Midterm Flashcards
Where do blood cell progenitors derive from embryologically
Yolk sac
Where do definitive hematopoietic stem cells arise from
Mesoderm of the intraembryonic aorta/gonad/mesonephros region; they then migrate to liver which becomes the chief site of blood cell formation until shortly before birth
What are the formed elements of the blood
Red cells, granulocytes, monocytes, platelets, lymphocytes
What are the progenitors of neutrophils,eosinophils basophils, platelet, and erythrocytes
- neutrophils: myeloblasts
- Monocytes: monoblast
- eosinophil: eosinophiloblast
- basophils: basophiloblast
- platelets: megakaryoblast
- erythrocytes: erythroblast
What are the characteristis of HSCs
Pluripotent and self renewal capability
What factors are expressed on every early committed progenitor
Receptors for KIT ligand, FLT3 Ligand; EPO, CS and thrombopoietin act on committed progenitor cells with more restricted differentiation potentials
What is the morphology of bone marrow
Megakaryocytes lie next to sinusoids and extend cytoplasmic processes that busy off into bloodstream to produce platelets; red cell precursors surround macrophages (nurse cells) that provide iron for hemoglobin; if marrow architecture distorted can lead to leukoerythroblastosis (release of immature precursors into peripheral blood); in normal adults, fat:hematopoietic elements is 1:1; in plastic anemia, fat cells increase; in hemolytic anemia’s, fat is lost
What is the most common cause of lymphopenia
HIV, after therapy with glucocorticoids or cytotoxic drugs, autoimmune disorders, malnutrition, acute viral infections (lymphocyte redistribution in last case)
What can cause neutropenia
- Inadequate or ineffective granulopoiesis: suppression o HSC (aplastic anemia, tumors, granulomatous dz - accompanied by anemia and thrombocytopenia), suppression of committed granulocytic precursors via drugs, megaloblastic anemia and myelodysplastic syndromes, congenital syndromes (kostmann)
- increased destruction or sequestration of neutrophils in periphery: immune mediated injury (SLE), splenomegaly, increased peripheral utilization (overwhelming bacterial, fungal, or rickettsial infections)
What is the most common cause of agranulocytosis
Drug toxicity: alkylating agents and antimetabolites in cancer treatment, aminopyrine, chloramphenicol, sulfonamides (ab mediated destruction of mature neutrophils), chlorpromazine (toxic to precursors), thiouracil, phenylbuazone
What is LGL leukemia
Can cause severe neutropenia; monoclonal proliferation’s of large granular lymphocytes
What is the morphology of the bone marrow in neutropenia
Vary with cause; with destruction of neutrophils in periphery, marrow is hypercellular (also with ineffective granlopoiesis - megaloblastic anemia’s and myelodysplasic syndromes); if destroy precursors - marrow hypocellularity
What infections are a result of agranulocytosis
Ulceration necrotizing lesions of gingiva, floor of mouth, Bucal mucosa, pharynx (agranulocytosis angina); covered by gray to green-black necrotic membranes; *high is for Candida and aspergillus; bacteria grow in colonies (botryomycosis)
What is the peripheral blood leukocyte count influenced by
- size of myeloid and lymphoid precursor and storage cell poools in BM, thymus, circulation, and periphery
- rate of release of cells from storage pools into circulation
- proportion of cells that are adherent to bv walls (marginal pool)
- rate of extravasation of cells from blood into tissue
What are the mechanisms and causes of leukocytosis
- increased production in marrow: chronic infection or inflammation (GF dependent), paraneoplastic (Hodgkin, GF dependent), myeloproliferative disorders(chronic myeloid leukemia, GF independent)
- increased release from marrow stores: endotoxemia, infection, hypoxia
- decreased margination: exercise, catecholamines
- decreased extravasation into tissues: glucocorticoids
What mediates the release of mature granulocytoes from BM during infection
TNF and IL-1; if prolonged, will stimulate macrophages, BM stromal cells, and T cells tp prude increased mounts of hematopoietic growth factors
What happens in sepsis or severe inflammatory disorders (Kawasaki)
Leukocytosis is accompanied by morphological changes in neutrophils ie: toxic granulation (axurophilic granules), Dohle bodies (patches of dilated ER that appear as sky-blue cytoplasmic puddles), cytoplasmic vacuoles
What are the causes of leukocytosis
- neutrophilic leukocytosis: acute bacterial infections (pyogenic), sterile inflammation caused by tissue necrosis (burns, MI)
- eosinophilic: allergic disorders, asthma, hay fever, parasite infections, drug reactions, malignancies (Hodgkin), AI (pemphigus, dermatitis herpetiformis), Vasculitis, atheroembolic dz
- basophils: rare indicative of myeloproliferative dz (CML)
- monocytosis: chronic infections (TB), bacterial endocarditis, rickettsiosis, malaria, AI (SLE), IBD
- lymphocytosis: chronic immune stimulation (TB, brucellosis), viral infections (Hep A, CMV, EPV), bordatella pertussis
What does acute nonspecific lymphadentitis of specific sites indicate
- cervical: teeth or tonsils
- axillary or inguinal: extremities
- mesenteric: appendicitis
What is follicular hyperplasia
Caused by stimuli that activate humoral immune responses; large ablong germinal centers surrounded by naive B cells (mantle zone); tingible-body macrophages ; causes: rheumatoid arthritis, toxoplasmosis, early stages of infection with HIV *features favoring reactive vs neoplastic hyperplasia: preservation of LN architecture (interfolliciular T cell zone and sinusoids), marked variation in shape and size of follicles, presence of frequent mitotic figures, phagocytic macrophages and recognizable light and dark zones
What is paracortical hyperplasia
Caused by a stimuli that triggers T cell mediated immune responses (acute viral infection) hypertrophy of sinusoidal and vascular endothelial cells
What are sinus histiocytosis
Aka reticular hyperplasia; increase in number and size of cells that line lymphatic sinusoids; prominent in LN draining cancers such as carcinoma of breast; but nonspecific
Are LN in chronic reactions tender
No; only acute; common in inguinal an axillary nodes
What is hemophagocytic lymphohistiocytosis
Reactive condition marked by cytopenias and signs and sx of systemic inflammation related to macrophage activation; referred to as macrophage activation syndrome; some forms are familial
What is the pathogensis of hemophagoytic lymphohistiocytosis
