Flashcards in CH6 - White Blood Cell Disorders Deck (283):
What does hematopoetic CD34+ stem cells produce?
Myeloid stem cells and lymphoid stem cells
What does myeloid stem cells produce?
Erythroblast, Myeloblast, Monoblast, Megakaryoblast
What does erythroblast produce?
What does myeloblast produce?
Neutrophils, basophils, Eosinophils
What does monoblast produce?
What does megakaryoblast produce?
What does lymphoid stem cells produce?
B lymphoblast and T Lymphoblast
What does B lymphoblast produce?
What does Naïve B cells produce?
What does T lymphoblast produce?
What does Naïve T cells produce?
CD8+ and CD4+ T cells
How does hematopoiesis occur?
via a stepwise maturation of CD34+ hematopoietic stem cells
What happens to hematopoetic stem cells?
Cells mature and are released from the bone marrow into the blood.
What is the normal white blood cell (WBC) count?
it is approximately 5-10 K/pL
What is a low WBC count? What is it called?
(< 5 K) is called leukopenia.
What is a high WBC count? What is it called?
(> 10 K) is called leukocytosis.
What is a low or high WBC count usually due to?
a decrease or increase in one particular cell lineage.
What is neutropenia?
refers to a decreased number of circulating neutrophils
What are some of the causes of neutropenia?
1) Drug toxicity 2) severe infection
How can drug toxicity lead to neutropenia?
e.g., chemotherapy with alkylating agents, cause damage to stem cells resulting in decreased production of WBCs, especially neutrophils.
How does severe infection lead to neutropenia?
e.g., gram-negative sepsis leads to increased movement of neutrophils into tissues resulting in decreased circulating neutrophils.
What is GM-CSF or G-CSF?
granulocyte monocyte stimulating factor or granulocyte stimulating factor, it can be used to boost the neutrophil count decreasing the risk of infection
What is lymphopenia?
it refers to a decreased number of circulating lymphocytes
What are the some of the causes of lymphopenia?
1) immunodeficiency 2) high cortisol state 3) autoimmune destruction 4) whole body radiation
What are some examples of immunodeficiency that lead to lymphopenia?
e.g., DiGeorge syndrome or HIV
How does a High Cortisol state lead to lymphopenia?
exogenous corticosteroids or Cushing syndrome, induces apoptosis of lymphocytes
What is an example of autoimmune destruction leading to lymphopenia?
e.g., systemic lupus erythematosus
How can whole body radiation lead to lymphopenia?
Lymphocytes are highly sensitive to radiation; lymphopenia is the earliest change to emerge after whole body radiation
What are the different types of leukocytosis?
1) neutrophilic leukocytosis 2) monocytosis 3) Eosinophilia 4) Basophilia 5) Lymphocytic leukocytosis
What does neutrophilic leukocytosis refer to?
increased circulating neutrophils
What are the causes of neutrophilic leukocytosis?
1) Bacterial infection 2) tissue necrosis 3) High cortisol state
How does Bacterial infection or tissue necrosis lead to neutrophilic leukocytosis?
It induces release of marginated pool and bone marrow neutrophils, including immature forms (left shift)
When immature cells are released into the blood, how are they characterized?
by decreased Fc receptors
What is the marker for the decreased Fc receptor?
Why are Fc receptors important?
They help the neutrophil to recognize immunoglobulin which is going to act as an opsonin for phagocytosis
How does high cortisol state lead to neutrophilic leukocytosis?
impairs leukocyte adhesion, leading to release of marginated pool of neutrophils
What does monocytosis refer to?
increased circulating monocytes
What are the causes of monocytosis?
inflammatory states (e.g., autoimmune and infections) and malignancy.
What does eosinophilia refer to?
increased circulating eosinophils
What are the causes of eosinophilia?
include allergic reactions (type I hypersensitivity), parasitic infections, and Hodgkin lymphoma,
What is eosinophilia driven by?
increased eosinophil chemotactic factor
What does basophilia refer to?
increased circulating basophils
What is basophilia classically seen in?
chronic myeloid leukemia
What does lymphocytic leukocytosis refer to?
increased circulating lymphocytes
What are the causes of lymphocytic leukocytosis?
1) viral infection 2) Bordetella pertussis infection
How does viral infections lead to lymphocytic leukocytosis?
