clean up Flashcards
- Proliferation of immature BM cells, with > 20% blasts (PB or BM)
- Associated with Down syndrome after 5 y/o
• Acute lymphocytic leukemia (ALL)
- Symptoms: aggressive, pancytopenia due to BM replacement
- Good: hyperdiploidy, t(12,21), 2 – 10 y/o
- Poor: hypodiploidy, t(9,22), 11q23 (MLL), CNS involvement, WBC > 100,000/µL
- First-line tx for Ph+ adults is dasatinib
- Excellent response to chemo, but scrotum and CNS require “prophylaxis”
• B lymphoblastic leukemia (B-ALL)
• Worse prognosis than B-ALL
• T lymphoblastic lymphoma (T-ALL)
- Symptoms: indolent, hypogammaglobulinemia, sometimes autoimmune hemolysis and thrombocytopenia
- Immunophenotype: CD5+, CD19+, CD20+, CD23+
- B cells with chromatin that looks like soccer balls or gingersnaps
- Presence of smudge cells on PBS
- Risk of Richter transformation to large B cell lymphoma
- Good: del13q, low Rai stage, mutated IgHV
- Intermediate: trisomy 12
- Poor: del11q, del17p, high Rai stage, unmutated IgHV, CD38+, ZAP70+
- Incurable, 5-yr survival is 75%
• Chronic lymphocytic leukemia (CLL)
- Symptoms: indolent, pancytopenia, splenomegaly (red pulp, which is unique), BM fibrosis (dry tap), absence of lymphadenopathy
- TRAP expression (=osteoclastic activity)
- Immunophenotype: CD19+, CD20+, CD11c+, CD22bright
- Cells with hairy projections and reniform nuclei
- Risk of Richter transformation to large B cell lymphoma
• Hairy cell leukemia (HCL)
- Proliferation of immature BM cells, with > 20% blasts (PB or BM)
- Natural course is fatal within weeks to months
- Comprises 80-90% of acute leukemias
- NSE+ (monoblasts only)
• Acute myelogenous leukemia (AML)
- De novo AML; no antecedent MDS
* Generally favorable prognosis
• AML with recurrent cytogenetic abnormalities
- DIC is common, contributes to early morbidity and mortality
- Atra Quickly corrects coagulopathy
- Morphology: atypical promyelocytes, generally hypergranular, reniform nuclei, multiple Auer rods ( can trigger coagulation DIC)
• AML with t(15;17) – acute promyelocytic leukemia (APL)
- Hypergranular form
- Hypergranular cells
- Leukopenia
- Hypogranular form
- Hypogranular (microgranular) cells
- Leukocytosis
• AML with t(15;17) – acute promyelocytic leukemia (APL)
• Morphology: dysplastic BM eosinophils, myelomonocytic immunophenotype
• AML with inv(16)
• Common AML among infants
• AML with 11q13 (MLL) rearrangement
- Dysplasia in > 50% of cells in 2 or more lineages
- Typically an antecedent MDS
- Karyotypic abnormalities (e.g. del7q, -7, del5q, -5)
- Occurs in older people
- Poor prognosis
• AML with myelodysplastic-related changes
- Cytogenetic abnormalities in chromosome 5 or 7
- Multilineage dysplasia (resembles AML with myelodysplastic-related changes)
- Very poor prognosis
• Alkylating agent related AML/MDS
- 11q23 (MLL) translocations are the most common
- Monocytic or myelomonocytic (resembles de novo AML with 11q13 rearrangement)
- Poor prognosis
• Topoisomerase II inhibitor related AML/MDS
• Monocytes characteristically invade the gums
- AML not otherwise specified (AML NOS)
* Acute monocytic leukemia
- Leukocyte alkaline phosphatase (LAP) negative
* Basophilia highly associated with CML (not seen in leukemoid reactions)
• Chronic myelogenous leukemia (CML)
- Affects adults and is rare
- Immunophenotype: CD8+
- Lymphocytes with eosinophilic granules
- Symptoms: indolent, neutropenia, anemia, splenomegaly, may be associated with autoimmune disease
• Large granular lymphocytic leukemia
• Lymphocytes with lobated nuclei (flower cells)
• Adult T cell leukemia/lymphoma (ATLL)
• Post-germinal B cells with crippling Ig mutations no Ab secretion
• Hodgkin’s lymphoma
- Most common subtype
* Fibrous bands with lacunar Reed-Sternberg cells
• Nodular sclerosis (NSHL)
• Lack fibrous bands and nodules, more commonly caused by EBV, more commonly has BM involvement
• Mixed cellularity (MCHL)
- Median age 35 y/o, mostly males, nodular lesions, no EBV-association
- Popcorn cells, no eosinophils or plasma cells
- Immunophenotype: CD20+, CD45+, CD15 negative, CD30 negative
- Can be treated more conservatively than classic Hodgkin’s lymphoma