*systemic activation of macrophages and CD8 cytotoxic T cells; phagocytosis blood cell progenitors and formed elements in peripheral tissues; sx of systemic inflammation; shock-like picture and cytopenia
What are familial forms of HLH associated with
Several mutations; all impact ability of cytotoxic T cells and NK cells to properly form or deploy cytotoxic granules; high levels of IFN-gamma, TNFalpha, IL-6, IL-12, IL-2R
What is the most common trigger for HLH
Infection, most EBV
What are the clincial features of HLH
ACute febrile illness assoc with HSM; hemophagocytosis seen on BM exam but not required to make diagnosis nor is it sufficient; anemia, thrombocytopenia, very high levels of plasma ferritin and soluble IL-2R; elevated liver function test and triglyceride levels; can progress to death if untreated; treat its immunosuppressive drugs and mild chemo; even with treatment, those who survive have significant sequelae such as renal damage and growth aNd mental retardation in children
What are the types of malignancies of white cells
- lymphoid neoplasms: B cell, Tcell, NK cell origin
- myeloid neoplasms: arise from early HSC progenitors; acute myeloid leukemia (accumulate in BM), myelodysplastic syndromes (ineffective hematopoietic aNd peripheral blood cytopenia), chronic myeloproliferative disorders (increased production of terminally diff myeloid elements)
- histiocytoses: uncommon; proliferative lesions of macrophages and dendritic cells; langerhans cell histiocytosis
Where are dominant negative mutations often seen
Acute Leukemias; causes arrest in differentiation
What is the function of AID (activation induced cytosine delaminase)
Causes class switching and somatic hypermutation (increases ab affinity for antigen); sufficient to induce MYC/Ig translocations in Normal germinal center B cells
What individuals are at increased risk for acute leukemia
Bloom syndrome, fanconi anemia, ataxia telangiectasia, Down syndrome, type I NF
What are the lymphotrophic viruses
HTLV-1: adult T cell leukemia/lymphoma
EBV: Burkett, Hodgkin lymphoma, B cell lymphomas arising insetting of T cell immunodeficiency and NK cell lymphomas
HHV-8: B cell lymphoma that presents as malignant effusion, often in pleural cavity
What are examples of chronic inflammation that have risk of lymphoid neoplasia
H pylori (B cell lymphoma), gluten sensitive enteropathy (T cell lymphoma), breast implants (T cell lymphoma), HIV (B cell)
What iatrogenic factors put people at risk or lymphoid neoplasia
Radiation and certain forms of chemo
What is the effect of smoking on risk of lymphoid neoplasia
Increased risk of acute myeloid leukemia
What are features of plasma cell neoplasms
Most often arise in BM and only infrequently involve LN or peripheral blood
How do Hodgkin and NH lymphomas present
Nontener LN; some NHL present its sx related to involvement of exranodal sites
How do lymphocytic Leukemias often present
Signs and sx of suppression of normal hematopoiesis
How does multiple myeloma (plasma cell neoplasm) present
Bony destruction of skeleton; presents with pain
What are the categories of lymphoid neoplasms
- precursor B cell: neoplasmas of immature B cells
- peripheral B cell: neoplasms of mature B cells
- precursor T cell
- peripheral T cell and NK cell
- Hodgkin lymphoma: neoplasms of reed-stern berg cells
What are the precursor B cell neoplasms
B cell acute lymphoblastic leukemia/lymphoma
What are the peripheral B cell neoplasms
Chronic lymphocytic leukemia/small lymphocytic lymphoma, B cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, splenic and nodal marginal zone lymphomas, extranodal marginal zone lymphoma, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, hairy cell leukemia, plasacytoma/plasma cell myeloma, diffuse large B cell lymphoma, Burkitt lymphoma
What are the precursor T cell neoplasms
T cell acute lymphoblastic leukemia/lymphoma
What are the peripheral T cell and NK cell neoplasms
T cell prolymphocytic leukemia, large granular lymphocytic leukemia, MYC os is fungoides/sezary syndrome, peripheral T cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T cell lymphoma, enteropathy associated T cell lymphoma, paniculitis-like T cell lymphoma, hepatosplenic T cell lymphoma, adult T cell leukemia/lymphoma, extranodal NK/T cel lymphoma, NK cell leukemia
What are the Hodgkin lymphoma subtypes
Nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depletion
What is significant about the antigen receptor of neoplasms
They will all be the same
Which lymphoid neoplasias are not always disseminated at time of diagnosis
Hodgkin and marginal zone B cell lymphomas
What are the the CD markers associated with primarily T cell associated lymphoid neoplasia
- CD1: thymocytes and langherans
- CD3: thymoytes and mature T cells
- CD4: helper T cells, subset of thymocytes
- CD5: T cells and small subset of B cells
- CD8: cytotoxic T cells, subset of thymocytes nad some NK cells
What are the CD markers that re primarily B cell associated
- CD10: pre-Bcells and germinal center B cells
- CD19: pre-B cells and mature B cells but not plasma cells
- CD20: pre B cells after CD19 and mature B cells but not plasma cells
- CD21: EBV receptor; mature B cells and follicular dendritic cells
- CD23: activated mature B cells
- CD79a: marrow pre-Bcells and mature bcells
What are the primarily monocyte or macrophage associated CD markers
- CD11c: granulocytes, monocytes, macrophages; hairy cell Leukemias
- CD13: immature and mature monocytes and granulocytes
- CD14: monocytes
- CD15: granulocytes, reed-sternberg cells
- CD33: myeloid progenitors and monocytes
- CD64: mature myeloid cells
What are the primarily NK cell associated CD markers
- CD16: NK cells and granulocytes
- CD56: NK cells and subset of T cells
What are the primarily stem cell and progenitor cell associated CD markers
CD34: pluripotent HSC and progenitor cells of many lineages
What re the activation CD markers
CD30: activated B, T cells and monocytes; Reed-Sternberg cells
What is the CD present on all leukocytes
CD45
What is the diff in Hodgkin and NHL in terms of spread
Hodgkin spread in orderly fashion; NHL spreads widely early in course and less predictable
What is acute lymphoblastic leukemia/lymphoma
Neoplasms composed of immature B or T cells (lymphoblasts); B-ALLs manifest in childhood as leukemia; T-ALLs manifest in adolescent males as thymic lymphomas; Hispanics have highest incidence; peaks in incidence at 3 for B-ALL; T-ALL peaks in adolescence
What is the pathogensis of ALL
Chrom ab that dysregulate the expression and function of TF required for normal B and T cell development; T-ALLs have GOF in NOTCH1; B-ALLs have LOF in PAX5, E2A, EBF or balanced 12;21 translocation involving ETV6-RUNX1; promote arrest and increased self renewal; hyperdiploidy and hypo diploids only seen in B-ALL
