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31. Skin Blood Lymph Exam 1 > 4. WBC Pathology > Flashcards

4. WBC Pathology Flashcards

1
Q

monocytes, megakaryocytes, granulocytes and erythrocytes MMEG all come from the same stem cell lineage- myeloid (MPO positive), where do B T NK cell derive from?

A

Lymphoid progenitor cell - NOTE NK cells have granules

TdT positive

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2
Q

Adult red bone marrow is ACTIVE meaning this is where you want to get a BM biopsy from, most specifically what region? Note: adult yellow bone marrow is mainly in the long bones and it is NOT active

A

BM bx in PSIS (ribs, skull, shoulder, clavicle hands, feet all active and pelvis)

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3
Q

Monocytes and granulocytes are from the same lineage (myeloid), granulocytes include eosinophils, basophils, and neutrophils, and then there are lymphocytes, all make up the white blood cells, normal WBC is around what?

A

4.8-10.8 x10^3
granulocytes make up 40-70% of WBC
RBC should have 5million (5x10^6)
platelets should be 150 x10^3 (150000)

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4
Q

Monocytes and granulocytes are from the same lineage (myeloid), granulocytes include eosinophils, basophils, and neutrophils, and then there are lymphocytes, all make up the white blood cells, normal WBC is around what?

A

4.8-10.8 x10^3
granulocytes make up 40-70% of WBC
RBC should have 5million (5x10^6)
platelets should be 150 x10^3 (150000)

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5
Q

Platelets are usually 150-450000, many produced each day, platelet production can be increased 10fold in response to need, lifespan is 7-10 days. RBC progenitor cells are regulated by what, which is mainly produced by peritubular capillary lining cells of the kidneys (90%) and liver, regulation of this is via O2 monitoring, so when Hemoglobin is above 15 it decreases its release and when Hgb is below 10 it increases its release from kidney to make more RBC?

A

Erythropoietin

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6
Q

An immature RBC is known as what, which contain remnant endoplasmic reticulum, and ribosomes (rER) that forms a reticulum (net) within RBC cytoplasm, they are 30% larger than RBC and circulate for 2-3 days before all remnants are extruded?

A

Reticulocytes

spleens degrade RBC after 120 days

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7
Q

What is aka ‘blasts’ are processes that distort the marrow architecture such as deposition of metastatic cancer or granulomatous disorders can cause the abnormal release of immature precursors into the peripheral blood?

A

Leukoerythroblastosis

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8
Q

Circulating lymphocytes in peripheral blood in adults contain 80% t cells (CD4>CD8), along with an equal presence of B and NK cells, Bcells last hours to days while T cells last days to years, marker for B cells is CD 19/20, and marker for NK cells is CD56 or?

A

16, MC is 56

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9
Q

When blood is centrifuged, plasma is on top, buffy coat in the middle and red blood cells at the bottom, plasma consists of mainly water, and proteins and nutrients (55% of total blood volume), RBC is mainly RBC and what is within the buffy coat, making up 45% of the total blood volume (with RBC)?

A

White blood cells and platelets

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10
Q

Plasma is fluid accelular portion of blood with mainly water (90%) and molecules such as proteins, organic and inorganic, to maintain plasma in drawn blood, anticoagulation must be added, what is it called when there is clear yellow liquid remain after blood has been allowed to clot, aka plasma with diminished fibrinogen and other clotting factors?

A

SERUM

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11
Q

Plasma is fluid accelular portion of blood with mainly water (90%) and molecules such as proteins, organic and inorganic, to maintain plasma in drawn blood, anticoagulation must be added, what is it called when there is clear yellow liquid remain after blood has been allowed to clot, aka plasma with diminished fibrinogen and other clotting factors?

A

SERUM

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12
Q

What is abnormally low WBC, often as a result of reduced neutrophils, so it is usually a neutropenia or ganulocytopenia, lymphopenia if present is due to HIV, steroids, AI do, malnutrition, acute viral infections?

A

Leukopenia (def of leukocytes)

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13
Q

Agranulocytosis is clinically significant reduction in neutrophils, pts have increased susceptibility to bacterial and fungal infections, it is MC due to inadequate granulopoiesis, such as suppression of HSCs (aplastic anemia) megaloblastic anemia, congenital conditions like hostmann suyndrome, and what, which is the MCC of neutropenia?

A

Drug toxicity

chloramphenicol, sulfa, chlorpromazine, thiouracil, phenylbutazone

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14
Q

INfections are a common consequence of agranulocytosis, ulcerating necrotizing lesions of the gingiva, floor of the mouth, buccal mucosa, pharynx, or elsewhere in the oral cavity are quite characteristic

A

meow

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15
Q

Leukocytosis is increase in number of WBCs in the blood, usually during inflam states due to infection, and if not, then due to a neoplastic disease, if a leukemoid reaction (immature granulocytes appear in blood due to infection) see elevated LAP, if leukemia see?

A

normal LAP

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16
Q

Sepsis of severe inflam disease on leukocytosis, might see changes in neutrophils, such as dohle bodies which are patches of dilated ER seen as sky blue cutoplasmic puddles in neutrophils, and what, which are coarser and darker abnormal azuorphilic neutrophilic granules due to strong response to infection?

A

Toxic granulations

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17
Q

Lymphopenia is caused by decreased number of circulating lymphocytes, di george, high cortisol state, AI destruction like SLE, and whole body radiation, elevated eosinophils is associated with allergic reactions, parasites, hodgkin, and drug reactions, and basophilic leukocytosis is RARE but present in what disease?

A

Chronic Myeloid Leukemia CML

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18
Q

What lymphadenitis can be localized, systemic and mesenteric, with large germinal centers, nodes are swollen, macrophages presents, may become necrotic, clinically affected nodes are enlarged and TENDER*, may move when abscess forms, overlying skin is red?

