Chapter 13: White Blood Cells Flashcards
What CDs are makers of HSC and ALL white blood cells?
HSC - CD34
WBC - CD45 (leukocyte common antigen)
What is HSC location throughout development?
3rd week –> yolk sac
3rd month –> liver
4th month –> bone marrow (puberty –> ONLY AXIAL)
Where is EPO generated from and what are its two production modes?
- generated by KIDNEY (peritubular capillary lining)
- released relative to Po2
contantly Hb >10 or logarithmically Hb <10
What is the normal % of T Cells in the peripheral blood?
80%
What is the most common cause of agranulocytopenia?
DRUG TOXICITY
- inc. susceptibility to bacterial or fungal infection, since it is a reduction in the number of neutrophils
What do infections occurring due to agranulocytosis look like (2)? When does serious infection normally occur?
- infections with ulcerating necrotizing lesions of mouth (agraun. angina)
- deep lesions w/dark necrotic membranes (Candida/Aspergillus)
serious infection occurs w/neutrophil count <500
How is Agranulocytosis treated?
broad spectrum antibiotics and GCSF to stimulate granulocyte production
When will LAP (Leukocyte alkaline phosphatase) be elevated vs normal?
Elevated –> leukemoid reactions
Normal –> leukemia
What is the effect of Sepsis on neutrophils morphology (2) specifically?
appearance of toxic granulations (abnormal, dark azurophilic granules) and Dohle bodies (dilated endoplasmic reticulum)
Acute Nonspecific Lymphadenitis:
What is the difference between Localized, Systemic, and Mesenteric forms?
L: from direct microbiological draining
S: from bacteriemia and viral infections (usually kids)
M: mesenteric LN enlargement (looks like appendicitis)
Where is Chronic Nonspecific Lymphadenitis commonly seen in? What does the lymph node look like?
- commonly occurs in inguinal and axillary LNs
- LNs are nontender without acute inflammation or tissue drainage
What development in nonlymphoid tissue can chronic immune reactions lead to, and what is the common cytokine required?
- leads to Tertiary Lymphoid Organs
- chronic gastritis (H. pylori) and Rhematoid arthritis lead to MALToma’s
- lymphotoxin required for Peyer Patch formation
What are 3 common causes of follicular hyperplasia and what are Tingible-body macrophages?
CC: rheumatoid arthritis, toxoplasmosis, early HIV
TBM = macrophages that have eaten apoptotic B Cells
What is a common cause of Paracortical Hyperplasia, and what happens when these reactions become exuberant?
- T cell mediated response like that to infectious mononucleosis (EBV)
- exuberant rxns cause immunoblasts to encroach on B-cell follicles, leading to sinusoidal/endothelial hypertrophy
- if immunoblasts (large, activated T-cells) are numerous, need special studies to exclude neoplasm from the differential
Sinus Histocytes (Reticular Hyperplasia)
- inc. in number and size of cells lining lymphatic sinusoids (expansion/distension)
- nonspecific, though seen in LNs draining carcinoma of the breast
Hemophagocytic Lymphohistiocytosis:
What is it and what is its pathogenesis? What is it most commonly caused by?
- aka “Macrophage Activating Syndrome” –> cytopenias and symptoms of systemic inflamm dur to macrophage activation
- macrophages and CD8+ cells destroy peripheral and marrow cell lineages, while releasing mediators that suppress hematopoiesis
- infection is most common trigger (EBV especially)
Hemophagocytic Lymphohistiocytosis:
What does it look like clinically and how can it be treated?
- acute febrile illness and hepatosplenomegaly with anemia/thrombocytopenia
- inc. LFTs/TG (hepatitis) and DIC may be present
Treatment: immunosuppressive drugs and mild chemo
- only about 50% survive (may have sequelae)
Myeloid Neoplasms
What is the difference between Acute Myeloid Leukemia, Myelodysplastic Syndrome, and Chronic Myeloproliferative Disease?
AML: blasts accumulate in bone marrow suppressing normal hematopoiesis (MOST SEVERE)
MDS: ineffective hematopoiesis, causing peripheral blood cytopenias (more severe than MPD)
CMD: inc. production of one or more adult myeloid elements leads to inc. peripheral blood counts
less severe types can evolve over time into more aggressive forms of disease
What kinds of cancer do these viruses lead to:
- HTLV1
- EBV
- KSHV/HHV8
- HIV
- adult T-cell leukemia/lymphoma (ATLL)
- Burkitt lymphoma, Hodgkins, other B-cell lymphoma
- paracortical response to B cell infection in Burkitt
- B-cell lymphoma (malignant pleural effusions)
- B-cell lymphoma
What is the difference in spread of Hodgkins vs Non-Hodgkins lymphoma?
