Search

Neoplasms of histiocytes and dendritic cells are rare, and their phenotypic and biological definition is incomplete. Seeking to identify antigens detectable in paraffin-embedded sections that might allow a more complete, rational immunophenotypic classification of histiocytic/dendritic cell neoplasms, the International Lymphoma Study Group (ILSG) stained 61 tumours of suspected histiocytic/dendritic cell type with a panel of 15 antibodies including those reactive with histiocytes (CD68, lysozyme (LYS)), Langerhans cells (CD1a), follicular dendritic cells (FDC: CD21, CD35) and S100 protein. This analysis revealed that 57 cases (93%) fit into four major immunophenotypic groups (one histiocytic and three dendritic cell types) utilizing six markers: CD68, LYS, CD1a, S100, CD21, and CD35. The four (7%) unclassified cases were further classifiable into the above four groups using additional morphological and ultrastructural features. The four groups then included: (i) histiocytic sarcoma (n=18) with the following phenotype: CD68 (100%), LYS (94%), CD1a (0%), S100 (33%), CD21/35 (0%). The median age was 46 years. Presentation was predominantly extranodal (72%) with high mortality (58% dead of disease (DOD)). Three had systemic involvement consistent with 'malignant histiocytosis'; (ii) Langerhans cell tumour (LCT) (n=26) which expressed: CD68 (96%), LYS (42%), CD1a (100%), S100 (100%), CD21/35 (0%). There were two morphological variants: cytologically typical (n=17) designated LCT; and cytologically malignant (n=9) designated Langerhans cell sarcoma (LCS). The LCS were often not easily recognized morphologically as LC-derived, but were diagnosed based on CD1a staining. LCT and LCS differed in median age (33 versus 41 years), male:female ratio (3.7:1 versus 1:2), and death rate (31% versus 50% DOD). Four LCT patients had systemic involvement typical of Letterer-Siwe disease; (iii) follicular dendritic cell tumour/sarcoma (FDCT) (n=13) which expressed: CD68 (54%), LYS (8%), CD1a (0%), S100 (16%), FDC markers CD21/35 (100%), EMA (40%). These patients were adults (median age 65 years) with predominantly localized nodal disease (75%) and low mortality (9% DOD); (iv) interdigitating dendritic cell tumour/sarcoma (IDCT) (n=4) which expressed: CD68 (50%), LYS (25%), CD1a (0%), S100 (100%), CD21/35 (0%). The patients were adults (median 71 years) with localized nodal disease (75%) without mortality (0% DOD). In conclusion, definitive immunophenotypic classification of histiocytic and accessory cell neoplasms into four categories was possible in 93% of the cases using six antigens detected in paraffin-embedded sections. Exceptional cases (7%) were resolvable when added morphological and ultrastructural features were considered. We propose a classification combining immunophenotype and morphology with five categories, including Langerhans cell sarcoma. This simplified scheme is practical for everyday diagnostic use and should provide a framework for additional investigation of these unusual neoplasms.

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. DESIGN AND 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.

Resume La valeur pronostique de la recherche clinique et histologique d'une infiltration leucemique testiculaire residuelle a l'arret du traitement est encore discutee. L'introduction des techniques immunohistochimiques modernes pourrait ameliorer les resultats. Patients et methodes . — De 1982 a 1992, 70 garcons traites consecutivement pour une leucemie aigue lymphoblastique (LAL) avec le meme protocole therapeutique ont ete inclus dans l'etude. Une biopsie testiculaire (BT) bilaterale a ete faire chirurgicalement. Une partie du matertel a ete fixee et examinee en microscopie conventionnelle. Sur l'autre partie, l'analyse immunohistochimique a ete realisee avec un panel d'Ac Mc anti-T et anti-B, dont le JCB 117 (anti-CD79a) qui marque les lymphoblastes pre-B precoces. Resultats . — Vingt-cinq enfants ont rechute pendant le traitement et n'ont pas es de BT. Panns les 45 garcons ayant en une BT protocolaire, un seul avait une infiltration massive en histologie conventionnelle. Trente-neaf avaient un examen morphologique et immunohistochimique normal: six d'entre eux rechuteront ulterienrement dans la moelle osseuse; leux survie sans evenement (SSE) est: 85 ± 10 % avec un recul median de 80 mois apres la biopsie. Chez cinq garcons, l'anti-CD79a etait positif sur les cellules blastiques dans quatre ces et l'anti-CD3 dans un cas: quatre d'entre eux rechuteront dont deux au niveau testiculaire dans l'annee suivant la biopsie; leur SSE etait de 20 ± 36 % (3 = 0,001). Conclusion . — De nouveaux Ac Mc tels que le JCB 117 (anti-CD79a) peuvent detecter une maladie residuelle minime dans les testicules des enfants traites pour une LAL B, en particulier sur le materiel de routine. Ces resultats, s'ils sont confirmes dans une plus vaste etude, pourraient influencer is strategie therapeutique ulterieure.

This highly illustrated, diagnostic guidebook provides a single comprehensive source of essential information to enable non-specialists to diagnose lymph node and related diseases with confidence. The text is didactic and practical, covering reactive as well as malignant conditions. Diagnosis of Lymphoproliferative Diseases approaches the disorders based on the WHO classification and is edited by members of the WHO panel for the classification of lymphomas. This second edition contains over 1000 high quality, digitised colour images and tables of essential criteria for each diagnosis. New features include: Full discussion of immunostaining, the core of modern diagnosis Variant forms and technical issues This authoritative guide is an essential reference for haematologists, haematopathologists, general pathologists, diagnostic histopathologists and oncologists. © 2012 Kevin C. Gatter, Georges Delsol, Roger A. Warnke and Francesco Pezzella.

International audience