Systemic Mastocytosis Workup

Author: Koyamangalath Krishnan, MD, FRCP, FACP; Chief Editor: Emmanuel C Besa, MD more...

Updated: Feb 15, 2012

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Laboratory Studies
Imaging Studies
Other Tests
Procedures
Histologic Findings
Staging
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References

Laboratory Studies

The peripheral blood picture can show anemia, thrombocytopenia, and leucocytosis. The most common abnormality found in the peripheral blood is anemia (45%). In some patients with systemic mastocytosis (systemic mast cell disease), eosinophilia, basophilia, thrombocytosis, and monocytosis can be observed.
Measurements of urinary N -methyl imidazole are useful in some patients with systemic mastocytosis (systemic mast cell disease).
Total serum tryptase levels of 20 ng/mL or higher in a baseline serum sample that is associated with a ratio of total–to–beta-tryptase ratio greater than 20:1 is suggestive of systemic mastocytosis (systemic mast cell disease).^[21]More than 50% of patients reveal a high tryptase level using the cut-off value of 11.5 ng/mL used in more recent studies.
Anemia (hemoglobin < 10.0 mg/dL), thrombocytopenia (platelet count < 150,000), hypoalbuminemia (albumin < 3.5 g/dL), and excess bone marrow blasts (>5%) have been shown on multivariate analysis to portend poor prognosis.^[13]

Imaging Studies

Some imaging studies may be necessary in patients with systemic mastocytosis (systemic mast cell disease) in order to identify the extent and stage of the disease.

For patients with abdominal pain, GI radiography, ultrasonography, and liver-spleen computed tomography (CT) scanning may be necessary.
Skeletal surveys and bone CT scanning may be necessary in patients with suspected bone involvement.

Other Tests

Cytogenetic data indicate that about 20% of patients with systemic mastocytosis have an abnormal karyotype. These include trisomy 8; monosomy 7; del (13q); del(5q); trisomy 10, 6, and 19; del(20q); and trisomy X. Cytogenetic abnormalities are more often seen with ASM and SM-AHNMD than with indolent SM.^[13]

Molecular testing for KIT D816V mutation is universally positive, whereas JAK2 V617F is rarely positive (4%).

The mast cell clone is CD-117 positive and CD-25 and/or CD-2 positive.

Bone marrow mast cells reveal 54% CD-2 positivity and 93% CD-25 positivity on flow cytometry, whereas on immunohistochemistry CD-2 positivity is 17% and CD-25 positivity is 100%.^[13]

Expression of CD-25 on mast cells is seen in systemic mastocytosis but is not noted in reactive states of mast cell hyperplasia.^[22]

Bone marrow aspiration and biopsy are essential in a patient who may have systemic mastocytosis (systemic mast cell disease).
When GI symptoms are present, perform GI procedures (eg, barium studies, endoscopy) to help confirm the diagnosis.
Patients with hepatomegaly can show evidence of mast cell infiltration on liver biopsy specimens.
Skin biopsy may be warranted in patients with skin manifestations.

Histologic Findings

Marrow cellularity ranges from normocellular to markedly hypercellular changes. Erythropoiesis is usually complete without any significant changes. Eosinophilia is a common finding from bone marrow histology. Hypocellular bone marrow and myelofibrosis are usually observed in late stages of systemic mastocytosis (systemic mast cell disease). Focal mast cell lesions in the bone marrow are found in approximately 90% of affected adult patients. A bone marrow smear is shown below.

Bone marrow aspirate, Romanowsky stain, high-definition magnification. Diagnosis is mastocytosis, and morphology is abnormal mast cells. This is a bone marrow smear from a patient with systemic mastocytosis. Several mast cells are present in this photograph. These mast cells are larger than normal mast cells and have more irregularly shaped nuclear outlines and less densely packed mast cell granules. Courtesy of the American Society of Hematology Slide Bank. Used with permission.

A typical mast cell has a spindle-shaped nucleus and fine eosinophilic granules visualized at high magnification. These cells are likely to return positive findings upon Giemsa staining. Other stains used to identify mast cells are toluidine blue, chloroacetate esterase, aminocaproate esterase, and tartrate-resistant acid phosphatase. Examples are shown in the images below.

Bone marrow aspirate, toluidine stain, low magnification. Diagnosis is mastocytosis, and morphology is abnormal mast cells. This is a toluidine blue stain of a bone marrow smear from a patient with marrow involvement by systemic mastocytosis. Five mast cells are present in this field. The mast cell granules are metachromatic with the toluidine blue reaction. Courtesy of the American Society of Hematology Slide Bank. Used with permission.