A

Acute lymphadenitis

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19
Q

What lymphadenitis is NONTENDER LN without inflammation or tissue damage, more likely due to cancer, common in inguinal and axillary LN, see follicular hyperplasia which is large germinal centers with dark mantle zone (naive b cells), may be due to rheumatoid arthritis, toxoplasmosis, early HIV = B cell responses?

A

Chronic Lymphadenitis

*apoptotic B cells in macrophage = Tingible Body macrophages= ALL and Burkitt Lymphoma

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20
Q

What type of hyperplasia is due to stimuli triggering the T cell mediated immune response such as EBV, T cell zones may encroach B cells follicles, hypertrophy of sinusoidal and vascular endothelial cells, may be assoc with macrophages and eosinophils?

A

Paracortical hyperplasia

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21
Q

Sinus histiocytes or what hyperplasia is increase in number of cells that line lymphatic sinusoids, NONSPECIFIC, but prominent in LN draining cancers such as carcinoma of breast= LN draining cancer- NOT metastasis?

A

Reticular Hyperplasia - macrophages/ medullary hyperplasia

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22
Q

Hemophagocytic Lymphohistiocytosis HLH is macrophage activating syndrome, reactive condition with cytopenias, due to systemic activation of macrophage and CD8 T cells, mo eat blood cell progenitors and lymphocytes causing a cytokine storm resulting in hyper/pothermia, tachy cardia, tachypnea, leukocytosis and leukopenia, appears shock like, what is the MC trigger for HLH?

A

infection- EBV
CLIN: acute febrile illness with hepatosplenomegaly, anemia, thormbocytopenia, increased ferritin IL2, LFTs, TGs, DIC– if untreated there is a grim prognosis

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23
Q

Lymphoid neoplasms are of B cell T cell and NK origin, myeloid are of early meatopoietic progenitors- evolve over time- ACute myeloid leukemia is immature progenitor cells (blasts) accumulate in BM suppressing normal hematopoeisis, myelodysplastic and chronic myeloproliferative disease is under this umbrella, histiocytoses are uncommon lesions of MO and DC such as essential thrombocytopenia and?

A

Polycythemia Vera

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24
Q

Lymphoid neoplasms are of B cell T cell and NK origin, myeloid are of early meatopoietic progenitors- evolve over time- ACute myeloid leukemia is immature progenitor cells (blasts) accumulate in BM suppressing normal hematopoeisis, myelodysplastic and chronic myeloproliferative disease is under this umbrella, histiocytoses are uncommon lesions of MO and DC such as essential thrombocytopenia and?

A

Polycythemia Vera

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25
Q

Factors influencing WBC neoplasia includes translocations (t9:22 philidelphia), inhereited genetic factors, viruses, chornic inflam, iatrogenic factors, smoking, oncogenic mutations occur most frequently in germinal center B cells during attempted antibody diversification, what is the MC abnormality seen in WBC neoplasms?

A

nonrandom chromosomal abnormalities which result in oncoproteins that protect cells from apoptosis and proto oncogenes are activated in lymphoid cells

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26
Q

Virusses such as HTLV1 = adult TLL, EBV- burkitt hodgkin, HHV8 - b cell lymphoma, and HIV and B cell lymphoma, chronic inflam causing WBC neoplasm includes H pylori and gastric b cell lymphoma, iatrogenic such as radiation and chemo can cause neoplasm, and SMOKING is most associated with what leukemia?

A

Acute Myeloid Leukemia

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27
Q

In lymhpoid neoplasms, all daughter cells derived from the malignant progenitor share the same antigen receptor gene configuration and sequence- *monoclonal is when all daughter cells express the same config and sequence synthesizing identical proteins- means cancer, what means they are immature and are reactive?

A

Polyclonal

anything monoclonal = cancer

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28
Q

Differentiation of neoplastic white cells is not typically a feature useful for the dx or determination of the prognosis of hematologic neoplasia, similarily, staging is of little utility except for which lymphoma?

A

Hodgkin Lymphoma, because starts at one LN and progresses to another
(non hodgkins spreads widely and is unpredictable)

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29
Q

Differentiation of neoplastic white cells is not typically a feature useful for the dx or determination of the prognosis of hematologic neoplasia, similarily, staging is of little utility except for which lymphoma?

A

Hodgkin Lymphoma, because starts at one LN and progresses to another- fever!
(non hodgkins spreads widely and is unpredictable)

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30
Q

What leukemia is neoplasm of immature lymphoblasts (B), seen in kids with very low platelet count***, MC leukemia of childhood, hispanics and whites most at risk, male predominance, 70% have GOF mutation in NOTCH1, majority have LOF mutations in PAX5, E2A, RBF, or a balanced t12:21 involving ETV6 and RUNX1?

A

Acute Lymphoblastic Leukemia ALL

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31
Q

Acute Lymphoblastic Leukemia ALL has hypercellular marrow packed with BLASTS that replace marrow elements, larger nuclei, high mitotic rate, starry sky due to mo ingestion of tumor cells, cells mark for CD10 antigen, lack granules in cytoplasm, MPO -, PAS+, bone pain, headache, vomiting, nerve palsies, B and T cell antibody stains are required for definitive diagnosis of ALL vs AML what is only expressed in pre-B and pre-T lymphoblasts and will be positive in ALL?

A

terminal deoxynucleotidyl transferase TdT

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32
Q

Signs and sx of Acute Lymphoblastic Leukemia ALL include fatigue, anemia, fever, infection, bleeding, bone pain, headache, vomiting nerve palsies due to meningeal spread, with aggressive chemo, 95% of children complete remission and 85% are cured, a favorable prognosis is associated with ages 2-10, low white cell count, trisomy of chr 4/7/10, presence of t12:21 ETV6/RUNX1 and?

A

hyperdiploidy

poor prog = less than 2, t9:22chr, high blast count

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33
Q

What type of Acute Lymphoblastic Leukemia ALL is associated with 3yo, present with cyclic tumors, TdT+, CD10/22/19/20 POSITIVE, PAX5 +, t9:22, tx with chemo?

