Neoplastic And Proliferative Disorders Of The Hematopoietic And Lymphoid Systems

Front 1

What are the general considerations of leukemia?

Back 1

1) Leukemia is a general term for a group of malignancies of either lymphoid or hematopoietic cell origin. The number of circulating leukocytes is often greatly increased.
2) Bone marrow is diffusely infiltrated with leukemic cells, often with encroachment on normal hematopoietic cell development. Consequent failure of normal leukocyte, red cell, and platelet production can result in anemia, infection, or hemorrhage.
3) Infiltration of leukemic cells in the liver, spleen, lymph nodes, and other organs is common.

Front 2

What is acute leukemias?

Back 2

1) Characterized by a predominance of blasts and closely related cells in the bone marrow and peripheral blood.
2) Occur most often in children and are the most common malignancies of the pediatric age group.
3) Exhibit a second incidence peak after 60 years of age
4) Are frequently associated with cytogenic abnormalities. For example, the 9;22 translocation results in a morphologically unique chromosome, the Philadelphia chromosome. This abnormality, the better known for its association with chronic myelogenous leukemia, is associated with a poorer prognosis when it occurs in acute leukemias.
5) Without therapeutic intervention, follow a short and precipitous course, marked by anemia, infection, and hemorrhage, and death occurs within 6 to 12 months.

Front 3

What is acute lymphoblastic leukemia (ALL)?

Back 3

1) Is the most common malignancy of children.
2) Characterized by a predominance of lymphoblasts in the circulating blood and in the bone marrow.
3) Occurs most often in CHILDREN and is the form of acute leukemia that is most responsive to therapy.
4) Further classified into a sumber of subgroups based on differences in morphology, cytogenetic changes, antigenic cell-surface markers, or rearrangement of the immunoglobulin heavy-chane or T cell receptor genes. The form that is most common and most amenable to therapy is characterized by blast cells that are postive for the CD10 or CALLA (common acute lymphoblastic leukemia antigen) marker.

Front 4

What is acute myeloid (myeloblastic) leukemia (AML).

Back 4

1) Characterized by a predominance of myeloblasts and early promylocytes
2) Occurs most often in ADULTS
3) Responds more poorly to current therapy than does ALL
4) Further classified into several subgroups based on morphology, cytochemical characteristic, surface markers, and genetic alterations.

Front 5

What is chronic leukemia?

Back 5

1) Characterized by proliferations of lymphoid or hematopoietic cells that are more mature than those of the acute leukemias.
2) Have a longer, less devastating clinical course than the acute leukemias but are less responsive to therapeutic intervention.

Front 6

What are the general considerations of chronic lymphocytic leukemia (CLL)?

Back 6

1) CLL is characterized by a proliferation of neoplastic lymphoid cells (almost always B cells) wiht widespread infiltration of bone marrow, peripheral blood, lymh nodes, spleen, liver, and other organs
2) Leukemic cells are less capable of differentiating into antibody-producing plasma cells
3) CLL most often occurs in persons older than 60 years of age and more frequently in men.

Front 7

What are the characteristics of CLL?

Back 7

1) Leukemic cells closely resemble normal mature peripheral blood lymphocytes an, like these cells, express surface immunoglobulin and pan-B cell markers such as CD19 and CD20. They are also CD5 positive and CD10 negative.
2) The cells are susceptible to mechanical disruption and often appear on the peripheral blood smear as smudge cells
3) The peripheral white blood cell count varies from 50,000/ul to 200,000/ul, wiht a preponderance of leukemic cells.
4) Leukemic cells diffusely infiltrate the bone marrow

Front 8

What are the complications of CLL?

Back 8

1) Warm antibody autoimmune hemolytic anemia
2) Hypogammaglu

Front 9

What are the clinical features of CLL?

Back 9

1) The clinical course is usually described as indollent, often with few symptoms and minor disability for protracted periods.
2) Generalized lymphadenopathy and moderate hepatosplenomegaly are frequent features.
3) Mean survival is 3-7 years; treatment relieves symptoms but has little effect on overall survival.

