• non Hodgkins
• Hodgkins
• plasma cell disorders
• histiocytic neoplasms

• chronic hyperplasia/dysreg. of immune system
• genetic mistakes affecting multiple oncogenes and/or tumor suppressor genes
• maturation arrest in single clone of cells
• overgrowth of neoplastic clone with characteristic morphologic features and growth potential; inhibition of normal clones

• hereditary factors
• immunodeficiencies
  • inheritied
  • acquired
  • iatrogenic
• autoimmune disorders
• chromosome/genetic abnormalities
• microorganisms

• modification and/or inappropriate activation
• oncogenes often encode for proteins regulating:
  • cell proliferation (ex: myc in 8:14 and and cyclin D1 in 11:14)
  • apoptosis (ex: 14:18 with BCL2)
  • maturation (ex: BCL6 maturation)

• age (childhood or elderly)
• male predominance
• symptoms
  • insidious onset
  • painless lymphadenopathy
  • w/ or w/o fever, night sweats, and/or weight loss
• sites
  • lymphoreticular (LN, spleen, thymus)
  • extranodal (bone marrow, GI tract, etc.)

• small lymphocytic
• mantle cell
• follicular
• marginal zone
• diffuse large B cell
• Burkitt's

• peripheral T cell
• anaplastic large cell
• mycosis fungoides/Sezary syndrome

• vaguely to distinct nodular aggregatoes of neoplastic cells
• several B cell subtypes exhibit this pattern
  • often recapitulate normal B cell counterparts
• ex: follicular lymphoma

• many B and T cell subtypes have this pattern
• diffuse growth of neoplastic cells

Loss of lymphoma architecture

• usually at age over 40
• second most common kind of NHL, esp. in West

• 14:18 translocation with BCL2
• nodules of small cleaved to large B cells
  • grade 1: most small cleaved cells
  • grade 2: small cleaved cells + few large B cells
  • grade 3: mostly large B cells
• disseminated at presentation and slowly progressive
• prognosis: grade 1,2 have mean survival of 8-10 yrs, but may progress to higher grade

• most common NHL worldwide
• occurs at any age

• diffuse prolif. of large B lymphocytes with open ("vesicular") chormatin, nucleoli, variable amount of cytoplasm
  • numerous mitoses
• many morphologic and genetic variants
• occurs at lymph nodes and extranodal
• usually localized at presentation
• aggressive if untx (half cure rate)

• low grade lymphoma of specialized type of small B  cells
• in extranodal sites
• cause chronic hyperplasia of B cells induced by autoimmune (in thyroid) or infectous process (in stomach)
• associated with H pylori infection causing MALT lymphoma in stomach
• occur at age over 40
• indolent clinical course
• often remains in extranodal sites for many years
• MALT lymphoma respond to antibiotics

• occurs mostly in kids or HIV infected patients
• endemic in Africa, but occurs worldwide

• myc abnormality usually 8:14 translocation
• prognosis- very rapid growing and very aggressive if untreated, but highly curable unless HIV infected
• EBV infection in most endemic, many other cases
• usually extranodal (esp. jaw, abdomen)
  • may become leukemia
• histopathology- diffuse prolif. of uniform intermediate size B lymphocytes with fine chromatin, small nucleoli, and extremely numerous mitoses
  • mixed with starry sky cells

• epidemiology- over 40
• primary skin involvement (plaque and tumor with MF and erythroderma with SS), peripheral blood (SS) anmd late LN and spleen involvement
• histopath- epidermal and high dermal infiltrrate of small T cells with ceribriform nuclei
• neoplasm of helpter T cells
• prognosis
  • MF usually slowly progressive
  • SS is clinically aggressive

• histopath- Reed Sternberg cells and variants surrounded by benign reactive cells
• associated classically with EBV
• characterized by abnormally heavy cytokine/ chemokine production and abnormal cytokine/ chemokine receptors

• age- bimodal incidence
  • 15-35 peaks
  • than after age 45
• male predominance (except NS)
• symptoms
  • painless lymphadenopathy w/ or w/o fever
  • night sweats
  • weight loss
• site- lymph nodees (mainly cervical and mediastinal), spleen, liver, bone marrow
• general patterns
  • young- localized, minimal symptoms
  • older- disseminated, "B" symptoms

