Expression of epstein-barr virus in carcinomas of major salivary glands: A strong association with lymphoepithelioma-like carcinoma

doi:10.1016/S0046-8177(96)90066-0

Human Pathology

Volume 27, Issue 3, March 1996, Pages 258-262

https://doi.org/10.1016/S0046-8177(96)90066-0 Get rights and content

Abstract

To elucidate the role of Epstein-Barr virus (EBV) in salivary gland carcinomas, 56 cases of carcinomas of major salivary glands were investigated. These included 14 mucoepidermoid carcinomas, 13 adenoid cystic carcinomas, seven malignant mixed tumors, four adenocarcinomas, four salivary duct carcinomas, two acinic cell carcinomas, two undifferentiated carcinomas without lymphoid stroma, seven lymphoepithelioma-like carcinomas (LELCs), two squamous cell carcinomas, and one small cell carcinoma. EBV transcripts were examined by in situ hybridization using digoxigenin-labeled oligonucleotide antisense probe for EBV-encoded RNA 1 (EBER1) on formalin-fixed paraffin-embedded tissue sections. EBER1 was detected in the malignant epithelial cells in all seven cases of LELC, but not in any of the other carcinomas and the neighboring normal salivary gland tissue. Because all the EBV-negative cases showed satisfactory labeling with the poly d(T) probe, the negative reaction with EBER1 was unlikely to be caused by poor RNA preservation in the tissues. The seven cases of LELC, which were histologically indistinguishable from undifferentiated nasopharyngeal carcinoma (NPC), had a disease-free 4-year survival rate of 85.7%. The results suggest that LELC of the salivary gland in Taiwanese Chinese may share similar EBVrelated pathogenesis with that of NPC.

References (31)

DG Morgan et al.
Site of Epstein-Barr virus replication in the oropharynx
Lancet
(1979)
SJ Hamilton-Dutoit et al.
Undifferentiated carcinoma of the salivary gland in Greenlandic Eskimos: Demonstration of Epstein-Barr virus DNA by in situ nucleic acid hybridization
Hum Pathol
(1991)
TC Wu et al.
Study of Epstein-Barr virus early RNA 1 (EBER1) expression by in situ hybridization in thymic epithelial tumors of Chinese patients in Taiwan
Hum Pathol
(1993)
LM Weiss et al.
Detection and localization of Epstein-Barr virus genomes in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma
Blood
(1992)
MR Spitz et al.
Major salivary gland carcinoma: Descriptive epidemiology and survival of 498 patients
Arch Otolaryngol
(1984)
GL Ellis et al.
Surgical Pathology of the Salivary Glands
H zur Hansen et al.
EBV DNA in biopsies of Burkitt's tumors and anaplastic carcinomas of the nasopharynx
Nature
(1970)
AP Lanier et al.
Association of Epstein-Barr virus with nasopharyngeal carcinoma in Alaskan native patients: Serum antibodies and tissue EBNA and DNA
Int J Cancer
(1981)
AK Saemundsen et al.
Epstein-Barr virus in nasopharyngeal and salivary gland carcinomas of Greenland Eskimos
Br J Cancer
(1982)
CL Chen et al.
Detection of Epstein-Barr virus genome in nasopharyngeal carcinoma by in situ DNA hybridization
Intervirology
(1993)

H Wolf et al.

Persistence of Epstein-Barr virus in the parotid gland

J Virol

(1984)

MM Hsu et al.

Epstein-Barr virus harboring in the parotid gland without tumor association

J Formos Med Assoc

(1994)

D Saw et al.

Malignant lymphoepithelial lesion of the salivary gland

Hum Pathol

(1986)

JD Bosch et al.

The malignant lymphoepithelial lesion of the salivary glands

J Otolaryngol

(1988)

S Leyvraz et al.

Association of Epstein-Barr virus with thymic carcinoma

N Engl J Med

(1985)

Cited by (107)

