Materiały źródłowe

• #1 Orphanet: Systemic mastocytosis

  https://www.orpha.net/en/disease/detail/2467

  Systemic mastocytosis (SM) is a heterogeneous group of rare, acquired and chronic hematological malignancies related to an abnormal accumulation/proliferation of neoplastic mast cells (MCs) in one or several organs, mainly the bone marrow (BM), associated frequently with skin involvement. […] Consensus criteria for the diagnosis of systemic mastocytosis established by the WHO include one major criterion – the presence of aggregates of at least 15 MCs identified in BM or other extracutaneous organ biopsies (usually revealed after tryptase staining of biopsies) – and four minor criteria: the presence of more than 25% of MCs with atypical morphology in BM smears (spindle-shaped, degranulated and/or multinucleated MCs); aberrant immunophenotype of MCs which frequently abnormally express non-mast cell markers (CD25 and/or CD2); presence of a point mutation in codon 816 of the KIT gene in BM; peripheral blood or other extracutaneous organs; and increased level of serum tryptase (above 20 ng/mL). For diagnosis of SM, at least the major and one minor criterion or at least three minor criteria are fulfilled. The disease is then categorized, as described above, according to the presence of B-findings and C-findings.

• #2 Diagnosis and treatment of systemic mastocytosis in Brazil: Recommendations of a multidisciplinary expert panel | Hematology, Transfusion and Cell Therapy

  http://www.htct.com.br/en-diagnosis-treatment-systemic-mastocytosis-in-articulo-S2531137922000803

  Mastocytosis is a group of neoplastic disorders characterized by expanding and accumulating clonal and neoplastic mast cells (MCs) in the skin and/or various internal organs, such as the bone marrow, spleen, lymph nodes and gastrointestinal tract. The updated 2016 World Health Organization broadly classifies mastocytosis into cutaneous and systemic forms. In cutaneous mastocytosis (CM), MCs are restricted to the skin, whereas systemic mastocytosis (SM) refers to systemic involvement of several organs by neoplastic MCs. […] Although published international consensuses of experts on the diagnosis and management of patients with SM exist, there have been no guidelines published on managing this disease in Brazil, a low and middle-income (LMIC) country. This study aims to establish expert panel recommendations regarding the diagnosis and management of SM adapted to the reality of the country.

• #3 Diagnosis and Medical Testing

  https://www.mastocytosis.ca/en/diagnosis/medical-testing

  Diagnosing these disorders is often a long, complicated process involving many areas of specialty medicine. Many patients suffer declining health for up to 10 years or longer before finally being diagnosed. […] Mastocytosis has a set of standard diagnostic testing. Those with skin or hematological involvement seem to have the best chance of their physicians diagnosing their illness. MCAS and Idiopathic Anaphylaxis involve many tests, most of which may be inconclusive. […] None of the current diagnostic tests are reliable for every patient. Some of these tests often return false-negatives. Some tests return positive results outside the normal range, yet the patient experiences few symptoms and enjoys a normal unrestricted life. Many patients have completely normal test results (eg. tryptase, urine, bone marrow) yet they are disabled by these disorders. The largest discrepancy is reported by patients who test positive for a cutaneous form of Mastocytosis, yet negative test results proving systemic involvement, even though the patients exhibit all the classic symptoms of Systemic Mastocytosis. Physicians and patients worldwide are aware of this.

• #4 Systemic Mastocytosis Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/203948-workup

  Interpretation of GI biopsies is difficult because mast cells are normally abundant in these tissues; in contrast to mast cell numbers, however, expression of CD25 on GI mast cells is a useful diagnostic marker for presence of systemic mastocytosis. […] In 2022, revised criteria for diagnosing systemic mastocytosis were released by the World Health Organization (WHO). […] The WHO classification for diagnosis of systemic mastocytosis requires the presence of a major criterion plus one minor criterion, or the presence of three minor criteria; ICC requires the presence of the major criterion or at least three minor criteria.

• #5 Diagnostic Workup for Advanced Forms of Mastocytosis – TMS – The Mast Cell Disease Society, IncAccessibilityIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://tmsforacure.org/expert-information/diagnostic-workup-advanced-forms-mastocytosis/

  Mastocytosis denotes a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MCs) that has a variable prognosis and course of disease. […] The diagnosis of mastocytosis is established in a stepwise approach, using WHO major and minor criteria (with one major and one minor or at least three minor criteria having to be fulfilled). […] The major criterion is multifocal mast cell infiltration in the bone marrow (BM) or in an extracutaneous organ, as assessed by histology. […] Minor SM criteria relate to the morphology of mast cells (histology and/or cytology), their cell surface markers (aberrant expression of CD2 and/or CD25), molecular findings (KIT mutation at codon 816), and serum tryptase level (>20 ng/ml). […] To diagnose an advanced form of mastocytosis, the presence of B-findings, C-findings, or an AHN is of importance.

• #6

  https://www.mastcellhope.org/education/testing-and-diagnosis/

  A diagnosis of systemic mastocytosis can be considered when: […] The World Health Organization outlines the standard for diagnostic criteria for mastocytosis. In 2019, the WHO updated these criteria. […] A diagnosis of systemic mastocytosis can be considered when: […] The major criterion plus one minor criterion are met, or […] Three minor criteria are met. […] Major criterion: Multifocal, dense clusters of 15 or more mast cells in an extracutaneous organ (an organ other than the skin, such as the bone marrow, liver, spleen, lymph nodes, etc.). […] Minor criteria: For bone marrow smears, greater than 25% of detected mast cells are either immature or atypical (abnormal size, shape, or color). For bone marrow and other organ biopsies, greater than 25% of mast cells seen in the biopsy have atypical morphology (abnormal shape, most commonly, a spindle shape).

• #7 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adults with systemic mastocytosis have infiltration of one or more internal organs with abnormal mast cells and can present with or without cutaneous mastocytosis. […] Mastocytosis is diagnosed by sampling the tissues where there is an abundance by using biopsies, measuring mast cell mediators in blood and urine, blood counts, liver function studies and genetic tests. […] Thus, in adults it is important to look for possible systemic mastocytosis using biopsies of organs in addition to the skin. […] The diagnosis of systemic mastocytosis is determined by criteria established by the World Health Organization consensus group and requires meeting the major criterion plus one minor criterion or, alternatively, three of the minor criteria. […] Multifocal dense infiltrates of mast cells (MCs) ( 15 MCs in aggregate) in tryptase stained biopsy sections of the bone marrow or other extracutaneous organs such as the gastrointestinal tract.

• #8 Orphanet: Systemic mastocytosis

  https://www.orpha.net/en/disease/detail/2467

  Systemic mastocytosis (SM) is a heterogeneous group of rare, acquired and chronic hematological malignancies related to an abnormal accumulation/proliferation of neoplastic mast cells (MCs) in one or several organs, mainly the bone marrow (BM), associated frequently with skin involvement. […] Consensus criteria for the diagnosis of systemic mastocytosis established by the WHO include one major criterion – the presence of aggregates of at least 15 MCs identified in BM or other extracutaneous organ biopsies (usually revealed after tryptase staining of biopsies) – and four minor criteria: the presence of more than 25% of MCs with atypical morphology in BM smears (spindle-shaped, degranulated and/or multinucleated MCs); aberrant immunophenotype of MCs which frequently abnormally express non-mast cell markers (CD25 and/or CD2); presence of a point mutation in codon 816 of the KIT gene in BM; peripheral blood or other extracutaneous organs; and increased level of serum tryptase (above 20 ng/mL). For diagnosis of SM, at least the major and one minor criterion or at least three minor criteria are fulfilled. The disease is then categorized, as described above, according to the presence of B-findings and C-findings.

