Nested code like that is nasty to write correctly, nasty to validate and nasty to maintain. Maybe you can achieve what you want as a two pass thing. Set a bunch of boolean variables to start:

my $isA = $sender eq "sender A";
my $isSpam = $subject =~ /\[SPAM\]/;
my $hasSig = $body =~ /^--/;
...
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then handle interesting cases as a second stage:

if ($isA && $isSpam && $hasSig) {
    blowRaspberry($sender);
} elsif ($isA && !$isSpam) {
    sendThankyou();
} ...
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which makes new cases much easier to deal with and existing code easy to write and understand.