T lymphocytes undergo hyperplasia in response to virally infected cells
How does Bordetella pertussis infection lead to lymphocytic leukocytosis?
Bacteria produce lymphocytosis-promoting factor, which blocks circulating lymphocytes from leaving the blood to enter the lymph node.
What is infectious mononucleosis?
EBV infection that results in a lymphocytic leukocytosis comprised of reactive CD8+ T cells; CMV is a less common cause
How is EBV transmitted?
by saliva (kissing disease); classically affects teenagers
What does EBV primarily infect?
1. Oropharynx, resulting in pharyngitis 2. Liver, resulting in hepatitis with hepatomegaly and elevated liver enzymes 3. B cells
CD8+ T-cell response leads to what?
1) LAD 2) Splenomegaly 3) High WBC count with atypical lymphocytes (reactive CD8+ T cells) in the blood
How does the CD8+ T cell response lead to generalized lymphadenopathy (LAD)?
It is due to T-cell hyperplasia in the lymph node paracortex
How does CD8+ T cell response lead to splenomegaly?
It is due to T-cell hyperplasia in the periarterial lymphatic sheath (PALS)
What is used for screening of IM?
The monospot test
What does the monospot test do?
Detects IgM antibodies that cross-react with horse sheep red blood cells (heterophile antibodies)
When would the monospot test turn positive?
Usually turns positive within 1 week after infection
What would a negative monospot test suggest?
CMV as a possible cause of IM
How is a definitive diagnosis for IM made?
by serologic testing for the EBV viral capsid antigen.
What are the complications of EBV?
1) increased risk for splenic rupture 2) Rash 3) Recurrence and B cell lymphoma
What are patients told who have an increased risk for splenic rupture?
patients are generally advised to avoid contact sports for one year.
When might a rash develop as a complication of EBV?
if exposed to ampicillin
With EBV complications, why is there a risk of recurrence and B cell lymphoma?
Dormancy of virus in B cells leads to increased risk for both recurrence and B-cell lymphoma, especially if immunodeficiency (e.g., HIV) develops.
What is acute leukemia?
Neoplastic proliferation of blasts; defined as the accumulation of >20% blasts in the bone marrow.
What is the acute presentation for acute leukemia?
Anemia (fatigue), thrombocytopenia (bleeding), or neutropenia (infection)
What is the reason for the acute presentation of acute leukemia?
Increased blasts crowd-out normal hematopoiesis,
In acute leukemia, why is there a high WBC count?
Blasts usually enter the blood stream, resulting in a high WBC count
they are large, immature cells, often with punched out nucleoli
What is acute leukemia subdivided into?
acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML)
The subdivision of acute leukemia is based on what?
the phenotype of the blasts.
What is acute lymphoblastic leukemia?
Neoplastic accumulation of lymphoblasts (> 20%) in the bone marrow
Why is TdT useful in characterizing lymphoblasts?
It is absent in myeloid blasts and mature lymphocytes.
Acute lymphoblastic leukemia most commonly arises in whom?
What is acute lymphoblastic leukemia associated with and when does it usually arise?
Down syndrome (usually arises after the age of 5 years)
Acute lymphoblastic leukemia is subclassified into? What is it based on?
B-ALL and T-ALL based on surface markers
What is the most common type of ALL?
What is B-ALL usually characterized by?
lymphoblasts (TdT+) that express CD10, CD19, and CD20.
What is the treatment for B-ALL?
Excellent response to chemotherapy; requires prophylaxis to scrotum and CSf
What is the prognosis B-ALL based on?
It is based on cytogenetic abnormalities,
Which B-ALL has a good prognosis and is more commonly seen in children?
Which B-ALL has a poor prognosis and in what population is it seen?
t(9;22) has a poor prognosis; more commonly seen in adults (Philadelphia+ALL)
What is T-ALL characterized by?
lymphoblasts (TdT+) that express markers ranging from CD2 to CDH (e.g., CD3, CD4, CD7). The blasts do not express CD10.
How does T-ALL usually present?
Usually presents in teenagers as a mediastinal (thymic) mass (called acute lymphoblastic lymphoma because the malignant cells form a mass)
What is acute myeloid leukemia?
