PHP MYSQL importa CSV e depois compara e remove entradas redundantes

Basta manter uma conta de suas chaves.

Salve cada $key em uma matriz no seu while e, no final, execute uma consulta que diz

DELETE FROM tabel WHERE key NOT IN (listofcommaseparatedkeysgoeshere)

$arrayThatYouNeedToTest = array();
$handle = fopen($file,"r");
fgetcsv($handle, 1000, ",");//skip first row since they are headers
while(($fileop = fgetcsv($handle, 1000, ",")) !== false) //read line by line into $fileop
{
  //read array values into vars
  $item1 = $fileop[0];
  $item2 = $fileop[1];
  $key = $fileop[2];
  // and a couple more

  // now INSERT / UPDATE data in MySQL table
  $sql = mysql_query("INSERT INTO table (item1,item2,key) 
    VALUES ('$item1','$item2','$key') 
    ON DUPLICATE KEY UPDATE item1='$item1',item2='$item2'");

   $arrayThatYouNeedToTest[] = $key;    

}

$stringThatYouNeedToInspect = implode(",",$arrayThatYouNeedToTest);
$queryYouREALLYneedToCheckFirst = "DELETE FROM tabel WHERE key NOT IN  (".$stringThatYouNeedToInspect.")";

//$result = mysql_query($queryYouREALLYneedToCheckFirst);