Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
130 Cards in this Set
- Front
- Back
|
What are some nonspecific reactive patterns in lymph nodes?
|
Follicular hyperplasia (indicates humoral response)
Paracortical expansion (indicates cellular response) Sinus histiocytosis (may indicate inc insoluble antigen) Marginal zone/monocytoid B cell hyperplasia (specialized B cell response) |
|
|
What are some specific reactive patterns in lymph nodes?
|
Granulomatous patterns
Stellate microabscesses Toxoplasmosis pattern |
|
|
What are the subtypes of the granulomatous reactive pattern in lymph nodes and what are each associated with?
|
Necrotizing: TB, fungal infections
Nonnecrotizing: sarcoid, foreign material |
|
|
What can cause stellate microabscesses as a reactive pattern in lymph nodes?
|
Cat scratch (B. Henselae)
Chlamydia Yersinia Other bacteria |
|
|
What is characteristic of the toxoplasmosis pattern of reactive lymph nodes?
|
Follicular hyperplasia, granulomas, monocytoid B cells
Organisms not found in lymph node |
|
|
What are some lymphomas with the EBV genome?
|
Lymphomas in HIV pts
Aggressive B cell lymphomas (DLBCL, Burkitt's, CNS lymphoma) Hodgkin's lymphoma in HIV pts |
|
|
What is the mechanism behind EBV induced lymphomas?
|
EBV latent membrane protein 1 (LMP1) activates NF-kB pathway
|
|
|
What are some causes of therapy related myelodysplastic syndrome or acute myeloid leukemia?
|
Etoposide topoisomerase type II inhibitor
Alkylating agents Radiotherapy |
|
|
What type of lymphoma is more common in US and Europe than in Asia?
|
Follicular lymphoma and chronic lymphocytic leukemia
|
|
|
What type of lymphoma is more common in Africa and New Guinea?
|
Endemic Burkitt
|
|
|
What type of lymphoma is more common in East Asia?
|
Nasal type NK/T cell lymphoma
|
|
|
What type of lymphoma is more common in the Caribbean and Southwestern Japan?
|
ATLL
|
|
|
In children what are the most common hematologic malignancies?
|
B-ALL most common
AML, T-ALL also |
|
|
In young adults what are the most common hematologic malignancies?
|
AML more common than ALL
Anaplastic large cell lymphoma (ALK+) Diffuse large B cell lymphoma Hodgkin's lymphoma Mediastinal (thymic) large B cell lymphoma |
|
|
What are the most common hematologic malignancies affecting middle aged people?
|
AML more common than ALL
DLBCL Hodgkin's Myeloproliferative diseases Some low grade lymphomas |
|
|
What are the common hematologic malignancies affecting older people?
|
MDS and AML with multilineage dysplasia
Multiple myeloma Low grade lymphoma DLBCL Myeloproliferative diseases |
|
|
When is a lymphoma called a leukemia?
|
If there are noticeable circulating cells in the peripheral blood with a phenotype usually seen in a lymphoma
Examples: plasma cell leukemia, mantle cell leukemia |
|
|
Acute leukemias have what characteristics?
|
Usually rapidly dividing cells
Acute refers to immature, precursor cells (blasts) |
|
|
Acute lymphoblastic leukemia?
|
Precursor (B or T) cell leukemia/lymphoma
Proliferation of malignant cells resembling lymphoblasts |
|
|
Acute myeloid leukemia?
|
Proliferation of immature myeloid cells (usually blasts) that is best defined by morphology
|
|
|
Chronic myeloproliferative diseases?
|
Cell proliferate and mature so the vast majority are recognizable differentiated blood elements
|
|
|
Chronic lymphoproliferative disease?
|
All mature lymphoid leukemias derived from mature lymphoid cells that have exited bone marrow or thymus but only one has the word chronic in the name
|
|
|
What is the definition of precursor B lymphoblastic leukemia/ lymphoma B-ALL?
|
Mass with less than 25% involvement of random marrow
Usually has blood involvement |
|
|
What is the typical presentation of precursor B lymphoblastic leukemia/ lymphoma B-ALL?
