L'Osservatore Romano, the Vatican newspaper, said: "The moment [that was] chosen reveals an attempt to raise a cloud of dust in order to manipulate."
Walter Kasper, a liberal cardinal closely in step with the Pope's views, said: "Certain people, both inside and outside the Church, are nervous about the outcome of the Synod."
The tumour story was an attempt to "upset" the final days of deliberation at the gathering, he said.
Italian newspapers speculated about "the shadow of a plot". "Who wants the Pope dead?" read the headline of Il Giornale, a conservative daily, which said the Church was "in chaos".
Massimo Franco, a leading Vatican expert, said that whoever had leaked the tumour story was aiming to undermine the "legitimacy" of the Pope.
"This nasty story seems to have been concocted by the enemies of Jorge Mario Bergoglio [as the Pope was known before his election in 2013] to let him know that he is in their sights," he wrote in Corriere della Sera.
The underlying aim may have been to cast doubt on the Pope's mental acuity, insinuating that his actions and statements were a result of "his brain not functioning properly", Franco suggested. It remained unclear who exactly was behind the alleged plot.
Vatican observers said they believed that if it really was engineered by insiders, it may have been the work of conservatives at the Synod.
In its story, Quotidiano Nazionale claimed that the Pope had been secretly visited at the Vatican by a Japanese surgeon who had found a benign, treatable, brain tumour.
The Holy See issued three increasingly exasperated denials of the story and the named brain cancer specialist, Dr Takanori Fukushima, said he had never medically examined the Pope.
The Rev Federico Lombardi, the chief Vatican spokesman, said: "As all can see, the Pope continues to exercise his intense activity without interruption and in an absolutely normal way."
Quotidiano Nazionale stood by its story. Editor Andrea Cangini said his journalists had worked for months to double-check the information and make sure their sources were reliable.
Catholic hierarchy slug it out over agenda for radical reform
At one point during a major summit of the Roman Catholic hierarchy that ends this weekend, a senior conservative bishop took the floor inside the Vatican's assembly hall and promptly charged his liberal peers with doing the devil's work.
The three-week gathering, known as a synod, has erupted into a theological slugfest over Pope Francis' vision for a more inclusive church, displaying the most bitter and public infighting since the heady days of Catholic reform in the 1960s.
Archbishop Tomash Peta of Kazakhstan captured the intensity of the divide, raising eyebrows - and even a few incredulous laughs - as he decried some of the policy changes being floated at the synod as having the scent of "infernal smoke".
It was just another day at a synod that - more than any single event since Francis began his papacy in 2013 - has highlighted the extent his outreach to once-scorned Catholics has triggered a tug-of-war for the soul of the Catholic Church. More important, it underscored just how hard it may be for Francis to recast the church he serves in his image.
In fact, the pushback by traditionalists has been so strong at the synod that the chances of fast changes on hot-button family issues - including whether to offer communion to divorced and remarried Catholics and more welcoming language to homosexuals - have substantially dimmed, if not gone completely out.
As the synod races towards a close, there has been a last-ditch push to find common ground that could at least open the door to policy alterations. But some observers are already comparing Pope Francis to United States President Barack Obama, whose reformist agenda was bogged down by a conservative Congress.
"Francis has the same problem that Obama had," said the Rev Thomas Reese, a senior analyst for the National Catholic Reporter. "He promised the world, but Congress wouldn't let him deliver. If nothing much comes of this synod, I think people will give the Pope a pass and blame the bishops for stopping change."
For Francis, the synod - the Vatican's second in 12 months on issues related to the family - sets up perhaps the most important decision of his papacy.
The 270 senior church officials from 122 countries are set to finish voting on a final document by tomorrow. Francis has the final say, holding the power to simply accept the synod's recommendations, go beyond them, or withhold judgment to encourage further debate.
All of those avenues, however, carry a measure of risk.
Using his powers to go beyond the synod's recommendations could rouse the wrath of conservatives, some of whom are already openly questioning the trajectory of his papacy. Yet if the final recommendation of the synod falls short of liberal hopes, simply rubber-stamping it, or encouraging more debate, could generate disappointment among Francis's fans worldwide. They may begin to see him as a revolutionary in gestures and words, but not on substance.
If he agrees fully with the synod's recommendations, "there might be a collapse of his popularity in world public opinion, but there might also be an increase of his popularity among Catholics", said Massimo Franco, author of The Crisis of the Vatican Empire and a columnist at the Italian daily Corriere della Sera.
Earlier this month, before this week's story claiming Francis has a brain tumour, another leak in the Italian press brought to light a letter to the Pope signed by 13 conservative cardinals that seemed to question the pope's handling of the synod process.
Adding to the mystery, some of the 13 denied they had signed the letter. Some Vatican watchers saw Francis' recent warning to the synod not to be taken in by conspiracy theories as a thinly veiled reference to the missive. To some senior Vatican officials, the letter appears close to open sedition.
"The widespread opinion I perceived among the fathers has been a sense of disgust," Bishop Marcello Semeraro, one of the senior clerics who will draft the final synod document, told the Vatican Insider website.
Yet by telling bishops that nothing is off the table for discussion, Francis has undoubtedly lifted the lid on what can be examined - including his management style.
Conservatives bishops, however, see him as having also opened a Pandora's box, allowing a free flow of ideas that have startled some traditionalists and provoked a sharp backlash.