NK and NK-like T-cell lymphoma in extranasal sites: a comparative clinicopathological study according to site and EBV status

• Published in: Histopathology 2004-05, Vol.44 (5), p.480-489
• Main Authors: Ko, Y H, Cho, E-Y, Kim, J-E, Lee, S-S, Huh, J-R, Chang, H-K, Yang, W-I, Kim, C-W, Kim, S-W, Ree, H J
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; CD56 Antigen - metabolism; EBV; extra-nasal; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - pathology; Gastrointestinal Neoplasms - virology; Gene Rearrangement; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - virology; Hematologic and hematopoietic diseases; Herpesvirus 4, Human - isolation & purification; Humans; In Situ Hybridization; Killer Cells, Natural; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; lymphoma; Lymphoma, T-Cell, Peripheral - diagnosis; Lymphoma, T-Cell, Peripheral - genetics; Lymphoma, T-Cell, Peripheral - metabolism; Lymphoma, T-Cell, Peripheral - mortality; Lymphoma, T-Cell, Peripheral - pathology; Lymphoma, T-Cell, Peripheral - virology; Male; Medical sciences; Middle Aged; Necrosis - pathology; Parotid Neoplasms - genetics; Parotid Neoplasms - pathology; Parotid Neoplasms - virology; Poly(A)-Binding Proteins; Prognosis; Proteins - metabolism; RNA, Viral - analysis; RNA-Binding Proteins; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Soft Tissue Neoplasms - genetics; Soft Tissue Neoplasms - pathology; Soft Tissue Neoplasms - virology; Survival Analysis; T-Cell Intracellular Antigen-1; Testicular Neoplasms - genetics; Testicular Neoplasms - pathology; Testicular Neoplasms - virology; Tumors
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2004.01867.x

Aims:  To analyse the clinicopathological findings of extranasal CD56+ cytotoxic T‐ or NK‐cell lymphomas in different organs and to compare Epstein–Barr virus (EBV)+ and EBV– lymphoma of non‐blastoid cytomorphology. Methods and results:  Fifty‐one cases of cCD3+ T‐cell intracellular antigen (TIA‐1)+ CD56+ lymphomas of extranodal/extranasal origin were included in the study. The primary sites of the CD56+ tumours were soft tissue (n = 10), the gastrointestinal (GI) tract (n = 13), the skin (n = 15), upper aerodigestive tract excluding nasal and nasopharyngeal regions (n = 11), the testis (n = 1), and parotid gland (n = 1). TCR gene rearrangement was detected in seven of 47 cases examined (16%). EBV was positive in 39 of 51 cases (76%). The positive rate of EBV was higher in tumours of soft tissue (80%), GI tract (92%), and skin (80%), and lowest in the upper aerodigestive tract excluding the nasal and nasopharyngeal region (50%). Tumours of the soft tissue and the upper aerodigestive tract tended to present with localized disease (P = 0.002). The 2‐year survival rate was lowest for tumours of the GI tract (P = 0.0256). EBV– TCR– lymphoma showed less necrosis (P = 0.0133) and a better 2‐year survival rate (P = 0.0066) than EBV+ TCR– lymphoma. Patients with EBV+ TCR+ lymphomas tended to present with localized disease, more often than EBV+ TCR– lymphoma (P = 0.0186). Significant prognostic factors in all CD56+ lymphomas were the site (P = 0.0256), EBV status (P = 0.0026), necrosis with or without perforation (P = 0.0338) and the presence of pleomorphic large tumour cells (P = 0.0428). Cox's regression analysis adjusting for other pathological parameters showed EBV status to be the only independent prognostic factor (P = 0.018). Conclusions:  Extranodal CD56+ EBV– lymphoma at extranasal sites is a clinically less aggressive malignancy and displays less necrosis than CD56+ EBV+ lymphoma. Because CD56+ EBV+ TCR+ lymphomas show similar pathological and clinical findings to CD56+ EBV+ TCR– lymphomas, nasal‐type NK/T‐cell lymphomas at extranasal sites should be diagnosed as such on the basis of EBV+, cytotoxic T or NK phenotype irrespective of the genotype determined by molecular study.