Pediatric Case Challenge: An 8-Year-Old Boy With Autism, Lupus, Fever, and Chest Pain

Agnes Reschke, MD; Liora Schultz, MD; Catherine Aftandilian, MD; Norman Lacayo, MD


May 03, 2023

Due to limited information about CMMRD, CMMRD-related tumors continue to be treated primarily based on the location and type of cancer. However, these tumors may not respond to traditional treatment strategies.

A functional DNA MMR system is often required for chemotherapeutic agents to exert damage, and a defect in this system makes these cells resistant to some chemotherapeutic agents.[6] For example, MMR-deficient cells have been found to be resistant to alkylating agents such as temozolomide, which is the standard of treatment for most patients with glioblastoma multiforme.[7] In addition, temozolomide has been shown to increase the accumulation of somatic mutations in patients, which increases their risk for secondary tumors; thus, it should be avoided in patients with CMMRD.[6]

The ultra-hypermutated phenotype of CMMRD-derived tumors does offer different opportunities for treatment. As a result of the high neoantigen load, these tumors are likely to respond to immune checkpoint blockers, such as PD1-blockers.[6,7] Unfortunately for the patient in this case, the presence of an underlying autoimmune disorder, SLE, is a contraindication for the use of checkpoint blockade due to concerns about increased toxicity.

Given the difficulty in treating a patient with a CMMRD tumor, particularly in the presence of an autoimmune disorder, the development and implementation of a preventive treatment is crucial. Although surveillance guidelines are available, they do not guarantee the detection of a precancerous lesion or cancer at a curable stage, particularly because the development of cancer often precedes the diagnosis of CMMRD.

Aspirin has been shown to be protective in colorectal cancer in adults with Lynch syndrome, which led to the hypothesis that it may be helpful in children with CMMRD. Different mechanisms for the protective effects of aspirin have been proposed, but all are hypothetical.[8] In these observational studies evaluating the protective capabilities of aspirin in adults, the protective effect had a delay of about 10 years. This is challenging, considering the average age of onset of the first tumor in children with CMMRD is in the first decade of life. Sufficient data to recommend the use of aspirin in children with CMMRD are lacking. Therefore, a risk-benefit analysis should be performed on individual patients. In this patient, due to his history of bilateral pulmonary emboli and the need to continue to receive prophylactic enoxaparin sodium, aspirin was not indicated.

Given his treatment with steroids for SLE, the patient was classified as high risk and started to receive treatment as per Children's Oncology Group protocol AALL1231. His course was complicated by the development of massive bilateral pulmonary emboli, which were likely caused by a combination of the mediastinal mass causing vascular compression, increased risk for a hypercoagulable state secondary to underlying SLE, and the administration of pegylated-asparaginase as part of his chemotherapy treatment.

This case highlights a few fundamental concepts in medicine. Cancer should be on the differential diagnosis of any patient with a protracted illness, particularly if the patient is not responding to traditional therapies. It also reinforces the need for physicians to look beyond their individual specialties to evaluate the whole patient and rely on the expertise of colleagues to help arrive at an underlying diagnosis. With the discovery of this patient's CMMRD, surveillance strategies have been implemented to allow for the early diagnoses of additional cancers, and family members have been appropriately tested. 


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