|
Young children
Fatigue, bleeding: marrow failure Bone pain - rapid growth of tumor in marrow Headache, vomiting, nerve involvement: may indicate CNS involvement Variable lymph node, organ infiltration |
|
|
What are the major diagnostic markers on precursor B lymphoblastic leukemia/ lymphoma B-ALL?
|
CD19+
CD10+ tdt+ |
|
|
Precursor B lymphoblastic leukemia/ lymphoma B-ALL most commonly involves trisomies of which chromosomes?
|
4
10 17 21 (with increased expression of reduced folate transporter) |
|
|
What is the presentation like in precursor T lymphoblastic leukemia/lymphoma (T-ALL)?
|
Typically mediastinal mass in a boy with difficulty breathing
Can also present similar to B-ALL |
|
|
What are major diagnostic markers of T-ALL?
|
CD3+
Variable expression of CD1a, tdt+. CD10+, and T-cell markers (CD 2,4,8,7,5) |
|
|
What are some prognostic factors in CLL/SLL?
|
Extent of bone marrow involvement
Good prognosis: del(13q), ZAP70-, mutated immunoglobulin genes Poor prognosis: ZAP70+, unmutated immunoglobulin genes, del(17p) p53 locus, del(11q22) |
|
|
What is the presentation of CLL/SLL?
|
Frequently asymptomatic or nonspecific symptoms in patients 50yrs or older
Variable involvement of tissue/lymph nodes (most have blood and bone marrow disease first then lymphadenopathy; some nodal disease w/ min. blood/bone marrow) Course is indolent, slowly progressive anemia |
|
|
What is the most common subtype of lymphoma in the US and Europe affecting older adults?
|
Follicular lymphoma
|
|
|
What is the presentation of follicular lymphoma?
|
Painless lymphadenopathy at single or multiple sites
Sometimes extranodal (FL of the skin is clinically and biologically different disease) |
|
|
What sites are typically affected by follicular lymphoma?
|
Lymph node
Spleen Liver Rarely blood, no lymphocytosis With bone marrow involvement see paratrabecular nodules |
|
|
What does follicular lymphoma usually transform to?
|
DLBCL (30-50% of cases eventually transform)
|
|
|
What are some factors that influence the transformation of follicular lymphoma to DLBCL?
|
p53 gene mutations
Inactivation of CDKN2A and CDKN2B (genes for CDK inhibitors p16/ink4a, p15/ink4b) Deregulation of C-MYC gene |
|
|
What is the pathogenesis of follicular lymphoma?
|
Anomalous recombination of IgH locus to bcl2 locus due to t(14;18) during VDJ recombination in the marrow
|
|
|
What is the presentation of diffuse large B cell lymphoma?
|
Site dependent symptoms or asymptomatic mass
Nodal or extranodal Blood rarely involved Bone marrow involvement indicates stage IV May arise de novo or by transformation of a low grade B cell lymphoma |
|
|
What is the immunophenotype of large B cell lymphoma?
|
Almost always CD20+
|
|
|
What is the presentation of Burkitt lymphoma?
|
Rapidly growing mass with early spread
In the endemic African setting frequently presents in jaw,ovaries in children & young adults, almost always with EBV In sporadic cases usually a peritoneal mass, sometimes has EBV present In HIV pts occurs early - before AIDS diagnosis and nodal involvement more common |
|
|
Is there blood and bone marrow involvement in Burkitt?
|
Blood involvement can occur with bulky disease but rare pure Burkitt leukemia
Bone marrow involved late in course |
|
|
What is characteristic of the cytogenetics in Burkitt?
|
Must have c-myc translocation t(8;14)
|
|
|
What is the immunophenotype of Burkitt lymphoma?
|
Germinal center B cell markers (CD20, CD10, bcl6)
Almost 100% Ki-67+ (proliferation marker) |
|
|
What is the pathogenesis of Burkitt lymphoma?
|
Both sporadic and endemic Burkitt have translocation of c-myc to the IgH locus but the IgM recombination breakpoint regions are different
|
|
|
What are some plasma cell and related neoplasms?
