INTRODUCTION

Extranodal T/NK lymphoma (ENTNHL) is a high-grade, non-Hodgkin, EBV-induced lymphoma [1]. It is a rare lymphoma that affects, in particular, the populations of East Asia and southern South America. There are two types: the nasal forms with primary involvement of the oropharyngeal sphere and the extranasal forms, also known as the nasal type, in which skin involvement is the most common location in terms of frequency, reported in 10% of cases [2]. The prognosis of these lymphomas remains poor because of late diagnosis and an aggressive evolution, complicated by visceral involvement. Herein, we describe a case of cutaneous, nasal-type LTNKEN revealed by a primary cutaneous localization with a fatal outcome in a young patient.

CASE REPORT

A 27-year-old, non-immunocompromised patient presented for four months with a rapidly progressive skin nodule of the leg in a context of fever, night sweats, and a profound alteration in the general condition.

An examination revealed a 20-cm long, violet, erythematous, necrotic skin tumor on the outer surface of the right leg (Fig. 1) associated with a mass of homolateral inguinal adenopathies and hepatosplenomegaly. A workup showed an inflammatory syndrome, functional renal failure, hepatic cytolysis, hypertriglyceridemia, hypercholesterolemia, and pancytopenia. A diagnosis of macrophagic activation syndrome (MAS) was retained.

Figure 1: Erythematous and violaceous, nodular tumor, necrotic on the external surface of the left leg.

A skin biopsy revealed a dense and atypical lymphocytic infiltrate (Figs. 2a and 2b). Immunohistochemistry revealed the expression of NK cell markers and cytotoxic molecules (TIA-1, granzyme B, and perforin), as well as the presence of Epstein–Barr virus (EBV) RNA in the tumor cells.

Figure 2: (a and b) Standard histology shows a malignant proliferation of round, spindle-shaped cells of lymphoid appearance with an angiocentric arrangement.

A cervico-thoraco-abdomino-pelvic CT scan revealed a free cavum and the integrity of the laryngo-pharyngeal carrefour. A homogeneous hepatosplenomegaly was also noted. There were no visceral metastases.

The diagnosis was extranasal ENKTL complicated by MAS. Systemic corticosteroid therapy was initiated as an emergency, yet the patient died by multivisceral failure.

DISCUSSION

LTNKEN accounts for 5–18% of non-Hodgkin lymphomas [2]. It occurs mainly in Southeast Asia and Central and South American populations, and is rare in Europe and the U.S. A male predominance is observed. It is a high-grade, malignant lymphoma with a poor prognosis [4].

Two entities of extranodal T/NK lymphoma are distinguished according to the initial location of the lesions. The nasal forms (nasal LTNKEN), which represent 80% of cases, begin in the nasal cavity or adjacent structures (orbits, oral cavity, sinuses, upper aerodigestive tract). The extranasal forms, known as the nasal type, represent 20% of cases. Skin involvement may be related to the metastatic extension of nasal LTNKEN to the skin or may be primary in the case of extranasal LTNKEN. Primary skin involvement is reported in 10–26% of cases of LTNKEN, the spleen and liver are the primary sites in 5% of cases, while initial lymph node involvement is exceptional [5].

A longer diagnostic delay and a different visceral involvement explain the poorer prognosis of the extranasal forms. Because of the structures invaded, the nasal forms are more symptomatic at an early stage (nasal obstruction, chronic rhinitis and sinusitis, epistaxis) and are, therefore, generally diagnosed at the localized stage, unlike the extranasal forms.

Skin involvement usually presents as ulcerated tumors, yet also as vasculitis, panniculitis, or cellulitis.

Histology reveals a dense infiltrate of lymphocytes of variable size associated with histiocytes, plasma cells, and eosinophils. This infiltrate is both dermohypodermal and epidermotropic, and frequently presents aspects of necrosis with angiocentricity and angiodestruction [6].

On immunohistochemistry, tumor cells typically express CD2, CD56, and cytotoxic proteins. There is intracytoplasmic CD3E yet no membrane expression of CD3. LMP-1 protein expression is inconsistent, but EBV may be detected by in situ hybridization in difficult cases [6].

The prognosis of these lymphomas is poor, particularly in the extranasal forms, due to a longer diagnostic delay and more extensive visceral involvement. In advanced stages, treatment is based on multidrug therapy with L-asparaginase, followed by autologous or even allogeneic hematopoietic stem cell transplantation [7,8].

CONCLUSION

The diagnosis of LTNKEN remains difficult and requires an anatomopathological and clinical confrontation. The cutaneous involvement in this type of lymphoma is often atypical and infrequent, which may lead to a diagnostic delay. The prognosis is generally poor and the diagnosis must be suspected early.

REFERENCES

1. World Health Organisation. WHO Classification of Tumors of Haematopoietic and Lymphoid tissues, Lyon, International Agency for Research on Cancer, 2017.

2. Suzuki R, Takeuchi K, Ohshima K, Nakamura S. Extra-nodal NK/T-cell lymphoma:Diagnosis and treatment clues. Hematol Oncol. 2008;26:66-72.

3. William BM, Armitage JO. International analysis of the frequency and outcomes of NK/T-cell lymphomas. Best Pract Res Clin Haematol. 2013;26:23-32.

4. Perry AM, Diebold J, Nathwani BN, MacLennan KA, Muller-Hermelink HK, Bast M, et al. Non-Hodgkin lymphoma in the developing world:Review of 4539 cases from the International Non-Hodgkin Lymphoma Classification Project. Haematologica. 2016;101:1244-50.

5. Au WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Song I, et al. Clinical differences between nasal and extra-nasal natural killer/T-cell lymphoma:A study of 136 cases from the International Peripheral T-Cell Lymphoma Project. Blood. 2009;113:3931-7.

6. Lee WJ, Jung JM, Won CH, Chang SE, Choi JH, Moon KC, et al. Cutaneous extra-nodal natural killer/T-cell lymphoma:A comparative clinicohistopathologic and survival outcome analysis of 45 cases according to the primary tumor site. J Am Acad Dermatol. 2014;70:1002-9.

7. Yamaguchi M, Suzuki R, Oguchi M, Asano N, Amaki J, Akiba T, et al. Treatments and outcomes of patients with extra-nodal natural killer/T-cell diagnosed between 2000 and 2013:A cooperative study in Japan. J Clin Oncol. 2017;35:32-9.

8. Marzouki-Zerouali A, Charbit L, Mitcov M, Violon F, Schmutz JL, Moawad S, et al. [Extra-nodal NK/T-cell lymphoma, nasal-type, revealed by cutaneous and ocular involvement]. Ann Dermatol Venereol. 2019;146:626-33.