Home   Chapter Home   Jobs   Conferences   Fellowships   Books



Advertisement

Chronic Myeloid Neoplasms

Myeloproliferative neoplasms (MPN)

Mast cell disease


Reviewer: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 11 August 2011, last major update August 2011
Copyright: (c) 2001-2011, PathologyOutlines.com, Inc.

Definition
=========================================================================

● See also discussions of mastocytosis in these chapters: Bone, Lymph Node, Skin-nontumor, Spleen
● Variable symptoms of diarrhea, weight loss, weakness, fractures or osteoporosis in 25%, arthralgia, flushing, bronchospasm
● Most commonly affected sites are skin (urticaria pigmentosa) and bone marrow
● Serum tryptase may predict bone marrow involvement (Haematologica 2008;93:120)
● May be associated with clonally related second myeloid neoplasm (J Clin Pathol 2004;57:604), including primary myelofibrosis (J Mol Diagn 2008;10:58)

Diagnosis
=========================================================================

● Examine bone marrow with tryptase stain to confirm presence of abnormal (spindle shaped) mast cells, use flow cytometry of bone marrow to look for CD25+ (phenotypically abnormal) mast cells, mutation screening to find KIT D816V and to exclude other abnormalities (Haematologica 2008;93:6)

Diagnostic criteria:
● Mast cell disease is working diagnosis if (a) bone marrow aggregates of morphologically abnormal mast cells are present, or (b) when histology is equivocal, if KIT D816V or phenotypically abnormal (CD25+) mast cells are present
● Other requirements: no BCR–ABL, no dyserythropoiesis, no granulocyte dysplasia, no monocytosis, no rearrangements of PDGFRA, PDGFRB or FGFR1

Cutaneous mastocytosis:
● Multifocal or diffuse infiltrates of morphologically abnormal or immunophenotypically clonal mast cells within the skin
● Absence of features of systemic mastocytosis
● Can have clinical findings of urticaria pigmentosa, diffuse cutaneous mastocytosis or solitary mastocytoma

Systemic mastocytosis (SM):
● Major criteria and one minor OR three minor criterion

Major criteria:
● Aggregates (>15 cells) of mast cells in bone marrow or extracutaneous organs

Minor criteria:
● >25% immature, spindled or atypical mast cells in bone marrow or extracutaneous organs
● Presence of KIT D816V point mutation
● Phenotypic expression of CD2 or CD25
● >20 ng/ml serum tryptase levels in the absence of clonal myeloid disorder

Various clinical patterns include:
● Indolent SM (low mast cell burden with no skin lesions)
● SM associated with clonal hematologic non-mast cell lineage disease (MDS, MPN, AML or lymphoma)
● Aggressive SM (meets criteria for SM, no evidence of mast cell leukemia or skin involvement)
● Mast cell leukemia (mast cells >20% of nucleated marrow cells, aleukemic if <10% of WBC are mast cells)
● Extracutaneous mastocytoma (unifocal mast cell tumor with nondestructive growth pattern)
● Mast cell sarcoma (unifocal, destructive growth pattern with high grade cytological features)

Treatment
=========================================================================

● May not be necessary if indolent
● IFN-alpha and cladribine if systematic
● Usually resistant to imatinib (since the D816V mutation causes ligand-independent activation of KIT tyrosine kinase) (Curr Allergy Asthma Rep 2007;7:248)

Poor prognostic factors
=========================================================================

● Late onset of symptoms, absence of cutaneous involvement, elevated LDH, anemia, bone marrow hypercellularity, qualitative peripheral blood abnormalities, elevated alkaline phosphatase, and organomegaly

Micro description
=========================================================================

● Paratrabecular aggregates resembling microgranulomas of oval or spindled cells with clear cytoplasm and distinct cell outlines resembling hairy cell leukemia
● Associated with eosinophils and thickened bone; focal lesions may be perivascular and associated with medial or adventitial hypertrophy and collagen fibrosis

Micro images
=========================================================================


Bone marrow biopsy:
   
Various images


Chymase staining


Sacrum (H&E and tryptase)

Bone marrow smear:

Various images

   
With an associated clonal hematological non-mast cell lineage disease

Positive stains
=========================================================================

● Tryptase, CD25 (Am J Surg Pathol 2004;28:1319)
● CD68, CD117/kit
● Also Giemsa, toluidine blue, polychrome methylene blue, chloroacetate esterase (Leder), CD2, CD9, CD33, CD45

Negative stains
=========================================================================

● Myeloperoxidase, CD20, CD14, CD15, CD16

Molecular description
=========================================================================

● KIT D816V mutation most common
● Other point mutations involve exon 17, such as D816Y, D816H, D816F (Proc Natl Acad Sci USA 1995;92:10560, Blood 2006;108:2366)

Differential diagnosis
=========================================================================

Mast cell hyperplasia: diffuse interstitial pattern in bone marrow, round CD25 negative mast cells (Am J Clin Pathol 2005;124:560)

Additional references
=========================================================================

eMedicine #1, #2, Arch Pathol Lab Med 2007;131:784

End of Chronic Myeloid Neoplasms > Myeloproliferative neoplasms (MPN) > Mast cell disease


This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).