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CHaPTEr 23 Mast Cells, Basophils, and Mastocytosis 345

TABLE 23.2 world Health Organization Most of the diagnostic criteria for mastocytosis (see Table
(wHO) Classification of Mastocytosis 23.3) depend on bone marrow histopathological findings. Bone
marrow biopsy is therefore an essential part of the diagnostic
Cutaneous mastocytosis process. It should be considered for adult patients with typical
Indolent systemic mastocytosis skin lesions and as a confirmatory test in patients with elevated
Systemic mastocytosis with an associated clonal hematologic non–
mast cell lineage disease tryptase levels. Typical findings on bone marrow biopsy in
Aggressive systemic mastocytosis mastocytosis include multifocal dense mast cell aggregates (>15
Mast cell leukemia mast cells per cluster) and abnormal morphological features of
Mast cell sarcoma mast cells (Fig. 23.5D). Such features include spindle shapes,
Extracutaneous mastocytoma bi- or multilobed nuclei, and expression of CD2 or CD25. 52
The differential diagnosis of SM includes a variety of disorders
with similar clinical manifestations, such as MMAS and MCAS
(described above), hereditary/acquired angioedema, carcinoid
TABLE 23.3 Diagnosis of Systemic syndrome, and pheochromocytoma.
Mastocytosis Based on world Health
Organization (wHO) Criteria a Treatment
Major Criterion
Multifocal, dense infiltrates of mast cells (≥ 15 mast cells in THEraPEUTIC PrINCIPLES
aggregates) detected in sections of bone marrow and/or other Approach to Treatment of Mastocytosis
extracutaneous organ(s)
• Avoidance of symptomatic triggers
Minor Criteria • Control of symptoms
1. More than 25% of mast cells in biopsy sections of bone marrow or • Antihistamines (H 1 and H 2 receptor antagonists)
other extracutaneous organs are spindle shaped or display atypical • CysLT receptor antagonists
morphology, or, of all mast cells in bone marrow aspirate smears, > • Aspirin
25 % are immature or atypical • Disodium cromoglycate
2. Detection of an activating point mutation at codon 816 of c-KIT in • Epinephrine
blood, bone marrow, or another extracutaneous organ • Management of osteoporosis
3. Mast cells in the bone marrow, blood, or other extracutaneous • Cytoreductive therapy for aggressive disease
organs express CD2 and/or CD25 in addition to normal mast cell • Imatinib
markers • Other tyrosine kinase inhibitors
4. Serum total tryptase persistently exceeds 20 ng/mL • Management of associated hematological disorders
a One major and one minor, or three minor, criteria are needed for the diagnosis of
systemic mastocytosis. There is no cure for mastocytosis, and treatment is focused on
Data from Horny HP, Metcalfe DD, Bennett JM, et al. Mastocytosis In: Swerdlow SH, control of symptoms. All patients with mastocytosis should avoid
Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, editors.
WHO classification of tumors of hematopoietic and lymphoid tissues. Lyon, France: exposures to symptomatic triggers. In addition, patients should
IARC Press; 2008: p. 54–63. have epinephrine autoinjectors available at all times to treat
possible anaphylaxis. Pharmacological treatment of mastocytosis
includes drugs that fall into three main categories: (i) those that
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anaphylaxis or for MMAS. Patients who have anaphylaxis of block or interfere with mast cell mediators, (ii) those that prevent
unknown etiology are more properly diagnosed with idiopathic mast cell activation, and (iii) those that affect mast cell survival
anaphylaxis. and proliferation.
Type 1 histamine (H 1 )-receptor antagonists are not only
Diagnosis particularly useful for the control of cutaneous symptoms,
For all patients with mastocytosis, the diagnostic process begins including pruritus and flushing, but may also aid in the manage-
with a thorough history and physical examination. The diagnosis ment of headache and neuropsychiatric symptoms (headache,
of CM is made based on the appearance of characteristic skin depression, cognitive impairment). Type 2 histamine (H 2 )-receptor
lesions and may be confirmed with skin biopsy showing mast antagonists are used in the treatment of GI symptoms, such as
cell infiltrates in the skin. In adults with cutaneous findings, abdominal pain, cramping, diarrhea, heartburn, nausea, and
systemic disease must be ruled out. vomiting. CysLT receptor antagonists are used in conjunction
The diagnostic process for patients with suspected mast cell with antihistamines as a second-line treatment for cutaneous
disease typically includes measurement of serum tryptase. If the symptoms. Aspirin may be helpful for some patients with flushing,
tryptase is found to be elevated during an anaphylactic episode particularly those with high levels of urinary prostaglandin D 2
or other symptomatic event, the measurement should be repeated or 11β-PGF 2α but must be used with caution, as NSAIDs may
at least 24 hours after symptoms have resolved. If basal tryptase trigger anaphylaxis in some patients. 52
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is elevated (>20 ng/mL), there is a high probability of SM. Disodium cromoglycate (cromolyn) is a weak in vivo inhibitor
Another blood test that may be useful, particularly in patients of mast cell activation but is used orally to reduce GI and
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with borderline tryptase levels or an indeterminate clinical neuropsychiatric symptoms. Certain H 1 -receptor antagonists,
presentation, is a screening test for the D816V mutation in including ketotifen and rupatadine, are reported to block mast
peripheral blood leukocytes. Both elevated tryptase and the D816V cell activation.
mutation are minor criteria for mastocytosis. Other blood tests Osteoporosis in patients with SM is typically treated in the
that should be performed to evaluate for specific organ involve- same manner as in patients in the general population. Bisphos-
ment include complete blood count and liver function tests. phonate drugs are the first line of treatment, along with