Extranodal natural killer/T-cell lymphoma with long-term survival and repeated relapses: does it indicate the presence of indolent subtype?

Seok Jin Kim,Yong Park,Byung Soo Kim,Insun Kim,Young Hye Ko,Won Seog Kim 대한혈액학회 2012 Blood Research Vol.47 No.3

Background Extranodal natural killer (NK)/T-cell lymphoma is a subtype of lymphoma that is derived from NK cells. It is considered as an aggressive form of non-Hodgkin’s lymphoma because of frequent relapses and resistance to treatment. Relapsed NK/T-cell lymphoma often follows a fulminant course that is refractory to conventional chemotherapy treatment. Methods Several patients with extranodal NK/T-cell lymphoma showed long-term survival in spite of frequent relapses. Thus, the medical records of patients diagnosed with extranodal NK/T-cell lymphoma from 1995 to 2007 were reviewed and assessed. Results Of the 140 cases reviewed, 6 were selected (4.29%). Each of these patients had a minimum of 3 relapses or disease progression during the follow-up period, and their median overall survival was 66 months (range, 42-89 months). They were grouped according to the atypical clinical behavior observed: (1) repeated relapses or progression (≥3 times) during follow-up; and (2) long-term survival of more than 40 months, as the longest overall survival median was previously considered at approximately 40 months. The clinicopathological and laboratory characteristics of these patients were similar to those of other extranodal NK/T-cell lymphoma patients. However, 5 of the studied cases involved relatively lower expression of the proliferation-related antigen Ki-67 (<40-50%), indicating less proliferative activity. Clinically, they showed delayed relapse for at least 20 months after the initial complete remission. Conclusion Our observations suggest that the clinical behavior of some extranodal NK/T-cell lymphoma patients differs from the typical clinical course.

CD21-independent Epstein-Barr virus entry into NK cells

Lee, Jeong Hoo,Choi, Jahyang,Ahn, Yong-Oon,Kim, Tae Min,Heo, Dae Seog Elsevier 2018 Cellular immunology Vol.327 No.-

<P><B>Abstract</B></P> <P>Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignant disease that is associated with Epstein-Barr viral (EBV) infection. To date, the mechanism of viral entry into NK cells remains uncertain. Here, we investigated this mechanism using human NK cells <I>in vitro</I>. CD21 mRNA expression, an EBV-entry receptor, was transiently detected in NK cells after exosome treatment, and levels decreased after further culture. CD21 protein expression was also transiently transferred to NK cells after co-culture with an EBV-positive Burkitt lymphoma cell line (Raji) via trogocytosis. However, EBV did not infect NK cells through CD21-mediated trogocytosis. Unexpectedly, when NK cell leukemia cells, as well as primary NK cells, were treated with viral supernatant, EBV genes, but not RNA, were detected in the NK cells, at latency stage 0. Therefore, these results suggest that EBV-NK cell infection results from the direct transfer of viral episomes, independent of EBV-positive B cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Transfer of EBV RNA in exosomes from the EBV-infected B cells to NK cells is transient. </LI> <LI> Trogocytosis of CD21, an entry receptor for EBV is not an NK infection mechanism. </LI> <LI> EBV viral episomes can be transferred into NK cells, without EBV-positive B cells. </LI> </UL> </P>

Epstein-Barr virus-positive nodal T/NK-cell lymphoma: an analysis of 15 cases with distinct clinicopathological features

Hematopathology Study Group of the Korean Society of Pathologists,Jeon, Y.K.,Kim, J.H.,Sung, J.Y.,Han, J.H.,Ko, Y.H. W. B. Saunders Co ; Centrum Philadelphia 2015 Human pathology Vol.46 No.7

