Bone Plasmacytoma in Patients Younger Than 30 Years-Case Report and Review of the Literature

This is the case report of a 26-year-old female who was diagnosed with bifocal bone plasmacytoma of the proximal femur and the proximal humerus. The tumour cells showed a plasmablastic morphology. After successful treatment with surgery and radiation therapy, the tumour recurred 10 years later in the left adrenal gland. We present the clinical, radiological and pathological findings and we discuss the differential diagnoses. We have also performed a review of the published cases younger than thirty years old.

Solitary plasmacytoma of the bone (SBP) is a rare plasma cell neoplasm without evidence of systemic plasma cell proliferative disease. It accounts for 2% to 5% of all plasma cell neoplasms [1,2,3]. The median age at diagnosis is 55 years, occurring 10 years earlier than multiple myeloma (MM) [4]. SBP has been reported in patient as young as 15 years (5), although reported cases in patients under 30 years of age are rare (Table 1) [6-26]. Males are more frequently affected than females. It occurs mostly in the vertebras and in the skull [2,3]. SBP is considered to be a precursor lesion to MM with conversion rates of 65% to 100% at 15 years. The morphologic spectrum of tumour cells ranges from cells with mature plasmacytic differentiation to large immature cells called plasmablasts. The immuno-phenotype is CD20, CD38+ and CD138+. SBP is a single lytic lesion without systemic marrow plasmacytosis. Multiple solitary plasmacytomas occur in up to 5% of patients and may involve the soft tissues or the bones [20]. Diagnostic criteria include normal bone marrow, normal skeletal survey, normal MRI of spine and pelvis and no related organ impairment. A monoclonal gammopathy may be seen in 24-72% of cases [21]; however, the monoclonal protein should disappear after resection of the lesion. Eighty five percent of SBP develop a local recurrence (12%), a new solitary lesion (15%), or MM (58%) [22]. Dissemination to MM is more commonly seen with primary lesions in the spine than with lesions in peripheral bones (61% vs 26%). Predictors of dissemination are age older than 50 years and the presence of monoclonal component after local treatment [22].

Table 1: Reported cases of bone plasmacytoma in young patients under 30 years of age.

A 26-year-old female, previously healthy, presented in 2009 with one month history of right hip heaviness and pain causing limping. The pain was aggravated by activity, improved by rest and absent at night. The patient denied any fever, chills, night sweats or weight loss. There were no palpable masses, lymphadenopathy, neurological deficiency or skin abnormality. The right hip joint range of motion was considerably decreased. The anteroposterior and lateral radiographs views revealed a radiolucent lesion with bone erosion and irregularity of right hip neck extending to the intertrochanteric area. The MRI revealed a 3.5 x 3 x 2 cm tumor in the right femur neck into the intertrochanteric area with irregular inferior border, iso signal on T1, faint hyper signal on T2 but shining hyper signal on STIR sequence. A biopsy was taken and before the results were finalized, the patient suffered a pathological fracture which required a right total hip replacement. The tumor was composed of a relatively monomorphic population of cells that have an abundant cytoplasm and mitotic activity, only mild pleomorphism and only mild cytological atypia. The cells showed no evidence of rosette formation or gland formation. The tumor cells expressed: strongly CD138, CD38, CD79a, IgG lambda and focally CD56. However, CD5, CD3 were expressed by scattered lymphocytes and CD117 CD99, CD34, CD63, CD45, CD15, CD30, CD20, S100, MPO and Alk were not expressed. Three months later, the patient underwent a total body MRI with background body signal suppression (DWIBS) which revealed a zone of diffusion in bone marrow at the level of the upper left humerus. Biopsies were taken and showed a large number of atypical cells (64%) of variable sizes, sometimes gigantic and strongly positive to immunostaining with CD138 and negative to PAS and CD99. Shortly after this finding the patient experienced a pathological spontaneous fracture which was surgically fixed. Bone marrow examination did not show any morphologic or phenotypic evidence of plasma cell dyscrasia or lymphoma. The serum and urinary protein electrophoresis and immunoelectrophoresis were normal. The complete blood cell count, liver function tests, serum lactate dehydrogenase and beta-2 microglobulin levels, renal function tests and calcium level were normal. The serologic screening assays for HIV and EBV were negative. Based on the imaging studies, the history and the pathological appearance with the presence of plasmablasts, nuclear inclusions (Dutcher bodies) and positive CD138 the patient was diagnosed as having a myelomatous proliferation with plasmablastic component and anaplastic cells and started on chemotherapy using bortezomib and dexametazone. She also received radiotherapy to the two involved region for a total dose of 36 Gy. The chemotherapy has been stopped 8 months later and the patient was followed up every 6 months for 18 months. Then she re-experienced heaviness in the right leg and limping. The imaging studies revealed a hyperintense signal on the pelvic girdle which seemed to arise from the hip joint just next to the radiation field. Further staging work-up including bone scan and PET CT scan were negative. The recurrence has been successfully treated by radiation therapy. The patient has remained in persistent complete remission for 9 years. Then she developed abdominal pain and distention, the PET CT scan revealed the presence of active bulky left adrenal gland, a big intra-abdominal mass causing intestinal obstruction and multiple lytic bone lesions. She underwent a palliative abdominal surgery. The biopsy confirmed the recurrence of plasmablastic plasmacytoma. The bone marrow studies revealed the presence of 10% plsma cells and the serum protein electrophoresis and immunoelectrophoresis showed an IgG lambda monoclonal gammopathy.

