B-23/118 Purpura/mastocytosis

Front 1

What precursors give rise to Mast Cells?

Back 1

CD34+ pluripotent cells

Front 2

What do mast cells precursors express?

Back 2

Express CD34, KIT & IgG receptors (FcγRII)
Do not express high affinity IgE receptors (FcεRI)

Front 3

Tyrosine Kinase Receptor aka?

Back 3

CD117

Front 4

What is KIT?

Back 4

protein product of proto-oncogene c-kit located on chromosome 4q12 (belongs to the type III receptor tyrosin kinase subfamily

Front 5

What cells express KIT?

Back 5

mast cells, melanocytes, primitive hematopoietic stem cells, primordial germ cells, and interstitial cells of Cajal

Front 6

What is the ligand for KIT?

Back 6

SCF = stem cell factor
aka mast cell growth factor

Front 7

SCF induces mast cell precursors to do with with their protein expression?

Back 7

In presence of SCF, peripheral blood mast cell precursors:
Become KIT+, CD34-, FcgammaRII- & FcepsilonRI+
Develop characteristic cytoplasmic granules

Front 8

What is the most common KIT mutation in Mastocytosis?
What other codon mutations have been reported?

Back 8

somatic point mutations in codon 816
- activation mutation of KIT

Other mutations: Codon 560 activating, Codon 820 activating, Codon 839 INactivating

(NO MUTATIONS FOUND IN FAMILIAL CASES)

Summary: Childhood Dz (no activating mutation in most, few 816, few 839)
Adult Dz (816 most, 560 few, 820 few)
Familial - none of either

Front 9

What other mutations have been identified in Mastocytosis?

Back 9

Chromosomal deletion 4q12 - juxtaposition of platelet derived growth factor receptor alpha & FIP1L1 (fusion protein that activates cells)

Front 10

What is another name for Leder Stain?

Back 10

Chloroacetate esterase - mast cells are red

Front 11

What are some Mast cell stains?

Back 11

Toluidine blue, Giemsa (blue), labeled avidin, Leder, mAb to tryptase or CD117 (KIT)

Front 12

What is formed in primary hemostasis?

Back 12

The platelet plug

Front 13

What is formed in secondary hemostasis?

Back 13

The clot

Front 14

What are the names given to the two pathways utilized in coagulation, and which lab test is used to measure each?

Back 14

Extrinsic: measured via PT
Intrinsic: measured via PTT

Front 15

What are the Vit K dependent coag factors and proteins

Back 15

Factors II, VII, IX, X and Proteins C & S

Front 16

Where does Vitamin K play a role?

Back 16

Factors are modified by a vitamin K-dependent post translational carboxylation of glutamic acid residues which allows these proteins to bind Ca and phospholipids. Allows them to function efficiently on plasma membranes.

Front 17

What two factors are inactivated by Protein C?

Back 17

Factors V and VIII

Front 18

Factor V leiden mutation leads to what?

Back 18

Unopposed thrombosis since the mutated Factor V is resistant to Protein C inactiviation

Front 19

What three labs are helpful in evaluating clotting d/o?

Back 19

Platelet count, PT, APTT

Front 20

High PT and normal PTT suggests?

Back 20

Factor VII deficiency OR coumadin use

Front 21

High PTT and normal PT suggests?

Back 21

von Willebrand Dz, lupus anticoagulant, heparin, acquired factor VIII inhibitor or deficiency of factor XII, XI, VIII, HMWK, or PK

Front 22

High PT and PTT suggests?

Back 22

Deficiency in fibrinogen, thrombin, factors V or X

Front 23

Name the test used to look for lupus anticoagulant activity?

Back 23

Russell viper venom test

Front 24

Name the five variants of the pigmented purpuras

Back 24

Schamberg's Disease
Purpura annularis telangiectodes of Majocchi
Pigmented purpuric lichenoid dermatitis of Gougerot and Blum
Eczematid-like purpura of Doucas and Kapetanakis
Lichen Aureus

Front 25

Schamberg's Dz -- aka? Describe.

Back 25

AKA, progressive pigmentary dermatosis of Schamberg
Most common pigmented purpura
Most typical on lower legs in older men

Front 26

Purpura annularis telangiectodes of Majocchi aka? Describe.

Back 26

AKA, Majocchi’s disease
Most common in adolescents or young adults (especially women)
1-3 cm annular plaques with telangiectasias and cayenne pepper petechiae in border
Asymptomatic

Front 27

PIgmented purpuric lichenoid dermatitis of Gougerot and Blum -- Describe

Back 27

Typically affect men 40-60 years of age
Lesions similar to Schamberg’s + lichenoid papules
Asymptomatic

Front 28

Lichen Aureus

Back 28

Usually solitary lesion on lower extremity
Patches with chronic rust- to purple-color and occasionally golden

Front 29

What is: Hypergammaglobulinemic Purpura of Waldenstrom? What Immune complexes are usu seen? What dz is it assoc with? Describe the lesions. Tx?

Back 29

Characterized by presence of immune complexes of IgG or IgA RF
Associated with autoimmune diseases (Sjogren’s, RA, SLE) or rarely lymphocytic or plasma cell malignancies
Recurring crops of macular hemorrhage (usually petechiae) or palpable purpura preceded by itch, tingling, or burning
Treatment:
Support stockings or ASA
Avoid precipitating factors (ETOH & prolonged standing)

Front 30

What is Gardner-Diamond Syndrome? Describe Lesions, length dz, histo? Clues to Dx?

Back 30

Clinical:
Psychiatric illness (depression, anxiety, personality disorders, etc.)
Lesions characterized by sudden onset of painful, swollen and hemorrhagic bruises of variable sizes on any area of body
Usually resolve in approx. 2 weeks
(Original reports with these lesions at injection sites of patient’s own blood and other agents)
Pathology:
Edema with mild perivascular mononuclear infiltrate
Clues to this diagnosis: atypical locations, geometric or peculiar morphology, lack of clear-cut precipitating factors

Front 31

Mondor’s Syndrome of Superficial Thrombophlebitis: Describe clinical picture and assoc sxs. Etiology? Treatment?

Back 31

Chest pain followed by one or more visible or palpable cords over chest wall
Tender and painful with elevation of breast and ipsilateral upper extremity
May see fever, arthralgias, erythema, and echymosis
Etiology
Trauma, excess activity, surgical procedure, infections, mastitis, or inflammatory conditions
Treatment
Heat, NSAIDs, rest, breast support
Aching pain usually ends within 10 days (cord may persist for weeks or months and may be tender)

Front 32

What CA is assoc with Mondor's Thrombophlebitis?

Back 32

Breast CA -- 12% of pts