonkeratinizing nasopharyngeal carcinoma [11]. In the present case, postoperative chemoradiotherapy has induced no recurrence. The present case had used low dose 5-fluorouracil/cisplatin therapy with 60 Gy radiotherapy, as a result, no recurrence has recognized. Further reports would be needed to build an optimal treatment for LEC.
[1] Schneider M, Rizzardi C. Lymphoepithelial carcinoma of the parotid glands and its relationship with benign lymphoepithelial lesions. Arch Pathol Lab Med 2008;132:278–82. [2] Hsiung CY, Huang CC, Wang CJ, Huang EY, Huang HY. Lymphoepithelioma-like carcinoma of salivary glands: treatment results and failure patterns. Br J Radiol 2006;79:52–5. [3] Kuo T, Hsueh C. Lymphoepithelioma-like salivary gland carcinoma in Taiwan: a clinicopathological study of nine cases demonstrating a strong association with Epstein-Barr virus. Histopathology 1997;31:75–82. [4] Tsai CC, Chen CL, Hsu HC. Expression of Epstein-Barr virus in carcinomas of major salivary glands: a strong association with lymphoepithelioma-like carcinoma. Hum Pathol 1996;27:258–62. [5] Hilderman WC, Gordon JS, Large HLJ, Carroll CFJ. Malignant lymphoepithelial lesion with carcinomatous component apparently arising in parotid gland. A malignant counterpart of benign lymphoepithelial lesion? Cancer 1962;15:606–10. [6] Ma H, Lin Y, Wang L, Rao H, Xu G, He Y, et al. Primary lymphoepithelioma-like carcinoma of salivary gland: sixty-nine cases with long-term follow-up. Head Neck 2014;36:1305–12. [7] Ban X, Wu J, Mo Y, Yang Q, Liu X, Xie C, et al. Lymphoepithelial carcinoma of the salivary gland: morphologic patterns and imaging features on CT and MRI. AJNR Am J Neuroradiol 2014;35:1813–9. [8] Wang YL, Zhu YX, Chen TZ, Weng Y, Sun GH, Zhang L, et al. Clinicopathologic study of 1176 salivary gland tumors in a Chinese population: experience of one cancer center 1997-2007. Acta Otolaryngol 2012;132:879–86. [9] Sheen TS, Tsai CC, Ko JY, Chang YL, Hsu MM. Undifferentiated carcinoma of the major salivary glands. Cancer 1997;80:357–63. [10] Abdelkrim SB, Trabelsi A, Hammedi F, Omezzine M, Rammeh S, Abdelkader AB, et al. Primary lymphoepithelial carcinoma of the parotid gland in a North African woman. Rare Tumors 2009;1:22–4. [11] Roy L, Moubayed SP, Ayad T. Lymphoepithelial carcinoma of the sublingual gland: case report and review of the literature. J Oral Maxillofac Surg 2015;73:1878.e1–5.
Ethical approval None. Declaration of Competing Interest None declared.
3
Contents lists available at ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Case Report
Lymphoepithelial carcinoma in the submandibular salivary gland: A rare case report Shiori Kuwasakia, Shogo Kikutaa,*,1, Joe Iwanagaa,b, Jingo Kusukawaa a b
Dental and Oral Medical Center, Kurume University School of Medicine, Fukuoka, Japan Seattle Science Foundation, Seattle, WA 98122, USA
A R T I C LE I N FO
A B S T R A C T
Keywords: Lymphoepithelial carcinoma Submandibular gland Chemoradiotherapy Oral cavity
Lymphoepithelial carcinoma (LEC) is a rare tumor characterized by the undifferentiated or poorly differentiated malignant epithelial cells with marked reactive lymphoplasmacytic infiltrate. In the major salivary glands, LEC commonly occurs in the parotid gland and rarely seen in the submandibular gland. We present a case of submandibular gland LEC found in a 64 years-old Japanese male with Epstein-Barr virus infection. The patient underwent radical neck dissection and postoperative chemoradiotherapy. No evidence of recurrence has been detected during the 5-year follow-up.
1. Introduction
2. Case report
Lymphoepithelial carcinoma (LEC) is a rare subtype carcinoma. LEC has been described as an undifferentiated carcinoma with lymphoid stroma, malignant lymphoepithelial lesion, malignant lymphoepithelioma, and lymphoepithelial-like carcinoma in literature [1]. The World Health Organization (WHO) defined it as “a poorly differentiated squamous cell carcinoma or histologically undifferentiated carcinoma accompanied by a prominent reactive lymphoplasmacytic infiltrate, morphologically similar to nasopharyngeal carcinoma” (WHO, 2005). LEC predominantly occurs in the nasopharynx and various organs [1–3], and the Epstein-Barr virus (EBV) is often associated with the endemic areas [4]. In 1962, Hilderman et al. first reported the LEC in the salivary gland that occupies only 0.3% of all the salivary gland cancers. LEC occurs nearly 80 % in the parotid gland in the nonendemic area and the majority (approximately 75%) are in the Mongolian population [1,5,6]. Less than 15% are in Caucasian, mostly North Americans, and the remainder includes those who are Indian, Japanese, and African-American [1,6]. Previous studies reported 24–28.5 % of LECs in the salivary glands occurred in the submandibular glands [6–8]. We report a rare case of the LEC in the submandibular gland found in a 64 years-old Japanese male with EBV infection.
