The first report of a previously undescribed EBV-negative NK-cell lymphoma of the GI tract presenting as chronic diarrhoea with eosinophilia

Zaheen, Ahmad; Delabie, Jan; Vajpeyi, Rajkumar; Frost, David

doi:10.1136/bcr-2015-212103

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…The diagnosis of EBV-negative aggressive NK-cell leukemia/lymphoma was made on the bone marrow biopsy in patient 1, bone marrow and liver biopsies in patient 2, and postmortem examination in patient 3. Although some of the previous reports hinted at a more indolent clinical course of patients with EBV-negative aggressive NKcell leukemia/lymphoma, 2,5,7,19 our findings indicate that the EBV-negative aggressive NK-cell leukemia/ lymphoma is highly aggressive and shares similar clinical features to EBV-positive counterpart, which is in agreement with the findings of the most recent study by Nicolae et al 9 Interestingly, the Asian predilection of EBV-positive aggressive NK-cell leukemia/lymphoma is not observed in this small series of EBV-negative cases (2 Caucasians, one African-American), which is also in agreement with the report by Nicolae et al (five white, one black, and one Asian). 9 An early diagnosis of EBV-negative aggressive NK-cell leukemia/lymphoma is difficult.…”

Section: Next-generation Sequencingmentioning

confidence: 99%

“…There are anecdotal case reports in the literature describing neoplastic proliferation of NK cells with aggressive clinical course but no EBV association. [2][3][4][5]19 Two small series on typical EBVpositive aggressive NK-cell leukemia/lymphoma included 2 out of 13 and 2 out of 14 EBV-negative patients. 6,7 One of the small series reported the absence of EBV had no prognostic significance as both EBV-negative patients died of aggressive disease within 1-2 months.…”

Section: Next-generation Sequencingmentioning

confidence: 99%

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EBV-negative aggressive NK-cell leukemia/lymphoma: a clinical and pathological study from a single institution

Gao

Behdad

et al. 2017

Modern Pathology

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Aggressive natural killer (NK)-cell leukemia/lymphoma is a systemic NK-cell neoplasm that preferentially affects Asians with a fulminant clinical course and is almost always associated with Epstein-Barr virus (EBV). The data on EBV-negative aggressive NK-cell leukemia/lymphoma are limited. Here we report a series of three patients (two Caucasians, one African-American) with EBV-negative aggressive NK-cell leukemia/lymphoma from a single institution, including a case diagnosed on post-mortem examination. Similar to EBV-positive aggressive NK-cell leukemia/lymphoma, our patients presented with constitutional symptoms and hepatosplenomegaly, and followed a highly aggressive clinical course. The disease involved peripheral blood, bone marrow, liver, spleen, and lymph node, and the neoplastic cells were pleomorphic with prominent azurophilic granules and demonstrated an atypical NK-cell phenotype. Lack of blood lymphocytosis (3 of 3), bone marrow interstitial infiltration (2 of 3), EBER negativity (3 of 3), and atypical phenotype including CD3 negativity by immunohistochemistry make an early recognition of the disease difficult. Ancillary studies revealed a complex karyotype (1 of 2), overexpression (3 of 3), and amplification (1 of 1) of c-MYC. The polycomb repressive complex 2 pathway-associated proteins EZH2 and H3K27me3 and immune checkpoint protein PD-L1 were overexpressed in three of three and two of three cases, respectively. Our findings indicate that the EBV-negative aggressive NK-cell leukemia/lymphoma shares similar clinicopathological features to the EBV-positive counterpart except for the high prevalence of Asian seen in EBV-positive cases. Overexpression of polycomb repressive complex 2 pathway-associated proteins and PD-L1 suggest potential therapeutic targets for this aggressive disease. Next-generation sequencing on two of three cases identified multiple genetic alterations but were negative for JAK-STAT pathway-associated gene mutations previously reported in EBV-positive NK/T-cell lymphoma, suggesting alternative molecular pathogenic mechanisms for EBV-negative aggressive NK-cell leukemia/lymphoma.

