WBC disorders

Question 1

Acute Leukemia

Answer 1

• neoplastic proliferation of blasts (> 20% blasts in BM)
• increased blasts “crowd out” normal hematopoiesis–> anemia, bleeding, infection
• acute onset
• blasts leak out into blood (large, immature cells with punched out nucleoli on blood smear)
• divided into ALL(TdT+) and AML (MPO+)
• high WBC
• younger population

Question 2

B-ALL

Answer 2

• B cell Acute Lymphoblastic Leukemia
• neoplastic proliferation of lymphoblasts
• most common form of childhood leukemia
• TdT (+)
• CD10, 19,20
• good prognosis for kids

Question 3

T-ALL

Answer 3

• T-cell Acute Lymphoblastic Leukemia/Lymphoma
• TdT (+)
• CD2-8
• T for teenagers and thymic mass (mediastinal adenopathy)

Question 4

chronic leukemia

Answer 4

• neoplastic proliferation of mature lymphocytes
• usually insidious onset; adults
• CLL, Hairy cell leukemia, ATLL, mycosis fungoides

Question 5

CLL

Answer 5

• Chronic Lymphocytic Leukemia
• lymphocytosis (hence the name! remember it’s a proliferation of mature B cells)
• involvement of LNs = small lymphocytic lymphoma (SLL)
• widespread lymphadenopathy + liver and spleen enlargement (unlike diffuse large B cell lymphoma)
• neoplastic proliferation of Naive B cells – antibody production is all screwed up –> hypogammaglobulinemia and autoimmune hemolytic anemia
• CD20 and CD5 (normally expressed on T cells)
• older adults; most common neoplasm overall
• smudge cells on blood smear
• Richter transformation: transform to diffuse large B-cell lymphoma (enlarging LN or spleen)

Question 6

Hairy Cell Leukemia

Answer 6

• neoplastic proliferation of mature B cells characterized by hairy cytoplasmic processes
• TRAP and TAP: TRAP stain, get trapped in spleen (no lymphadenopathy), “dry tap” (marrow fibrosis), trapped in hair

Question 7

ATLL

Answer 7

• Adult T Cell Leukemia
• neoplasm of mature T cell
• associated with HTLV-1 infection (Japan and Caribbean)
• rash
• hypercalcemia (lytic punched out bone lesions)

Question 8

Mycoses Fungoides

Answer 8

• neoplastic proliferatrion of mature CD4+ T cells that infiltrate skin –> skin rash, plaques and nodules
• Sezary cells: lymphocytes with cerebriform nuclei

Sezary and Mycoses Fungoides are very fancy

Question 9

myeloproliferative disorders

Answer 9

• neoplastic proliferation of mature cells of myeloid lineage (the mature version of AML)
• CML, PV, ET, myelofibrosis
• late adulthood
• high WBC with hypercellular BM (cells of all myeloid lineages are increased but disease defined by the predominant type)
• increased risk for hyupericemia and gout (due to increased cell turnover)
• progression to myelofibrosis (“burn out”) or AML (“blast out”)

Question 10

CML

Answer 10

• Chronic Myeloid Leukemia
• neoplastic proliferation of myeloblasts (neutrophils, eosinophils and basophils)
• Philly Chromo t(9;22) —BCR-ABL fusion protein (Philly CreaML cheese)
• can transform to AML or ALL (“blast crisis”) since mutation is in pluripotent stem cell
• low LAP as a result of low activity in mature granulocytes (vs. leukemoid rxn)
• responds to imatinib (blocks tyr kinase actvity of fusion protein)

Question 11

polycythemia vera

Answer 11

• neoplastic proliferation of mature myeloid cells, esp RBCs
• hematocrit > 60%
• JAK2 kinase mutation
• hyperviscous blood: blurry vision and HA, venous thrombosis (Budd-Chiari)
• intense itching after hot shower
• hyperuricemia and gout (due to rapid cell turnover)
• distinguished from reactive polycythemia by low EPO and normal SaO2

Question 12

AML

Answer 12

• acute myeloid leukemia
• myeloblasts characterized by MPO and Auer rods
• subtypes include APL, AMoL, AMegL
• may arise from pre-existing myeloproliferative disorders
• risk factors: exposure to alkylating agents, chemo, radiation