Neoplastic accumulation of myeloblasts (> 20%) in the bone marrow
How are myeloblasts usually characterized?
by positive cytoplasmic staining for myeloperoxidase (MPO)
What may be seen in the characterization of myeloblasts?
Crystal aggregates of MPO may be seen as Auer rods
In whom does acute myeloid leukemia most commonly arise?
older adults (average age is 50-60 years)
What is the subclassification of AML based on?
cytogenetic abnormalities, lineage of myeloblasts, and surface markers.
What are the high-yield subtypes?
Acute promyelocytic leukemia, Acute monocytic leukemia and acute megakaryoblastic leukemia
What is acute promyelocytic leukemia characterized by?
t(15;17), which involves translocation of the retinoic acid receptor (RAR) on chromosome 17 to chromosome 15
What is the effect of RAR disruption?
It blocks maturation and promyelocytes (blasts) accumulate
How does acute promyelocytic leukemia lead to increased risk for DIC?
Abnormal promyelocytes contain numerous primary granules that increase the risk for DIC
What is the treatment for acute promyelocytic leukemia?
with all-trans retinoic acid (ATRA, a vitamin A derivative)
How does ATRA work?
It binds the altered receptor and causes the blasts to mature (and eventually die)
What is acute monocytic leukemia?
Proliferation of monoblasts; usually lack MPO
In acute monocytic leukemia what do blasts characteristically do?
What is acute megakaryoblastic leukemia?
Proliferation of megakaryoblasts; lack MPO
What is acute monocytic leukemia associated with?
Down syndrome (usually arises before the age of 5)
What is myelodysplastic syndrome?
acute myeloid leukemia may also arise from pre-existing dysplasia = myelodysplastic syndromes, especially with prior exposure to alkylating agents or radiotherapy
What do myelodysplastic syndromes usually present with?
cytopenias, hypercellular bone marrow, abnormal maturation of cells, and increased blasts < 20%
With myelodysplastic syndromes resulting in acute myeloid dysplastic syndrome what do most patients die from?
Most patients die from infection or bleeding, though some progress to acute leukemia.
What is chronic leukemia?
Neoplastic proliferation of mature circulating lymphocytes
What is chronic leukemia characterized by?
a high WBC count
Describe the onset of chronic leukemia?
Usually insidious in onset and seen in older adults
What is chronic lymphocytic leukemia?
Neoplastic proliferation of naive B cells that co-express CD5 and CD20;
What is the most common leukemia overall?
Chronic lymphocytic leukemia (CLL)
In CLL what is seen on the blood smear?
Increased lymphocytes and smudge cells are seen on blood smear
small lymphocytic lymphoma
In CLL, with involvement of lymph nodes leads to generalized lymphadenopathy
What are the complications of CLL?
1) Hypogammaglobulinemia, 2) autoimmune hemolytic anemia, 3) Richter transformation
What is the most common of death in CLL?
What is Richter transformation?
transformation to diffuse large B-cell lymphoma
What is Richter transformation marked clinically by?
an enlarging lymph node or spleen
What is Hairy cell leukemia?
Neoplastic proliferation of mature B cells
What characterizes hairy cell leukemia?
hairy cytoplasmic processes
What are hairy cell leukemia cells positive for?
tartrate-resistant acid phosphatase (TRAP).
What are the clinical features for hairy cell leukemia?
Splenomegaly, dry tap on bone marrow aspiration
Why is there splenomegaly in hairy cell leukemia?
Due to accumulation of hairy cells in red pulp
Why is there a dry tap on bone marrow aspiration in hairy cell leukemia?
due to marrow fibrosis
How is lymphadenopathy related to hair cell leukemia?
Lymphadenopathy is usually absent
What drug is used in the treatment of hairy cell leukemia?
How does hair cell leukemia respond to cladribine?
How does cladribine work?
Its an adenosine deaminase inhibitor, adenosine accumulates to toxic levels in neoplastic B cells.
What is adult T cell leukemia?
Neoplastic proliferation of mature CD4+ T cells (ATLL)
What is adult T cell leukemia associated with?
Associated with HTLV-I (human T cell lymphotrophic virus -1)
Where is ATLL associated with HTLV-1 most commonly seen in?
