Natural killer cell-derived large granular lymphocyte lymphoma of lung developed in a patient with hypersensitivity to mosquito bites and reactivated Epstein-Barr virus infection

Mizuki, Masao; Ueda, Shuji; Tagawa, Shinichi; Shibayama, Hirohiko; Nishimori, Y; Shibano, Masaru; Asada, Hideo; Tanaka, Masato; Nagata, Shinji; Koudera, Urara; Suzuki, Kenichi; Machii, Takashi; Ohsawa, Masahiko; Aozasa, Katsuyuki; Kitani, Teruo; Kanakura, Yuzuru

doi:10.1002/(sici)1096-8652(199812)59:4<309::aid-ajh7>3.0.co;2-b

Cited by 30 publications

(27 citation statements)

References 23 publications

(28 reference statements)

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“…[24][25][26][27][28] A significant proportion of these patients die of Epstein-Barr virus-positive NK/T-cell lymphoma or hemophagocytic syndrome. [21][22][23]29 A comparable scenario can be proposed regarding the possible role of insect bites as a triggering factor in the presentation of ALCL. Insect bite-associated antigens could result in an influx of CD4 + T lymphocytes, some of them bearing the t(2;5) translocation.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous presentation of ALK-positive anaplastic large cell lymphoma following insect bites: evidence for an association in five cases

Lamant¹,

Pileri²,

Sabattini³

et al. 2009

Haematologica

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BackgroundSkin involvement is frequent in ALK-positive anaplastic large cell lymphomas. The role of an insect bite as a triggering event has been postulated but not well documented. Design and MethodsWe retrospectively investigated five cases of ALK-positive anaplastic large cell lymphoma who presented with skin lesions occurring after an insect bite. Biopsies were immunostained with antibodies against CD30, ALK, T-and B-cell antigens. ResultsPersistent skin lesions developed after solitary insect bites in three patients and after multiple bites in two. Regional lymphadenopathy developed within weeks after the bite in three cases. In four cases the correct diagnosis was delayed due to misinterpretation of the findings as a reactive infiltrate in the skin (n=2) or lymph nodes (n=2); all cases subsequently showed small numbers of cells with nuclear and cytoplasmic staining for ALK. The final diagnoses were lymphohistiocytic variant (n=3) and composite common/small cell type (n=2) anaplastic large cell lymphoma. The patients were treated and three were alive at the last follow-up. Two patients died, one of pneumonia and the other of disseminated disease. ConclusionsIn these cases the sequence of events between the insect bites and the occurrence of both skin lesions and satellite lymphadenopathy suggest a direct relationship between the bite and the presentation with anaplastic large cell lymphoma. We postulate that insect bite-associated antigens could result in an influx of T lymphocytes, some bearing the t(2;5). The subsequent release of cytokines at the site of the bite could act as a 'second hit', eliciting activation of the latter cells, which would then express the oncogenic NPM-ALK protein and undergo uncontrolled proliferation.Key words: ALK-positive ALCL, NPM-ALK, skin involvement. Haematologica. 2010;95:449-455. doi:10.3324/haematol.2009 This is an open-access paper. Citation: Lamant L, Pileri S, Sabattini E, Brugières L, Jaffe ES, and Delsol G. Cutaneous presentation of ALK-positive anaplastic large cell lymphoma following insect bites: evidence for an association in five cases. Cutaneous presentation of ALK-positive anaplastic large cell lymphoma following insect bites: evidence for an association in five cases

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Section: Discussionmentioning

confidence: 99%

Cutaneous presentation of ALK-positive anaplastic large cell lymphoma following insect bites: evidence for an association in five cases

Lamant¹,

Pileri²,

Sabattini³

et al. 2009

Haematologica

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“…The development of NK/T-cell lymphoma in patients with chronic active EBV infection is well-documented. A history of mosquito allergy was mentioned in patients with NK/T-cell lymphoma and leukemia [19,20] and was suggested to be pathognomonic for the development of these diseases. In the present series, only one patient with an EBV-positive nonnasal NK/T-cell lymphoma had a history of mosquito allergy.…”

Section: Discussionmentioning

confidence: 99%

NK‐cell related neoplasms in Osaka, Japan

et al. 2004

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The frequency of NK-cell related neoplasms was estimated among lymphoproliferative diseases diagnosed and treated in Osaka, Japan, from 1999 to 2003. The total number of registered cases was 1,400, among which 1,092 patients were diagnosed as having malignant lymphomas. There were 987 cases of non-Hodgkin's lymphoma (NHL) and 105 (9.6%) of Hodgkin's lymphoma. Immunophenotypic analysis revealed that 743 patients had B-cell lymphomas and 209 T/NK-cell lymphomas. Among the T/NK-cell lymphomas, 40 showed positive immunoreactivity for CD56, and thus they were judged to be NK/T-cell lymphomas. They included one blastic NK-cell lymphoma and 39 NK/Tcell lymphomas. NK/T-cell lymphomas were further divided into three categories based on the main site of lesions: nasal type (23 cases), non-nasal extranodal type (11 cases), and nodal type (5 cases). The positive rate of infection with the Epstein-Barr virus determined by in situ hybridization was 83%, 36%, and 25% in the nasal, non-nasal, and nodal type, respectively. A mosquito allergy was found in one patient with EBVpositive non-nasal NK/T-cell lymphoma. The present study showed that the frequency of NK-cell related neoplasms among all NHLs was 4% in an ATL-non-endemic area of Japan.

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“…The close association between HMB and NK cell proliferative disorders/ lymphomas has been known [8,9]. The affinity of EBVinfected lymphoid cells to blood vessels has been previously reported in EBV-positive NK/T-cell lymphomas [8,10,11]. The term angiocentric or angiodestructive pattern is often used to describe these lesions of the lymphoma tissue.…”

Section: Discussionmentioning

confidence: 99%