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123 Cards in this Set

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Why does leukopenia occur
Because of decreased numbers of any of the specific leukocyte types. Neutrophils are most often involved
When does lymphopenia occur
With rare congenital immunodeficiency diseases, and in specific settings (HIV, drug therapy)
When does clinically relevant neutrophenia occur
Neutrophil counts below 1000 cells per mm3. When counts are below 300, the condition is called agranulocytosis
What is the half life of neutrophils, and why is this significant
6-7 hours. Insults that impair granulopoiesis quickly produce neutropenia.
What are some of the mechanisms that produce neutropenia
Inadequate or ineffective granulopoiesis
Accelerated removal or destruction of neutrophils
What are some of the causes of inadequate or ineffective granulopoiesis
Suppression of myeloid stem cells (aplastic anemia) and various infiltrative marrow disorders (tumors, granulomatous disease)
Suppression of committed granulocytic precursors after exposure to drugs
Diseases such as megaloblastic anemia
Kostmann syndrome
What are some of the causes of accelerated removal or destruction of neutrophils
Immunologic disorders such as SLE
Splenic sequestration
Increased peripheral utilization due to overwhelming infections
What causes the most significant neutropenias
Drugs. They can be dose related (occuring in a predictable fashion) or idiosyncratic and unpredictable (chloramphenicol, sulfonamides)
In what type of neutropenia is only the granulocytic lineage affected
Isolated neutropenia
Marrow hypercellularity in neutrophenia is due to what
Increased numbers of granulocytic precursors. Caused by increased destruction of mature neutrophils or ineffective granulopoiesis
Marrow hypocellularity in neutropenia is due to what
Agents, such as drugs, that suppress granulocyte progenitor cell growth and survival
What is the clinical course of neutropenia
Intercurrent bacterial or funal infections. Malaise, chills, fever, with marked weakness and fatigability. Ulcerating necrotizing legions show massive growth of microorganisms with relatively poor leukocytic response
What is the prognosis in neutropenia
Infections are often fulminant, and should be treated with broad spectrum antibiotics. Granulocyte-colony stimulating factor therapy decreases drug effects
What are three diseases caused by reactive (inflammatory) proliferations of white blood cells and nodes
Leukocytosis, Acute nonspecific lymphadenitis, Chronic nonspecific lymphadenitis
Define leukocytosis
an abnormally large number of leukocytes; a white blood cell count of 10,000 or more per cu mm. Most examples of leukocytosis represent a disproportionate increase in the neutrophils, and the term is frequently synonymous with neutrophilia.
What are the main types of leukocytosis
Polymorphonuclear leukocytosis (neutrophilic granulocytosis, neutrophilia); Eosinophilic leukocytosis; Basophilic leukocytosis; Monocytosis; Lymphocytosis
Describe polymorphonuclear leukocytosis
Accompanies acute inflammation associated with infection or tissue necrosis. Sepsis or severe inflammatory disorders cause neutrophils to develop so-called toxic changes
Describe toxic changes seen in neutrophils
Abnormally course, dark neutrophilic granules (toxic granulations)
Blue cytoplasmic patches of dilated endoplasmic reticulum (Dohle bodies)
When will eosinophilic leukocytosis be seen
Allergic disorders; parasitic infestations; Drug reactions; malignancies (Hodgkin and non-Hodgkin lymphoma); Collage vascular disorders and some vasculitides; atheroembolic disease
When is basophilic leukocytosis seen
It is rare, and suggests an underlying myeloproliferative disease
When will monocytosis be seen
Chronic infections (tuberculosis, bacterial endocarditis, malaris)
Collage vascular disease (SLE)
Inflammatory bowel disease
When will lymphocytosis been seen
Usually accompanies monocytosis in many disorders associated with chronic immunologic stimulation (tubercullosis, brucellosis), viral infections, and Bordetella pertussis infections
What is the pathogenesis of circulating neutrophil counts, the most common form of leukocytosis
Various mechansisms including:
Expansion of marrow neutrophilic progenitor cell and storage pools, secondary to elevated CSFs, brought on by sustained elevations of IL-1 and TNF
Increased release of mature neutrophils from bone marrow storage pools following elevations of TNF and IL-1
Increased demargination of peripheral blood neutrophil (acute stress or glucocorticoids)
Decreased extravasation of neutrophils into tissues seen with glucocorticoids
What sort of leukocytosis does IL5 cause
Eosinophilic leukocytosis
What sort of leukocytosis does c-kil ligand and IL-7 cause
Lymphopoiesis
When is distinguishing reactive leukocytosis from neoplastic (leukemia) problematic
Childhood acute viral infections; Severe inflammatory states
Define lymphadenitis
inflammation of a lymph node or lymph nodes.