A

B-ALL

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34
Q

What type of Acute Lymphoblastic Leukemia ALL presents in adolescent male teens as thymic mass (medistinal) and thymocytes, may evolve to leukemia, usually NOTCH1 GOF, TdT+ CD1/8 positive ?

A

T-ALL

T cell lymphomas/leukemias ALWAYS more aggressive than B cell

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35
Q

Although ALL and AML are gentically and immunphenotypically distinct, they are clincally similar, including abrupt onset, symptoms due to depression of marrow including fever, infection and bleeding, mass effects due to neoplastic infiltration (ALL) and CNS manifestations such as HA, vomiting, nerve palsies and meningeal spread, ALL is associatd with what kind of onset?

A

Abrupt stormy onset, bone pain, lymphadenopathy, hepatosplenomegaly, testicular enlargement

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36
Q

What leukemia is the MC of adults in the western world, morphologically, phenotypically, and genotypically indistinguishable from SLL, differ only in the degree of peripheral blood lymphocytosis (absolute WBC >5000), more common in men, age 60, translocations are rare, NOTCH1 receptor GOF mutations are a poor prognostic factor, have pathognomonic* proliferation centers- larger lymphocytes gathered in loose aggregates that contain mitotically active cells?

A

Chronic Lymphocytic leukemia CLL (SLL= small lymphocytic leukemia)

*MC genetic anomalies are deletions of 13q14.3, 11q,17p, and trisomy 12q

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37
Q

Chronic Lymphocytic leukemia CLL is associated with smudge cells which are small round lymphocytes in ther PB with scant cytoplasm- disrupted when making the smear, low levels of surface Ig seen, positive for CD19, 20, 23 AND CD5, pt is 60 and asymptomatic, with generalized lymphadenopathy and hepatosplenomegaly, fatigue, wt loss, anorexia, see excess leukocytes (unlike SLL which has leukopenia), small monoclonal Ig Spike present in some pt blood, what is common and contributes to an increased susceptibility to BACTERIAL INFECTIONS?

A

Hypogammaglobulinemia

*see prolymphocytes in LN, along with smudge cells see spherocytes due to Ab damage

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38
Q

Chronic Lymphocytic leukemia CLL is treated with BTK inhibitors, poor prognosis is associated with 11q/17p deletions, lack of hypermutation, NOTCH1 mutations, what syndrome is the tendency of CLL/SLL to transform to a more aggressive tumor in the form of a diffuse large B cell lymphoma - transformation of CLL/SLL to an aggressive B cell lymphoma*- leading to a very poor prognosis of less than 1 year?

A

Richter Syndrome

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39
Q

What lymphoma is a tumor of LNs that causes obliteration of the LN and loss of architecture, effaces LN architecture- nodular aggregates of lymphoma cells, it is the MC form of nonaggressive (indolent) non-hodkins lymphoma in the US, arises in germinal center cells, STRONGLY associated with chromosomal translocation involving BCL2***, t14:18 BCL2/Ig heavy chain seen in 90%? (BCL2 antagonized apoptosis promotes cell survival)

A

Follicular Lymphoma

same in m/f, germinal center location

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40
Q

Follicular Lymphoma is devoid of apoptotic cells because BCL2 is antiapoptotic, MLL2 is mutated in 90% as well, lymphocytosis is seen in 10% in peripheral blood, BM is involved in 85% and takes the form of paratrabecular lymphoid aggregates, also seen in splenic white pulp and ?

A

hepatic portal triads

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41
Q

Follicular Lymphoma has centrocytes and centroblasts (less common), are CD 10/19/20 + CD5-***, BCL6 + (anti apoptotic) and BCL2 + (nl follicular cells are devoid of this marker), clinically presents in middle age as painless lymphadenopathy, extranodal site is uncommon, it has what kind of course, with a survival of 7-9 years NOT improved by aggressive chemo?

A

waxing and waning course

histologic transformation to diffuse b cell lymphoma common, or to burkitt if MYC translocation

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42
Q

What type of lymphoma is BAD, MC form of non hodgkins, age 60, male predominance, most are due to dysregulation of BCL6 required for normal germinal centers, some associated with t14:18 (like follicular), are large destructive masses with extranodal involvement, see large cells, diffuse growth pattern, with multiple nucleoli, are CD19/20+ sometimes CD10/BCL6, most have surface immunoglobulins?

A

Diffuse Large B cell Lymphoma

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43
Q

Diffuse Large B cell Lymphoma are rapidly enlarging mass at nodal or extranodal sites, may arise anywhere in body, liver and spleen involvement, extranodal common – GI skin bone and brain, Bone marrow is not usually involved, is commonly associated with what, whihc is oropharyngeal lymphoid tissue including the tonsils and adenoids?

A

Waldeyer Ring

see sx related to extranodal sites

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44
Q

Diffuse Large B cell Lymphoma is aggressive and fatal without treatment, 80% remission, 50% cured, MYC translocations have worse outcomes, 2 variants include immunodeficiency assoc large b cell lymphoma seen with HIV or *ebv, and what subtype, which is ALWAYS associated KSHV/HHV8 - kaposi’s ?

A

Primary Effusion Lymphoma

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45
Q

What lymphoma has a HIV, african and sporadic type, with starry sky pattern, virtually always fails to express BCL2, MC assoc with translocations of the c-MYC oncogene on chr 8***, t8:14, MYC normally increases genes for aerobic glycolysis (warbug effect) allowing cells to biosynthesize building blocks for growth and cell division, if glucose and glutamine are availble?

A

Burkitt Lymphoma

starry sky due to monotonous appearance with clear macrophages spread throughout dark purple cells

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46
Q

Burkitt Lymphoma is due to dysregulation of c-MYC d/t translocation at t8:14 = MYC/Ig heavy chain, it is the fastest growing tumor- doubles in size q 36 hours- mainly in children or young adults- most manifest at extranodal sites, has high mitotic index, if BM involved has 2-5 nucleoli and what kind of cytoplasm with clear cytoplasmic vacuoles?

