Mastocytosis Flashcards

1
Q

What are the differenti categories of

Mastocytosis ?

A
  • Cutaneous mastocytosis
  • Systemic mastocytosis
  • Mast cell sarcoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What subcategories are listed

under cutaneous mastocytosis ?

A
  • urticaria pigmentosa/maculopapular cutaneous mastocytosis
  • diffuse cutaneous mastocytosis
  • mastocytoma of the skin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the different subcategories of

systemic mastocytosis ?

A
  • indolent systemic mastocytosis (including the bone marrow)
  • smouldering systemic mastocytosis
  • systemic mastocytosis with an associated hematological neoplasm
  • aggressive systemic mastocytosis
  • mast cell leukemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

When can the diagnosis of

systemic mastocytosis be rendered ?

A
  • when the major criterion and at least 1 minor criterion are present
  • OR
  • when >3 minor criteria are seen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the basic definition of

Mastocytosis?

A
  • clonal neoplastic proliferation of mast cells that accumulate in one or more organ systems
  • disorder can be heterogeneous
    • can have skin lesions that spontaneously regress to overtly aggressive systemic disease with poor survival
  • Cutaneous mastocytosis
    • cellular infiltrate remains localized to the skin
  • Systemic mastocytosis
    • involement of at least one extracutaneous organ with or witout evidence of skin lesions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What must be distinguished in mast cell disease?

A
  • neoplastic vs. mast cell hyperplasia and mast cell activation states
    • the reactive mast cells do not have the IHC and molecular abnormalities that the neoplastic ones do
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the epidemiology of mast cell disease ?

A
  • mastocytosis can occur at any age but certain types occur at different time periods
  • cutaneous mastocytosis
    • more comon in children and can present at birth
    • much less common than adults with slight male predominance
  • systemic mastocytosis
    • diagnosed after the second decade
    • equal M:F
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Review localization

p. 62 other notes next slide

A
  • >80% with mastocytosis have skin involvement
  • systemic mastocytosis
    • BM is always involved
    • rarely have circulating mast cells
    • any tissue can be affected in systenic disease
    • note: aggressive variants usually do not have skin lesions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are key clinical features of

cutaneous mastocytosis ?

A
  • the three types all can urticate when stroked (Darier’s sign)
    • intraepidermal accumulation of melanin pigment also occurs
  • Urticaria Pigmentosa
    • blistering usually in patients < 3 years old
    • but blistering is non-specific
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the 4 clinical groups of

presenting symptoms of

systemic mastocytosis ?

A
  1. Constitutional symptoms
    1. fatigue, weight loss, fever, diaphoresis
  2. Skin manifestations
    1. pruritus, urticaria, dermatographism, flushing
  3. Mediator-related systemic events
    1. abdmonal pain, GI distres, syncope, headache, hypotension, tachicardia, respiratory symptoms
  4. Muskuloskeletal symptoms
    1. bone pain, osteopenia/osteoporosis, fractures, arthralgias, and myalgias
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What physical findings can be seen

at diagnosis in mastocytosis ?

A
  • splenomegaly (often minmal)
  • lymphoadenopathy
  • hepatomegaly
  • Organomegaly is often absent in indolent systemic mastocytosis
    • impaired organ function is seen in aggressive systemic mastocytosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is Mast Cell Activation Syndrome ?

A
  • severe mediator related symptoms occurring in temporal association with increased serum tryptase levels
  • this is NOT a subset of systemic mastocytosis
    • but it can occur in that setting as well as in other disorders
      • including IgE dependent allergic reactions
  • diagnosis in some patients does not fulfill criteria for systemic mastocytosis
    • but can have clonal mast cells with aberrant CD25 and KIT D816V mutations
    • these are called monoclonal MCAS

IMP: if there is diagnosed systemic mastocytosis it is key to mention MCAS because the symptoms are critical

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the hematological manifestations

of systemic mastocytosis ?

A
  • anemia, leukocytosis, eosinophilia (common), neutropenia and thrombocytopenia
  • bone marrow failure can occur in patients with systemic disease
  • circulating mast cells are rare and should raise the possibility of mast cell leukemia

Note: in 30% of cases of there is an associated hematological neoplasm

  • myeloid neoplasms are more common
  • prognosis depends on the hematological disorder and the mastocytosis but outcome usually determined by myeloid neoplasm
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the significance of elevated

serum tryptase levels ?

A
  • elevated serum tryptase levels >20 ng/mL suggests systemic mastocytosis and is one of the minor criterion
    • IMP: if there is an associated myeloid neoplasm paramter is not valid
  • in cutaneous mastocytosis
    • serum tryptase levels are not that elevated
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Review microscopic findings

p. 64

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are morphologic features of

atypical mast cells ?

A
  • marked spindling or hypogranularity
  • in high-grade mastocytosis
    • cytological atypia is pronounced
    • metachromatic blast cells are often seen in mast cell leukemia
    • bilobed or multilobed mast cells = promastocytes
      • generally indicate an aggressive mast cell proliferation
  • Mitosis can occur but even in high grade disease are not frequent
  • normal morphology can also been seen in neoplastic processes
17
Q

What immunohistochemical findings

are helpful in identifying neoplastic mast cells ?

A
  • tryptase
  • CD117
  • CD2, CD25 and CD30
18
Q

What is the definition of

cutaneous mastocytosis ?

A
  • need proof of an abnormal mast cell proliferation of the dermis
  • no evidence of systemic involvement
    • bone marrow, peripheral organs
    • criteria are not met
  • can have one or 2 of the minor diagnostic criteria
19
Q

What is the diagnosis of urticaria pigmentosa/

maculopapular cutaneous mastocytosis ?

