[size=20px]An asymptomatic 2 month old boy presents with a moderate sized left cervical mass. There was poor prenatal care and no prenatal diagnosis. MRI of the neck shows a mixed-cystic lymphatic malformation which was judged not amenable to sclerotherapy. Recent studies have shown benefit with adjuvant administration of which of the following?

 

A Prednisone

 

B Rapamycin

 

C Tacrolimus

 

D Methotrexate

 

E Cyclophosphamide​[/size]

C

C

C

correct answer

B Rapamycin

 

Management of complex lymphatic malformations can be challenging. Previous approaches have included multimodal approaches including sclerotherapy and excision. More diffuse lesions are often associated with significant morbidity in the process of achieving local control. Recent studies have shown the mTOR inhibitors such as sirolimus may be beneficial secondary to their anti-lymphangiogenic property. Early phase studies have shown an efficacious result with good patient tolerance.

 

A review of the mechanisms of actions of different immunosuppressants are as follows:

 

- Glucocorticoids: Inhibition of intracellular NF-κB leading to multiple inflammatory and immune mediators are inhibited.

 

- Tacrolimus (also FK-506 or fujimycin): Binding to FK506 binding protein (FKBP) and inhibition of calcineurin leading to inhibition of NFAT activation and decreased IL-2 transcription resulting in decreased activation of T cells

 

- Sirolimus (rapamycin): Binds to FKBP leading to inhibition of mTOR kinase and subsequent inhibition of the IL-2-mediated cell cycle which prevents response to IL-2 and blocks T-cell activation and B-cell differentiation leading to decreased IgM, IgG, and IgA production

 

- Azathioprine (mercaptopurine): Purine analog (antimetabolite precursor of 6-mercaptopurine ) which blocks nucleotide synthesis and inhibits proliferation of lymphocytes

 

- Mycophenolate mofetil: Inhibition of inosine monophosphate dehydrogenase which leads to selective inhibition of lymphocyte proliferation

Methotrexate: Folic acid antagonist (antimetabolite): inhibition of dihydrofolate reductase (DHFR) which decreases pyrimidine and purine nucleotide synthesis leading to decreased DNA synthesis

 

- Cyclophosphamide: Alkylating agent: alkylation of DNA/RNA → cross-linking and strand breaks → impaired DNA synthesis​

Edited January 31, 20233 yr by Admin

B. Sirolimus