A

Royal blue cytoplasm

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47
Q

Burkitt Lymphoma is CD10/19/20+ BCL6+ surface IgM+, BCL2 -, MYC+, makes up 30% of childhood NHL, aggressive but responds well to chemo, sporadic is assoc w t8:14, HIV assoc with t8:14 25% have EBV, and what type is asscoaited w t8:14 - all patients are latently infected with EBV, presents as mass of mandible/face and or abdominal viscera- BM or PB involement is rare?

A

African (endemic) Burkitt Lymphoma

48
Q

What is the most common plasma cell dyscrasia, (MC plasma cell malignancy = multiple myeloma), cells secrete monoclonal Ig= M component, neoplastic plasma cells synthesize excess light chains along with complete immunoglobulins, light chains are small in size and excreted in the urine as what proteins?

A

Bence-Jones Proteins

49
Q

What is monoclonal gammopathy (plasma cell neoplasm) that is rare seen in assoc with diverse group of disorders including lymphoplasmacytic lymphoma and an unusual small bowel marginal zone lymphoma that occur in malnourished populations (mediterranean lymphoma)- see synthesis and secretion of free *heavy chain fragments of IgA** (most are light chain)?

A

Monoclonal Gammopathy- Heavy Chain Disease

50
Q

What is the MC plasma cell neoplasm, causes bony destruction of the skeleton and presents with pain due to fractures, causes tumorous masses throughout skeleton - termed moth eaten, with lytic bone lesions, hypercalcemia, renal failure and acquired immune problems***, MC in african Men, at 65-70 years old, with variants including solitary (single bone mass) and smoldering (no lytic lesions)?

A

Multiple Myeloma

51
Q

Multiple Myeloma is assoc with high levels of IL6 which is important for growth of plasma cells, produced by neoplastic plasma cells and resident marrow stromal cells, associated with rouleaux formation - high level of M proteins causes RBCs in blood smears to stick together linearly (seen whenever Ig levels are elevated), see flame cells and mott cells which are grapelike cytoplasmic droplets (blue), the plasma cells are often positive for CD56 and what CD which is syndecan 1?

A

CD138

52
Q

Multiple Myeloma are associ with more than 3gm/dL of serum Ig and more than 6mg/dL of urinary bence jones proteins, MC monoclonal Ig is IgG and then IgA, hypercalcemia causes neurologic signs and symptoms (confusion, weakness, lethargy) - think stones bones groans and psychiatric moans + shortened Qt, renal failure + bacterial infection (MCC death), bence jones proteinuria is when what are toxic to renal tubular cells causing failure?

A

Excreted Light chains

****high k light chain on electrophoresis, (IgG)

53
Q

Multiple Myeloma has excessive production and aggregation of M proteins especially IgA or IgG3 which causes what? Diagnosis required BM tap, marrow gives rise to NC/NC anemia +/- moderate leukopenia/thrombocytopenia, tx thalidomide or proteasome inhibitors but die in 4-7 years- no cure

A

Hyperviscosity

monoclonal immunoglobulin = M protein

54
Q

What type of myeloma is a solitary lesion of bone, usually results in multiple myeloma, see solitary osseous plasmacytoma almost inevitably progresses to MM, modest increase in M proteins in blood or urine?

A

Solitary Myeloma (plasmacytoma)

55
Q

What type of myeloma is middle between MM and MGUS, plasma cells are 10-30% marrow cellularity, has elevated serum M proteins BUT no signs and symptoms, and patients are asymptomatic, 75% progress to MM?

A

Smoldering Myeloma

56
Q

What is a syndrome in which high elvels of IgM lead to symptoms related to hyperviscosity of the blood, occurs in older adults assoc with lymphoplasmacytic lymphoma?

A

Waldonstrom Macroglobulinemia

57
Q

What is the MC plasma cell disorder/dyscrasia, >50>70, asymptomatic pt with small to larger M components in blood, low but constant rate of transformation to monoclonal gammopathies?

A

Monoclonal Gammopathy of Uncertain Significance MGUS

58
Q

What lymphoma is B cell neoplasm of 60-70s, with substantial fraction of the tumor cells undergo terminal differentiation to plasma cells (differs from CLL/SLL), can cause hyperviscosity, acquired MYD88** mutation which activate NFkB, see russell bodies - PAS+ inclusions with Ig in cytoplasm and Dutcher bodies = PAS+ Ig inclusions in nucleus, present with weakness, fatigue, weight loss,lymphadenopathy and hepatosplenomegaly, no bone lesions?

A

Lymphoplasmacytic Lymphoma

_hyperviscosity can lead to retinopathy, neuro such as HA and vertigo to seizures coma, spontaneous bleeding = waldonstrom + cryoglobulinemia = raynaud phenomenon

59
Q

What lymphoma is uncommon non-hodgkins lymphoma, tumor cells closely resemble the normal mantle zone B cells that surround germinal zones, usually 50-60s, male, translocation t11:14 cyclin D1/IgH leads to overexpression of cyclin D1 promotes G1 to S phase progression, IgH, pt with painless lymphadenopathy, extranodal sites include BM, spleen, liver gut, and ****lymphomatoid polyposis = mucosal involvement of the small bowel or colon = polyps ?

A

Mantel Cell Lymphoma MCL

60
Q

Mantel Cell Lymphoma MCL - all have t11:14 overexpression of cyclin D1, can look like follicular lymphoma but follicular doesnt have germinal center and mantle cell does, increased cyclin D1, chemo is not helpful, HSC and proteasome inhibs are now being used, median survival is?

A

3-4 years

61
Q

What lymphoma is a heterogenous group of B cell tumors in LN, spleen, or extranodal tissue, referred to as MALTOMAS, arise in tissues affected by chronic inflammation (autoimmune or infectious), such as sjoogrens hashimotos and h pylori in the stomach, a continuum between reactive lymphoid hyperplasia and full blown lymphoma, *polyclonal to Monoclonal transformation?

