Histiocytic cell neoplasms involving the bone marrow: summary of the workshop cases submitted to the 18th Meeting of the European Association for Haematopathology (EAHP) organized by the European Bone Marrow Working Group, Basel 2016

Abstract

The bone marrow is a preferential site for both reactive and neoplastic histiocytic proliferations. The differential diagnosis ranges from reactive histiocyte hyperplasia in systemic infections, vaccinations, storage diseases, post myeloablative therapy, due to increased cell turnover, and in hemophagocytic lymphohistiocytosis, through extranodal Rosai-Dorfman disease to neoplasms derived from histiocytes, including histiocytic sarcomas (HS), Langerhans cell histiocytoses (LCH), Erdheim-Chester disease (ECD), and disseminated juvenile xanthogranuloma (JXG). One of the most important recent developments in understanding the biology of histiocytic neoplasms and in contributing to diagnosis was the detection of recurrent mutations of genes of the Ras/Raf/MEK/ERK signaling pathway, in particular the BRAFV600E mutation, in LCH and ECD. Here, we summarize clinical and pathological findings of 17 histiocytic neoplasms that were presented during the bone marrow symposium and workshop of the 18th European Association for Haematopathology (EAHP) meeting held in Basel, Switzerland, in 2016. A substantial proportion of these histiocytic neoplasms was combined with clonally related lymphoid (n = 2) or myeloid diseases (n = 5, all ECD). Based on the latter observation, we suggest excluding co-existent myeloid neoplasms at initial staging of elderly ECD patients. The recurrent nature of Ras/Raf/MEK/ERK signaling pathway mutations in histiocytic neoplasms was confirmed in 6 of the 17 workshop cases, illustrating their diagnostic significance and suggesting apotential target for tailored treatments.

Rare myeloid sarcoma with KMT2A (MLL)-ELL fusion presenting as a vaginal wall mass

“…The t(14;18) and trisomy 8 have been reported in rare cases of HS arising in the setting of previously diagnosed follicular lymphoma or chronic myelomonocytic leukemia, probably from a common neoplastic precursor [15]. On the other hand, recurrent gene mutations in the Ras/Raf/MEK/ERK signaling pathway have been detected in histiocytic neoplasms [16]. For example, BRAF V600E mutation is well described in histiocytic neoplasms such as langhans cell histiocyotosis, Erdheim-Chester disease, and histiocytic sarcoma.…”

Myeloid Neoplasms with Elevated Plasmacytoid Dendritic Cell Differentiation Reflect the Maturation Process of Dendritic Cells

“…pDCs are scarce in normal conditions (14) but can be elevated in many abnormal states, such as inflammatory diseases, immune responses (15,16) and malignant neoplasms (17). Two types of malignancies originating from pDCs have been described: blastic plasmacytoid dendritic cell neoplasm (BPDCN) and mature plasmacytoid dendritic cell proliferation (MPDCP) or pDC proliferation in patients with myeloid disorders (PPMD) (14,(17)(18)(19)(20). Concerning morphology, tumor cells in BPDCN are undifferentiated blast cells, while those in MPDCP are mature and recognizable for their highly characteristic morphology of normal pDCs.…”

Bone Marrow Langerhans Cell Histiocytosis in Association with Kasabach-Merritt Syndrome: The Difficulty of a Differential Diagnosis

“…The differential diagnosis of LCH includes reactive histiocyte hyperplasia in systemic infections, storage diseases, or haemophagocytic lymphohistiocytosis [13]. DIC, KMS, and tuberculosis played a major dissimulating role in this case, since not only skin, lung, and consumptive findings were attributed to these conditions, but also prevented other diagnostic invasive examinations such as a bone marrow biopsy due to severe anaemia and thrombocytopenia.…”