What are the two types of acute nonspecific lymphadenitis
Localized-commonly caused by direct microbiologic drainage, associated with dental or tonsillar infections
Systemic- Associated with bacteremia and viral infections, esp children
What is the morphology of Acute nonspecific lymphadenitis
Nodes are swolledn, gray-red, and engorged. Large germinal centers with numerous mitotic figures. Pyogenic organisms may cause necrosis
What are the clinical features of Acute nonspecific lymphadenitis
Affected nodes are enlarged, tender, and fluctuant (with estensive abscess formation). Overlying skin is frequently red.
What are the three common patterns of chronic nonspecific lymphadenitis
Follicular hyperplasia, Paracortical hyperplasia, sinus histiocytosis (Reticular Hyperplasia)
What are the common features of Follicular hyperplasia
Inflammatory processess that activate B cells
Prominent large, round, or oblong germinal centers that have a dark zone (blastlike B cells) and a light zone (B cells with irregular or cleaved nuclear contours)
Follicular hyperplasia (don't confuse with lymphoma) with preserved architecture, variation in shape and size of nodules, frequent mitotic figures
What are the causes of Follicular hyperplasia
Rheumatoid arthritis, toxoplasmosis, early stages of HIV infection. Can be accompanied by marginal zone B-cell hyperplasia
What are the common features of Paracortical Lymphoid hyperplasia
Reactive changes within T cell regions
Activated parafollicular T cells (immunoblasts 3-4 time larger) that proliferate and efface B-cell follicles
Caused by immunologic reactions induced by drugs (Dilantin) and actute viral infections (mononucleosis)
What are the common features of Sinus Histiocytosis (Reticular hyperplasia)
Distended, prominent lymphatic sinusoids due to marked hypertrophy of lining endothelial cells and infiltration with macrophages
Often observed in lymph nodes draining tissues involved by epithelial cancers
What are the three categories of white blood cell neoplasms
Lymphoid neoplasms, encompassing tumors of B-cell, T-cell, or NK origin
Myeloid neoplasms, originating from transformed hematopoietic stem cells that normally produce myeloid lineage cells
Histiocytoses, representing proliferative lesion of histiocytes, including Langerhans cells
What are some of the major factors in white blood cell neoplasia
Chromosomal translocations and oncogenes; Inherited genetic factors; viruses and environmental agents; Iatrogenic factors
What type of cell do most human lymphoid neoplasms derive from
B cells that have passed through germinal centers
t(15;17) is seen only in what type of Leukemia
Acute promyelocytic leukemia
t(9;22), the Ph1 chromosome, occurs in what forms of leukemia
Acute lymphoblastic, acute myelogenous, chronic myelogenous
What are three genetic diseases that increase the rick of developing acute leukemia
Bloom syndrome, Fanconi anemia, ataxia telangiectasia. You could also include Down syndrome and neurofibromatosis type 1
What type of tumor cells contain clonal EBV genomes
Burkitt lymphomas, Hodgkin lymphomas, diffuse large B cell lymphomas occurring in the setting of T cell immunodeficiency, and natural killer cell lymphomas
HTLV-1 is highly associated with what leukemia
Adult T cell leukemia
HHV8 is found in what lymphomas
Unusual large B-cell lymphomas presenting as lymphomatous effusions
What are two environmental agents causing chronic immune stimulatio that can predispose to lymphoid neoplasia
H. pylori infection and gluten-sensitive enteropathy
Define leukemias
Usually exhibit widespread involvement of bone marrow, accompanied by large numbers of circulating tumor cells
Define lymphomas
