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Lymphoepithelioma-Like Carcinoma of the Skin: a Case of One Patient Presenting with Two Primary Cutaneous Neoplasms

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Lymphoepithelioma-Like Carcinoma of the Skin: a Case of One Patient Presenting with Two Primary Cutaneous Neoplasms Lymphoepithelioma-like Carcinoma of the Skin: A Case of One Patient Presenting with Two Primary Cutaneous Neoplasms Jacqueline C. Fisher, DO,* Rachel M. White, BA,** Daniel S. Hurd, DO, FAOCD*** *Dermatology Resident, PGY-2, VCOM/LewisGale Hospital Montgomery, Blacksburg, VA **Medical Student, OMS IV, Philadelphia College of Osteopathic Medicine, Philadelphia, PA ***Dermatology Residency Program Director, VCOM/LewisGale Hospital Montgomery, Blacksburg, VA Abstract Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare cutaneous neoplasm most frequently found on the head and neck of elderly patients. Debate exists regarding its histogenesis, but it’s believed to be of epithelial origin. Histologically, LELCS is remarkably similar to undifferentiated nasopharyngeal carcinoma, a neoplasm associated with Epstein-Barr virus (EBV) infection. EBV reactivity is the main distinguishing factor between these two cutaneous neoplasms, with LELCS rarely documented to test positive for EBV. In general, those diagnosed with LELCS are advised to undergo evaluation of the nasopharynx as well as other internal organ systems that may harbor a lymphoepithelioma-like carcinoma to exclude cutaneous metastasis. Current treatment guidelines recommend wide local excision or Mohs micrographic surgery to prevent local recurrence of LELCS. To the best of the authors’ knowledge, this case is the first to report a patient with two separate lymphoepithelioma-like carcinomas of the skin presenting simultaneously. Introduction Case Report neck and left parietal scalp neoplasms showed Lymphoepithelioma-like carcinoma of the skin An 83-year-old Caucasian female was referred a dermal proliferation of atypical epithelioid (LELCS) is a rare cutaneous neoplasm with low to our dermatology clinic for surgical excision cells forming well-defined nests invested by malignant potential. It is currently classified as of a previously biopsied lesion on her left a dense lymphocytic infiltrate (Figure 2). a variant of squamous-cell carcinoma (SCC), neck reported initially as a nodular basal-cell The atypical epithelioid cells were basophilic although historically, its etiology has been debated. carcinoma with focal morpheaform features. The and featured enlarged nuclei with prominent LELCS demonstrates nearly identical histologic patient also complained of an asymptomatic, nucleoli. A central ulceration was present under features to undifferentiated nasopharyngeal slowly enlarging lesion to her left parietal scalp microscopic examination of the cutaneous carcinoma, also known as metastatic believed to be present for at least three months. biopsy on the patient’s left parietal scalp. The lymphoepithelioma of the nasopharynx, classically The patient’s past medical history was non- overlying epidermis appeared uninvolved in differentiated from LELCS by positive reactivity contributory, and she denied any constitutional both samples. Each specimen stained positive for an associated infection with Epstein-Barr symptoms at the time of clinical presentation. for cytokeratin (CK) 5/6 and epithelial 1,2 Therefore, an evaluation of the virus (EBV). Clinical examination revealed a solitary, 2.0 cm x nasopharynx with an ear, nose, and throat (ENT) 2.2 cm, tan to pink, indurated ulcerative plaque examination is advised to exclude undifferentiated (Figure 1). There were no naso-oropharyngeal nasopharyngeal carcinoma.2-4 LELCS generally abnormalities or regional lymphadenopathy. A is a slow-growing neoplasm with a good overall shave biopsy was performed to the left parietal prognosis. However, due to multiple cases of scalp to exclude both basal-cell carcinoma and recurrence after initial surgical excision, the gold squamous-cell carcinoma. standard of treatment for LELCS is wide local excision or Mohs micrographic surgery.2,5 The histopathological findings for both the left Figure 2. H&E staining of LELCS (20x). Figure 3. In situ hybridization Epstein-Barr virus encoded RNA (ISH/EBER) of LELCS on parietal scalp. Demonstrates absence of blue staining; determined to be EBV negative Figure 1. Lymphoepithelioma-like carcinoma of the skin on parietal scalp. (20x). Page 40 LYMPHOEPITHELIOMA-LIKE CARCINOMA OF THE SKIN: A CASE OF ONE PATIENT PRESENTING WITH TWO PRIMARY CUTANEOUS NEOPLASMS incidence is equal in men and women.8 LELCS the spindle-cell variant of melanoma.23 often presents as a solitary, flesh-colored to red, However, unlike LELCS, melanoma is positive firm papule, plaque, or nodule.2 The average size for S100 and other neuroectodermal markers is fairly large, measuring about 2 cm to 3 cm in such as HMB-45 and melan-A. LELCS