mysql uses too much memory
(adding a second answer -- to address the VARIABLES and STATUS)

Observations:

Version: 5.6.24
52 GB of RAM
Uptime = 21d 02:26:20
You are not running on Windows.
Running 64-bit version
You appear to be running entirely (or mostly) InnoDB.


The More Important Issues


table_open_cache = 200K, yet 156 tables opened per second, and all are misses/overflows from the cache.  You must redesign you schema to have a civilized number of tables.
Are there really 403 ROLLBACKs per second?  If so, think about how to avoid some of them.  That's probably more than 10% of the transactions.
innodb_lock_wait_timeout = 300 -- Assuming you really need transactions to hang around waiting for 5 minutes, this could be consuming RAM.
tmp_table_size = 8M, together with 51 tmp tables created per second, may be leading to quite a few GB of transient MEMORY tables.  Look through the slowlog to find which queries need tmp tables and see if they can be rewritten.
Decrease long_query_time to 2 (now 10), turn on the slowlog, wait a day, run pt-query-digest.  Then study the worst few queries -- improving them will speed up the entire system and probably decrease RAM usage.


Details and other observations

( Innodb_buffer_pool_reads ) = 329,533,959 / 1823180 = 180 /sec -- InnoDB buffer_pool I/O read rate
-- check innodb_buffer_pool_size

( Innodb_buffer_pool_pages_flushed ) = 589,768,119 / 1823180 = 323 /sec -- Writes (flushes)
-- check innodb_buffer_pool_size

( innodb_buffer_pool_size / _ram ) = 16,106,127,360 / 53248M = 28.8% -- % of RAM used for InnoDB buffer_pool

( Opened_tables ) = 285,544,112 / 1823180 = 156 /sec -- Frequency of opening Tables
-- increase table_open_cache

( table_open_cache ) = 200,000 -- Number of table descriptors to cache
-- Several hundred is usually good.

( Table_open_cache_overflows ) = 285,343,673 / 1823180 = 156 /sec
-- May need to increase table_open_cache

( Table_open_cache_misses ) = 285,544,112 / 1823180 = 156 /sec
-- May need to increase table_open_cache

( (Innodb_buffer_pool_reads + Innodb_buffer_pool_pages_flushed) ) = ((329533959 + 589768119) ) / 1823180 = 504 /sec -- InnoDB I/O
-- Increase innodb_buffer_pool_size?

( innodb_log_buffer_size ) = 128M -- Suggest 2MB-64MB, and at least as big as biggest blob set in transactions.
-- Adjust innodb_log_buffer_size.

( Innodb_log_writes ) = 167,769,519 / 1823180 = 92 /sec

( Innodb_os_log_written / (Uptime / 3600) / innodb_log_files_in_group / innodb_log_file_size ) = 332,945,398,784 / (1823180 / 3600) / 2 / 100M = 3.13 -- Ratio

( Uptime / 60 * innodb_log_file_size / Innodb_os_log_written ) = 1,823,180 / 60 * 100M / 332945398784 = 9.57 -- Minutes between InnoDB log rotations Beginning with 5.6.8, this can be changed dynamically; be sure to also change my.cnf.
-- (The recommendation of 60 minutes between rotations is somewhat arbitrary.) Adjust innodb_log_file_size.

( Com_rollback ) = 735,486,482 / 1823180 = 403 /sec -- ROLLBACKs in InnoDB.
-- An excessive frequency of rollbacks may indicate inefficient app logic.

( innodb_lock_wait_timeout ) = 300 -- Two battling InnoDB transactions, but not a deadlock -- one will wait this long (seconds) in hopes of getting the desired locks.
-- Fix the cause of timeouts rather than increasing this value.

( Innodb_dblwr_writes ) = 14,574,293 / 1823180 = 8 /sec -- "Doublewrite buffer" writes to disk. "Doublewrites" are a reliability feature. Some newer versions / configurations don't need them.
-- (Symptom of other issues)

( local_infile ) = ON
-- local_infile = ON is a potential security issue

( Questions ) = 7,836,091,851 / 1823180 = 4298 /sec -- Queries (outside SP) -- "qps"
-- >2000 may be stressing server

( Queries ) = 8,262,090,685 / 1823180 = 4531 /sec -- Queries (including inside SP)
-- >3000 may be stressing server

( Created_tmp_tables ) = 92,537,439 / 1823180 = 51 /sec -- Frequency of creating "temp" tables as part of complex SELECTs.

( Created_tmp_disk_tables ) = 6,158,440 / 1823180 = 3.4 /sec -- Frequency of creating disk "temp" tables as part of complex SELECTs
-- increase tmp_table_size and max_heap_table_size.
Check the rules for temp tables being able to use MEMORY instead of MyISAM. It may be possible to make a minor schema or query change to avoid MyISAM.
Better indexes and reformulation of queries can

( Handler_read_rnd_next ) = 266,467,437,770 / 1823180 = 146155 /sec -- High if lots of table scans
-- possibly inadequate keys

( Com_rollback / Com_commit ) = 735,486,482 / 741864016 = 99.1% -- Rollback : Commit ratio
-- Rollbacks are costly; change app logic

( Com_show_variables ) = 6,666,028 / 1823180 = 3.7 /sec -- SHOW VARIABLES ...
-- Why are you requesting the VARIABLES so often?

( Select_scan ) = 315,076,005 / 1823180 = 172 /sec -- full table scans
-- Add indexes / optimize queries (unless they are tiny tables)

( Select_scan / Com_select ) = 315,076,005 / 3888296954 = 8.1% -- % of selects doing full table scan. (May be fooled by Stored Routines.)
-- Add indexes / optimize queries

( Com_insert + Com_delete + Com_delete_multi + Com_replace + Com_update + Com_update_multi ) = (613230844 + 1238003 + 0 + 30479625 + 71282659 + 0) / 1823180 = 392 /sec -- writes/sec
-- 50 writes/sec + log flushes will probably max out I/O write capacity of normal drives

( ( Com_stmt_prepare - Com_stmt_close ) / ( Com_stmt_prepare + Com_stmt_close ) ) = ( 23 - 22 ) / ( 23 + 22 ) = 2.2% -- Are you closing your prepared statements?
-- Add Closes.

( slow_query_log ) = OFF -- Whether to log slow queries. (5.1.12)

( long_query_time ) = 10.000000 = 10 -- Cutoff (Seconds) for defining a "slow" query.
-- Suggest 2

( Com_change_db ) = 31,947,189 / 1823180 = 18 /sec -- Probably comes from USE statements.
-- Consider connecting with DB, using db.tbl syntax, eliminating spurious USE statements, etc.

( max_connect_errors ) = 10,000 -- A small protection against hackers.
-- Perhaps no more than 200.

( Connections ) = 21,121,749 / 1823180 = 12 /sec -- Connections
-- Increase wait_timeout; use pooling?

( Threads_running - 1 ) = 22 - 1 = 21 -- Active threads (concurrency when data collected)
-- Optimize queries and/or schema

You have the Query Cache half-off. You should set both query_cache_type = OFF and query_cache_size = 0 . There is (according to a rumor) a 'bug' in the QC code that leaves some code on unless you turn off both of those settings.

39 issues flagged, out of 125 computed Variables/Status/Expressions. Settings not mentioned are mostly OK.