Nodal peripheral T-cell lymphoma, not otherwise specified, is a heterogeneous entity with variable biologic behavior. We analyze the clinicopathological features of 15 patients with Epstein-Barr virus-positive (EBV+) nodal T/NK-cell lymphoma, including 9 males and 6 females, with a median age of 64 years. All patients presented with multiple lymphadenopathy with common B symptoms (80%, 12/15) at an advanced Ann Arbor stage (III, IV) (87%, 13/15). The International Prognostic Index was high or high/intermediate in 87% (13/15) of patients, and the prognostic index for peripheral T-cell lymphoma was group 3 or 4 in 73% (11/15). Spleen and liver involvement was observed in 73% (11/15) and 60% (9/15) of patients, respectively. In contrast, extranodal involvement was infrequent, with no more than 1 site in 71% (10/15) of patients. Moreover, none had nasal lesions, and only 1 had mucocutaneous involvement. The cell lineage of EBV+ tumor cells was determined to be T cell in all except 1 patient, who was NK-cell lineage. Cytotoxic molecules were expressed in all cases, and 64% (9/14) of patients expressed the αβT-cell receptor. Moreover, most patients (67%, 10/15) showed CD8 positivity, with 2 of them being CD4CD8 double positive; the others were CD4 positive (n = 2) or CD4CD8 double negative (n = 3). The clinical course was very aggressive, with a median survival time of 3.5 months, and 10 patients died within 6 months of diagnosis. Taken together, our data demonstrate that EBV+ nodal T/NK-cell lymphoma is a distinct clinicopathological entity characterized by cytotoxic molecule expression, a frequent CD8-positive αβT-cell lineage, and a very aggressive clinical behavior.

괴저고름피부증과 유사한 임상 양상을 보인 비강형 NK/T-세포 림프종 1예

이승훈 ( Seung Hun Lee ),김성민 ( Seong Min Kim ),윤태진 ( Tae Jin Yoon ) 대한피부과학회 2009 대한피부과학회지 Vol.47 No.6

NK/T-cell lymphoma is rare type of lymphoproliferative disorder, but it is clinically aggressive with a poor prognosis. The World Health Organization (WHO) classified mature NK cell neoplasms into extranodal NK/T-cell lymphoma nasal type and aggressive NK cell leukemia. NK/T-cell lymphoma is characterized by a strong association with Epstein-Barr virus (EBV), and when it involved the skin, the lesions clinically appear as deep nodules, infiltrative plaques and ulcerative plaques. We herein report on a case of the nasal type of extranodal NK/T-cell lymphoma that showed the immunophenotype of CD20?, CD56+ and CD45RO+, and it was positive on in situ hybridization for EBV. Our case was characterized by the clinical resemblance with pyoderma gangrenosum and this malady generally displays chronic painful ulcer and necrotic lesions. (Korean J Dermatol 2009;47(6):732∼735)

림프절외 림프종의 WHO 분류 : 임상적 및 면역학적인 표현형의 분석 Clinical and Immunophenotypic Analysis

김진만,설지영,강대영 충남대학교 의학연구소 2001 충남의대잡지 Vol.28 No.2

The authors retrospectively reviewed extranodal malignant lymphomas which include various distinctive clinicopathologic entities according to the new WHO lymphoma classification system. The aim of this study was to analyze the clinical characteristics of extranodal lymphomas and the relative frequency of the subtypes with immunophenotype in the Daejeon city and Chungcheong province. The authors reviewed 134 cases of extranodal lymphoma out of 220 cases of total non-Hodgkin's lymphoma which was diagnosed during the last 10 years. Among the cases, gastric lymphomas (26.1%) were the most common anatomic site. Nasal and paranasal (14.4%), skin (13.4%), and Waldeyer's tonsillar ring (11.2%) lymphomas were relatively common in order of frequency. The most frequent subtypes of extranodal lymphoma were marginal zone B-cell lymphoma of MALT (31%), diffuse large B-cell lymphoma (20%), peripheral T-cell lymphoma, unspecified (15.7%), and nasal NK/T cell lymphoma (13.4%), in decreasing order. Compared with a previous studies, the relative frequency of nasal NK/T cell lymphoma was much higher in our study than western countries and similiar to East Asia. The immunophenotype of our extranodal lymphomas was mainly B-cell type (68%) and the remaining cases were T- or NK-cell origin. In conclusion, the occurrence rates for various subtypes of extranodal lymphoma in Daejeon and Chungcheong province were distinct from those in western countries and similiar to those in East Asian countries. The most distincitive entities in our study were marginal zone B-cell lymphoma of MALT and nasal NK/T cell lymphoma. It also appears that the frequency of lymphoma subtypes is changing according to the classification system.