|
Monoclonal gammopathy
Waldenstrom's macroglobulinemia Heavy chain disease Primary amyloidosis Monoclonal gammopathy of uncertain significance (MGUS) Multiple myeloma Solitary plasmacytoma |
|
|
What is monoclonal gammopathy?
|
Disorders characterized by a persistant M-spike
Homogenous protein produced by clone of neoplastic immunoglobulin secreting cells (usually plasma cells) |
|
|
What is heavy chain disease?
|
Lymphoid malignancy secreting heavy chain without light chain
Rare |
|
|
Primary amyloidosis?
|
Amyloid AL - usually lambda light chain, symptoms depend on deposition site:
Kidney - proteinuria, nephrotic syndrome, renal failure Heart - cardiomegaly, HF GI tract - dysmotility, malabsorption, diarrhea Peripheral nerves Vessels Hematologic - can cause acquired factor X deficiency |
|
|
What is MGUS?
|
Monoclonal gammopathy of uncertain significance
No myeloma symptoms IgG < 3.5g/dL No lytic bone lesions <10% marrow plasmacytosis 1% conversion/year to myeloma |
|
|
What is Waldenstrom's macroglobulinemia?
|
Syndrome with IgM paraprotein that produces hyperviscosity and characteristic clinical sequelae
|
|
|
What are the criteria for multiple myeloma?
|
Major:
- 3.5g/dL IgG or 2g/dL IgA paraprotein or Bence Jones proteinuria >1g/25hr - marrow plasmacytosis >30%, plasmacytoma Minor: - lytic lesions, reduced normal Igs |
|
|
What is the presentation of multiple myeloma?
|
Marrow failure symptoms
Bone fracture Infections Hypercalcemia |
|
|
Where is multiple myeloma usually located?
|
Bone
Infrequent in soft tissue or blood involvement |
|
|
What are some prognostic factors for multiple myeloma?
|
Extent of bone lesions
Calcium level Renal function Hb concentration Beta-2-microglobulin (released from tumor cells, MOST important predictor) Any karyotype abnormality indicator of poor prognosis Anaplastic or plasmablastic morphology predictor of poor prognosis |
|
|
What are the differences in the 2 types of solitary plasmacytoma?
|
Extraosseous: usually upper aerodigestive tract and localized, not related to myeloma and better prognosis
Osseous: usually treated with local irradiation, high frequency of systemic spread |
|
|
What is lymphoplasmacytic lymphoma?
|
B-cell neoplasm of older adults that usually secretes monoclonal IgM often in amounts sufficient to cause the hyperviscosity syndrome Waldenstrom macroglobulinemia
|
|
|
What is the presentation of Waldenstrom's macroglobulinemia?
|
Visual impairment, stroke related to hyperviscosity
Raynaud's phenomenon due to cold agglutinins and cryoglobulins Some have organomegaly, lymphadenopathy Anemia due to marrow infiltration Bleeding - paraprotein interferes with platelet functions and coagulation factors |
|
|
What is the epidemiology of mantle cell lymphoma?
|
Male predominance, middle age and older
|
|
|
How does mantle cell lymphoma present?
|
Usually presents at late stage with lymph node involvement
|
|
|
What are the sites of involvement for mantle cell lymphoma?
|
Lymph nodes
Marrow Spleen Peripheral blood involvement (leukemia) common GI tract involvement very common (lymphomatoid polyposis) |
|
|
What is the cell of origin in mantle cell lymphoma?
|
Cell similar to naive B cell because immunoglobulin variable region gene usually not hypermutated
|
|
|
Are extranodal or nodal marginal zone lymphomas more common?
|
Extranodal
Stomach most common site, others being orbit, lung, salivary gland, thyroid, bowel |
|
|
What is the presentation of hairy cell leukemia?
|
Marked male predominance
Splenomegaly and pancytopenia |
|
|
What is the therapy for hairy cell leukemia?
|
90% respond to 2-chlorodeoxyadenosine (2-CDA)
|
|
|
What is peripheral T cell lymphoma, unspecified?
