Plasma cell dyscrasias Notes

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This Osmosis High-Yield Note provides an overview of Plasma cell dyscrasias essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Plasma cell dyscrasias:

Monoclonal gammopathy of undetermined significance

Multiple myeloma

Waldenstrom macroglobulinemia

NOTES NOTES PLASMA CELL DYSCRASIAS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Acquired/inherited disorders ▫ Impaired platelet function, decreased platelet count, sequelae ▪ Accelerated destruction/consumption → decreased platelets SIGNS & SYMPTOMS ▪ Mucocutaneous bleeding (e.g. epistaxis, gingival bleeding, petechiae, purpura) DIAGNOSIS LAB RESULTS ▪ Complete blood count (CBC) ▪ Peripheral blood smear analysis ▪ Platelet function tests TREATMENT OTHER INTERVENTIONS ▪ Mitigate complications of deranged platelet function MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS) osms.it/monoclonal-gammopathy PATHOLOGY & CAUSES ▪ Asymptomatic premalignant plasma cell proliferative disorder; M protein < 3g/dL ▪ Most common plasma cell dyscrasia ▪ M protein ▫ IgM, IgA, IgG of free light chains ▪ 25% progress to multiple myeloma, early stage TYPES ▪ Non-IgM MGUS (IgG, IgA, IgD MGUS) ▪ IgM MGUS 438 OSMOSIS.ORG CAUSES Genetic mutations ▪ t(14,11) ▫ Translocation between Ig heavy chain gene on chromosome 14, oncogene (cyclin D1) on chromosome 11 ▪ t(14,6) ▫ Translocation between Ig heavy chain gene on chromosome 14, oncogene cyclin D3 on chromosome 6 ▪ Deletion of gene TP53 tumor suppressor locus on chromosome 17
Chapter 55 Plasma Cell Dyscrasias RISK FACTORS ▪ More commons in individuals who are biologically male; increased incidence with age ▪ Agent Orange exposure COMPLICATIONS ▪ Multiple myeloma (IgA, IgG MGUS), Waldenström macroglobulinemia, AL amyloidosis, light chain deposition disease (IgM MGUS) ▪ Venous thromboembolism (VTE), fractures, infections SIGNS & SYMPTOMS DIAGNOSIS LAB RESULTS ▪ Monoclonal proteins < 3mg/dL ▪ Plasma cells CD38+, CD56+, CD19- Bone marrow biopsy ▪ Mild hypercellularity ▫ Plasma cells < 10% TREATMENT OTHER INTERVENTIONS ▪ No treatment ▪ Regular observation; assess progression ▪ Mostly asymptomatic ▪ Rash, paresthesias, hypoesthesia MULTIPLE MYELOMA osms.it/multiple-myeloma PATHOLOGY & CAUSES ▪ Neoplasm of plasma cells (myeloma cells) in bone marrow ▫ Overproduction of M protein ▪ M protein ▫ IgG, IgA, free light chains ▪ Bone marrow cells, myeloma cells secrete cytokines, interleukin 6 (IL6), NF-κB → promote proliferation, survival of myeloma cells MNEMONIC: CRAB Features of Multiple myeloma Calcium elevated Renal disease Anemia Bone lesions Calcium (elevated) ▪ Increased bone resorption → hypercalcemia Renal disease ▪ Monoclonal free light chains (к, λ) ▫ Low molecular mass, filter easily in renal glomeruli → Bence Jones proteins in urine, toxic to proximal tubules → proximal tubular necrosis ▫ Bence Jones, Tamm-Horsfall proteins, albumin form obstructive proteinaceous casts in distal convoluted tubules, collecting ducts ▫ Hypercalcemia, hypercalciuria → nephrocalcinosis Anemia ▪ Neutropenia, thrombocytopenia ▪ Bone marrow infiltration by myeloma cells, cytokines → inhibits hematopoiesis Bone lesions (osteolytic) ▪ Neoplastic cells secrete cytokines (IL1β, TNFɑ) → activate osteoclasts → increase bone resorption → hypercalcemia, OSMOSIS.ORG 439
pathologic fractures ▪ Axial skeleton (skull, spinal vertebrae, ribs, pelvic bones), long bones ▪ Pathologic fractures along vertebrae → spinal cord compression SIGNS & SYMPTOMS Symptomatic multiple myeloma ▪ Hypercalcemia ▫ Confusion, somnolence, constipation, nausea, thirst ▪ Anemia, neutropenia, thrombocytopenia ▫ Fatigue, pallor, fever, infections, bleeding ▪ Bone lesions ▫ Pain, pathologic fractures; spinal cord compression → neuropathies (hypoesthesia, paresthesia) Non-secretory multiple myeloma ▪ Less common (3%) DIAGNOSIS TYPES Smoldering multiple myeloma (SMM) ▪ Asymptomatic CAUSES DIAGNOSTIC IMAGING Genetic mutations ▪ t(14,11) ▫ Translocation between Ig heavy chain gene on chromosome 14, oncogene (cyclin D1) on chromosome 11 ▪ t(14,6) ▫ Translocation between Ig heavy chain gene on chromosome 14, oncogene cyclin D3 on chromosome 6 ▪ Deletion of gene TP53 tumor suppressor locus on chromosome 17 X-ray (skeletal survey) ▪ Multiple rounded lytic bone lesions in skull, long bones, spine