What is the cell of origin for burkitt lymphoma
Germinal center B cell; translocations involving MYC-Ig 8;14 - subset is EBV related; clin presentation: adolescents or young adults with extranodal masses; aggressive
What is the cell of origin of diffuse large B cell lymphoma
Germinal center or postgerminal center B cell; rearragnemts o BCL6, BCL or MYC; presents at all ages but more common in adults; appears as rapidly growing mass; aggressive
What is the cell of origin of extranodal marginal zone lymphoma
Memory B cell; translocations: 11;18, 1;14, 14;18 - MALT1-IAP2, BCL10-IgH, MALT-IgH union genes; arises at extranodal sites in adults with chronic inflammatory dz; indolent
What is the cell of origin for follicular lymphoma
Germinal center B cell; translocation: 14;18 - BCL2-IgH; presents in older adults with generalized LAD and marrow involvement; indolent
What is the cell of origin of hairy cell leukemia
Memory B cell; activating BRAF mutation; seen in older males with pancytopenia and splenomegaly; indolent
What is the cell of origin of mantle cell lymphoma
Naive B cell; 11;14 translocation - cylinD-IgH fusion; older males with disseminated dz; moderately aggressive
What is the cell of origin of multiple myeloma/solitary plasmacytoma
Post germinal colter bone marrow homing plasma cell; diverse rearragnemtns involving IgH; 13q deletions; myeloma seen in older adults with lytic bone lesions, hypercalcemia, and renal failure; moderately aggresive; plasmacytoma - see isolated plasma cell masses in bone or soft tissue; indolent
What is the cell of origin for small lymphocytic lymphoma/ chronic lymphocytic leukemia
Naive B cell or memory B cell; trisomy 21, deletions of 11q, 13 and 17p; seen in older adults with BM, LN, spleen and liver dz; AI hemolysis and thrombocytopenia; indolent
What is the cell of origin of adult T cell leukemia/lyphoma
Helper T cell; HTLV-1 povirus present in tumor cells; presents in adults with cutaneous lesions, marrow involvement and hypercalcmia; mainly in Japan, west Africa and Caribbean; aggressive
What is the cell of origin of peripheral T cell lymphoma
Helper or cytotoxic T cell; no specific chrom ab; seen in older adults with LAD; aggresive
What is the cell of origin of anaplastic large cell lymphoma
Cytotoxic T cell; rearrangements o ALK (anaplastic large cell lymphoma kinase); seen in children and young adults with LN and soft tissue dz; aggresive
What is the cell of origin of extranodal NK/Tcell lymphoma
NK cell (common) or cytotoxic T cell (rare); EBV associated; seen in adults with destructive extranodal masses; most commonly sinonasal; aggressive
What is the cell of origin of mycosis fungoides/sezary syndrome
Helper Tcell; no chrom ab; seen in adult patients with cutaneous patches, plaques, nodules or generalized erythema; indolent
What is the cell of origin of large granular lymphocytic leukemia
2 types: cytotoxic T cell and NK cell; point mutations in STAT3; seen in adult patients with splenomegaly, neutropenia and anemia;
What is the morphology of ALL
In leukemia presentation: marrow is hypercellular and packed with lymphoblasts; mediastinal thymic masses occur in most T-ALLs and more likely to be assoc with LAD and splenomegaly; scant basophils cytoplasm; starry sky appearance; compared to myeloblasts, lymphoblasts have more condensed chromatin, less conspicuous nucleoli and smaller amounts of cytoplasm that usually lacks granules *also lymphoblasts are myeloperoxisdase neagtive
What staining is positive in ALL
Immunostaining for terminal deoxynucleotidyl transferase (TdT)
B-ALL: CD19 and PAX5; CD10; in very mature B-ALL, CD10 is negative; IgM in late pre-B ALLs
T-ALL: CD1, CD2, CD5, CD7; more mature CD3, CD4, CD8
What are the clinical features of ALL
- abrupt stormy onset within days to weeks of first sx
- sx related to depression of BM function; fatigue due to anemia ,fever (neutropenia), bleeding (thrombocytopenia)
- mass effects: bone pain resulting from marrow expansion and infiltration of subostium, generalized LAD, HSM, testicular enlargement, in T-ALL - compression of vessels and airways in mediastinum
- CNS manifestations such as HA, vomiting and nerve palsies resulting from meningeal spread (more common in ALL than AML)
What factors are assoc with a worse prognosis in ALL
Age <2 yrs (b/c involve translocations involving MLL gene), presentation in adolescence or adulthood, peripheral blood blast counts >100,000 (high tumor burden)
What are good prognostic factors in ALL
Age btw 2-10, low white cell count, hyperdiploidy, trisomy of chromosomes 4,7,10, presents of 12;21
What dos the 9;22 translocation form of ALL do
Creates fusion gene that encodes an active BCR-ABL tyrosine kinase; treatment with BCR-ABL kinase inhibitors in combo with chemo is effective
What is the most common leukemia in adults in the western world
chronic lymphocytic leukemia; median age: 60; more common in males
What is the pathogensis of CLL/SLL
Most common anomaly is deletion of 13q14.3, 11q, 17p, and trisomy 12q; tumors with unmutated Ig segments (naive B cell origin) have a more aggresive course;GOF in notch1 receptor; tour cells rely on signals enervated b B ell receptor transducer by BTK (defective in x linked BTK)
What is the morphology of CLL/SLL
LN diffusely effaced by infiltrated of small lymphocytes; proliferation centers - pathognomonic for CLL/SLL; blood contains large numbers of small round lymphocytes with scant cytoplasm; smudge cells; BM almost always involved by interstitial infiltrates or aggregates of tumor; also seen in splenic white and red plump and hepatic portal tracts
What is the immunophenotype of SLL/CLL
Pan Bcell markers; CD19 and CD20; CD23, CD5
What is the clinical presentation of CLL/SLL
Asymptomatic at diagnosis; when sx, nonspecific - fatiguability, weight loss, anorexia; generalized LAD, HSM; leukopenia or Leukocytosis; disrupts normal immune function hypogammaglobulinemia hemolytic anemia or thrombocytopenia due to abs produced by NON-neoplastic B cells
What correlates with a worse outcome of CLL/SLL
Presence of deletions of 11q and 17p; lack of somatic hypermutation, expression of ZAP-70, presence of NOTCH1 mutation
How is CLL/SLL treated
Gentle chemo and immunotherapy with abs against CD20
What factors impacts patient survival in CLL/SLL
It can transform to more aggresive tumor; most commonly in form of diffuse large B cell lymphoma (richter syndrome) - rapidly enlarging mass in LN or spleen; not good survival