A

Marginal Zone Lymphoma

maltomas: T11:18, t14:18, t1:14**8 characteristic

62
Q

What leukemia is a rare B cell neoplasm that has hair like projections coming out of the leukemic cells, 55 yo 5x MC in MEN, BRAF activating mutation, is positioned immediately downstream of ras in the mapk signaling cascade, moderate amounts of pale blue cytoplas with bleb like extensions, dry tap becuase tumor cells are trapped in the ECM on BM, CD11C/19/20/25/103+, surface IgG +** and tartrate resistant acid phosphatase TRAP +?

A

Hairy Cell Leukemia

63
Q

Hairy Cell Leukemia presents with pancytopenia, 1/3 have infection with atypical mycobacteria, exceptionally sensitive to gentle chemo - long lasting remission, relapse in 5 yrs, BRAF inhibitors show excellent tumor response in patients who fail chemo, excellent prognosis, TRAP positive, what is the most significant presentation?

A

MASSIVE SPLENOMEGALY

64
Q

What lymphoma is derived from mature T cells, CD2/3/5+ some CD4/8+ requires immunphenotyping, tumors efface LN diffusely, mix of variably sized malignant T cells, prominent infiltrate of reactive cells (EOSINOPHILS) and mo, neoangiogenesis is seen, clinically pts present with general lymphadenopathy with itchy, eosinophilia, fever, weight loss, cure is rare and WORSE prognosis because T cell tumor?

A

Peripheral T cell lymphoma unspecified (means after going through all other options, this is last resort)

65
Q

What is a T cell lymphoma with a good prognosis (uncommon), see ALK rearrangement on chr 2p23, causing expression of ALK which is PATHOGNOMINIC, tests CD30+** and CD8 cell is anaplastic, there are large anaplastic cells with horseshoe nuclei and voluminous cytoplasm which are hallmark cells, clinically MC in children, involve soft tissue = very good prognosis?

A

Anaplastic large Cell Lymphoma ALK+

66
Q

What lyphoma is a neoplasm of CD4 T cells, pt infected with HTLV1*, in japan/w3est africa, virus produces tax protein that activates NFkB, cells have multi lobulated nuclei (cloverleaf or flower cells), skin leasions with lymphadenopatthy, hepatosplenomegaly, and rapidly progressive disease fatal in montsh to 1 year despite aggressive chemo?

A

Adult T Cell Leukemia/Lymphoma

*may cause a demyelinating disease

67
Q

Mycosis fungoides is a tumor of CD4 t cells that homes to the skin, cutaneous lesions progress through three phases include premycotic, plaque and tumor, epidermis and dermis are infiltrated by t cells with cerebriform appearance, what syndrome is associated with this, and is CLA+ (cutaneous leukocyte antigen***), and CCR4 and CCR10 + chemokine receptors- see exfoliative erythroderma with characteristic cerebriformnuclei?

A

Sezary Syndrome + Mycosis Fungoides

68
Q

What lymphocytic leukemia has t cell and NK cell variants which are CD3+ and CD56+ respectively, due to STAT3 mutation, see neutropenia and anemia, increased incidence of rhematoid DOs, commonly associated with Felty syndrome which is RA, splenomegaly and neutropenia?

A

Large Granular Lymphocytic Leukemia

69
Q

What lymphoma is associated with a destructive nasopharyngeal mass (extranodal), may also be seen in testes and skin, surrounds small vessels causing ischemic necrosis, tumor originates in a single EBV infected cell***, no CD21/no CD3, highly agressive respond well to radiation but poor prognosis in advanced disease?

A

Extranodal NK/TCell Lymphoma

70
Q

What lymphoma is often localized to a single axial group of LN (cervical) arises in a single node and spreads to first anatomically contiguous lymphoid tissues, mesenteric and waldeyer ring rarely involved, presence of reed sternberg cells (transformed B cells) and a FEVER is present, around 32, tx with radiation and chemo - curable in most cases, freq assoc with acquired mutations that activate NFkB and with EBV (classic case)?

A

Hodgkin Lymphoma

Reed Steinberg cells release cytokines, chemokines to accum reactive lymphocytes, macrophages and granulocytes- they are aneuploid and possess diverse clonal chromosonal abberations

71
Q

Hodgkin Lymphoma- dx depends on reed steinberg cells in background of non neoplastic inflam cells,they are aka owl-eyed nuclei, and large cells, derived from germinal center or post germinal center b cells, large aneuploid with multiple nuclei or a single nucleus with multiple lobes, usually CD15/30/40 positive, what variant is seen in the nodular sclerosis subtype which has RS cells with delicate folded nuclei and abundant pale cytoplasm?

A

Lacunar variants

72
Q

The classic Hodgkin Lymphoma is PAX5 positive, CD15/30 positive, and does not present in extra nodal sites, What subtype is the MC form (70%) in adolescents and young adults, excellent prognosis, has lacunar variant RS cells, NO EBV, propensity for lower cervical and supraclavicular but especially mediastinal involvement?

A

Nodular Sclerosis subtype

see pink collagen that divides tumor into nodules

73
Q

What subtype of Hodgkin Lymphoma is the 2nd MC, male predominance, sx include night sweats and weight loss, pronosis is very good, plentiful RS cells, 70% are EBV positive, PAX5 pos, CD15/30 positive?

A

Mixed Cellularity Subtype

74
Q

What subtype of Hodgkin Lymphoma is associated with reactive lymphocytes that make up the vast majority of the cellular infiltrate, uncommon, LN are diffusely effeaced, very good to excellent prognosis, has RS cells, 40% EBV +, ?

A

Lymphocyte Rich Subtype

75
Q

What subtype of Hodgkin Lymphoma is least common form, elderly, HIV+ pts, advanced stage and systemic signs are frequent, **Prognosis is LESS favorable than others, abundant RS cells, EBV in 90% with classic hodgkin immunophenotype?

