Systemic Mastocytosis (SM)

Systemic mastocytosis (SM) is a condition in which mast cells proliferate uncontrollably and accumulate in 1 or more extracutaneous organs. The most typically implicated extracutaneous location is the bone marrow, and bone marrow aspiration and biopsy are frequently used to confirm the diagnosis. Patients with SM have a wide range of clinical outcomes and prognoses, varying from indolent to aggressive. In more than 90% of SM cases, gain-of-function D816V point mutations in KIT have been found.¹

Gastrointestinal Comorbidities

Gastrointestinal (GI) manifestations are identified in 60% to 80% of SM cases. They are one of the leading causes of disease morbidity. GI symptoms are mostly induced by mediator release, and mast cells can infiltrate the intestines and cause malabsorption in advanced disease states. The most typically reported GI clinical characteristics are diarrhea and bloating, followed by nausea and abdominal pain. Vomiting is observed in 10% of cases. Patients with SM are more likely to develop peptic ulcers, probably due to increased histamine levels causing acid hypersecretion in the stomach.² 

Hepatomegaly and Splenomegaly 

SM disease comorbidities are associated with organ infiltration and the release of mediators. All forms of systemic disease have shown involvement of the liver and spleen. In a case series of 26 patients, 45% had hepatomegaly and 50% had splenomegaly. An increased serum alkaline phosphatase level is the most frequent liver abnormality and has been linked to hepatomegaly; however, transaminases can also be raised. Portal hypertension and ascites, which are caused by the infiltration of mast cells and fibrosis, are the most significant complications of liver involvement in SM.³ 

Splenomegaly is more frequently noted in cases of aggressive SM. Extramedullary hematopoiesis is also possible. Mast cell infiltration can either be diffuse involving the sinuses and cords of the red pulp or focal in areas of the white pulp.³ 

Comorbidities Related to Mast Cell Degranulation

Extensive release of mediators from mast cells can cause life-threatening anaphylactic reactions. Flushing, hypotension, tachycardia, loss of consciousness, and abdominal cramps are all manifestations.⁴ 

Hematologic Associations 

For the diagnosis of SM with an associated hematological neoplasm (SM-AHN), fulfillment of standard criteria for SM and criteria for an ASN, including myelodysplastic syndrome, myeloproliferative neoplasm, acute myeloid leukemia, lymphoma, or another hematological neoplasm, is required. Chronic myelomonocytic leukemia is the most common hematological malignancy associated with SM.⁵ The most common hematological disorders linked with SM-AHN are myeloproliferative and myelodysplastic syndromes.⁴ Nonmalignant hematologic abnormalities can be found in all subtypes of SM. The most common abnormality is anemia, which affects 30% to 50% of patients. Thrombocytopenia and leukopenia are seen in 20% to 30% of cases, while leukocytosis is seen in approximately 25% of cases. About 15% of patients develop monocytosis, but lymphocytosis and thrombocytosis are uncommon. Eosinophilia can occur in up to 40% of patients with SM.³ 

Bone Comorbidities 

Mast cell infiltration of the bone marrow can cause radiographically identifiable lesions in up to 70% of cases, as well as related abnormalities on bone scans. Diffuse osteopenia is the most prevalent radiographic finding. There have also been reports of lytic and sclerotic lesions. Back pain caused by osteoporosis and vertebral compression fractures could be a symptom of SM. Radiographic abnormalities such as osteopenic, lytic, or sclerotic changes may be found, even in asymptomatic patients. Multifocal abnormalities can be seen on bone scans, as well as diffuse increased uptake.³ 

Lung Comorbidities 

Pulmonary involvement is unusual, occurring in only around 20% of patients with SM. Cough, dyspnea, and asthma-like symptoms are all possible signs. Interstitial fibrosis and pulmonary nodules can be seen on chest radiography. Nodular and reticular opacities, as well as mediastinal lymph node enlargement, may be found on computed tomography.⁶ 

Lymphadenopathy 

Lymphadenopathy has been seen in as many as 60% of patients with SM. Mast cell infiltration can cause central or peripheral adenopathy. Infiltrates can be focal or diffuse, causing partial or complete loss of lymph nodes’ normal architecture, as well as eosinophilia, fibrosis, and even extramedullary hematopoiesis.³

References

1. Wang SA, Hutchinson L, Tang G, et al. Systemic mastocytosis with associated clonal hematological non-mast cell lineage disease: clinical significance and comparison of chomosomal abnormalities in SM and AHNMD components. Am J Hematol. 2013;88(3):219-224. doi:10.1002/ajh.23380
2. Zanelli M, Pizzi M, Sanguedolce F, et al. Gastrointestinal manifestations in systemic mastocytosis: the need of a multidisciplinary approach. Cancers (Basel). 2021;13(13):3316. doi:10.3390/cancers13133316
3. Robyn J, Metcalfe DD. Systemic mastocytosis. Adv Immunol. 2006;89:169-243. doi:10.1016/S0065-2776(05)89005-4
4. Systemic mastocytosis.​​ National Organization for Rare Disorders (NORD). Accessed April 25, 2022. 
5. Mai B, Wahed MA, Chen L, Nguyen ND, Wang XI, Hu Z. Educational case: systemic mastocytosis with an associated hematological neoplasm. Acad Pathol. 2020;7:2374289520906526. doi:10.1177/2374289520906526
6. Pillai R, Maehara D, Chitkara N. Systemic mastocytosis with pulmonary involvement. Chest. 2016;150(4):1136A. doi:10.1016/j.chest.2016.08.1246

Reviewed by Kyle Habet, MD, on 4/21/2022.

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Harshi Dhingra, MD

Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.