Ch 6 Pathoma WBC Disorders Flashcards
Hematopoiesis occurs via a stepwise maturation of CD__ hematopoietic stem cells. From the stem cell, they can become either __ stem cells or __ stem cells.
34+; myeloid; lymphoid
____ stem cells give rise to erythroblasts, myeloblasts, monoblasts, and megakaryoblasts.
Myeloid
____ stem cells give rise to B lymphoblast and T lymphoblast
lymphoid
____ give rise to neutrophils, basophils, and eosinophils.
Myeloblast
A normal WBC count is ___ K/microL. A low WBC is less than ___ and called ___. A high WBC count is greater than ___ and called ____. A low or high WBC count is usually due to a decrease or increase in ONE particular cell lineage
5-10; 5; leukopenia; 10; leukocytosis
Name the 2 main causes of neutropenia and the 2 tx.
drug toxicity (e.g. chemo with alkylating agents - cause damage to stem cells); severe infection (e.g. gram negative sepsis - increased mvmc of neutrophils into tissues results in decreased circulating neutrophils); GM-CSF or G-CSF boost granulocyte production
Name 4 main causes of lymphopenia.
1) Immunodeficiency (eg DiGeorge’s or HIV); 2) high cortisol state (exogenous corticosteroids or Cushings - induce apoptosis of lymphocytes); 3) autoimmune destruction (e.g. SLE produces ABs against blood); 4) whole body radiation (lymphocytes are highly sensitive to radiation - its the earliest change after WBodRT)
Name the 3 major causes of neutrophilic leukocytosis.
Bacterial infection; tissue necrosis; high cortisol state (all 3 induce release of marginated pool (cortisol impairs leukocyte adhesion) (1st two also induce bone marrow neutrophils including immature forms (left shift)
Bacterial infection or tissue necrosis can both induce release of bone marrow ___, including immature forms (right/left shift). Immature cells are characterized by decreased ___ (CD__)
neutrophils; left; Fc receptors; CD16
Monocytosis is seen in ___ and ___
chronic inflammatory states (e.g. autoimmune and infectious); malignancy
Eosinophilia is caused by allergic reactions (type __ hypersensitivity), ___ infections, and this malignancy (due to increased IL-__). Eosinophilia is driven by increased ____ factor.
I; parasitic; Hodgkin lymphoma (mixed cellularity type); IL5; eosiniphil chemotactic
Basophilia is classically seen in ____.
Chronic myeloid leukemia (CML)
Name 2 causes of lymphocytic leukocytosis
Viral infections (T lymphocytes undergo hyperplasia in response to virally infected cells); bordetella pertussis (*exception since it’s a bacteria)
Bordella pertussis (bacteria) infection causes lymphocytic leukocytosis (usually bacteria cause ___ leukocytosis), because it produces ___, which blocks circulating lymphocytes from leaving the blood to enter the ___.
neutrophilic; lymphocytosis-promoting factor; LN
Infectious mononucleosis is a __ infection that results in ___ leukocytosis comprised of ____. ___ is a less common cause. It is transmitted by ___, and classically infects ___.
EBV; lymphocytic; reactive CD8+ t cells; CMV; saliva; teenagers
EBV primarily infects these 3 places
oropharynx (resulting in pharyngitis); liver (resulting in hepatitis w/hepatomegaly and elevated liver enzymes); B cells
The CD8+ T cell response in infectious mononucleosis leads to these 3 clinical/lab findings (and why)
1) Generalized lymphadenopathy (due to T cell hyperplasia in LN paracortex); 2) splenomegaly (due to T cell hyperplasia in the periarterial lymphatic sheath (PALS)); 3) high WBC count with atypical lymphocytes (reactive CD8+ t cells)
The CD8+ T cell response causes splenomegaly due to T cell hyperplasia in the ____ of the spleen, and causes generalized LAD due to t-cell hyperplasia in the lymph node ___.
periarterial lymphatic sheath; paracortex (outer layer is cortex, middle is paracortex, inner is medulla)
In infectious mononucleosis, the ___ test is used for screening. It detects ___ that cross react with horse or sheep red blood cells, and usually turns positive within 1 hour/day/week after infection. A negative test suggests __ as possible cause of IM. Definitive dx is ___.
monospot; IgM antibodies (heterophile antibodies); week; CMV; serologic testing for EBV viral capsid antigen
Name the 3 complications of infectious mononucleosis.