위의 CD56 음성 자연살해 T세포 림프종 1예

정주홍,지삼룡,최은정,유승정,윤준식,이홍섭,이상헌,박성재,박하영 대한소화기학회 2022 대한소화기학회지 Vol.80 No.4

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL-NT) is the most common subtype of Epstein-Barr virus-associated NK/T-cell lymphomas. ENKTCL-NT occurs infrequently in the gastrointestinal tract. In particular, reports of ENKTCL-on NT arising from the stomach are extremely rare. Several clusters of differentiation (CDs) have been useful in recognizing NK-cells, T-cells, and tumor cells of NK/T-cell lymphomas. Among them, the CD56 antigen is considered the most sensitive marker for ENKTCL-NT and is expressed in almost all cases of ENKTCL-NT. Thus, the development of CD56-negative ENKTCL-NT is highly atypical. This paper reports a case of a young Asian female who presented with gastric ulcer bleeding. The patient was histologically diagnosed with ENKTCL-NT. No tumor cells for CD56 were observed, whereas no monoclonality of the T-cell receptor gamma gene rearrangement was detected in the tumor cells. The patient was scheduled for systemic chemotherapy six times and achieved complete remission. Peripheral blood-hematopoietic stem cell transplantation was performed later.

식도의 원발성 NK-/T- 세포 림프종 1예

김태형,유호상,김창하,홍호철,고진성,전훈재,김창덕,김인선 대한소화기내시경학회 2010 Clinical Endoscopy Vol.41 No.4

Extranodal natural killer/T-cell lymphoma (ENKL) is an uncommon neoplasm, and it is a subtype of non-Hodgkin’s lymphoma. It most commonly presents in the nasal cavity and nasopharynx. But only 10% of ENKL may present on the skin or the gastrointestinal tract and this has a poor prognosis. We report here on a case of CD56+ NK/T-cell lymphoma that limited to the esophagus. A 55-year-old male patient presented with epigastric soreness. Esophagogastroduodenoscopy (EGD) showed well demarcated, longitudinal ulcerative lesions with an irregular base and a discrete margin on the lower esophagus. We performed EGDs and endoscopic biopsies 2 times, but these were insufficient to make a diagnosis. The 3rd time, we finally took a big piece of tissue using endoscopic mucosal resection with a cap-fitted panendoscope (EMR-C). The biopsies showed surface ulceration and a heavy lymphoid infiltration and a positive pattern for CD3, CD56 and granzyme B. The pathologic diagnosis was NK/T-cell lymphoma. The patient was treated with concurrent chemoradiation followed by additional chemotherapy and he achieved a complete response. 림프절외 NK/T 세포 림프종은 비호지킨 림프종의 아형으로 비강이나 부비동에서 흔히 관찰되며 위장관에서 원발성으로 나타나는 경우는 극히 드물다. 진단이 되더라도 병의 경과가 진행되어 예후가 좋지 않다. 본 증례는 명치통증의 보편적인 증상을 통해 내시경검사를 시행하여 하부 식도에서 불규칙한 표면에 변연이 약간 융기되고 경계가 예리하게 잘 지어진 종축 양상의 식도 궤양형 병변이 발견되었다. 반복적인 내시경과 조직검사 및 endoscopic mucosal resection with a cap-fitted panendoscopy를 통해 조기 진단을 내리고, 치료를 통해 완전 관해를 이룬 원발성 식도 NK/T 세포 림프종 1예를 경험하였기에 문헌 고찰과 함께 보고한다.

