Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 1801
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size

  Table of Contents    
Year : 2016  |  Volume : 59  |  Issue : 4  |  Page : 521-523
An atypical nonsebaceous lymphadenoma with diffuse lymphoepithelial differentiation

1 Department of Pathology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
2 Department of Radiology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea

Click here for correspondence address and email

Date of Web Publication10-Oct-2016


Nonsebaceous lymphadenoma is an uncommon salivary gland tumor. It consists of lymphoid and epithelial components that lack sebaceous differentiation. Herein, we present a 44-year-old woman with left a submandibular gland tumor. The tumor is well-circumscribed and solid without ductal or cystic formation. The epithelial cells intermingle with lymphoplasma cells. The epithelial cells show moderate cytologic atypia and a few mitoses with no viral infection. Histologically, the tumor had features of nonsebaceous lymphadenoma with unusual findings of nuclear atypia and marked lymphoepithelial differentiation. Atypical nonsebaceous lymphadenoma with diffuse lymphoepithelial differentiation is rare and important to recognize to avoid misdiagnosis.

Keywords: Lymphadenoma, lymphoepithelial lesion, salivary gland

How to cite this article:
Yeo MK, Kim DM, Kim JM. An atypical nonsebaceous lymphadenoma with diffuse lymphoepithelial differentiation. Indian J Pathol Microbiol 2016;59:521-3

How to cite this URL:
Yeo MK, Kim DM, Kim JM. An atypical nonsebaceous lymphadenoma with diffuse lymphoepithelial differentiation. Indian J Pathol Microbiol [serial online] 2016 [cited 2020 Dec 1];59:521-3. Available from: https://www.ijpmonline.org/text.asp?2016/59/4/521/191810

   Introduction Top

Lymphadenoma is a rare benign salivary gland tumor that is classified as sebaceous or nonsebaceous lymphadenoma by the World Health Organization in 2005. [1] Nonsebaceous lymphadenoma consists of epithelial components that lack sebaceous differentiation intermingled with lymphoid tissue, displaying a wide range of histological differences. Here, we present a case of atypical nonsebaceous lymphadenoma of the submandibular gland with diffuse lymphoepithelial differentiation.

   Case Report Top

A 44-year-old woman presented with a 3-month history of an enlarged, movable, and asymptomatic neck mass. She had no medical history of Sjögren disease, autoimmune disease, or infection. On computed tomography, the left submandibular gland was mildly enlarged and showed an ill-margined solid mass, measuring 12 mm 11 mm in size in the lower portion [Figure 1]a. The mass had similar attenuation in precontrast images and slightly less enhancement in postcontrast images [Figure 1]b and c. The right submandibular gland and neck lymph nodes were unremarkable. Fine needle aspiration cytology (FNAC) of the left submandibular gland mass showed scattered large clusters of epithelial cells, displaying round to oval nuclei that were associated with a fibrillary matrix. The epithelial cells were intermixed with numerous lymphocytes. The lymphocytes were also dispersed in the background [Figure 2]a. The epithelial cells had anisocytic vesicular nuclei with prominent nucleoli [Figure 2]b. The FNAC was diagnosed as "atypical epithelial cell clusters with scattered lymphocytes, which favors malignancy." She underwent left total submandibulectomy. Grossly, the specimen harbored an 11 mm 11 mm solid, well-marginated, tan colored mass. Histologically, the mass was well-circumscribed with smooth pushing margins [Figure 3]a. The tumor exhibited loose irregular anastomosing epithelial nests with the lymphoid cells without a tubular or cystic structure [Figure 3]b. The epithelial components were difficult to appreciate due to obscuring from dense lymphoplasma cells, forming an extensive lymphoepithelial lesion [Figure 3]c. The epithelial cells had round, vesicular nuclei with distinct, small nucleoli accompanied by scattered large pleomorphic epithelial cells [Figure 3]d. Mitosis was identified in 1-2/10 high power fields.
Figure 1: Neck computed tomography. (a) The left submandibular gland was slightly enlarged. (b) The lesion was iso - dense in precontrast images and less - enhanced in postcontrast images. (c) The lesion measured 12 mm × 11 mm in size and located in the lower portion of the left submandibular gland

