Multiple myeloma

Other names: - Plasmacytic myeloma1 - Plasma cell myeloma1,2 - Myelomatosis1 - Kahlers disease1 - Plasmacytoma1,2. - Myeloma2. Impression: Belong to a group of lesions: Other lesions in this group: Classification: - Malignant2. o Malignant neoplasm of plasma cells2. - Poorly defined radiolucencies1 - Neoplastic proliferation of plasma cells1 - Tumor1. Variants: Types - Solitary myeloma1 o Single lesions are called plasmacytoma2. - Multiple myeloma1. o Contain multiple lesions, hence the name multiple 2. - Diffuse, generalized skeletal form1. o Can be confused with osteoporosis1. Patients with multiple myeloma are grouped according to the type of Ig produced by the tumor: 1. - IgG myeloma (55-56%)1. - IgA myeloma (20%)1. - IgD myeloma (2%)1. Note: - Plasma cells o are found in various areas of human body, particularly in the lymph nodes, bone marrow, and submucsa of the GI tract1. o are the functional unit of the B-cell line of the immune system & are responsible for the production of immunoglobulin (Ig) 1. Ig = proteins of high molecular weight that function as antibodies as they circulate throughout the tissues1. o In the presence of infectious disease and other disorders, the number of plasma cells increases within the bone marrow, resulting in an increase in Ig level1. Aka plasmocytosis1. Is a normal consequence of infection1. o There are 5 major classes of Igs: IgG, IgM, IgA, IgD, IgE1. The type of Ig that is being abnormally made can be identified by its electrophoretic pattern and varies among plasma cell dyscreasias1.

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Disproportional or uncontrolled plasma proliferation is called plasma cell dyscrasias [Isobe & Osserman, 1971] 1. o Type of plasma cell dyscrasias: 1. Multiple myeloma1. Waldenstrm macroglubulinemia1. in plasmacytoid lymphocytes1. Amyloidosis1. Deposition of a specific Ig in tissue1. - How to differentiate between between benign plasma cell infiltrates & myeloma? o Myelomatous regions are composed purely of plasma cells that obliterate the marrow1. o Normal marrow aspirates contain few plasma cells, approximately 3% or less1. o Conditions such as infections, RA & cirrhosis may contain many plasma cells (as many as 30%) but the plasma cells are admixed with other cell types and the marrow fat is not totally obliterated1. Etiology: - Cause of increased plasma is not known1. Pathophysiology: - Uncontrolled or disproportional plasma production (=plasma dyscrasias) causes clinical manifestations which is directly related to effects of expanding collections of cells or abnormal accumulations of substances produced by these cells1. - Neoplastic proliferation of plasma cells may occur in several forms1. - Plasma cells when stimulated can o produce an osteoclastic stimulating factor, responsible for the osteolytic lesions1. o Inhibit osteoblasts1. - When this clonal cellular proliferation occurs, these cells occupy first cancellous and later cortical bone, replacing the normally radiopaque bone with areas of radiolucency2. o Serum globulin (Ig) = Homogeneous protein M 1,3 Genetic: Epidemiology: Incidence: - Incidence in the skeletal bone o 35% of all skeletal bone tumors1. & 45% of all malignant skeletal tumors1. Is it myelomas in general or multiple myeloma? - Incidence in the jaws: o Vary from 2% to 78%2. - Multiple myeloma: o (50%) of all myeloma cases1. It is the most common malignancy of bone in adults2. o 10% of all malignant disease1. o > 10% of all hematologic cancers1. Multiple myeloma Page 2 Serum Ca+ Serum (PO4) Serum Alkaline phosphatase No change3 or 3 Bence-Jones Protein (in urine) 1,3

No change3

Age: - Usually between ages of 35 70 years (mean age of 60 years) 2. Gender: - M>F2. Race: Familial prevalence: Other:

Incidence of various types of myeloma: Multiple myeloma: most common form of myeloma1. Solitary myeloma: 25% of all myelomas1. Diffuse (generalized) myeloma: 15% of all myelomas1.

Findings:

Clinical presentation: Symptoms: - Associated with pain1,2. o Especially bone pain2. o +/- Oral pain2. o +/- back pain1. Associated with multiple myeloma (a multifocal type myeloma) 1. Typical feature of multiple myeloma is low back pain2. 1,2 - +/- Anemia . Associated with multiple myeloma (a multifocal type of myeloma) 1. - +/- Renal damage1. - +/- Numerous osteolytic lesions1. - +/- Hypercalcemia1. - +/- increased susceptibility to bacterial infection1. - +/- fatigue2. - +/- weight loss2. - +/- fever 2. Clinical findings: Various findings in Multiple myeloma: - Primary o Increased # of abnormal , atypical, or immature plasma cells in the bone marrow1. Plasma Ig levels are increased1. o Histologic proof of plasmacytoma1. o consistent with those of myeloma1. o Anemia is seen in most patients1. o Typical presenting feature is low back pain2. - Secondary: o Mayloidosis2. o Hypercalcemia2. o Presence of momoclonal proteins (ie Bence-jones) in the serum or urine or bone lesions1,2. Seen in half of the patients2. Which causes the urine to become foamy2. - Oral signs & symptoms: o Dental pain2. Multiple myeloma Page 3

o o o o o

Swelling2. Hemorrhage2. Paresthesia2. dysesthesia2. Or may be asymptomatic2.