In summing up, this is a young female patient found to have two osteolytic lesions showing plasmablastic morphology with normal bone marrow and normal blood chemistry. We discuss in this report the differential diagnoses and the relationship between plasmablastic bone plasmacytoma and plasmablastic lymphoma.

Figure 1: A 4.1 x 3.2 x 2 cm cystic lesion in the neck of the right hip into the intertrochanteric area.

Figure 2: Total body MRI, diffusion in the bone marrow at the level of the upper left humerus.

Figure 3: Atypical cells of variable sizes, sometimes gigantic, from the bone marrow of the left humerus.

Figure 4: PET CT scan showing the left adrenal recurrence 10 years after remission.

The osteolytic, intramedullary lesion extending from the proximal femoral metaphysis through the subchondral bone occurring in this 26-year-old lady suggested differential diagnoses including; giant cell tumor, benign fibrous histiocytoma (BFH), Langerhans cell histiocytoma (LCH), plasmacytoma, lymphoma, osteosarcoma and osseous Ewing sarcoma. Based on the lesion location and the patient age the most likely diagnosis was giant cell tumor of bone, which represents 15% of all bone tumors with a peak incidence between 10 and 45 years and female predilection. Although, pathological fracture may ensue patients with BFH and LCH report pain with no impairment of the joint function. LCH usually occurs in children and adolescents and there is no defined age group for BFH occurrence. Osteosarcoma and Ewing sarcoma were considered less likely because of the absence of periosteal reaction, soft tissue extension and intra-lesion mineralization. Primary lymphoma of the bone has been defined variably as lymphoma arising in the medullary cavity of one or multiple bones without regional lymph node involvement. In SBP There is a male predilection with a median age at presentation of 55 years.  Sarcoma and carcinoma markers were negative in histopathology and the cytomorphological studies confirm the plasmablastic nature of this tumor. The full skeletal survey, the MRI and the PET CT scan revealed the involvement of two different and unusual skeletal sites with normal bone marrow and normal serum and urine protein electrophoresis and immunofixation. These characteristics could fit with the diagnosis of high-grade lymphoma or plasmablastic plasmacytoma. The clinical behaviors of these tumors and their treatments are radically different.