1) splenic rupture (advised to avoid contact sports); 2) rash if exposed to ampicillin; 3) dormancy of virus in B cell can lead to recurrence and/or B cell lymphoma (esp if pt is immunodeficient (HIV))
Acute leukemia is a neoplastic proliferation of ___, defined as the accumulation of greater than __% ___ in the bone marrow.
blasts; 20; blasts
In acute leukemia, increased blasts “crowd out” normal hematopoiesis, resulting in “acute” presentation with these 3 things (and symptoms)
anemia = fatigue; thrombocytopenia = bleeding; neutropenia = infxn
In acute leukemia, blasts usually enter the blood stream, resulting in a high ___ count. Blasts are large/small, immature/mature cells, often with ___. Acute leukemia is subdivided into ___ or ___ based on the phenotype of the blasts.
WBC; large; immature; punched out nucleoli; acute lymphoblastic leukemia (ALL); acute myelogenous leukemia (AML)
____ is a neoplastic accumulation of lymphoblasts (greater than __%) in the bone marrow. Lymphoblasts have positive nuclear staining for ___, a DNA polymerase (found in the ___). It is absent in ___ and ___.
Acute lymphoblastic leukemia; 20; TdT; nucleus; myeloid blasts; mature lymphocytes
Acute lymphoblastic leukemia most commonly arises in ___, and is associated with ____. It can be sub-classified into ___ and ___ based on ___ (which one is more common?).
children; Down syndrome (after age of 5); B-ALL; T-ALL; surface markers; B-ALL is more common
Which leukemia is seen in down syndrome before age of 5 and which one after?
Acute megakaryoblastic leukemia (under the umbrella of acute myeloid leukemia); after 5 is acute lymphoblastic leukemia
B-ALL is characterized by lymphoblasts (__+), that express these 3 markers. There is excellent/poor response to chemo, and it requires prophyalxis to __ and __.
TdT; CD10, CD19, and CD20; excellent; scrotum; CSF
There are 2 common cytogenic abnormalities in B-ALL, ___ has a good prognosis and is more commonly seen in children; __ has a poor prognosis and is more commonly seen in adults.
t(12;21); t(9;22) (Philadelphia+ ALL)
T-ALL is characterized by lymphoblasts (__+) that express markers ___. The blasts do not express ___. T-ALL usually presents in ___ as a ___ mass (and is therefore called acute lymphoblastic __, since the malignant cell form a mass)
TdT; CD2 to CD8; CD10; teenagers; mediastinal (thymic); lymphoma
Acute myeloid leukemia is a neoplastic proliferation of ___ (greater than __%) in the bone marrow. Myeloblasts are usually characterized by positive cytoplasmic staining for ___, which can form crystal aggregates called ___.
myeloid cells; 20; myeloperoxidase (MPO); Auer rods
A ___ shift, is a shift to a more immature cell in the maturation process
left
Acute myeloid leukemia most commonly arises in ___. Subclassifcation is based on ___ abnormalities, ___ of immature myeloid cells, and ___ markers.
older adults (50-60 yrs); cytogenetic; lineage; surface
Name 3 common subtypes of acute myeloid leukemia
acute promyelocytic leukemia (APL); acute monocytic leukemia; acute megakaryoblastic leukemia
Acute promyelocytic leukemia (APL) is characterized by a ___ translocation, which involves disruption of the ___ (move it from chromosome __ to __). This disruption blocks ___ and ___ accumulate.
t(15;17); retinoic acid receptor (RAR); 17; 15; maturation; promyelocytes (blasts)
In acute promyelocytic leukemia, abnormal promyelocytes contain numerous ___ that increase the risk for ___. Treatment is with ___ (a vitamin A derivative), which binds the altered retinoid acid receptor and causes the blasts to ___.
