Synonyms: Urticaria pigmentosa, telangiectasia macularis eruptive perstans, mastocytoma, mastocytosis
Etiology: Unknown
Associations: Nausea, vomiting, diarrhea, syncope, mast cell leukemia, other hematologic malignancies
Clinical: Papules or nodules with or without associated
hyperpigmentation and telangiectasia; positive Darier’s sign
Histology: Increased dermal mast cells perivascular or as tumor nodules, basilar hyperpigmentation, vascular ectasia
IHC repertoire: CD117 (c-kit) and mast cell tryptase positive
Staging: Bone marrow involvement conveys poor prognosis
Prognosis: Varies with subtype of disease; benign in children
Adverse variables: Bone marrow involvement
Treatment: Chemotherapy including interferon alfa if bone marrow involvement; topical steroids; close clinical follow-up in patients with adult-onset disease
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Mast Cell Disease (Urticaria Pigmentosa)
Cutaneous mast cell disease has several different manifes- tations. It can present during the neonatal period or throughout life. Different age populations generally develop different clinical manifestations and different associated conditions. It is the systemic form of mastocy- tosis in adults that has the most potentially severe com- plications. It has been estimated that from 15% to 50% of patients with adult-onset mast cell disease will have sys- temic involvement (1,2). However, for the sake of com- pleteness, the other variants of this disease spectrum will also be considered. Urticaria pigmentosa is the global term for all conditions that are characterized by increased numbers of mast cells within the dermis. There is no gender predilection.
Mast cell disease in childhood is only rarely associated with systemic disease (less than 2% of the time in one series). About one-third of all patients with mast cell disease are less than 15 years old (3). The disease resolves spontaneously in two to three years in the vast majority of these patients, by adolescence in virtually all. Children with mast cell disease often have single or a few large, nodular lesions called mastocytomas (Figure 6.1). These most commonly appear within the first three years of life.
These lesions urticate easily with stroking (Darier’s sign).
Bullous lesions may be present due to extensive papillary dermal edema secondary to histamine release from mast cells. Vesicles do not generally occur as part of cutaneous mast cell disease in patients older than 10 years of age.
Rarely, children with diffuse mast cell disease may present with erythroderma (Figure 6.2). Despite the absence of systemic disease, these children are at risk for hypoten- sion, shock, and even death.
Adults with mast cell disease are more likely to present with a widely scattered macular eruption. Individual lesions are often red-brown or hyperpigmented. The lesions are randomly distributed and generalized, but are accentuated on the chest. Petechiae and ecchymoses may occur. Depending upon the mast cell burden within each lesion, an urticarial reaction can be elicited by gently stroking these lesions. Pruritus is the most common symptom. Less commonly, nausea, vomiting, diarrhea, and abdominal pain may be reported. These symptoms occur in patients with limited cutaneous disease as fre- quently as those with systemic involvement. One type of adult-onset form of the disease is known as telangiectasia macularis eruptive perstans (TMEP). In this variant, abundant hyperpigmented 2–6-mm macules are present on the back and chest in concert with telangiectasias. Pru-
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ritis and urtication are not common. It is currently not possible to distinguish adult patients with disease limited to the skin from those with systemic disease based purely on the cutaneous disease. There is no difference in the age of presentation between those with and without systemic involvement. The mean age of presentation is in the fourth decade. Systemic disease presents much later, often with as much as 20 years separating these fi ndings from the initial cutaneous presentation (3). Patients with systemic disease may remain alive with persistent disease for many years, or may succumb to their illness.
In adults with cutaneous mast cell disease, hepato- splenomegaly is often seen in addition to the macular, hyperpigmented eruption. Lymph node involvement is not uncommon. Osteoblastic lesions can be detected with radiographs. The bone marrow is the most frequently involved extracutaneous site. Eosinophilia is present in 15% of all patients with systemic disease.
In these patients, pancytopenia may be present and a bone marrow biopsy and aspiration is necessary to eliminate the presence of mastocytosis or leukemia (mast cell leukemia or chronic myelogenous leukemia).
Leukemia is reported to develop in 4% –5% of patients with systemic mastocytosis (4). Involvement of the gas- trointestinal tract has been reported but is very uncom- mon. Increased serum tryptase and increased urinary levels of t-methyl histamine may also be detected in these patients (5).