Lymphoepithelial carcinoma of the submandibular gland in a Japanese woman: A case report
2021, Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
Lymphoepithelial carcinoma (LEC) of the submandibular gland is a very rare neoplasm that constitutes only 0.4 % of the salivary gland neoplasms, mainly involving the parotid glands, and is well known to have a racial prevalence in Southwest Asia, southern China, Africa, and the Arctic Circle. This report describes the case of a 49-year-old Japanese woman who was diagnosed with an LEC of the right submandibular gland. The patient presented with a painless, gradually enlarging mass in the right submandibular gland for 2 years. Computed tomography scanning showed a 20 × 16 mm, slightly enhanced solid mass in the right submandibular gland; magnetic resonance imaging revealed an isointense and hyperintense mass in T1- and T2-weighted images. Fine-needle aspiration cytology revealed a few small salivary gland cells and acidophilic cells against a background of lymphocytes, suggesting Warthin tumor or chronic sialadenitis. The right submandibular gland was resected, and intraoperative frozen section analysis suggested a diagnosis of LEC of the submandibular gland. Histopathological findings from the resected submandibular gland were consistent with a diagnosis of LEC, and a definitive pathologic staging of T3N0M0. Postoperative adjuvant radiation therapy was administered, and the patient was disease free at the 4-year follow-up.
Lymphoepithelial Carcinoma of Salivary Glands
2021, Surgical Pathology Clinics
Citation Excerpt :
It may be that therapy was excluded from the article, data was aggregated, or the treatment and outcome were not the end points of the evaluation. Suffice it to say that large clinicopathologic series included radiation in the management,4,6,12,20,21,24,26,32,37,38,49,60,74,82,88 and it is well known that LEC is highly radiosensitive with high rates of locoregional tumor control. However, additional study is needed to establish the appropriate radiation field and dose for LECSG.35
Lymphoepithelial carcinoma in the submandibular salivary gland: A rare case report
2020, Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
Citation Excerpt :
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.
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.
Primary parotid lymphoepithelial carcinoma: A case report and literature review of a rare pathological entity
2020, International Journal of Surgery Case Reports
Citation Excerpt :
However, LEC has been reported to arise primarily in various organs such as lungs, stomach, breast, ovaries, uterus, renal pelvis, bladder and skin [15,20]. In addition to the nasopharynx, within the head and neck region, LECs can arise in salivary glands, tonsils, thymus, larynx, and soft palate [15,20]. Primary LEC of the salivary gland, first described by Hilderman et al. in 1962, is very rare and accounts for 0.4% of all malignant tumors of the salivary glands [1,2].
Lymphoepithelial carcinoma (LEC) of the salivary glands is a rare, but distinct, poorly-differentiated neoplasm that resembles undifferentiated nasopharyngeal carcinomas (NPC). Among primary salivary gland LECs, they most commonly arise in the parotid gland. These lesions have a noticeable racial predilection, mostly occurring in Asians and Arctic region native populations. They are strongly associated with Epstein-Barr virus (EBV), and are more common in EBV-endemic areas. The most common presenting symptoms of primary parotid LEC are parotid mass development and cervical lymphadenopathy. We report an unusual case of EBV-negative LEC in a Canadian Caucasian woman.
A 40-year-old female from Atlantic Canada presented with a rapidly enlarging preauricular mass and cervical lymphadenopathy. Preoperative diagnostics via radiology and fine needle aspiration alluded to an ambiguous primary parotid malignancy. She underwent a total parotidectomy with facial nerve sacrifice and ipsilateral selective neck dissection. The facial nerve was reconstructed with a lateral antecubital nerve graft. Pathology came back positive for LEC, and she began adjuvant radiotherapy. At her 1-year follow up, she was disease-free and obtained a House-Brackmann facial nerve function grade of 3.
The case report highlights the importance of having a high index of suspicion and the need for interdisciplinary collaboration in reaching the diagnosis of primary parotid LEC. LEC can afflict patients of any ethnicity in non-EBV endemic areas and should therefore be considered in all patients with a painless parotid mass regardless of ethnicity. Further studies are required to elucidate the oncogenic role of EBV in these cancers.
Clinical pathologic conference case: An older woman with a painless, deep, and indurated ulcer on her mandibular alveolar mucosa
2020, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Lymphoepithelial carcinoma in parotid gland related to EBV infection: A case report
2018, Auris Nasus Larynx
Lymphoepithelial carcinoma commonly occurs at the nasopharynx and rarely occurs at other sites in the head and neck region. It is well known to occur at limited patients of local area as Asia or Arctic Circle. Related to this point, it is pointed out that this tumor has strong relation with Epstein–Barr Virus (EBV) infection.
In this time, we experienced to treat lymphoepithelial carcinoma with metastatic cervical lymph nodes occurring at parotid gland. The morbidity ratio of this tumor is less than one percent of all parotid gland tumors. Moreover, we proved the infection of EBV to tumor cell by in situ hybridization (ISH).
Incidentally, because it is considered that this tumor has well sensitivity against irradiation or anti-tumor drugs, prognosis of this tumor is better than that of other head and neck tumors with different pathological type. Actually, we tried to perform chemotherapy twice in (Nedaplatin (CDGP) 60 mg/m² × day 2 and 5-FU 600 mg/m² × day 5) and to irradiate about 70 Gy dose against parotid gland and cervical lymph nodes. It could not find local recurrence or metastasis as of now after five years from treatment.

View all citing articles on Scopus

^☆: Supported by a grant from the National Science Council of the Republic of China (grant No. NSC 83-0412-B002-218).

View full text

Original contributionExpression of epstein-barr virus in carcinomas of major salivary glands: A strong association with lymphoepithelioma-like carcinoma☆

Abstract

Lancet

Hum Pathol

Hum Pathol

Blood

Major salivary gland carcinoma: Descriptive epidemiology and survival of 498 patients

Arch Otolaryngol

Surgical Pathology of the Salivary Glands

EBV DNA in biopsies of Burkitt's tumors and anaplastic carcinomas of the nasopharynx

Nature

Association of Epstein-Barr virus with nasopharyngeal carcinoma in Alaskan native patients: Serum antibodies and tissue EBNA and DNA

Int J Cancer

Epstein-Barr virus in nasopharyngeal and salivary gland carcinomas of Greenland Eskimos

Br J Cancer

Detection of Epstein-Barr virus genome in nasopharyngeal carcinoma by in situ DNA hybridization

Intervirology

Persistence of Epstein-Barr virus in the parotid gland

J Virol

Epstein-Barr virus harboring in the parotid gland without tumor association

J Formos Med Assoc

Malignant lymphoepithelial lesion of the salivary gland

Hum Pathol

The malignant lymphoepithelial lesion of the salivary glands

J Otolaryngol

Association of Epstein-Barr virus with thymic carcinoma

N Engl J Med

Original contribution
Expression of epstein-barr virus in carcinomas of major salivary glands: A strong association with lymphoepithelioma-like carcinoma☆