Mastocytosis

Definition

Mastocytosis is a term collectively used for a group of disorders in which there is abnormal accumulation of mast cells in one or multiple organs.

Epidemiology

Diagnostic criteria

major criterion: multifocal dense infiltrates of mast cells in extracutaneous biopsy, confirmed by special stains

minor criteria:

a: in an extracutaneous biopsy or bone marrow smear, more than 25% of the mast cells have a spindle-cell or atypical morphology

b: detection of c-kit mutation at codon 816

c: extracutaneous mast cells that co-express (CD2 or CD25) and CD117

d: serum total tryptase persistently >20ng/ml, in the absence of a myeloid disorder

"B" findings;

1. bone marrow shows >30% infiltration by mast cells OR serum total tryptase > 200 ng/ml.

2. signs of dysplasia/myeloproliferation in non-mast cell lineage but insufficient for a definite diagnosis of a haematopoietic neoplasm by WHO criteria.

3. hepatomegaly without impairment of liver function OR splenomegaly without hypersplenism OR lymphadenopathy.

"C" findings;

1. bone marrow dysfunction manifested by a cytopenia (ANC < 1.0.109/l OR haemoglobin<10g/dl OR platelets <100.109/l) but no frank non-mast cell haemopoietic neoplasm.

2. palpable hepatomegaly with impaired liver function, ascites or portal hypertension.

3. skeletal involvement with large foci of osteolysis or pathological fractures.

4. palpable splenomegaly with hypersplenism

5. malabsorption with weight loss due to gastrointestinal mastocytosis.

"B" findings;

1. bone marrow shows >30% infiltration by mast cells OR serum total tryptase > 200 ng/ml.

2. signs of dysplasia/myeloproliferation in non-mast cell lineage but insufficient for a definite diagnosis of a haematopoietic neoplasm by WHO criteria.

3. hepatomegaly without impairment of liver function OR splenomegaly without hypersplenism OR lymphadenopathy.

"C" findings;

1. bone marrow dysfunction manifested by a cytopenia (ANC < 1.0.109/l OR haemoglobin<10g/dl OR platelets <100.109/l) but no frank non-mast cell haemopoietic neoplasm.

2. palpable hepatomegaly with impaired liver function, ascites or portal hypertension.

3. skeletal involvement with large foci of osteolysis or pathological fractures.

4. palpable splenomegaly with hypersplenism

5. malabsorption with weight loss due to gastrointestinal mastocytosis.

"C" findings;

1. bone marrow dysfunction manifested by a cytopenia (ANC < 1.0.109/l OR haemoglobin<10g/dl OR platelets <100.109/l) but no frank non-mast cell haemopoietic neoplasm.

2. palpable hepatomegaly with impaired liver function, ascites or portal hypertension.

3. skeletal involvement with large foci of osteolysis or pathological fractures.

4. palpable splenomegaly with hypersplenism

5. malabsorption with weight loss due to gastrointestinal mastocytosis.

Positivity for CD2 or CD25 on flow cytometry has been described as highly diagnostic of systemic mastocytosis5.

Clinical features

signs and symptoms:

Histopathology

The infiltrating mast cells may be loosely scattered or form obvious clusters. Staining with Giemsa or for mast cell tryptase is strongly recommended for confirmation of their identity.

Immunohistochemistry

 

reactive bone marrow

myelogenous neoplasms

myelomastocytic leukaemia

 

number of cases

545

165

55

 

CD2

negative5

negative5

negative5

 

CD25

negative5

negative5

negative5

 

CD117

positive5

minority positive5

positive5

 

chloroacetate esterase

positive5

majority positive5

positive5

 

Tryptase

positive5

negative5

positive5

 
         

 

generally in mastocytosis

systemic indolent mastocytosis

systemic mastocytosis with associated clonal haemotologic non-mast cell lineage disease

aggressive systemic mastocytosis

mast cell leukaemia

isolated bone marrow mastocytosis

napthol ASD chloroacetate esterase

positive (may be negative poorly granulated neoplastic mast cells)0

 