Japan and the Caribbean
What are the clinical features for ATLL?
include rash (skin infiltration), generalized lymphadenopathy with hepatosplenomegaly, and lytic (punched-out) bone lesions with hypercalcemia
What is mycosis fungoides?
Neoplastic proliferation of mature CD44 T cells that infiltrate the skin, producing localized skin rash, plaques, and nodules
What are Patitrier microabscesses?
Aggregates of neoplastic cells in the epidermis
cells can spread to involve the blood, producing Sezary syndrome.
What are Sezary cells?
Characteristic lymphocytes with cerebri form nuclei
What would you see on blood smear in mycosis fungoides?
What are myeloproliferative disorders?
Neoplastic proliferation of mature cells of myeloid lineage; disease of late adulthood (average age is 50-60 years)
What does myeloproliferative disorders result in?
high WBC count with hypercellular bone marrow
How are myeloproliferative disorders characterized?
Cells of all myeloid lineages are increased; classified based on the dominant myeloid cell produced
What are the complications for myeloproliferative disorders?
1) Increased risk for hyperuricemia and gout due to high turnover of cells 2) Progression to marrow fibrosis or transformation to acute leukemia
What is chronic myeloid leukemia?
Neoplastic proliferation of mature myeloid cells, especially granulocytes and their precursors;
In chronic myeloid leukemia what are characteristically increased?
What is chronic myeloid leukemia driven by?
driven by t(9:22) - Philadelphia chromosome - which generates a BCR-ABL fusion protein with increased tyrosine kinase activity
What is the first line treatment for chronic myeloid leukemia?
What does imatinib do?
It blocks tyrosine kinase activity
How is splenomegaly related to chronic myeloid leukemia?
Splenomegaly is common, enlarging spleen suggests accelerated phase of disease;
In chronic myeloid leukemia what usually follows after splenomegaly?
transformation to acute leukemia
What can chronic myeloid leukemia transform to?
AML in 2/3 of cases or ALL in 1/3 of cases since mutation is in a pluripotent stem cell,
What is a leukemoid reaction?
Reactive neutrophilic leukocytosis
How is CML distinguished from a leukemoid reaction (reactive neutrophilic leukocytosis)?
Negative LAP stain, inc basophils, t(9;22)
What is a LAP stain?
leukocyte alkaline phosphatase (LAP) stain
How is a LAP stain related to a leukemoid reaction?
granulocytes in a leukemoid reaction are LAP positive
Why are basophils useful in determining the difference between a leukemoid reaction and CML?
Basophils are increased in CML and are absent with a leukemoid reaction
How is t(9;22) useful in determining the difference between a leukemoid reaction and CML?
It is present in CML and absent in leukemoid reaction
What is polycythemia vera?
Neoplastic proliferation of mature myeloid cells, especially RBCs
In polycythemia vera, in addition to the RBC increase what are also increased?
Granulocytes and platelets are also increased
What mutation is associated with polycythemia vera?
JAK2 kinase mutation
What are the clinical symptoms for polycythemia vera due to?
they are mostly due to hyperviscosity of blood
What are the clinical symptoms for polycythemia vera?
1. Blurry vision and headache 2. Increased risk of venous thrombosis (e.g., hepatic vein, portal vein, and dural sinus) 3. Flushed face due to congestion (plethora) 4. Itching, especially after bathing (due to histamine release from increased mast cells)
What is plethora in relation to PV?
One of the clinical symptoms; flushed face due to congestion
Why is there itching in PV?
Itching, especially after bathing due to histamine release from increased mast cells
What is the treatment for PV?
What is the second-line therapy for PV?
What happens to a patient with PV who goes intreated?
Without treatment, death usually occurs within one year.
How can PV be distinguished from reactive polycythemia?
1. In PV, erythropoietin (EPO) levels are decreased, and Sao, is normal. 2. In reactive polycythemia due to high altitude or lung disease, SaO2 is low, and EPO is increased. 3. In reactive polycythemia due to ectopic EPO production from renal cell carcinoma, EPO is high, and Sao2 is normal.
What are the EPO and SaO2 levels in PV?
EPO is decreased and SaO2 is normal
What are the EPO and SaO2 levels in reactive polycythemia due to high altitude or lung disease?
EPO is increased and SaO2 is low
What are the EPO and SaO2 levels in reactive polycythemia due to renal cell carcinoma?
