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


METHODS
We 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.


RESULTS
Persistent 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.


CONCLUSIONS
In 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.
Lamant
Laurence
L
INSERM, U.563, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France.
Pileri
Stefano
S
Sabattini
Elena
E
Brugières
Laurence
L
Jaffe
Elaine S
ES
Delsol
Georges
G
D000077548:Anaplastic Lymphoma Kinase; D002648:Child; D005260:Female; D006801:Humans; D007299:Insect Bites and Stings / Q000150:complications* / Q000473:pathology; D008206:Lymphatic Diseases / Q000175:diagnosis / Q000209:etiology; D017728:Lymphoma, Large-Cell, Anaplastic / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D008297:Male; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D012871:Skin Diseases / Q000201:enzymology / Q000209:etiology* / Q000473:pathology
C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases