White Blood Cell/Lymph Node Neoplasms Flashcards
CLL/SLL
Chronic lymphocytic leukemia/Small lymphocytic lymphoma
Most common in western world
Morphology: Proliferation centers of small lymphocytes contain mitotically active cells in lymph nodes
Smudge cells present in blood smears
Immunophenotype: tumor cells express CD19, CD20 and CD23, CD5
Low levels of Ig
Clinical:
Asymptomatic at diagnosis-slow progression
Fragility, weight loss and anorexia
Lymphadenopathy and hepatosplenomegaly
Leukopenia in SLL
increased peripheral blood lymphocytosis in CLL
Median diagnosis is 60
Prognosis: median survival is 4-6 years
Treatment: Chemotherapy with Abs against proteins on CLL surface (CD20)
Can transform to diffuse large B cell lymphoma
B-ALL/T-ALL
B-ALL in children (more common) T-ALL in adolescents
Pathogenesis: Chromosomal aberrations lead to dysregulation of transcription factors required for normal B and T development
Genetic Abnormalities: t(12, 21)=better prognosis,
t (9,22)
Morphology: Hypercellular lymphoblastic marrow
Punched out nucleoli
Starry sky appearance due to macrophages ingesting apoptotic tumor cells,
Increased lymphoblasts in bone marrow
Acid-Schiff positive cytosplasmic material
Immunophenotype: Tdt+
B-ALLs express CD19, PAX5 and CD10
T-ALLs express CD1, CD2, CD4, CD5, CD7, CD8
Clinical: Abrupt onset
Fever, fatigue, infections, thrombocytopenia, pallor
Mass effects by infiltration, bone pain, lympadenopathy, splenomegaly, hepatomegaly and testicular enlargement
Headache, vomiting and nerve palsies (Can spread to CNS, testes)
T-ALL can cause mediastinal mass to cause trouble with swallowing, inspiratory stridor, dyspnea
Associated with Down Syndrome
Prognosis: Aggressive chemotherapy 95% cured
Follicular Lymphoma
Pathogenesis: Arises from germinal center B cells
T(14;18) translocation between IgH and BCL2
BCL2 antagonizes apoptosis
Morphology: centrocytes (small cleaved nucleus) centroblasts (large cleaved nucleus)
Immunophenotype: CD19, CD20, CD10, CD79a surface Ig BCL2 and BCL6
No CD5
Clinical: Indolent course, Painless generalized lymphadenopathy-waxing and waning course
Prognosis: survival 7-9 years not improved with aggressive therapy
low dose chemotherapy and immunotherapy when symptomatic
Histologic transformation to diffuse large B cell lymphoma or Burkitts
Diffuse Large B cell
Most common NHL in male and old adults
Pathogenesis: Dysregultation of BCL6 (lower levels)
BCL6 is normally promotes B cell differentiation, growth arrest and apoptosis
t(14;18)
Morphology: Relatively large size and diffuse pattern growth in lymph node
Immunophenoytpe: CD19 and C20 variable expression of CD10 and BCL6, surface Ig
Clinical: rapidly enlarging mass at nodal or extranodal site-oropharyngeal lymph most common, also GI tract
Prognosis: rapidly fatal without treatment
Treatment: intensive combo of chemotherapy most remit
Adjuvant therapy with anti-CD20
Burkiitt Lymphoma
Pathogenesis: Translocations of c-MYC on chromosome 8 with IgH on 14 t(8;14)
MYC increases expression of genes required for aerobic glycolysis (Warburg effect) leading to fastest growing tumor controls cell proliferation, differentiation and apoptosis
Morphology: high mitotic index and numerous apoptotic cells leading to starry sky pattern-round nuclei, prominent nucleoli, increased mitotic index (high Ki-67)
Bone marrow cells have royal blue cytoplasm with clear cytoplasmic vacuoles
Immunophenotype: surface IgM, CD19, CD20 and CD10
Almost always fail to express BCL2
Clinical: Most tumors at extranodal ssites
Endemic=mass involving mandible (associated with EBV)
Sproadic=mass involving ileocecum and peritoneum, pelivs and abdomen (ascites and anorexia)
Treatment/Prognosis: responds well to chemotherapy most children and young adults cured
Multiple Myeloma
Monoclonal plasma cell
Morphology
Destructive plasma cell tumor involving axial skeleton leading to pathological fractures
Normal plasma cells with single nucleolus or bizarre multinucleated cells-increased chromatin and intracytoplasmic inclusions containing immunoglobin
Dysregulated and secretion of Ig (IgG or IgA) lead to intracellular accumulation of protein (lambda leads to amyloidosis)
Russel bodies (cytoplasm) and Dutcher bodies (nuclear)
High level of M proteins cause red cells in peripheral blood to stick to one another (rouleaux formation)
Bence Jones proteins in kidney and urine
Immunophenotype: CD138 (adhesion molecule syndecan-1) CD56
Clinical: increased IgG leads to kidney failure (amyloidosis-apple green biferengence) so no EPO (normochromic normocytic anemia-also bone marrow infiltration of plasma cells) and increased Ca (stones, groans, bones, psych overtones)
Back pain
Recurrent bacterial infections
Light chains are toxic to renal tubular epithelial cells
Diagnosis: Igs detected by electrophoresis (monoclonal)
Most common M protein is IgG
Excessive M protein leads to hyperviscocity
Prognosis: median survival is 4-7 years
Treatment: inhibitors of proteasome leading to more misfolded proteins and apoptosis
Thalidomide and thalidomide-ubiquitin ligases target proteins required for myeloma growth
Bisphosphonates and HSC trasnplantations
Monoclonal Gammopathy of Uncertain Significance
monoclonal expansion of plasma cells within serum
Persons older than 50
Asymptomatic and serum M protein is less than 3gm/dL (M spike)
Can progress to multiple myeloma check serum IgM components and Bence Jones Proteinuria
Mantle Cell Lymphoma
Uncommon
Pathogenesis: t(11;14) involving Igh and cylin D1 on 11
Leading to promotion of G1 to S phase
Morphology: Generalized lymphadenopathy-extranodal involvement
Small lymphocytes with irregular to occasionally deeply clefted nuclear contours
No centroblasts (found in follicular) No proliferations (found in CLL)
Immunophenotype: High levels of cyclin D1
CD19, CD20 and moderately high Ig
CD5+ but CD23- (CLL is CD23+)
Clinical: painless lymphadenopathy
Prognosis: poor-median survival is 3-4 years
Lymphoma not curable with chemotherapy most patients succumb to organ dysfunction
Marginal Zone lymphomas
Arise in lymph nodes, spleen, extranodal tissues-extranodal mucosa associated lymphoid tumors
Somatic hypermutation-memory B cell origin
Extanodal sites associated with chronic inflammtory disorders-can regress if inciting agent is eradicated
Sjogren disease, thyroid gland of Hashimoto, stomach in helicobacter
Can acquire additonal mutations that render their growth and survival Ag independent
translocatiotns (11;18) (14, 18) or (1:14)
Lead to upreguation of BCL10 or MALT1 of NF-kB promoting growth and survival
Can transform into diffuse B cell lympoma
Hairy Cell Leukemia
Middle aged males median age of 55
Pathogenesis: Point mutations in serine/threonine of BRAF-downsream of RAS in MAPK pathway
Morphology: fine hairlike projections, fiborsis of bone marrow cannot be aspirated (dry tap), red pulp heavily infiltrated
Immunophenotype: CD19, CD20 (mature B cell tumor), surface Ig
CD11c, CD25, CD103, and annexin A1
tartrate resitant acid phosphatase + (TRAP)
Clinical:
Massive splenomegaly
Pancytopenia resulting from marrow involvement and splenic sequestriation
mycobacterial infections common
Treatment/Prognosis: Cladribine
Tumors relaspe over 5 years but respond to same treatments
BRAF inhibitors used
Prognosis is excellent
Adult T cell leukemia/Lymphoma
Neoplasm of CD4+ T cells in adults infected with leukemia retrovirus type 1 (HTLV-1)
Occurs in japan, west africa and caribbean
HTLV1 associated with IV drug abuse
Clinical: skin lesions, generalizd lymphadenopathy, hepatosplenomegaly, peripheral blood lymphocytosis and hypercalcemia, lytic bone lesions
