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WBC Path


Tennis rackets, Seborrheic eruptions, otitis media and mastoiditis Langerhans cell histiocytosis
IgM Spike, hepatosplenmegaly and lacking hypercalcemia lymphoplasmacytic lymphoma
Leukocytosis, immature myeloid cells in blood, increased leukocyte ALK PHOS leukemoid reaction
Leukocytosis, immature myeloid cells in blood, low leukocyte ALK PHOS CML
t(8;14), illeocecal mass, med. Leuks w/ coarse chromatin, high mitotic, starry sky sporadic Burkitts
no HSM; Node/extranodal/tonsils large lymphoid cells large nuclei, CD 19, 20, 10 and BCL6 DLCBL
High RBC(marked), platelets, & WBC; low erythropoietin Polycythemia Vera
Polycythemia Vera “burns out” to myelofibrosis
Polycythemia Ver ‘blast out” to AML
Ringed sideroblasts, mafaloblasts, abnormal megakaryocytes, myeloblasts in marrow myelodysplasia
Myelodysplasia with 5q deletion is caused by post-therapy
High platelets &WBC, no marrow fibrosis, no polycythemia;large platelets Essential Thrombocytosis
Virus associated w/ endemic Burkits lymphoma EBV
Mass lesion in stomach, thyroid, or salivary, CD19/20+, CD3-, better after treatment MALToma
<2yo, skin&pulmonary lesions, osteolytic lesion;Birbek granules Letterer-Siwe Disease (Langerhans)
Typical cytoplasmic PAS + finding in AML Auer Rod
anemia, thrombo/neutrocytopenia, marrow: delicate chromatin, nucleoli, az.granules AML
Adult, cutaneous rash/lesions, numb, LA&HSM, anemic, lymphocytosis “clover leaf” cells Adult TCL
Adult T-Cell Lymphoma/ Leukemia associated virus / countries HTLV-1, Japan, W. Africa, Caribean
T or B Cell: CD1 T-Cell
T or B Cell: CD3 T-Cell
T or B Cell: CD4 T-Cell
T or B Cell: CD5 T-Cell
T or B Cell: CD8 T-Cell
T or B Cell: CD10 B-Cell
T or B Cell: CD19 B-Cell
T or B Cell: CD20 B-Cell
T or B Cell: CD21 B-Cell
T or B Cell: CD23 B-Cell
T or B Cell: CD79a B-Cell
Lymphoid neoplasms mostly B or T cell? B cell, 85-90%
BALL or TALL more common? BALL 85%
Most common cancer of children? ALL
ALL more common in what race? hispanics
B-ALL age peak 3yo
T-ALL age peak “adolescence”
Mass present in 50-70% of T-ALLs mediastinal thymic mass
ALL vs AML. ALL: ____chromatin, ______cytoplasm lacking ______ difuse ; smaller amount; granules
ALL stains vs AML: myeloperoxidase ____ and cytoplasm PAS____ myeloperoxidase negative; PAS +
Positive stain in 95% of both B-and T- ALL TdT
TdT + and CD19+, CD10+ most likely Dx B-ALL
Poor prognosis for ALL. Age? Genetics? Under 2yo; peripheral blast >100k; t(9;22) Philadelphia chrm
Favorable prognosis for ALL. Age? Genetics? 2-10yo; low WBC count; hyperploidy; trisomy 4,7,10; t(12;21)
Hyperdiploidy only seen in which? T-ALL or B-ALL? B-ALL
GOF NOTCH1 mutation in T-ALL or B-ALL? T-ALL
Philidelphia Chromosome # and fusion? t(9;22); activated BRC-ABL gene
Most Common Cause of agranulocytosis drug toxicity.