Proliferations involving discrete tissue masses (within lymph nodes, spleen, or extranodal tissue). Categorizid into Hodgkins and Non-Hodgkins
Define Plasma cell neoplasms
Tumors composed of terminally differentiated B cells
What is classification of lymphoid neoplasms based on
Clinical features, morphology, immunophenotype, genotype
Lymphocytic leukemias, lymphomas, and plasma cells neoplasms are sorted into what four broad categories based on immunophenotype
Precursonr B-cell neoplasms (immature B cells)
Peripheral B cell neoplasms (mature B cells)
Precursor T cell neoplasms (immature T cells)
Peripheral T cell and NK cell neoplasms (mature T cells and NK cells)
What are the general principles relevant to lymphoid neoplasms
Diagnosis requires histological examination of lymph nodes or other involved tissue
All lymphoid neoplasms are derived from a single transformed cell and are therefore monoclonal
Most lymphoid neoplasms are of B cell origin. NK or histiocyte is rare
Frequently leads to immunologic dysfunction
Tend to grow with normal counterparts
What is the main precursor B cell and T cell neoplasm covered in the book
Acure lymphoblastic leukemia/lymphoma
What composes Acute lymphoblastic leukemias or lymphomas
Immature, precursor B (pre-B) or precursor T (pre-T)lymphocytes (lymphoblasts)
The less common pre-T Acute Lymphoblastic leukemias/lymphomas (ALLs) tend to present in whom and in what
Adolescent boys as lymphomas involving the thymus
In ALL, how do lymphoblasts appear in Wright-Giemsa stains
Relatively condensed chromatin, lack conspicuous nucleoli, and have scant, agranular cytoplasm containing periodic acid-Schiff (PAS) positive material. PreB and preT lymphoblasts are identical
What is expressed only by preB and preT lymphoblasts, and is present in over 95% of ALL cases
Terminal deoxytransferase (TdT), a specialized DNA polymerase
When in development are preB ALL cells arrested
At stages preceding surface immunoglobulin expression. Express CD19
When in development are PreT ALL cells arrested
Early intrathymic stages of maturation. Often express CD1a
Chromosomal changes are present in what percentage of ALL
90%
What are some important chromosomal or genetic aberrations in ALL
Hyperdiploidy (51-60 chromosomes)-preB, good prognosis
t(12;21)-preB, good prognosis
t(9;22) Philadelphia-preB, 5% kids 25% adults, poor prognosis
Translocations involving chromosome 11 at band q23 (MLL gene)- early onset, early preB, poor prognosis
What are the major clinical feature of ALL (and sometimes AML)
Abrubt, stormy onset
Symptoms related to depressed marrow function
Bone pain and tenderness
Generalized lymphadenopathy, splenomegaly, and hepatomegaly
Central nervous system manifestations
What is the general prognosis with ALL
90% will achieve complete remission, unless under age 2 or over age 10
What are the common Peripheral B-cell neoplasms
Chronic lymphocytic leukemia/Small lymphocytic lymphoma
Follicular lymphoma
Diffuse Large B-cell lymphoma
Burkitt lymphoma
What is lymphocytic leukemia
A variety of leukemia characterized by an uncontrolled proliferation and conspicuous enlargement of lymphoid tissue in various sites (e.g., lymph nodes, spleen, bone marrow, lungs), and the occurrence of increased numbers of cells of the lymphocytic series in the blood
What is the difference between Chronic lymphocytic leukemia and Small lymphocytic lymphoma
the are morphologically, phenotypically, and genotypically indistinguishable. They differ only in the degree of peripheral blood lymphocytosis
What is the morphology of Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL)
Lymph node architecture is diffusely effaced by small lymphocytes containing round to slightly irregular nuclei mixed with cariable numbers of larger cells actively dividing (proliferation centers)