A

Lymphocyte Depletion Subtype

all these past subtypes are classic so all have CD30

76
Q

What subtype of Hodgkin Lymphoma is NONclassic, in men less than 35 with cervical lymphadenopathy, excellent prognosis,but recurs, have L and H vairants express B cell markers in contrast to RS cells, CD20/BCL6 POS, CD15/30 NEGATIVE, not assoc with ebv, L&H popcorn cells seen, a % transforms to diffuse large B cell lymphoma?

A

Lymphocytic Predominance Subtype Non Classical

77
Q

What lymphoma is more frequently involve peripheral multiple nodes, noncontiguous spread, waldeyer ring and mesenteric nodes commonly involved, extranodal presentation is common?

A

Non Hodgkin Lymphoma

78
Q

Myeloid Neoplasms*
AML is accumulation of immature myeloid forms (blasts) in the bone marrow suppresses normal hematopoiesis.
Myelodysplastic syndromes-defective maturation of myeloid progenitors gives rise to ineffective hematopoeisis leading to cytopenia (poor prog)
Myeloproliferative disorders: there is usually increased production of one or more types of blood cells
NOTE: diagnosis of AML (via PB or BM) is based on the presence of at least?

A

20% myeloid blasts in the bone marrow**!

79
Q

Myeloid Neoplasms*
AML is accumulation of immature myeloid forms (blasts) in the bone marrow suppresses normal hematopoiesis.
Myelodysplastic syndromes-defective maturation of myeloid progenitors gives rise to ineffective hematopoeisis leading to cytopenia (poor prog)
Myeloproliferative disorders: there is usually increased production of one or more types of blood cells
NOTE: diagnosis of AML (via PB or BM) is based on the presence of at least?

A

20% myeloid blasts in the bone marrow**!

80
Q

What leukemia causes marrow failure, assoc with anemia, thrombocytopenia, and neutropenia, peaks at 60 years, dx confirmed with MYELOID SPECIFIC ANTIGEN STAINS such as MPO, two MC chr rearrangements is t8:21 and inv16 which disrupted RUNX1 and CBFB respectively which are required for normal hematopoeisis?

A

Acute Myeloid (myelogenous) Leukemia AML

81
Q

Acute Myeloid (myelogenous) Leukemia AML class 1 has genetic aberations with FAVORABLE prognosis, t15/17 is acute promyelocytic leukemia and has intermediate prognosis, poor prognosis assoc with t11q23v, what class has prior MDS (myelodysplastic syndrome) is multi lineage dysplasia, mDS LIke cyotgenic aberrations and ALL HAVE POOR PROGNOSIS?

A

Class 2 = AML with MDS like features

82
Q

Class IV Acute Myeloid (myelogenous) Leukemia AML are all other AMLs that lack features of the other clases NOS*, have intermediate prognosis, Class 3 AML is related to what, post alkylating agen 2-8 yr latency and post topois 2 inhib 1-3 yr latency, with very poor prognosis?

A

Class 3 AML THREAPY related (radiation)

83
Q 
NOTE:
M2 = AML with t8:21- favorable prog (class 1)
M4eo = AML with inv16 = favorable prog class 1
M3 ApML = AML t15:17 clAss 1 intermediate prog
M4/M5= AML with t11q23v - poor prog class 1
A

M2 >M1 >M4>M3

M4 is acute myelomonocytic leukemia AMML

84
Q

Acute Myeloid (myelogenous) Leukemia AML pathogenesis is based around genetic abberation disrupting genes encoding transcription factors required for normal myeloid differentiation (RUNX/INV6), or mutations activating GF signlaing pathways such as t15;17 for promyelocytic leukemia or epigenetic alterations such as DNA methylation and posttranslational modification of histones is altered, def dx is made via what in the BM?

A

> 20% myeloid BLASTS in BM including myeloblasts, monoblasts, megakaryoblast, erythroblasts

***BM may not be in PB

85
Q

Myeloblasts have delicate nuclear chromatin, 2-4 nucleoli, lots of cytoplasm, peroxidase+ azurophilic granules, with WHAT, which are distinctive needle like purple granules, numerous in AML t15;17, APML, and are formed of the cytoplasmic granules of the myeloid blasts of acute myelogenous leukemia and are a typical finding, ?

A

Auer Rods*

NOTE: Monoblast morph: lack auer rods, nonspecific esterase+ and peroxidase -

86
Q

Clinically, Acute Myeloid (myelogenous) Leukemia AML, signs and symptoms are similar to ALL, including anemia, fatigue and neutropenia, fever due to opportunistic infections of oral cavity skin lungs kidneys bladder colon, thrombocytopenia with spont mucosal and cutaneous bleeding exacerbated by procoagulants and fibrinolytics release by leukemic cells (t15;17), CNS involvement less common, leukemic cutis and gingiva is common, may present as localized soft tissue mass, 60% remission with chemo, 5 yr survival of?

A

70-85%

87
Q

What syndrome is referred to as clonal stem cell disorders with maturation defects assoc with ineffective hematopoiesis, inc risk of transformation to AML, more severe than myeloproliferative with poor prognosis, peripheral blood shows pancytopenia, primary cause is idiopathic or secondary to genotoxic drug or radiation (t-MDS = worse prog), typically seen in older adults and are CHARACTERIZED by thrombocytopenia?

A

Myelodysplastic Syndromes MDS

88
Q

Myelodysplastic Syndromes MDS path is assoc with MYC gene on chr 8, (?) there is disordered differentiation of erythroid, granulocytic monocytic and megakaryocytic lineages, see ring sideroblasts which are rbc with iron laden mT in perinuclear granules, see toxic granulation sor Dohle bodies in granulocytes along with pseudo pelger huet cells which are neutrophils with only 2 nuclear lobes, and megakaryocytes with single nuclear lobes or multiple separate nuclei aka what?

A

pawn ball are characteristic

note myeloid blasts are increased but make up less than 20% of overall marrow cellularity, if not then AML

89
Q

Primary Myelodysplastic Syndromes MDS presents at 70, 50% discovered incidentally on blood draw, 9-29 months survivial, sx of weakness, infection and hemorrhage, worse outcomes assoc with high blsts, severe cytopenias, 40% progress to AML, cause of death is thrombocytopenia (bleeding) and neutropenia (infection), what type appears 2-8 yrs after treatment with genotoxic agents mean survival is 4.8 months, TERRIBLE prognosis, cytopenias severe and progression to AML rappid?

