Myelomas and Hodgkins Lymphoma
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| 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.
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| 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
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| MM Molecular patho ? | * IL-6 – produced by myeloma cells
--- * Bone destruction & Hypercalcemia --- * IgH rearrangements on chromo 14q32
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| MM - Morphology ? | * >30% plasma cells for diagnosis that leads to pancocytopenia..... * Axial skeleton containing plasmacytomas ..... * punched holes in skull and hemorrhagic lesions in vertabrae
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| 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
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| Solitary Myeloma (Plasmacytoma)basics ? | * Solitary lesion of bone or soft tissue
---- * Same bone locations as MM ----- * almost all progress to MM
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| Smoldering Myeloma basics ? | * Between MM and MGUS (monoclonal gammopathy of undetermined significance)
---- * 75% progress to MM and they are Asymptomatic
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| MGUS (monoclonal gammopathy of undetermined significance)basics ? | * Most common plasma cell dyscrasia
---- * Asymptomatic ---- * Small M spike
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| Lymphoplasmacytic Lymphoma basics ? | * B-cell neoplasm ...... * Waldenstrom Macroglobulinemia – monoclonal IgM --> hyperviscosity syndrome.... * common is deletion involving chromo 6q
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| 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
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| 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
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| 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
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| Lymphocyte-Rich HL basics ? | * good prognosis ... * seen in 40% of pts. .... * see RS cells with high levels of lymphocytes
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| 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
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| 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
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| 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 .
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| continued... | * Copy number gains of c-REL proto-oncogene on chromo 2p common increase activity of NF-KB
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| 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
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