EPO is high, SaO2 is normal
What is essential thrombocythemia?
Neoplastic proliferation of mature myeloid cells, especially platelets
In ET, in addition to the platelets what else is increased?
RBCs and granulocytes are also increased.
What is mutation is ET associated with?
JAK2 kinase mutation
What do the symptoms of ET result from?
they are related to an increased risk of bleeding and/or thrombosis.
What do the symptoms of ET rarely progresses to?
marrow fibrosis or acute leukemia
In ET what is there no significant risk for?
hyperuricemia or gout
What is myelofibrosis?
It is neoplastic proliferation of mature myeloid cells, especially megakaryocytes
What mutation is associated with myelofibrosis?
JAK2 kinase mutation in 50% of cases
In myelofibrosis, what causes marrow fibrosis?
Megakaryocytes produce excess platelet-derived growth factor (PDGF) causing marrow fibrosis
What are the clinical features for myelofibrosis?
1) splenomegaly 2) leukoerythroblastic smear 3) Increased risk of infection, thrombosis, and bleeding
In myelofibrosis what is splenomegaly due to?
In myelofibrosis what is the leukoerythroblastic smear?
It’s tear-drop RBCs, nucleated RBCs, and immature granulocytes
What is lymphadenopathy (LAD)?
it refers to enlarged lymph nodes
Painful LAD is usually seen in what?
lymph nodes that are draining a region of acute infection (acute lymphadenitis)
Painless LAD can be seen with what?
chronic inflammation (chronic lymphadenitis), metastatic carcinoma, or lymphoma.
In inflammation, lymph node enlargement is due to what?
hyperplasia of particular regions of the lymph node
What is follicular hyperplasia seen with?
(B-cell region) rheumatoid arthritis and early stages of HIV infection, for example.
What is paracortex hyperplasia seen with?
(T-cell region) viral infections (e.g., infectious mononucleosis).
What is involved with hyperplasia of sinus histiocytes?
It is seen in lymph nodes that are draining a tissue with cancer.
What is lymphoma?
Neoplastic proliferation of lymphoid cells that forms a mass; may arise in a lymph node or in extranodal tissue
What is lymphoma divided into?
non-Hodgkin lymphoma (NHL 60%) and Hodgkin lymphoma (HL 40%)
NHL further classified based on what?
cell type (e.g., B versus T), cell size, pattern of cell growth, expression of surface markers, and cytogenetic translocations, - small, intermediate and large B cells
What are some examples of small B cells?
follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma (i.e.. CLL cells that involve tissue)
What are some examples of intermediate-sized B cells
What are some examples of large B cells
diffuse large B-cell lymphoma
What is the overall frequency for NHL?
What is the overall frequency for HL?
What are the malignant cells of NHL?
What are the malignant cells of HL?
What is the composition of mass for NHL?
What is the composition of mass of HL?
Predominantly reactive cells (inflammatory cells and fibrosis)
How does NHL present clinically?
Painless lymphadenopathy, usually arises in late adulthood
How does HL present clinically?
Painless lymphadenopathy occasionally with 'B' symptoms, usually arises in young adults
What is the spread of NHL?
Diffuse: often extranodal
What is the spread of HL?
Contiguous; rarely extra nodal
Do you use staging in NHL?
Do you use staging in HL?
Guides therapy; radiation is the mainstay of treatment.
Is there a Leukemic phase in lymphoma?
Occurs in NHL but not in HL
What is follicular lymphoma?
Neoplastic proliferation of small B cells (CD20+) that form follicle-like nodules
How does follicular lymphoma present clinically?
in late adulthood with painless lymph adenopathy
What is follicular lymphoma driven by?
How does t(14:18) result in follicular lymphoma?
BCL2 on chromosome 18 translocates to the Ig heavy chain locus on chromosome 14 this results in overexpression of Bcl2, which inhibits apoptosis
What is the treatment for follicular lymphoma?
is reserved for patients who are symptomatic and involves low-dose chemotherapy or rituximab (anti-CD20 antibody).
What does follicular lymphoma progress to and how does it present?
diffuse large B-cell lymphoma which is an important complication and presents as an enlarging lymph node
How is follicular lymphoma distinguished from reactive follicular hyperplasia?