What is pathognomonic for CLL/SLL
Proliferation centers, which are where dividing centers are gathered together in close aggregates
What is the most common adult leukemia in the Western world
Chronic lymphocytic leukemia
What are the clinical features of chronic lymphocytic leukemia
Onset after age 50
Male predominance
Nonspecific symptoms
lymphadenopathy and hepatosplenomegaly
Immune abnormalities
What are the characteristics of CLL/SLL that has undergone Prolymphocytic transformation
Worsening cytopenias, increasing splenomegaly, large numbers of prolymphocytes in circulation
What are the characteristics of CLL/SLL that has undergone transformation to diffuse large B-cell lymphoma (Richter syndrome)
Rapidly enlarging mass within a lymph node or spleen
What is the most common form of non-Hodgkin leukemia in the US
Follicular lymphoma (45% of adult lymphomas)
In lymph nodes, follicular (nodular) and diffuse proliferations are composed of what two principal cell types
Centrocytes and centroblasts. Centrocytes predominate in most tumors. Involvement of spleen, liver, and marrow is common
What is the immunophenotyp of B cells in follicular lymphoma
Neoplastic cells resemble normal follicular center B cells. However, they consistently express BCL2 protein [(14;18) translocation]
What are the clinical features of Follicular lymphoma
Painless, generalized lymphadenopathy in middle-aged adults, and follows an indolent waxing-waning course
What are diffuse large B-cell lymphomas
A hetergeneous group of tumors constituting 20% of NHLs and 60-70% of of aggressive lymphoid neoplasms
What is the morphology of Diffuse Large B-cell lymphoma (DLBCL)
Large cell size, diffuse growth pattern that obliterates the underlying architecture. Contains one to three prominent nucleoli
What are the two common chromosomal rearrangements in DLBCL
Translocations involving the BCL6 (zinc finger transcription factor) locus on chromosome 3; (14;18) translocation involving BCL2
When do Immunodeficiency-associated large B cell lymphomas occur
Severe Tcell immunodeficiency, often with latent EBV infection
Body cavity-based large cell lymphomas arise as malignant pleural or ascitic effusions in what types of patients
Those with advanced HIV, or elderly patients. Herpesvirus 8 plays a causal role
What are the clinical features of DLBCL
Older adults; rapidly enlarging, symptomatic mass at a single nodal or extranodal site. Extranodal presentation is relatively frequent. Liver, spleen, and marrow involvement occurs late
What is the general prognosis for DLBCL
These are aggressive, rapidly fatal tumors if left untreated
What is Burkitt lymphoma
A form of malignant lymphoma reported in African children, frequently involving the jaw and abdominal lymph nodes. Geographic distribution of Burkitt lymphoma suggests that it is found in areas with endemic malaria. It is primarily a B-cell neoplasm and is believed to be caused by Epstein-Barr virus, a member of the family Herpesviridae, which can be isolated from tumor cells in culture; occasional cases of lymphoma with similar features have been reported in the United States.
What is Multiple myeloma
an uncommon disease that occurs more frequently in men and is associated with anemia, hemorrhage, recurrent infections, and weakness. A malignant neoplasm that originates in bone marrow and involves chiefly the skeleton; characterized by numerous diffuse foci or nodular accumulations of abnormal or malignant plasma cells in the marrow of various bones and abnormal proteins in the serum and urine; the most frequent abnormalities in the metabolism of protein are Bence Jones proteinuria, an increase in monoclonal +-globulin in the plasma, the formation of cryoglobulin, and a form of primary amyloidosis.