Front 10

What is Hairy cell leukemia?

Back 10

1) A B cell disease in which the leukemic cells exhibit characteristic hair-like filamentous projections. This cells can be further identified by their positive straining for tartrate-resistant acid phosphatase (TRAP).
2) Has received major attention because of its dramatic response to several therapeutic agents, including alpha-interferon, 2-chlorodeoxyadenosine, and deoxyconformycin.
3) Most often affects middle-aged men, who present with prominent splenomegaly and pancytopenia.

Front 11

What is CML?

Back 11

1) Chronic myelogenous leukemia
2) A neoplastic clonal proliferation of myeloid stem cells, the precursor cells of erythrocytes, granulocytes, monocytes, and platelets.
3) Is one of the myeloproiferative syndromes.

Front 12

What are the molecular changes of CML?

Back 12

1) Characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22. The Philadelphia chromosome represents a remnant of chromosome 22 with the addition of small segment of chromosome 9. This cytogenetic change is found in all blood cell lineages (erythroblasts, granulocytes, monocytes, megakaryocytes, B and T cell progenitors) but not in the majority of circulating B or T lymphocytes.
2) The c-able proto-oncogene on chromosome 9 is transposed to an area on chromosome 22, adjacent to an oncogene referred to as bcr, forming a new hybrid, or fusion gene, bcr-abl
3) Bcr-abl codes for a protein (p210) with tyrosine kinase activity, which plays a critical role in the etiopathogenesis of CML.

Front 13

What are the characteristics of CML?

Back 13

1) Marked leukocytosis, with white blood cell counts varying form 50,000/ul to 200,000/ul
2) Leukemic cells in the peripheral blood and bone marrow, mainly middle-to-late myeloid (granulocytic) precursor cells, including myelocytes, metamyelocytes, bands, and segmented forms.
3) Small numbers of blasts and promyelocytes
4) The philadelphia chromosome, found in granulocytic and erythroid precursor cells and in megakaryocytes
5) Marked reduction in leukocyte alkaline phosphatase activity in the leukemic leukocytes

Front 14

What are the clinical features of CML?

Back 14

1) Prominent splenomegaly and modest enlarged liver and lymph nodes.
2) Peak incidence in middle-age group (age 35-50)
3) Terminates, in most cases, in an accelerated phase leading to so-called blast crisis marked by increased numbers of primitive blast cells and promyelocytes.

Front 15

What are myeloproliferative diseases?

Back 15

1) Neoplastic clonal proliferations of myeloid stem cells.
2) Represent a group of relative disorders, which include chronic myelogenous leukemia, polycythemia vera, chronic idiopathic myelofibrosis (agnogenic myeloid metaplasia), and essential thrombocythemia.

Front 16

What are the common characteristics of myeloproliferative diseases?

Back 16

1) Peak incidence in middle-aged and elderly persons.
2) Proliferation of one or more of the myeloid series (erythroid, granulocytic, and megakaryocytic) cell types
3) Increase in peripheral blood basophils and nucleated red cells
4) Increase in serum uric acid
5) Prominent splenomegaly

Front 17

What are the clinical characteristics of polycythemia vera?

Back 17

1) Marked erythrocytosis
2) Moderate increase in circulating granulocytes adn platelets
3) Splenomegaly
4) Decreased erythropoietin
5) Sludging of high hematocrit blood often leads to thrombotic or hemorrhagic phenomena
6) PV often progresses to a late phase in which anemia supervenes. This phase is often marked by bone marrow fibrosis nd extramedullary hematopoiesis and a rising white blood cell count, and it can mimic CML.
6) Acute leukemia may supervene in approximately 3% of patients, most of whom have received antimitotic drugs or radiation therapy.

Front 18

How do you diagnos polycythemia vera?

