Pandas docs says it uses openpyxl for xlsx files. Quick look through the code in ExcelWriter
gives a clue that something like this might work out:
import pandas
from openpyxl import load_workbook
book = load_workbook('Masterfile.xlsx')
writer = pandas.ExcelWriter('Masterfile.xlsx', engine="openpyxl")
writer.book = book
## ExcelWriter for some reason uses writer.sheets to access the sheet.
## If you leave it empty it will not know that sheet Main is already there
## and will create a new sheet.
writer.sheets = dict((ws.title, ws) for ws in book.worksheets)
data_filtered.to_excel(writer, "Main", cols=['Diff1', 'Diff2'])
writer.save()