SDL 18: plasma cell neoplasms

plasma cell neoplasms (plasma cell dyscrasias)

clonal proliferations of immunoglobulin (Ig)- producing plasma cells or lymphocytes that make and secrete a single class of Ig or a polypeptide subunit that is detectable as a monoclonal protein (M-protein) on serum or urine protein electrophoresis

a destructive plasma cell tumor involving the axial skeleton

multiple myeloma presents as

presence of ≥10% plasma cells on bone marrow biopsies (normal: 0 - 3.5%)

most important diagnostic criterion off multiple myeloma

-mature: indistinguishable from normal cells, clock face

-immature

-pleomorphic

what are the 3 classes of myeloma cells?

Dutcher body

an intranuclear globular inclusion that is highly specific to neoplastic myeloma cells, and there is little doubt regarding the neoplastic characteristics if observed.

russel body

grapelike globular inclusion associated in a Mott cell

-associated with multiple myeloma

CD38 and CD138

-CD138 more specific for plasma cells

CD marker for both normal and myeloma plasma cells

CD56

70% of myeloma cells express this CD marker, which is negatively on normal plasma cells

(i) infiltration of plasma cells into the bone or other organs, (ii) kidney damage from the production of excessive immunoglobulins, which often have abnormal physicochemical properties, and (iii) suppression of normal humoral immunity

main clinical features of multiple myeloma

C (calcium elevated in plasma), R (renal failure), A (anemia), and B (bone pain).

CRAB acronym for multiple myeloma menas

light chain cast nephropathy

most frequent form of renal damage inn multiple myeloma

normocytic and normochromic

type of anemia associated with multiple myeloma

spine

-results in neuro symptoms

______ is the bone site that is most frequently affected by myeloma induced bone osteolysis

Symptoms of hyperviscosity are much less frequent in myeloma than in Waldenström macroglobulinemia

is hyperviscosity common in multiple myeloma

3.2 centipoise

the reference range of whole blood viscosity at a physiologic hematocrit

Streptococcus pneumoniae and Gram-negative organisms

bacteria most frequently impacting pts with MM

-bleeding problems AND VTE

bleeding problems associated with multiple myeloma

10-15%

up to ____% of MM develop overt clinical AL amyloidosis

the myeloma cell mass

the amount of M protein reflects

-B2 microglobulin

-LDH

-elevated ESR

general lab findings associated with multiple myeloma

proteinuria

urine findings of MM

skeletal surveys

-reveal lytic lesions

-not as sensitive as PET

first image in assessment of MM

trisomies and translocations

the two main types of of cytogenic abnormalities in MM

mutations in KRAS, NRAS, BRAF, and TP53.

-effect the MAPK pathway

mutations associated with MM

monoclonal gammopathy of undetermined significance (MGUS)

Virtually all MM cases are preceded by a premalignant plasma cell proliferative disorder known as

cytogenetic abnormalities, which are the product of an abnormal plasma cell response to antigenic stimulation----> plasma cell producing monoclonal immunoglobulin

-classic two-hit genetic model of malignancy

MGUS develops as the result of

-additional genetic abnormalities

-some pts go to more advanced pre-malignant stage of smoldering multiple myeloma

how does MGUS progress to MM

IL-6 and IGF-1

cytokines associated with the progression of MGUS to MM

smoldering multiple myeloma

a more advanced premalignant stage of plasma cell proliferation, in the spectrum between MGUS and symptomatic MM and is characterized by a much higher risk of progression to MM

IgH translocations involving the MYC oncogene, activating mutations of RAS gene, and deletions at 17p13

second 'hits' causing transformation of MGUS to SMM or MM

extramedullary myeloma

a clonal plasmacytic infiltrate at anatomic sites distant from the bone marrow in a patient with underlying MM

focal adhesion kinase (FAK)

enzyme that is critical in progression of MM to extramedullary myeloma

MGUS (monoclonal gammopathy of undetermined significance)

-the most common plasma cell dyscrasia

-characterized by excess serum M protein

MGUS (monoclonal gammopathy of undetermined significance)

patients are asymptomatic, the serum M protein level is <3 g/dL, and bone marrow biopsies reveal <10% monoclonal plasma cells

-absent CRAB

-imaging norrmal

The risk of progression to active myeloma is 1% per year

prognosis associated with MGUS

-one type arises from lymphoid cells

-one type arises from plasma cells

what are the two types of MGUS

smoldering multiple myeloma

presence of a serum monoclonal protein (IgG or IgA) of ≥3 g/dL and bone marrow plasma cells of >10% of all nucleated cells

bone, can be foundd in soft tissues

solitary plasmacytoma most frequently occurs in

-SP lacks CRAB features, bone lytic changes, and serum or urinary monoclonal protein

how is solitarry plasmacytoma distinct from MM?

plasma cell leukemia

a clinically aggressive variant of MM

-may present with CRAB features , or manifestations of other leukemias

total leukocyte count is elevated with >20% plasma cells on the differential count.

lab criteria to diagnose plasma cell leukemia

light chain deposition disease

caused by the deposition of monoclonal light chains in multiple organs

-DIFFERENT from AL amylodosis

hypertension, micro-hematuria and proteinuria (often in the nephrotic range)

typical presentation of light chain deposition disease

nodular glomerulosclerosis

granular deposits are present on glomerular basement membrane, mesangium and tubular basement membranes

kidney biopsy finding associated with LCDD

restrictive cardiomyopathy. Liver involvement is asymptomatic. Involvement of peripheral nerves is associated with pain, loss of sensation and muscle weakness.

non-kidney manifestations of light chain deposition disease

peripheral neuropathy (P), a monoclonal protein in plasma (M), and other paraneoplastic features, the most common of which include organomegaly (O), endocrinopathy (E), and skin changes (S).

define the features of POEMS syndrome

symmetric peripheral polyneuropathy ----> pt in wheelchair

this sign dominates the clinical picture of POEMS syndrome

lambda

type of light chain almost always seen with POEMS syndrome

hyperpigmentation, hemangiomas, and hypertrichosis.

major dermatologic findings associated with POEMS

Lymphoplasmacytic lymphoma

a low-grade non-Hodgkin lymphoma composed of cells exhibiting a spectrum of B-cell differentiation ranging from small lymphocytes to plasmacytoid lymphocytes and plasma cells.

syndrome of Waldenström macroglobulinemia (WM)

-LPL cells have capacity to synthesize and secrete high amounts of immunoglobulins

-associated with lymphoplasmacytic lymphoma

pancytopenia

most lymphoplasmacytic lymphoma pts present with

epistaxis, gingival and gastrointestinal bleeding or menorrhagia, visual disturbances because of retinal hemorrhages, headaches, vertigo, and dizziness

hyperviscouos symptoms associated with lymphoplasmacytic lymphoma

The hyperviscosity-related retinopathy features central retinal hemorrhages and blood vessel dilation

fundoscopic findings associated with lymphooplasmacytic lymphoma

Myelin Associated Glycoprotein (MAG)

most frequently reported antigen recognized by monoclonal IgM in lymphoplasmacytic lymphhoma

normocytic and normochromic

type of anemia associated with lymphoplasmacytic lymphoma

MYD88 gene

-dimerizes to form myddosome

gene mutation assciated with LPL

indolent, incurable disease with a median survival of 5 to 10 years

prognosis associated with lymphoplasmacytic lymphoma