The diagnosis and management of NK/T-cell lymphomas

Abstract

Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignancy of putative NK-cell origin, with a minority deriving from the T-cell lineage. Pathologically, the malignancy occurs in two forms, extranodal NK/T-cell lymphoma, nasal type; and aggressive NK-cell leukaemia. Lymphoma occur most commonly (80%) in the nose and upper aerodigestive tract, less commonly (20%) in non-nasal areas (skin, gastrointestinal tract, testis, salivary gland), and rarely as disseminated disease with a leukemic phase. Genetic analysis showed mutations of genes involved in the JAK/STAT pathway, RNA assembly, epigenetic regulation, and tumor suppression. In initial clinical evaluation, positron emission tomography computed tomography, and quantification of plasma EBV DNA are mandatory as they are useful for response monitoring and prognostication. In stage I/II diseases, combined chemotherapy and radiotherapy (sequentially or concurrently) is the best approach. Conventional anthracycline-containing regimens are ineffective and should be replaced by non-anthracycline-containing regimens, preferably including L-asparaginase. Radiotherapy alone is associated with high systemic relapse rates and should be avoided. In stage III/IV diseases, non-anthracycline-regimens-containing L-asparaginase are the standard. In relapsed/refractory cases, blockade of the programmed death protein 1 has recently shown promising results with high response rates. In the era of effective non-anthracycline-containing regimens, autologous haematopoietic stem cell transplantation (HSCT) has not been shown to be beneficial. However, allogeneic HSCT may be considered for high-risk or advanced-stage patients in remission or relapsed/refractory patients responding to salvage therapy. Prognostic models taking into account presentation, interim, and end-of-treatment parameters are useful in triaging patients to different treatment strategies.

Keywords: EBV DNA quantification; Extranodal; Immunotherapy; L-asparaginase; NK/T-cell lymphoma; Nasal; Non-nasal; PD1; Prognostication.

Fig. 1

Clinical features of NK/T-cell lymphomas. a Nasal lesion that has ulcerated into the face. b Nasal lesion with extension to the orbit. c Cutaneous lesion in the knee that has ulcerated. Note the two adjacent lesions in their early stages. d Perforation of the hard palate, leading to a communication between the oral and nasal cavities

Fig. 2

Positron emission tomography computed tomography of NK/T-cell lymphomas. a Nasal lesion that shows avidity for 18F-fluorodeoxyglucose. b Disseminated disease. Note the large nasal tumor (arrow) and multiple hypermetabolic lesions in other anatomical sites