1) disruption of normal lymph node architecture (maintained in follicular hyperplasia) 2) Lack of tangible body macrophages in germinal centers (tangible body macrophages are present in follicular hyperplasia) 3) Bcl2 expression in follicles (not expressed in follicular hyperplasia) 4) Monoclonality (follicular hyperplasia is polyclonal)
What is mantle cell lymphoma?
Neoplastic proliferation of small B cells (CD20+) that expands the mantle zone
How does mantle cell lymphoma present clinically?
presents in late adulthood with painless lymph adenopathy
What is mantle cell lymphoma driven by?
How does t(11;14) result in mantle cell lymphoma?
1) Cydin D1 gene on chromosome 11 translocates to Ig heavy chain locus on chromosome 14. 2) Overexpression of cydin Dl promotes Gl/S transition in the cell cycle, facilitating neoplastic proliferation
What is marginal zone lymphoma?
Neoplastic proliferation of small B cells (CD 20+) that expands the marginal zone
What is marginal zone lymphoma associated with?
chronic inflammatory states such as Hashimoto thyroiditis, Sjogren syndrome, and H pylori gastritis
What is the marginal zone formed by?
post-germinal center B cells.
What is MALToma?
it is marginal zone lymphoma in mucosal sites.
How might Gastric MALToma regress
with treatment of H Pylori,
What is burkitt lymphoma?
Neoplastic proliferation of intermediate-sized B cells (CD20+);
What is butkitt lymphoma associated with?
How does burkitt lymphoma classically present?
as an extranodal mass in a child or young adult
What is specific about the african form of burkitts lymphoma?
usually involves the jaw
What does the sporadic form of Burkitts lymphoma usually involve?
What is Burkitt lymphoma driven by?
Driven by translocations of c-myc (chromosome 8)
What is the most common translocation for Burkitts lymphoma?
t(8;14) is most common,
In Burkitts lymphoma what does t(8:14) result in?
translocation of c-myc to the Ig heavy chain locus on chromosome 14.
What does overexpression of c-myc oncogene do?
promotes cell growth
How is Burkitts lymphoma characterized?
by high mitotic index and 'starry-sky' appearance on microscopy
What is diffuse large B-cell lymphoma?
Neoplastic proliferation of large B cells (CD20+) that grow diffusely in sheets
What is the most common form of non-hodgkins lymphoma?
Diffuse large B-cell lymphoma
Describe diffuse large B-Cell lymphoma clinically?
Clinically aggressive (high-grade)
How does diffuse large B-cell lymphoma arise?
either sporadically or from transformation of a low-grade lymphoma (e.g., follicular lymphoma)
How does diffuse large B-cell lymphoma present?
Presents in late adulthood as an enlarging lymph node or an extranodal mass
What is Hodgkins Lymphoma?
Neoplastic proliferation of Reed-Slernberg (RS) cells,
What are Reed-Slernberg cells?
large B cells with multilobed nuclei and prominent nucleoli ('owl-eyed nuclei');
Hodgkins lymphoma is classically positive for what?
CD15 and CD30
What do RS cells secrete?
What are the symptoms for HL
Occasionally results in 'B' symptoms (fever, chills, and night sweats)
In HL what do the RS cells attract?
reactive lymphocytes, plasma cells, macrophages, and eosinophils
What may the RS cells in HL lead to?
What makes up a bulk of the tumor and form the basis for classification of HL?
Reactive inflammatory cells
What are the subtypes of reactive inflammatory cells in HL?
Include 1. Nodular sclerosis 2. Lymphocyte-rich 3. Mixed cellularity 4. Lymphocyte-depleted
What is the most common subtype of HL?
Nodular sclerosis (70% of all cases),
What is the classic presentation for nodular sclerosis?
it is an enlarging cervical or mediastinal lymph node in a young adult, usually female
Dsecribe the lymph node in nodular sclerosis?
It is divided by bands of sclerosis; RS cells are present in lake-like spaces (lacunar cells),
What are lacunar cells?
Lake like spaces in the lymph node where the RS cells are present
What type of HL has the best prognosis of all types?
In HL mixed cellularity is often associated with what?
abundant eosinophils (RS cells produce IL-5).
What is the most aggressive HL type and in whom is it usually seen?