• #9 Mastocytosis Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1057932-workup

  WHO major criteria for the diagnosis of systemic mast cell disease include the following: Multifocal dense infiltrates of mast cells (15 close to each other) observed in bone marrow biopsy specimens and/or mast cells stained for tryptase in biopsy specimens from other extracutaneous organs. […] WHO minor major criteria for the diagnosis of systemic mast cell disease include the following: Mast cells in bone marrow, or other extracutaneous organs show abnormal (spindling) morphology (25%) or the presence of greater than 25% atypical mast cells in bone marrow aspirates.

• #10 Orphanet: Systemic mastocytosis

  https://www.orpha.net/en/disease/detail/2467

  Systemic mastocytosis (SM) is a heterogeneous group of rare, acquired and chronic hematological malignancies related to an abnormal accumulation/proliferation of neoplastic mast cells (MCs) in one or several organs, mainly the bone marrow (BM), associated frequently with skin involvement. […] Consensus criteria for the diagnosis of systemic mastocytosis established by the WHO include one major criterion – the presence of aggregates of at least 15 MCs identified in BM or other extracutaneous organ biopsies (usually revealed after tryptase staining of biopsies) – and four minor criteria: the presence of more than 25% of MCs with atypical morphology in BM smears (spindle-shaped, degranulated and/or multinucleated MCs); aberrant immunophenotype of MCs which frequently abnormally express non-mast cell markers (CD25 and/or CD2); presence of a point mutation in codon 816 of the KIT gene in BM; peripheral blood or other extracutaneous organs; and increased level of serum tryptase (above 20 ng/mL). For diagnosis of SM, at least the major and one minor criterion or at least three minor criteria are fulfilled. The disease is then categorized, as described above, according to the presence of B-findings and C-findings.

• #11 Immunophenotyping in systemic mastocytosis diagnosis: ‘CD25 positive’ alone is more informative than the ‘CD25 and/or CD2’ WHO criterion | Modern Pathology

  https://www.nature.com/articles/modpathol2011192

  Aberrant expression of CD2 and/or CD25 by bone marrow, peripheral blood or other extracutaneous tissue mast cells is currently used as a minor World Health Organization diagnostic criterion for systemic mastocytosis. […] Here we evaluate the sensitivity and specificity of CD2 versus CD25 expression in the diagnosis of systemic mastocytosis. […] The CD25+ and/or CD2+ bone marrow mast cells World Health Organization criterion showed an overall sensitivity of 100% with 99.0% specificity for the diagnosis of systemic mastocytosis whereas CD25 expression alone presented a similar sensitivity (100%) with a slightly higher specificity (99.2%). […] In summary, CD2 expression does not contribute to improve the diagnosis of systemic mastocytosis when compared with aberrant CD25 expression alone, which supports the need to update and replace the minor World Health Organization CD25+ and/or CD2+ mast cell phenotypic diagnostic criterion by a major criterion based exclusively on CD25 expression.

• #12 Untangling Systemic Mastocytosis: An Update on Challenges in the Diagnosis and Treatment of Myeloid Neoplasms with Systemic Mastocytosis – European Medical Journal

  https://www.emjreviews.com/hematology/symposium/untangling-systemic-mastocytosis-an-update-on-challenges-in-the-diagnosis-and-treatment-of-myeloid-neoplasms-with-systemic-mastocytosisj060122/

  Rossignol stressed that bone marrow biopsy is not routinely performed in all countries, and where it is performed, it may be challenging for an inexperienced pathologist to recognise mast cells in bone marrow biopsy if not using appropriate mast cell biomarkers, such as tryptase and cluster of differentiation 117 (CD117). Rossignol suggested that these issues may contribute to the underdiagnosis of the SM component of SM-AHN. […] Another minor diagnostic criterion for SM is the detection of baseline serum tryptase concentration 20 ng/mL. Rossignol pointed out that tryptase is not routinely assessed in patients diagnosed with myeloid neoplasms (especially those with CMML), and suggested that this test should be more commonly performed to screen for SM in this population, in order to alert the clinician to the possibility of concurrent SM disease.

• #13 Tests – TMS – The Mast Cell Disease Society, IncAccessibilityIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://tmsforacure.org/tests/

  If lesions are found, the physician should stroke the lesion firmly with a tongue depressor 5 or 6 times to see if it urticates (Darier’s sign). […] An international consensus task force of mast cell disease specialists has recently proposed that Darier’s sign be included as part of the major criterion for diagnosing skin involvement in mastocytosis patients. […] Examinations should occur periodically and include: Dermatological exam (with stroking for Darier’s sign). […] In patients who demonstrate a mediator rise, mediator testing should be repeated periodically.

• #14 Systemic Mastocytosis | Huntsman Cancer Institute | University of Utah Health

  https://healthcare.utah.edu/huntsmancancerinstitute/hematologic-cancers/systemic-mastocytosis

  Systemic mastocytosis is a rare disorder that happens when too many mast cells build up in parts of your body. […] Your doctor can answer any questions you may have about each type of systemic mastocytosis. […] Doctors use these tests to diagnose systematic mastocytosis: […] A health care provider examines your body for signs of disease. Your personal health habits, past illnesses, history of allergies to food or drugs, and symptoms of systemic mastocytosis guide the exam. […] Your health care team tests your blood for evidence of mastocytosis and checks to see how well your organs are functioning. […] The health care provider removes a small sample of bone marrow to look for abnormal cells under a microscope. […] Using CT scans, MRIs, and ultrasounds, your health care provider can create detailed images of internal organs.

• #15 Diagnostic Workup for Advanced Forms of Mastocytosis – TMS – The Mast Cell Disease Society, IncAccessibilityIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://tmsforacure.org/expert-information/diagnostic-workup-advanced-forms-mastocytosis/

  In patients with two or more B-findings the diagnosis of smoldering systemic mastocytosis (SSM) can be established. […] C-findings (one is enough to diagnose aggressive SM) are indicative of ASM or MCL. […] It is of particular importance that organ damage caused by MC infiltration only counts as an SM-related C-finding. […] In case of suspected AHN, further markers and criteria to classify the AHN according to WHO criteria have to be applied to fully diagnose both the SM component and the AHN component of the disease and to identify potential drug targets. […] Elevated serum tryptase is the key finding in patients with SM. […] Tryptase measurement is also of importance for the monitoring of SM. […] Many patients with advanced SM present with abnormal peripheral blood counts. […] An abnormal blood count is also a key finding to detect an AHN and to diagnose SM-AHN.

• #16 Systemic Mastocytosis Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/203948-workup

  Blood studies used in the diagnosis of systemic mastocytosis include the following: […] The World Health Organization has established diagnostic and classification criteria for systemic mastocytosis. […] Total serum tryptase levels of 20 ng/mL or higher in a baseline serum sample that is associated with a ratio of total to beta-tryptase ratio greater than 20:1 is suggestive of systemic mastocytosis. […] However, a normal serum tryptase level does not exclude the diagnosis of systemic mastocytosis. […] Molecular testing for KIT D816V mutation is universally positive, whereas JAK2 V617F is rarely positive (4%). […] Bone marrow aspiration and biopsy is essential for the diagnosis of systemic mastocytosis. […] When GI symptoms are present, perform GI procedures (eg, barium studies, endoscopy) to help confirm the diagnosis.

• #17

  https://www.haematologica.org/content/93/1/120.long

  Although it is not necessary to choose any particular threshold for assessment of test accuracy of the various biochemical markers, we selected various thresholds to be used in patient care. This means that a patient with only cutaneous involvement and a serum tryptase level below 20 g/L (threshold used by the WHO as minor criterion) would have a 16% risk of bone marrow involvement, and thus a diagnosis of indolent systemic mastocytosis. The probability that a patient with a serum tryptase level of 21.9 g/L had bone marrow involvement was 98%, and with a level of 30.8 g/L this rose even to 100%.