- Good prognosis
• Lymphocyte rich (NLPHL)
- Immunophenotype: CD10+, CD20+, CD5 negative
- Presents in late adulthood with generalized painless lymphadenopathy
- Tx symptomatic patients with low dose chemo, rituximab
- May progress to large B cell lymphoma
• Follicular cell lymphoma
- Immunophenotype: CD5+, CD20+, CD23 negative
* Presents in late adulthood with generalized painless lymphadenopathy
• Mantle cell lymphoma
Immunophenotype: CD5 negative, CD10 negative
• MALToma
- Most common kind of non-Hodgkin’s lymphoma
- Presents in late adulthood as an enlarged LN or extranodal mass
- Aggressive
• Diffuse large B cell lymphoma (DLBCL)
- Caused by c-MYC translocations
- With IgH t(8;14)
- With kappa t(2;8)
- With lambda t(8;22)
- Immunophenotype: CD10+, CD19+, CD20+, Bcl2+, KI-67+
- Aggressive cancer that presents in as an extranodal mass in adolescents and adults
- Starry sky appearance on histology
• Burkitt’s lymphoma
- EBV-related
- Endemic to Africa
- Affects the jaw
• Endemic
• Affects the abdomen
• Sporadic
• EBV-related
• Immunosuppression-related
• Caused by ALK-NPM rearrangement t(2;5)
Aggressive lymphoma of children and young adults, more common in males
• Anaplastic large cell lymphoma
• Lymphocytes with cerebriform nuclei and powdery chromatin
• Cutaneous T cell lymphoma
- BRAF mutations
* CD1a+, MHC-II+, langerin+ (found in Birbeck granules, look like tennis rackets)
• Langerhans cell histiocytosis (LCH)
- Painful bone lesions
* Peak incidence between 5 – 10 y/o
• Eosinophilic granuloma
- Rapid proliferation of Langerhans cells in multiple tissues
- Mostly seen in children
• Letterer-Siwe disease
- Very high ferritin (>10,000µg/L)
- Hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis
- 1-yr survival with SCT is 92%; without treatment, 0%
• Hemophagocytic lymphohistiocytosis (HLH)
• Caused by mutations related to perforin or granzyme secretion
• Primary (familial) HLH
• Occurs after strong immunologic activation (e.g. EBV, leukemias, lymphomas, autoimmunity)
• Secondary (acquired) HLH
- Symptoms: malaise, SOB, headaches, night sweats, bleeding from gums or gut, hepatosplenomegaly, gout, venous thrombosis, Budd-Chiari syndrome, face may look red, itching especially after showers (due to increased mast cells)
- Tx is phlebotomy, aspirin, hydroxyurea, anagrelide
• Polycythemia vera
- Elevation of platelets with abnormal morphology (large, hypogranular)
- Occurs in people 50 – 70 y/o, also young females
- Tx is aspirin, hydroxyurea, anagrelide, alkylating agents, SCT
• Essential thrombocythemia
- Extramedullary hematopoiesis spleen, liver, LNs
- Leukoerythroblastic smear (BM shows trapped WBC and RBC)
- Immature RBC and WBC in the blood
- Anemia with misshapen RBC (teardrop cells)
- Occurs in people 50 – 70 y/o
- May develop into AML
- Tx is ruxolitinib (JAK2 inhibitor), hydroxyurea, SCT
• Primary myelofibrosis
- Caused by del5q, -5, del7q, +8
- Dysplastic HSCs with ineffective hematopoiesis
- Dysplastic neutrophils are hyolobated and hypogranular
- Dysplastic platelets are large and hypogranular
- Cytopenias (uni, bi, or pan)
- Myeloblasts are increased but are still
• Myelodysplastic syndrome (MDS)
- Symptoms: anemia, bacterial infections, pathologic bone fractures, bone pain, proteinuria, proteinemia, hypercalcemia, renal failure
- Tx with chemo, thalidomide derivatives, proteasome inhibitors (bortezomib, carfilzomib), corticosteroids, autologous SCT, radiation for local lesions
• Multiple myeloma
- Symptoms: hyperviscosity syndrome, visual impairment, Raynaud’s syndrome, autologous IgM (rheumatoid factor, cold agglutinins)
- Tx is plasmaphoresis, corticosteroids, alkylating agents, nucleoside analogs, rituximab, bortezomib, thalidomide, lenalidomide
• Waldenström’s macroglobulinemia (lymphoplasmacytic lymphoma)
• Symptoms: typically asymptomatic, peripheral neuropathy, bone fractures, primary amyloidosis
• Monoclonal gammopathy of undetermined significance (MGUS)
- Two-month incubation period before symptoms arise
* Oncogenesis may be direct (transformation) or indirect (chronic inflammation-inducing hit-and-run bystander)
• Infectious mononucleosis
