The Non-Langerhans Cell Histiocytoses (Rare Histiocytoses) – Clinical Aspects and Therapeutic Approaches

Abstract

Rare histiocytoses, also called non-Langerhans cell histiocytoses, include all proliferative disorders of histiocytes, macrophages and dendritic cells that are not classified as Langerhans cell histiocytosis (LCH) and do not belong to the hemophagocytic lymphohistiocytosis (HLH) group of diseases. Thus, the term includes numerous benign or malignant, localized or systemic, adult or pediatric diseases. The classification of the histiocytic disorders has been revised several times. Here, we follow the classification recently published by Jean Francois Emile and an international expert panel, defining subgroups of histiocytoses described as L-Group, C-Group, M-Group, R-Group, and H-Group, which stands for LCH-like, cutaneous or mucocutaneous, malignant, Rosai-Dorfman-Disease like and HLH like. Some of the diseases have an excellent prognosis after resection or even disappear spontanously, others progress rapidly, requiring intensive systemic therapies. The malignant non-Langerhans cell histiocytoses in general have a poor prognosis, here, complex chemotherapy protocols are usually applied, with inconsistant results. An interesting perspective in non-malignant rare histiocytoses might be small molecular inhibitors, in particular BRAF inhibitors, since BRAF mutations have been found in some subtypes of non-Langerhans cell histiocytoses. By prospective and retrospective collection of experiences in a new registry (the “International Rare Histiocytic Disorders Registry”, IRHDR), knowledge about these rare diseases might hopefully be improved.

Zusammenfassung

Seltene Histiozytosen, auch non-Langerhans-Zell-Histiozytosen, umfassen alle proliferativen Erkrankungen der Histiozyten, Makrophagen und Dendritischen Zellen, die nicht klassifiziert sind als Langerhans-Zell-Histiozytosen (LCH) und nicht zur Gruppe der als Hämophagozytische Lymphohistiozytosen (HLH) zusammengefassten Erkrankungen. Somit schließt dieser Begriff eine Vielzahl benigner oder maligner, lokalisierter oder systemischer, adulter oder pädiatrischer Erkrankungen ein. Die Klassifikation dieser Erkrankungen ist wiederholt revidiert worden. Hier folgen wir der Klassifikation, die kürzlich durch JF Emile und ein internationales Expertenpanel publiziert wurde, welche Subgruppen der Histiozytosen definiert als L-Gruppe, C-Gruppe, M-Gruppe, R-Gruppe und H-Gruppe, womit gemeint sind die LCH-ähnlichen, die Haut- oder Schleimhaut-bezogenen, die malignen, die der Rosai-Dorfman-Erkrankung entsprechenden und die HLH-ähnlichen Erkrankungen. Manche der Erkrankungen haben eine exzellente Prognose nach Resektion oder verschwinden sogar spontan, andere sind rasch progredient, was dann intensive systemische Therapien erforderlich macht. Insgesamt haben die malignen non-Langerhans-Zell-Histiozytosen eine schlechte Prognose; hier kommen Chemotherapieprotokolle vom Typ der Weichteilsarkom- oder non-Hodgkin Lymphom-Therapien zur Anwendung, mit unterschiedlichem Erfolg. Eine interessante Perspektive bei den non-malignen seltenen Histiozytosen mögen kleinmolekulare Inhibitoren, insbesondere BRAF-Inhibitoren sein, denn BRAF-Mutationen wurden in einigen Subtypen der non-Langerhans-Zell-Histiocytosen gefunden. Mittels prospektiver und retrospektiver Datensammlung in einem neuen Register (dem “International Rare Histiocytic Disorders Registry”, IRHDR), wird zukünftig hoffentlich das Wissen um diese seltenen Erkrankungen besser gebündelt werden können.

Keywords

Rare Histiocytoses - Non-Langerhans Cell Histiocytoses - Xanthogranuloma - Rosai-Dorfman Disease - Erdheim-Chester Disease - Histiocytic sarcoma

Schlüsselwörter

Seltene Histiozytosen - Non-Langerhans-Zell-Histiozytosen - Xanthogranulom - Rosai-Dorfman-Erkrankung - Erdheim-Chester-Erkrankung - Histiozytäres Sarkom

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