• classical (MAJOR)
  • nodular sclorsis
  • mixed cellularity
  • lymphocyte rich HL
  • lymphocyte depleted HL
• nodular lymphocyte predominant HL

• stage I- single node group or extranodal site
• stage II- multiple node gropus or nodes with extranodal sites on same side of diaphragm
• stage III- node groups on both sides of diaphragm, with possible localized extranodal site or spleen
• stage IV- disseminated nodal and extranodal
  • modifiers
    • A: no specific symptoms
    • B: fever, sweats, weight loss

• plasma cell myeloma
• Waldenstrom macroglobinemia (lymphoplasmacytic lymphoma)
• heavy chain diseases
• primary amyloidosis
• monoclonal gammopathy of undetermined significance

neoplastic disorders which are solitary (plasmacytoma) or multiple (plasma cell myeloma) collections of mature plasma cells usually in bone, producing a single species of Ig

• epidemiology- most over age of 50
• presenting findings
  • monoclonal gammopathy
  • anemia
  • bone pain
  • lytic bone lesions

• clinical course- can be indolent or aggressive
• complications
  • excess plasma cells: hypercalcemia, bone fractures, marrow failure
  • excess monoclonal Ig: renal insufficiency, amyloidosis
  • decrease norman Ig: infection

• peripheral blood
  • monoclonal gammopathy
  • anemia
  • hypercalcemia
• urine
  • free light chains (Bence Jones)
  • proteinuria
• bone marrow (used to confirm dx)
  • increase plasma cells, usually in clusters vary from mature to immature

• excess production of single species of Ig by a single clone of Ig secreting cells
• both single heavy and light chain class produced
  • mostly IgG
  • some IgA
  • some light chain
  • very rarely, IgM, IgD, IgE
  • very rarely non secretory
• detect in serum and or urine protein electrophoresis
  • heavy and light chain class determined by immmunofix electrophoresis
• also detect serum free kappa and lambda light chain assays

• free light chain in urine due to overproduction of light chains by neoplastic cells
• most of myeloma cases
• best detected by urine protein elctrophoresis w/ or w/o immunofixation

• bone disease in most cases
• bone lysis and hypercalcemia secondary to overproduction of osteoclasts via activating cytokines from neoplastic cells
• sites most common
  • vertebrae
  • ribs
  • skull
  • pelvis
  • femur

• tubular (MAJOR)- myeloma kidneys
  • deposition of light chain proteinaceous casts in DCT and collecting tubules
• glomerular disease
  • amyloid and/or light chain deposition in glomeruli

More common with high bence jones proteinuria

• clinicopathologic criteria
  • significant monoclonal gammapathy found in serum and/or urin
  • increase in monoclonal plasma cells in bone marrow
  • with or without related organ or tissue impairment (ex: anemia, hypercalcemia, bone lesions, renal insufficiency)

• def.- disorder associated with lymphoplasmacytic lymphoma char by infiltration of small lymphocytes and plasmacytoid lymphocytes in bone marrow, LN, spleen, and liver
• unlike multiple myeloma neoplastic cells secrete single species of IgM
• serum hyperviscocity is common complication based on large pentamer structure of IgM

• result in only heavy chain being produced by neoplastic cells

• single clone of plasma cells secretes excess monoclonal intact Ig or free light chain that is deposited as amyloid in may tissues and organs, often lead to organ failure
• usually manifestation of myleoma, but most patients have only minimal bone marrow plastacytosis and no other myeloma findings

• monoclonal Ig in serum of patients with no evidence of plasma cell neoplasma
• epi- associated with age
• usually no or only minimal Bence Jones proteinuria
• a good amount do eventually develop plasma cell neoplasm

• Langerhan cells
  • usually happens in children (can be in one organ system or multiple)
  • benign and highly aggressive
  • neoplasma of specialized dendritic cells
• histiocytic sarcoma
  • occur at any age, highly malignant
  • neoplasm of mature histiocytes/macrophages

These are very rare