primary granules (Auer rods); DIC; all-trans-retinoic acid (ATRA); mature/differentiate (and eventually die)
____ is a proliferation of mono blasts (usually lack ___). The blasts classically infiltrate ___.
Acute monocytic leukemia; MPO; gums
___ is a proliferation of megakaryoblasts (lack ___); it is associated with ____.
acute megakaryoblastic leukemia; MPO (since plts don’t need to do oxygen dependent killing); Down syndrome (before age 5)
Acute myeloid leukemia may arise from pre-existing ___ (___ syndromes), especially with prior exposure to ___ or ___.
dysplasia; myelodysplastic; alkylating agents; radiotherapy
Myelodysplastic syndromes usually present with ___, ___ bone marrow, abnormal ___ of cells, and increased ___ (less than __%). Most patients die from __ or __, though some progress to ___.
cytopenias, hypercellular (though its hyper cellular, its being formed poorly so cells don’t get out into blood); maturation; blasts; 20% (greater than would be leukemia); infection or bleeding; acute leukemia
Chronic leukemia is a neoplastic proliferation of ___. It is characterized by a high/low WBC count. Usually insidious (slow) in onset and seen in ___.
mature circulating lymphocytes; high; older adults
What is the most common leukemia overall?
Chronic lymphocytic leukemia (naive B cells)
___ is a neoplastic proliferation of naive B cells that co-express CD__ and CD__.
Chronic lymphocytic leukemia; CD5 and CD20
Chronic lymphocytic leukemia (CLL), increased ___ and ___ are seen on blood smear. Involvement of lymph nodes leads to generalized ___, and is called ___.
lymphocytes; smudge cells; lymphadenopathy; small lymphocytic lymphoma
(naive B cell proliferation)
Name 3 complications of chronic lymphocytic leukemia, and what is the most common cause of death in CLL?
1) hypogammaglobulinemia (B cells are not turning in to plasma cells to make Ig; infxn is the most common cause of death); 2) autoimmune hemolytic anemia (if cell manages to make Ig, it attacks RBCs); 3) transformation to diffuse large B cell lymphoma (Richter transformation - marked by enlarging LN or spleen)
The transformation of chronic lymphocytic leukemia to diffuse large B cell lymphoma is called the ____. It is marked clinically by an enlarging ___ or ___.
Richter transformation; LN; spleen
Hairy cell leukemia is a neoplastic proliferation of ___ characterized by ____. Cells are positive for ____. There is an excellent response to ____, an adenosine deaminase inhibitor, which causes adenosine accumulation to toxic levels in neoplastic ____.
mature B cells; hairy cytoplasmic processes; tartrate-resistant acid phosphatase (TRAP); 2-CDA (cladribine); B cells
Name the 3 clinical features of hairy cell leukemia
1) splenomegaly (accumulation of hairy cells in RED pulp); 2) dry tap on BMA (marrow fibrosis); 3) LAD is absent
(TRAP - TRAP+ cells, trapped in red pulp and marrow, so can’t get to LN’s to cause LAD)
Name the Chronic Leukemia which involves neoplastic proliferation of naive B cells, mature CD4+ T cells, and mature B cells.
1) Chronic lymphocytic leukemia
2) Adult T-cell leukemia/lymphoma and mycosis fungoides
3) Hairy cell leukemia
___ is a neoplastic proliferation of mature CD4+ T cells associated with HTLV-1. It is most commonly seen in these 2 regions.
Adult T-cell leukemia/lymphoma (ATLL); Japan, Caribbean
Name the 3 clinical features of Adult T cell leukemia/lymphoma (ATLL)
Rash (CD4+T cells like to go to skin!); generalized LAD with hepatosplenomegaly; lytic (punched out) bone lesions with hypercalcemia (when you see this, think multiple myeloma, but the rash helps you know it’s ATLL)
Mycosis fungoides is a neoplastic proliferation of ____ that infiltrate the skin, producing localized skin rash, plaques, and nodules. Aggregates of neoplastic cells in the epidermis are called ____.
mature CD4+ t cells; Pautrier microabscesses
In mycosis fungoides, cells can spread to involve the blood, producing ___ syndrome. Characteristic lymphocytes with ___ nuclei (__ cells) are seen on blood smear.