Lymphocyte-depleted is the most aggressive of all types; usually seen in the elderly and HIV-positive individuals
What are the plasma cell disorders?
Dyscrasias: 1) multiple myeloma 2) MGUS 3) Waldenstrom Macroglobulinemia
What is multiple myeloma?
Malignant proliferation of plasma cells in the bone marrow
Whis the most common primary malignancy of bone?
What is the most common malignant lesion of bone overall?
In multiple myeloma what is usually present?
High serum IL-6 is sometimes present; stimulates plasma cell growth and immunoglobulin production
What are the clinical features for multiple myeloma?
1) Bone pain with hypercalcemia 2) Elevated serum protein 3) increased risk of infection 4) Rouleaux formation of RBC’s on blood smears 5) Primary AL amyloidosis 6) Proteinuria
Why is there bone pain with hypercalcemia in multiple myeloma?
Neoplastic plasma cells activate the RANK receptor on osteoclasts, leading to bone destruction.
With multiple myeloma what might you see on x-ray?
Lytic, 'punched-out' skeletal lesions are seen on x-ray, especially in the vertebrae and skull; increased risk for fracture
Why is there elevated serum protein in multiple myeloma?
Neoplastic plasma cells produce immunoglobulin;
In multiple myeloma, what is seen on electrophoresis?
M spike is present on serum protein electrophoresis (SPEP), most commonly due to monoclonal IgG or IgA
In multiple myeloma why is there increased risk of infection?
Monoclonal antibody lacks antigenic diversity
What is the most common cause of death in multiple myeloma?
Why is there rouleaux formation of RBCs on blood smear?
increased serum protein decreases charge between RBCs
Why is there primary AL amyloidosis in multiple myeloma?
Free light chains circulate in serum and deposit in tissues.
Why is there proteinuria in multiple myeloma? What does this increase the risk for?
Free light chain is excreted in the urine as Bence Jones protein; deposition in kidney tubules leads to risk for renal failure (myeloma kidney).
What is monoclonalgammopathy of undetermined significance?
Increased serum protein with M spike on SPEP; other features of multiple myeloma are absent (no lytic bone lesions, hypercalcemia, AL amyloid, or Bence Jones proteinuria)
MGUS is common in what group of people?
elderly (seen in 5% of 70-year-old individuals);
What are the odds of a patient with MGUS developing multiple myeloma?
1% of patients with MGUS develop multiple myeloma each year.
What is Waldenstrom macroglobulinemia?
B-cell lymphoma with monoclonal IgM production
What are the clinical features for waldenstrom macroglobulinemia?
1) Generalized lymphadenopathy, lytic bone lesions are absent 2) Increased serum protein with M spike (comprised of IgM) 3) Visual and neurologic deficits (e.g., retinal hemorrhage or stroke) IgM (large pentamer) causes serum hyperviscosity. 4) Bleeding
Why is there bleeding in waldenstrom macroglobulinemia?
Viscous serum results in defective platelet aggregation
What are the complications for waldenstrom macroglobulinemia treated with?
plasmapheresis, which removes IgM from the serum
What are langerhans cells?
specialized dendritic cells found predominantly in the skin.
What are langerhans cells derived from?
bone marrow monocytes
What do langerhans cells present?
Present antigen to naive T cells
What is langerhans cell histiocytosis?
it is a neoplastic proliferation of Langerhans cells
What is seen on electron microscopy in langerhan cell histiocytosis?
Characteristic Birbeck (tennis racket) granules are seen on electron microscopy;
What is langerhan cell histiocytosis immunochemistry?
cells are CDla+ and S100+
What is Letterer-Siwe disease?
Malignant proliferation of Langerhans cells
What is the classic presentation of Letterer-Siwe?
it is a skin rash and cystic skeletal defects in an infant (< 2 years old).
Can Letterer-Siwe be fatal?
Multiple organs may be involved; rapidly fatal
What is eosinophilic granuloma?
Benign proliferation of Langerhans cells in bone
What is the classic presentation for eosinophilic granuloma?
it is a pathologic fracture in an adolescent; skin is not involved
What does biopsy of eosinophilic granuloma show?
Langerhans cells with mixed inflammatory cells, including numerous eosinophils
What is Hand-Schuller-Christian disease?
Malignant proliferation of Langerhans cells