Mastocytosis Flashcards
What are the differenti categories of
Mastocytosis ?
- Cutaneous mastocytosis
- Systemic mastocytosis
- Mast cell sarcoma
What subcategories are listed
under cutaneous mastocytosis ?
- urticaria pigmentosa/maculopapular cutaneous mastocytosis
- diffuse cutaneous mastocytosis
- mastocytoma of the skin
What are the different subcategories of
systemic mastocytosis ?
- indolent systemic mastocytosis (including the bone marrow)
- smouldering systemic mastocytosis
- systemic mastocytosis with an associated hematological neoplasm
- aggressive systemic mastocytosis
- mast cell leukemia
When can the diagnosis of
systemic mastocytosis be rendered ?
- when the major criterion and at least 1 minor criterion are present
- OR
- when >3 minor criteria are seen
What is the basic definition of
Mastocytosis?
- 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
What must be distinguished in mast cell disease?
- 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
What is the epidemiology of mast cell disease ?
- 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
Review localization
p. 62 other notes next slide
- >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
What are key clinical features of
cutaneous mastocytosis ?
- 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
What are the 4 clinical groups of
presenting symptoms of
systemic mastocytosis ?
- Constitutional symptoms
- fatigue, weight loss, fever, diaphoresis
- Skin manifestations
- pruritus, urticaria, dermatographism, flushing
- Mediator-related systemic events
- abdmonal pain, GI distres, syncope, headache, hypotension, tachicardia, respiratory symptoms
- Muskuloskeletal symptoms
- bone pain, osteopenia/osteoporosis, fractures, arthralgias, and myalgias
What physical findings can be seen
at diagnosis in mastocytosis ?
- splenomegaly (often minmal)
- lymphoadenopathy
- hepatomegaly
- Organomegaly is often absent in indolent systemic mastocytosis
- impaired organ function is seen in aggressive systemic mastocytosis
What is Mast Cell Activation Syndrome ?
- 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
- but it can occur in that setting as well as in other disorders
- 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
What are the hematological manifestations
of systemic mastocytosis ?
- 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
What is the significance of elevated
serum tryptase levels ?
- 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
Review microscopic findings
p. 64
What are morphologic features of
atypical mast cells ?
- 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
What immunohistochemical findings
are helpful in identifying neoplastic mast cells ?
- tryptase
- CD117
- CD2, CD25 and CD30
What is the definition of
cutaneous mastocytosis ?
- 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
What is the diagnosis of urticaria pigmentosa/
maculopapular cutaneous mastocytosis ?
- 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
- in adults lesions are usually disseminated and red-brown
- 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
What is diffuse cutaneous mastocytosis ?
- 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
What is typically seen in mastocytoma of the skin ?
- 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
What are the major criteria for
systemic mastocytosis ?
- multifocal, dense infiltrates of mast cells
- >15 mast cells per aggregate
- detected in sections of bone marrow or other extracutaneous organs
What are the minor criteria for
systemic mastocytosis ?
- 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
What are the B findings
in systemic mastocytosis ?
- 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
What are the C symptoms in systemic
mastocytosis ?
- 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
What are the criteria for indolent
systemic mastocytosis ?
- 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.
What are the criteria for
bone marrow mastocytosis ?
- similar findings to indolent SM
- burden of neoplastic cells is usually low
- serum tryptase levels are often normal or nearly normal
What is the morphology
of bone marrow mastocytosis ?
- 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
What are the criteria for
smoldering mastocytosis?
- 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
What are the criteria for Systemic Mastocytosis
with an associated hematological neoplasm ?
- 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
What are the criteria for Aggressive
Systemic Mastocytosis ?
- 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
What are the criteria for
mast cell leukemia ?
- 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
What are the criteria for
a mast cell sarcoma ?
- extremely rare entity
- localized destructive growth of mast cells
- distant spread occurs in the terminal phase and it can look like mast cell leukemia
