Synchronous clonally related anaplastic large cell lymphoma and malignant histiocytosis

Abstract

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.

Keywords: Anaplastic large cell lymphoma; Case report; Secondary malignant histiocytosis; Synchronous malignant histiocytosis.

Fig. 1

A: Cytological examination of the bone marrow aspiration showing massive infiltration by large pleiomorphic cells with some of them displaying the morphological features of “hallmark” cells that are typically associated with anaplastic large cell lymphomas [x1000, May Grunwald-Giemsa [MGG] stain]. B: Histiocytic neoplastic proliferation with some cells displaying cytological atypias including spindle shape or emperipolesis images [x1000, May Grunwald-Giemsa [MGG] stain]. C: Representative image of a multinucleated histiocyte [double arrowheads] in the bone marrow aspiration displaying emperipolesis with the cytoplasmic engulfment of two large lymphomatous cells [single arrow heads], and one small normal lymphocyte [arrow]. One of the lymphomatous cells shows a cytoplasmic engulfment of an erythrocyte [x1000, May Grunwald-Giemsa [MGG] stain]. D: Representative image of two histiocytic cells [x1000, May Grunwald-Giemsa [MGG] stain]. E: FISH analysis showing the same cells seen in Panel C : each of the two lymphomatous cells [single arrow heads] display one red signal illustrating the monosomy 13 identified on karyotype and three green signals for the centromeric 12 probes. Multiple copies of the same pattern are shown within the nuclei of the multinucleated histiocyte [double arrowheads], while the small lymphocyte is displaying a normal pattern with two green and two red signals [arrow] [x1000]. F: FISH analysis on the same two histiocytic cells [from panel D]: one cell shows loss of one chromosome 13 signal and three signals for chromosome 12 while the other cell exhibits a duplication of the same pattern [x1000]

Fig. 2

Flow cytometry plots showing lymphomatous cells in red and histiocytes in dark blue. Lymphoma cells expressed the following immunophenotype: CD30 + CD4+/- CD56- CD13- HLADR- CD3- CD7+/- CD14-. Histiocytes expressed the following immunophenotype:CD30- CD4 + + CD56 + + CD13 + + HLADR + + CD3- CD7- CD14-

Fig. 3

Histopathological features of the bone marrow biopsy BMB: Some areas show diffuse infiltration of the marrow by lymphoma cells with a predominant intrasinusoidal location and occasional images of emperipolesis or hemophagocytosis [hematoxylin eosin A [H&E], original magnification x200]. Lymphoma cells are strongly positive for CD30 B [Immunohistochemical [IHC] staining, original magnification x200]. Other marrow spaces show a complete replacement of the hematopoietic tissue by a neoplastic proliferation of atypical histiocytes within a fibrous stroma C: [H&E], original magnification x100]. Malignant histiocytes are strongly positive for CD68 D and CD163 E [IHC staining, original magnification x100]. The histiocytic area shows no CD30 expression F [IHC staining, original magnification x200]