 

 

 

 

tryptase

positive0

19/191

 

 

1/11

2/21

chymase

positive in a subpopulation0

 

 

 

 

 

lysozyme

positive

 

 

 

 

 

CD2

positive: negative in normal mast cells0, the proportion of positive cells is less than for CD255

13/191, 35/435

11/205

2/75

1/11, 2/35

2/21

CD14

negative0

 

 

 

 

 

CD15

negative0

0/191

 

 

0/11

0/21

CD16

negative0

 

 

 

 

 

CD20

 negative

 

 

 

 

 

CD25

positive (negative in normal mast cells)0

42/435

20/205

7/75

3/35

 

CD29

 

7/171

 

 

1/11

0/11

CD30

 

0/181

 

 

0/11

0/11

CD31

 

0/171

 

 

 

0/11

CD33

positive0

 

 

 

 

 

CD34

negative0 

0/181

 

 

0/11

0/21

CD45

positive0

18/181

 

 

1/11

2/21

CD51

 

7/141

 

 

 

 

CD56

 

0/141

 

 

 

0/21

CD68 (PG-M1)

positive0

18/181

 

 

1/11

2/21

CD117

positive0

19/191

 

 

1/11

2/21

bcl-xL

 

18/181

 

 

1/11

2/21

bcl-2

 

0/171

 

 

<5% of cells positive1

0/21

HLA-DR

 

17/171

 

 

1/11

2/21

myeloperoxidase

 negative

0/121

 

 

0/11

0/21

 

Cytogenetics

Point mutations in c-kit have been demonstrated in a very high proportion of cases of systemic mastocytosis5 and a new classification based on the type of mutation has been proposed. The predominant mutation in adult sporadic mastocytosis is Asp816Val, resulting in constitutive phosphorylation and activation of c-kit2. This mutation is rarely seen in paediatric cutaneous mastocytosis; when it is, the presentation and course are atypical. Myeolmastocytic leukaemia lacks c-kit mutations5.

Differential diagnosis

 

Prognosis

References

0World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

1Jordan, J. H., Walchshofer, S., Jurecka, W., Mosberger, I., Sperr, W. R., Wolff, K., Chott, A., Buhring, H. J., Lechner, K., Horny, H. P., Valent, P. Immunohistochemical properties of bone marrow mast cells in systemic mastocytosis: evidence for expression of CD2, CD117/Kit, and bcl-x(L) Hum Pathol 2001;32:545-552.

2Gibson, P. C., Cooper, K. CD117 (KIT): a diverse protein with selective applications in surgical pathology. Adv Anat Pathol 2002;9:65-69.

3Sperr, W.R., Walchshofer, S., Horny, H.P., Fodinger, M., Simonitsch, I., Fritsche-Polanz, R., Schwarzinger, I., Tschachler, E., Sillaber, C., Hagen, W., Geissler, K., Chott, A., Lechner, K. and Valent, P. Systemic mastocytosis associated with acute myeloid leukaemia: report of two cases and detection of the c-kit mutation Asp-816 to Val. Br J Haematol 1998;103:740-9.

4Li, W.V., Kapadia, S.B., Sonmez-Alpan, E. and Swerdlow, S.H. Immunohistochemical characterization of mast cell disease in paraffin sections using tryptase, CD68, myeloperoxidase, lysozyme, and CD20 antibodies. Mod Pathol 1996;9:982-8.

5Sotlar, K., H. P. Horny, et al. (2004). "CD25 indicates the neoplastic phenotype of mast cells: a novel immunohistochemical marker for the diagnosis of systemic mastocytosis (SM) in routinely processed bone marrow biopsy specimens." Am J Surg Pathol 28(10): 1319-25.

This page last revised 28.12.2002.