Mastocytosis Flashcards
What drives the proliferation of mast cells in mastocytosis?
Activating somatic mutation of c-kit receptor (CD117) on mast cells
What are the cutaneous forms of mast cell dz?
- urticaria pigmentosa
- diffuse
- mastocytoma (single or multiple)
- telangiectasia macularis eruptiva perstans (TMEP) [more adults]
When does cutaneous mastocytosis usually present by?
70% appear before puberty, most present before 2 years of age
What does age of presentation have to do with prognosis for systemic mastocytosis?
Childhood (more benign course - resolves by puberty) vs adult (more likely to have systemic involvement - chronic course)
Clinical characteristics of urticaria pigmentosa?
Occurs in adults and children (most common presentation in children)
- Favors the trunk and proximal extremities, spares central face, palms/soles
- lesion morphology: papular and papulonodular lesions in children and small red-brown macules and papules in adults
How is the morphology of urticaria pigmentosa different between adults and children?
Adults: small red-brown macules and papules in adults
Children: papules and papulonodules
When do solitary mastocytomas usually appear?
Most common at birth or in infancy
Clinical presentation of mastocytoma (solitary or multiple)?
One to several papules, nodules, or plaques with yellow-tan to red-brown color (lots of mast cells infiltrating the papillary dermis) –> give skin leathery appearance and texture)
In what age group is diffuse cutaneous mastocytosis most commonly seen in?
Infants most commonly, less common in adults
Clinical presentation of diffuse cutaneous mastocytoma?
Diffuse infiltration of mast cells with multiple erosions: so many mast cell (+) that you get widespread degranulation and edema which leads to bulla and erosions
look for a blister on top of an orange-brown plaque
In what age group is TMEP most common in?
Adults
What is the most common presentation of TMEP?
Telangiectatic macules and patches w/o significant hyperpigmentation
Note: there are few mast cells and these are focused around papillary dermal vessels. This leads to vessel dilation and edema leading to telangiectasia
Does the childhood variant have a high risk of systemic manifestations of mastocytosis?
NO, the adult variant is a higher risk for underlying systemic disease/involvement
What systemic manifestations are seen in systemic mastocytosis and is there high risk of heme malignancy?
- Adult variant commonly have bone marrow involvement BUT no long-term hematologic sequelae (not paraneoplastic or underlying heme malignancy)
- Systemic mastocytosis pts occasionally develop bone loss, hepatosplenomegaly, LAN and infiltration of mast cells into GI tract
What mutation should be looked for in evaluating mastocytosis?
c-kit mutation at codon 816
What workup should be performed for mastocytosis when working up if there is systemic disease?
- look for c-kit mutation at codon 816 (tx with TKI - dasatinib, nilotinib, midostaurin –> multitargeted TKI)
- check CBC –> if abnormal (neutrophilia/eosinophilia) –> bone marrow bx (look for CD2 and/or CD25 positive mast cells) - remember: CD25 also a/w HTLV (+) ATCL
- check tryptase levels (> 20 ng/ml) and urine 1,4-methylimidazole acetic acid (histamine metabolite)
- r/o underlying clonal myeloid disorder that can also increase tryptase levels (r/o hypereosinophilic syndrome)
What levels of tryptase are concerning for systemic mastocytosis?
> 20 ng/ml
What can be given if the patient has GI sx’s from mastocytosis?
Cromolyn sodium can stabilize mast cells and treat GI complaints
What drugs can trigger degranulation of mast cells?
NSAIDs, opiates, aspirin, vancomycin, polymyxin B, curare
What is the other name for the Leder stain/
Chloroacetate esterase
What part of the cell does leder stain stain?
Mast cell cytoplasm, colors it red
What stains are not dependent on the presence of granules (good for degranulated lesions)
CD117 (c-kit)
Leder
What mast cell disease can the Leder stain be particularly useful in?
TMEP (mast cell burden is low)
What is the location in the skin for most mastocytomas histologically?
Deep papillary dermis > reticular dermis > sub-cutaneous
What kinase inhibitor can you not use in mastocytosis?
Imatinib (resistant)
What is the prognosis of solitary mastocytoma?
Self resolves in most over 1-3 years
What is the prognosis of urticaria pigmentosa usually?
Symptoms usually improve by early adolescence, but skin lesions may not completely resolve
What cutaneous exam finding may be more associated with systemic symptoms in urticaria pigmentosa?
Increased number of lesions
What are the most common systemic sx’s in urticaria pigmentosa?
Diarrhea, abdominal pain, and wheezing.
Dyspnea are most common symptoms. Anaphylaxis is rare, but possible
What physical exam finding is present in all forms of cutaneous mastocytosis (except TMEP)?
Darier’s sign (local irritation or rubbing leads to urticarial wheal after friction)
What symptoms occur in systemic mastocytosis?
Symptoms include skeletal lesions, bone marrow involvement, hepatosplenomegaly, lymphadenopathy, GI symptoms (diarrhea, abdominal pain, nausea/ vomiting, and GI hemorrhage), and mixed organic brain syndrome
In what form of systemic mastocytosis can imatinib be used in?
Those with FIP1L1-PDGFRA gene rearrangement
Treatments for systemic mastocytosis?
Antihistamines (H1 and H2 antagonists), topical/ systemic steroids, topical calcineurin inhibitors, oral cromolyn, PUVA/UVA1, intramuscular epinephrine, other kinase inhibitors
