Osteolytic Bone Lesions in Patients with Primary Myelofibrosis: A Systematic Review

Background: Philadelphia negative Myeloproliferative neoplasms classically characterized by excess production of terminal myeloid cells in the peripheral blood. Among this group, primary myelofibrosis is the least common and usually carries the worst prognosis. Bone involvement in primary myelofibrosis has many forms and tend to manifest as osteosclerotic lesions in vast majority of cases, however osteolytic lesions are reported in exceptional occasions. In this review, we tried to shed the light on this rare association. Methods: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the English literature (Google scholar, PubMed, and SCOPUS) for studies, reviews, case series, and case reports about patient with myelofibrosis who develop lytic bone lesion. We used the terms in combination: "Myelofibrosis'" or "Primary myelofibrosis" OR "chronic idiopathic myelofibrosis" OR "agnogenic myeloid metaplasia" and "Osteolytic bone lesion", "Osteolytic lesion", "lytic bone lesion". The review included patients with primary myelofibrosis confirmed by biopsy. The reference lists of the included studies were scanned for any additional articles. The search included all articles published up to 10th April 2021. Two independent reviewers screened the titles and abstracts of the records independently and papers unrelated to our inclusion criteria were excluded. A total of 13 articles were included in the review. Results : Total of 13 patients were included in the review. 7 patients were males, male to female ratio almost of 1:1. The mean age at time of diagnosis was 57.69 year, only two cases were diagnosed at young age, however the majority have osteolytic bone lesion at age above 50 years (12/13) of cases. The mean time between the diagnosis of primary myelofibrosis until the osteolytic bone lesion capturing was approximately 8.8 years. 9 out of 13 patients have painful bone lesion, others were incidental finding during a scan for other reasons. All patients have significant splenomegaly. All patients had the lytic lesion detected on x ray, and 2 patients had confirmed findings on magnetic resonance imaging (MRI). The most common affected bones were the vertebrae, pelvis, ribs, humerus then the scapula, femur and skull and less frequently wrist bones and calcaneus. Only one case has reported involvement of the tibia and fibula. The shape, the extension and the numbers of lesion were variable, some showed cortical sparing and others come with cortical destruction. 10 out of 13 cases have confirmed the nature of the osteolytic lesion containing hematopoietic stem cells with or without fibrosis, 2 cases were positive for JAK2 mutation. 2 patients have received ruxolitinib, one of them preceded with bone marrow transplant, others received nonspecific therapies. Discussion: The hyperdynamic ineffective bone marrow can have a negative impact on the bone structure resulting in different types of bone pathology including lytic and sclerotic lesions. The exact mechanism beyond developing lytic lesions is not fully studied, observations revealed two possible causes: systemic inflammation and direct mechanical compression from para-osseus lymph nodes. Lesions prevalence was equal in both genders which can be attributable to a small sample size, in addition, most of the patients were in advanced stages when the lytic lesions discovered and this observation can be explained by the needed time to generate extramedullary hematopoiesis and its subsequent effect on bone structure. The variation in time between the diagnosis of PMF and development of osteolytic bone lesions could be due to the indolent phase of the disease, in which patients can survive for decades without symptoms. Until recently the treatment of myelofibrosis was supportive, but after establishing the JAK2-stat pathway role in myeloproliferative disorders the FDA approved ruxolitinib a JAK2 inhibitor which shows not only survival benefit but also has a significant impact on the resolution of the lytic bone lesions as well. conclusion Osteolytic bone lesions in patients with primary myelofibrosis is extremely rare finding, and noticed shortly after diagnosis in elderly and after longer duration in young patients. The lytic lesion seems to have a bad prognostic value as we can notice 11 out of 13 patients died within one year of detection. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