• #18 Testing for Systemic Mastocytosis | Blueprint Medicines

  https://itssmthing.com/diagnosis.php

  Getting an SM diagnosis can be a complicated process. Since there are so many different symptoms, it can be tough to connect the pieces of the puzzle. […] Given the rarity of SM, the variety of symptoms are sometimes attributed to other causes before an actual SM diagnosis is made. For example, SM can sometimes be mistaken for a GI disorder or cutaneous mastocytosis. […] Because SM is so rare and awareness of the disease may be low, it often gets misdiagnosed. […] There are several tests that your doctor may use to evaluate for SM. […] This test measures the amount of tryptase (an enzyme that is released by mast cells) in the blood. […] Biopsies are tissue samples taken for closer examination. […] A KIT D816V blood test can help aid in the diagnosis of SM by identifying a genetic mutation that has been found in approximately 95% of patients with SM. […] While one test alone cannot confirm an SM diagnosis, it may help your doctor determine what additional diagnostic testing is needed.

• #19 Tests – TMS – The Mast Cell Disease Society, IncAccessibilityIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://tmsforacure.org/tests/

  To understand why KIT testing is necessary, one must first understand the difference between clonal and non-clonal mast cell diseases. […] There has been a peptide nucleic acid mediated PCR based test available for years that can identify the KIT D816V mutation in peripheral blood, and it has been able to detect the mutation in 44% of systemic mastocytosis patients tested. […] Although the more sensitive test for the KIT D816V mutation (the allele-specific qPCR, with a sensitivity of 0.01%) that can be performed in peripheral blood samples has been developed, is not yet widely available here in the US. […] Standard technique can be used to obtain an iliac crest bone marrow biopsy and aspirate smear for diagnosis. […] When advanced disease or an associated hematological disorder is suspected, further evaluation of the patient beyond a bone marrow biopsy and aspirate with flow cytometry may include: Other tests may include next-generation sequencing and myeloid gene panels for additional genetic lesions.

• #20 Mast Cell Disorders | Choose the Right Test

  https://arupconsult.com/content/mast-cell-disorders

  Mast cell disorders (MCDs), including mast cell activation syndrome (MCAS) and mastocytosis, are a diverse group of conditions characterized by inappropriate mast cell activation and/or the proliferation and accumulation of abnormal mast cells throughout the body. […] The diagnostic approach depends on the type of MCD but often involves laboratory testing such as serum tryptase measurement and KIT gene mutational analysis on bone marrow and/or peripheral blood. […] Ultrasensitive testing methods such as digital droplet polymerase chain reaction (ddPCR) are the preferred first-line methods for KIT mutational analysis to diagnose mast cell disorders (MCDs), given that these methods are sensitive, highly specific, and can be performed on peripheral blood. […] When evaluating an individual for nonclonal mast cell activation syndrome (NC-MCAS), an increase in the serum level of tryptase above baseline and within a narrow window of time (generally 30 minutes to 2 hours) after a symptomatic episode is the preferred method to provide evidence of mast cell involvement.

• #21 Mast Cell Disorders | Choose the Right Test

  https://arupconsult.com/content/mast-cell-disorders

  When bone marrow is examined for MCD, good practice is to examine a blood smear, a bone marrow aspirate smear, and a bone marrow biopsy. […] If KIT D816V testing is negative and eosinophilia is present, testing for the FIP1L1::PDGFRA fusion gene is recommended. […] Laboratory monitoring is recommended every 6-12 months for SM and yearly for indolent SM.

• #22 Mastocytosis Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1057932-workup

  In many patients, urticaria pigmentosa (UP) can be diagnosed when history and physical examination findings reveal the characteristic lesions that demonstrate the Darier sign. Usually, a skin biopsy is a necessary confirmatory test, typically through a 3- or 4-mm punch biopsy. It may be helpful to complete two biopsies, one of the suspected lesion and the other of unaffected skin, in order to compare the presence of mast cells. For aid in the diagnosis, the following stains are recommended to be completed with biopsy: hematoxylin, eosin, toluidine blue, Giemsa, and monoclonal antibodies to tryptase, CD117 and KIT. […] CBC count: In systemic mastocytosis, CBC counts may reveal anemia, thrombocytopenia, thrombocytosis, leukocytosis, and eosinophilia. […] Total tryptase level: Tryptase is a marker of mast cell degranulation released in parallel with histamine. Total tryptase levels in plasma correlate with the density of mast cells in urticaria pigmentosa lesions in adults with systemic mastocytosis. Patients with only cutaneous mastocytosis typically have normal levels of total tryptase. Total tryptase values are recommended by the WHO as a minor criterion for use in the diagnostic evaluation of systemic mastocytosis.

• #23 Mast Cell Disorders | Choose the Right Test

  https://arupconsult.com/content/mast-cell-disorders

  Testing should include serum tryptase and peripheral blood testing for the KIT D816V mutation. […] The major and minor diagnostic criteria for SM are based on the results of laboratory testing. […] The diagnosis and classification of MCDs is based on the above SM criteria and other findings: […] All individuals suspected of having SM should undergo KIT mutational analysis. […] If a KIT D816V mutation is detected in peripheral blood, a bone marrow biopsy should be performed to evaluate for SM, including the subtype of the disease. […] The NCCN recommends that the evaluation for suspected SM include a biopsy (bone marrow or involved organ), immunophenotyping of mast cells (flow cytometry or immunohistochemistry [IHC]), and KIT gene testing. […] Bone marrow biopsy remains the gold standard for establishing the diagnosis of mastocytosis.

• #24 Diagnostic Workup for Advanced Forms of Mastocytosis – TMS – The Mast Cell Disease Society, IncAccessibilityIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://tmsforacure.org/expert-information/diagnostic-workup-advanced-forms-mastocytosis/

  Although the presence of the major criterion for diagnosis of SM can be evaluated with a biopsy from any organ involved in disease other than skin (e.g., liver, gastrointestinal tract), bone marrow is the most common site. […] There are many pros of a bone marrow biopsy/aspirate, including providing information on an AHN, rendering differential diagnosis with other possible malignancies, and being easy and safe. […] The most important molecular marker to show monoclonality in SM is the KIT point mutation D816V that can be analyzed in the bone marrow and the peripheral blood. […] Diagnostic work-up should include: careful history and physical exam, serum tryptase, bone marrow biopsy and aspirate with appropriate analyses, if serum tryptase is high and/or blood counts are abnormal, molecular testing from bone marrow, abdominal ultrasound, dexa scan and/or other skeletal imaging, endoscopies with biopsies in cases with gastrointestinal symptoms, chest CT, in patients with pulmonary symptoms (very rarely).

• #25 Untangling Systemic Mastocytosis: An Update on Challenges in the Diagnosis and Treatment of Myeloid Neoplasms with Systemic Mastocytosis – European Medical Journal

  https://www.emjreviews.com/hematology/symposium/untangling-systemic-mastocytosis-an-update-on-challenges-in-the-diagnosis-and-treatment-of-myeloid-neoplasms-with-systemic-mastocytosisj060122/

  Deepti Radia, Consultant Haematologist at Guys and St Thomas Hospitals NHS Foundation Trust, London, UK, explained that SM-AHN has a complex, heterogenous clinical presentation, involving the SM variant, SM burden, AHN subtype, and AHN risk profile. This can make accurate diagnosis of advanced SM challenging, yet it is extremely important because of the substantial impact it has on patient management decisions. […] Reiter highlighted that approximately 20% of cases of SM may initially be missed in patients with chronic myeloid neoplasms, leading to delayed diagnosis and treatment for patients. Reiter explained that SM should be suspected in patients presenting with anaphylaxis, flushes, fatigue, typical skin lesions, or symptoms in bones or the gastrointestinal tract. […] The 2022 World Health Organization (WHO) and International Consensus Classification (ICC) criteria for the diagnosis of SM are very similar. For SM diagnosis, a patient needs to meet one major and one minor, or three minor criteria. The major criterion for diagnosis of SM is the presence of multifocal dense infiltrates of mast cells (15 mast cells in aggregates) in bone marrow biopsies and/or in sections of other extracutaneous organ(s) component of SM.

