。
What could she possibly be so sad about?
Literal
She [topic-は] what [subject-が] that-so sad [I wonder-のだろう].
Posed as a question to the air rather than to anyone in particular — そんなに ('that much') paired with sentence-final のだろう gives a self-directed wondering tone, half-asking, half-reflecting. The が on 何 (rather than は) singles out the unknown cause as the focal point: 'of all the possible things, which is the one making her so sad?' The construction is quietly observational, the speaker watching from a slight distance.