Extranodal NK/T-cell Lymphoma Mimicking Erythema Multiforme.

Extranodal natural killer/T-cell lymphoma (ENKTL) is an extremely rare and an aggressive lymphoma. We report an interesting case of extranodal natural killer/T-cell lymphoma in a middle-aged woman which mimicked erythema multiforme. The skin lesions of this case looked like erythema multiforme due to the tagetoid lesions and mucosal erosions. The two biopsies from her chest and scalp lesions were different. One exhibited the characteristics of CD4+ CD56+ CD8-mycosis fungoides whereas the other biopsy from her scalp showed classical ENKTL histopathological manifestation with positive CD56, cytotoxic proteins and Epstein-Barr virus encoded RNA (EBER).

What was known?

The major manifestations of extranodal natural killer/T-cell lymphoma are cellulitis and ulcers with aggressive clinical course and poor prognosis. Histologically, it is characterized with atypical lymphocytes which are positive for CD56 and Epstein-Barr virus.

Introduction

Extranodal natural killer/T-cell lymphoma (ENKTL) is an extremely rare and an aggressive lymphoma. We present a case of extranodal natural killer/T-cell lymphoma in a middle-aged woman which mimicked erythema multiforme.

Case Report

A 39-year-old Chinese woman attended to our department complaining about intermittent fever and lesions for 2 months. Physical examination revealed dark to purple red scaly plaques and nodules on the scalp, numerous erythematous lesions (some of which showed targetoid features) on the trunk and extremities, nipple erosion, conjunctival congestion, oral and vulval erosion [Figure 1a-c]. Nikolsky's sign was negative. Laboratory work-up showed increased lactate dehydrogenase (842U/L) and negative blood bacterial culture. Blood and urine routine tests were normal. The initial diagnosis was presumed to be erythema multiforme. A skin biopsy from her chest lesion showed superficial infiltration by small to large-sized atypical lymphoid cells with epidermotropism. The atypical cells were positive for CD3, CD4 (sparsely), CD45RO, perforin, GranB, T-cell intracellular antigen 1 (TIA-1) and CD56, negative for in situ hybridization for EBV (Epstein–Barr virus) encoded RNA (EBER) and CD8. So we preliminarily considered the patient as CD4+ CD56+ CD8-mycosis fungoides even though atypical clinical features. Interferon-α-1b was used subcutaneously every other day. She continued to have daily fever despite the treatment. Thus, we reconsidered the diagnosis due to her aggressive course. Then we performed the other skin biopsy from her scalp which revealed a patchy and diffuse infiltration of intermediate-sized to large atypical lymphoid cells into dermis and subcutaneous tissue with epidermotropism. The atypical cells were positive for CD3, CD56, Ki67, perforin, GranB, TIA-1 and EBER, supporting the modified diagnosis of ENKTL [Figure 2]. Positron emission computed tomography revealed multiple tumors in skin, conjunctiva, nose, thyroid gland, breasts, lungs, gastrointestinal tract and bones. Based on the results of these studies, the diagnosis of ENKTL (stage IV) was established. We excluded the diagnosis of aggressive NK cell leukemia for normal results of bone marrow aspiration and biopsy. Three days after the results of the second biopsy coming out, she experienced epistaxis and gastrointestinal bleeding. She gave up on therapy and died 2 days after being discharged from hospital.

Figure 1

(a) Oral erosion (b) Vulval erosion (c) Numerous erythematous lesions, some of which showed targetoid lesions, on the trunk

Figure 2

(a) Biopsy specimens taken from chest showed superficial infiltration by small to large-sized atypical lymphoid cells with epidermotropism (H and E, ×200). (b) The atypical cells were positive for CD4 (×100). (c) The atypical cells were positive for CD56 (×100). (d) The atypical cells were positive for GranB (×200). (e) Biopsy specimens taken from scalp showed a patchy and diffuse infiltration of intermediate-sized to large atypical lymphoid cells into dermis and subcutaneous tissue with epidermotropism (H and E, ×200). (f) The atypical cells were positive EBER in situ hybridization (×200)

Discussion

Our case was of particular interest because the clinical and histopathological manifestations of this patient were different from typical ENKTL,[12] which caused misdiagnosis twice. First, the skin lesions of this case looked like erythema multiforme due to the targetoid lesions and mucosal erosions. Up to now, a thorough PubMed search has failed to identify cases of ENKTL presenting like erythema multiforme (EM). Only Charli-Joseph et al.[3] reported one case of ENKTL presenting as genital ulcers in 2012. There are two possibilities regarding the association between EM-like lesions and T cell or NK/T-cell lymphoma: (1) the skin manifestations of lymphomas are EM-like clinically but histologically with the infiltration of lymphomas cells; (2) EM is as a skin reaction to lymphoma and coexistent with lymphoma lesions. One Japanese patient with adult T-cell lymphoma/leukemia had EM-like lesions which showed an dermal infiltration of leukemic cells.[4] For our case, the skin manifestations of ENKTL are EM-like because of the infiltration of atypical lymphocytes expressing CD3, CD56, perforin, GranB, and TIA-1. Secondly, the two biopsies from her chest and scalp lesions were different. Chest lesion exhibited the characteristics of CD4+ CD56+ CD8-mycosis fungoides whereas the other biopsy from her scalp showed classical ENKTL histopathological manifestation with positive CD56, cytotoxic proteins and EBER. The scalp lesions appeared before trunk lesions and were consist of plaques and nodules rather than targetoid lesions as on the chest. This suggested that the different stage of the disease might cause the different results of biopsy and immunophenotypes. Therefore, we should perform multiple biopsies from different lesions, especially early mature lesions when the diagnosis based on biopsy results doesn’t match the clinical manifestation of the disease. It is noteworthy that the biopsy of the late onset chest lesion revealed epidermotropism and negative ERBR which was similar to other reports of ENKTL.[56] This indicated that late immature chest lesion still remained partial characteristics of ENKTL.

Although ENKTL is often noted as violet plaques and ulcers of nose and skin, we shouldn’t neglect ENKTL when the disease presents as an aggressive progression with atypical lesions, such as erythema multiforme. The selection of the biopsy site and multiple biopsies are very important for correct diagnosis of ENKTL.

What is new?

We shouldn't neglect ENKTL when it presents as an aggressive progression with atypical lesions, such as erythema multiform.