Sezary; cerebriform; Sezary
mature CD4+ t cell proliferation
Myeloproliferative disorders are neoplastic proliferations of ___ cells of ___ lineage. It is a disease of early/late childhood/adulthood (avg age is ___). Cells of all ___ lineages are increased, and each disorder is characterized based on the dominant __ cell produced.
mature; myeloid; late adulthood; 50-60; myeloid; myeloid
high WBC count with hyper cellular bone marrow
Myeloid stem cells give rise to these 4 cell types
erythroblasts, myeloblasts (granulocytes), monoblasts, megakaryoblasts
Name 3 complications of myeloproliferative disorders
1) increased risk for hyperuricemia/gout due to high turnover of cells; 2) progression to marrow fibrosis; 3) transformation to acute leukemia
Chronic myeloid leukemia (CML) is a neoplastic proliferation of ___ cells, especially ___ and their precursors. ___ are characteristically increased. It is driven by ___ translocation, which generates a ___ protein. First line tx is ___, a ___ inhibitor.
mature myeloid; granulocytes; basophils; t(9;22) (philadelphia chromosome); BCR-ABL fusion; imatinib; tyrosine kinase
In chronic myeloid leukemia, ___ is common. Enlarging ___ suggests progression to accelerated phase of disease. Transformation to ___ usually follows shortly. CML can transform to ___ (2/3 of cases) or ___ (1/3 of cases) since mutation is in a ____ cell.
splenomegaly; spleen; acute leukemia; AML; ALL; pluripotent stem
CML can be distinguished from a leukemia reaction (reactive neutrophilic leukocytosis) by these 3 things.
negative leukocyte alkaline phosphatase (LAP) stain (+ in leukemoid rxn); increased basophils (absent); t(9;22) (absent)
___ is a neoplastic proliferation of mature myeloid cells, especially RBCs (___ and ___ are also increased). Associated with a ___ mutation. Tx is ___; 2nd line tx is ___. W/o tx death usually occurs within one day/month/year.
Polycythemia Vera (PV); granulocytes; platelets; JAK2 kinase; phlebotomy; hydroxyurea (suppress BM); year
Clinical symptoms of PV are mostly due to hyper/hypo-viscosity of blood. Name 4.
1) blurry vision/headache; 2) inc risk of venous thrombosis (Budd chiari - hepatic vein - infarction of liver; portal vein, dural sinus); 3) flushed face due to congestion (plethora); 4) itching, esp after bathing (due to inc mast cells releasing histamine)
PV must be distinguished from reactive polycythemia. In PV, EPO levels are H/N/L and SaO2 is H/N/L. In reactive polycythemia due to lung disease or high altitude, SaO2 is H/N/L and EPO is H/N/L. In reactive due to ectopic EPO production from this cancer, EPO and SaO2 are H/N/L.
low EPO; normal SaO2; low SaO2; high EPO; renal cell carcinoma; high EPO; normal SaO2
Name 4 myeloproliferative disorders and the dominant myeloid cell produced
CML (granulocytes, esp basophils); PV (RBCs); ET (platelets); myelofibrosis (megakaryocytes)
Which 3 disorders are associated with a JAK2 kinase mutation?
PV, ET, and myelofibrosis (seen in 50% of cases)
Essential thrombocythemia (ET) is a neoplastic proliferation of ___ cells, especially ___. Also see increased __ and ___. Associated with a __ mutation.
mature myeloid; platelets; RBCs; granulocytes; JAK2 kinase
Symptoms of essential thrombocythemia are related to an increased risk of ___ and/or ___. It commonly/rarely progresses to marrow fibrosis or acute leukemia. There is no significant risk for ___ or ___.
bleeding; thrombosis (depends if plts are functioning or not); rarely; hyperuricemia; gout (no nuclear material being turned over)
_____ is a neoplastic proliferation of mature myeloid cells, especially megakaryocytes. Associated with a ___ mutation (50% of cases). Megakaryocytic produce excess ___ causing ___.
