Disclosures: The authors report no relevant financial disclosures.
June 26, 2020
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Pulmonary abnormalities, lung cysts seen in children, young adults with MEN2B

Disclosures: The authors report no relevant financial disclosures.
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More than half of a cohort of children and young adults with multiple endocrine neoplasia type 2B had restrictive and obstructive lung abnormalities and 94% showed some degree of diminished lung function, NIH study data showed.

“This study evaluated lung function and anatomy in patients with MEN2B using pulmonary function tests and available CT images,” Jaydira Del Rivero, MD, an assistant research physician in medical oncology and endocrinology and director of the Center for Cancer Research Rare Tumor Clinic at the National Cancer Institute of the NIH, told Healio.

statistics among young adults with MEN2b

“Restrictive pulmonary function test abnormalities were observed in 57% of patients, and obstructive pulmonary function test abnormalities were observed in 39% of patients. Moreover, diffusion abnormalities were observed in 94% of the patients, with 63% having moderate to severe defects. [Although] we can tentatively rule out some potential underlying etiologies for these abnormalities in pulmonary function, a singular mechanism is not apparent.”

In the retrospective study, Del Rivero and colleagues analyzed pulmonary function tests and CT chest imaging of 36 children and young adults (mean age, 17.6 years; range, 5-35; 50% female) enrolled in the Natural History Study of Children and Adults with MEN2A or MEN2B at the NIH between June 2009 and May 2019. All participants had MEN2B confirmed by genetic analysis of the RET proto-oncogene, all had the M918T genotype and nine had a history of pheochromocytoma. Pulmonary function tests included forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), lung volume, total lung capacity and carbon monoxide diffusion capacity. Researchers classified abnormalities as restrictive (normal FEV1/FVC and low total lung capacity), obstructive (low FEV1/FVC and normal total lung capacity) or mixed (low FEV1/FVC and reduced total lung capacity).

Jaydira Del Rivero

Researchers observed diffusion abnormalities in 33 of 35 evaluable participants (94%), with 22 participants (63%) having moderate to severe defects. Researchers also observed a declining trend in diffusion capacity over time, with an estimated slope of –2.9% per year (P = .0001). Restrictive and obstructive abnormalities were observed in 57% and 39% of patients, respectively.

In assessing CT imaging, researchers observed lung cysts in nine of 32 evaluable participants (28%) and metastatic lung disease in 11 participants (34%). Those with metastatic lung lesions also tended to have thin-walled cavities (P = .035).

Marfanoid body type, tyrosine kinase inhibitor (TKI) exposure and cancer burden were identified as independently associated with diminished lung function in prior studies, the researchers wrote. In this cohort, researchers noted that body type and spine curvature appeared to correlate with pulmonary function tests; however, TKI exposure and cancer burden had a “questionable correlation” with lung diffusion and no correlation with restrictive or obstructive findings.

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“Our findings have potential implications on routine monitoring and pre-TKI treatment evaluation of patients with MEN2B,” Del Rivero said. “Based on this information, it appears reasonable to obtain pulmonary function tests prior to initiating TKI therapy due to the previously reported potential negative impact on pulmonary function. Future study of the pulmonary changes in this cohort should include more functional assessments, such as walk tests, sitting and supine spirometry and respiratory muscle strength testing.”

Del Rivero said the study was not designed to determine the cause of diffusion capacity degeneration over time and further investigation is needed.

“It is possible that there is an unidentified molecular mechanism arising from a germline RET mutation,” Del Rivero said. “RET is an important gene for the normal development of the kidney, enteric nervous system development and spermiogenesis, with less clear implications in lung development ... It is possible that an aberration in this pathway is causing a subclinical yet atypical innervation pattern in the lung. However, further studies are warranted to explore the mechanism of pulmonary abnormalities seen in these patients.”

For more information:

Jaydira Del Rivero, MD, can be reached at the CCR Rare Tumor Clinic, Developmental Therapeutics Branch, National Cancer Institute/NIH, 10 Center Drive, MSC 1906, Building 10, CRC 13C-434, Bethesda, MD 20892; email: jaydira.delrivero@nih.gov; Twitter: @JaydiDelRivero.