CLINICOPATHOLOGICAL STUDY OF MULTIPLE MYELOMA WITH EXPRESSION OF CD56

Background: Multiple myeloma (MM) is a plasma cell neoplasm with spectrum of clinical presentation and multisystem involvement. CD56 (a neural cell adhesion molecule, NCAM) is a membrane glycoprotein belonging to the immunoglobulin superfamily. Normal plasma cells do not express CD56, but it is frequently expressed by malignant plasma cells in patients with MM. The present study was conducted to evaluate the expression of CD56 in MM and its association with disease characteristics. Methods: We analysed CD56 expression in 34 newly diagnosed MM cases using immunohistochemistry in bone marrow core biopsies processed routinely. Results: CD56 expression was found in 70.97% cases. The clinicopathological disease characteristics such as age, serum creatinine level, serum β2-microglobulin level and plasmablastic morphology showed no statistically signicant difference between CD56 positive and negative groups. Bone lesions were signicantly higher in positive cases than in negative cases. Conclusion: CD56 expression dene a unique clinicopathological entity in MM. Expression of CD56 correlate well with lytic bone lesion and may correlate with its pathogenesis.

POEMS SYNDROME ET COVID 19: LES RETOMBEES DUNE PANDEMIE !

POEMS syndrome defines a rare multisystem syndrome due to the paraneoplastic manifestation of plasma cell dyscrasia. The diagnosis is based on the clinic and the laboratory: this acronym includes part of all the current criteria on this disease: Polyradiculoneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disease (PCD) and Skin changes. Peripheral neuropathy is often the revealing symptom of the disease. Bone involvement is present in 54 to 97% and is typically osteosclerotic. POEMS syndrome with plasmacytoma lytic bone lesion remain exceptional. In the case of patients with less than three solitary bone plasmacytomas, radiotherapy is recommended as a therapeutic approach with variable efficacy. Relapses remain frequent requiring systemic treatment. The management of the pandemic had indirect effects on serious diseases in fact, fear of the crisis caused by the epidemic is pushing a large number of patients to delay their request for care. In addition to chronic patient monitoring, the practitioners primary concern is to detect emergency situations. We report the case of a 45-year-old right-handed patient with a progressive symmetrical ascending four-limb sensory motor deficit over the past five months, suggesting polyradiculoneuropathy, associated with rib pain from the 7th to the 9th right ribs. The assessment confirms demyelinating and axonal polyradiculoneuropathy and demonstrates the presence of a monoclonal IgG λ gammopathy, in connection with a solitary osteolytic right costal plasmacytoma of the 7th rib, without organomegaly on thoraco-abdomino-pelvic CT scan. We suspected the diagnosis of POEMS syndrome which was confirmed by elevated serum VEGF dosage. He is receiving corticosteroid therapy with localized radiotherapy with good clinical outcome and biological stabilization. However, the patient had presented during confinement for Covid-19 a worsening of the progressive symptomatology evolving for 6 months. He presented to the emergency room with a picture of flaccid quadriplegia and fatal respiratory distress.

Brown tumor due to primary hyperparathyroidism resulting in acute paraparesis: Case report and literature review

Background: Brown tumor (Osteoclastoma) is a rare benign, focal, lytic bone lesion most commonly attributed to a parathyroid adenoma; it occurs in approximately 5% of patients with primary hyperparathyroidism, and 13% of patients with secondary hyperparathyroidism. Most tumors are located in the mandible, pelvis, ribs, and large bones; only rarely is it found in the axial spine. Case Description: A 37-year-old male with primary hyperparathyroidism presented with an MR-documented T4 and T5 brown tumor (Osteitis Fibrosa Cystica) resulting in an acute paraparesis. The patient successfully underwent excisional biopsy of an expansile, enhancing, bony destructive lesion at the T4-5 level. Subsequently, he required subtotal excision of a left upper parathyroid tumor. Conclusion: Patient with primary hyperparathyroidism may acutely present with paraparesis attributed to brown tumors of the spine warranting emergent operative decompression.

Pigmented epithelioid melanocytoma: a rare lytic bone lesion involving intradural extension and subtotal resection in a 14-month-old girl

Pigmented epithelioid melanocytomas (PEMs) are low-grade, intermediate-type borderline melanocytic tumors with limited metastatic potential. To date, PEMs have been treated via gross-total resections. Postoperative recurrence and mortality are rare. This case highlights a unique presentation of a PEM that involved bone destruction and intradural infiltration, which required a subtotal resection. To the authors’ knowledge, this is the first report of a PEM extending through the dura and necessitating subtotal resection, which is contrary to the standard of care, gross-total resection. Surveillance imaging 10 months after resection remained negative for clinical and radiological recurrence.