Back 18

1) Marked by decreased erythropoietin, which distinguishes it form other forms of poycythemia, all of which are associated with increased erythropoietin.
2) Must be distinguished from secondary polycythemia: chronic hypoxia, associated with pulmonary disease, congenital heart disease, residence at high altitudes, and heavy smoking; inappropriate production of erythropoietin, associated with androgen therapy, adult polycystic kidney disease, and tumors, such as renal cell carcinoma, hepatocellular carcinoma, and cerebellar hemangioma; Endocrine abnormalities, prominently including pheochromocytoma and adrenal adenoma with Cushing syndrome

Front 19

What is chronic idiopathic myelofibrosis (agnogenic myeloid metaplasia, myelofibrosis with myeloid metaplasia)?

Back 19

1) Characterized by extensive extramedullary hematopoiesis involving the liver and splen and sometimes than lymph nodes.
2) Further characterized by proliferation of non-neoplastic fibrous tissue within the bone marrow cavity (mylofibrosis). The fibrous tissue replaces normal hematopoietic cells. this late manifestation is often preceded by marrow hypercellularity.

Front 20

What are the postulated pathogenetic factors of chronic idiopathic myelofibrosis?

Back 20

1) Megakaryocytic proliferation may be the primary abnormality; the elaboration of platelet-derived growth factor and of transforming growth factor Beta (TGF-beta) by platelets and megakaryocytes may be the cause of the fibroblastic proliferation.
2) Megakaryocytes are spared in the marrow fibrotic process and increase in number, resulting in prominent bone marrow megakaryocytosis and peripheral blood thrombocytosis.

Front 21

What are the clinical features of chronic idiopathic myelofibrosis?

Back 21

1) Peripheral blood smear; teardrop-shaped erythrocytes; granulocytic precursor cells and nucleated red cell precursors in variable numbers
2) Anemia and massive splenomegaly

Front 22

What is essential thrombocythemia?

Back 22

1) Characterized by marked thrombocytosis in teh peripheral blood and megakaryocytosis in the bone marrow. Platelet counts in excess of 1,000,000/ul are common (normal value is 150,000 - 300,000/ul)

Front 23

What are the general considerations of non-neoplastic lymphoid proliferations?

Back 23

These reactions include acute and chronic nonspecific lymphadenitis occurring in response to a number of infectious agents or immune stimuli.

Front 24

What is infectious mononucleosis?

Back 24

1) Benign, self-limited disorder caused by Epstein-Barr virus (EBV), which has an affinity for B lymphocytes.
2) Occurs frequently in young adults
3) Characterized by circulating atypical lymphocytes (reactive CD8+ T lymphocytes).
4) Marked by a number of serum antibodies, including anti-EBV antibodies and heterophil antibodies directed at sheep erythrocytes; so-called heterophil-negative infectious mononucleosis is most often associated with cytomegalovirus infection.
5) Clinically characterized by prominent sore throat, fever, generalized lymphadenopathy, and often by hepatosplenomegaly. The spleen is especially susceptible to traumatic rupture.

Front 25

What are plasma cell disorders?

Back 25

1) Neoplastic proliferations of well-differentiated immunoglobuin-producing cells.
2) Include multiple myeloma, Waldenstrom macroglobulinemia, primary amyloidosis, benign monoclonal gammopathy, and heavy-chain (Franklin) disease.
3) Most frequently occur in persons older than 40-50 years of age.

Front 26

What is myltiple myeloma?

Back 26

Malignant plasma cell tumor usually affecting older persons that typically involves bone and is associated with prominent serum and urinary protein abnormalities.

Front 27

What are neoplastic cells and how are they identified in multiple myeloma?

Back 27

1) neoplastic cell is an end-stage derivative of B lymphocytes that is clearly identifiable as a plasma cell.
2) Neoplastic cells can easily be identified by bone marrow biopsy or aspiration smears.

Front 28

What do tumor cells produce in multiple myeloma?

Back 28

1) Tumor cells produce lytic lesions in bone, especially in the skull and a xial skeleton.
2) Bone lesions appear lucent on radiographic examination, with characteristic sharp borders, and are referred to as "punched-out lesions".
3) May be manifest radiographically as diffuse demineralization of bone (osteopenia)
4) Are caused by an osteoclast-activating factor secreted by the neoplastic plasma cells.
5) Are often associated with severe bone pain and spontaneous fractures.