A

t-MDS

90
Q

What disorder includes CML, PV, essential thrombocytosis and primary myelofibrosis, due to mutated active tyrosine kinase leading to growth factor independence so LOTS of cells, do not impair differentiation, increased prodcution of one or more mature blood elements = high counts of everything = pancytosis, bleeding common cause platelets abnl even tho there are alot, extramedullary hematopoiesis common, spent phase leads to cytopenias in later dz, a few will turn into AML or ALL= have terrible prognosis*?

A

Myeloproliferative Disorders

91
Q

What myeloproliferative leukemia is associated with chimeric BCR-ABL gene driven by t9;22 philadelphia chromosome = constitutive tyrosine kinase activation driving growth factors, does not interfere with differentiation, MC myeloproliferative DO, see BASOPHILIA and eosinophilia, inc megakaryocytes and hypercellular marrow with characteristic sea blue histiocytes ?

A

Chronic Myeloid Leukemia CML

92
Q

Chronic Myeloid Leukemia have scattered mo with abundant wrinkled green blue cytoplsm, clinically is a dz of 50-60s male predom, HUGE spleen (due to extramedullary hematopoeisis), fatigue, weakness, wt loss and anorexia common, LUQ pain, dx via BCR-ABL, leukocytosis >100,000 with <10% blasts, and historically what is LOW?

A

Leukocyte Alkaline Phosphatase LAP LOW

93
Q

Chronic Myeloid Leukemia prognosis without treatment is 3 years, 50% enter accelaerated phase where there is increased anemia and thrombocytopenia +/- basophilia, after 6 months the accelerated phase terminates in a picture resembling acute leukemia NOTE 70% are AML like and 30% are ALL like so originates froms pluripotent stem cell with both?

A

myeloid and lymphoid potential

94
Q

What myeloproliferative DO is assoc with increased red cell mass, see activating point mutation in JAK2 (tyrosine kinase) greatly increased RBCs slight increase in granulocytes and platelets, see valine to phenylalanine at residue 617, serum erythropoietin levels are suppressed due to decreased requirement, insidious in adults, see hyperviscosity causing abnl blood flow, elevated hematocrit leading to thrombosis and bleeding, leukocytosis and thrombocytosis (>500000), 25% come to attention via DVT MI or stroke, hyperuricemia common?

A

Polycythemia Vera

inc Hgb, inc hematocrit, iron def d/t chronic bleeds, inc WBC, inc platelet count

untreated = death within months
tx is phlebotomy/JAK2 inhib

spent stage = marrow fibrosis + massive spleen

95
Q

What myeloproliferative DO is markedly inc platelet cell mass, without polcythemia or marrow fibrosis, inc mega, mild leukocytosis, dx of exclusion, activating JAK2 mut/MPL mut, seen in adults >60, extramedullar hematopoiesis = splenomegaly, thrombosis/hem due to platelet dysfunction and increased number, DVT portal and hepatic vein thromb + MI common, erythromelalgia is occlusion small arterioles by platelets causing burning of hands and feet, survival 12-15 yrs?

A

Essential Thrombocytopenia

BM bx shows large increase in megakaryocytes and mild inc in the rest

96
Q

What myeloproliferative DO is due to development of obliterative marrow fibrosis, see cytopenia and extramed hematopoiesis, appears identical to spent phase of other MPD, least common, see **extensive deposition of collagen in marrow by non-neoplastic fibroblsts due to activating JAK2/MPL mut, inc released megakaryocyte factors = PDGF and TGFB cause fibrosis and scarring, splenomegaly and anemia, 60s, early hypercellular marrow with large dysplastic megakaryo, late phase marrow hypocellular and fibrotic, cloudlike, osteosclerosis, splenomegaly*?

A

Primary Myelofibrosis

97
Q

Primary Myelofibrosis in the blood see leukoerythroblastosis which is premature release of nucleated erythroid and early granulocyte precursors - NC/NC anemia, what are common in blood which are tear drop shaped cells damaged during release from the fibrotic marrow, see night sweats fatigue, wt loss, prognosis is 3-5 years?

A

daCRYocytes

98
Q

What term is an umbrella designation for a variety of proliferative disorders of dendritic cells or mo, considered neoplasms, see abundant vacuolated cytoplasms, vesicular nuclei with linear grooves or folds, and **birbeck granules in cytoplasm is characteristic: plantalaminar tubules with a dilated terminal end (tennis racket appearance) contain langerin?

A

Langerhans Cell Histiocytosis

99
Q

Langerhans Cell Histiocytosis is HLA-DR S100 and CD1a positive, due to BRAF mutation (activating) as seen in hairy cell leukemia, other mutations as well such as tp5, RAS and MET. What type of LCH is most freq before 2 years, assoc with cutaneous lesions resembling seborrheic eruption, fevere infection s, chronic otitis media mastoidtis, have anaplastic morpholophy, hepatosplenomegaly, lymphadenopathy, pulm lesions and destructive osteolytic bone lesions,chemo = 50% 5yr survival?

A

Multifocal Multisystem Langerhans Cell Histiocytosis

= Letterer-Siwer Disease

100
Q

What type of Langerhans Cell Histiocytosis is a benign proliferation of langerhans cells in medullary cavity of bone in the calcarium ribs and femur, in adolescents, clinically see pain tenderness and pathologic fractures, skin lungs stomach uncommonly involved, bx shows langerhans cells mixed inflam cells **many eosinophils?

A

Unifocal Unisystem Langerhans Cell Histiocytosis (eosinophilic granulomas)

101
Q

What type of Langerhans Cell Histiocytosis is a benign prolife of langerhans cells affecting young children, there are multiple* erosive bone masses, extending into soft tissue, may involve posterior pituitary stalk = diabetis insipidus (50%) with spont regression or treatment with chemo, what triad for this includes calvarial bone defects, diabetes insipidus and exopthalmos**?