should diameter.3 Typically, LELSC is asymptomatic be distinguished from malignant lymphoma and slowly enlarges over a period of months to by the absence of atypical lymphocytes in years.8 LELCS.1 Epithelial markers such as epithelial- membrane antigen and cytokeratins will react Histology positive in LELCS and negative in malignant On histology, LELCS presents as a dermal lymphoma. LELCS has shown the presence of proliferation of atypical polygonal epithelioid occasional binucleated cells resembling Reed- cells arranged in nests, cords, or sheets surrounded Sternberg cells; however, Hodgkin lymphoma is by a peripheral dense lymphocytic infiltrate.6 negative for cytokeratins and positive for CD30 Figure 4. Control slide demonstrating positive 1,2,21,23 Cellular atypia includes vesicular hyperchromatic and CD15. Basal-cell carcinoma will reaction to ISH/EBER immunohistochemical nuclei and prominent nucleoli with scant demonstrate neoplastic basophilic cells extending stain (20x). amphophilic-to-eosinophilic cytoplasm.2 The downward from the epidermis, whereas LELCS reactive lymphoid stroma is comprised of small does not typically have an epidermal connection membrane antigen (EMA), suggesting tumors B- and T-lymphocytes, staining positive for and lacks peripheral palisading. Inflamed, poorly differentiated squamous-cell carcinoma (SCC) of epithelial origin. Staining for CK7 and CD3 and CD20, with an occasional plasma cell 1,19 CK20 yielded negative results, excluding Paget’s present.2,8 LELCS generally extends into the strongly resembles LELCS. However, LELCS disease and Merkel-cell carcinoma (MCC), reticular dermis with occasional involvement into typically does not involve overlying epidermis, respectively, from the differential diagnosis. Due the subcutis and even skeletal muscle.6,10 LELCS and poorly differentiated SCC usually has an area of well-differentiated carcinoma or overlying to the concern for an underlying metastatic stains positively for pancytokeratin, CK5, CK6, 1,3,5 undifferentiated nasopharyngeal carcinoma or p63 and EMA reactivity, likely indicating a SCC in situ. Cutaneous lymphadenoma lymphoepithelioma-like carcinoma (LELC) of neoplasm of epithelial origin.2,7 These markers demonstrates a similar dense lymphocytic infiltrate as LELCS, but these lymphocytes another internal organ, an in situ hybridization also indicate that LELCS may derive from an 1,2 for Epstein-Barr virus-encoded RNA (ISH/ epidermal, follicular, glandular, sudoriferous appear benign and monomorphic. Follicular EBER) was performed for detection of an active origin.2,5,7,11-14 In fact, the histogenesis of LELCS dendritic-cell tumor (FDCT) is similar to or latent EBV infection (Figure 3). The patient’s is controversial. Historically, LELCS was thought LELCS by way of syncytial-appearing plump cells surrounded by reactive lymphoid cells, but histologic slides were compared to a control ISH/ to derive from adnexal origin, supported by the 2 EBER immunohistochemical stain (Figure 4). fact that LELCS is located in the dermis and FDCT stains negative for cytokeratin markers. 6,15 FDCT will demonstrate positive reactivity to Ki- The negative ISH/EBER stain for both lesions usually lacks a connection with the epidermis. 2 strongly favors two primary LELSC in our patient Also, within LELCS, there is often sebaceous, M4, CD21, and CD35. and does not favor a metastatic disease related to eccrine and trichilemmal differentiation.8 In Histologically, LELCS is remarkably similar an EBV-driven undifferentiated nasopharyngeal more recent literature, some consider LELCS to metastatic lymphoepithelioma of the carcinoma or internal LELC. to be a variant of squamous-cell carcinoma nasopharynx, also known as undifferentiated (SCC).2,4,16-20 For instance, Wang et al. presented 1,3,22 Our patient was referred to an oncologist for nasopharyngeal carcinoma. Epstein-Barr a case of LELCS occurring below a scar from medical evaluation to exclude cutaneous metastasis virus (EBV) reactivity is the main distinguishing removal of multiple recurrent, well-differentiated of an undifferentiated nasopharyngeal carcinoma factor between LELCS and undifferentiated and subsequent moderately differentiated 1,2,4,24 or lymphoepithelioma-like carcinoma of other nasopharyngeal carcinoma. In general, SCC.19 However, SCC is typically located in internal organs. Given the patient’s advanced LELCS is negative for EBV reactivity, whereas the superficial dermis and maintains connectivity age and frail status, the patient refused oncologic undifferentiated nasopharyngeal carcinoma will with the epidermis.4 Finally, others believe that 1,2,4,24 examination as she planned to decline systemic test positive for EBV. There has been only LELCS is a morphologic pattern as opposed to a treatment if an underlying internal malignancy one reported case, that of a Japanese woman, of distinct clinicopathologic entity.17,21,22
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