weekly_question 23/7/2023

[Admin]

A 3-month-old baby has a large microcystic malformation of the neck. The malformation abuts the trachea and bilateral carotid sheaths. The malformation has been enlarging at a rapid pace. Initial management of this lesion should include:

A Administration of sirolimus

B Administration of alpelisib

C Administration of trametinib

D Surgical debulking

E Drain placement and sclerotherapy

[Admin]

Correct answer
A Administration of sirolimus

Cystic lymphatic malformations occur as somatic mutations that occur within the tissue itself and are not germline (inherited) mutations.

The most common mutations in lymphatic malformations are activating mutations in cellular signaling pathways such as as the PI3K/mTOR and RAS pathway. Cystic malformations more commonly occur due to mutations in the PI3KCA pathway. Lymphatic malformations occurring along the RAS pathway are complex, can be multifocal, and result altered lymphatic transit.

Sirolimus, an mTOR (mammalian target of rapamycin) inhibitor, has proven efficacy for treatment of patients with cystic lymphatic malformations and should be used for this patient. mTOR regulates cell proliferation, autophagy and apoptosis by participation in multiple signaling pathways. Administration of sirolimus requires monitoring of serum drug levels. Sirolimus does not seem to affect postoperative wound healing. It may be used for primary therapy or as a “neoadjuvant” agent potentially to shrink a lesion before surgical therapy.

Lesions in the RAS pathway may have favorable response to trametinib, a MEK inhibitor. Lymphatic malformations in patients with PIK3CA-related overgrowth syndromes may respond to alpelisib, a direct PI3K inhibitor. Currently, a tissue biopsy is necessary to understand the genetic profile of a malformation that requires alpelisib therapy.

[Ahmed Nabil]

A Administration of sirolimus

[Admin]

Correct answer
A Administration of sirolimus

Cystic lymphatic malformations occur as somatic mutations that occur within the tissue itself and are not germline (inherited) mutations.

The most common mutations in lymphatic malformations are activating mutations in cellular signaling pathways such as as the PI3K/mTOR and RAS pathway. Cystic malformations more commonly occur due to mutations in the PI3KCA pathway. Lymphatic malformations occurring along the RAS pathway are complex, can be multifocal, and result altered lymphatic transit.

Sirolimus, an mTOR (mammalian target of rapamycin) inhibitor, has proven efficacy for treatment of patients with cystic lymphatic malformations and should be used for this patient. mTOR regulates cell proliferation, autophagy and apoptosis by participation in multiple signaling pathways. Administration of sirolimus requires monitoring of serum drug levels. Sirolimus does not seem to affect postoperative wound healing. It may be used for primary therapy or as a “neoadjuvant” agent potentially to shrink a lesion before surgical therapy.

Lesions in the RAS pathway may have favorable response to trametinib, a MEK inhibitor. Lymphatic malformations in patients with PIK3CA-related overgrowth syndromes may respond to alpelisib, a direct PI3K inhibitor. Currently, a tissue biopsy is necessary to understand the genetic profile of a malformation that requires alpelisib therapy.