Common clinical manifestation of agranulocytosis ulcerating, necrotizing lesions of the oropharyngeal mucosa
agranulocytosis predisposes to these deep fungal infections Candida and Aprergillus
Below ___/mm3 neutrophils, serious Infx are likely 500
This IL stimulates mainly eosinophils IL-5
This GF induces neutrophilia G-CSF
In sepsis or sever inflammatory reactions, leukocytosis is usually accompanied by these morphologic changes in neutrophils toxic granulations, Dohle Bodies, and cytoplasmic vacuoles
Sky blue cytoplasmic puddles of dilated ER Dohle bodies
Coarse, markedly darker abnormal azurophilic granules toxic granules
Causes of neutrophilia Acute bacterial Infx, usually pyogenic; MI or burns
Causes of eosinophilia allergic disorders; parasite Infx; drug reactions; collagen vascular disorders
Causes of basophilia rare; CML
Causes of monocytosis chronic INFx; rickettsiosis, malaria; SLE; IBD
Causes of lymphosytosis Viral Infx; pertussis; w/ monocytosis in chronic immunological stimulation (Tb)
t(9,22) is associated with what disease(s)? ALL, AML, CML
what inherited genetic factors predispose to WBC neoplasias? Bloom syndrome, Fanconi anemia, ataxia telangiectasia = Acute leukemias
Inherited genetic condition predisposing to childhood leukemias +21, NF-1
Which viruses predispose to WBC neoplasias? HTLV-1, EBV, KSHV
Virus associated with adult T cell leukemia/lymphoma HTLV-1
Virus associated with Burkitt lymphoma, Hodgkin lymphoma, other B cell lymphomas in setting of T-cell immunodeficiency and NK-cell lymphomas EBV
Virus associated with Kaposi sarcoma KSHV
what environmental agent is associated with gastric B-cell lymphomas? H. pylori infection
chronic immune stimulation in what disease is associated with intestinal T-cell lymphomas? gluten-sensitive enteropathy
which plasma cell neoplasm often presents as pain d/t pathologic fractures? multiple myeloma
which WBC neoplasms cause symptoms through the secretion of circulating factors? plasma cell tumors (secretion of antibodies or fragments) Hodgkin lymphoma (fever d/t release of inflammatory cytokines)
MCC of cancer in children? ALL
which subset of ALL presents as childhood leukemia? B-ALL
which lymphoid neoplasm presents in adolescent males as thymic lymphomas (mediastinal mass)? T-ALL
lymphoblasts express CD19 and karyotype shows hyperdiploidy and t(12,21)? B ALL
lymphoblasts often express CD1a and gain-of-fxn mutations in NOTCH1? T ALL
which WBC neoplasm causes compression of large vessels and airways in the mediastinum? T-ALL
which drug is used in t(9,22)+ ALLs and inhibits BCR-ABL kinase? Imatinib (Gleevec)
ALL responsiveness to aggressive chemo (including CNS prophylaxis)? CR in 90% of children, 2/3 cured
MCC of leukemia of adults in Western world? CLL
difference between CLL and SLL? degree of peripheral blood lymphocytosis
WBC neoplasm in which abnml cells gather in LNs in proliferation centers; PBS contains smudge cells? CLL/SLL
Neoplastic cells are positive for CD19, CD20, CD23, and CD5; deletions in 13q, 11q, 17p, trisomy 12q? CLL/SLL
poor prognosis in CLL/SLL is associated with what progression of disease? prolymphocytic transformation (worsening cytopenias, inc splenomegaly, inc # prolymphocytes) Richter syndrome - transformation to diffuse large B-cell lymphoma (rapidly enlarging mass in LN or spleen)
tumor that arises from germinal center B cells and is strongly assoc'd w/ translocations involving BCL2
t(14,18)]? Follicular lymphoma
LN findings in follicular lymphoma? centrocytes - small, cleaved cells centroblasts - larger cells w/ open chromatin, several nucleoli, modest amts of cytoplasm
what are the results of t(14,18) mutation? BCL2 and Ig heavy chain loci switch, BCL2 is overexpressed, promotes survival of follicular lymphoma cells by blocking bax channel
MCC of NHL in United States? follicular lymphoma
response of follicular lymphomas to chemo/rad? survival is not improved by aggressive therapy
mature B-cell tumors that express CD19, CD20 and sometimes translocation of BCL6; typically present at extranodal sites (GI, skin, bone, brain); aggressive, rapidly proliferating; may respond to therapy? Diffuse large B-cell lymphoma
neoplasm with medium sized lymphocytes, "starry-sky" appearance, c-MYC t(8,14)? Burkitt lymphoma
B-cell neoplasm assoc'd with EBV, presents in maxilla or mandible, involves kidneys, ovaries, adrenal glands? African (endemic) Burkitt lymphoma
B-cell neoplasm with high incidence in AIDS, presents as mass involving ileocecum or peritoneum? American (sporadic) Burkitt lymphoma
