Mastocytoma_1212 Derm Clinic 1
A boy, aged 7 years, was seen for evaluation of a “bumpy beauty mark.” The lesion had been present for several years with no noticeable change in appearance. No pain or itching was associated with the lesion. No significant medical history, family history of skin disease, or known allergies were reported.
Physical exam revealed a brown-orange round papule on the upper chest. No pigment network was appreciated on dermoscopy. After mild rubbing, the lesion appeared to become more edematous and erythematous. Histopathology revealed a diffuse infiltrate of mast cells throughout the dermis.
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A mastocytoma is a benign tumor of active mast cells. Mast cells are derived from pluripotent CD34+ cells that reside in the bone marrow. Their role is to carry preformed mediators, including histamine, heparin, prostaglandins, and cytokines.
Mast-cell disease is most frequently manifested as cutaneous mastocytosis with disease limited to the skin only; however, infrequently, it may present more seriously as systemic mastocytosis with a proliferation of mast cells in the bone marrow, spleen, lymph nodes, GI tract, bones, and skin.
Cutaneous mastocytosis is classified into several distinct subtypes: urticaria pigmentosa (UP), diffuse cutaneous mastocytosis, solitary mastocytoma and—rarely—telangiectasia macularis eruptiva perstans.1
UP, also termed childhood maculopapular mastocytosis, is the most common form and presents with rose/brown, round or oval-shaped macules and urticarial papules distributed symmetrically on the trunk and extremities. Onset of UP is usually in the first few weeks or years of life.
In diffuse cutaneous mastocytosis, an uncommon form of the disease, the entire skin is thickened and infiltrated with mast cells, resulting in an orange hue called homme orange. In the more severe variant, bullae may be seen. Diffuse cutaneous mastocytosis is usually seen in children younger than age 3 years.
Approximately 10% to 40% of childhood mastocytosis cases present in the neonatal period with a mastocytoma—a solitary brown macule—typically located on the dorsum of the hand or wrist.
When affected skin in individuals with cutaneous mastocytosis is stroked or rubbed, local urticaria and surrounding erythema develops, demonstrating a positive Darier sign. Because physical stimulation of the mast cells triggers degranulation and mediator release, uncontrolled stroking should be avoided, as it may produce local and, rarely, systemic symptoms.
Systemic mastocytosis is primarily seen in adults and may or may not be accompanied by skin lesions.2 The most common type of systemic disease is the indolent type, and these patients lack evidence of other hematologic disorder, end-organ dysfunction, or mast-cell leukemia.
Individuals with aggressive systemic mastocytosis will have such symptoms of end-organ disease as bone pain, cytopenia, or hepatosplenomegaly. Individuals with coexisting non-mast-cell hematologic disease usually do not have any skin symptoms, and their prognosis is directly related to the underlying disease process. Mast-cell sarcoma and mast-cell leukemia are much rarer and carry a poorer prognosis.
Systemic disease is only diagnosed after one major and one minor criterion or three minor criteria are fulfilled. The major criterion is finding dense infiltrates of mast cells in bone marrow or other extracutaneous organs. The minor criteria are atypical mast-cell morphology, aberrant mast-cell surface phenotype, baseline serum tryptase >20 ng/mL, and detection of a codon 816 c-KIT mutation.
A thorough history, physical examination, and skin biopsy are usually sufficient to confirm the diagnosis of cutaneous disease. Routine staining may not clearly demonstrate the excess number of mast cells, so such special stains as toluidine blue, Giemsa, or fluorescein isothiocyanate-avidin are required with histologic analysis of skin samples. Be sure to inform the histopathologist of the suspected diagnosis.
Recognizing the disease in individuals who do not have the characteristic skin lesions of mastocytosis may be difficult. A delay in diagnosis can prove fatal in those with widespread disease, so clinicians should maintain a high index of suspicion.
If systemic disease is suspected or if the disease appears after age 5 years, further workup may include a complete blood count, plasma or urinary histamine level, total tryptase level, and bone scan/radiologic survey. If any of these tests are abnormal, consider a bone-marrow biopsy to rule out an associated hematologic disorder.
The symptoms of mastocytosis occur when pharmacologic or physical stimuli cause mast-cell degranulation and the release of mediators. These episodic symptoms include dyspnea, flushing, heart palpitations, syncope, diarrhea, abdominal pain, anorexia, neuropsychiatric symptoms, and urticaria.
Common triggers include emotional stress, physical stress (e.g., trauma, extreme heat or cold, exercise), insect bites, bacterial toxins, alcohol, medications, and general anesthesia. In more widespread mastocytosis, episodes of vascular collapse may be spontaneous and life-threatening.
Most cases of adult mastocytosis are viewed as a myelodysplastic disorder and likely secondary to a genetic mutation localized to the c-Kit protooncogene or 4q12 gene, causing the neoplastic proliferation of mast cells. Most childhood cases do not demonstrate these mutations and are thought to occur from cytokine-derived hyperplasias or from other mutations not yet identified.3
Childhood-onset cutaneous mastocytosis usually resolves by puberty. Potent topical or intralesional injection of corticosteroids may be beneficial for a solitary mastocytoma and contribute to lesion involution. However, since the disease is so limited and systemic symptoms are uncommon, no treatment is usually needed.
Treatment for UP is also conservative and aimed at symptom relief. H1 and H2 antihistamines provide relief of histamine-mediated symptoms. Oral psoralen plus UVA (PUVA) therapy results in general and cosmetic benefits in the treatment of widespread cutaneous disease.
Late-onset or systemic disease is usually more persistent and carries a higher risk of vascular collapse. In addition, adult-onset systemic mastocytosis has a malignant transformation rate as high as 30%; these patients should be managed by a hematologist.
Individuals with mastocytoma should be taught to identify and avoid triggering factors. Substances to avoid include aspirin, nonsteroidal anti-inflammatory drugs, codeine, morphine, thiamine, quinine (Qualaquin), reserpine, procaine, radiographic dyes, dextran, polymyxin B, scopolamine (Transderm Sco¯p), and D-tubocurarine. Medical-alert bracelets should be made available, and patients should carry an epinephrine self-injector with directions for proper use.
The boy described in this case was diagnosed with a solitary mastocytoma. His parents were educated on the diagnosis and instructed to be alert for the development of any new lesions. Watchful waiting was the elected treatment approach.
Esther Stern, NP-C, is a family practitioner at Advanced Dermatology & Skin Surgery, P.C., in Lakewood, N.J.
- Valent P, Horny HP, Escribano L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res. 2001;25:603-225.
- Soter NA. The skin in mastocytosis. J Invest Dermatol. 1991;96(3 Suppl): 32S-38S.
- James WD, Berger TB, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, Pa,: Saunders-Elsevier; 2011:615-618.