Hodg: spreads in an orderly fashion, staging useful
- distinctive pathological features, unique treatment
NonHodg: spreads widely and is less predictable
Acute Lymphoblastic Leukemia (ALL):
What is it, who does it commonly affect, and what is its pathogenesis between T and B cells?
- immature lymphoblast neoplasm (mostly B-ALL)
- affects hispanics > white > blacks and is the MOST COMMON cancer/leukemia of childhood (< 15)
- B cells: 90% t(12;21) translocation (ETV6/RUNX1)
- also LOF in PAX5, E2A, RBF
- T cells: GOF in NOTCH1
Acute Lymphoblastic Leukemia (ALL):
What is the morphology and how can you tell this neoplasm apart from Acute Myeloid Leukemia?
- hypercellular bone marrow with “starry sky” appearance due to macrophages eating tumor cells
- scant basophilic cytoplasm with large nuclei
- ALL stains MPO (-) and TdT (+), while AML is MPO (+) and TdT (-), also more likely to cause NERVE PALSIES than AML
Acute Lymphoblastic Leukemia (ALL):
What does it look like clinically (4) and how is it treated?
- mass effect, “storm-onset” (onset in days to weeks), fatigue, fever, bleeding (due to cytopenia), and NEUROLOGICAL problems (nerve palsies, headaches, vomiting)
Treat: aggressive chemo (95% remission, 75-85% cured)
Acute Lymphoblastic Leukemia (ALL):
What is the difference between a good prognosis and bad prognosis?
Good: age 2-10, low WBC count, HYPER-DIPLOIDY, and t(12;21) translocation
Bad: age < 2, t(9;22) translocation (seen in adolescence w/WBC count >100,000)
What are common B and T cell markers that can be checked for when determining the kind of lymphoid neoplasm?
B cell: CD 10, 19, 20
- very immature will be CD 10 (-)
T cell: CD 1, 8
- very immature will be CD 3, 4, 8 (-)
What are the three “T’s” of T-cell ALL?
presents Teenaged males as a Thymic mass (mediastinal) and has Thymocytes
- also see splenomegaly
Chronic Lymphocytic Leukemia (CLL):
What is it, who does it affect, and what chromosomal anomalies does it show?
- most common leukemia of adults in Western World
- affects males (2:1) that are 60 yo in Western countries
- translocations are RARE, has deletion 13q14.3 (microRNA 15/16) and 11q, 17q
PNEUMONIC: 11, tr12, 13q14, 15, 16, 17
Chronic Lymphocytic Leukemia (CLL):
What is the morphology and immunophenotype? What are 3 indicators of BAD prognosis?
M: develop proliferation centers (large lymphocytes gather in aggregates - mitotically active); promylocytes if LN is involved (Small Lymphocytic Lymphoma)
I: CD 5, 19, 20, 23 (B cell prolif. w/CD5 = CLL)
B: 11q, 17p deletions, ZAP70(+), NOTCH1 mutations
Chronic Lymphocytic Leukemia (CLL):
What are the clinical aspects and treatments for patients?
C: asymptomatic –> nonspecific signs (hepatosplenomegaly and lymphadenopathy), monoclonal Ig spike may be preset
- can cause hypogammaglobulinemia (low IgG)
T: gentle chemo, immunotherapy (CD20), BTK inhibitors, HSC transplant (median survival 4-6 yrs)
Richter Syndrome and CLL
- tendency of CLL/SLL to transform to diffuse B-cell lymphoma
- rapidly enlarging mass within LN or spleen
- BAD (survival < 1 yr)
Follicular Lymphoma:
What is it, what is its pathogenesis (translocation?), and what is its morphology (3 places)?
- LN tumor causing obliteration of architecture and is the most common indolent form NHL in the US
P: germinal centers; associated with t(14;18) BCL2/IgH
- devoid of apoptotic cells do to BCL2 blockage
- MLL2 (histone methyltransferase mutation)
M: diffuse proliferation of centrocytes/centroblasts
- also lymphoid aggregates in bone, spleen white pulp, and hepatic portal triads
Follicular Lymphoma:
What is its immunophenotype and what is its clinical presentation? What two types of cancer can it progress to?
I: CD10, 19, 20 (+) and CD5 (-)
- also BCL6/BCL2 (+)
C: painless presentation in middle-age w/generalized lymphadenopathy; INCURABLE; “waxing-waning” course with 7-9 yr survival –> PALLITATE
**can transform to Diffuse Large B-cell Lymphoma (30-50%) or Burkitt Lymphoma
Diffuse Large B-cell Lymphoma (DLBCL):
What is it, what is its pathogenesis, and what other mutations can it have (2 major)?
