Diagnostischer Stellenwert und klinische Bedeutung der Analyse von T-Zellrezeptor-Genumlagerungen beim kutanen T-Zell-Lymphom

Zusammenfassung

Kutane T-Zell-Lymphome (CTCL) stellen eine Gruppe lymphoproliferativer Hauterkrankungen dar, die durch klonale Akkumulation von T-Lymphozyten-Populationen charakterisiert sind. Die Diagnose wird in der Regel aufgrund klinischer und histologischer charakteristischer Eigenschaften der CTCL gestellt. Schwierigkeiten bereitet die Diagnosestellung insbesondere in frühen Stadien, aber auch in seltenen Varianten der CTCL. In diesen Fällen ist der Nachweis klonaler T-Zell-Populationen durch identisch umgelagerte T-Zellrezeptor-Gene eine wertvolle Hilfe. So zeigen PCR-basierende Techniken zum Nachweis klonaler T-Zell-Populationen eine hohe Sensitivität von 70 - 90 % in Hautbiopsien früher CTCL-Stadien. Nach Diagnosestellung ist der nächste wichtige Schritt die Ausbreitungsdiagnostik des CTCL, sinkt doch die Überlebensrate drastisch bei Auftreten extrakutaner Manifestationen wie z.B. bei Infiltration der Lymphknoten oder viszeraler Organe. Ein Stadienwechsel, d.h. die Progression der Erkrankung, wird in der Regel klinisch erst spät entdeckt. Insbesondere der Lymphknotenbefall, der erfahrungsgemäß als erste extrakutane Manifestation des CTCL gilt, stellt sowohl den Kliniker als auch den Histologen vor diagnostische Probleme. Hier konnten wir in einer aktuellen Studien zeigen, dass in ca. 50 % der dermatopathischen Lymphknoten identische klonale T-Zell-Populationen wie in den CTCL-Läsionen der Haut nachweisbar sind. Des Weiteren zeigte sich, dass diese Patienten eine reduzierte Überlebensrate haben, ähnlich denen, die eine histologisch manifeste Lymphknoteninfiltration durch das CTCL haben. Diese Daten belegen, dass T-Zellrezeptor-Umlagerungsanalysen bei Patienten mit CTCL sowohl eine diagnostische als auch prognostische Bedeutung haben und somit ein akkurates Staging ermöglichen.

Abstract

Cutaneous T-cell lymphoma (CTCL) is a clonal lymphoproliferative malignancy primarily involving the skin. Routine diagnosis of CTCL is based on its characteristic clinical and histopathologic features. However, the broad clinical and histological spectrum of the disease, especially of its early stages and rare variants, often complicates the differentiation between malignant CTCL and benign lymphoproliferative or reactive skin diseases. In these cases demonstration of a clonal T-cell population by detection of identically rearranged T-cell receptor genes (TCR) provides an adjunct. Using this approach clonality could be demonstrated in 70-90 % in CTCL biopsies of early stages by recent PCR-based studies, indicating a high sensitivity. After achieving the correct diagnosis the next important step is to stage the disease in CTCL-patients. Patients with CTCL usually have an indolent course with a 5-year survival of approximately 87%. However, in a significant number of patients the disease may progress and disseminated extracutaneous manifestations may develop involving the lymph nodes, blood and visceral organs. The prognosis for patients with widespread manifestation of CTCL beyond the skin is poor. Therefore, accurate evaluation in each individual case is crucial for an adequate, stage-adapted therapeutic approach. Determining the status of peripheral lymph nodes, generally the first site of extracutaneous dissemination is particularly important for clinical staging of patients with CTCL. Recently we could demonstrate in a large cohort of CTCL patients that nearly 50 % of dermatopathic lymph nodes of CTCL patients harbor a clonal T-cell population. Moreover, clonal T-cell detection in dermatopathic lymph nodes of CTCL patients was associated with limited survival similar to patients with histologically confirmed lymph node involvement, whereas all patients without T-cell clonality in the lymph nodes were alive at the last follow-up. In conclusion, these results suggest that TCR rearrangement analysis has an important impact in the initial diagnosis of CTCL and, moreover PCR analysis of lymph nodes is an important additional step in achieving an accurate clinical staging.

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