Guidelines Summary
The National Comprehensive Cancer Network (NCCN) has published guidelines for the diagnosis and management of systemic mastocytosis. [57]
Diagnosis
For diagnosis, the NCCN guidelines recommend the following testing [57] :
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Bone marrow aspirate and biopsy
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Immunophenotyping using flow cytometry and/or immunohistochemistry (IHC) of mast cells
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Molecular testing for KIT D816V, additional KIT genetic sequencing as needed; if KIT D816V negative and eosinophilia is present, screen for FIP1L1::PDGFRA
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Multigene next-generation sequencing (NGS) panel that includes genes such as SRSF2, ASXL1, and RUNX
Diagnosis is based on 2022 World Health Organization (WHO) or International Consensus Classification (ICC) criteria. Once the diagnosis of systemic mastocytosis is confirmed, further workup to determine subtype and organ involvement includes [57] :
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CT/MRI or ultrasound of the abdomen/pelvis
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Dual x-ray absorptiometry (DEXA) scan to evaluate for osteopenia/osteoporosis
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Metastatic skeletal survey to evaluate for osteolytic lesions
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Organ-directed biopsy (eg, endoscopy, liver biopsy) as needed with immunohistochemistry (CD117, CD25, tryptase, and CD3 as a control T-cell marker)
Treatment for indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM)
Treatment considerations for ISM and SSM are as follows [57] :
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Referral to specialized centers with expertise in mastocytosis
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Patients should carry injectable epinephrine to manage anaphylaxis
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Assessment of symptom burden and quality of life (QOL) using the Mastocytosis Symptom Assessment Form (MSAF) and the Mastocytosis Quality of Life Questionnaire (MQLQ)
Asymptomatic patients can be monitored for signs and symptoms of disease; symptomatic patients are managed with anti-mediator drug therapy. Both asymptomatic and symptomatic patients should be offered enrollment in clinical trials. [57]
Treatment for aggressive systemic mastocytosis (ASM)
The treatment recommendations for ASM are as follows [57] :
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Enrollment in clinical trial or
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Avapritinib (if platelets ≥50 × 10 9/L) or midostaurin
Cladribine or peginterferon alfa-2a with or without prednisone are other recommended regimens. Imatinib is useful for KIT D816V mutation negative or unknown; well-differentiated SM or if eosinophilia is present with FIP1L1::PDGFRA gene fusion. [57]
Patients with an adequate response to treatment may be considered for allogeneic hematopoietic cell transplant (HCT); patients with an inadequate or loss of response to treatment should be restaged. [57]
Treatment for systemic mastocytosis with an associated hematologic neoplasm (SM-AHN)
If the associated hematologic neoplasm (AHN) requires more immediate treatment, the guidelines recommend AHN-directed therapy following the guidelines relevant to the AHN. Management of SM is determined by the number of C-findings. If no C-findings are present, monitor the patient for development of new C-findings and/or severe/ refractory symptoms of mast cell activation. [57]
If there are one or more C-findings, the guidelines recommend the following treatment of the SM:
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Enrollment in clinical trial or
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Avapritinib (if platelets ≥50 × 10 9 /L) or
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Midostaurin
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Cladribine is particularly useful when rapid debulking of disease is required
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Peginterferon alfa-2a ± prednisone may be more suitable for patients with slowly progressive disease without the need for rapid cytoreduction
Treatment for mast cell leukemia (MCL)
Key treatment recommendations for MCL include the following [57] :
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Enrollment in clinical trial or
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Avapritinib (if platelets ≥50 x 10 9/L) or
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Midostaurin
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Cladribine is also recommended
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Systemic mastocytosis. Bone marrow aspirate, Romanowsky stain, high-definition magnification. Diagnosis is mastocytosis, and morphology is abnormal mast cells. This is a bone marrow smear from a patient with systemic mastocytosis. Several mast cells are present in this photograph. These mast cells are larger than normal mast cells and have more irregularly shaped nuclear outlines and less densely packed mast cell granules. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
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Systemic mastocytosis. Bone marrow aspirate, toluidine stain, low magnification. Diagnosis is mastocytosis, and morphology is abnormal mast cells. This is a toluidine blue stain of a bone marrow smear from a patient with marrow involvement by systemic mastocytosis. Five mast cells are present in this field. The mast cell granules are metachromatic with the toluidine blue reaction. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
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Systemic mastocytosis. Bone marrow biopsy, toluidine stain, low magnification. Diagnosis is mastocytosis, and morphology is abnormal mast cell infiltrate. This is a toluidine blue stain of a bone marrow biopsy from a patient with systemic mastocytosis. The mast cells are metachromatic with toluidine blue and contain numerous purple granules. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
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Systemic mastocytosis. Lymph node biopsy. Diagnosis is mastocytosis, morphology is mast cell infiltrate, and the organ is the lymph nodes. This is a lymph node biopsy from a person with systemic mastocytosis. The mast cells have a characteristic perifollicular distribution. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
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Systemic mastocytosis. Lymph node biopsy, chloroacetate esterase stain. Diagnosis is mastocytosis, and morphology is mast cell infiltrate. This is a portion of a lymph node biopsy from a patient with systemic mastocytosis. The mast cells are chloroacetate esterase positive, which is characterized by an orange granular appearance. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
Tables
| Criteria | WHO | ICC |
|---|---|---|
| Major Criterion | Presence of multifocal and dense infiltrates of mast cells in bone marrow or in other extracutaneous tissues. Mast cells should be seen in aggregates of 15 cells or more. | Presence of multifocal dense infiltrates of tryptase- and/or CD117 positive mast cells detected in bone marrow or in other extracutaneous tissues. Mast cells should be seen in aggregates of 15 cells or more. |
Minor Criteria |
Spindle shape or atypical mast cell morphology (type I or type II) in 25% or more of the mast cells in biopsy sections of bone marrow or other extracutaneous organs | Spindle shaped or atypical immature morphology in more than 25% of mast cells in biopsy sections of bone marrow or other extracutaneous organs |
| Minor Criteria | Presence KIT-activating KIT point mutation(s) at codon 816 or in other critical regions of KIT in bone marrow or another extracutaneous organ |
Presence of KIT D816V mutation or other activating KIT mutation in bone marrow, peripheral blood, or other extracutaneous organs |
| Minor Criteria | Expression of CD25 and/or CD2 and/or CD30 in addition to normal mast cell markers |
Expression of CD25 and/or CD2 and/or CD30 in addition to normal mast cell markers |
| Minor Criteria | Serum/plasma total tryptase levels persistently greater than 20 ng/mL | Serum tryptase level persistently greater than 20 ng/mL. In cases of SM-AMN an elevated tryptase does not count as a SM minor criterion. |