What is the most common form of indolent NHL in the US
Follicular lymphoma; presents in middle age and affects both genders equally; strongly assoc with chrom translocations involving BCL2 14;18; devoid of apoptosis cells; mutations in MLL2 (encodes histone methyltranserase that regulations gene expression - epigenetics impt) response to therapy influenced by surrounding microenvironment
What is the morphology of follicular lymphoma
Predominantly nodular or diffuse pattern in involved LN; 2 cell types present: small cells with irregular or cleaved nuclear contours (centroytes) and larger cells with open nuclear chromatin, several nucleoli (centroblasts); BM involved in most cases - paratrabecular lymphoid aggregates* splenic white pulp and hepatic portal triads frequently involved
What is the immunophenotype of follicular lymphoma
CD19, CD20, CD10, surface Ig, BCl6; CD5 NOT expressed; BCL2 in most cases
What are the clinical features of follicular lymphoma
Painless generalized LAD; involvement of extranodal sites is uncommon; incurable, but follows indolent waxing and waning course; survival not improved by aggressive therapy; palliative care with low dose chemo or immunotherapy when become sx; histo transformation occurs in half of cases most commonly to diffuse B cell lymphoma; can also transform to burkitt lymphoma; not long survival after transformation
What is the most common form of NHL
Diffuse large B cell lyphoma; slight male predominance; median age 60 but can occur in young adults and kids
What is the pathogenesis of DLBCL
Dysregulation of BCL6 (required for formation of normal germinal centers) - product of somatic hypermutation that results in overexpression of BCL6; BCL6 normally represses expression of factors t hat promote germinal center B cell diff, growth arrest, and apoptosis; some assoc with 14;18 translocation; mutations in p300 (histone acetylase) and CREBP
What is the immunophenotype of DLBCL
CD19 CD20; variable expression of CD10 and BCL6
What are the subtypes of DLBCL
- immunodeficiency associated: occurs in setting of severe T cell immunodeficiency (HIV and allogeneic BM transplant); usually infected with EBV restoration of T cell immunity may lead to regression
- primary effusion lymphoma: malignant pleural or ascitic effusion mostly in patients with advanced HIV or older adults; tumor cells are anaplastic and fail to express surface B or T cell markers but have long as IgH gene arrangements; in all cases* tumor cells are infected with HHV-8
What are the clinical features of DLBCL
Presents as rapidly enlarging mass at nodal or extranodal site; can arise anywhere; waldeyer ring (oropharyngeal lymphoid tissue) commonly involved; extranodal sites include GI, skin, bone, brain; BM involvement uncommon; aggressive and rapidly fatal without treatment; with chemo good prognosis; anti-CD20 improves outcome; if have a MYC translocation, worse prognosis
What are the categories of burkitt lymphoma
African (endemic) burkitt lymphoma; sporadic (nonendemic) burkitt lymphoma, and subset of aggresive lymphomas occuring in individuals with HIV; histologically identical but differ in clinical, genotype, and virologic characteristics
What is the pathogenesis of burkitt lymphoma
All forms assoc with translocations of MYC on chrom 8 that leads to increased MYC protein levels; Warburg effect - increases genes that are required for aerobic glycolysis *fastest growing human tumor; 8;14 translocation (IgH locus) or 2;8 (Igk) or 8;22 (gamma light chain); breakpoint in sporadic in class switch regions; in endemic in VDJ sequences
What are all endemic burkitt lymphomas infected with
latent EBV; also present in 1/4 of HIV assoc tumors and some sporadic cases
what is the morphology of burkitt lymphoma
Diffuse infiltrate of intermediate size lymphoid cells; coarse chromatin, several nucleoli; high mitotic index and numerous apoptotic cells - phagocytosed by macrophages which creates starry sky appearance; in BM, royal blue cytoplasm containing clear cytoplasmic vacuoles
What is the immunophenotype of burkitt
IgM, CD19, CD20, CD10, BCL6; does not express BCL2 (unlike other tumors of germinal center origin)
What are the clinical features of burkitt lymphoma
Both endemic and sporadic found mainly in children; most manifest as tumors in extranodal sites; endemic usually presents as a mass involving mandible and abdominal viscera (kidneys, ovaries, and adrenal glands); sporadic appears as mass involving ileocecum and peritoneum; involvement of BM and peripheral blood uncommon; very aggressive but responds well to intense chemo
What are the plasma cell neoplasms referred to as
Dyscrasias; most common and deadly is multiple myeloma; identified by monoclonal Ig in blood (M component); neoplastic plasma cells can synthesize excess light chains and complete Igs; light chains can be excreted in urine (bence-jones protein)
what are the terms used to describe abnormal Igs in plasma cell neoplasms
Monoclonal gammapathy, dysproteinemia, paraproteinemia
What pathologies are associated with abnormal igs
- multiple myeloma (plasma cell myeloma): presents as tumorous masses scattered throughout skeletal system; solitary myeloma (plasmacytoma) is variant that presents as single mass in bone or soft tissue; smoldering myeloma is variant with lack of sx and a high plasma M component
- waldenstrom macroglobulinemia: high levels of IgM lead tot sx related to hyperviscosity of blood; older adults in association with lymphoplasmacytic lymphoma
- heavy chain dz: monoclonal gammopaty seen in assoc with lymphoplasmacytic lymphoma and small bowel marginal zone lymphoma (malnourished - Mediterranean lyymphoma); synthesis of free heavy chain
- primary or immunocyte assoc amyloidosis: monoclonal proliferation of plasma cells secreting light chains (usually gamma) that are deposited as amyloid
- monoclonal gammopathy of undetermined significance: patients w/o sx who have small to moderately large M components in blood; common in older adults and low, but constant rate of transformation to sx monoclonal gammopathies, mostly multiple myeloma
What is multiple myeloma
Plasma cell neoplasm assoc with lytic bone lesions, hypercalcemia, renal failure, and acquired immune abnormalities; can spread in late course to LN and extranodal sites; higher in men and Africans; peak incidence age 65
What is the pathogenesis of multiple myeloma