• #26 Systemic Mastocytosis: Causes, Symptoms, Diagnosis, and Treatment

  https://www.webmd.com/allergies/systemic-mastocytosis

  Imaging tests. X-rays, ultrasounds, and CT scans may show problems such as bone loss or an enlarged liver, spleen, or lymph nodes. […] Endoscopy or colonoscopy. In an endoscopy or colonoscopy, a doctor puts a thin, flexible tube with a camera into your mouth or rectum. This can show ulcers, bleeding, or other damage to your digestive tract. Sometimes, your doctor may remove a sample of your tissue and check it for mast cells.

• #27 Diagnosis and treatment of systemic mastocytosis in Brazil: Recommendations of a multidisciplinary expert panel | Hematology, Transfusion and Cell Therapy

  http://www.htct.com.br/en-diagnosis-treatment-systemic-mastocytosis-in-articulo-S2531137922000803

  Recommendation: Doppler abdominal ultrasound should be performed for all patients with Systemic Mastocytosis to evaluate hepatomegaly, portal hypertension and ascites (GRADE 3). […] Recommendation: CT scans and MRI should be used to evaluate Systemic Mastocytosis C findings. The FDG-PET/CT scans should not be part of the initial assessment of the most common forms of the disease (GRADE 3). […] Recommendation: The clinical or hybrid Mayo criteria should be used to determine prognosis (GRADE 4). […] Recommendation: The cytoreductive therapy is indicated for patients with advanced systemic mastocytosis and for patients with indolent or smouldering Systemic Mastocytosis, for whom symptom therapy fails. […] Recommendation: The allogeneic stem cell transplantation should be considered in eligible patients with advanced SM with an estimated survival of fewer than 5 years and/or patients with SM-AHN with hematological neoplasms who have an indication for allogeneic stem cell transplantation (GRADE 4).

• #28 Advanced systemic mastocytosis

  https://www.medicalnewstoday.com/articles/advanced-systemic-mastocytosis

  A doctor may perform several examinations and tests to help diagnose advanced systemic mastocytosis. These include the following: […] Blood test: Complete blood count and elevated tryptase levels can help differentiate the variants of advanced systemic mastocytosis. Tryptase is an enzyme that primarily comes from mast cells. […] Bone marrow biopsy: Using a long needle, the doctor will remove a sample of bone marrow tissue for further testing. A person will receive a local anesthetic before this procedure. […] Imaging tests: Imaging tests, such as ultrasounds, can help the doctor view internal organs and tissues clearly. Additionally, dual-energy X-ray absorptiometry scans can help assess bone density. […] It is best to contact a doctor as soon as there are concerns about advanced systemic mastocytosis. They can order tests to confirm the diagnosis and advise on suitable treatments.

• #29 Diagnosis and treatment of systemic mastocytosis in Brazil: Recommendations of a multidisciplinary expert panel | Hematology, Transfusion and Cell Therapy

  http://www.htct.com.br/en-diagnosis-treatment-systemic-mastocytosis-in-articulo-S2531137922000803

  Recommendation: Doppler abdominal ultrasound should be performed for all patients with Systemic Mastocytosis to evaluate hepatomegaly, portal hypertension and ascites (GRADE 3). […] Recommendation: CT scans and MRI should be used to evaluate Systemic Mastocytosis C findings. The FDG-PET/CT scans should not be part of the initial assessment of the most common forms of the disease (GRADE 3). […] Recommendation: The clinical or hybrid Mayo criteria should be used to determine prognosis (GRADE 4). […] Recommendation: The cytoreductive therapy is indicated for patients with advanced systemic mastocytosis and for patients with indolent or smouldering Systemic Mastocytosis, for whom symptom therapy fails. […] Recommendation: The allogeneic stem cell transplantation should be considered in eligible patients with advanced SM with an estimated survival of fewer than 5 years and/or patients with SM-AHN with hematological neoplasms who have an indication for allogeneic stem cell transplantation (GRADE 4).

• #30 Diagnosis and treatment of systemic mastocytosis in Brazil: Recommendations of a multidisciplinary expert panel | Hematology, Transfusion and Cell Therapy

  http://www.htct.com.br/en-diagnosis-treatment-systemic-mastocytosis-in-articulo-S2531137922000803

  Recommendation: Doppler abdominal ultrasound should be performed for all patients with Systemic Mastocytosis to evaluate hepatomegaly, portal hypertension and ascites (GRADE 3). […] Recommendation: CT scans and MRI should be used to evaluate Systemic Mastocytosis C findings. The FDG-PET/CT scans should not be part of the initial assessment of the most common forms of the disease (GRADE 3). […] Recommendation: The clinical or hybrid Mayo criteria should be used to determine prognosis (GRADE 4). […] Recommendation: The cytoreductive therapy is indicated for patients with advanced systemic mastocytosis and for patients with indolent or smouldering Systemic Mastocytosis, for whom symptom therapy fails. […] Recommendation: The allogeneic stem cell transplantation should be considered in eligible patients with advanced SM with an estimated survival of fewer than 5 years and/or patients with SM-AHN with hematological neoplasms who have an indication for allogeneic stem cell transplantation (GRADE 4).

• #31 Systemic Mastocytosis Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/203948-workup

  Blood studies used in the diagnosis of systemic mastocytosis include the following: […] The World Health Organization has established diagnostic and classification criteria for systemic mastocytosis. […] Total serum tryptase levels of 20 ng/mL or higher in a baseline serum sample that is associated with a ratio of total to beta-tryptase ratio greater than 20:1 is suggestive of systemic mastocytosis. […] However, a normal serum tryptase level does not exclude the diagnosis of systemic mastocytosis. […] Molecular testing for KIT D816V mutation is universally positive, whereas JAK2 V617F is rarely positive (4%). […] Bone marrow aspiration and biopsy is essential for the diagnosis of systemic mastocytosis. […] When GI symptoms are present, perform GI procedures (eg, barium studies, endoscopy) to help confirm the diagnosis.

• #32 Systemic Mastocytosis: Causes, Symptoms, Diagnosis, and Treatment

  https://www.webmd.com/allergies/systemic-mastocytosis

  Imaging tests. X-rays, ultrasounds, and CT scans may show problems such as bone loss or an enlarged liver, spleen, or lymph nodes. […] Endoscopy or colonoscopy. In an endoscopy or colonoscopy, a doctor puts a thin, flexible tube with a camera into your mouth or rectum. This can show ulcers, bleeding, or other damage to your digestive tract. Sometimes, your doctor may remove a sample of your tissue and check it for mast cells.

• #33 Mastocytosis — DermNet

  https://dermnetnz.org/topics/mastocytosis

  Systemic mastocytosis is usually diagnosed in adulthood after the second decade of life. […] Systemic mastocytosis is diagnosed when a patient has a positive bone marrow biopsy or other extracutaneous biopsy. Specific laboratory and genetic tests may also support the diagnosis. […] Relevant tests include: Full blood count, Serum biochemistry, Liver function tests, Serum tryptase level (systemic mastocytosis less likely with tryptase level), Abdominal ultrasound, Bone density scan, Bone marrow trephine, Blood and marrow smears, Flow cytometry (to measure CD2, CD25, and CD30), Genetic testing (KIT mutations in bone marrow mast cells). […] Major criteria: Multiple areas of dense infiltrate of mast cells in the bone marrow or other extracutaneous organs, confirmed by special stains on histology, such as mast cell tryptase (15 mast cells aggregating).

• #34 Tests – TMS – The Mast Cell Disease Society, IncAccessibilityIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://tmsforacure.org/tests/

  If you suspect that you or a loved one has a mast cell disease, such as Systemic Mastocytosis or MCAS. It is important to get the appropriate testing to get a proper diagnosis. A proper diagnosis is critical to making sure you get the best care possible to improve daily life with these conditions. […] An increase in the serum level of tryptase, above baseline and within a narrow (generally accepted as one to two hour) window of time after a symptomatic episode, is proposed as the preferred method for providing evidence of mast cell involvement. […] Consensus members also agreed that when serum tryptase evaluation is not available or when the tryptase level does not rise sufficiently to meet the required increase for the co-criterion, other mediator tests could suffice. […] TMS does recognize, however, that capturing a mediator rise is not always easy, and depends on many factors, internal and environmental.