RISK FACTORS ▪ Alcohol consumption, obesity, radiation exposure, family history COMPLICATIONS ▪ Free light chains deposit in kidneys, heart, other organs → immunoglobulin light chain amyloidosis (AL amyloidosis) ▪ Renal failure ▪ Infection → death ▫ Most common, urinary tract infections (UTIs); pneumonia ▪ Hyperviscosity syndrome 440 OSMOSIS.ORG CT scan ▪ Radiodense bone lesions; in advanced disease, lesions in spleen, lymph nodes, lungs, etc. MRI ▪ Radiodense lesions in thoracic, lumbar vertebrae Fluorescent in situ hybridization (FISH) ▪ Detection of chromosomal mutations (translocations, deletions) LAB RESULTS ▪ Cormocytic, normochromic anemia, thrombocytopenia, leukopenia ▪ Increased monoclonal proteins (free light chains, ↑IgG > 3mg/dL, ↑IgA) ▪ Monoclonal protein measurement with densitometer ▪ Calcium blood test ▫ > 2.7mmol/L ▪ Bence Jones proteins (> 6mg/dL) ▪ Quantification of Bence Jones proteins ▪ Proteinuria greater than 1g/24hr ▪ Myeloma cells CD36+, CD56+, CD138+, CD319+
Chapter 55 Plasma Cell Dyscrasias Bone marrow biopsy ▪ Neoplastic infiltration → hypercellularity (> 30% plasma cells) ▪ Cytology ▫ Plasma cells: 2–3 times larger, eccentric nuclei, perinuclear halo (prominent Golgi apparatus) ▫ Other variants: mott cells (multiple grapelike cytoplasmic inclusions), flame cells (fiery red cytoplasm) TREATMENT ▪ Treatable, incurable ▫ If untreated, survival 5–12 months; with treatment, 48% survival for five years Figure 55.1 An X-ray image of the skull displaying numerous lytic lesions caused by myelomatous deposits. This radiological presentation is commonly known as a pepper pot skull. MEDICATIONS ▪ Chemotherapy ▫ Bortezomib, lenalidomide– dexamethasone, melphalan ▪ Immunomodulators ▫ Thalidomide, lenalidomide ▪ Bisphosphonates: prevent bone loss ▪ Antibiotics: infections ▪ Glucocorticoids: hypercalcemia OTHER INTERVENTIONS ▪ Autologous hematopoietic stem-cell transplantation (ASCT) ▪ Allogeneic stem cell transplantation with chemotherapy, glucocorticoids Figure 55.2 A histological section of the kidney from an individual with multiple myeloma. The myeloma cast colors a light pink on PAS stain. Figure 55.3 An X-ray image of the forearm demonstrating multiple lytic lesions in an individual with multiple myeloma. Figure 55.4 The histological appearance of a plasmacytoma, an aggregate of malignant plasma cells found in the soft tissues or axial skeleton. OSMOSIS.ORG 441
WALDENSTRÖM MACROGLOBULINEMIA osms.it/waldenstrom-macroglobulinemia PATHOLOGY & CAUSES ▪ Neoplasm of plasma cells, lymphoplasmacytoid cells; high levels of M protein as IgM antibodies ▪ AKA lymphoplasmacytic lymphoma ▪ Preceded by MGUS ▪ Neoplastic plasma, lymphoplasmacytoid cells infiltrate, crowd out normal hematopoietic cells → anemia ▪ High levels of IgM antibodies aggregate ▫ Hyperviscosity syndrome ▫ Cryoglobulinemia: IgM proteins become insoluble at reduced temperatures CAUSES ▪ Somatic mutations of MYD88, CXCR4 genes RISK FACTORS ▪ Autoimmune diseases mediated by antibodies ▪ HIV, hepatitis, rickettsiosis ▪ Pesticides exposure COMPLICATIONS ▪ Autoimmune hemolysis, raynaud phenomenon secondary to cryoglobulinemia ▪ Amyloidosis of heart, kidney, liver, lungs, joints SIGNS & SYMPTOMS ▪ Infiltration of neoplastic plasma cells ▫ Splenomegaly, hepatomegaly, lymphadenopathy ▪ Anemia ▫ Weakness, fatigue, weight loss 442 OSMOSIS.ORG Hyperviscosity syndrome triad ▪ Retinopathy ▫ Stasis + venous congestion, distention, hemorrhage of retinal veins → vision loss ▪ Neurologic symptoms ▫ Venous congestion of cerebral veins → hypoperfusion → headache, vertigo, hearing loss, parestesias, ataxia, stupor ▪ Mucosal bleeding ▫ IgM antibodies interfere with coagulation → gum bleeding, epistaxis, rectal bleeding, menorrhagia DIAGNOSIS DIAGNOSTIC IMAGING CT scan ▪ Hepatomegaly, splenomegaly LAB RESULTS ▪ Normocytic, normochromic anemia ▪ IgM ≥ 3000mg/dL TREATMENT ▪ If asymptomatic, observation MEDICATIONS ▪ Chemotherapy ▪ Plasmapheresis for hyperviscosity syndrome OTHER INTERVENTIONS ▪ Rarely autologous stem cell transplantation
Chapter 55 Plasma Cell Dyscrasias Figure 55.5 A peripheral blood film demonstrating rouleaux formation. Rouleaux may be seen in many infections, autoimmune conditions and plasma cell diseases, including Waldenstrom macroglobulinemia. OSMOSIS.ORG 443

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