Pathoma Chapter 6: Part 2 Flashcards
What are myeloproliferative disorders (MPDs)?
neoplastic proliferation of mature cells of myeloid lineage
When do MPDs usually present?
late adulthood (50-60 y/o)
T or F. in MPDs cells of all myeloid lineages are increased.
T. Subtypes are classified based on the major cell type produced
Complications with MPDs include what?
- increased risk for hyperuricemia and gout due to high turnover of cells
- progression to marrow fibrosis or transformation to acute leukemia
What are some types of MPDs?
- chronic myeloid leukemia (CML)
- polycythemia vera (PV)
- essential thrombocytopenia
- myelofibrosis
What is CML caused by?
neoplastic proliferation of mature myeloid cells, especially granulocytes and their precursors
What is characteristically increased in CML?
basophils
Cause of CML?
t(9,22) Philadelphia chromosome which generates a BCR-ABL fusion protein with increased tyrosine kinase activity
Treatment for CML?
Imatinib, which blocks tyrosine kinase activity
Progression of CML?
-splenomegaly common and enlarging spleen suggest progression to accelerated phase of the disease and can transform to acute leukemia (ALL 1/3 of times and AML 2/3 of times- because mutation is in a pluripotent stem cell) shortly after
How is CML distinguished from a leukomoid reaction (reactive neutrophilic leukocytosis)?
1) Negative leukocyte alkaline phosphatase (LAP stain) in CML
2) Increased basophils in CML
3) t(9,22) presence
What is polycythemia vera (PV) caused by?
proliferation of mature myeloid cells- especially RBCS (granulocytes and platelets also increased)
Clinical symptoms of PV?
due to hyper viscosity of blood:
1) blurry vision and headache
2) flushed face due to congestion
3) itching after bathing (histamine mediated)
4) risk of venous thrombosis
Treatment for PV?
1) phlebotomy
2) hydroxyurea
without treatment, death usually occurs in 1 year
How is PV distinguished from reactive polycythemia?
1) In PV, EPO levels are decreased and SaO2 is normal
2) In reactive polycythemia, SaO2 is low and EPO is increased
What is essential thrombocythemia (ET) caused by?
neoplastic proliferation of mature myeloid cells, especially platelets
PV and ET (and myelofibrosis sometimes) are both associated with what?
Jak2 kinase mutation
T or F. ET commonly progresses to acute leukemia
F, hardly ever progress and no significant risk for hyperuricemia or gout
What is myelofibrosis caused by?
neoplastic proliferation of mature myeloid cells, especially megakaryocytes
What is the root cause of marrow fibrosis in myelofibrosis?
megakaryocytes produce excess platelet- derived growth factor (PDGF)
What is common on a smear in myelofibrosis?
tear drop RBCs
Painful LAD is indicative of what?
acute infection
Painless LAD is indicative of what?
- chronic inflammation
- metastatic carcinoma
- lymphoma
What are lymphomas caused by?
noeplastic proliferation of lymphoid cells that forms a mass; may arise in lymph node or extranodal tissue
Subtypes of lymphoma?
-Hodgkins (40%) and non-Hodgkins (60%)
NHL is further divided based on what?
cell type (B vs T cell), pattern of cell growth expression of surface markers, and cytogenetic translocations
Subtypes of NHL?
1) small B cell (many types)
2) intermediate sized B cell (Burkitt lymphoma)
3) large B cell (diffuse large B-cell lymphoma)
High yield subtypes of small B cell NHL?
- follicular lymphoma
- mantle cell lymphoma
- marginal zone lymphoma
- small lymphocytic lymphoma
What is follicular lymphoma?
neoplastic proliferation of small B cell (CD20+) that form follicle-like nodules
Patient population in follicular lymphoma?
late adulthood (with painless LAD)
Root cause of follicular lymphoma?
t(14,18) translocation in which BCL2 on chrome 18 translocates to the Ig heavy chain locus on chrome 14 resulting in over-expression of BCL2
Treatment for follicular lymphoma?
rituximab or low-dose chemo
Follicular lymphoma can progress to what?
diffuse large B-cell lymphoma (lymph nodes enlarge)
How is follicular lymphoma distinguished from reactive follicular hyperplasia?
- disruption of normal lymph node architecture
- lack of tangible body macrophages in germinal centers
- Bcl2 expresison in follicles
- monoclonality
What is mantle cell lymphoma?
neoplasitc proliferation of small B cell (CD20+) that expands the mantle zone
Patient population in mantle cell lymphoma?
late adulthood (with painless LAD)
Root cause of mantle cell lymphoma?
t(11,14) - Cyclin D1 gene on chrom 11 translocates to Ig heavy chain locus on chrome 14 causing over-expression of cyclin D1
What is marginal zone lymphoma?
neoplasitc proliferation of small B cell (CD20+) that expands the marginal zone
What is marginal zone lymphoma associated with?
- Hashimoto thyroiditis
- Sjogren syndrome
- H pylori gastritis
What is Burkitt lymphoma?
neoplastic proliferation of intermediate-sized B cells (CD20+)
What is Burkitt lymphoma associated with?
EBV
How does burkitt lymphoma classically present?
as an extranodal mass in a child or young adult
i. african form usually involves the jaw
ii. sporadic form usually involves the abdomen
What drives Burkitt lymphoma?
t(8,14) translocation of c-myc (8) to the Ig heavy chain locus (14) promoting cell growth
What is diffuse large B-cell lymphoma?
neoplastic proliferation of large B cells (CD20+); most common form of NHL
clinically aggressive
How does diffuse large B-cell lymphoma arise?
sporadically or from transformation of a low-grade lymphoma (e.g. follicular lymphoma)
How does diffuse large B-cell lymphoma present?
in late adulthood as an enlarging lymph node or an extranodal mass
What is Hodgkin lymphoma (HL)?
neoplastic proliferation of Reed-Sternberg (RS) cells, which are large B cells with multi lobed nuclei and prominent nucleoli (owl-eyed)
HL is classically positive for?
CD15, CD20
RS cells secrete cytokines. What can this lead to?
- occasionally results in ‘B’ symptoms (fever, chill, weight loss, and night sweats)
- attract reactive lymphocytes, plasma cells, macrophages, and eosinophils
- possibly fibrosis
Subtypes of HL:
- nodular sclerosis (most common)
- lymphocyte-rich (best prognosis)
- mixed cellularity(abundant eosinophils via IL-5)
- lymphocyte-depleted (most aggressive type)
Lymphocyte-depleted HL is common in what patient population?
- elderly
- HIV+