neoplasm of older adults presenting with hypercalcemia, bone pain, pathologic fxrs; inc gamma proteins, Bence-Jones proteins, and "punched-out" lesions of skull? Multiple myeloma (plasma cell myeloma)
what causes lytic bone lesions in multiple myeloma? inc osteoclast activating factor (OAF, IL-6) MIP1a induces expression of RANKL which activates osteoclasts Modulators of Wnt pathway inhibit osteoblasts
Disorder in which protein casts in DCT and collecting ducts are surrounded by multinucleated giant cells? myeloma kidney
MCC of death in multiple myeloma? infection (inc susceptibility d/t dec production of serum Ig's)
most common plasma cell dyscrasia? monoclonal gammopathy of uncertain significance (MGUS)
MCC of elevated serum M protein level (< 3gm/dL) in asymptomatic older patient? MGUS
B-cell neoplasm that infiltrates many organs, has M spike (IgM), but no hypercalcemia, and no lytic bone lesions present? Lymphoplasmacytic lymphoma
what are Russell bodies and Dutcher bodies? Russell bodies - cytoplasmic immunoglobulin Dutcher bodies - intranuclear immunoglobulin
characteristic of lymphoplasmacytic lymphoma hyperviscosity syndrome
hyperviscosity syndrome causes what complications? vascular dilations and retinal hemorrhages --> visual problems neuro sxs (HA, confusion) abnml globulins cause bleeding and cryoglobulinemia (precipitate at low temp and cause Raynaud phenomenon)
lymphoid neoplasm of older males consisting of small, cleaved lymphocytes, but no proliferation centers, no large centroblasts; t(11,14), high levels of cyclin D, CD5+, CD23-? Mantle cell lymphoma
B-cell tumor that commonly occurs at sites of chronic immune or inflammatory reactions? marginal zone lymphomas (MALTomas)
Disease of middle-aged white males, may cause "dry tap" BM aspirate, presents with red beefy splenomegaly d/t infiltration of red pulp; stains positive for tartrate-resistant acid phosphatase (TRAP) Hairy cell leukemia
neoplasm of CD4+ T-cells in adults infected with HTLV-1, esp. in Japan, W Africa, Caribbean; presents w/ skin lesions, hypercalcemia, enlarged LN, liver, and spleen; cloverleaf nuclei? Adult T-cell Leukemia/Lymphoma (ATLL)
tumor of CD4+ T-cells that causes generalized pruritic erythematous rash (w/o hypercalcemia); abnml cells have cerebriform nuclei? Mycosis fungoides/Sezary syndrome
difference btwn MF and Sezary syndrome? skin lesions of sezary syndrome rarely become tumors sezary cells (cerebriform nuclei) are found in peripheral blood in sezary syndrome, only found in epidermis/dermis in MF
rare neoplasm of CD8 T-cells, lymphocytes have abundant cytoplasm with coarse azurophilic granules? Large granular lymphocytic leukemia
neoplasm presenting as descructive midline mass involving nasopharynx, skin, or testes; highly associated with EBV? extranodal NK/T-cell lymphoma
how is HD different from NHL? - presents with fever - spread is to contiguous (adjacent) nodal groups - characterization based on inflammatory response instead of malignant cell - no leukemic state - extranodal spread uncommon
neoplastic cell of this disease has "owl eye" bilobed nucleus w/ central nucleoli surrounded by clear space Hodgkin lymphoma (Reed-Sternberg cells)
HL variant that has L&H "popcorn" cells and are negative for CD15 and CD30, but positive for B-cell markers CD20 and BCL6? lymphocyte predominance type
most common type of HL; has lacunar variant Reed-Sternberg cells that are positive for PAX5, CD15 and CD30; nuclear deposition of collagen in bands? Nodular sclerosis type
type of HL with infiltrate of T-cells, eosinophils, plasma cells, benign macrophages with Reed-Sternberg cells; RS cells often infected with EBV? Mixed-cellularity type
type of HL with few lymphocytes, many RS cells? lymphocyte depleted type
stereotyped progression of spread of HL? nodal dz --> splenic dz --> hepatic dz --> marrow and other tissues
clinical presentations of HL? usually painless lymphadenopathy disseminated dz, mixed-cellularity or LD types may have B-cell symptoms: waxing/waning fever, wt loss, night sweats
population at risk for AML? adults
dx of AML is based on what? >= 20% myeloid blasts in bone marrow
many myeloblasts on PBS, auer rods, peroxidase+ azurophilic cytoplasmic granules - Dx? AML
auer rods are especially pronounced in what neoplasia (specific translocation)? t(15,17) - acute promyelocytic leukemia
treatment of M3 subtype AML? all-trans retinoic acid (ATRA) - induces differentiation of myeloblasts