Myelofibrosis; JAK2 kinase; platelet derived growth factor (PDGF); marrow fibrosis
Name 3 clinical features of myelofibrosis
1) splenomegaly due to extramedullary hematopoiesis (BM is all fibrosed); 2) leukoertyoroblastic smear (tear drop RBCs, nucleated RBCs, immature granulocytes); 3) inc risk of infxn, thrombosis, and bleeding (spleen can’t keep up with producing cells needed)
Tear drop RBCs are seen in which disorder and why?
myelofibrosis; fibrosed BM can still produce some RBCs, but they are stretched and squeezed when trying to get out from all the fibrosis
Lymphadenopathy refers to ___. Painful LAD is usually seen in lymph nodes draining a region of ___. Painless LAD can be seen with ___, ___, or ___.
enlarged lymph nodes; acute infection (acute lymphadenitis); chronic inflammation (chronic lymphadenitis); metastatic carcinoma; lymphoma
In inflammation, lymph node enlargement is due to ___ of particular regions of the LN. Follicular hyperplasia (__ cell region), is seen with ___ and early stages of ___. Paracortex hyperplasia (__ cell region), is seen with ___. Hyperplasia of ___ is seen in LN’s that are draining a tissue with cancer.
hyperplasia; B-cell; rheumatoid arthritis; HIV infxn (follicular cells can be CD4+); t cell; viral infxns (e.g. infectious mononucleosis); sinus histiocytes (found in medulla)
Which types of cells are found in the cortex, paracortex, and medulla of the LN?
b-cells; t-cells; reticular cells and macrophages (aka sinus histiocytes)
Lymphoma is a neoplastic proliferation of ___ cells that forms a ___. May arise in a __ or in __ tissue. Divided into ___ (60%) and ___ (40%).
lymphoid cells; mass; lymph node; extra nodal tissue; non-Hodgkin; Hodgkin
Non-hodgkin lymphoma can be classified based on cell type (__ vs __), cell size (__, __, or __), pattern of cell growth (__ or __), expression of surface markers (help determine __ or __), and cytogenetic translocations.
b-cell vs t-cell; small, intermediate, large; diffuse sheets or follicular; b-cell or t-cell
Of the Non-hodgkin lymphoma, name the 4 small B cells, the 1 intermediate B cell, and the 1 large B cell
1) follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, small lymphocytic lymphoma (when CLL moves in to LNs); 2) Burkitt lymphoma; 3) diffuse large b-cell lymphoma
Follicular lymphoma is a neoplastic proliferation of ___ cells (CD__) that form ___-like nodules. Present in early/late childhood/adulthood with painful/painless LAD. Treatment is reserved for symptomatic pts and involves low dose ___ or ___ (anti-CD__ antibody)
small B cells; 20+; follicle; late adulthood; painless; chemotherapy; rituximab; 20
___ is driven by t(14;18). BCL2 on chromosome __ translocates to the Ig heavy chain locus on chromosome __, which results in overexpression of ___, which inhibits ___.
Follicular lymphoma; 18; 14; Bcl2; apoptosis
An important complication of follicular lymphoma is progression to ___, which presents as an enlarging __.
diffuse large B cell lymphoma; lymph node
Follicular lymphoma is distinguished from reactive follicular hyperplasia (due to infxn) by these 4 things.
1) disruption of normal LN architecture (follicles move deep into LN); 2) lack of tangible body macrophages in germinal centers (normally see them cause they eat up the apoptosing failed hyper mutated b cells); 3) Bcl2 expression in follicles (normally don’t want Bcl2 so cells can apoptose); 4) monoclonality (20:1 kappa lambda ratio; normal is 3:1)
In a normal follicle of a LN, b-cells challenged by antigen come in and undergo ___ in a ___. If they can then bind antigen they leave to participate in fight. If they fail, they ___, which they cannot do if __ is over expressed as in follicular lymphoma.
somatic hypermutation (seen in class switching); germinal center; apoptose; Bcl2
Mantle cell lymphoma is a neoplastic proliferation of __ cells (CD__), that expands the mantle zone (immediately adjacent to the ___). Presents in early/late adulthood/childhood with painful/painless LAD.
small B cells; 20+; follicle; late adulthood; painless
Mantle cell lymphoma driven by a __ translocation, in which the ___ gene on chromosome 11 translocates to the ___ locus on chromosome 14. Overexpression of __ promotes __ transition in the cell cycle.