Front 29

From what does multiple myeloma arrise?

Back 29

1) Proliferation of a single clone of malignant antibody-producing cells.
2) Tumor cells produce massive quantities of identical immunoglobulin molecules demonstrable electrophoretically as a narrow serum band or, after densitometric scanning, as a sharp spike referred to as an M protein.
3) M protein in multiple myeloma is most often an IgG or IgA immunoglobulin of either kappa or lambda light-chain specificity
4) Synthesis of normal immunoglobulins is often impaired.
5)Marked serum immunoglobulin increase is often initially detected by laboratory screening as increased total protein with an increase in serum globulin (hyperglobulinemia).
6) Urine often contains significant quantities of free Ig light chains, either kappa or lambda which are referred to Bence Jones protein.
7) As a consequence of hyperglobulinemia, the red cells tend to congregate together in a manner reminiscent of a stack of poker chips (rouleaux formation). There is also a marked increase in the ESR.

Front 30

What are some "other" clinical characteristics of multiple myeloma?

Back 30

1) Anemia; due to neoplastic encroachment on myeloid precursor cells; possible leukopenia and thrombocytopenia
2) Increased susceptibility to infection because of impaired production of normal immunoglobulins
3) Hypercalcemia secondary to bone destruction
4) Renal insufficiency with azotemia due to myeloma kidney. The renal lesion is characterized by prominent tubular casts of Bence Jones protein, numerous multinucleated macrophage-derived giant cells, metastatic calcification, and sometimes by interstitial infiltration of malignant plasma cells.
5) Amyloidosis of the primary amyloidosis type.

Front 31

What is waldenstrom macroglobulinemia?

Back 31

1) Manifestation of lymphoplasmacytic lymphoma, a B-cell neoplasm of lymphoid cells of an intermediate stage between B lymphocytes and plasma cells referred to as plasmacytoid lymphocytes.
2) The neoplastic cells produce a monoclonal IgM protein.

Front 32

What are the defining characteristics of waldenstrom macroglobulinemia?

Back 32

1) Serum IgM immunoglobulin of either kappa or lambda specificity occurring as an M protein.
2) Plasmacytoid lymphocytes infiltrating the blood, bone marrow, lymph nodes, and spleen
3) Bence Jones proteinuria in aabout 10% of cases
4) Absence of bone lesions

Front 33

What are the clinical features of waldenstrom macroglobulinemia?

Back 33

1) Most frequently seen in men older than 50 years of age.
2) Slowly progressive course, often marked by generalized lymphadenopathy and mild anemia.

Front 34

What are the complications of waldenstrom macroglobulinemia?

Back 34

1) Hyperviscosity syndrome, resulting from marked increase in serum IgM
2) Includes retinal vascular dilation, sometimes with hemorrhage, confusion, and other CNS changes.
3) Sometimes requires emergency plasmapheresis to prevent blindness.
4) Abnormal bleeding, which may be due to vascular and platelet dysfunction secondary to the serum protein abnormality.

Front 35

What is benign monoclonal gammopathy (monoclonal gammopathy of undetermined significance, or MGUS)

Back 35

1) Occurs in 5%-10% of otherwise healthy older persons.
2) Characterized by a monoclonal M protein spike of less than 2g/100ml, minimal or no Bence Jones proteinuria, less than 5% plasma cells in the bone marrow, and no decrease in concentration of normal immunoglobulins.
3) Most often without clinical consequence.

Front 36

What is Hodgkin lymphoma (Hodgkin disease)?

Back 36

1) Malignant neoplasm with feature resembling an inflammatory disorder.
2) Characteristically affects young adult; an exception is nodular sclerosis, which frequently affects young women.
3) Often associated with pruritus and fever, diaphoresis, and leukocytosis reminiscent of an acute infection.
4) With modern staging and aggressive therapy, a clinical cure is often achieved.

Front 37

What are reed-sternberg cells?