What are Bence Jones protein
Free light chain, which is excreted in the urine. Associated with Plasma cell neoplasms and related disorders
What is Bence Jones proteinuria
presence of Bence Jones protein in the urine, indicative of multiple myeloma, amyloidosis, or Waldenström macroglobulinemia.
What is multiple myeloma characterized by
Destructive bony lesions at multiple sites; Renal disease; Hyperviscosity syndrome
What are the seven common plasma cell neoplasms and related disorders
Multiple Myeloma
Solitary Myeloma (Plasmacytoma)
Monoclonal Gammopathy of uncertain significance
Lymphoplasmacytic Lymphoma
Mantle cell lymphoma
Marginal zone lymphomas
Hairy cell leukemia
How do Solitary myelomas (plasmacytomas) present
Plasma cell neoplasms that are solitary lesions of either bone or soft tissue
What are the characteristics of Monoclonal Gammopathy of uncertain significance
M proteins are detected in the sera, but they are asymptomatic and have no Bence Jones proteinuria
What are M proteins
Monoclonal immunoglobulins identified in blood or urine, in reference to myeloma
What are the characteristics of Lymphoplasmacytic lymphoma
Secret monoclonal IgM in amounts sufficient to cause hyperviscosity syndrome known as Waldenstrom macroglobulinemia
What are the characteristics of Mantle cell lymphoma
Distinct t(11;14) causes overexpressing of cyclin D1; Extranodal disease is relatively common, marrow and splenic involvement are not usual
What are the characteristics of Marginal Zone lymphomas
A heterogeneous group of neoplasms originating from the B-cell–rich zones of the lymph nodes, spleen, or extranodal lymphoid tissue. Those tumors originating from mucosa-associated lymphoid tissue (MALT), most often in the stomach, intestines, salivary glands, and lungs, are called MALTomas.
What is the pathogenesis of marginal zone lymphomas
Begins as a reactive, polyclonal immune reaction (tends to occur at sites of chronic inflammation e.g. Helicobacter). Can transform into DLBCL
What are the characteristics of Hairy cell leukemia
A rare, usually chronic disorder characterized by proliferation of hairy cells in reticuloendothelial organs and blood. Spleenomegaly, often massive, is the most common and sometimes only abnormal physical finding
Peripheral T-cell lymphoma, Unspecified
A heterogeneous group of T-cell neoplasms expressing typical mature T-cell markers such as CD2 and CD3. They lack TdT
What are the characteristics of Anaplastic Large cell lymphoma
Strong association with chromosomal rearrangements involving the ALK gene on chromosome 2p23
Adult T-cell Leukemia/lymphoma occurs secondary to what
Infections by human T-cell leukemia virus type 1 (HTLV-1). Extremely aggresive disease
What is characteristic in Mycosis Fungoides and Sezary syndrome
T cells that home to the skin. Mycoides fungoides presents with an inflammatory premycotic phase and progresses through a plaque phase to a tumor phase
Sezary syndrome is a variant with an associated leukemia of Sezary cells
What are some characteristics of Large Granular lymphocytic leukemia
Lymphocytes with abundant cytoplasm containing scattered coarse azurophilic granules. Increased incidence of rheumatologic disorders
What are the six main types of Peripheral T-cell and NK cell neoplasms
Peripheral T-cell lymphoma, Unspecified
Anaplastic large cell lymphoma
Adult T-cell leukemia/lymphoma
Mycosis Fungoides and Sezary Syndrome
Large Granular lymphocytic leukemia
Extranodal Nk/T-cell lymphoma
What is characteristic in Extranodal Nk/T-cell lymphoma
Destructive midline mass involving the nasopharynx, skin, or testis. Causes extensive ischemic necrosis. Usually NK cell origin
What are the five types of Hodgkin's lymphoma
Nodular Sclerosis type
Mixed cellularity type
Lymphocyte-rich type
Lymphocyte-depletion type
Lymphocyte predominance type
How is Hodgkin lymphoma characterized morphologically
