Question | Answer |
WBC count | Normal: 5-10 K/µL
Leukopenia: <5 K/µL
Leukocytosis: >10 K/µL |
Causes of neutropenia | Drug toxicity (e.g. chemotherapy)//Severe infection (e.g. gram |
Causes of lymphopenia | Immunodeficiency (e.g. DiGeorge syndrome [no thymus] or HIV)// High cortisol state (e.g. exogenous corticosteroids or Cushing syndrome)// Autoimmune destruction (e.g. SLE)// Whole body radiation |
Causes of neutrophilic leukocytosis | Bacterial infection or tissue necrosis (release of marginated pool and recruitment of bone marrow neutrophils/ High cortisol state (release of marginated pool) |
Marginated pool | leukocytes "hang" in lung vasculature//cortisol disrupts adhesion, releases marginated pool// causes leukocytosis |
Fc receptors | Fc receptors help neutrophils recognize immunoglobulin (opsonin for phagocytosis)//lack of CD16 indicates lack of Fc receptors |
Causes of monocytosis | chronic inflammatory states (autoimmune or infectious)// malignancy |
Causes of eosinophilia due to increased IL | 5 production//allergic reactions//parasitic infections//Hodgkin lymphoma |
Causes of basophilia | classically seen in chronic myeloid leukemia |
Causes of lymphocytic leukocytosis | viral infections//B. pertussis infection |
Acute leukemia | accumulation of neoplastic blasts (>20% in the bone marrow)//blasts crowd out normal hematopoiesis// blasts enter blood, result in high WBC count with large appearance and "punched out" nucleoli |
TdT | DNA polymerase in lymphoblasts, but not myeloblasts or mature lymphocytes// can stain for TdT to diagnose ALL |
ALL | accumulation of >20% lymphoblasts in bone marrow// positive stain for TdT// most commonly arises in children// association with Down syndrome (usually >5yo)// subclassified into B |
B- ALL | accumulation of TdT+ lymphoblasts expressing CD10, CD19, and CD20//excellent response to chemo// requires prophylaxis to scrotum and CSF// t(12,21) has good prognosis (usually in kids), t(9,22) has poor prognosis (usually in adults) |
T-ALL | usually presents in teenagers as a thymic mass (called "lymphoma")// remember T's: T cells, teenagers, thymic mass |
AML | accumulation of >20% myeloblasts in bone marrow// positive stain for myeloperoxidase// crystal aggregates of MPO: Auer rods// may arise from myelodysplastic syndromes |
Acute promyelocytic leukemia | subtype of AML// has t(15;17): translation of retinoic acid receptor// RAR blocks maturation of promyelocytes// treatment = atra |
Acute monocytic leukemia | subtype of AML//blasts usually lack MPO //characteristically infiltrate gums// |
Acute megakaryoblastic | subtype of AML// blasts usually lack MPO //associated with Down syndrome (usually <5yo) |
Chronic leukemia | accumulation of mature LYMPHOcytes, characterized by a high WBC count with blasts <20%// often insidious onset// usually seen in older adults |
CLL | accumulation of naive B cells that co// most common type of leukemia// see increased lymphocytes and smudge cells// can involve lymph nodes |
Complications of CLL | hypogammaglobulinemia (infection most common cause of death)// autoimmune hemolytic anemia//transformation to large B cell lymphoma (will see enlarging lymph nodes or spleen) |
Hairy cell leukemia | accumulation of mature B cells with "hairy" cytoplasmic processes// TRAP+ // features: splenomegaly (hairy cells in red pulp), "dry" bone marrow tap (due to marrow fibrosis)// excellent response to cxtrpy |
Adult T cell leukemia/lymphoma (ATLL) | accumulation of mature CD4+ T cells//associated with HTLV// presents with rash, generalized lymphadenopathy, hepatosplenomegaly, punched out bone lesions with hypercalcemia |
Mycosis fungoides | accumulation of mature CD4+ T cells that infiltrate skin// presents with localized skin rash, plaques, nodules: called Pautrier microabscesses// cells can spread to the blood// characteristic lymphocytes with cerebriform nuclei (Sezary cells) |
Myeloproliferative disorders | accumulation of mature myeloid cells// usually in late adulthood(50//high WBC count with hypercellular bone marrow// all myeloid cells are increased, but classified based on dominant myeloid cell producedall myeloid cells are increased, but classified bas |
Complications of MPD | - increased risk for hyperuricemia and gout (high cell turnover)
- progression to marrow fibrosis
- transformation to acute leukem |
CML | - type of MPD, granulocytes are predominant cell type
- basophils characteristically increased
- t(9;22): Philadelphia chromosome --> BCR-ABL fusion protein with increased tyrosine kinase activity |
Treatment for CML | Imatinib// blocks tyrosine kinase activity of BCR |
Outcomes of CML | can transform to AML (2/3) or ALL (1/3) because mutation is in the pluripotent stem cell |
How to distinguish CML from leukemoid reaction CML will have: | negative LAP stain//increased basophils//t(9;22) |
Polycythemia vera | - type of MPD, RBCs are predominant cell type
- assoc with JAK2 kinase mutation