• #35 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  In addition to the initial diagnosis, systemic mastocytosis is divided into subtypes determined by findings such as the amount of organ infiltration by mast cells (mast cell burden), presence or absence of other blood malignancies, and organ involvement with mast cell related damage such as enlarged liver, spleen or lymph nodes, or bone damage. […] There are five systemic mastocytosis subtypes and other rare variants have been described, including well differentiated systemic mastocytosis. […] Determining the subgroup helps in directing therapy and establishing prognosis. […] Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers.

• #36

  https://www.mastcellhope.org/education/testing-and-diagnosis/

  Molecular testing reveals a KITD 816V mutation or any other KIT mutation in a sample from the blood, bone marrow, or another organ. […] Flow cytometry and/or immunohistochemistry reveal abnormal mast cell CD25 markers (clusters of differentiation). May occur with or without CD2 markers. […] A serum tryptase test with total tryptase blood levels greater than 20 ng/mL. This criterion is not valid if the patient has an associated myeloid neoplasm (a tumor of the bone marrow). […] B and C findings are utilized to diagnose subtypes of systemic mastocytosis. […] All sub-types of systemic mastocytosis must meet the criteria for systemic mastocytosis in addition to the criteria defined below. […] Indolent systemic mastocytosis (ISM): Does not present C findings. […] Smoldering systemic mastocytosis (SSM): Presents the same criteria for ISM in addition to the following: Two or more B findings.

• #37

  https://www.mastcellhope.org/education/testing-and-diagnosis/

  Systemic mastocytosis with an associated hematological neoplasm (SM-AHN): In addition to meeting the criteria for systemic mastocytosis, also meets the criteria for an associated hematological neoplasm, per classification outlined by the WHO. […] Aggressive systemic mastocytosis (ASM): Meets the systemic mastocytosis criteria. […] Mast cell leukemia (MCL): Diagnosed with the following studies: Bone marrow biopsy: Dense infiltration of atypical, immature mast cells. […] Mast cell sarcoma (MCS): Mast cell sarcoma does not present with evidence of systemic mastocytosis. This diagnosis generally presents as a localized destructive growth pattern.

• #38 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  In addition to the initial diagnosis, systemic mastocytosis is divided into subtypes determined by findings such as the amount of organ infiltration by mast cells (mast cell burden), presence or absence of other blood malignancies, and organ involvement with mast cell related damage such as enlarged liver, spleen or lymph nodes, or bone damage. […] There are five systemic mastocytosis subtypes and other rare variants have been described, including well differentiated systemic mastocytosis. […] Determining the subgroup helps in directing therapy and establishing prognosis. […] Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers.

• #39 Diagnostic Workup for Advanced Forms of Mastocytosis – TMS – The Mast Cell Disease Society, IncAccessibilityIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://tmsforacure.org/expert-information/diagnostic-workup-advanced-forms-mastocytosis/

  In patients with two or more B-findings the diagnosis of smoldering systemic mastocytosis (SSM) can be established. […] C-findings (one is enough to diagnose aggressive SM) are indicative of ASM or MCL. […] It is of particular importance that organ damage caused by MC infiltration only counts as an SM-related C-finding. […] In case of suspected AHN, further markers and criteria to classify the AHN according to WHO criteria have to be applied to fully diagnose both the SM component and the AHN component of the disease and to identify potential drug targets. […] Elevated serum tryptase is the key finding in patients with SM. […] Tryptase measurement is also of importance for the monitoring of SM. […] Many patients with advanced SM present with abnormal peripheral blood counts. […] An abnormal blood count is also a key finding to detect an AHN and to diagnose SM-AHN.

• #40 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #41 Untangling Systemic Mastocytosis: An Update on Challenges in the Diagnosis and Treatment of Myeloid Neoplasms with Systemic Mastocytosis – European Medical Journal

  https://www.emjreviews.com/hematology/symposium/untangling-systemic-mastocytosis-an-update-on-challenges-in-the-diagnosis-and-treatment-of-myeloid-neoplasms-with-systemic-mastocytosisj060122/

  This symposium was held on the first day of the 2023 European Hematology Association (EHA) Congress, held in Frankfurt, Germany. The main objective of the symposium was to gather experts from the field to raise awareness of the challenges in diagnosing and treating systemic mastocytosis (SM) with an associated haematologic neoplasm (AHN). Presentations focused on optimising the diagnosis of the SM component and recognising the different types of myeloid AHN. The expert panel considered the clinical management of SM-AHN, and how and when to prioritise the various disease components. […] The overarching message from the symposium was that diagnosis of SM-AHN is challenging, and SM is often missed in patients with a myeloid neoplasm, such as chronic myelomonocytic leukaemia (CMML), myelodysplastic/myeloproliferative neoplasm (MDS/MPN), myelodysplastic syndrome (MDS), and myeloproliferative neoplasm (MPN), as well as AHN being missed in patients with SM. Identification of a SM-AHN through serum tryptase and/or molecular testing for KIT D816V mutation in peripheral blood in a patient with a previous diagnosis of a myeloid neoplasm allows potentially efficacious targeted treatment with KIT inhibitors, such as midostaurin and avapritinib.

• #42 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #43 Multidisciplinary Collaboration Is Vital for Timely, Definitive Diagnosis of Indolent Systemic Mastocytosis

  https://www.onclive.com/view/multidisciplinary-collaboration-is-vital-for-timely-definitive-diagnosis-of-indolent-systemic-mastocytosis

  Despite advancements in diagnostic testing, patients with indolent systemic mastocytosis (ISM) often experience delays in diagnosis due to the diseases heterogeneous presentation, highlighting the need for an integrative, multidisciplinary approach to improve early recognition of this condition and optimize patient care, according to Andrew Kuykendall, MD. […] In an interview with OncLive, Kuykendall expanded on the diagnostic process in ISM, discussing the importance of biopsy, KIT mutation testing, and serum tryptase levels in diagnosing ISM. […] When we think about the diagnostic criteria of systemic mastocytosis in general, one of the most critical things is [to obtain] a biopsy of an extracutaneous organ that shows these clusters of atypical mast cells. […] Importantly, that mutation can occur at very low levels. It’s important to send this test to be done in a highly sensitive fashion.

• #44 DISCOVERSM Differentiate SM and Case Studies | Information for HCPs

  https://www.systemicmastocytosis-hcp.com/discover-sm/

  Patients with systemic mastocytosis (SM) report a substantial delay in diagnosis. Median time from symptom onset to diagnosis is 7 years. Recognising common symptoms may help with earlier identification of SM. Symptoms of SM can mimic other disorders. Diagnosis of CM requires a bone marrow assessment, which may aid in confirming or excluding SM in the next step. Recognising severe and recurrent instances of the common symptoms can raise the suspicion of SM: mast cell examination, serum tryptase assessment or high-sensitivity KIT D816V mutation testing can help diagnose SM. Combined with the bone marrow mast cell aggregates, a confirmed KIT D816V mutation status allowed Victor’s diagnosis to be revised to SM with an associated haematological neoplasm (SM-AHN). With persistently elevated serum tryptase, 30% mast cell infiltration of bone marrow and a positive KIT D816V mutation status, Katherine’s diagnosis was revised to indolent systemic mastocytosis (ISM). With a positive KIT D816V mutation status, 35% infiltration of cellularity by mast cells, aberrant expression of CD25 and irregular, spindle-shaped mast cells, the haematologist was able to diagnose Maria with ISM. With a positive KIT D816V mutation status, 40% infiltration of cellularity by mast cells, aberrant expression of CD25 and irregular, spindle-shaped mast cells, the haematologist was able to diagnose Peter with ISM.