Assoc with frequent rearrangements involving IgH locus with cyclinD1 and D3; deletions on chrom 17p that involves TP53 indicate poor outcome; frequent mutationis of NFkB; survival of tumor dependent on IL-6* - high levels seen in active dz and assoc with poor prognosis; MIP1alpha up regulates express ion of receptor activator of NFkB (RANKL) which activates osteoclasts (increased bone resorption) - hypercalcemia and breakdown of bone
what is the morphology of multiple myeloma
Destructive plasma cell tumors involving axial skeleton; most effected: vertebral column, ribs, skull, pelvis, femur, clavicle, scapula; lesions begin in medullary cavity and erode callous bone, destroy the bony cortex; bone lesions appear as punched out defects on radiograph and consist of soft gelatinous red tumor masses; some variants can have flame cells with fiery red cytoplasm, Mott cells with multiple grasp like cytoplasmic droplets; globular inclusions (Russell bodies - if cytoplasmic) (duthcer bodies if nuclear) *M protein causes rouleaux formation
what is the immunophenotype of multiple myeloma
CD138 (adhesion molecule aka syndecan-1), often express CD56
what are the clinical features of multiple myeloma
Pathologic fractures and chronic pain; hypercalcemia - neuro sx, weakness, lethargy, constipation, polyuria; recurrent bacterial infxn; renal insufficiency - trails infections as COD; can cause amyloidosis if AL type; most common monoclonal lgis IgG
What does definitive diagnosis of multiple myeloma rely on
Bone marrow exam; often gives rise to normochomic anemia
What is assoc with a good outcome of multiple myeloma
Translocations involving cyclin D1; deletions of 13q, 17p, ad 4;14 translocation have more aggressive course
What is being explored s a treatment for multiple myeloma
Proteasome inhibitors; thalidomide also has activity against myeloma
What is solitary myeloma (plasmacytoma)
Solitary lesion of bone o soft tissue; extraosseous lesions found in lungs, oronasopharynx or nasal sinuses; progresses to multiple myeloma but can take 10 years; extraosseus can be cured by local resection
What is smoldering myeloma
Middle ground btw multiple myeloma and monoclonal gammopathy; asymptomatic; about 75% progress to multiple myeloma in 15 years
What is monoclonal gammopathy of uncertain significance
Most common plasma cell dyscrasia; asymptomatic Nd serum M protein <3gm/dL; 1% envelop symptomatic plasma cell neoplasm (multiple myeloma)
What is lymphoplasmacytic lymphoma
B cell neoplasm of older adults that usually presents in 6th or 7th decade; substantial reaction of tumor cells undergo. Terminal differentiation to plasma cells; secretes IgM -> hyperviscosity syndrome known as waldenstrom macroglobulinemia; does not have complications of renal and amyloidosis like multiple myeloma
What is the pathogensis of lymphoplasmacytic lymphoma
All have mutations in MYD88 (encodes adaptor protein for signaling evens that activate NFkB and augment signals downstream of Bcell receptor
What is the morphology of lymphoplasmacytic lymphoma
Marrow contains infiltrate of lymphocytes, plasma cells, and plasmacytoma lymphomcytes accompanied by mast cell hyperplasia; Russell bodies or dutcher bodies; at diagnosis usually disseminated to LN, spleen, and liver; infiltration of n roots, meninges and brain can also occur
What is the immuophenotype of lymphoplasmacytic lymphoma
CD20 and surface Ig; secrets IgM or IgG or IgA
What are the clinical features of lymphoplasmacytic lymphoma
Nonspecific complaints; half have LAD, HSM; anemia is common; autoimmune hemolysis caused by gold glutinous (IgM binds to red cells at temp <37 degrees)
What symptoms do patients with IgM secreting tumors
Hyperviscosity syndrome: visual impairment (venous congestion, totuosity and distention of retinal veins, retinal hemorrhages and exudates), neuro problems (HA, dizziness, deafness, stupor from sluggish blood flow), bleeding (formation of complexes btw macroglobulinemia and clotting factors), cryoglobulinemia (precipitation of macroglobulinemia at low temps - raynauds and cold urticaria)
Is lymphoplasmacytic lymphoma curable
No; symptoms alleviated by plasmapharesis; median survival is 4 years
What is extramedullary plasmacytoma
Solitary mass usually in aero digestive tract; rarely progresses to systemic dz
What is mantle cell lymphoma
Uncommon; presents in 5ht-6th decade and shows male predominance
What is the pathogenesis of mantle cell lymphoma
11;14 translocation involving IgH locus and cylin D1
What is the morphology of mantle cell lymphoma
Generalized LAD; 40% have peripheral blood involvement; extranodal involvement: bon marrow, spleen liver and gut; can produce polyp like lesions - most likely to spread in this fashion of all NHL; nodular appearance; proflieration of small lymphocytes with irregular to deeply clefted nuclear contours
What is the immunophenotype of mantle cell lymphoma
cyclin D1; CD19, CD20 and high levels of IgM and D; usually CD5+ and CD23 - (distinguishes it from CLL/SLL); lacks somatic hypermutation
What are the clinical features of mantle cell lymphoma
Painless LAD; sx related to gut and spleen common; prognosis is poor* blastoid variant and proliferative expression assoc with even shorter survival
What are marginal zone lymphomas
Arise within LN, spleen or extranodal tissues; often referred to as MALTomas; somatic hypermutation - memory B cell origin
What are the 3 exceptional characteristics of marginal zone lymphomas
- often arise within tissue involved by chronic inflammatory disorders; ie: sjogren, hashimotos, h pylori
- remain localized for prolonged periods spreading only late in course
- may regress if inciting agent is eradicated
What translocations are specific for mantle zone lymphomas
11;18 14;18 1;14 - all unregulated function of BCL10 or MALT1 which activate NFkB; with further Clonal evolution, spread to distant sites and transformation to DLBCL can occur
What is hairy cell leukemia
Disease of middle aged white males; median age of 55
What is the pathogensis of hairy cell leukemia
Assoc with activating point mutations in BRAF (serine/threonine kinase) - downstream of RAS in MAPK cascade; mutation is valine to glutamate substitution (also sen in melanoma and langerhans cell histiocytosis)
What is the morphology of hairy cell leukemia
Fine hairlike projections; on blood smear has round, oblong nuclei and pale blue cytoplasm with bleblike projection; cannot be aspirated - “dry tap” and are only seen in marrow biopsies; splenic red pulp usually heavily infiltrated leading to obliteration of white pulp and beefy red. Gross appearance; hepatic portal triad involved frequently
What is the immunonphenotype of hair cell leukemia
CD19 CD20, surface Ig (IgG), CD11c, CD25, CD103, annexin A1
What are the clinical features of hairy cell leukemia