|
Wastebasket category of tumors of mature T cells with many different histologies
Usually very aggressive Usually nodal |
|
|
Anaplastic large cell lymphoma?
|
ALK + (good prognosis) or ALK - (poor prognosis)
Always express CD30 Of the T cell lineage but notorious for lacking lymphoid markers |
|
|
What is the presentation of adult T cell leukemia/lymphoma?
|
Skin lesions
Lymphadenopathy Lymphocytosis Hypercalcemia due to osteoclast activation |
|
|
Cloverleaf nuclei are characteristic to what disease?
|
Adult T cell leukemia/lymphoma
|
|
|
Which neoplasm is associated with HTLV-1 virus?
|
Adult T cell leukemia/lymphoma
|
|
|
How does mycosis fungoides present?
|
In adults and elderly presents with a rash
Long natural history until nodules develop Progresses through spongiotic dermatitis phase then plaque and tumor |
|
|
What is the immunophenotype of mycosis fungoides?
|
Same as regulatory T cells: CD4+, CD25+
|
|
|
What is sezary syndrome?
|
Erythroderma, lymphadenopathy, neoplastic T lymphocytes in blood which have convoluted nuclear contours
|
|
|
What is the usual pattern of spread in classical Hodgkin's lymphoma?
|
Almost always nodal or anterior mediastinal, then spreads to spleen, then bone marrow
Liver, lung involved late but more commonly involved sites at relapse |
|
|
What is the cell of origin of classical Hodgkin's lymphoma?
|
Germinal center or post germinal center B cells
Lack Ig expression Frequent crippling mutations in Ig genes |
|
|
What are Reed-Sternberg cells?
|
Distinctive neoplastic giant cells characteristic to Hodgkin's lymphoma
|
|
|
What cytokines do Reed-Sternberg cells produce?
|
TGF-B (cause fibrosis)
Eotaxin, IL-5 (attract eosinophils) Cytokines that attract lymphocytes |
|
|
What is the specific immunophenotype of Hodgkins?
|
CD45 -
CD30+ CD15+ CD20+/- |
|
|
What is characteristic of the nodular sclerosis subtype of Hodgkin's?
|
Usually young adults, cervical/mediastinal disease, asymptomatic
Lacunar cells, mixed infiltrate background, dense sclerosis, mummified cells Rarely EBV infected |
|
|
What is characteristic of the mixed cellularity subtype of Hodgkin's lymphoma?
|
Bimodal age distribution
More extensive disease, B symptoms more common Classical Reed-Sternberg cells, mummified cells, mixed infiltrate background Frequently EBV + |
|
|
What is characteristic of lymphocyte rich Hodgkin's lymphoma?
|
Uncommon
May be confused with nodular lymphocyte predominant Hodgkin's lymphoma without immunostaining |
|
|
What is characteristic of lymphocyte depletion Hodgkin's lymphoma?
|
Uncommon, mostly seen in advanced disease or HIV setting
Many cases diagnosed before immunostaining probably represented other entities |
|
|
What are the clinical characteristics of lymphocyte predominant Hodgkin's lymphoma?
|
Young males, < 35 yrs
Axillary and cervical lymphadenopathy Tends to relapse, but prognosis is excellent Rarely transforms to DLBCL Treatment different from classical Hodgkin's lymphoma |
|
|
What is the histology of lymphocyte predominant Hodgkin's lymphoma?
|
Germinal center cell origin
Popcorn cells rather than Reed-Sternberg cells Malignant cells ringed by CD4+, CD57+ T cells (germinal center typed T cells) |
|
|
What is the pathogenesis of lymphocyte predominant Hodgkin's lymphoma?
|
Malignant cells show ongoing somatic hypermutation
Ambiguous relationship to benign progressive transformation of germinal centers No association with EBV |
|
|
What is the Ann Arbor staging system for Hodgkin's lymphoma?
|
Used to predict prognosis
I: one node or adjacent node II: 2 or more node regions on same side of diaphragm III: sites below & above diaphragm involved IIIS: spleen IV: bone marrow/organ involvement Suffix: A for asymptomatic, B for night sweats or weight loss |
|
|
What are the 2 major components of the thymus?