• #45 Systemic Mastocytosis: Symptoms, Causes, Diagnosis, and Treatment

  https://www.everydayhealth.com/rare-diseases/systemic-mastocytosis/

  Systemic mastocytosis (SM) is a rare blood disorder in which the body produces too many mast cells. […] This is a very rare disease, and many doctors aren’t familiar enough with the condition to recognize it. Because of that, many people can go undiagnosed for years, says Gotlib. […] Typically, doctors will begin with a physical exam and a thorough review of symptoms. If mastocytosis is suspected, several diagnostic tests may be used: […] Elevated levels of certain markers, such as tryptase (a protein released by mast cells), can suggest mastocytosis. […] A sample of bone marrow may be taken to check for abnormal mast cells. […] Tests to detect mutations in the KIT gene can help confirm a diagnosis of systemic mastocytosis. […] CT scans, MRIs, bone scans, or ultrasounds may be used to check for organ involvement.

• #46 Untangling Systemic Mastocytosis: An Update on Challenges in the Diagnosis and Treatment of Myeloid Neoplasms with Systemic Mastocytosis – European Medical Journal

  https://www.emjreviews.com/hematology/symposium/untangling-systemic-mastocytosis-an-update-on-challenges-in-the-diagnosis-and-treatment-of-myeloid-neoplasms-with-systemic-mastocytosisj060122/

  Rossignol stressed that bone marrow biopsy is not routinely performed in all countries, and where it is performed, it may be challenging for an inexperienced pathologist to recognise mast cells in bone marrow biopsy if not using appropriate mast cell biomarkers, such as tryptase and cluster of differentiation 117 (CD117). Rossignol suggested that these issues may contribute to the underdiagnosis of the SM component of SM-AHN. […] Another minor diagnostic criterion for SM is the detection of baseline serum tryptase concentration 20 ng/mL. Rossignol pointed out that tryptase is not routinely assessed in patients diagnosed with myeloid neoplasms (especially those with CMML), and suggested that this test should be more commonly performed to screen for SM in this population, in order to alert the clinician to the possibility of concurrent SM disease.

• #47 Untangling Systemic Mastocytosis: An Update on Challenges in the Diagnosis and Treatment of Myeloid Neoplasms with Systemic Mastocytosis – European Medical Journal

  https://www.emjreviews.com/hematology/symposium/untangling-systemic-mastocytosis-an-update-on-challenges-in-the-diagnosis-and-treatment-of-myeloid-neoplasms-with-systemic-mastocytosisj060122/

  Rossignol stressed that bone marrow biopsy is not routinely performed in all countries, and where it is performed, it may be challenging for an inexperienced pathologist to recognise mast cells in bone marrow biopsy if not using appropriate mast cell biomarkers, such as tryptase and cluster of differentiation 117 (CD117). Rossignol suggested that these issues may contribute to the underdiagnosis of the SM component of SM-AHN. […] Another minor diagnostic criterion for SM is the detection of baseline serum tryptase concentration 20 ng/mL. Rossignol pointed out that tryptase is not routinely assessed in patients diagnosed with myeloid neoplasms (especially those with CMML), and suggested that this test should be more commonly performed to screen for SM in this population, in order to alert the clinician to the possibility of concurrent SM disease.

• #48 Multidisciplinary Collaboration Is Vital for Timely, Definitive Diagnosis of Indolent Systemic Mastocytosis

  https://www.onclive.com/view/multidisciplinary-collaboration-is-vital-for-timely-definitive-diagnosis-of-indolent-systemic-mastocytosis

  This is often the first thing that’s done to get a sense for whether we may be dealing with systemic mastocytosis because tryptase levels are often in excess of 20 ng/mL, with normal [levels] being less than approximately 11 ng/mL. […] The biggest challenge is having that pre-test probability or clinical suspicion for this rare disease. […] This is hugely important, but it can be a challenge. […] Our advances in understanding the biology behind this disease and our ability to have more sensitive testing have allowed for an increase in diagnoses and awareness. […] However, in the past, we didn’t even have the technology to test to a level where we could rule this disease in or out. […] With that, [we have a better] understanding of the tryptase values and some of these stains that need to be done on these cells, so we certainly have an enhanced ability to capture these patients.

• #49 Recent advances in diagnosis and therapy in systemic mastocytosis

  https://www.bloodresearch.or.kr/journal/view.html?pn=myread&uid=2610&vmd=Full

  Diagnostic algorithm for patients with suspected systemic mastocytosis. In all adult patients with documented mastocytosis in the skin (MIS), a complete staging, including a bone marrow (BM) examination, is required. […] a core biopsy specimen may be used to diagnose MCL if the aspirate is a dry tap.

• #50 Recent advances in diagnosis and therapy in systemic mastocytosis

  https://www.bloodresearch.or.kr/journal/view.html?uid=2610

  Diagnostic algorithm for patients with suspected systemic mastocytosis. In all adult patients with documented mastocytosis in the skin (MIS), a complete staging, including a bone marrow (BM) examination, is required. […] a) Independent of the serum tryptase level; b) Basal tryptase levels at least 48 hours after resolution of all MC-MRSs; c) in ICC, a core biopsy specimen may be used to diagnose MCL if the aspirate is a dry tap.

• #51 Untangling Systemic Mastocytosis: An Update on Challenges in the Diagnosis and Treatment of Myeloid Neoplasms with Systemic Mastocytosis – European Medical Journal

  https://www.emjreviews.com/hematology/symposium/untangling-systemic-mastocytosis-an-update-on-challenges-in-the-diagnosis-and-treatment-of-myeloid-neoplasms-with-systemic-mastocytosisj060122/

  Deepti Radia, Consultant Haematologist at Guys and St Thomas Hospitals NHS Foundation Trust, London, UK, explained that SM-AHN has a complex, heterogenous clinical presentation, involving the SM variant, SM burden, AHN subtype, and AHN risk profile. This can make accurate diagnosis of advanced SM challenging, yet it is extremely important because of the substantial impact it has on patient management decisions. […] Reiter highlighted that approximately 20% of cases of SM may initially be missed in patients with chronic myeloid neoplasms, leading to delayed diagnosis and treatment for patients. Reiter explained that SM should be suspected in patients presenting with anaphylaxis, flushes, fatigue, typical skin lesions, or symptoms in bones or the gastrointestinal tract. […] The 2022 World Health Organization (WHO) and International Consensus Classification (ICC) criteria for the diagnosis of SM are very similar. For SM diagnosis, a patient needs to meet one major and one minor, or three minor criteria. The major criterion for diagnosis of SM is the presence of multifocal dense infiltrates of mast cells (15 mast cells in aggregates) in bone marrow biopsies and/or in sections of other extracutaneous organ(s) component of SM.

• #52 Mast Cell Disorders | Choose the Right Test

  https://arupconsult.com/content/mast-cell-disorders

  Testing should include serum tryptase and peripheral blood testing for the KIT D816V mutation. […] The major and minor diagnostic criteria for SM are based on the results of laboratory testing. […] The diagnosis and classification of MCDs is based on the above SM criteria and other findings: […] All individuals suspected of having SM should undergo KIT mutational analysis. […] If a KIT D816V mutation is detected in peripheral blood, a bone marrow biopsy should be performed to evaluate for SM, including the subtype of the disease. […] The NCCN recommends that the evaluation for suspected SM include a biopsy (bone marrow or involved organ), immunophenotyping of mast cells (flow cytometry or immunohistochemistry [IHC]), and KIT gene testing. […] Bone marrow biopsy remains the gold standard for establishing the diagnosis of mastocytosis.