- most common form of NHL (median 60 yo)
P: 3q27 mutation involving BCL6 (inhibits GC diff., growth arrest, and apoptosis)
- also see t(14;18) with BCL2 (anti-apoptosis) –> not normal to see BCL2 and BCL6
- also see Myc mutations
Diffuse Large B-cell Lymphoma:
What does it look like, what is its immunophenotype, and where is it located?
M: massive cells with ROUND-OVAL nucleus, diffuse growth pattern (rapidly enlarging mass)
I: CD19, 20 (+)
L: can arise anywhere in the body, but common at Waldeyer Ring (oropharyngeal tonsils/adenoids)
- can go extranodally to GI/skin/bones (rare)/brain
Diffuse Large B-cell Lymphoma:
What does it look like clinically and what finding leads to a worse outcome?
C: aggressive and rapidly fatal without treatment
- 60-80% remission, 40-50% cured
WO: Myc translocation = treat like Burkitt Lymphoma
What is the difference between Immunodeficient-associated Large B-cell Lymphoma and Primary Effusion Lymphoma?
- both are DLBCL subtypes
I = severe T-cell immunodeficiency from EBV B-cell inf.
P = malignant pleural or ascitic effusion
- tumor cells have no cell markers
- infected with KSHV/HHV8
Burkitt Lymphoma:
What is its pathogenesis (translocation?), morphology, and immunophenotype?
P: t(8;14) translocation - Myc/IgH
- can also have t(2;8) or t(8;22) light chains
- FASTEST GROWING TUMOR (doubles 36 hrs)
M: high mitotic index (Tingible-body MO) and “starry sky” pattern
- if BM - royal blue cytoplasm w/clear cyto vacoules
I: CD 10, 19, 20; BCL6 (+)/BCL2 (-), MYC (+)
What is the difference between Sporadic, African (endemic), and HIV-associated Burkitt Lymphoma?
S: t(8;14) w/mass of ileocecum and peritoneum
- 15-20% EBV infection
A: t(8;14) w mandible mass and or abdominal masses
- all patients have EBV
H: t(8;14) and 25% of pts have EBV
Burkitt Lymphoma:
What does it look like clinically?
- 30% of NHL in the United States
- very aggressive, but responds well to intense chemo; children/young adults are usually cured
What are Plasma Cell Neoplasms (dyscrasias)? What are M components and Bence-Jones proteins?
- neoplastic plasma cells that typically secrete monoclonal Igs
- M component = monoclonal Ig in blood (not urine)
- BJ proteins = excess light chains passed in urine
What is the most common plasma cell dyscrasias and what is the most common plasma cell malignancy?
PCD = Monoclonal Gammopathy of Uncertain Significance (MGUS)
PCM = Multiple Myeloma
Multiple Myeloma:
- What is it, who is at risk, and what is the CRAB pneumonic for symptoms?
- MOST COMMON plasma cell neoplasm
- causes bony destruction of the skeleton (pain via pathologic fractures –> hypercalcemia/renal failure)
- affects 60-75 yo males of African descent
C (hyperCalcemia), R (renal failure), A (acquired immune problems), B (bone lytic lesions)
What is the difference between Solitary and Smoldering myeloma?
Solitary - single mass in bone/soft tissue
- almost always progresses to multiple myeloma
Smolder - lacks signs/symptoms with HIGH plasma M
- no lytic bone lesions, 75% progress to MM in 15 yrs
- middle ground between MM and MGUS
Multiple Myeloma:
How does the tumor survive and what is the morphology of the bone lesions?
S: IL-6 (plasma cell growth) –> high = BAD prognosis
- MIP1a inc. NFkB (RANKL) activating osteoclasts
- leads to inc. bone resorption
M: in axial skeleton
- 1-4 cm punches with soft, gelatinous red tumor masses
Multiple Myeloma:
What is the morphology of the neoplastic cells (FM) and what is their immunophenotype?
M: M protein causes Rouleaux formation (RBC “sticks)
- Flame cells: red cytoplasm; degraded proteins
- Mott cells: grape-like cytoplasmic droplets
may have Russell (cytoplasmic) or Dutcher (nuclear) bodies of fibrils, crystalline rods, and globules
I: CD138 (+) and CD56 (+)
What are the two most common causes of death for Multiple Myeloma pts? What are two types of light chains that can be deposited as amyloids, causing amyloidosis?
- infections (dec. prod. of normal Igs)
- renal failure
- due to Bence-Jones Proteinuria
- excreted light chains are toxic to renal tubular cells
- due to Waldernstrom Macroglobulinemia
- excess IgA/IgG –> hyperviscous blood
amyloidosis –> lambda 3 and 6 light chains