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"A substantial part of the core of the heart of the Old Town of Edinburgh has been destroyed," he said.
"We really only have the facades, the outside walls standing, and sadly they may have to be removed as well."
The fire is believed to have started at about 2015 GMT on Saturday 7th December above La Belle Angele nightclub, located behind the Gilded Balloon comedy venue.
It was among several properties burnt out in the area, Historic Scotland said was at the periphery of the city's World Heritage Site.
About 150 people were forced to spend two nights in temporary accommodation as firefighters continued to battle against pockets of fires burning within the complex network of business and residential properties.
Council leader Anderson said Saturday's fire was the biggest in living memory.
"We have a gaping hole in the very heart of the city, so this is a very serious blow for us," he said.
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