t(11;14); cyclin D1; Ig heavy chain; cyclin D1; G1/S
Name the translocations and what is overexpressed seen with follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and burkitt lymphoma
t(14;18) - Bcl2 (cell does not apoptose); t(11;14) - Cyclin D1 (cell goes from G1 to S); none!; t(8;14) - c-myc (nuclear regulator that promotes cell growth)
Marginal zone lymphoma is a neoplastic proliferation of ___ cells (CD__) that expands the marginal zone. It is associated with chronic inflammatory states such as these 3. The marginal zone is formed by ___ B cells
small B cells; 20+; Hashimoto thyroiditis, Sjogren syndrome, H pylori gastritis; post-germinal center (B cells that have left the germinal center)
MALToma is ___ lymphoma in __ sites. Gastric MALToma may regress with tx of ___.
marginal zone; mucosal; H pylori
Burkitt lymphoma is a neoplastic proliferation of ___ cells (CD__); associated with ___. It classically presents as a ___ mass in children/young adult/elderly adult. __ form usually involves the jaw, and __ form usually involves the abdomen.
intermediate sized b cells; 20+; EBV; extra nodal; children and young adults (unique to the NHLs); African; sporadic
Burkitt lymphoma is driven by a __ translocation, in which __ on chromosome __ gets translocated to __ locus on chromosome __. Overexpression of ___ oncogene promotes cell growth. Burkitt lymphoma is characterized by a H/N/L mitotic index and ‘____’ appearance on microscopy.
t(8;14); c-myc; 8; Ig heavy chain locus; 14; c-myc (it’s a nuclear regulator that promotes growth); low; starry-sky
What is the most common form of non-hodgkin lymphoma?
Diffuse large b-cell lymphoma
___ is a neoplastic proliferation of large B cells (CD__) that grow diffusely in sheets. It is clinically aggressive (low/high grade). It arises in these 2 ways. It presents in early/late adulthood/childhood as an enlarging ___ or an ___ mass.
Diffuse large b-cell lymphoma (DLBCL); 20+; high; sporadically or transformation from a low-grade lymphoma (e.g. follicular); late adulthood; LN; extra nodal
Hodgkin lymphoma is a neoplastic proliferation of ___ cells, which are large B cells with ___ nuclei and prominent ___ (‘___’ nuclei). They are classically positive for CD__ and CD__ and NOT positive for CD__.
Reed-Sternberg (RS); multilobed; nucleoli; owl-eyed; 15; 30; 20.
Reed sternberg cells are positive for CD__ and __, and secrete ___. This can result in __ symptoms (such as these 4). It also attracts these 4 cells. And can lead to ___.
15; 30; cytokines; B symptoms; fever, chills, weight loss, night sweats; reactive lymphocytes, plasma cells, macrophages, eosinophils (reactive inflammatory cells); fibrosis
In Hodgkin lymphoma, ___ makes up a bulk of the tumor and form the basis for classification. Name the 4 subtypes and the most common type
reactive inflammatory cells; nodular sclerosis (most common - 70%); lymphocyte rich; mixed cellularity; lymphocyte depleted
Nodular sclerosis (a subtype of HL) classically presents as an enlarging ___ or ___ in a young/old adult/child female/male. The lymph node is divided by bands of ___. __ cells are present in __-like spaces (__ cells)
cervical or mediastinal LN; young adult female; sclerosis; Reed-sternberg; lake; lacunar
Which subtype of Hodgkin lymphoma has the best prognosis, the worst prognosis, is associated with abundant eosinophils (due to RS cells producing __)? Which one is usually seen in the elderly and HIV positive individuals?
lymphocyte-rich; lymphocyte-depleted; mixed cellularity; IL-5; lymphocyte-depleted
In which, NHL vs HL, is staging less important? Which one has more constitutional symptoms? Which one is strongly associated with EBV? Which one has a leukemic phase? Which one is rarely extra nodal? Which one has the better prognosis?