Result from infiltration of BM, liver, spleen; massive splenomegly*, hepatomegaly not as common; LAD is rare; pancytopenia, infections - risk of atypical mycobacterial infections; indolent course; sensitive to gentle chemo; relapse in 5 or more years; BRAF inhibitors produce excellent response; excellent prognosis
What is peripheral T cell lymphoma unspecified
Face LN diffusely and are typically composed of pleomorphic mixture of malignant T cells; prominent infiltrate of reactive cells; express CD2, CD3, CD5, and either alphabeta or deltagamma T cell receptor; most present with LAD, eosinophilia, pruritis ever and wight loss; worse prognosis than mature B cell neoplasms
What is anaplastic large cell lymphoma (ALK positive)
Uncommon; presence of rearrangements of ALK gene on chrom 2p23; break ALK locus and lead to ALK fusion proteins - trigger JAK/STAT signaling; horseshoe shaped nuclei and voluminous cytoplasm (hallmark cells) clusters around venules and infiltrates lymphoid sinuses mimicking met carcinoma *ALK is not present in normal lymphocytes; occurs in children or young cults and involves soft tissue and have good prognosis; if no ALK rearrangement (adults) poor prognosis; both express CD30
What is adult T cell leukemia/lymphoma
Neoplasm of CD4 cells only observed in adults infected with HTLV-1; skin lesions, generalized LAD, HSM, peripheral blood lymphocytosis and hypercalcemia; cloverleaf or flower cells; HTLV-1 encodes Tax that is an activator of NFkB; most p resent with rapidly progressive dz that is fatal within months to 1 year
What else can HTLV-1 infection lead to
Progressive Demyelinating dz of CNS and SC
What is mycosis fungoides
Different manifestation of a tumor of CD4 helper T cells that home to the skin; progresses through premycotic phase, plaque phase and tumor phase; epidermis and dermis infiltrated by neoplastic T cells which have cerebriform appearance
what is sezary syndrome
Variant in which skin involvement is manifested as generalized exfoliative erythroderma; in contrast to mycosis fungoides, skin lesions rarely proceed to tumefaction; associated leukemia of sezary cells with charactestic cerebriform nuclei
What is the immunophenotype of s early syndrome and mycosis fungoides
adhesion molecule cutaneous leukocyte antigen (CLA) and chemokine receptors CCR4 and CCR10; indolent tumors
What is large granular lymphocytic leukemia
T and NK cel variants; adults; in T cell dz (CD3 positive) -> lymphocytosis and splenomegaly; NK dz (CD3 negative, CD56) more subtle; mutations in STAT3; neutropenia and anemia ; T cell indolent; NK more aggressive
What is felty syndrome
Complication of large granular lymphocytic leukemia; triad of RA, splenomegaly, and neutropenia
What is extranodal NK/T cell lymphoma
Rare in US; Asia; presents as destructive nasopharyngeal mass; surrounds and invades small vessels leading to extensive ischemic necrosis; large azurophilic granules seen in cytoplasm; assoc with EBV but tumor cells do not express CD21; CD3 -; highly aggresive but respond well to radiation, not hemo; prognosis is poor
What is the presentation of Hodgkin lymphoma
Arises in single node or chain of nodes and spreads first to anatomically continuous lymphoid tissues; reed stern berg cells (neoplastic giant cells) derived from germ center or post germ center B cells
What are the subtypes of Hodgkin lyphoma
Nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depletion, lymphocyte predominance
What are the classical forms of Hodgkin
Nodular sclerosis, mixed cellularity, lymphocyte rich and lymphocyte depletion; have similar immunophenyote.
What is the pathogenesis of Hodgkin
Ig genes of reed sternberg cells have undergone VDJ recombination and somatic hypermutation; don’t express B cell specific genes; activation of NFkB
How can NFkB b activated in Hodgkin
- EBV infection
- EBV +tumor cells express latent membrane proline 1 (LMP-1) encoded by EBV genome that upregulates NFkB
- result of acquired LOF in IkB or A20 (TNF alpha induced protein 3 or TNFAIP3)
- rescues crippled germ center B cells that cannot express Igs from apoptosis
- gains in REL Proto-oncogene
What is the morphology of Hodgkin
Reed-Sternberg cells are large with multiple nuclei or single nucleus with multiple lobes; mononuclear variants; lacunae cells seen in nodular sclerosis type have folded or multilobate nuclei
What conditions can cells that resemble reed sternberg cells be seen
Mono, solid tissue cancers, and large cell NHL
What does the diagnosis of Hodgkin lymphoma depend on
Reed sternberg cells in background of non-neoplastic inflammatory cells
What is the morphology of the nodular sclerosis type of Hodgkin
Most common* lacunae variant Reed-Sternberg cells; deposition of collagen in bands that divide involved LN into circumscribed nodules *PAX5, CD15 and CD30 positive, negative for other B cell markers, T cell markers, and CD45; not assoc with EBV; equal in males and females; *involves lower cervical, supraclavicular and mediastinal LN; excellent prognosis
What is the morphology of mixed cellularity type Hodgkin
LN usually diffusely effaced by infiltrate; *diagnostic reed sternberg cells usually plentiful - most are infected with EBV; immunophenotype same as nodular sclerosis; more common in males, older age, and systemic sx; very good prognosis
What is the morphology lymphocyte-rich type Hodgkin
Uncommon; reactive lymphocytes make up majority of infiltrate; LN diffusely effaced; *presence of mononuclear variants and diagnostic Reed-Sternberg cells; excellent prognosis
What is the morphology of the lymphocyte depletion type of Hodgkin
Least common form*; abundance of reed sternberg cells; *most infected with EBV; occurs in old adults, in HIV+ ppl of any age and in non industrialized countries; less favorable outcome
What is the morphology of the lymphocyte predominance type of Hodgkin
Uncommon; effaced by nodular infilatred of small lymphocytes with variable number of macrophages; reed-sternberg hard to find contains lymphocytic and histioctic variants which have multilobed nucleus resembling popcorn kernel* - express B cell markers typical of germinal center B cells (CD20, BCL6, neg for CD15 and CD30); can transform to DLBCL; not assoc with EBV; males <35, cervical or axillary LAD; excellent prognosisi
What are the clinical features of Hodgkin
Presents as painless LAD; patients with nodular sclerosis or lymphocyte predominance tend to have stage I-II dz and free of systemic sx; cutaneous immune unresponsiveness (anergy) also seen; factors released from Reed-Sternberg cells suppress Th1 immune responses