The histologic fi ndings in child-onset mast cell disease include a very dense dermal infiltrate of mast cells, often filling the entire dermis and extending into the subcuta- neous fat. In some cases, prominent papillary dermal edema leads to a subepidermal bulla, correlating with the blisters encountered clinically.
The histologic fi ndings in adult-onset mast cell disease fall into two general categories. Mast cells may be distrib- uted in a perivascular pattern or diffusely (Figure 6.3A and 6.3B).
Neither pattern is predictive of systemic involvement, though the superficial perivascular pattern is more common (3). The number of perivascular mast cells varies widely, but in most cases is relatively slight, with only a minimal increase in cellularity over physiologic levels.
FIGURE 6.1. Erythematous/tan plaque of mastocytosis in a child.
FIGURE 6.2. Erythroderma with islands of sparring and hepato- splenomegaly associated with par- enchymal organ infiltration in systemic mastocytosis.
Morphometric point counting has sug gested that while the absolute numbers may be small, there is a nine-to-160- fold increase in numbers of mast cells in these cases com- pared with normal patients (6). Dense diffuse infiltrates within the papillary dermis are encountered less com- monly (Figure 6.4).
In these cases, prominent nuclear atypia and presence of nucleoli and multinucleation may be present; however,
these fi ndings do not associate invariably with systemic involvement. Mitotic activity is rare in all cases of mast cell disease (Figure 6.5).
In one study, electron microscopy suggested that mast cells from patients with systemic disease are larger, and have more cytoplasm and larger cytoplasmic granules (7). In biopsies from both patterns, an ad mixture of lymphocytes and eosinophils are present within FIGURE6.3. (A) Low power photo-
micrograph depicting superficial dermal infiltrate of mastocytosis.
(B) Low power photomicrograph depicting superficial dermal infil- trate of mastocytosis in adult T.M.E.P.
A
B
the dermis. In more subtle cases, mast cell numbers can be better assessed with special stains such as toluidine blue or Giemsa’s stains, or more specifi - cally, staining with CD117 (c-kit) or mast cell tryptase (Figure 6.6).
Bone marrow involvement with mast cell disease may be very focal and a negative biopsy does not guarantee limited cutaneous disease (3). Conversely, skin involve-
ment is not present in all cases of systemic mast cell disease (8,9).
Treatment options vary with the extent of disease.
Cutaneous lesions can be watched or treated with topical steroids or even surgical excision of limited lesions. More extensive disease requires topical steroids, anti histamines, chemotherapy, interferon, and ultraviolet light therapy.
None of these options are entirely effective.
FIGURE6.4. Medium power photo- micrograph depicting uniform population of epithelioid cells within the superficial dermis.
FIGURE 6.5. High power photo- micrograph depicting uniform population of rounded cells pos- sessing oval nuclei with ampho- philic staining cytoplasm.
References
1. Caplan RM. The natural course of urticaria pigmentosa. Arch Dermatol 1983; 87: 146–157.
2. Ridell B, Olafsson JH, Roupe G, Swolin B, Granerus G, Rodjer S, Enerback L. The bone marrow in urticaria pigmentosas and systemic mastocytosis. Arch Dermatol 1986; 122: 422–427.
3. Travis WD, Li C-Y, Su WPD. Adult-onset urticaria pigmentosa and systemic mast cell disease. Am J Clin Pathol 1985; 84:
710–714.
4. DiBacco RS, DeLeo VA. Mastocytosis and the mast cell. J Am Acad Dermatol 1982; 7: 709–722.
5. Asmis LM, Cirardet C. Systemic mast-cell disease (masto- cytosis): Letter to the editor. N Eng J Med 2002; 346: 174.
6. Kaspar CS, Freeman RG, Tharp MD. Diagnosis of mastocytosis subsets using a morphometric point counting technique.
Arch Dermatol 1987; 123: 1017–1021.
7. Soter NA. The skin in mastocytosis. J Invest Dermatol 1991;
96: 32S–39S.
8. Mutter RD, Tannenbaum M, Ultmann JE. Systemic mast cell disease. Ann Int Med. 1963: 59: 887–906.
9. Roberts LJ II, Fields JP, Oates JA. Mastocytosis without urti- caria pigmentosa: A frequently unrecognized cause of recur- rent syncope. Trans Assoc Am Physicians 1982; 85: 36–41.
FIGURE 6.6. Giesma stains reveal metachromatic staining of cyto- plasmic granules within mast cells.
