Bone Marrow Findings at Diagnosis in Patients with Multisystem Langerhans Cell Histiocytosis

Abstract

This study was designed to describe the bone marrow features of multisystem Langerhans cell histiocytosis (LCH) at diagnosis in patients with or without hematologic dysfunction. A retrospective review of bone marrow biopsies from patients with multisystem LCH was performed. Cases were diagnosed at the Garrahan Hospital between 1987 and 2004. Routine and immunohistochemistry techniques (hemaloxylin-eosin, periodic acid-Schiff, Giemsa, Gomori reticulin, and CD1a, CD68, and CD61) were evaluated. Clinical outcome and laboratory data were obtained from the medical charts. Twenty-two bone marrow biopsies from patients with multisystem LCH were reviewed at onset of disease. Four patients had no hematologic dysfunction and the other 18 patients had monocytopenia (9), bicytopenia (7), or tricytopenia (2). Increased number and dysplasia of megakaryocytes were evident in 22/22 samples and emperipolesis was present in 21/22 (95%). Aggregates of histiocytes and hemophagocytosis were seen in 9/22 samples. Myelofibrosis was found in 16/17 (94%) evaluable samples at diagnosis. No association of myelofibrosis and cytopenias or clinical outcome was found. Positive CD1a confirmed the presence of LCH cells in 3/22 (14%) samples. Hemophagocytosis and poor outcome were significantly more common in patients with bilineage and trilineage cytopenias. Langerhans cell histiocytosis cells were rarely seen in the bone marrow of these patients (14%); increased histiocytes and hemophagocytosis were more commonly found (41 %). Hemophagocytosis was associated with severe cytopenias. Bicytopenia and tricytopenia were associated with poor outcome (death). Myelofibrosis, megakaryocytic dysplasia, and emperipolesis were common findings.

Real-time genomic profiling of histiocytoses identifies early-kinase domain BRAF alterations while improving treatment outcomes

“…For example, in patients with LCH and bone marrow involvement, CD1a-positive cells are not consistently identified in the bone marrow (24,32,33). In several patients, exemplified by patients 1 and 3 in this report, we detected infiltration of LCH cells in the bone marrow and liver by the presence of BRAF V600E-positive cells.…”

Is Langerhans cell histiocytosis a neoplasia?

“…LCH patients with a worse prognosis are those who at diagnosis present with hematologic or hepatic involvement, frequently with high requirements of albumin and blood cells. Nevertheless, in those patients, no significant number of mitosis in the biopsies or clear cellular abnormalities was found that would be consistent with neoplasia …”

Splenomegaly unresponsive to standard and salvage chemotherapy in Langerhans cell histiocytosis: A case of extramedullary hematopoiesis

“…There have been no reports in the literature of splenic extramedullary hematopoiesis in LCH. While peripheral cytopenias are observed in LCH and predict a poor outcome, the underlying biologic mechanism remains unclear as recent bone marrow studies in LCH reject an infiltrative cause 13–15. In our case, the origin of this patient's cytopenias and extramedullary hematopoiesis with resulting hepatosplenomegaly is also unclear.…”