By the presence of scattered distinctive neoplastic giant cells called Reed-Sternberg (RS) cells
What are the four different morphologies of Reed-Sternberg cells and variants
Classic, diagnostic-large, single bilobed nucleus or multiple nuclei. Nucleolis the size of a small lymphocyte
Mononuclear variants-contain only a single round or oblong nucleus
Lacunar cells- more delicte folded or multilobate nuclei surrounded by abundant pale cytoplasm
Lymphocytic and histiocytic variants (L&H cells)- polypoid nuclei resembling popcorn kernels
Define Hodgkin's disease
A disease marked by chronic enlargement of the lymph nodes, often local at the onset and later generalized, together with enlargement of the spleen and often of the liver, no pronounced leukocytosis, and commonly anemia and continuous or remittent (Pel-Ebstein) fever; considered to be a malignant neoplasm of lymphoid cells of uncertain origin (Reed-Sternberg cells), associated with inflammatory infiltration of lymphocytes and eosinophilic leukocytes and fibrosis
Describe Nodular sclerosis type HL
Most common form, more in women; lower cervical, supraclavicular, and mediastinal lymph nodes; Lacunar cell RS variant; collagen bands; EBV uncommon
Describe mixed cellularity type HL
EBV 70%; B symptoms; Classic RS cells; diffuse effacement of lymph nodes by a heterogeneous cellular infiltrate
Describe lymphocyte-rich type HL
Reactive lymphocytes make up the vast majority of the non-neoplastic portion of the infiltrate
Describe Lymphocyte-depletion type HL
Immunosuppressed patients; uniformly associated with EBV; RS cells and variants are frequent, reactive cells are relatively sparse
Describe lymphocyte predominance type HL
Younger Men; Isolated cervical or axillary lymphadenopathy; L&H RS cell variants
What do cytokines released from RC cells likely induce
The accumulation of reactive cells, wich may, in turn, support the growth and survival of tumor cells
Transforming growth factor Beta, a fibrogenic cytokine, is produced almost exclusively in what type of HL
The nodular sclerosis variant (synthesized by infiltrating eosinophils)
What role does NF-kappaBeta play in HL
Signals elicited by EBV LMP-1 activate NK-kappaBeta, a transcription factor that promotes B-cell survival and proliferation
Define Acute myelogenous leukemia
A form of leukemia characterized by an uncontrolled proliferation of myelopoietic cells in the bone marrow and in extramedullary sites, and the presence of large numbers of immature and mature granulocytic forms in various tissues (and organs) and in the circulating blood. The predominant cell is usually of the neutrophilic series, but, in a few instances, eosinophilic or basophilic granulocytes, or even megakaryocytes, may represent the chief form
What is Acute myelogenous leukemia characterized by
Marrow accumulation of immature myeloid cells
What are Auer rods
rod-shaped structures of uncertain nature in the cytoplasm of immature myeloid cells, especially myeloblasts, in acute myelocytic leukemia.
How do patients with Acute myelogenous leukemia present
Findings related to anemia, neutropenia, and thrombocytopenia, most notably fatigue, fever, and spontaneous mucosal and cutaneous bleeding
What are the four chronic myeloproliferative disorder
Chronic myelogenous leukemia
Polycythemia vera
Essential thrombocytosis
Myelofibrosis with myeloid metaplasia
What is Chronic myelogenous leukemia
CML is a neoplasm of pluripotent hematopoietic stem cells leading to preferential proliferation of granulocytic progenitors
How is Chronic myelogenous leukemia distinguished from from other chronic myeloproliferative disorders
Presence of the t(9;22) Philadelphia chromosome (Ph1). Results from a BCR-ABL fusion gene
Describe polycythemia vera
Characterized by increased proliferation and production of erythroid, granulocytic, and megakaryocytic elements. Absolute increase in red blood cell mass is responsible for most of the clinical symptoms