Osteolytic Lesions in Primary Myelofibrosis and Effect of Ruxolitinib Therapy: Report of a Case and Literature Review

Abstract

Here, we report the case of a young female affected by primary myelofibrosis (PMF) who developed an osteolytic lesion of the humerus during the follow-up, and the possible efficacy of ruxolitinib in controlling this rare event. After 26 years of follow-up, the patient reported onset of acute pain at the proximal region of the left upper limb. An X-ray revealed an osteolytic bone lesion in the proximal third of the humeral shaft, which was then confirmed by magnetic resonance imaging. A biopsy of the lytic lesion was done, revealing hypercellular bone marrow with hyperplastic granulopoiesis associated with megakaryocytic proliferation and atypia, accompanied by a diffuse and dense increase in reticulin fibrosis with extensive intersections and coarse bundles of thick fibers, consistent with a grade 3 collagen fibrosis. No new therapeutic intervention was initially required; however, 2 years later, the patient reported symptomatic splenomegaly and drenching night sweats, so ruxolitinib therapy was started. By week 8, the patient had near resolution of constitutional symptoms and a reduction of > 50% of the spleen size that normalized by 6 months; in addition, a repeat bone marrow biopsy showed a decrease in reticulin fibrosis grade. Interestingly, after 9 months of ruxolitinib therapy, further magnetic resonance imaging of the left upper limb showed the absence of bone lytic lesions and a substantial normalization of the bone tissue. In conclusion, with the present case report, we confirm ruxolitinib efficacy in reducing bone marrow fibrosis grade and assume its possible role in the resolution of osteolytic lesions in PMF. Obviously, further studies with a greater number of patients are needed to document the exact frequency of these unusual findings and the possible role of ruxolitinib in their treatment.

Osteolytic lesion in polycythemia vera: First report and review of literature

“…Investigations for other malignancies including multiple myeloma were normal. 18 Fluorodeoxyglucose positron emission tomography (PET) scan confirmed the right femur lesion with increased metabolic activity, but found no other abnormalities. Subsequent CT-guided biopsy of Coinciding with the osteolytic lesion the patient lost phlebotomy requirements (hemoglobin 125 g/L, hematocrit 0.40).…”

“…JAK-inhibitor [18], and chemotherapy [6,10,14]. In 14 cases, therapies only provided temporary symptomatic relief; and the osteolytic lesions either remained unchanged [6-11, 13, 15-17, 19, 21] or additional osteolytic lesions developed [20].…”

“…In all 16 cases investigations revealed progressive disease (i.e., worsening fibrosis, accelerated phase MPN or AML) along with the presence of osteolytic lesions; though diagnostic procedures were often delayed until further symptoms or cytopenias developed [6][7][8][9][10][11][12][13][14][15][16][18][19][20][21]. Chambers et al reported a patient with longstanding history of PV managed with hydroxyurea who presented to her local hospital after a fall and imaging revealed the presence of an osteolytic lesion [17].…”

“…Microenvironment changes in the bone marrow include abnormal production of granulocytes, megakaryocytes, fibroblasts, osteoblasts, and release of pro-inflammatory cytokines, which lead to marrow fibrosis, osteosclerosis, compressive atrophy, and bone destruction [18,[22][23][24] Osteosclerosis can be seen in 40%-70% of patients with MF, and less commonly in other MPNs [18,23,24]. The literature suggests that osteolytic lesions occur in areas where there has been…”

“…Patients with MPN can experience a constellation of debilitating symptoms that negatively impact their quality of life [2][3][4][5]. In prior surveys of patients with MPNs, bone pain was the fourth most common symptom reported by 44% of patients and rated as "very severe" in up to a third of MF patients [2][3][4][5].In very rare situations, patients with MPN can develop osteolytic lesions [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. We report the first case of an osteolytic lesion in a chronic-phase PV patient, and review published case reports of MPN patients with osteolytic lesions to summarize the clinical characteristics and implications for patient care.…”