This is a Powerpoint presentation by Dr. Jerriton Brewin DVL 1st year PG on Mastocytosis.

2. INTRODUCTION
• Rare acquired condition.
• Characterized by too many mast cells
in the skin and other tissues.
• Reported first in 1869 as a form of
urticaria.
• 1877 - mast cell was discovered (by
Paul Ehrlich).
• 1878 - UP got its name (by Sangster).

3. EPIDEMIOLOGY
• M/C in children (55% by 2 years)
• Childhood form - before puberty.
• No sex preference.
• Mostly no positive family history.

4. PATHOGENESIS

5. • SCF is a growth factor & ligand of KIT,
which inturn increases growth & reduces
apoptosis of mast cells.
• SCF encoded by chr. 12; has membrane
bound & soluble form.
• SCF also produced by keratinocytes.

6. • Normally, SCF (the ligand) binds to KIT &
matures the mast cell in tissue.
• Activating mutations of KIT leads to
ligand-independent activation of KIT,
leading to proliferation, maturation &
reduced apoptosis of mast cells.

8. WHO CLASSIFICATION (2008)

9. REVISED SM CLASSIFICATION (2010)
• Indolent SM
• Smoldering SM
• Aggressive SM
• SM associated with an unclassifiable
myeloproliferative neoplasm

10. WHO SM CLASSIFICATION 2016 (UPDATE)
• ISM
• SSM
• SM with AHN
• ASM
• MCL
• MC Sarcoma

11. CLINICAL SPECTRUM

12. CLINICAL SPECTRUM
CHILDHOOD
ONSET
ADULT ONSET
AGE First 2 – 4 years 26 – 32 years
RISK OF SYSTEMIC DS Rare; brief &
undergoes
spontaneous
resolution
Progressive & chronic
course
PROGNOSIS 50% resolve by
puberty
Persists lifelong
C-KIT MUTATION Absent Present

13. CLINICAL FEATURES (CM)
URTICARIA PIGMENTOSA
• CHILDREN: Tan to brown papules (or
macules) 1 – 2.5 cm on trunk, sparking face,
scalp, palms, soles. Numbers ↓ with age.
• ADULTS: Reddish brown macules (and
papules) less than 0.5 cm, more on trunk &
proximal extremities. Numbers ↑ with age.
Can present with ISM.

15. VARIABLE DEGREE OF
HYPERPIGMENTATION

16. POSITIVE DARIER’S SIGN

17. Darier’s Sign –
• Absent in adult UP and childhood UP with
resolving lesions.
• Also in childhood mastocytomas.
• Due to 150 fold increase in mast cell conc. in
lesions of childhood UP and 40 fold increase
in childhood mastocytomas.
• False positive in xanthogranuloma and acute
lymphoblastic leukaemia of neonates.

18. MASTOCYTOMA
• M/C before 6 months.
• Distal extremities.
• Tan-brown nodules.
• Positive Darier’s sign.
• Trauma to lesion -> flushing / hypotension.

19. MASTOCYTOMA

20. DIFFUSE CUTANEOUS MASTOCYTOSIS
• Exclusively in infants; less < 3 years.
• Generalised Peau d’ orange skin with yellow-
brown discoloration.
• Doughy cossistency & leather grain app.
• Dermographism & blister formation
frequently occurs in first few years.

21. DIFFUSE CUTANEOUS MASTOCYTOSIS

22. PSEUDOXANTHOMATOUS MASTOCYTOSIS
• Variant of DCM.
• Infants.
• Non-pigmented form.
• Generalized yellowish, ovoid, and skin color
papular eruption.
• Partial Darier’s sign – erythema without
whealing on stroking the skin.
• Brown or tawny olive stains.

23. PSEUDOXANTHOMATOUS MASTOCYTOSIS

24. TELANGIECTASIA MACLURARIS ERUPTIVA PERSTANS
• M/C in adults.
• Obese mid-age women.
• Ill defined tan to brown generalized, red,
telangiectatic macules, 2-6 mm.
• Absent pruritis, purpura & blister formation.
• Absent Darier’s sign.
• Dermascopy: Reticular pattern telangiectasia.

25. TELANGIECTASIA MACLURARIS ERUPTIVA PERSTANS

26. DIAGNOSTIC CRITERIA: CM
Major –
Typical skin lesion
Minor –
(1) Monomorphic mast cell infiltrate that consists of
either:
a. Large aggregates of tryptase-positive mast cells
(>15 cells/cluster) or
b. Scattered mast cells exceeding 20 cells per
microscopic high power field.
(2) Detection of a c-KIT mutation at codon 816 in
lesional skin.

