Mastocytosis

Question 1

What drives the proliferation of mast cells in mastocytosis?

Answer 1

Activating somatic mutation of c-kit receptor (CD117) on mast cells

Question 2

What are the cutaneous forms of mast cell dz?

Answer 2

• urticaria pigmentosa
• diffuse
• mastocytoma (single or multiple)
• telangiectasia macularis eruptiva perstans (TMEP) [more adults]

Question 3

When does cutaneous mastocytosis usually present by?

Answer 3

70% appear before puberty, most present before 2 years of age

Question 4

What does age of presentation have to do with prognosis for systemic mastocytosis?

Answer 4

Childhood (more benign course - resolves by puberty) vs adult (more likely to have systemic involvement - chronic course)

Question 5

Clinical characteristics of urticaria pigmentosa?

Answer 5

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

Question 6

How is the morphology of urticaria pigmentosa different between adults and children?

Answer 6

Adults: small red-brown macules and papules in adults

Children: papules and papulonodules

Question 7

When do solitary mastocytomas usually appear?

Answer 7

Most common at birth or in infancy

Question 8

Clinical presentation of mastocytoma (solitary or multiple)?

Answer 8

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)

Question 9

In what age group is diffuse cutaneous mastocytosis most commonly seen in?

Answer 9

Infants most commonly, less common in adults

Question 10

Clinical presentation of diffuse cutaneous mastocytoma?

Answer 10

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

Question 11

In what age group is TMEP most common in?

Answer 11

Adults

Question 12

What is the most common presentation of TMEP?

Answer 12

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

Question 13

Does the childhood variant have a high risk of systemic manifestations of mastocytosis?

Answer 13

NO, the adult variant is a higher risk for underlying systemic disease/involvement

Question 14

What systemic manifestations are seen in systemic mastocytosis and is there high risk of heme malignancy?

Answer 14

• 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

Question 15

What mutation should be looked for in evaluating mastocytosis?

Answer 15

c-kit mutation at codon 816

Question 16

What workup should be performed for mastocytosis when working up if there is systemic disease?

Answer 16

• 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)

Question 17

What levels of tryptase are concerning for systemic mastocytosis?

Answer 17

> 20 ng/ml

Question 18

What can be given if the patient has GI sx’s from mastocytosis?

Answer 18

Cromolyn sodium can stabilize mast cells and treat GI complaints

Question 19

What drugs can trigger degranulation of mast cells?

Answer 19

NSAIDs, opiates, aspirin, vancomycin, polymyxin B, curare

Question 20

What is the other name for the Leder stain/

Answer 20

Chloroacetate esterase

Question 21

What part of the cell does leder stain stain?

Answer 21

Mast cell cytoplasm, colors it red

Question 22

What stains are not dependent on the presence of granules (good for degranulated lesions)

Answer 22

CD117 (c-kit)

Leder

Question 23

What mast cell disease can the Leder stain be particularly useful in?

Answer 23

TMEP (mast cell burden is low)

Question 24

What is the location in the skin for most mastocytomas histologically?

Answer 24

Deep papillary dermis > reticular dermis > sub-cutaneous

Question 25

What kinase inhibitor can you not use in mastocytosis?

Answer 25

Imatinib (resistant)

Question 26

What is the prognosis of solitary mastocytoma?

Answer 26

Self resolves in most over 1-3 years

Question 27

What is the prognosis of urticaria pigmentosa usually?

Answer 27

Symptoms usually improve by early adolescence, but skin lesions may not completely resolve

Question 28

What cutaneous exam finding may be more associated with systemic symptoms in urticaria pigmentosa?

Answer 28

Increased number of lesions

Question 29

What are the most common systemic sx’s in urticaria pigmentosa?

Answer 29

Diarrhea, abdominal pain, and wheezing.

Dyspnea are most common symptoms. Anaphylaxis is rare, but possible

Question 30

What physical exam finding is present in all forms of cutaneous mastocytosis (except TMEP)?

Answer 30

Darier’s sign (local irritation or rubbing leads to urticarial wheal after friction)

Question 31

What symptoms occur in systemic mastocytosis?

Answer 31

Symptoms include skeletal lesions, bone marrow involvement, hepatosplenomegaly, lymphadenopathy, GI symptoms (diarrhea, abdominal pain, nausea/ vomiting, and GI hemorrhage), and mixed organic brain syndrome

Question 32

In what form of systemic mastocytosis can imatinib be used in?

Answer 32

Those with FIP1L1-PDGFRA gene rearrangement

Question 33

Treatments for systemic mastocytosis?

Answer 33

Antihistamines (H1 and H2 antagonists), topical/ systemic steroids, topical calcineurin inhibitors, oral cromolyn, PUVA/UVA1, intramuscular epinephrine, other kinase inhibitors