How does Hodgkin spread
Nodal dz first -> splenic dz, hepatic dz and then marrow and other tissues; staging involves PE, radiologic imaging of ab, pelvis, chest and bx of BM; tumor stage rather than histo subtype is most impt for prognosis
How can you cure low stage localized Hodgkin
Field radiotherapy; but risks lung cancer, melanoma, an breast cancer; patients treated with early chemo regimens containing alkylating agents had high incidence of secondary tumors (AML)
What factors do Reed-Sternberg cells release
TNF, bFGF (leads to fibrosis); IL-5, galectin-1 (enhances Treg response), inhibits Th1 and CTL with IL-10; M-CSF, IL-13 which binds to a receptor on its membrane
What is the common feature among myeloid neoplasms
Origin from hemtopoietic progenitor cells; present with sx related to altered hematopoiesis
What are the categories of myeloid neoplasia
- acute myeloid Leukemias: accumulation of immature myeloid forms (blasts) in BM and suppresses normal hematopoiesis
- myelodysplastic syndromes: defective maturation of myeloid progenitors gives rise to ineffective hematopoiesis leading to cytopenias
- myeloproliferative disorders: increased production of. One or more types of blood cells
What are the manifestations of myeloid neoplasms influenced by
- position of transformed cell within the hierarchy of progenitors
- effect of transforming events on differentiation
What is acute myeloid leukemia
Tumor of hematopoietic progenitors caused by acquired oncogene culture mutations that impede differentiation leading to accumulation of immature myeloid blasts in marrow; leads to marrow failure and anemia, thrombocytopenia and neutropenia; occurs at all ages but rises throughout life (peak in 60s)
What is the classification of AML
Heterogenous; 4 categories: AML with genetic aberrations, AML with MDS-like features, AML therapy related and AML NOS
What are the AML with genetic aberrations
- AML w/ (8;21)(q22;q22) RUNX1/ETO fusion: favorable prognosis; full range of myelocytic maturation; auger rods easily found; abnormal cytoplasmic granules
- AML w/ inv(16)(p13;q22); CBFB/MYH1 fusion: favorable prognosis; myelocytic and monocytes diff; abnormal eosinophilic precursors with ab basophilic granules
- AML w/ t(15;17)(q22;11-12); RARA/PML fusion: favorable; numerous Auer rods in bundles primary granules prominent; high incidence of DIC*
- AML w/ t(11q23;v) diverse MLL fusion: poor, monocyte diff
- AML w normal cytogenetic and mutated NPM: favorable; detected by immuno histo staining for NPM
What are the AML with MDS like features
- with prior MDS: poor prognosis; diagnosis based on clin history
- AML with multilineage dysplasia: poor; maturing cells with dysplastic features typical of MDS
- AML with MDS-like cytogenetic aberrations: poor assoc with 5q, 7q, 20q aberrations
What is AML therapy related
Very poor prognosis; if following alkylation or radiation therapy, 2-8 year latency period; MDS like cytogenic aberrations; if following topoisomerase II inhibitor (etoposide) 1-3 year latency, translocations involving MLL
What is AML NOS
- AML, min diff: intermediated prognosis; neg for myeloperoxidase, myeloid antigens detected on blasts by flow cytomegalovirus
- AML without maturation: intermediate; >3% of blasts pos for myeloperoxidase
- AML with myelocytic maturation: intermediate; full range of myelocytic maturation
- AML with myelomonocytic maturation: intermediate; myelocytic and monocyte diff
- AML with monocytes maturation: intermediate; nonspecific esterase positive monoblasts and pro monocytes predominate in marrow
- AML with erythroid maturation:: intermediate; erythroid/myeloid subtype >50% dysplastic maturing erythroid precursors and >20% myeloblasts; pure erythroid subtype defined by >80% erythroid precursors without myeloblasts
- AML with megakarytocyte maturation: intermediate; blasts of megakaryocytic lineage; detected with abs against megakaryocyte markers (GPIIb/IIIa or vWF); assoc with marrow fibrosis; *most common AML in Down syndrome
What are the most common rearrangements seen in AML
Genetic aberrations disrupt genes encoding TF required for normal myeloid diff; *2 most common are t(8;21) and inv(16) - disrupte RUNX and CBFB genes respectively which encode polypeptide that bind each other to form RUNX1-CBF1beta required for normal hematopoiesis
What growth factor signaling pathways are mutated in AML
Ex: AML with t(15;17) - acute promyelocytic leukemia; creates retinoids acid receptor fusion with PML which interferes with terminal diff of granulocytes - can be overcome with all-trans retinoids acid or arsenic trioxide; but this is not enough to cause dz; also have mutations in FLT3 (RTK)
What epigenomic mutations have been seen in AML
Genes that influence DNA methylation or histone modifications; mutations of cohesion complex (proteins that regulate 3D structure of chromatin)
What is the diagnosis of AML based on
Presence of at least 20% myeloid blasts in the BM; myeloblasts have delicate nuclear chromatin, 2-4 nucleoli and lots of cytoplasm containing peroxidase pos granules; auer rods - distinct needle like azurophilic granules (acute promyelocytic leukemia is most prominent), monoblast: folded or lobulated nuclei, lack serum rods
What is aleukemic leukemia
When blasts are entirely absent from blood in AML
What marker do myeloid blasts express
CD34 (marker of pluripotency) and CD33 (marker of immature cells) but not CD64
What are AMLs arising de novo in younger adults assoc with
Balanced chromosomal translocations particularly t(8;21), inv(16) and t(15;17)
What are AMLs following myelodysplastic syndromes or exposure to DNA damaging agents assoc with
Deletions or monosomies invovling chrom 5 and 7; lack translocations *exception is those that arise after treatment with topoisomerase II inhibitors - assoc with translocations involving MLL gene on chrom 11q23
What are the clinical features of AML
Present within weeks or months of onset of sx with complaints related to anemia, neutropenia and thrombocytopenia (fatigue, fear and spontaneous mucosal and cutaneous bleeding); infections in oral cavity, skin, bladder, kidneys, colon usually caused by fungi, pseudomonas and commensals; tumors with monocytes diff infiltrate skin(leukemia cutis) and gingiva; CNS spread less common than ALL; can present as localized soft tissue mass known as myeloblastoma, granuloccytic sarcoma or chloroma
What is the prognosis of AML