Back 37

1) May be the actual malignant cells of Hogkin lymphoma.
2) Binucleated, or multinucleated, giant cells with eosinophilic inclusion-like nucleoli.
3) differing numbers are found in varying forms of Hodgkin lymphoma, and the severity of the disease variants is directly proportional to the number of Reed-Sternberg cells found in the lesions.
4) Conversely, the greater the number of reacctive lymphocytes in the Hodgkin lymphoma variant, the better will be the prognosis.

Front 38

What are the classifications of Hodgkin lymphoma by the WHO?

Back 38

1) Lymphocyte-rich classical Hodgkin lymphoma;
2) Mixed cellularity Hodgkin lymphoma;
3) Lymphocyte depletion Hodgkin lymphoma
4) Nodular sclerosis Hodgkin lymphoma

Front 39

What is lymphocyte-rich classical Hodgkin lymphoma?

Back 39

1) Characterized by large numbers of lymphocytes and histiocytes and paucity of Reed-Sternberg cells
2) Associated with a relatively good prognosis

Front 40

What is mixed cellularity Hodgkin lymphoma?

Back 40

1) Variant of Hodgkin lymphoma that is found most often in older persons
2) Characterized by a polymorphic infiltrate of eosinophils, plasma cells, histiocytes, and Reed-Sternberg cells, and by areas of necrosis and fibrosis.

Front 41

What is lymphocyte depletion Hodgkin lymphoma?

Back 41

1) The least frequently occurring form of Hodgkin lymphoma
2) Marked by few lymphocytes, numerous Reed-Sternberg cells, and extensive necrosis and fibrosis
3) Has the poorest prognosis among the Hodgkin lymphoma variants.

Front 42

What is Nodular sclerosis Hodgkin lymphoma?

Back 42

1) The most frequently occurring form of Hodgkin lymphoma
2) Occurs more frequently in women, unlike other forms of Hodgkin lymphoma
3) Characterized by nodular division of affected lymph nodes by fibrous bands and by the presence of lacunar cells, Reed-Sternberg cell variants
4) Often arises in the upper mediastinum or lower cervical or supraclavicular nodes
5) Associated with a relatively good prognosis

Front 43

What is clinical staging - Ann Arbor classification?

Back 43

1) Based on the degree of dissemination, involvement of extralymphatic sites, and presence or absence of systemic signs such as fever.
2) Is an essential part of the diagnostic evaluation of patients with Hodgkin lymphoma
3) Although grading of histopathologic variants roughly correlates with clinical behavior, prognosis is better predicted by staging

Front 44

What is non-Hodgkin lymphoma?

Back 44

1) Malignant neoplasm arising from lymphoid cells or other cells native to lymphoid tissue.
2) Originate most frequently within lymph nodes are in other lymphoid areas. Tumor involvement of the periaortic lymph nodes is frequent.

Front 45

What are WHO classification of lymphoid neoplasms?

Back 45

Includes Hodgkin lymphoma and all lymphoid neoplasms, including not only the non-Hodgkin lymphomas but also the lymphoid leukemias and multiple myeloma.

Front 46

What is stage I classification of Hodgkin and non-Hodgkin lymphomas?

Back 46

Involvement of a single lymph node region or involvement of a single extra-lymphatic organ or site.

Front 47

What is stage II classification of Hodgkin and non-Hodgkin lymphomas?

Back 47

Involvement of two or more lymph node regions on the same side of the diaphrams alone or with involvement of limited contiguous extraalymphatic organ or tissue.

Front 48

What is stage III classification of Hodgkin and non-Hodgkin lymphomas?

Back 48

Involvement of lymph node regions on both sides of the diaphragm, which may include the spleen, limited contiguous extralymphatic organ or site, or both.

Front 49

What is stage IV classification of Hodgkin and non-Hodgkin lymphomas?

Back 49

Multiple or disseminated foci of involvement of one or more extralymphatic organs with or without lymphatic involvement.

Front 50

What is small lymphocytic lymphoma?

