6 - 42 - MASTOCYTOSIS Flashcards
hallmark of mastocytosis
pathologic accumulation of mast cells in tissues
Mastocytosis is usually associated with what somatic activating mutations?
**c-kit **with the 816 codon mutation being most common
Somatic mutations in codon 816 of c-kit, lead to amino acid substitutions (D816V, D816Y, D816F, D816I, and D816H), and cause constitutive activation of KIT, resulting in continued mast cell growth and development
ligand for KIT and is required for mast cell proliferation and survival
Stem cell factor
- Mast cells arise from the bone marrow as agranular, undifferentiated, CD34+, KIT+ (CD117) pluripotent progenitor cells.
- After migrating into tissues, immature mast cells assume their typical granular morphology.10 KIT, a Type III tyrosine kinase is the product of the protooncogene c-kit located on chromosome 4q12.
- This enzyme is expressed on mast cells, as well as melanocytes, primitive hematopoietic stem cells, primordial germ cells, and interstitial cells of Cajal and serves as the receptor for its ligand, stem cell factor (SCF).
- Crosslinking of KIT by SCF is essential for mast cell maturation.
- Mature mast cells require SCF for survival
Diagnostic Criteria for Systemic Mastocytosis (Major and One Minor or Three Minor Criteria Are Needed)
originally described in children and is the most common skin manifestation of childhood-onset CM
Urticaria pigmentosa
UP manifestation in children
- UP lesions in children appear as tan to brown papules and, less commonly, as macules, ranging in size from 1.0 to 2.5 cm in diameter
- These lesions may be present at birth or arise during infancy.
- They frequently appear on the trunk and often spare the central face, scalp, palms, and soles.
area of predilection of urticaria pigmentosa
trunk
They frequently appear on the trunk and often spare the central face, scalp, palms, and soles.
Area of predilection of CM on adults
trunk and proximal extremities
Adult skin lesions are most numerous on the trunk and proximal extremities and appear less frequently on the face, distal extremities, or palms and soles.
Area of predilection of solitary mastocytomas
distal extremities
How do you elicit Darier Sign
Scratching or rubbing skin lesions leads to urtication and erythema
- This reaction is readily demonstrated in childhood UP and mastocytomas, but often is less pronounced in adult skin lesions
- The difference in lesional skin reactivity between children and adults with CM is best explained by the observation that mast cell concentrations in mastocytomas and childhood UP are 150-fold and 40-fold greater than in normal skin, respectively, whereas the mast cell content in lesions of adult mastocytosis is only 8 times greater than normal controls
- Because trauma to mastocytomas is associated with systemic symptoms such as flushing and hypotension, vigorous scratching of UP lesions or mastocytomas is not advised
Diffuse CM (DCM) is seen almost exclusively in what age group
infants
Telangiectasia macularis eruptiva perstans is rare, and is seen almost exclusively in what age group?
adults
what type of cutaneous mastocytosis are usually positive to darier sign?
Childhood UP and mastocytomas
Extracutaneous disease is extremely uncommon in children, but when present, what symptoms are the most frequent?
GI symptoms are the most frequent.
GI symptoms in adults ranges from 25% to 70%. What is the most common symptom?
- Diarrhea is the most common symptom and may result from gastric hypersecretion, increased motility, and/or malabsorption.
- Increased gastric acid secretion is likely a result of elevated histamine release, which may cause gastritis and peptic ulcer disease.
- Malabsorption with associated diarrhea is limited to a subset of patients with usually more advanced disease.
special stains for mast cells
toluidine blue, Giemsa, or monoclonal antibodies that recognize mast cell tryptase or CD117 (KIT)
correlate with the extent of mast cell disease.
Total (α + β) serum tryptase levels
may be worthwhile as a diagnostic test in patients without cutaneous lesions and in whom the diagnosis of mastocytosis is unclear.
Determinations of urinary histamine metabolite levels
major urinary metabolite of histamine: 1,4-methylimidazole acetic acid
Methylhistamine is next most common urinary histamine metabolite, and can be measured if 1,4-methylimidazole acetic acid levels are not available in commercial laboratories
often persistently elevated in SM patients and correlates with the extent of mast cell disease
Algorithm for a diagnostic evaluation of new-onset mastocytosis
Treatment of Cutaneous Mastocytosis
Treatment of Noncutaneous Mastocytosis Symptoms
