6

Mast Cell Disease (Urticaria Pigmentosa)

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 Dariers
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

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 rst three years of life.
These lesions urticate easily with stroking (Dariers 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 26-mm macules are present
on the back and chest in concert with telangiectasias. Pru-
27
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FIGURE 6.1. Erythematous/tan plaque of mastocytosis in a
child.
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 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.
Deadly Dermatologic Diseases
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 ndings in child-onset mast cell disease
include a very dense dermal inltrate of mast cells, often
lling 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 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 supercial 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 6.2. Erythroderma with
islands of sparring and hepato-
splenomegaly associated with par-
enchymal organ inltration in
systemic mastocytosis.
6. Mast Cell Disease (Urticaria Pigmentosa) 29

FIGURE 6.3. (A) Low power photo-

micrograph depicting supercial
dermal inltrate of mastocytosis.
(B) Low power photomicrograph
depicting supercial dermal inl-
trate of mastocytosis in adult
T.M.E.P.

Morphometric point counting has suggested 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 inltrates
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 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 admixture
of lymphocytes and eosinophils are present within
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the dermis. In more subtle cases, mast cell numbers
can be better assessed with special stains such
as toluidine blue or Giemsas stains, or more speci-
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-
Deadly Dermatologic Diseases
FIGURE 6.4. Medium power photo-
micrograph depicting uniform
population of epithelioid cells
within the supercial dermis.
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, antihistamines,
chemotherapy, interferon, and ultraviolet light therapy.
None of these options are entirely effective.
FIGURE 6.5. High power photo-
micrograph depicting uniform
population of rounded cells pos-
sessing oval nuclei with ampho-
philic staining cytoplasm.
6. Mast Cell Disease (Urticaria Pigmentosa)
FIGURE 6.6. Giesma stains reveal
metachromatic staining of cyto-
plasmic granules within mast cells.
References
1. Caplan RM. The natural course of urticaria pigmentosa. Arch
Dermatol 1983; 87: 146157.
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: 422427.
3. Travis WD, Li C-Y, Su WPD. Adult-onset urticaria pigmentosa
and systemic mast cell disease. Am J Clin Pathol 1985; 84:
710714.
4. DiBacco RS, DeLeo VA. Mastocytosis and the mast cell. J Am
Acad Dermatol 1982; 7: 709722.
31
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: 10171021.
7. Soter NA. The skin in mastocytosis. J Invest Dermatol 1991;
96: 32S39S.
8. Mutter RD, Tannenbaum M, Ultmann JE. Systemic mast cell
disease. Ann Int Med. 1963: 59: 887906.
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: 3641.