담낭에 단독으로 재발한 림프절외(Extranodal) NK/T세포 림프종 1예

고희자,김한조,윤진아,이상철,배상병,이남수,이규택,원종호,홍대식,박희숙,박성규,양미연,김현정,김찬규,김희경 대한혈액학회 2009 Blood Research Vol.44 No.4

Extranodal NK-T cell lymphoma is a subtype of non-Hodgkin’s lymphoma (NHL) and this most commonly affects the nasal and paranasal cavities. Primary lymphoma of the gallbladder is extremely rare and solitary relapsed extranodal NK-T cell lymphoma of the gallbladder has not yet been reported in Korea. We experienced a case of a solitary relapsed extranodal NK-T cell lymphoma of the gallbladder. One year earlier, a 55-year-old man was diagnosed with extranodal NK-T cell lymphoma of the anus, and he underwent six cycles of chemotherapy with CHOP (cyclophosphamide, adriamycin, vincristine and prednisone), and he achieved complete remission. The patient was admitted for right upper quadrant pain. Computed tomography (CT) performed on readmission revealed gallbladder wall thickening. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed hypermetabolic lesions along the gallbladder wall. The specimen obtained at cholecystectomy revealed CD3(+) and CD56(+) lymphoma, which is characteristic of NK-T cell lymphoma.

A case report of the extranodal NK/T-cell lymphoma, nasal type

( Yeo-rye Cho ),( Ho-jin Kim ),( Jeong-wan Seo ),( Tae-hoon Kim ),( Ki-hoon Song ),( Ki-ho Kim ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.1

Extranodal NK/T cell lymphoma is a lymphoma belonging to the mature T and NK neoplasm in the 2016 WHO classification. Skin is the second most common site of this disease, and when it appears on the skin, it shows various clinical features such as nodule and necrosis from erythema, so it is difficult to distinguish it from other skin diseases. We report a case of multiple necrotic lesions of the skin that had not improved with antibiotics and repeated incision and drainage and debridement, which diagnosed after skin biopsy with extranodal NK/T cell lymphoma, nasal type. Histologic examination revealed lymphoma in H & E stain, and immunohistochemistry staining showed positive for CD56 and EBV in situ hybridization. EBV was also detected quantitatively by EBV PCR. It is important to perform skin biopsy early in case of a skin ulcer that does not have a common cause of chronic ulcers, has a random site of occurrence, and does not improve on the general treatment of chronic ulcers. And we present this case to emphasize that early skin biopsy and diagnosis is important for the rapid start of treatment of extranodal NK/T cell lymphoma.

Identification of T-cell receptor expression in EBV-positive neoplastic cells in extranodal NK/T-cell lymphoma, nasal-type, and comparison with T-cell receptor gene rearrangement by BIOMED-2 assay

Takayama, Takuya,Shin, Sohyun,Kang, SoYoung,Kim, Suk Jin,Kim, Won Seog,Ko, Young Hyeh Elsevier 2018 Human pathology Vol.73 No.-

<P>The cellular lineage of extranodal NK/T-cell lymphoma, nasal-type (ENKTL), is determined by expression of T-cell receptor (TR) or TR gene rearrangement. In ENKTL, from TR immunohistochemistry, it may often be difficult to decide whether TR-positive cells are tumor cells or not, especially when TR is expressed in a subset of tumor cells. To analyze TR expression pattern and TR rearrangement in T lineage ENKTL, we performed double immunofluorescence staining for Epstein-Barr virus encoded small RNAs (EBER)/T-cell receptor (TCR) beta F1 and CD56/TCR beta F1 in 12 cases of ENKTL that showed TCR beta F1 expression in immunohistochemistry. TR gene rearrangement was analyzed using a commercial BIOMED-2 multiplex polymerase chain reaction system. Immunohistochemistry showed that all 12 cases expressed TCR beta F1 in a wide range of infiltrating cells from 100% to <1%. Two of them expressed both TCR beta F1 and TCR c gamma M1. EBER/TCR-beta F1 positivity was confirmed in 10 cases by double staining. One case failed to show EBER/TCR-beta F1 positive cells but showed a CD56/TCR beta F1 positive result. Among 12 cases, 5 had poor-quality DNA, 3 of them showed no polymerase chain reaction product, and 2 cases showed nonspecific peak of low height. Five of 7 cases with good DNA quality demonstrated monoclonal TR gene rearrangement. Based on TR expression and TR gene rearrangement, 10 of 12 cases of ENKTL were decided as a T-lineage tumor. In conclusion, because of common TR silence and poor DNA quality, consideration of both immunohistochemistry and TR gene rearrangement is necessary to determine the lineage of ENKTL. (C) 2017 Elsevier Inc. All rights reserved.</P>