Bone marrow biopsy, toluidine stain, low magnification. Diagnosis is mastocytosis, and morphology is abnormal mast cell infiltrate. This is a toluidine blue stain of a bone marrow biopsy from a patient with systemic mastocytosis. The mast cells are metachromatic with toluidine blue and contain numerous purple granules. Courtesy of the American Society of Hematology Slide Bank. Used with permission.

The peripheral blood picture can show anemia, leukopenia, thrombocytopenia, and lymphopenia. The most common abnormality found in the peripheral blood is anemia. Eosinophilia, leukocytosis, basophilia, thrombocytosis, and monocytosis can be observed in some patients.

Spleen and lymphoid tissue involvement is an important manifestation in systemic mastocytosis (systemic mast cell disease). Mast cell infiltrates in the spleen can cause nodular areas that could be confused with lymphomas. A biopsy sample from the spleen can reveal findings similar to a myeloproliferative disorder or hairy cell leukemia. Histopathology of the spleen can show 2 types of involvement: (1) diffuse infiltration of the red pulp and sinuses and (2) focal infiltration of the white pulp.

Lymph node biopsy can show mast cell infiltrates, particularly in the paracortex. Follicles and medullary involvement can be observed in some cases. Lymph node biopsy samples are shown below.

Lymph node biopsy. Diagnosis is mastocytosis, morphology is mast cell infiltrate, and the organ is the lymph nodes. This is a lymph node biopsy from a person with systemic mastocytosis. The mast cells have a characteristic perifollicular distribution. Courtesy of the American Society of Hematology Slide Bank. Used with permission.

Lymph node biopsy, chloroacetate esterase stain. Diagnosis is mastocytosis, and morphology is mast cell infiltrate. This is a portion of a lymph node biopsy from a patient with systemic mastocytosis. The mast cells are chloroacetate esterase positive, which is characterized by an orange granular appearance. Courtesy of the American Society of Hematology Slide Bank. Used with permission.

Diagnostic criteria for systemic mastocytosis (systemic mast cell disease) are as follows:

Major criteria: Dense infiltrates of mast cells can be seen in bone marrow or other extracutaneous tissues. Mast cells should be seen in aggregates of 15 or more. Tryptase immunohistochemistry or metachromatic staining (eg, Giemsa, toluidine blue) should be used to confirm the presence of mast cells. Immunohistochemical staining for mast cells is more reliable than metachromatic staining.
Minor criteria: Major criteria may be absent in early disease. In this situation, the minor criteria are used to make the pathological diagnosis. Three of the following 4 minor criteria are required to make the diagnosis:
- Atypical mast cell morphology in 25% or more of the mast cells.
- Expression of CD2and /or CD25 in addition to normal mast cell markers
- Serum/plasma tryptase levels greater than 20 ng/mL.
- A codon-816 c-kit mutation in peripheral blood, bone marrow, or involved tissue.

Types of mastocytosis (World Health Organization criteria) are as follows:

Cutaneous mastocytosis
Indolent systemic mastocytosis (systemic mast cell disease)
Systemic mastocytosis with associated clonal hematologic non–mast cell lineage disease
Aggressive systemic mastocytosis
Mast cell leukemia
Mast cell sarcoma
Extracutaneous mastocytoma

Staging

The following is a classification for mastocytosis provided by Metcalfe in 1991.^[23]

Category I is indolent mastocytosis.
- Category IA is associated with skin involvement.
- Category IB is associated with systemic involvement, with or without skin involvement.
Category II is associated with a hematopoietic disorder.
- Category IIA is a dysmyelopoietic disorder.
- Category IIB encompasses myeloproliferative disorders.
- Category IIC is acute nonlymphocytic leukemia.
- Category IID is malignant lymphoma.
- Category IIE is chronic neutropenia.
Category III is associated with mast cell leukemia.
Category IV is associated with lymphadenopathic mastocytosis with eosinophilia (aggressive mastocytosis).

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Contributor Information and Disclosures

Author

Koyamangalath Krishnan, MD, FRCP, FACP Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Devapiran Jaishankar, MBBS Associate Professor, Division of Oncology, East Tennessee State University, James H Quillen College of Medicine

Devapiran Jaishankar, MBBS is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Thomas H Davis, MD, FACP Associate Professor, Fellowship Program Director, Department of Internal Medicine, Section of Hematology/Oncology, Dartmouth Medical School

Thomas H Davis, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Education, American College of Physicians, New Hampshire Medical Society, Phi Beta Kappa, and Society of University Urologists

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Ronald A Sacher, MB, BCh, MD, FRCPC Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Rajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Stephen J Smith, MD, Harsha G Vardhana, MD, and Guha Krishnaswamy, MD, to the development and writing of this article.