Diagnostic Considerations

The three most important conditions in the differential diagnosis are carcinoid syndrome, VIPoma, and Zollinger-Ellison syndrome. Like systemic mastocytosis (systemic mast cell disease), each of these conditions causes diarrhea, abdominal pain, and some degree of malabsorption.

Urticaria pigmentosa can help distinguish systemic mastocytosis from the other disorders. Plasma hormone measurements can also help in identifying these disorders: Gastrin levels can be elevated in persons with Zollinger-Ellison syndrome, and serotonin levels can be elevated in persons with carcinoid syndrome. Other malabsorption syndromes, such as celiac sprue, are also in the differential diagnosis.

Three other disorders of mast cell activation with overlapping clinical and pathological features are monoclonal mast cell activation syndrome, idiopathic mast cell activation syndrome, and idiopathic anaphylaxis. Systemic mastocytosis is a histopathologic and genetic diagnosis and should not be based solely on clinical presentation.

Bone marrow involvement can have a differential diagnosis that includes primary myelofibrosis, reactive mastocytosis, and other myeloproliferative disorders, especially chronic eosinophilic leukemia. These disorders can be distinguished from systemic mastocytosis by differences on bone marrow biopsy as well as the presence or absence of characteristic clinical and laboratory features. Distinguishing lymph node involvement from a wide variety of lymphomas is based on histomorphology and staining. However, clinicians should remain aware that systemic mastocytosis can coexist with other primary hematologic disorders.

Differential Diagnoses

Workup

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Media Gallery

Systemic mastocytosis. 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.
Systemic mastocytosis. 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.
Systemic mastocytosis. 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.
Systemic mastocytosis. 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.
Systemic mastocytosis. 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.

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Diagnostic Criteria for Systemic Mastocytosis

Diagnostic Criteria for Systemic Mastocytosis

Criteria	WHO	ICC
Major Criterion	Presence of multifocal and dense infiltrates of mast cells in bone marrow or in other extracutaneous tissues. Mast cells should be seen in aggregates of 15 cells or more.	Presence of multifocal dense infiltrates of tryptase- and/or CD117 positive mast cells detected in bone marrow or in other extracutaneous tissues. Mast cells should be seen in aggregates of 15 cells or more.
Minor Criteria	Spindle shape or atypical mast cell morphology (type I or type II) in 25% or more of the mast cells in biopsy sections of bone marrow or other extracutaneous organs	Spindle shaped or atypical immature morphology in more than 25% of mast cells in biopsy sections of bone marrow or other extracutaneous organs
Minor Criteria	Presence KIT-activating KIT point mutation(s) at codon 816 or in other critical regions of KIT in bone marrow or another extracutaneous organ	Presence of KIT D816V mutation or other activating KIT mutation in bone marrow, peripheral blood, or other extracutaneous organs
Minor Criteria	Expression of CD25 and/or CD2 and/or CD30 in addition to normal mast cell markers	Expression of CD25 and/or CD2 and/or CD30 in addition to normal mast cell markers
Minor Criteria	Serum/plasma total tryptase levels persistently greater than 20 ng/mL	Serum tryptase level persistently greater than 20 ng/mL. In cases of SM-AMN an elevated tryptase does not count as a SM minor criterion.

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Author

Devapiran Jaishankar, MBBS Professor of Medicine, Division Chief of Oncology-Hematology, Director of Oncology Fellowship Program, James H Quillen College of Medicine, East Tennessee State University

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

Disclosure: Nothing to disclose.

Coauthor(s)

Sukesh Manthri, MBBS, MD Chief Fellow in Medical Oncology, East Tennessee State University, James H Quillen College of Medicine

Sukesh Manthri, MBBS, MD is a member of the following medical societies: American Medical Association, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MD, FRCPC, DTM&H Professor Emeritus of Internal Medicine and Hematology/Oncology, Emeritus Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MD, FRCPC, DTM&H 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, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, 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 Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Koyamangalath Krishnan, MD, FRCP, FACP Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine, 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, Royal College of Physicians

Disclosure: Nothing to disclose.

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

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, Society of University Urologists

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference 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.

Systemic Mastocytosis Differential Diagnoses

Diagnostic Considerations

Differential Diagnoses

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