A

Hand-Schuller-Christian Triad

102
Q

What type of Langerhans Cell Histiocytosis is reactive proliferation- nodules and cysts in middle/upper lobes of the lungs, 40% assoc with BRAF mutations and may be neoplastic in origin, **SMOKING highly associated - dz may regress with cessation of smoking?

A

Pulmonary Langerhans Cell Histiocytosis

103
Q

The spleen is an ingeniously designed blood filter and a site of immune responses to blood borne antigens, it is 150gm and 12cm in length, congenital absence is rare, accessory spleens are common (25%), largest unit of mononuclear phagocyte system, functions include removal of unwanted elements from blood(filter and recycling - iron and globin proteins), phagocytosis, antibody production, hematopoiesis, and sequestration… What are responsible for RBC pitting: process by which incldusions of Heinz bodies and Howell Jolly Bodies are excised?

A

Marcophages!

104
Q

Splenomegaly is the major manifestation of DOs of the spleen, infections, alcohol and disease. Asplenia leads to increased susceptibility to sepsis causes by what type of bacteria, which are blood borne, note- Sickle cell patient sshow increased autoinfarction of the spleen = functionally asplenic, assoc with dec phagocytic capacity, dec antibody production and pts should be vax against pneumococci, meningococci and H. influenza?

A

ENCAPSULATED BACTERIA

105
Q

Dragging sensation in LUQ due to splenomegaly, discomfort after eating due to pressure by stomach, can cause hypersplenism leading to anemia, leukopenia, and thrombocytopenia either alone or in combination, what is the MCC of splenomegaly?

A

due to portal HTN from cirrhosis of the liver

is the MCC of hypersplenism and splenomegaly

106
Q

Lymphoid and myeloid tumors often cause splenomegaly, NOTE: PRIMARY neoplstic involvement is rare AND there are almost NEVER metastases to the spleen, MC tumors of spleen include hamartoma, hemangioma and lymphangioma

A

MEOW

***Diffuse Large B Cell Lymphoma MC involves spleen lesions secondarily

107
Q

What type of splenitis is secondary non specific reaction to ANY blood borne infections, mild splenomegaly, soft and fluctuant, acute congestion of red pulp and infiltrates of neutrophils plasma cells +/- eosinophils is common?

A

Nonspecific Acute Splenitis

108
Q

What type of splenomegaly can by system/central or venous issue such as cardiac decompensation with moderate enlargement, cirrhosis of the liver is the MCC of this type of splenomegaly, and or due to obstruction oof the extrahepatic portal or splenic vein via thromboses, compression of BV?

A

Congestive Splenomegaly*

See thick capsule, cut surface gray red to deep red
red pulp is congested early, becomes more fibrous and cellular with long standing congestion, also see pigment deposition

109
Q

Splenic infarcts occur because the spleen lacks an extensive collateral blood supply like the brain and kidneys, so emboli frequent lodge and cause infarcts- either due to splenic arteries such as cardiac emboli or SCD, and can lead to what, with increased risk of infections with encapsulate bacteria?

A

Hyposplenism = decreased splenic function

due to infarcted spleen= less function

110
Q

hypoplasia of spleen is MC than aplasia, accessory spleens are common, rupture typically occurs in the setting of BLUNT force trauma but chronically enlarged spleens are less ?

A

susceptible to rupture (ruptures with mononucleosis too)

111
Q

What is derived from the 3rd and 4th pharyngeal pouches, grows until puberty then disappears, lobular structure that contains thymic epithelial cells = hassall corpuscles with keratinized cores, immature T lymph and location of T cell maturation, there is some scattered myoid cells in the thymus and this is thought to be why myasthenia gravis attacks this organ because the anti bodies attach the myoid muscle like cells here?

A

Thymus

112
Q

What syndrome is known as thymic hypoplasia/aplasia with severe defects in cell mediated immunity, anomalies of parathyroid development hypoPTH leading to hypocalcemia, chr 22q11 deletion= CATCH22 see cardiac defects, abnormal facies, thymic hypoplasia, cleft palate,hypocalcemia?

A

Digeorge Syndrome

113
Q

What are uncommon and an incidental finding, less than 4cm in diameter, spherical, lined with stratified squam to columnar epi, fluid may be mucinous, note neoplastic thymic masses compress and distort adjacent NL thymus and causes cysts?

A

Thymic Cysts

114
Q

What occurs as B cell proliferation in the thymus, see B cell germinal centers in thymus, MC in myasthenia gravis or graves disease SLE scleroderma RA, may be naturally large for a patients age and can be mistaken for thymoma, true enlargement of the thymus is rare?

A

Thymic Follicular Hyperplasia

115
Q

What is a true tumor of thymic epithelial squamous cells, typically contain benign immature t cells, adults >40, look for cellular atypia to differentiate between benign and malignant, rare in children, MC IN ANTERIOR SUPERIOR MEDIASTINUM, sx from impingement of other structures, present with MG, paraneoplastic syndromes?

A

Thymoma

116
Q

There are three types of thymomas, benign but invasive which by definition penetrates through the capsule into surrounding tissue, or cytologically malignant, most are squamouss cell carcinomas, but if they are what type then they are more likely to be associated with EBV?

A

Lymphoepithelioma- commonly nasopharyngeal carcinoma with lymphocytic infiltrates and epithelial neoplasticity, high met but responds well to radiotherapy

117
Q

Benign encapsulated thymoma 50% cytologically and biologically benign - medullary type epithelial cells or a mixture of medullary and cortical type cells, malignant thymoma- type 1 invasive but cytologically bland, MC of the cortical type 25% all thymomas, type 2 thymic carcinoma cytologically malignant most are SCC either well or poor differentiated, 2nd MC variant of type II is lymphoepithelial like carcinoma 50% assoc with EBV

A

naH

31. Skin Blood Lymph Exam 1 (9 decks)

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