NHL; HL has B symptoms; HL; NHL; HL (usually single group of nodes); HL
Name 3 plasma cell disorders (aka ___).
dyscrasias; 1) multiple myeloma; 2) monoclonal gammopathy of undetermined significans (MGUS); 3) waldenstrom macroglobulinemia
What is the most common primary malignancy of bone?
multiple myeloma (metastatic cancer, carcinomas specifically, is the most common malignant lesion of bone overall)
Multiple myeloma is a malignant proliferation of ___ cells in the ___. High serum __ may be present, which stimulates __ cell growth and __ production.
plasma; bone marrow; IL-6; plasma; immunoglobulin
Name the 6 clinical features of multiple myeloma and the most common cause of death.
1) bone pain w/hypercalcemia; 2) elevated serum protein (Ig); 3) inc risk of infxn (monoclonal ABs only- most common cause of death); 4) Rouleaux formation of RBCs on blood smear (due to inc. protein, which decreases charge btwn RBCs); 5) primary AL amyloidosis (excess free light chains deposit); 6) proteinuria (free light chains)
In multiple myeloma, you see bone pain with hypercalcemia, because neoplastic plasma cells activate the ___ on osteoclasts, leading to __ skeletal lesions seen on x-ray, especially in these two bones. You therefore have an increased risk for ___.
RANK receptor; lytic (punched out); vertebrae and skull; fracture
In multiple myeloma, there is elevated serum protein since the neoplastic plasma cells produce ___. A __ is present on serum protein electrophoresis (SPEP), most commonly due to ___ (and a little ___)
immunoglobulin; M-spike; IgG; IgA
In multiple myeloma, you have proteinuria because ___ is excreted in the urine as ___ protein. If it deposits in the kidney tubules, it leads to risk for ___ (___ kidney)
free light chain; Bence Jones; renal failure; myeloma
In monoclonal gammopathy of undetermined significance (MGUS), you see increased ___ with ___ on SPEP. Other features of multiple myeloma are absent (name 4)
serum protein; M-spike; no lytic bone lesions, hypercalcemia, AL amyloid, or Bence Jones protein
MGUS is common in ___ (seen in 5% of __ yo individuals); __% of patients develop multiple myeloma each year. Acute complications are treated with ___.
elderly; 70; 1; plasmapheresis (removes IgM from the serum)
Waldenstrom macroglobulinemia is a __-cell lymphoma with ____ production. Name 4 clinical features
B; IgM; 1) generalized LAD (no lytic bone lesions); 2) increased serum protein with M spike (comprised of IgM); 3) visual and neurologic deficits (retinal hemorrhage or stroke) due to IgM caused serum hyper viscosity; 4) bleeding (viscous serum results in defective plt aggregation)
In which malignancy do you see an IgG M-spike and in which one do you see an IgM M-spike?
multiple myeloma; waldenstrom macroglobulinemia
Name 3 langerhans cell histiocytoses (and the pneumonic trick)
Letterer-Siwe disease; Eosinophilic granuloma; Hand-Schuller-Christian disease
(if named after someone, it’s malignant and causes skin rash; if 2 people’s names it’s in children less than 2, and if 3 names, children greater than 3)
Langerhans cells are specialized ___ cells found predominantly in the ___. Derived from bone marrow ___. They present antigen to ___.
dendritic; skin; monocytes; naive T cells
In Langerhans cell histiocytosis, characteristic ___ are seen on electron microscopy. The cells are __+ and __+ by IHC
Birbeck granules (tennis racket); CD1a; S100
___ disease is a malignant proliferation of Langerhans cells that presents with skin rash, cystic skeletal defects, in an infant less than 2 years old. Multiple organs may be involved, and it is rapidly curable/fatal.
Letterer-Siwe disease; fatal
___ is a benign proliferation of Langerhans cells in bone, that classically presents with pathologic fracture in an adolescent. Skin is not involved. Bx shows langerhans cells with mixed inflammatory cells, including numerous ___.
Eosinophilic granuloma; eosinophils
____ is a malignant proliferation of Langerhans cells that classically presents with a scalp rash, lytic skull defects, diabetes insipidus, and exopthalmos in a child (greater than 3)
Hand-Schuller-Christian disease
