eMedicine Specialties > Dermatology > Benign Neoplasms

Mastocytosis

Author: Daniel J Hogan, MD, Clinical Professor of Internal Medicine (Dermatology), NOVA Southeastern University; Investigator, Hill Top Research, Florida Research Center
Coauthor(s): Christin Martino, Louisiana State University School of Medicine-Shreveport
Contributor Information and Disclosures

Updated: Sep 11, 2009

Introduction

Background

Mastocytosis is a disorder characterized by mast cell proliferation and accumulation within various organs, most commonly the skin.

The World Health Organization (WHO) classification of mastocytosis includes the following1,2 :

  • Cutaneous mastocytosis
    • Urticaria pigmentosa 
    • Maculopapular cutaneous mastocytosis 
    • Diffuse cutaneous mastocytosis 
    • Mastocytoma of skin
  • Indolent systemic mastocytosis
  • Systemic mastocytosis with an associated (clonal) hematologic non–mast cell lineage disease
  • Aggressive systemic mastocytosis
  • Mast cell leukemia
  • Mast cell sarcoma
  • Extracutaneous mastocytoma1,2
This article focuses on cutaneous mastocytosis (CM). The single World Health Organization (WHO) major criterion is multifocal dense infiltrates of mast cells in bone marrow and/or other extracutaneous organs. One major and 1 minor criterion or 3 minor diagnostic criteria are needed to establish a diagnosis of systemic mastocytosis. Minor criteria include baseline total tryptase level of greater than 20 ng/mL; greater than 25% of the mast cells in bone marrow aspirate smears or tissue biopsy sections having spindle atypical morphology; mast cells in bone marrow, blood, or other lesional tissue expressing CD25 or CD2; or detection of a codon 816 c-kit point mutation in blood, bone marrow, or lesional tissue.3

Types of cutaneous mastocytosis include solitary mastocytoma, diffuse erythrodermic mastocytosis, paucicellular mastocytosis (also termed telangiectasia macularis eruptiva perstans [TMEP]), and urticaria pigmentosa (UP). Urticaria pigmentosa is the most common form and is characterized by oval or round red-brown macules, papules, or plaques ranging in number from a few to thousands (see Media Files 1-2). Lesions may vesiculate in infancy (see Media File 3). 
 

Urticaria pigmentosa lesions on the face of a chi...

Urticaria pigmentosa lesions on the face of a child. Courtesy of Lee H. Grafton, MD.

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Urticaria pigmentosa lesions on the face of a chi...

Urticaria pigmentosa lesions on the face of a child. Courtesy of Lee H. Grafton, MD.


Urticaria pigmentosa lesions on the back of a chi...

Urticaria pigmentosa lesions on the back of a child. Courtesy of Lee H. Grafton, MD.

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Urticaria pigmentosa lesions on the back of a chi...

Urticaria pigmentosa lesions on the back of a child. Courtesy of Lee H. Grafton, MD.


Lesion on the scalp of an infant.

Lesion on the scalp of an infant.

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Lesion on the scalp of an infant.

Lesion on the scalp of an infant.


When a urticaria pigmentosa or mastocytoma lesion is stroked, it typically urticates, becoming pruritic, edematous, and erythematous. This change is referred to as the Darier sign, which is explainable on the basis of mast cell degranulation induced by physical stimulation. Uncontrolled stroking of mastocytomas should be avoided in patients who have had a systemic reaction such as miosis and asthmalike symptoms in their past.4 The Darier sign usually is not positive in patients with TMEP because the lesions are paucicellular, and, therefore, mast cells may not be present in sufficient numbers for significant degranulation to occur.

Also see Mastocytosis, Systemic.

Pathophysiology

Whether mastocytosis is a hyperplastic reaction to an unknown stimulus or whether it is a neoplastic condition is unknown. Increased local concentrations of soluble mast cell growth factor in lesions of cutaneous mastocytosis are believed to stimulate mast cell proliferation, melanocyte proliferation, and melanin pigment production. The induction of melanocytes explains the hyperpigmentation that commonly is associated with cutaneous mast cell lesions. Impaired mast cell apoptosis has been postulated to be involved, as evidenced by up-regulation of the apoptosis-preventing protein BCL-2 demonstrated in patients with mastocytosis.5 Activating mutations of the proto-oncogene c-kit have been identified but do not explain the initiation of the disease.6 Interleukin 6 levels have been shown to be elevated and correlated with disease severity, indicating interleukin 6 is involved in the pathophysiology of mastocytosis.7

Associated systemic manifestations are believed to reflect the release of mast cell–derived mediators, such as histamine, prostaglandins, heparin, neutral proteases, and acid hydrolases. Symptoms and signs induced by mediators may include headache, neuropsychiatric symptoms (cognitive disorganization), flushing, dizziness, tachycardia, hypotension, syncope, anorexia, nausea, vomiting, abdominal pain, and diarrhea. The skeletal, hematopoietic, gastrointestinal (GI), cardiopulmonary, and central nervous systems may be involved either directly, via mast cell infiltration, or indirectly, via mast cell mediator release.

Frequency

United States

Of new patients visiting dermatology clinics, 0.1-0.8% have some form of mastocytosis.

International

The international incidence of mastocytosis is not known to differ from the incidence observed in the United States.

Mortality/Morbidity

Most cases of urticaria pigmentosa in children resolve spontaneously, although acute extensive degranulation rarely can cause life-threatening episodes of shock. Patients with adult or adolescent-onset urticaria pigmentosa are more likely to have persistent disease and are at greater risk for systemic involvement. Juvenile-onset systemic mastocytosis has a malignant transformation rate as high as 7%, while adult-onset systemic mastocytosis has a malignant transformation rate as high as 30%.