Click here to view
Figure 2: Fine needle aspiration cytology. (a) Three - dimensional cellular fragments of epithelial cells were intermixed with abundant lymphoid cells in a fibrillary matrix. (b) Epithelial cells had pleomorphic nuclei with coarse chromatin and prominent nucleoli

Click here to view
Figure 3: A Histologic findings. (a) The left submandibular gland showed a well - circumscribed mass. (b) The tumour had loose epithelial nests admixed with dense lymphoplasma cells. (c) Lymphoplasma cells obscured epithelial cells, forming a lymphoepithelial lesion. (d) Epithelial component showed scattered atypical cells

Click here to view

Pan-cytokeratin and cytokeratin-7 strongly highlighted epithelial islands, indicating the presence of a diffuse lymphoepithelial lesion [Figure 4]a. Cytokeratin-19 was negative. Smooth muscle actin and calponin highlighted myoepithelial cells of epithelial nests [Figure 4]b. Cytokeratin-5/6 and cytokeratin-8/18 were positive for the basal layer of epithelial cells [Figure 4]c. P63 demonstrated some scattered epithelial cells [Figure 4]d. Intraepithelial lymphocytes were mixed positive for CD3 and CD20 and showing reactive B- and T-cell. Viral studies for Epstein-Barr virus (EBV) and human papillomavirus in situ hybridization and immunohistochemical staining for human herpes virus-8, herpes simplex virus-1, adenovirus, SV40T, and cytomegalovirus were all negative. P16 was focally positive for epithelial cells. A proliferation index (Ki-67) had an occasional expression (9%) in the epithelial cells. During the 36-month of follow-up, the patient lacked recurrence and metastasis.
Figure 4: Immunohistochemical staining properties (×400). (a) Cytokeratin - 7 highlighted lymphoepithelial lesion. (b) Smooth muscle actin and (c) cytokeratin 5/6 revealed myoepithelial cells of epithelial nests. (d) P63 demonstrated some scattered basal cells

Click here to view

   Discussion Top

Nonsebaceous lymphadenoma is defined as a tumor consisting of variable shaped nonsebaceous epithelia in a background of lymphocytes. [1] The epithelial component frequently has cystically dilated ducts surrounded by basement membrane-like materials. The lymphoid component commonly forms lymphoid follicles. A lack of familiarity with nonsebaceous lymphadenoma and a wide spectrum of epithelial differentiation make confusion with other benign and malignant tumor entities. In the present case of nonsebaceous lymphadenoma, there is diffuse lymphoepithelial differentiation and cytologic atypia.

The lymphoid component of nonsebaceous lymphadenoma had made some authors to suggest that the pathogenic development of the tumor originated from intra- or peri-salivary lymph nodes. [2] However, many authors considered the lymphoid component as tumor-associated reactive lymphoid tissue. [3],[4],[5] In the present case, the architectural arrangement of the hilus, nodal capsule, and follicular structure of lymph node was not identified. Dense reactive lymphoid cells diffusely infiltrated and surrounded epithelial nests and formed lymphoepithlial lesion. The lymphoepithelial lesions could be observed in lymphoepithelial sialadenitis, extranodal marginal zone B-cell lymphoma (EMZBCL), and IgG4-related diseases such as a Kuttner tumor. Lymphoepithelial sialadenitis could be ruled out by well-circumscribed borders and proliferative epithelial components. A mixed population of B- and T-cell and no elevation of the IgG4/IgG ratio in the background plasma cells could extinguish EMZBCL and IgG4-related diseases from this case. Lymphoepithelial differentiation of nonsebaceous lymphadenoma was not a common but was described by Kang et al.[6] They described nonsebaceous lymphadenoma with undifferentiated anastomosing trabeculae as "nonsebaceous lymphoepithelioma." Weiler et al. [2] regarded the histologic findings of lymphoepithelial differentiation in nonsebaceous lymphadenoma as part of a wide spectrum of epithelial metaplasia such as ductal or basaloid differentiation.

