Lymphoepithelial Carcinomystery: A Curious Case of a Rare Parotid Tumor

Christopher G. Tang, M.D. Kaiser Permanente Oakland Medical Center Department of Head and Neck Surgery 280 W. MacArthur Blvd. Oakland, CA 94611 510-752-6400 (voice) 510-752-1526 (fax) e-mail: Christopher.G.Tang@kp.org CONTACT Christopher G. Tang1, Shivan Amin1, Thomas M. Schmidtknecht2, Luke J. Schloegel1, Grace Y. Tang3, Barry M. Rasgon1. 1. Department of Head and Neck Surgery, Kaiser Oakland Medical Center, Oakland, CA 2. Department of Pathology, Kaiser Oakland Medical Center, Oakland, CA 3. Lynbrook High School, San Jose, CA Figure 1: Intraparotid lymph node adjacent to tumor. Lymphoplasmacytic cell infiltrate surrounding nests of tumor cells suggests lymphoepithelial carcinoma. Adjacent lymph node appears reactive with a starry sky pattern. Figure 2: Brown cytokeratin stain (CK 5/7), an immunoperoxidase stain, reveal tumor cells staining positive for cytokeratin. However, tumor cells are also seen within the lymph node suggestive of intraparotid spread. All other lymph nodes were negative in the patient. Figure 3: Epstein-Barr Encoded RNAs (EBER) stain shows EpsteinBarr Virus (EBV) positivity within tumor cells. Tumor scattered within lymph nodes also stain positive for EBER. Figure 4: High power view of specimen reveal classic lymphoplasmacytic cell infiltrate among nests of poorly differentiated tumor cells. A 29 year old Female referred from an outside hospital presents to clinic with a 10 month history of an enlarging left facial mass. At that time, the patient had no pain and her facial nerve was intact with House-Brackman score grade I. Fine needle aspirate (FNA) was done at the outside facility showing cells suggestive of a poorly differentiated neoplasm with spindle cell and epithelioid features, but additional biopsy material was needed for definitive classification. Computed tomography (CT) scan done at that time showed a 4.1 x 2.9 x 3.7 cm mass in the superficial lobe of the left parotid with left cervical lymphadenopathy. Patient was seen at our facility 9 days after initial FNA and CT scan were performed. As pathological results may have altered surgical planning, a core needle biopsy was then completed to rule out lymphoma. Core needle biopsy revealed tumor cells that stained negative for CD20, C3, CD45, synaptophysin and CD30, and confirmed the FNA results of a poorly differentiated carcinoma. Six days after the core needle biopsy, the patient received a total left parotidectomy, and a selective neck dissection involving the level II nodes only. A complete neck dissection was not performed since frozen section of level II nodes were negative for carcinoma. Specimen was sent to pathology and revealed: What is your diagnosis? CASE Lymphoepithelial carcinoma accounts for 0.4% of malignant salivary gland tumors and is a variant of anaplastic carcinoma with a dense lymphoid stroma.1 Although Schminke first described lymphoepithelial carcinoma in the nasopharynx in 19212, it wasn’t until 1952 that Godwin described the first case series of benign lymphoepithelial lesions of the salivary gland with 11 patients.3 Epidemiologically, tumors account for less than 1% of all salivary gland tumors and has a unique ethnic predilection for Arctic region natives (particularly Eskimos/Inuits), southeastern Chinese, and Japanese. The most common site of occurrence is the parotid gland and has a near 100% association with Epstein-Barr virus in endemic areas.4 Patient usually present with a mass swelling with or without facial nerve paralysis and pain. There is a high frequency (10-40%) of concurrent cervical lymphadenopathy.5 The patient in our case had all these clinical risk factors as she was of southeastern Chinese/Asian decent, had disease in the parotid gland, and histological specimens stained positive for Epstein-Barr Encoded RNAs (EBER) (Figure 3). The patient did present with facial swelling, but did not have any facial nerve paralysis or any pain. She did not have any cervical lymph node involvement and pathological specimens of level IIa nodes showed 19 negative lymph nodes. The patient did have one lymph node involved that was directly adjacent to the tumor (Figure 1), but no regional metastases. The tumor was classified as a stage II T2N0M0 grade 3 poorly differentiated lymphoepithelial carcinoma as the tumor was greater than 2 cm and less than 4 cm and did not appear to have any lymph node or distant metastases.6 The patient did not have any perineural invasion and all margins were clear. Histologically, specimens of lymphoepithelial carcinomas normally are characterized by a rich non-neoplastic lymphoplasmacytic cell infiltrate present in between and around tumor nests (Figure 1, 4). Abundant histiocytes may be present demonstrating a starry sky appearance.5 Immunohistochemistry shows neoplastic cells that are cytokeratin (Figure 2) and EMA positive with variable expression of EBER.4 Lymphoid cells are reactive for both CD20 and CD3 markers suggestive of B-cell and Tcell presence respectively. Current treatment recommendations involve completely excising the primary lesion with a selective neck dissection followed by postoperative radiotherapy to the local site as well as to the neck if there were positive lymph node involvement. As the majority of lymphoepithelial carcinomas of the parotid gland are radiosensitive, combination therapy with surgery and radiation is desirable to control the disease.7 Our patient received a total parotidectomy on the affected side followed by a selective level IIa neck dissection. Since the lymph nodes were negative on frozen section intraoperatively, it was decided that the patient only needed her level IIa lymph nodes removed. The patient will be referred to radiation therapy for discussion for possible post-operative radiotherapy. PATHOPHYSIOLOGY REFERENCES 1 Schneider M., Rizzardi C., Lymphoepithelial carcinoma of the parotid glands and its relationship with benign lymphoepithelial lesions. Arch Pathol Lab Med. 2008 Feb;132(2):278-282. 2 Schminke, A. Uber lymphepithelial Geschwulste. Beitr Pathol Anat Allg Pathol 1921. 68:161–170. 3 Godwin, J. T. Benign lymphoepithelial lesion of the salivary gland: report of eleven cases. Cancer 1952. 5:1089–1103. 4 Lanier AP, Bornkamm GW, Henle W, Henle G, Bender TR, Talbot ML, Dohan PH. Association of Epstein-Barr virus with nasopharyngeal carcinoma in Alaskan native patients: serum antibodies and tissue EBNA and DNA. Int J Cancer. 1981 Sep 15;28(3):301-5. 5 Wenig, B. Heffess, C. Atlas of Head and Neck Surgery, 2nd Edition. 2008. Saunders Elsevier. Pg. 672-674 6 AJCC cancer staging manual. 6th ed. New York, NY: Springer; 2002. 7 Abdulla AK, Mian MY. Lymphoepithelial carcinoma of salivary glands. Head Neck. 1996 Nov-Dec;18(6):577-81. TREATMENT