One study shows that anaphylaxis is common in patients with mastocytosis (4.3-5.5% per year disease duration) and appears higher than in the healthy population. In childhood, the risk of anaphylactic episodes has been shown to be limited to those with extensive blistering skin disease, but nonexistent for children with mastocytoma or limited disease. In adults, anaphylactic episodes generally appear to be more severe in patients with extensive systemic disease.8

Race

Most reported cases are in whites. The cutaneous lesions of most types of mastocytosis are less visible in persons with more heavily pigmented skin.

Sex

Mastocytosis affects males and females equally (no known sex predilection).

Age

Most patients with mastocytosis are children; 75% of cases occur during infancy or early childhood and usually resolve by puberty. Mastocytosis incidence peaks again in patients aged 30-49 years.

Clinical

History

Mastocytosis patients may present with cutaneous lesions, systemic symptoms of an acute nature, and/or chronic systemic symptoms.

  • Most patients have pruritic cutaneous lesions.
  • Some patients, especially those with extensive cutaneous disease, experience acute systemic symptoms exacerbated by certain activities or ingestion of certain drugs or foods. Possible systemic symptoms include flushing, headache, dyspnea, wheezing, rhinorrhea, nausea, vomiting, diarrhea, and syncope.
  • Patients also may have chronic systemic symptoms involving various organ systems.
    • Involvement of the skeletal system may be manifested as bone pain or the new onset of a fracture. Long-term exposure to heparin and stem cell factor from degranulated mast cells is believed to put patients at risk for osteoporosis.9
    • Involvement of the central nervous system may produce neuropsychiatric symptoms, as well as nonspecific changes such as malaise and irritability.
    • GI involvement may yield weight loss, diarrhea, nausea/vomiting, and abdominal cramps.
    • Cardiovascular effects can include shock, syncope (resulting from vascular dilatation), or angina.
    • Anaphylactic reactions to hymenoptera stings may be the first sign of mastocytosis.

Physical

The most common physical findings in mastocytosis involve the skin, liver, spleen, and cardiovascular system.

  • Skin - Lesion types
    • Macules, papules, nodules, and plaques (see Media File 4)
    • Blisters and bullae in children (see Media File 5)
    • Diffuse induration
    • Isolated nodule or tumor
Lesion on the arm. Courtesy of Lee H. Grafton, MD.

Lesion on the arm. Courtesy of Lee H. Grafton, MD.

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Lesion on the arm. Courtesy of Lee H. Grafton, MD.

Lesion on the arm. Courtesy of Lee H. Grafton, MD.


Blistering lesion.

Blistering lesion.

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Blistering lesion.

Blistering lesion.

  • Skin - Distribution
    • Widespread symmetric distribution
    • Trunk involved more than extremities
    • Tendency to spare the face, scalp, palms, and soles; however, a patient with scarring alopecia has been reported10
  • Skin - Lesion color, quantity, and size 
    • Yellow-tan to red-brown
    • From 1 to more than 1000
    • From 1 mm to several centimeters
  • Skin - Special characteristics
    • Darier sign: Wheal and surrounding erythema develop in a lesion after rubbing it.
    • Dermatographism: In approximately half the patients, stroking macroscopically uninvolved skin produces dermographia.
    • Flushing: Flushing may occur spontaneously following skin stroke or after ingesting a mast cell degranulating agent.
  • Liver - Possible hepatomegaly (present in 40% of adult patients with systemic mastocytosis)
  • Spleen - Possible splenomegaly (present in 50% of patients with systemic mastocytosis)
  • Cardiovascular - Hypotension and tachycardia
  • Gastrointestinal - Abdominal pain, diarrhea, vomiting, weight loss (frequency of involvement currently uncharacterized in patients with systemic mastocytosis)11

Causes

Mastocytosis probably is a hyperplastic response to an abnormal stimulus. Rare cases of familial urticaria pigmentosa have been recorded.12 Rarer cases of cutaneous mastocytosis have been associated with radiotherapy fields in patients with breast cancer.13  

One case report describes an apparent temporal association between the development of cutaneous mastocytosis and HIV seroconversion, proposing similarities of immunoglobulin E receptors on mast cells and basophils and the association of basophils in HIV pathophysiology.14

More on Mastocytosis

Overview: Mastocytosis
Differential Diagnoses & Workup: Mastocytosis
Treatment & Medication: Mastocytosis
Follow-up: Mastocytosis
Multimedia: Mastocytosis
References
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Further Reading

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Keywords

mastocytosis, mastocytoma, telangiectasia macularis eruptiva perstans, TMEP, urticaria pigmentosa, mast cell proliferation

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Contributor Information and Disclosures

Author

Daniel J Hogan, MD, Clinical Professor of Internal Medicine (Dermatology), NOVA Southeastern University; Investigator, Hill Top Research, Florida Research Center
Daniel J Hogan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Contact Dermatitis Society, and Canadian Dermatology Association
Disclosure: Nothing to disclose.

Coauthor(s)

Christin Martino, Louisiana State University School of Medicine-Shreveport
Christin Martino is a member of the following medical societies: American Medical Association and Student National Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Timothy McCalmont, MD, Director, UCSF Dermatopathology Service, Professor of Clinical Pathology and Dermatology, Departments of Pathology and Dermatology, University of California at San Francisco
Timothy McCalmont, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society of Dermatopathology, California Medical Association, College of American Pathologists, and United States and Canadian Academy of Pathology
Disclosure: Apsara Consulting fee Independent contractor

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Rosalie Elenitsas, MD, Herman Beerman Associate Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System
Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology and American Society of Dermatopathology
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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