Synchronous clonally related anaplastic large cell lymphoma and malignant histiocytosis.

Background: Synchronous malignant histiocytoses are rare conditions that occur concurrently with another hematologic neoplasm. Most reported cases are associated with B-cell lymphoproliferative disorders, while associations with T-cell hemopathies are less common. These two diseases may share mutations and/or cytogenetic anomalies, which can lead to malignant proliferations. In such cases, the term "secondary malignant histiocytosis" can be applied.

Case description: A 26-year-old patient was diagnosed with anaplastic lymphoma kinase negative anaplastic large cell lymphoma [ALK-ALCL] associated with synchronous malignant histiocytosis. Neoplastic cells were distinguished by the exclusivity of the rearrangement of TCR genes within the lymphoma cells, whereas mutations in the KRAS and TP53 genes affected mono-histiocytic cells. However, these two cells populations shared common chromosomal abnormalities. First line treatment protocol included Brentuximab vedotin, cyclophosphamide, doxorubicin, and methylprednisolone. Despite a partial clinical and biological response after cycle 1 of treatment, the patient was refractory at the end of cycle 2. Patient died in the intensive care unit from a multiple-organ failure related to lymphohistiocytic hemophagocytosis.

Conclusion: This case represents the first documented instance of synchronous malignant histiocytosis associated with anaplastic large cell lymphoma. Notably, the uniqueness of this case lies in the absence of TCR rearrangement in the histiocytic cells, despite the presence of shared chromosomal abnormalities with the lymphomatous cells indicating a common origin for both neoplastic proliferations. Considering the rarity of such occurrences, the use of histiocytosis targeted therapy alongside conventional lymphoma treatment warrants consideration in such a context.