Common sequel: Distribution of lesion: Size of lesion: Expansile: Laboratory findings: - Associated with a protein called Bence-Jones1. Histology: - Myeloma is composed of nodular or diffuse aggregates of plasma cells1. - The infiltrate of plasma cells is pure to almost totally pure, with an absence of fibrosis and marrow fat cells1. - The lesional infiltrates also completely lacks bone spicules, which explains the radiologic appearance of lysis1. - Multiple myeloma o Nodular foci1. - Generalized myeloma o Diffuse infiltrates of plasma cells result in the generalized form of multiple myeloma1. - Solitary myeloma o A single nodular mass1. Radiographic features: Number of patients with demonstrable radiologic findings in the jaws at the time of diagnosis is relatively small2. Multiple myeloma - Locularity: o Untreated or aggressive areas of destruction may become confluent, giving the appearance of multilocularity2. - Location: o Mand > Max but is uncommon in either 2. Mand: Posterior body is favored2. Ramus is favored2. Max: Usually in the posterior sites2. o Soft tissue lesions have been reported in the jaws and nasopharynx2. When seen on radiographs, they appear as smooth-bordered soft tissue masses, possibly with underlying bone destruction2. - Extension - Periphery (Edge, Margin): o Well-defined2. o Non-corticated2. Multiple myeloma Page 4

o Shape: o o o o o o

No signs of host bone reaction2. punched-out 2. May appear ragged2. May appear infiltrative2. Some have an oval shape2. Some have a cystic shape 2. If the lesion is located in the Periapical periodontal ligament space, it may have a border similar to that seen in inflammatory or infectious periapical disease2.

Size: Internal: o No internal structure is radiographically visible2. o Occasionally islands of residual bone, yet unaffected by tumor, give the appearance of the presence of new trabecular bone within the mass2. o Very rarely the lesions appear radiopaque internally2. Tooth resorption: Effect on surrounding structures: o Mand lesions may cause thinning of the lower border of the mandible2. May cause endosteal scalloping2. o Any cortical boundary may be effaced if lesions involve them2. o Periosteal reaction is uncommon2. But if it is present takes the form of a single radiopaque line or more rarely a sunray appearance2. o If a large amount of bone mineral is lost, teeth may appear to be too opaque and may stand out conspicuously from their osteopenic background2. o In a radiographic appearance similar to hyperparathyroidism, lamina dura and follicles of impacted teeth may lose their typical corticated surrounding bone2. o Mandibular neurovascular canal, which usually has visible walls, loses its cortical boundary in part or in whole2. o In the presence of renal disease, these changes are profound2. Tooth displacement: Number: Description:

Tumor Grading: Preferred Diagnostic modality: Imaging: - Plain film: - CT: - Ultrasonic: - MRI: Imaging challenges: - Correction Laboratory tests: - Immunoelectrophoresis1. Multiple myeloma Page 5

The type of Ig that is being abnormally made can be identified by its electrophoretic pattern and varies among plasma cell dyscrasias1. ? ?????? ? 1. o

Diagnostic checklist: Differential dx: Radiographically: - Radiolucent form of metastatic carcinoma2. o The most likely dz to be mistaken for multiple myeloma is the 2. o Knowledge of a prior malignancy in a patient may help differentiate multiple myeloma from metastatic carcinoma2. - Osteomyelitis2. o If severe may have a radiologic appearance similar to multiple myeloma2. Usually a visible cause for osteomyelitis is visible2. o Inflammatory & infectious lesions generally cause sclerosis in adjacent bone2. Multiple myeloma does not 2. - Simple bone cyst2. o If bilateral in the mandible may be mistaken for multiple myeloma2. o SBC is usually corticated in part2. o SBC is characteristically interdigitate between the roots of the teeth2. o SBC is generally seen in a much younger population2. - Hyperparathyroidism2. o Generalized radiolucency of the jaws may be caused by hyperparathyroidism2. o Differentiated based on abnormal blood chemistry (in hyperparathyrodisim)2. o Brown tumor of hyperparathyroidism, if present with generalized radiolucency of the jaws and similar symptoms, can readily be confused with multiple myeloma radiographically2. - Gauchers disease2. - Oxalosis2. Histologically Clinical Association with Syndromes: Association with other lesions: Mimicking of other lesions: Malignant transformation: Management: Biopsy: Surgical management: Radiographic management: Chemotherapy: - With or without autologous or allogenic bone marrow transplantation2. Multiple myeloma Page 6

Radiation Therapy: - May be used for treatment of symptomatic osseous lesions when palliation is required2. Medication: Prognosis: - Fatal systemic malignancy2. Recurrence Rate: Metastasis to: Complication:

Modality: Panoramic radiograph Revealing several small punched-out leisons of multiple myeloma involving the body and ramus of the mandible2

Modality A: Skull radiograph Modality B: Cropped panoramic radiograph Several small punched-out leisons of multiple myeloma involving the body and ramus of the mandible Modality: Cropped panoramic radiograph Shows a solitary lesion in the condylar neck region and a pathologic fracture (arrow)2

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Modality: Cropped panoramic radiograph Depicting multiple areas of well-defined bone destruction lacking any cortical boundary. The lesion are multiple, separate, and appear to be punched out, typical of changes seen in multiple myeloma2

References:
1. 2. 3.

Langlais R, Langland O, Nortje CJ. Diagnostic Imaging of the Jaws: Williams & Wilkins. White S, Pharoah M. Oral Radiology Principles and Interpretation. 6th ed2006. Langlais R. Lecture # 82009-2012.

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