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Myelomas and Hodgkins Lymphoma

Myelomas basics ? * B-cell proliferations with neoplastic plasma cells ---Always a monoclonal Ig or Ig fragment... *Rouleauxing.... * se increased Ca lvls and elevated protein M spike in electrophoresis (monoclonal Ig)... *can have multiple, solitary, or smoldering myl.
Multiple Myeloma (MM)basics ? * Plasma cell neoplasm characterized by multifocal involvement of the skeleton ---May spread to lymph nodes and extranodal sites (skin) ---Higher in men and African descent --- Cell of origin is the plasma cell
MM Molecular patho ? * IL-6 – produced by myeloma cells --- * Bone destruction & Hypercalcemia --- * IgH rearrangements on chromo 14q32
MM - Morphology ? * >30% plasma cells for diagnosis that leads to pancocytopenia..... * Axial skeleton containing plasmacytomas ..... * punched holes in skull and hemorrhagic lesions in vertabrae
MM - Clinical ? * triad of Anemia, Bence Jone proteins from renal failure, HyperCa (ABC)..... * Bone marrow biopsy for Dx and there is no cure for MM yet
Solitary Myeloma (Plasmacytoma)basics ? * Solitary lesion of bone or soft tissue ---- * Same bone locations as MM ----- * almost all progress to MM
Smoldering Myeloma basics ? * Between MM and MGUS (monoclonal gammopathy of undetermined significance) ---- * 75% progress to MM and they are Asymptomatic
MGUS (monoclonal gammopathy of undetermined significance)basics ? * Most common plasma cell dyscrasia ---- * Asymptomatic ---- * Small M spike
Lymphoplasmacytic Lymphoma basics ? * B-cell neoplasm ...... * Waldenstrom Macroglobulinemia – monoclonal IgM --> hyperviscosity syndrome.... * common is deletion involving chromo 6q
Hodgkin Lymphoma (HL) Overview ? * Arises in single node or chain of nodes and spread in order ----- * Progresses to anatomically contiguous lymphoid tissues ---- * Neoplastic cell is Reed-Sternberg Cell
Nodular Sclerosis HL basics ? * Most common – 65-70% of cases; Equal in men and women .... * Lacunar variant R-S cells .... * Immunophenotype – PAX5 (B cell transcription factor), CD15, CD30; CD45(-) .... * see in Lower cervical, supraclavicular & mediastinal lymph nodes
Mixed Cellularity HL basics ? * 20-25% of cases; Male predominance; Older age..... * Classic and mononuclear variant RS cells plentiful.... * Diffuse effacement of lymph nodes ..... * 70% RS cells infected with EBV .... * Cx Sx = – Nights sweats & weight loss common
Lymphocyte-Rich HL basics ? * good prognosis ... * seen in 40% of pts. .... * see RS cells with high levels of lymphocytes
Lymphocyte Depletion HL basics ? * rarest HL form of all ..... * seen in HIV+ individuals of all ages and 90% infected with EBV .... * See RS cells with low lymphocyte levels
Lymphocyte Predominance HL basics ? * usu in males and under 35 y/o .... * small lymphocytes and macrophages with RS cells and POPCORN cells..... * Immunophenotype – CD20, BCL6 (different than the other HL).... * no EBV ..... * IgH gene hypermutations.... * likely to reoccur
HL Molecular Pathogenesis ? * Activation of NF-KB (nuclear factor kappa-light-chain- enhancer of activated B-cells; Controls transcription of DNA) ...... * CCL28 = secreted by RS cells to attract reactive cells ...... * Reactive cells support growth and survival of RS cells .
continued... * Copy number gains of c-REL proto-oncogene on chromo 2p common  increase activity of NF-KB
HL Staging ? * a = absent b = present .... * I = one node site above diaphragm.... * II = over 1 site aboe diaphragm... * III = both sides of diaphragm ... * IV = extranodal sites
Created by: thamrick800