• #53 Mast Cell Disorders | Choose the Right Test

  https://arupconsult.com/content/mast-cell-disorders

  Testing should include serum tryptase and peripheral blood testing for the KIT D816V mutation. […] The major and minor diagnostic criteria for SM are based on the results of laboratory testing. […] The diagnosis and classification of MCDs is based on the above SM criteria and other findings: […] All individuals suspected of having SM should undergo KIT mutational analysis. […] If a KIT D816V mutation is detected in peripheral blood, a bone marrow biopsy should be performed to evaluate for SM, including the subtype of the disease. […] The NCCN recommends that the evaluation for suspected SM include a biopsy (bone marrow or involved organ), immunophenotyping of mast cells (flow cytometry or immunohistochemistry [IHC]), and KIT gene testing. […] Bone marrow biopsy remains the gold standard for establishing the diagnosis of mastocytosis.

• #54 Diagnosis and treatment of systemic mastocytosis in Brazil: Recommendations of a multidisciplinary expert panel | Hematology, Transfusion and Cell Therapy

  http://www.htct.com.br/en-diagnosis-treatment-systemic-mastocytosis-in-articulo-S2531137922000803

  The diagnosis of SM can be made when the major criterion and one minor criterion or at least three minor criteria are present. Major Criterion Multifocal, dense infiltrates of mast cells (≥15 mast cells in aggregates) detected in sections of bone marrow and/or other extracutaneous organs. […] The SM should always be suspected and investigated in adult patients with cutaneous disease. […] Recommendation: Cutaneous Mastocytosis should be diagnosed only after the dermatological clinical evaluation, anatomopathological examination and exclusion of Systemic Mastocytosis criteria (GRADE 1). […] Recommendation: Tryptase level measurements are necessary for the Systemic Mastocytosis diagnosis and follow-up (GRADE 2) at least once a year (GRADE 5). […] Recommendation: The D816V KIT mutations should be investigated in all patients with Systemic Mastocytosis.

• #55 Diagnostic Workup for Advanced Forms of Mastocytosis – TMS – The Mast Cell Disease Society, IncAccessibilityIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://tmsforacure.org/expert-information/diagnostic-workup-advanced-forms-mastocytosis/

  Although the presence of the major criterion for diagnosis of SM can be evaluated with a biopsy from any organ involved in disease other than skin (e.g., liver, gastrointestinal tract), bone marrow is the most common site. […] There are many pros of a bone marrow biopsy/aspirate, including providing information on an AHN, rendering differential diagnosis with other possible malignancies, and being easy and safe. […] The most important molecular marker to show monoclonality in SM is the KIT point mutation D816V that can be analyzed in the bone marrow and the peripheral blood. […] Diagnostic work-up should include: careful history and physical exam, serum tryptase, bone marrow biopsy and aspirate with appropriate analyses, if serum tryptase is high and/or blood counts are abnormal, molecular testing from bone marrow, abdominal ultrasound, dexa scan and/or other skeletal imaging, endoscopies with biopsies in cases with gastrointestinal symptoms, chest CT, in patients with pulmonary symptoms (very rarely).

• #56 Systemic mastocytosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/systemic-mastocytosis/diagnosis-treatment/drc-20450478

  To diagnose systemic mastocytosis, your doctor will likely start by reviewing your symptoms and discussing your medical history, including medications you’ve taken. He or she can then order tests that look for high levels of mast cells or the substances they release. Evaluation of organs affected by the condition also may be done. […] Tests may include: Blood or urine tests, Bone marrow biopsy, Skin biopsy, Imaging tests such as an X-ray, ultrasound, bone scan and CT scan, Biopsy of organs affected by the disease, such as the liver, Genetic testing. […] Your doctor regularly monitors the status of your condition using blood and urine samples. You may be able to use a special home kit to collect blood and urine samples while you’re experiencing symptoms, which gives your doctor a better picture of how systemic mastocytosis affects your body. Regular bone density measurements can monitor you for problems such as osteoporosis. […] After getting detailed information about the symptoms and your family’s medical history, your doctor may order tests to help with diagnosis and treatment planning.

• #57 Mast Cell Disorders | Choose the Right Test

  https://arupconsult.com/content/mast-cell-disorders

  When bone marrow is examined for MCD, good practice is to examine a blood smear, a bone marrow aspirate smear, and a bone marrow biopsy. […] If KIT D816V testing is negative and eosinophilia is present, testing for the FIP1L1::PDGFRA fusion gene is recommended. […] Laboratory monitoring is recommended every 6-12 months for SM and yearly for indolent SM.

• #58 Orphanet: Smoldering systemic mastocytosis

  https://www.orpha.net/en/disease/detail/158775

  A rare, slowly progressive form of systemic mastocytosis (SM) characterized by gradual accumulation of neoplastic mast cells in the visceral organs. Patients typically present with splenomegaly, hypercellular marrow and, in most cases, urticaria pigmentosa-like skin lesions. […] Diagnosis of SSM is achieved by first establishing a diagnosis of SM, based on the WHO consensus criteria. The disease is then categorized according to the presence of B-findings and C-findings. For SSM, at least two B-findings (but no C-findings) should be present. […] In stable SSM patients, symptomatic treatment may be the only therapy. Avoidance of known triggers, prophylactic prescription of an epi-pen, and medications such as antihistamines, antileukotrienes, cromolyn sodium, omalizumab and aspirin may all have a role in the prevention or treatment of MC-mediated symptoms. Regular follow-up and assessment for transformation to more aggressive disease variants is required. Serum tryptase, which may be used to assess disease response, may be evaluated biannually to monitor disease activity and appropriately adjust therapy. […] Some SSM patients may remain stable for years, while others may progress to more advanced variants of the disease (ASM or MCL), with a poorer prognosis.

• #59 Systemic mastocytosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/systemic-mastocytosis/diagnosis-treatment/drc-20450478

  To diagnose systemic mastocytosis, your doctor will likely start by reviewing your symptoms and discussing your medical history, including medications you’ve taken. He or she can then order tests that look for high levels of mast cells or the substances they release. Evaluation of organs affected by the condition also may be done. […] Tests may include: Blood or urine tests, Bone marrow biopsy, Skin biopsy, Imaging tests such as an X-ray, ultrasound, bone scan and CT scan, Biopsy of organs affected by the disease, such as the liver, Genetic testing. […] Your doctor regularly monitors the status of your condition using blood and urine samples. You may be able to use a special home kit to collect blood and urine samples while you’re experiencing symptoms, which gives your doctor a better picture of how systemic mastocytosis affects your body. Regular bone density measurements can monitor you for problems such as osteoporosis. […] After getting detailed information about the symptoms and your family’s medical history, your doctor may order tests to help with diagnosis and treatment planning.

• #60 Systemic mastocytosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/systemic-mastocytosis/diagnosis-treatment/drc-20450478

  To diagnose systemic mastocytosis, your doctor will likely start by reviewing your symptoms and discussing your medical history, including medications you’ve taken. He or she can then order tests that look for high levels of mast cells or the substances they release. Evaluation of organs affected by the condition also may be done. […] Tests may include: Blood or urine tests, Bone marrow biopsy, Skin biopsy, Imaging tests such as an X-ray, ultrasound, bone scan and CT scan, Biopsy of organs affected by the disease, such as the liver, Genetic testing. […] Your doctor regularly monitors the status of your condition using blood and urine samples. You may be able to use a special home kit to collect blood and urine samples while you’re experiencing symptoms, which gives your doctor a better picture of how systemic mastocytosis affects your body. Regular bone density measurements can monitor you for problems such as osteoporosis. […] After getting detailed information about the symptoms and your family’s medical history, your doctor may order tests to help with diagnosis and treatment planning.

