How do you approach a young patient with metastatic poorly differentiated thyroid cancer with rhabdoid/non-anaplastic features?

Unfortunately, this patient has a very poor prognosis. Due to the nature of her tumor being poorly differentiated, her disease is more likely than not to be refractory to radioiodine. If her disease in the thyroid and neck has not been addressed, external beam radiation therapy should be offered for symptomatic control. Likewise, local areas such as painful boney lesions can also be addressed focally with EBRT. Lenvatinib is the systemic treatment of choice and should be started at a dosage of 2...

Unfortunately, this is an aggressive tumor that will not respond to RAI. While details of the case are not known (extent of disease, prior treatment such as thyroidectomy etc...), I would treat this as anaplastic, with NGS testing ASAP and target-specific treatment if appropriate. If no specific actionable targets are noted, I would initiate treatment with lenvatinib as detailed by Dr. @Dr. First Last. If there are clinical trials nearby for anaplastic thyroid, this patient may qualify. Addition...

Locally advanced thyroid cancer, multimodality treatment

Poorly differentiated thyroid cancer occupies a middle ground between differentiated thyroid cancers and the very terrible anaplastic thyroid cancer.

If your patient was able to have a total thyroidectomy, I would not completely rule out I-131 therapy as it seems your patient requires an all-hands-on-deck approach. Is it less likely to work than in differentiated cancers? Yes, but at the very least, consider a proper diagnostic I-131 scan before dismissing.