Question 13

APL

Answer 13

• Acute Promyelocytic Leukemia/ M3 (subtype of AML)
• MPO + Auer rods
• t(15;17) —- translocation of RAR –> RAR disruption blocks maturation and promyelocytes/blasts accumulate
• tx: all-trans RA (vit A)
• DIC: high concentration of Auer rods released upon chemotx

Question 14

ET

Answer 14

• Essential Thrombocytopenia
• neoplastic proliferation of mature myeloid cells, esp platelets
• JAK2 mutation
• increased risk of bleeding (dysfunctional platelets) and/or thrombosis (hyperactive platelets)
• throbbing, burning pain in extremities caused by clotting of arterioles

Question 15

Myelofibrosis

Answer 15

• neoplastic proliferation of mature myeloid cells, esp megakaryocytes
• megakaryocytes produce PDGF –> marrow fibrosis
• splenomegaly due extramedually hematopoeisis
• tear-drop RBCs (RBCs squeezed out of fibrotic marrow)

Question 16

Follicular Lymphoma

Answer 16

• neoplastic proliferation of small B cells (CD20+) that form follicle-like nodules
• painless lymphadenopathy
• t(14:18) bcl-2 activation
• disruption of normal LN architecture with many follicles (as opposed to reactive follicular hyperplasia)
• can progress to diffuse large B-cell lymphoma (enlarging LN)

Fourteen starts with F t(14;18)

Question 17

Mantle Lymphoma

Answer 17

• neoplastic proliferation of small B cells (CD20+) that expands mantle zone (zone surrounding germinal center)
• t (11;14) – cyclin D1 activation (“cycle the mantle”)

Mantlle = 11;14

Question 18

Burkitt Lymphoma

Answer 18

• Neoplastic proliferation of B cells (CD20+)
• young African children (jaw) and AIDS PTs associated with EBV
• sporadic form in young adults (abdomen)
• t (8;14) – c-myc activation
• “starry sky” appearance (sheets of lymphos with interspersed macros)

B=8 t(8;14)

Question 19

diffuse large B-cell lymphoma

Answer 19

• neoplastic proliferation of large B cells (CD20+)
• localized disease – presents with enlarging LN or extranodal mass (Waldeyer ring)
• arises sporadically or from transformation of follicular lymphoma
• older adults
• clinically aggressive (large cells are poorly differentiated)

Question 20

Hodgkin Lymphoma

Answer 20

• neoplastic proliferation of Reed Sternberg cells (large B cells - CD15+)
• RS cells secrete cytokines –> attract reactive cells (lymphocytes, plasma cells, macros) and “B” symptoms: fever, chills, weight loss, night sweats
• nodular sclerosis is most common subtype (LN node divided by bands of sclerosis – creates nodules) –> enlarging cervical or mediastinal LN in young adult
• lymphocyte rich type has best prognosis; lymphocyte depleted worst
• mixed cellularity type characterized by eosinophils (RS cells secrete IL5)
• 50% of cases associated with EBV

Question 21

multiple myeloma

Answer 21

• malignant proliferation of plasma cells in BM
• M spike: large amts of IgG or IgA
• punched out lytic bone lesions (neoplastic cells activate osteoclasts)
• increased risk of infection (monoclonal Ab lacks antigenic diversity)
• primary amyloidosis (AL) – free light chain deposition and excretion in urine (Bence Jones proteinuria)
• rouleaux formation of RBCs

Question 22

MGUS

Answer 22

• Monoclonal Gammopathy of Undetermined Significance
• plasma cell dyscrasia
• isolated M spike w/o findings of MM

Question 23

Waldenstrom Macroglobulinemia

Answer 23

• plasma cell dyscrasia
• B-cell lymphoma with monoclonal IgM production (M spike due to IgM)
• hyperviscosity symptoms

**IgM is very large – hence “macro” and viscosity

Question 24

Langerhans cell histiocytosis

Answer 24

• proliferative disorder of dendritic cells in skin (present antigen to naive T cells)
• child with lytic bone lesion and skin rash
• Birbeck granules (“tennis rackets” on EM)