• #61 Orphanet: Smoldering systemic mastocytosis

  https://www.orpha.net/en/disease/detail/158775

  A rare, slowly progressive form of systemic mastocytosis (SM) characterized by gradual accumulation of neoplastic mast cells in the visceral organs. Patients typically present with splenomegaly, hypercellular marrow and, in most cases, urticaria pigmentosa-like skin lesions. […] Diagnosis of SSM is achieved by first establishing a diagnosis of SM, based on the WHO consensus criteria. The disease is then categorized according to the presence of B-findings and C-findings. For SSM, at least two B-findings (but no C-findings) should be present. […] In stable SSM patients, symptomatic treatment may be the only therapy. Avoidance of known triggers, prophylactic prescription of an epi-pen, and medications such as antihistamines, antileukotrienes, cromolyn sodium, omalizumab and aspirin may all have a role in the prevention or treatment of MC-mediated symptoms. Regular follow-up and assessment for transformation to more aggressive disease variants is required. Serum tryptase, which may be used to assess disease response, may be evaluated biannually to monitor disease activity and appropriately adjust therapy. […] Some SSM patients may remain stable for years, while others may progress to more advanced variants of the disease (ASM or MCL), with a poorer prognosis.

• #62 Diagnosis and treatment of systemic mastocytosis in Brazil: Recommendations of a multidisciplinary expert panel | Hematology, Transfusion and Cell Therapy

  http://www.htct.com.br/en-diagnosis-treatment-systemic-mastocytosis-in-articulo-S2531137922000803

  Recommendation: Doppler abdominal ultrasound should be performed for all patients with Systemic Mastocytosis to evaluate hepatomegaly, portal hypertension and ascites (GRADE 3). […] Recommendation: CT scans and MRI should be used to evaluate Systemic Mastocytosis C findings. The FDG-PET/CT scans should not be part of the initial assessment of the most common forms of the disease (GRADE 3). […] Recommendation: The clinical or hybrid Mayo criteria should be used to determine prognosis (GRADE 4). […] Recommendation: The cytoreductive therapy is indicated for patients with advanced systemic mastocytosis and for patients with indolent or smouldering Systemic Mastocytosis, for whom symptom therapy fails. […] Recommendation: The allogeneic stem cell transplantation should be considered in eligible patients with advanced SM with an estimated survival of fewer than 5 years and/or patients with SM-AHN with hematological neoplasms who have an indication for allogeneic stem cell transplantation (GRADE 4).

• #63 Multidisciplinary Collaboration Is Vital for Timely, Definitive Diagnosis of Indolent Systemic Mastocytosis

  https://www.onclive.com/view/multidisciplinary-collaboration-is-vital-for-timely-definitive-diagnosis-of-indolent-systemic-mastocytosis

  Despite advancements in diagnostic testing, patients with indolent systemic mastocytosis (ISM) often experience delays in diagnosis due to the diseases heterogeneous presentation, highlighting the need for an integrative, multidisciplinary approach to improve early recognition of this condition and optimize patient care, according to Andrew Kuykendall, MD. […] In an interview with OncLive, Kuykendall expanded on the diagnostic process in ISM, discussing the importance of biopsy, KIT mutation testing, and serum tryptase levels in diagnosing ISM. […] When we think about the diagnostic criteria of systemic mastocytosis in general, one of the most critical things is [to obtain] a biopsy of an extracutaneous organ that shows these clusters of atypical mast cells. […] Importantly, that mutation can occur at very low levels. It’s important to send this test to be done in a highly sensitive fashion.

• #64 Untangling Systemic Mastocytosis: An Update on Challenges in the Diagnosis and Treatment of Myeloid Neoplasms with Systemic Mastocytosis – European Medical Journal

  https://www.emjreviews.com/hematology/symposium/untangling-systemic-mastocytosis-an-update-on-challenges-in-the-diagnosis-and-treatment-of-myeloid-neoplasms-with-systemic-mastocytosisj060122/

  This symposium was held on the first day of the 2023 European Hematology Association (EHA) Congress, held in Frankfurt, Germany. The main objective of the symposium was to gather experts from the field to raise awareness of the challenges in diagnosing and treating systemic mastocytosis (SM) with an associated haematologic neoplasm (AHN). Presentations focused on optimising the diagnosis of the SM component and recognising the different types of myeloid AHN. The expert panel considered the clinical management of SM-AHN, and how and when to prioritise the various disease components. […] The overarching message from the symposium was that diagnosis of SM-AHN is challenging, and SM is often missed in patients with a myeloid neoplasm, such as chronic myelomonocytic leukaemia (CMML), myelodysplastic/myeloproliferative neoplasm (MDS/MPN), myelodysplastic syndrome (MDS), and myeloproliferative neoplasm (MPN), as well as AHN being missed in patients with SM. Identification of a SM-AHN through serum tryptase and/or molecular testing for KIT D816V mutation in peripheral blood in a patient with a previous diagnosis of a myeloid neoplasm allows potentially efficacious targeted treatment with KIT inhibitors, such as midostaurin and avapritinib.

• #65 Multidisciplinary insights: Navigating the challenges of systemic mastocytosis diagnosis and management – touchIMMUNOLOGY

  https://touchimmunologyime.org/mdt-insights-systemic-mastocytosis/

  Multidisciplinary insights: Navigating the challenges of systemic mastocytosis diagnosis and management […] Describe the signs, symptoms and diagnostic pathway for systemic mastocytosis […] Explain how to apply personalized treatment strategies using a multidisciplinary approach to effectively manage systemic mastocytosis […] In this activity, an allergist, dermatologist and haemato-oncologist discuss the diagnosis and management of systemic mastocytosis, including current and emerging treatment options and multidisciplinary approaches to optimize patient care. […] Current ICC/WHO guidelines outline the role of B and C findings in the classification of SM subtypes. The presence of C findings support the diagnosis of ASM, while evaluation of B findings can distinguish between SSM and ISM, and help identify BMM. The presence of two or more B findings in the absence of C findings suggests a diagnosis of SSM.

• #66 Systemic mastocytosis in adults: 2023 update on diagnosis, risk stratification and management – PubMed

  https://pubmed.ncbi.nlm.nih.gov/37309222/

  Systemic mastocytosis (SM) results from clonal proliferation of mast cells (MC) in extracutaneous organs. […] The major criterion is presence of multifocal MC clusters in the bone marrow and/or extracutaneous organs. Minor diagnostic criteria include elevated serum tryptase level, MC CD25/CD2/CD30 expression, and presence of activating KIT mutations. […] Establishing SM subtype as per the International Consensus Classification/World Health Organization classification systems is an important first step.

• #67 Advanced Systemic Mastocytosis: Expert Insight into Epidemiology, Diagnosis, and Treatment

  https://www.onclive.com/view/advanced-systemic-mastocytosis-expert-insight-into-epidemiology-diagnosis-and-treatment

  However, they noted that this path can be complicated. […] Moreover, according to Wang, hematologists often cannot afford to do an [MC] workup for every GI biopsy. […] Treatment options for advanced SM are limited, which likely reflects the diagnostic challenges and lack of clinical biomarkers. […] Historically, clinicians have relied on chemotherapy and stem cell transplants to treat aggressive SM, but targeted options are available, and others are in development. […] Midostaurin is an oral multikinase inhibitor that inhibits D816V-mutated KIT. […] It is FDA approved for the treatment of patients with advanced SM. […] Avapritinib is a potent and selective KIT D816V inhibitor. […] Avapritinib therapy led to a notable reduction in BM MCs, with 88% of patients achieving a greater than 50% reduction and 60% of patients achieving elimination of marrow MC aggregates.

• #68 Multidisciplinary insights: Navigating the challenges of systemic mastocytosis diagnosis and management – touchIMMUNOLOGY

  https://touchimmunologyime.org/mdt-insights-systemic-mastocytosis/

  As a complex, multisystem disease with a varied clinical course, SM requires a multidisciplinary approach. Patients with SM may need psychological or psychiatric support to adjust to their diagnosis. […] Based on the results of the phase II PIONEER trial (NCT03731260) in patients with ISM, avapritinib is currently approved for the treatment of ISM in adults (US), and patients with moderate-to-severe symptoms inadequately controlled on symptomatic treatment (Europe). Avapritinib was superior to placebo in reducing uncontrolled symptoms and mast cell burden in patients with ISM.

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