Back 50

1) B cell lymphoma that follows an indolent course and occurs most often in older persons.
2) Characterized by diffuse effacement of lymph node architecture by small mature-appearing lymphocytes.
3) Frequently characterized by widespread nodal involvement and involvement of the liver, spleen, and bone marrow.
4) Closely related to CLL. In the WHO classificatin, this disorder is called B cell chronic lymphocytic leukemia/small lymphocytic lymphoma. the neoplastic cells express surface immunoglobulin and pan-B cell markers and are positive for CD5 but negative for CD10

Front 51

What is follicular lymmphoma?

Back 51

1) B cell lymphoma, often following an indolent course in older persons.
2) Most common form of non-Hodgkin lymphoma
3) Characterized by proliferation of angulated grooved cells that closely resemble the cells of the lymphoid follicular center, commonly in a follicular (nodular) pattern. These cells express surface immunoglobulin and B cell markers such as CD19 and CD20, are sometimes positive for CD10, and are CD5 negative.
4) Marked by a characteristic cytogenetic change, t(14;18), and by expression of bcl-2, an oncogene; bcl-2 codes for a mitochondrial protein that inhibits apoptosis.

Front 52

What is mantle cell lymphoma?

Back 52

1) Arises form the mantle zone of lymphoid follicles.
2) Morphologically and immunophenotypically similar to small lymphocytic lymphoma, with slightly different cellular detail.
3) Characterized by a translocation, t(11;14), which results in activation of the cyclin D1 gene (bcl-1)
4) Most often manifest as a disseminated, aggressive, incurable disease that occurs predominantly in older men

Front 53

What is extranodal marginal zone B cell lymphoma of MALT type.

Back 53

1) Tends to arise in sites of chronic inflammation or sites of autoimmune disease such as the salivary glands in Sjogren syndrome, the thyroid in Hashimoto thyroiditis, or the stomach in Helicobacter pylori gastritis
2) Often referred to as a MALToma.

Front 54

What does MALT stand for?

Back 54

Mucosal-associated lymphoid tissue

Front 55

What is diffuse large B cell lymphoma?

Back 55

1) Most commonly occurs in older persons; however, the age range is wide adn many of these lymphomas occur in children
2) Usually presents as a large, often extranodal mass followed by wide-spread aggresive dissemination. Leukemic involvement is rare.

Front 56

What is precursor T lymphoblastic lymphoma/leukemia?

Back 56

1) Characterized by convoluted-appearing nuclei
2) Occurs most often in children
3) Most often arises from thymic lymphocytes.
4) Rapidly disseminates and progresses to T-ALL
5) Often presents clinically as a combination of T-ALL and a mediastinal mass.

Front 57

What is Burkitt lymphoma?

Back 57

1) Aggressive B cell lymphoma. The African form frequently involves the maxilla or mandible; the American form usually involves abdominal organs.
2) Closely linked to EBV infection
3) Characterized histologically by a "starry-sky" appearance. As a result of rapid cell turnover, the lesions contain abundant cellular debris that is taken up by non-neoplastic macrophages, resulting in this appearance
4) Closely related to B-ALL, which is called Burkitt cell leukemia in the WHO classification.
5) Associated with a characteristic cytogenic change, t(8;14).

Front 58

What are cutaneous T cell lymphomas?

Back 58

Mycosis fungoides
Sezary syndrome

Front 59

What is mycosis fungoides?

Back 59

1) Preents as an erythematous, eczematoid, or psoriasiform process, progressing to raised plaques adn then to a tumor stage
2) Marked histologically by dermal infiltrates of atypical CD4+ T cells with cerebriform nuclei. Small pockets of tumor cells within the epidermis are referred to as Pautrier microabscesses.
3) Eventually disseminates lymph nodes and internal organs.

Front 60

What is Sezary syndrome?

Back 60

1) Leukemic form of cutaneous T cell lymphoma.
2) Characterized by teh combination of skin lesions and circulating neoplastic cells with cerebriform nuclei

Front 61

Describe the cytogenic changes of Burkitt lymphoma.

Back 61

1) C-myc proto-oncogene located on chromosome 8 is transposed to a site adjacent to the immunoglobulin heavy chain locus on chromosome 14
2) Increased expression of the c-myc gene, presumably caused by the proximity of regulatory sequences of the immunoglobulin heavy chain gene, is characteristic.