Primary bone lymphomas account for approximately 3% to 7% of all primary osseous malignancies and 92% of them are diffuse large B-cell lymphoma. The peak age at presentation is during the fifth decade. Tumors are located in lower extremities in 30% of cases, most frequently in metadiaphysal femur and pelvis. The lesions are purely lytic in 70% of cases without appreciable matrix production. Periosteal reaction is evident in 50% of cases and 20% of patients present with an associated pathological fracture [23]. They are usually CD20 positive and occasionally CD10 positive. Highly aggressive plasma cell MM or SBP may contain a predominance of plasmablasts which can closely resemble the malignant cells of plasmablastic lymphoma and other B-cell lymphoma with predominant plasmablastic features including Alk positive large B-cell lymphoma, HHV8 positive, Castelman disease and lymphoma of pleural effusion [27-32]. In both cases, plasmablasts express weakly the conventional B-cell markers and strongly the post-germinal center B-cell and plasma cell markers: CD138, MUM1, CD38 and CD56. In this case, the tumor cells did not express CD19 and CD45, while focally expressed CD56 and strongly CD38, CD138 and CD79a. The EBV is usually negative in plasmacytoma and positive in 60% of plasmablastic lymphoma. The distinction between plasmablastic lymphoma and plasmablastic myeloma depends heavily on clinical correlation. The presence of two distant lytic bone lesions favors the diagnosis of plasma cell neoplasm. Although MM and SBP may occasionally occur in the setting of HIV positive individuals, they do not have the strong association with AIDS that has been reported in plasmablastic lymphoma.

Although plasmablastic morphology has been reported to confer a poor clinical prognosis in plasma cell tumors [38]. However, the risk stratification relies primarily on clinical staging and cytogenetic abnormalities. It has also been suggested that in immunocompromized patients, plasmablastic tumors may have been driven by EBV to gain the plasmablastic cytomorphologic features and high proliferation index. EBER-positive plasmablastic plasma cell tumors rarely exist in immunocompetent patients [38]. Vega et al [32] found that the only significant difference between MM and PL was the presence of EBV-encoded RNA (EBER) which was positive in all plasmablastic lymphoma cases with or without HIV positive status. They suggested that when considering a single case with differential diagnosis between MM and PL, a positive EBER result makes the diagnosis of MM unlikely.  Neither immunostaining for EBV nor in situ hybridization for EBV-encoded RNA was performed in the tumor specimen; however, the serologic studies were negative for IgM and IgG. 

Young patients with plasma cell neoplasm, who present with multiple lytic bone lesions but without intervening infiltration of bone marrow, have been identified as having macro-focal MM. They usually are less anemic, with no hypercalcemia or renal failure, normal LDH level and uninvolved immunoglobulins and better response rate to primary treatment and long-term survival. A retrospective study of SEER database [40] collected 1164 patients over a 30-year-period. Only 1.1% was younger than 30 years and had better prognosis with 90% 5-year survival. No significant difference in survival between patients with single or 2 lesions was found; however, patients with more than 2 lesions had poorer prognosis. The use of any local disease control modality, either surgery or radiation therapy was associated with better outcomes. A preceding trauma was identified in a number of reported cases [7, 8, 9, 14, 15, 16, 17, 19] of SBP and given the rarity of such a tumor some authors suggested that trauma may play a role in the pathogenesis by acting as triggering stimulus for plasma cells to proliferate.

CD56 is expressed in NK cells and NK-like T-cells but it is aberrantly expressed in MM (75%) and it can distinguish plasma cells of MM from those of reactive plasmacytosis, MGUS, and lymphoplasmacytic lymphoma. CD56 expression has also been associated with osteolysis and poorer outcome [41]. Progression to multiple myeloma is the most important factor for overall survival in patients with SBP. The role of surgery alone and chemotherapy alone in achieving long term remission remains controversial. Radiation therapy; 30-50 Grays, may achieve 82% complete response rate with acceptable toxicity.