CD56-Negative Extranodal NK/T-Cell Lymphoma, Nasal Type, with Extranasal Cutaneous Involvement.

Abstract

Dear Editor: Extranodal NK/T-cell lymphoma (ENTCL), nasal type, is a well-defined aggressive cytotoxic lymphoma1. Although immunophenotyping with CD56 is known to be positive in practically all cases, CD56-negative cases have also been reported, particularly in the upper respiratory tract. However, there are very few reports of skin involvement2. Here, we report a unique case of a CD56-negative, Epstein-Barr virus (EBV)-positive ENTCL, nasal type, with cutaneous involvement. A 35-year-old Korean female patient presented with a tender violaceous crusted indurated plaque on the right thigh and a light brown ill-defined induration on the right upper arm (Fig. 1). Histopathologic examination showed an atypical lymphocytic infiltration composed of small- to medium-sized cells with irregular folded nuclei, and inconspicuous nucleoli. The infiltrate demonstrated angiocentric growth with frequent mitoses. Focal epidermal and dermal necrosis were also noted (Fig. 2A, B). The infiltrated cells stained positively for antibodies against surface CD3, CD8, and granzyme B, whereas they were negative against CD4, CD56, and CD20 (Fig. 2C~E). EBV-encoded RNA (EBER) in situ hybridization was positive in many infiltrated cells (Fig. 2F). Three months before, the patient had been diagnosed with ENTCL, nasal type, for her recurrent nasopharyngeal ulcer. The microscopic evaluation of the uvula showed similar findings to that of the skin. Bone marrow biopsy, computed tomography and whole body 18-fluoro-2-deoxyglucose positron emission tomography scan revealed no systemic invasion of the lymphoma. Despite cisplatin-based concurrent chemoradiation therapy, there was only a partial reduction of the tumor. Fig. 1 Clinical manifestation of the skin lesions. (A) A tender dark erythematous scaly indurated plaque with oozing on the right thigh. (B) A tender light brown, ill-defined induration with cigarette-paper-like fine scales on the right upper lateral arm. Fig. 2 Microphotograph of the lesion on the right thigh. (A) Dense cellular infiltrates involving the deep dermis. Angiocentricity is conspicuous and epidermal necrosis is visible (H&E, ×12). (B) Atypical lymphocytes composed of small- to medium-sized ... ENTCL, nasal type, is a rare aggressive lymphoma that occurs more commonly in East Asia. Patients are typically middle-aged adults and have a male predominance3. The prognosis is poor regardless of therapeutic strategies, with a median survival no more than 12 months. The skin is known to be the second most common site of involvement and the disease usually manifests as multiple ulcerated plaques or tumors on the trunk or extremities. Histopathologically, ENTCL is characterized by dense infiltrates involving the dermis and often the subcutis. The cells have irregular or oval nuclei, moderately dense chromatin, and a pale cytoplasm. Prominent angiocentricity and angiodestruction often accompany extensive necrosis1. Immunophenotypically, the neoplastic cells typically stain for antibodies against CD2, CD56, cytoplasmic CD3, and cytotoxic proteins (TIA-1, granzyme B, and perforin), but lack surface CD34. However, rare cases are CD56 negative, and they stain positively for surface CD3, CD5 and CD8. Detection of EBV and expression of cytotoxic proteins are required for the diagnosis of these CD56-negative cases4. Most of the reported CD56-negative cases occurred in the upper respiratory tract5. Concerning skin involvement, to our knowledge, there have only been three cases recorded in the literature2. CD56-negative cases seem to be as aggressive as CD56-positive cases, and are usually unresponsive to conventional chemotherapy, with poor prognosis and a short median survival2. This case emphasizes that CD56 might not be invariably positive in ENTCL even in cases with extranasal cutaneous involvement. The immunohistochemistry and EBER in situ hybridization would be important ancillary studies for the accurate diagnosis of this rare aggressive cytotoxic lymphoma.