A
  • most common form
  • in kids lesions are larger and more papular than other skin lesions
    • in adults lesions are usually disseminated and red-brown
      • generally have fewer mast cells
  • Microscopically
    • aggregates of spindle shaped mast cells filling the papillary dermis with extension into the reticular dermis
    • often perivascular and periadnexal
    • subset in kids can be non-pigmented
20
Q

What is diffuse cutaneous mastocytosis ?

A
  • much less common than urticaria pigmentosa
  • presents almost exclusively in childhood
  • skin is diffusely thickened and there are no individual lesions
    • peau d’orange look
    • can have a band-like infiltrate of mast cells or if massively infiltrated you will see features similar to a mastocytoma
21
Q

What is typically seen in mastocytoma of the skin ?

A
  • single lesion, almost exclusively in children
    • may see up to 2-3 lesions
  • histology
    • usually sheets of mature mast cells in the papillary or reticular dermis
    • may extend into subcutaneous tissue
    • no cytologic atypia which differentiates from mast cell sarcoma
22
Q

What are the major criteria for

systemic mastocytosis ?

A
  • multifocal, dense infiltrates of mast cells
    • >15 mast cells per aggregate
    • detected in sections of bone marrow or other extracutaneous organs
23
Q

What are the minor criteria for

systemic mastocytosis ?

A
  • In biopsy sections of BM or other organs
    • >25% of mast cells are spindle shaped or have atypical morphology
    • or >25% of mast cells on the aspirate smear are immature or atypical
  • Detection of activating point mutation KIT D816V
  • Mast cells express CD25 with or without CD2 in addition to normal mast cell markers
  • Serum total tryptase >20 ng/mL
    • unless there is an associated myeloid neoplasm and then the paramter is not valid
24
Q

What are the B findings

in systemic mastocytosis ?

A
  • high mast cell burden on bone marrow: >30% of total cells and serum tryptase > 200 ng/mL
  • signs of dysplasia or myelofproliferation in non-mast cell lineages but criteria are not met for another neoplasm
  • hepatomegaly without impairment of liver function, palpable splenomegaly without hypersplenism or lymphoadenopathy on palpation or imaging
25
Q

What are the C symptoms in systemic

mastocytosis ?

A
  • bone marrow dysfunction caused by infiltrating mast cells
    • >1 cytopenia
    • absolute neutrophil count < 1000
    • hemoglobin <10
    • platelet count. <100
  • palpable hepatomegaly with impairment of liver function, ascites or portal hypertension
  • skeletal involvement with osteolytic lesions with or without pathological fractures (not osteoporosis related)
  • palpable splenomegaly with hypersplenism
  • malabsorption with weight loss due to GI mast cell infiltration
26
Q

What are the criteria for indolent

systemic mastocytosis ?

A
  • meets general criteria for SM
  • No C findings
  • No evidence of associated hematological neoplasm
  • Low mast cell burden
  • Skin lesions are almost invariably present
  • KIT D816V is present >90%

Note: they can have one B finding but not more for this category.

27
Q

What are the criteria for

bone marrow mastocytosis ?

A
  • similar findings to indolent SM
  • burden of neoplastic cells is usually low
  • serum tryptase levels are often normal or nearly normal
28
Q

What is the morphology

of bone marrow mastocytosis ?

A
  • generally lesions have a core of small lymphocytes (target lesion) surrounded by polygonal mast cells with pale, faintly granular cytoplasm
  • reactive eosinophils are at the edges
  • lesions are usually well circumscribed
  • can be paratrabecular or perivascular
    • sometimes randomly distributed in bone marrow

IMP: mast cell proliferations induce fibrosis and osteosclerosis

29
Q

What are the criteria for

smoldering mastocytosis?

A
  • meets general criteria for SM
  • >2 B findings but NO C findings
  • No evidence of associated hematological neoplasm
  • High mast cell burden **
  • does not meet criteria for mast cell leukemia
    • but progression to aggressive SM or mast cell leukemia can occur
  • most have sin lesions
  • most have KIT D816V
    • mutation is detectable in many lineages
30
Q

What are the criteria for Systemic Mastocytosis

with an associated hematological neoplasm ?

A
  • meets general criteria for SM
  • meets criteria for a secondary neoplasm as a distinct WHO entity
    • most common is CMML
    • lymphoid neoplasms such as MM and lymphoma are rare
  • most cases have the KIT D816V mutation
    • also present in the myeloid compartment
31
Q

What are the criteria for Aggressive

Systemic Mastocytosis ?

A
  • meets the general criteria for SM
  • >1 C finding
  • does not meet criteria for mast cell leukemia
  • skin lesions are usually absent ***
  • mast cell burden
    • <20% in bone marrow but >5% are diagnosed as ASM in transformation
    • in these cases progression to mast cell leukemia is common
  • most have the KIT D816V mutation
32
Q

What are the criteria for

mast cell leukemia ?

A
  • meets general criteria for SM
  • BM biopsy with diffuse infiltration by atypical, immature mast cells
  • BM aspirate smears show >20% mast cells
  • mast cells account for >10% of the PB WBC
    • aleukemic variant is more common with only rare if any mast cells in the PB
  • skin lesions are usually absent
33
Q

What are the criteria for

a mast cell sarcoma ?

A
  • extremely rare entity
  • localized destructive growth of mast cells
  • distant spread occurs in the terminal phase and it can look like mast cell leukemia