The most common and most likely answer to this crossword clue is the 6 plus 10 letter word ENIGMA VARIATIONS
I've seen this crossword clue in The Sunday Telegraph
E
N
I
G
M
A
V
A
R
I
A
T
I
O
N
S
More clues leading to the result ENIGMA VARIATIONS
Buddy explains!
The straight part
We know that ": Pieces by 21 Down, such as 4 — and 22?" is the straight/definition part of the clue. The straight part is often a synonym or definition, in this case : pieces by 21 down, such as 4 — and 22? = enigma variations.The cryptic/wordplay part
In cryptic crossword there's often an wordplay/cryptic part as well.This part involves a more complex hint, such as an anagram, homophone, hidden word, etc.
Sadly, We don't have an explanation for this specific crossword clue yet.