difference between acute leukemias and chronic leukemias? mostly blasts (acute), more mature cells (chronic) children or elderly (acute), midlife (chronic) short and drastic (acute), longer, less devastating (chronic)
karyotypic abnormalities associated with AML? de novo: t(8;21), inv(16), t(15;17) following MDS or exposure to DNA-damaging agents: del or monosomies of 5 & 7 after tx w/ topoisomerase II inhibitors: MLL chromosome (11q23)
disorder associated with t(8;14)? burkitt lymphoma (c-myc activation)
disorder associated with t(14;18)? follicular lymphomas (bcl-2 activation)
disorder associated with t(15;17)? M3 type AML
disorder associated with t(11;22)? Ewing's sarcoma
disorder associated with t(11;14)? Mantle cell lymphoma
most common presentation of AML? sxs related to anemia, neutropenia, TCpenia (fatigue, fever, spontaneous mucosal and cutaneous bleeding)
what factors contribute to bleeding diathesis in AML? thrombocytopenia procoagulants and fibrinolytic factors released by leukemic cells (esp in t
which types of AML are high-risk? those that follow MDS or genotoxic therapy or that occur in elderly
primary and t-MDS are associated with what karyotypic abnormalities? monosomy 5 and 7; del 5q, 7q, 20q; trisomy 8
most common finding in MDS? dysplastic differentiation affecting all three myeloid lineages (erythroid, granulocytic and megakaryocytic)
morphological changes seen in MDS? erythroid: ringed sideroblasts, megaloblastoid maturation, nuclear budding abnormalities granulocytic; neutrophils with dec or abnml/toxic granules, pseudo-Pelger-Huet cells Megakaryocytic: pawn ball meg.cytes
what are pseudo-Pelger-Huet cells? neutrophils with only two lobes (seen in MDS)
primary MDS affects what age group? > 60 y
what are the chronic myeloproliferative disorders? - CML - polycythemia vera - essential thrombocytosis - myelofibrosis w/ myleoid metaplasia
what features are common to all MPDs? - neoplastic stem cells home in to secondary hematopoietic organs, esp spleen, leading to splenomegaly - terminal spent phase: marrow fibrosis and peripheral cytopenias - progression to acute leukemia
what is the biomechanical change that occurs in CML? BCR gene (22) fuses with ABL gene (9) and synthesizes a constitutively active tyr-kinase, stimulating proliferation and survival of marrow progenitors does not interfere with differentiation --> increase in mature cells in blood, esp granulocytes and plt
what lab finding helps differentiate between CML and other leukemoid reactions? absence of leukocyte alk phos in CML
cell counts in CML - RBCs, WBCs, Plts? dec RBCs inc WBCs inc Plts
pharm tx of CML? Imatinib (anti-bcr-abl antibody)
disease characterized by increased marrow production of RBCs, granulocytes, and plts? polycythemia vera
mutation implicated in polycythemia vera? activating point mutations in tyr-kinase JAK2
difference between polycythemia vera and secondary absoulte polycythemia? PCV = low EPO secondary polycythemias = high EPO
pathogenesis of essential thrombocytosis? same JAK2 point mutation as in PCV - receptor tyr-kinase activation makes progenitors thrombopoeitin-independent
what is erythromelalgia? throbbing and burning of hands and feet caused by occlusion of small arterioles by plt aggregates seen in ET and PCV
pathogenesis of primary myelofibrosis? inappropriate release of PDGF and TGF-beta from neoplastic megakaryocytes (fibrogenic factors)
in what disease are large platelets and dacryocytes found? myelofibrosis (dacryocytes = teardrop shaped RBCs damaged during birthing process in fibrotic marrow)
secondary disorder that can complicate the picture of MPDs? hyperuricemia and gout (from high cell turnover rate)
infant develops cutaneous seborrheic-like eruption on chest, back, and scalp; also has hepatosplenomegaly, lymphadenopathy, pulmonary lesions. Dx? Letterer-Siwe disease (Multifocal multisystem Langerhans cell histiocytosis)
What is the Hand-Schuller-Christian triad? calvarial bone defects, diabetes insipidus, and exophthalmos (multifocal unisystem Langerhans cell histiocytosis that involves the posterior pituitary stalk)
MCC of splenic infarctions? emboli arising from the heart
MCC of thymic hypoplasia? DiGeorge syndrome
MCC of thymic hyperplasia? myasthenia gravis (also seen in other AI dz: Graves, SLE, scleroderma, RA)
difference between invasive thymoma and thymic carcinoma? invasive thymoma is cytologically benign but locally invasive thymic carcinoma is invasive, somtimes accompanied by metastases, usually squamous cell carcinoma
Created by: csheck