|
Cortex: positive selection
Medulla: negative selection |
|
|
What is DiGeorge syndrome?
|
Failure of development of 3rd & 4th pharyngeal pouches
Thymic hypoplasia/aplasia causing defect in T cell mediated immunity Hypoparathyroidism Developmental defects of heart and great vessels |
|
|
What is the presentation of DiGeorge syndrome?
|
Tetany due to hypocalcemia
CHF or cyanosis from heart defects (22q11 deletion syndrome) Infections |
|
|
What is thymic (follicular) hyperplasia associated with?
|
Myasthenia gravis and can be seen with other autoimmune diseases
|
|
|
What are the primary thymic neoplasms?
|
Thymomas
Thymic carcinoma Lymphomas Germ cell tumors (teratomas) |
|
|
What is a thymoma?
|
Benign neoplasms of thymic epithelial cells
Can show associated, nonneoplastic, immature, and maturing T cells as in a normal thymus Multiple histological patterns and classification schemes (cortical, medullary, mixed) Can present with myasthenia gravis or red cell aplasia Surgical resection is curative |
|
|
Which specific T cell lymphoma is associated with the thymus?
|
Precursor T-lymphoblastic lymphoma/leukemia
|
|
|
What is the clinical presentation of AML?
|
Fatigue
Bleeding Infection May rarely present with mass of AML cells months before marrow and blood involvement |
|
|
What are the characteristics of AML with recurrent translocations?
|
Generally younger age adults
Better cure rates with chemotherapy Translocations are pathogmnomonic |
|
|
What are characteristics of acute promyelocytic leukemia?
|
t(15;17) translocations
Distinctive blasts with prominent primary granules and Auer rods Intense myeloperoxidase staining Frequent DIC at presentation PML/RARa gene fusion (but not in all cases) |
|
|
What are Auer rods?
|
Crystalline forms of primary granule contents
|
|
|
Why is APL repsonsive to all trans retinoic acid therapy (ATRA)?
|
PML/RARa gene fusion accounts for this differentiation therapy
BUT some cases have translocation of RARa gene to loci other than PML Also responds to arsenic therapy |
|
|
What genetic changes are characteristic of acute myelomonocytic leukemia with eosinophilia
|
Inv(16) or t(16,16)
|
|
|
Which AML has the best prognosis?
|
AML with t(8;21) AML1/ETO fusion protein
|
|
|
What are the differences in the therapy-related AMLs?
|
After alkylating agents: same cytogenetics & morphology as AML in setting of myelodysplastic syndrome
After topoisomerase type II inhibitors: tends to have monocytic differentiation and MLL translocationss |
|
|
When is an MDS classified as an MDS/MPD?
|
If there is a mixed picture of anemia along with monocytosis or neutrophilia with no evident underlying cause
|
|
|
What special type of MDS is seen in older females with thrombocytosis and anemia and has a long survival?
|
5q- syndrome
|
|
|
What is the etiology of MDS?
|
Primary unknown, rare cases linked to specific agents like benzene
Therapy related |
|
|
What are the general features of chronic myeloproliferative diseases?
|
Increased blood and marrow cellularity of one or more lineages with normal maturation
Hepatosplenomegaly common Minimal morphological atypia in chronic phase May progress to acute leukemia (usually AML, sometimes ALL) Most types considered to be stem cell defect with propensity to variably affect different lineages |
|
|
What is the pathogenesis of chronic myeloproliferative diseases?
|
Alterations of tyrosine kinases found in every class of myeloproliferative disorder
CML: BCR-ABL Polycythemia vera: Jak2 point mutation V617F |
|
|
What is characteristic of the PB smear in CML?
|
Increased normal looking mature and immature neutrophils
Basophilia (<20% in chronic phase) Blasts are usually seen in normal, low proportion to the immature granulocytes Platelets elevated or in normal range |
|
|
What is characteristic about the bone marrow in CML?