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Section: Next-generation Sequencingmentioning

confidence: 99%

Section: Next-generation Sequencingmentioning

confidence: 99%

EBV-negative aggressive NK-cell leukemia/lymphoma: a clinical and pathological study from a single institution

Gao

Behdad

et al. 2017

Modern Pathology

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“…The putative cell of origin is the NK cell, but a third of the cases are derived from γδ or, rarely, αβ T cells (Gaulard & de Leval, ). EBV is always positive although rare EBV‐negative cases have been reported (Zaheen et al , ). EBV contributes to the pathogenesis though production of cytokines, such as interleukins 9 and 10.…”

Section: Extranodal Nk/t Cell Lymphoma; Nasal Extra‐nasalmentioning

confidence: 99%

Mature T‐ and NK‐cell non‐Hodgkin lymphoma in children and young adolescents

et al. 2016

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Mature T/Natural killer (NK)-cell neoplasms of children and the young adolescent population exhibit higher prevalence in Central and South American and Asian populations and many are associated with Epstein-Barr virus (EBV). They are represented in large part by extranodal T/NK cell lymphomas- nasal-type or extra nasal-type, chronic lymphoproliferative disorders of T/NK cells or chronic active EBV disease, systemic EBV-positive lymphoproliferative disorders of childhood, hydroa vacciniforme-like lymphoma, hepatosplenic T-cell lymphoma and primary cutaneous gamma/delta T-cell lymphoma among others. Many T/NK cell neoplasms in this age group are derived from cells of the innate immune system, in contrast to adults where they are predominantly from the adaptive immune system. The genetic basis of T/NK cell lymphomas in children and young adolescents remains largely unknown. Anthracycline-based regimens and haematopoietic stem cell transplants (allogeneic and autologous) are current treatment modalities, however it is anticipated that novel targeted therapeutic agents will be available in the near future.

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Clinicopathological features and EBV infection status of lymphoma in children and adolescents in South China: a retrospective study of 662 cases

et al. 2018

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BackgroundThe clinicopathological features and Epstein-Barr virus (EBV) infection status of lymphoma in children and adolescents in South China is under-researched. South China is a well-known high-incidence area of EBV-associated nasopharyngeal carcinoma.MethodsA cohort of 662 consecutive children and adolescents’ lymphomas was retrospectively analyzed and Epstein-Barr virus encoded RNAs (EBERs) in situ hybridization was performed to detect the EBV infection.ResultsThe majority (501/662, 75.7%) of lymphomas in children and adolescents was Non-Hodgkin lymphoma (NHL). One hundred sixty one cases (24.3%) were Hodgkin lymphoma (HL). Of the NHL, precursor cell lymphoma, mature B-cell lymphoma and peripheral T/NK-cell lymphoma accounted for 32.0%, 41.1% and 26.9% respectively. The five common subtypes were lymphoblastic lymphoma (32.0%), Burkitt lymphoma (BL) (21.0%), anaplastic large-cell lymphoma (ALCL) (14.2%), diffuse large B-cell lymphoma (DLBCL) (13.8%) and extranodal NK/T-cell lymphoma, nasal type (ENKTCL) (6.2%). EBV infection was detected in 58.9% classical Hodgkin lymphomas (CHLs), 21.4% mature B-cell lymphomas and 52.4% peripheral T/NK-cell lymphomas. Moreover, EBV was associated with high grade NHL including ENKTCL (100.0%), BL (30.5%) and DLBCL (17.6%).ConclusionThe high proportion of peripheral T/NK-cell lymphomas in children and adolescents in South China are presented in this study and compared to western countries due to the high percentage of ENKTCL. ENKTCL is firmly associated with EBV infection, while more than half of HL, a portion of BL and DLBCL are related to EBV infection. This study conclusively demonstrates that EBV infection is more prevalent in children and adolescents with lymphomas in South China compared to western countries.Electronic supplementary materialThe online version of this article (10.1186/s13000-018-0693-0) contains supplementary material, which is available to authorized users.

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The first report of a previously undescribed EBV-negative NK-cell lymphoma of the GI tract presenting as chronic diarrhoea with eosinophilia

Cited by 4 publications

References 22 publications

EBV-negative aggressive NK-cell leukemia/lymphoma: a clinical and pathological study from a single institution

EBV-negative aggressive NK-cell leukemia/lymphoma: a clinical and pathological study from a single institution

Mature T‐ and NK‐cell non‐Hodgkin lymphoma in children and young adolescents

Clinicopathological features and EBV infection status of lymphoma in children and adolescents in South China: a retrospective study of 662 cases

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