27. CLINICAL FEATURES (SM)

29. ABSENT PULMONARY FEATURES!

31. DIAGNOSTIC CRITERIA: SM
2016 WHO UPDATE

32. DIAGNOSTIC CRITERIA: SM
ISM
WHO criteria for SM met, MC burden low, +/- skin
lesions, no C findings, no evidence of AHNMD
SSM
WHO criteria for SM met, typically with skin lesions,
with 2 or more B findings, but no C findings.
BMM
ISM with BM involvement

34. DIAGNOSTIC CRITERIA: SM
SM-AHNMD/AHN
Meets criteria for SM and also criteria for an
AHNMD (MDS, MPN, MDS/MPN, AML), or other
WHO-defined myeloid hematologic neoplasm, +/-
skin lesions.
ASM
Meets criteria for SM with one or more C
findings. No evidence of MCL, +/- skin lesions.

35. DIAGNOSTIC CRITERIA: SM
MCL
• Meets criteria for SM. BM biopsy shows a diffuse
infiltration, usually compact, by atypical, immature
MCs. BM aspirate smears show 20% or more MCs.
• Typical MCL: MCs comprise 10% or more of
peripheral blood white cells.
• Aleukemic MCL: < 10% of peripheral blood white
cells are MCs. Usually without skin lesions.

36. DIFFERENTIALS: CM
• Urticaria (Transcient; no hyperpigmentation as
UP)
• Epidermolysis bullosa or toxic epidermal
necrolysis (DCM)
• Bullous d/o (bullous arthropod bites, bullous
impetigo, herpes simplex viral infection, BP,
LABD, etc.)
• LP Pigmentosus (TMEP)

37. DIFFERENTIALS: CM
• Multiple nevi
• Langerhan Cell Histiocytosis
• Juvenile xanthogranulomas
• Nodular scabies
• Café-au-lait spots
• Multiple cutaneous lentiginosis
• Post-inflammatory hyperigmentation

38. DIFFERENTIALS: SM
• Flushing resembles carcinoid syndrome.
• Headache resembles migaine.
• Palpitation, tachycardia, syncope – CVS.
• Chronic diarrohea, abdomen pain –
Malabsorption syndrome, gastritis.

39. INVESTIGATIONS
• For CM -> Skin biposy (lesional skin)
Precautions:
1. Don’t rub / scratch skin before Bx.
2. Don’t over-manipulate tissue by forceps.
3. Infiltrate around lesion.
4. Avoid adrenaline combination.
5. Transport in normal saline.

41. • Perivascular accumulation of mast cells in all
types.
• In UP, mast cells are in perivascular papillary
dermis.
• In mastocytomas, mast cells are in entire
dermis.
• In DCM, band-like infiltrate of mast cells.
• TMEP – Few mast cells around superficial
vascular plexus.

42. LEDER METHOD GIEMSA STAIN

43. IHC: MAB recognize KIT IHC: MAB - Tryptase

44. For SM -
1. CBC (reflects BM failure)
2. BM biposy
3. Molecular diagnostic studies for c-KIT mutations.
4. Serum α-Tryptase > 20 ng/ml
5. Plasma histamine (highest at 2 AM, lowest at 2 PM)
6. Urinary:
N-Methyl-histamine
N-Methyl-imidazole-acetic acid
Prostaglandin D2 metabolite

46. TREATMENT
AVOID TRIGGERS
• Alcohol
• Anticholinergic medications
• Aspirin
• NSAIDS
• Heat
• Friction
• Narcotics (e.g. morphine, codeine)
• Polymyxin B sulfate
• Systemic anesthetics

47. FOR CM
FIRST LINE –
1. Emollients
2. H1 +/- H2 Antihistamines
SECOND LINE –
1. Topical steroids, calcineurin inhibitors
2. Leukotriene antagonists
3. Oral cromolyn sodium
4. PUVA (adults)
5. Pulsed dye laser (TMEP)

48. FOR SM
GIT SYMPTOMS
H2 blockers, oral cromolyn, PPIs
CVS SYMPTOMS
SC adrenaline (anaphylaxis), H1, H2 blockers, steroids
MUSCULOSKELETAL
Calcium & Vit D supplement, Bisphosphonates
HAEMATOLOGICAL
Appropriate systemic chemotherapy

49. For Cytoreductive surgeries -
1. IFN-α (ASM)
2. Cladribine (2-Chloro-deoxy-adenosine)
TK inhibitors (Imatinib, Masitinib)
Splectomy
Allogenic BMT

50. 2016 NEWER UPDATES IN TREATMENT
HSCT
• Patients with advanced SM, including MCL.
• Should be considered for those who are young
and fit and have a suitable transplant donor.
TKi
• KIT inhibitor, Midostaurin.
• For ASM & MCL.
• Waiting to be approved as first line for
advanced SM.

51. REFERENCES
1. Valent, Peter et al. “Mastocytosis: 2016 updated WHO
classification and novel emerging treatment concepts” Blood
vol. 129,11 (2017): 1420-1427.
2. Valent P, Escribano L, et. al., Proposed diagnostic algorithm for
patients with suspected mastocytosis: a proposal of the
European Competence Network on Mastocytosis. Allergy 2014;
69: 1267–1274.
3. Rooks Textbook of Dermatology.
4. IADVL Textbook of Dermatology.
5. Bolognia’s Dermatology.
6. Fitzpatrick’s Dermatology.