|
Myeloid precursors are markedly increased, usually at expense of erythroid precursors
Megakaryocytes tend to be small and mono/hypolobated |
|
|
What is an absolute requirement for CML diagnosis?
|
Bcr/abl gene fusion
|
|
|
What is characteristic of the chronic phase of CML?
|
< 10% blasts
Stable cytopenias Bcr/abl fusion Philadelphia chromosome found in > 90% |
|
|
What is characteristic of the accelerated phase of CML?
|
>20% basophils
10-19% blasts Thrombocytosis or thrombocytopenia refractory to therapy Splenomegaly refractory to therapy Cytogenetic progression: frequent i(17q), 2+ Philadelphia chromosomes |
|
|
What is characteristic of the blast phase of CML?
|
Increased blasts, > 20%
Blasts are lymphoblasts in 1/4 of cases |
|
|
How does essential thrombocythemia present?
|
Usually an incidental finding on CBC
But 20-50% have vascular occlusion or hemorrhage and may present with paresthesia, transient ischemic attacks, gangrene from microvascular occlusion |
|
|
What is the epidemilogy of essential thrombocythemia?
|
Usually older adults but a second peak in young women which may complicate pregnancy
|
|
|
What is polycythemia vera?
|
Red cell mass 25% above normal with low erythropoietin levels
Endogenous erythropoietin independent erythroid colony forming units |
|
|
What are the symptoms of polycythemia vera?
|
HTN, hemorrhage
Thrombosis causing headache, dizziness, paresthesias, visual disturbances, pruritis, gout Can have variable thrombocytosis and granulocytosis |
|
|
What is characteristic of the spent phase of polycythemia vera?
|
Marrow fibrosis
Myeloid metaplasia Indistinguishable from late stage idiopathic myelofibrosis |
|
|
What mutation is common to polycythemia vera?
|
Jak2 V617F
|
|
|
How does the early phase of idiopathic myelofibrosis present?
|
Thrombocytosis and granulocytosis
May be difficult to distinguish from a mixed myelodysplastic/myeloproliferative disorder |
|
|
What are the various clinical presentations of Langerhans cell histiocytosis?
|
Unifocal and multifocal forms (single lesion more common, usually involves bone)
Unisystem or multisystem (both usually involve young children and calvarium is frequent site |
|
|
What is Letterer-Siwe disease?
|
Multifocal, multisystem langerhans cell histiocytosis
|
|
|
What is Hand-Schuller-Christian syndrome?
|
Multifocal bone involvement with posterior pituitary stalk compression with diabetes insipidus
|
|
|
What is the cell of origin in Langerhans cell histiocytosis?
|
Immature dendritic cell within the epidermis
|
|
|
What is the red pulp of the spleen?
|
Site of splenic conditioning
Cells must squeeze through holes in the basement membrane of the cords of Billroth to reach macrophage lined sinusoids |
|
|
What is the white pulp of the spleen?
|
Periarteriolar lymphoid sheets (rich in T lymphocytes)
Lymphoid follicles (rich in B lymphocytes) |
|
|
What are the symptoms of splenomegaly?
|
Early satiety, discomfort after eating
|
|
|
What is the triad that characterizes hypersplenism?
|
Splenomegaly
Sequestration of red cells, white cells, and/or platelets but usually not severe enough to cause symptoms Correction of cytopenia by splenectomy |
|
|
What are causes of splenomegaly?
|
Red pulp expansion (cirrhosis, splenic vein thrombosis, HF)
White pulp expansion (infections, immunologic-inflammatory diseases, ITP) Neoplasms |
|
|
What are some neoplasms that would cause red pulp expansion in the spleen?
|
Chronic myeloproliferative disorders (CML)
Hairy cell leukemia |
|
|
What are some neoplasms that would preferentially cause white pulp expansion in the spleen?
|
Indolent B cell lymphomas
|
|
|
What are some neoplasms that would cause discrete masses in the spleen?
|
DLBCL
Hodgkin lymphoma |
|
|
What are some potential causes of spontaneous splenic rupture?
|
Rapid expansion from an acute infection or aggressive lymphoma stretches and weakens capsule
|