A 64-year-old Japanese male was referred to our department with a chief complaint of two painless masses in the right submandibular region which had been noticed for a month. His medical history was benign prostate hyperplasia and segmental gastric resection for gastric ulcer. The patient was an occasional drinker and had no habit of smoking or drug usage. Physical examination disclosed two non-tender masses in the right submandibular region. The anterior mass was 30 × 15 mm in size and soft, and the posterior one was 15 × 15 mm and slightly hard, respectively. Both masses were movable and no adhesion. Other lymphadenopathies such as swollen nodes were not noted. On intraoral examination, the secretions of saliva from the opening of the right submandibular duct was not observed. Laboratory data were within a normal range. No malignancy was detected by the fine needle aspiration (FNA) of the right submandibular gland. Computed tomography (CT) and magnetic resonance imaging (MRI) visualized a 25 × 26 mm mass with lobulated shape and partially ill-defined margin within the right submandibular gland (Fig. 1a). The rim-enhanced swollen lymph node was observed anterior to the submandibular gland (Fig. 1b). There was no evidence of the mass invasion in the mandible. The positron emission tomography and the contrast CT showed no evidence of the distant metastasis. All modality revealed no nasopharyngeal lesion. The clinical diagnosis was the malignant tumor of the right submandibular gland (T2N2bM0).
⁎
Corresponding author at: Dental and Oral Medical Center, Kurume University School of Medicine, Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan. E-mail address: [email protected] (S. Kikuta). 1 Equally contributed. https://doi.org/10.1016/j.ajoms.2019.10.012 Received 3 September 2019; Received in revised form 1 October 2019; Accepted 25 October 2019 2212-5558/ © 2019 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd All rights reserved.
Please cite this article as: Shiori Kuwasaki, et al., Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, https://doi.org/10.1016/j.ajoms.2019.10.012
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
S. Kuwasaki, et al.
Fig. 1. Axial contrast-enhanced CT showing a mass with a lobulated shape and partially ill-defined margin within the right submandibular gland (a; black triangles) and the rim-enhanced swelling lymph node anterior to the submandibular gland (b; white triangles).
Fig. 2. Histopathological specimens showing irregular tumor nests of atypical epithelial cells closely mixed with lymphocytes and plasma cells in the tumor of the submandibular gland (a) and metastatic lymph node (b) (Hematoxylin and Eosin stain, 400 × magnification). EBER in situ hybridization in the tumor of the submandibular gland showed strong expression of EBER signals in the neoplastic cells (c) (40 × magnification).
tumor and histologically similar to undifferentiated carcinoma of the nasopharynx. The most common site is the parotid gland and rarely seen in the submandibular gland. Compared to the undifferentiated carcinoma of the salivary gland, LEC shows a better prognosis because the lymphoid stroma limits the aggressiveness of LEC [1]. LEC develops with the EBV infection especially in the Eskimo, Chinese, and Japanese populations [5,9]. Pathological observation of the present case revealed the patient had been infected with EBV. FNA is a safe, simple, and primary diagnostic tool for detection of the salivary gland tumor. A recent study has reported that the sensitivity and specificity of FNA for salivary gland tumors are respectively 87.2% and 96.7% [8]. However, FNA occasionally aspirates only normal tissues that might have happened in the present case. In such as pleomorphic low-grade adenocarcinoma, carcinoma ex pleomorphic adenoma and cystic lesions, the accuracy is lower, and imaging examinations and intraoperative frozen sectioning is necessary for confirmation of diagnosis [8]. LEC in the submandibular gland may be indistinguishable from pleomorphic adenoma or Warthin’s tumor by imaging of the corresponding site itself when FNA aspirates normal tissues. Abdelkrim et al. [10] recommended that when clinical characteristics do not suggest malignancy, intraoperative frozen section analysis should be used to determine the appropriate treatment. The morphologic patterns of LEC are classified into three types by the margin and shape of the lesions in CT and MRI images; round or
An intraoperative excisional biopsy for the swollen lymph node showed malignancy, and right radical neck dissection with the resection of the submandibular gland was performed. Histopathological examination of the resected specimen revealed irregular tumor nests of atypical epithelial cells closely intermingled with lymphocytes and plasma cells in the tumor of the submandibular gland and metastatic lymph node. Immunohistochemically, the tumor cells were positive for P40 and p63, weakly positive for AE1/AE2, and negative for α-SMA. In situ hybridization for EBV coded RNA (EBER) returned positive results for EBV showed strong expression of EBER signals in the neoplastic cells (Fig. 2). The resected specimen showed no lymphovascular invasion and perineural invasion. The metastatic lesion was detected without extracapsular spread in 3 of 34 detected lymph nodes in level IIb. The metastatic lymph nodes showed the same histological characteristics as the mass lesion within the submandibular gland. Pathological diagnosis was the lymphoepithelial carcinoma (pT2N2bM0). Postoperatively, the patient received radiotherapy at 60 Gy to the right neck region including the primary site and three cycles of low dose 5-fluorouracil/ cisplatin therapy. No evidence of recurrence has been observed for 5 years. 3. Discussion Lymphoepithelial carcinoma (LEC) of salivary glands is a very rare 2