Morphology: cells with mutliobulated nuclei (clover leaf), tumor cells have HTLV-1 provirus,
Pathogenesis: HTLV-1 encodes Tax protein that activates NF-kB enhancing lymphocyte growth and survival
Prognosis: rapidly progressive that is fatal within months to a year despite aggressive chemotherapy
Can also give rise to demyelinating disease of the spinal cord
Mycosis Fungoides/sezary syndrome
Tumor of CD4+ T cells that home to skin
Clinical: sezary=skin involvement manifested as generalized exfoliative erythroderma proceeding to tumor
Cutaneous patches or plaques that can spread to local lymph nodes
Circulating malignant cells seen in Sezary syndrome
Immunophenotype: express cutaneous leukocyte Ag and chemokine receptors CCR4 and CCR10 which contribute to homing to skin
Prognosis: median survival is 8-9 years transformation to aggressive T cell lymphoma the terminal event
Hodgkin Lymphoma
Arises in single node or chain of nodes (contiguous spread)
Pathogenesis: Ig genes of RS cells have undergone VDJ recombination and somatic hypermutation establishing origin from germinal center or postgerminal B cell
Activation of transcription factor NF-kB:
EBV infection promotes lymphocyte survival and proliferatoin,
Morphology: Reed-Sternberg cells with multiple nuclei (CD15 and CD30 positive). lacunar cells (nucleus sitting in hole)
lymphocytes, histiocytes, and eosinophils also seen
Clinical: night sweats, weight loss, low grade fever, associated with EBV in 70%
Prognosis: very good treated with radiation or chemotherapy
Better prognosis with stromal or lymphocytic reaction against RS cells
Subtypes:
Nodular sclerosing form most common (affects men and women equally)
Lymphocyte rich form has best prognosis
Lymphocyte mixed or depleted forms have poor prognosis
Acute Myeloid Leukemia
Pathogenesis: t(8;21) disrupts the RUNX1and inv(16) disrupt the CBFB genes. RUNX1/CBF1B transcription factor required for normal hematopoiesis
t(15, 17) creates fusion protein encoding a chimeric protein of RARA fused to PML (abnormal retinoic acid receptor that inhibits differentiation-responds to vitamin A
Morphology: 20% blasts in bone marrow
Myeloblasts: delicate nuclear chromatin, 2-4 nucleoli and voluminous cytoplasm containing Auer rods-myeloperoxidase+
AMLs following myelodysplastic syndromes or exposure to DNA damaging agents have deletions of chromosomes 5 and 7 and no trans locations
Older adults have deletions of 5q and 7q
Other Risk factors: Down Syndrome
Clinical: Symptoms of anemia, neutropenia, and thrombocytopenia
Spontaneous mucosal and cutaneous bleeding
Bleeding diathesis, cutaneous petechiae, serosal hemorrhages into gingivae and urinary tract
infections of caused by opportunists-fungi, psuedomonas and commensals
Auer Rods can lead to DIC
Prognosis: 60% achieve complete remission with chemotherapy
t(15;17) best prognosis
t(8;21) and inv(16) relatively good prognosis with conventionally chemotherapy in absence of KIT mutations
Chronic Myeloid Leukemia
Pathogenesis: Chimeric BCR-ABL gene derived from portions of he BCR gene on chormosome 22 and the ABL gene on chromosome 9 t(9,22) translocation (cell of origin is HSC)
BCR-ABL self associates leading to activation of ABL TK which activates RAS and JAK/STAT pathways
Preferentially drives proliferationn of granulocytic and megakaryocytic progenitors
Morphology: Hypercellular marrow due to increased granulocytic precursors (increased proportion of eosinophils and basophils)
Leukocytosis-increased neutrophils, meetamyelocytes, basophils
Spleen enlarged due to extramedullary hematopoiesis
Low alkaline phosphatase
Clinical: anemia, fatigability, weakness, weight loss, and anorexia
May progress to AML or ALL
Prognosis/Treatment: median survival is 3
Treat with BCR-ABL inhibitors-imantinib (not curative) HSC transplantation is curative