- blood becomes hyperviscous, requires phlebotomy (without, death usually within a year) |
S/sx of polycythemia vera | - splenomegaly (extramedullary hematopoiesis)
- leukoerythroblastic smear (teardrop RBCs, nucleated RBCs, immature granulocytes)
- increased risk of infection, thrombosis, bleeding |
How to distinguish polycythemia vera from reactive polycythemia In polycythemia vera: | EPO levels are decreased// oxygen saturation is normal |
Essential thrombocythemia | type of MPD, platelets are particularly increased// assoc with JAK2 kinase mutation //symptoms related to increased risk of bleeding AND/OR thrombosis (platelets either working really well or not at all)//rarely progresses to marrow fibrosis or acute leuk |
Myelofibrosis | - type of MPD, megakaryocytes are particularly increased
- assoc w/ JAK2 kinase mutation (50% of cases)
- megakaryocytes produce excess PDGF --> marrow fibrosis |
Causes of painful vs. painless lymphadenopathy | lymphadenopathy Painful: usually draining region of acute infection// Painless: seen w/ chronic inflammation, metastatic carcinoma, or lymphoma |
Follicular lymphoma | - NHL of small CD20+ B cells that form follicle-like nodules
- typically late adulthood
- can progress to diffuse large B-cell lymphoma |
Pathophys of follicular lymphoma | - Bcl2 normally inhibits apoptosis in peripheral cells
- follicular cells generally lack Bcl2 so they can undergo testing
- t(14;19) --> overexpression of Bcl2 --> cells that fail testing no longer die --> neoplasm |
Treatment of follicular lymphoma | reserved for symptomatic pts//involves low |
How to distinguish follicular lymphoma from reactive follicular hyperplasia Follicular lymphoma shows: | disruption of LN architecture// lack of tingible body macrophages (white spaces in follicle indicate macrophages are gobbling up apoptotic B cells)// Bcl2 expression //monoclonality |
Mantle cell lymphoma | NHL of small CD20+ B cells that expand mantle zone around follicle //typically late adulthood |
Pathophys of mantle cell lymphoma | t(11;14) --> overexpression of cyclin D1 --> promotes G1/S transition in cell cycle --> neoplasm |
Marginal zone lymphoma | - NHL of small CD20+ B cells that expand the marginal zone around the mantle/follicle
- assoc with chronic inflammatory states (e.g. Hashimoto thyroiditis, Sjogren syndrome, H. pylori gastritis)... marginal zone typically only present with chronic inflam |
Burkitt lymphoma | - NHL of intermediate-sized CD20+ B cells
- associated with EBV
- translocations of c-myc (nuclear regulator) --> cell growth
- high mitotic index and "starry sky" appearance under microscope |
Classic presentation of Burkitt lymphoma extranodal mass in a child or young adult | extranodal mass in a child or young adult
- African form: jaw
- Sporadic form: abdomen |
Diffuse large B | - most common form of NHL
- large CD20+ B cells grow diffusely in sheets
- clinically aggressive
- arises sporadically or from transformation of lower-grade lymphoma
- presents in late adulthood |
Hodgkin lymphoma overview | - proliferation of Reed-Sternberg cells
- cytokine release attracts other inflammatory cells, may lead to fibrosis and "B" symptoms (night sweats, fever, chills)
- reactive cells are the bulk of the tumor
- nodular sclerosis is most common subtype |
Reed Sternberg cells | - large B cells with multilobed nuclei & prominent nucleoli ("owl eye" appearance)
- neoplastic in Hodgkin lymphoma
- classically CD15 and CD30+ with NO CD20 expression
- secrete cytokines that attract lymphos, plasma cells, macrophages and eosinophils |
Nodular sclerosis | - most common subtype of Hodgkin lymphoma
- classically presents with enlarging cervical or mediastinal lymph node in young adult, usually female
- lymph node divided by bands of sclerosis
- Reed Sternberg cells present in lake-like spaces (aka lacunar |
Best/worst prognosis for Hodgkin lymphoma | - lymphocyte-rich subtype has best prognosis
- lymphocyte-deprived has worst prognosis (usually in elderly and HIV+) |
Multiple myeloma | malignant proliferation of plasma cells in marrow// high serum IL //plasma cells overproduce osteoclast activating factor, Igs, light chain |
S/sx of multiple myeloma | osteoclast activating factor// IgA & IgG// = bence jones protiens |
Monoclonal gammopathy of undetermined significance (MGUS) | increased serum protein with M spike// other features of multiple myeloma are ABSENT// common in elderly, some will develop multiple myeloma |
Waldenstrom macroglobulinemia | B cell lymphoma with monoclonal IgM production// similar to multiple myeloma but: no lytic bone lesions// visual and neurologic deficits (due to serum hyperviscosity)// bleeding (defective platelet aggregation)// treat with plasmapheresis |
Langerhans cell histiocytosis | neoplastic proliferation of Langerhans cells// characteristic Birbeck (tennis racket) granules seen on EM// cells are CD1a+ and S100+// |
data source | clarebp on quizlet(dot)com |