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
S. Kuwasaki, et al.
References
oval mass with a well-defined margin (type 1), lobulated or plaque-like shape mass with a partially or ill-defined margin (type 2), and irregularshaped mass with an ill-defined margin and diffuse invasive growth (type 3) [7]. Since the present case showed the lobulated shape with partially ill-defined margin, it could have been diagnosed as type 2. In general, initial treatment of LEC of salivary glands is surgical resection and followed by adjuvant radiotherapy. In contrast to other high-grade salivary carcinomas, LEC is more radiosensitive. Chemotherapy for LEC has not been well described in the literature due to a small number of reported cases. In the previous case report, a chemotherapy regimen for the nasopharyngeal cancer was applied for the treatment of LEC of salivary gland because of the similar histological characteristics of LEC of salivary glands and nonkeratinizing nasopharyngeal carcinoma [11]. In the present case, postoperative chemoradiotherapy has induced no recurrence. The present case had used low dose 5-fluorouracil/cisplatin therapy with 60 Gy radiotherapy, as a result, no recurrence has recognized. Further reports would be needed to build an optimal treatment for LEC.
[1] Schneider M, Rizzardi C. Lymphoepithelial carcinoma of the parotid glands and its relationship with benign lymphoepithelial lesions. Arch Pathol Lab Med 2008;132:278–82. [2] Hsiung CY, Huang CC, Wang CJ, Huang EY, Huang HY. Lymphoepithelioma-like carcinoma of salivary glands: treatment results and failure patterns. Br J Radiol 2006;79:52–5. [3] Kuo T, Hsueh C. Lymphoepithelioma-like salivary gland carcinoma in Taiwan: a clinicopathological study of nine cases demonstrating a strong association with Epstein-Barr virus. Histopathology 1997;31:75–82. [4] Tsai CC, Chen CL, Hsu HC. Expression of Epstein-Barr virus in carcinomas of major salivary glands: a strong association with lymphoepithelioma-like carcinoma. Hum Pathol 1996;27:258–62. [5] Hilderman WC, Gordon JS, Large HLJ, Carroll CFJ. Malignant lymphoepithelial lesion with carcinomatous component apparently arising in parotid gland. A malignant counterpart of benign lymphoepithelial lesion? Cancer 1962;15:606–10. [6] Ma H, Lin Y, Wang L, Rao H, Xu G, He Y, et al. Primary lymphoepithelioma-like carcinoma of salivary gland: sixty-nine cases with long-term follow-up. Head Neck 2014;36:1305–12. [7] Ban X, Wu J, Mo Y, Yang Q, Liu X, Xie C, et al. Lymphoepithelial carcinoma of the salivary gland: morphologic patterns and imaging features on CT and MRI. AJNR Am J Neuroradiol 2014;35:1813–9. [8] Wang YL, Zhu YX, Chen TZ, Weng Y, Sun GH, Zhang L, et al. Clinicopathologic study of 1176 salivary gland tumors in a Chinese population: experience of one cancer center 1997-2007. Acta Otolaryngol 2012;132:879–86. [9] Sheen TS, Tsai CC, Ko JY, Chang YL, Hsu MM. Undifferentiated carcinoma of the major salivary glands. Cancer 1997;80:357–63. [10] Abdelkrim SB, Trabelsi A, Hammedi F, Omezzine M, Rammeh S, Abdelkader AB, et al. Primary lymphoepithelial carcinoma of the parotid gland in a North African woman. Rare Tumors 2009;1:22–4. [11] Roy L, Moubayed SP, Ayad T. Lymphoepithelial carcinoma of the sublingual gland: case report and review of the literature. J Oral Maxillofac Surg 2015;73:1878.e1–5.
Ethical approval None. Declaration of Competing Interest None declared.
3