Difficult to treat; *AML with 15;17 treated with all-trans retinoids acid and arsenic salts has best prognosis; AMLs with 8;21 or inv(16) have good prognosis with chemo especially in absence of KIT mutations; prognosis is dismal for AMLs that follow MDS or genotoxic therapy to that occur in older adults (treat with hematopoietic stem cell transplant)
What are myelodysplastic syndromes
Group of Clonal stem cell disorders characterized by maturation defects assoc with ineffective hematopoiesis and high risk of transformation to AML; BM is replaced by Clonal progeny of neoplastic multipotent stem cell that can differentiate but does so in an ineffective and disordered fashion; all forms can transform to AML, but the ones after therapy (t-MDS) occur more frequently and rapidly
What is the pathogenesis of MDS
- epigenetics: mutations in DNA methylation and histone modifications
- RNA splicing factors: mutations involving 3’ end of RNA splicing machinery
- TF
- 10% have LOF in TP53 high correlates with complex karyotype and poor clinical outcom
- assoc with chrom ab including monosomies 5 and 7 deletions of 5q (RPS14) 7q 20q Nd trisomy 8 (MYC located here)
What is the morphology of MDS
Hypercellular at diagnosis; most characteristic finding is disordered diff affecting erythroid, granulocytic, monocytes and megakaryocytic lineages; *ring siderobblasts, erythroblast with iron-laden macrophages, megaloblastoid maturation (as seen in B12 and folate def) and nuclear budding abnormalities (misshapen nuclei); pseudo-pelger-Huet cells (neutrophils with only 2 nuclear lobes); pawn ball megakaryocytes (single nuclear lobes or multiple separate nuclei); myeloid blasts increased but make up less than 20% of marrow; blood contains pelger-huet, giant platelets, macrocytes and poikilocytes
What are the clinical features of primary MDS
Older adults (mean age 70); half discovered incidentally on blood testing; when sx present with weakness, infections and hemorrhages; worse outcomes predicted by higher blast counts and more severe cytopenias as wel las presence of multiple Clonal chrom ab
What are the tyrosine kinase mutations in myeloproliferative disorders
- chronic myelogenous leukemia: BCR-ABL fusion
- polycythemia Vera: JAK2 point mut
- essential thrombocythemia: JAK2 point mut; MPL point mut
- primary myelofibrosis: JAK2 and MPL point mut
- systemic mastocytosis: KIT point mut
- chronic eosinophilic leukemia: FIP1L1-PDGFRA fusion (common)and PDE4DIP-PDGFRB fusion (rare - responds to imatinib therapy) assoc with Loeffler endocarditis
- stem cell leukemia:: FGFR1 fusion genes
What is the median survival in primary MDS
9 - 24 month; in tMDS only 4-8 months
What are the treatment options for MDS
Allogeneic hematopoietic stem cell transplant in younger patients; older patients treated with supportive abx Nd transfusions
What is the common pathogenic features of myeloproliferative disorders
Mutated constitutively active tyrosine kinase or other abberations in pathways that lead to growth factor independence
What are the common clinical features of myeloproliferative disorders
- increased proliferative drive in BM
- Homing of neoplastic stem cells to secondary hematopoietic organs producing extramedullary hematopoiesis
- variable transformation to spent phase characterized by marrow fibrosis and peripheral blood cytopenias
- variable transformation to acute leukemia
What is CML
BCR-ABL fusion - created by a reciprocal (9;22)(q34;q11) translocation (philly chrom); cell of o robin is pluripotent hematopoietic stem cell
What is the pathogenesis of CML
Activation of RAS and JAK/STAT; preferentially drive proliferation of granulocytic and megakaryocytic progenitors and causes ab release of immature granulocytic forms from marrow into blood *does not effect diff so will have mature elements in peripheral blood
What is the morphology of CML
Hypercellular marrow *scattered macrophages with abundant wrinkled green-blue cytoplasm called sea-blue histiocytes ; increased deposition of reticulum is typical; blood reveals leukocytosis (often >100,000); platelets increased; spleen is enlarged (increased red pulp) and contains infarcts of varying age
What are the clinical features of CML
Adults primarily but can occur in children; peak indigene 5th-6th decade; mild anemia and hyper metabolism bc increased cell turnover leading to fatigue, weakness, weight loss, anorexia; dragging sensation in ab (splenomegaly) or LUQ pain due to splenic infarct; slow progression even without treatment - median survival 3 years
What is the accelerated phase of CML
Half of patients experience it; increasing anemia and thrombocytopenia; additional ab (trisomy 8, isochromosome 17q or duplication of Ph chrom seen); within 6-12 months terminates in a picture resembling acute leukemia (blast crisis)
What mutation has been linked to lymphoid blast crisis in CML
Mutations that interfere with activity of Ikaros (transcription factor that regulates diff of hematopoietic progenitors) - also seen in BCR-ABL positive B-ALL
How is CML treated
BCR-ABL inhibitors
What is polycythemia Vera
Characterized by increased marrow production of red cells, granulocytes, and platelets (panmyelosis)
What are the serum erythropoietin levels in polycythemia Vera
Low; (secondary forms have high); increased hematocrit leads to increased viscosity and sliding; thrombocytopenia and ab platelet function (prone to thrombosis and bleeding)
What is the pathogenesis of polycythemia Vera
Valine to phenylalanine sub at 617; mutation in JAK2; if 2 mutated copies, higher white cell count, more sig splenomegaly, sx prutrits and greater rate of progression to spent phase
What is the morphology of polycythemia Vera
Marrow is hypercellular; increase in red cell progenitors is subtle and accompanied by increase in granulocytic precursors and megakaryocytes; blood contains increased number of basophils and abnormally large platelets; late in course, PCV progresses to spent phase characterized by extensive marrow fibrosis accompanied by increased extramedullary hematopoiesis in splen and liver
What are the clinical features of polycythemia Vera
Uncommon; adults; abnormal blood flow particularly on low-pressure venous side; patients are plethora can and cyanotic due to stagnation and deoxygenation of blood; HA, dizziness, HTN, and GI sx common; intense pruritis and peptic ulcer can occur (release of histamine from basophils); high cell turnover gives rise to hyperuricemia sx gout seen sometimes; DVT, MI, stroke; can cause budd chiari if thrombosis in hepatic vein or bowel infarction; minor hemorrhages common
What is the prognosis for PCV without treatment
Die in months of diagnosis; treatment is maintaining red cell mass levels by phlebotomy - median survival is 10 years