The most significant differential diagnosis, in this case, was lymphoepithelial carcinoma. Lymphoepithelial carcinoma is an undifferentiated tumor that exhibits aggressive behavior and frequent involvement of neck lymph nodes. [1] The features of distinguishing between lymphadenoma and lymphoepithelial carcinoma were known as lack of atypia, the absence of mitotic activity, and the presence of ductal formation. The present case had a significant nuclear atypia, presence of a few mitoses, and no ductal differentiation. However, invasive growth, necrosis, and EBV infection were not identified. Lymphoepithelial carcinoma usually grew in an infiltrative pattern and has frequent necrosis, mitoses, and a near 100% association with EBV-infection. [7] Considering the pathologic and clinical features, the present case was diagnosed as nonsebaceous lymphadenoma.

The cytologic atypia in the present case gave diagnostic difficulty. Lymphoepithelial carcinoma arising from lymphadenoma or borderline malignancy arising in lymphadenoma had not been reported. Seethala et al. described a case of basal cell adenocarcinoma developed from nonsebaceous lymphadenoma. [5] They diagnosed malignant transformation, based on cytologic atypia, mitosis, and increased cellularity in the area of malignant transition even in the absence of invasive growth. Possible immune reactions such as EBV and other viral infections had not been found in nonsebaceous lymphadenoma and this case. [5] The implication of cytologic atypia in nonsebaceous lymphadenoma was not validated and needed to be carefully observed.

Herein, we report a rare feature of nonsebaceous lymphadenoma that is characterized by atypical epithelial cells with lymphoepithelial differentiation. Understanding of the wide spectrum of nonsebaceous lymphadenoma is important for preventing misdiagnosis. Further careful follow-up is warranted to elucidate the behavior of atypical nonsebaceous lymphadenoma of the salivary gland.

Financial support and sponsorship

This study was financially supported by research fund of Chungnam National University in 2014.

Conflicts of interest

There are no conflicts of interest.

   References Top

Barnes L, Eveson JW, Reichart P, Sidransky D. Pathology and Genetics of Head and Neck Tumours. World Health Organization Classification of Tumours: IARC Press; 2005. p. 269.  Back to cited text no. 1
Weiler C, Agaimy A, Zengel P, Zenk J, Kirchner T, Ihrler S. Nonsebaceous lymphadenoma of salivary glands: Proposed development from intraparotid lymph nodes and risk of misdiagnosis. Virchows Arch 2012;460:467-72.  Back to cited text no. 2
Auclair PL. Tumor-associated lymphoid proliferation in the parotid gland: A potential diagnostic pitfall. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1994;77:19-26.  Back to cited text no. 3
Dardick I, Thomas MJ. Lymphadenoma of parotid gland: Two additional cases and a literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:491-4.  Back to cited text no. 4
Seethala RR, Thompson LD, Gnepp DR, Barnes EL, Skalova A, Montone K, et al. Lymphadenoma of the salivary gland: Clinicopathological and immunohistochemical analysis of 33 tumors. Mod Pathol 2012;25:26-35.  Back to cited text no. 5
Kang J, Kim SY, Cho KJ. Lymphadenoma of the salivary gland: A novel classification based on immunohistochemical comparison of benign and malignant lymphoepithelial neoplasms. Basic Appl Pathol 2008;1:18-22.  Back to cited text no. 6
Anantharajan N, Ravindranathan N, Rajadurai P. Lymphoepithelial carcinoma of the parotid gland, a very unusual tumor: Case report and review. Ear Nose Throat J 2013;92:E7-9.  Back to cited text no. 7

Correspondence Address:
Jin Man Kim
Department of Pathology, School of Medicine, Chungnam National University, Munwha-Dong, Jung-Gu, Daejeon 301-131
Republic of Korea
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.191810

Rights and Permissions


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

This article has been cited by
1 Nonsebaceous lymphadenoma of the sublingual gland: A case report and literature review
Genki Yamaya,Ikuya Miyamoto,Ryousuke Abe,Daishi Saito,Yasunori Takeda,Hiroyuki Yamada
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology. 2017; 29(6): 559
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report
    Article Figures

 Article Access Statistics
    PDF Downloaded53    
    Comments [Add]    
    Cited by others 1    

Recommend this journal