Study hints at new directions on LAMNs

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Karen Titus

August 2014—A slow leak in a tire may not be all that interesting— until one is cruising down the highway at 75 m.p.h. Suddenly, that same leak becomes much more compelling.

Joseph Misdraji, MD, recalls a conversation he had at a meeting about pseudomyxoma peritonei that skirted a similar curve in the road. Approached by a pathologist who expressed a desire to collaborate with him, Dr. Misdraji suggested a study he was working on, looking at the significance of proximal margin involvement in low-grade appendiceal mucinous neoplasms, or LAMN.

The pathologist’s response was as unequivocal as a negative node. “I’m paraphrasing, but it was basically, ‘I’ll wait until you’re doing something more important,’” recalls Dr. Misdraji, associate pathologist, Massachusetts General Hospital, and associate professor of pathology, Harvard Medical School, Boston.

Dr. Misdraji laughs about that conversation—he harbors more curiosity than ill will about the response. Any topic can seem small “if you’re not dealing with it right now,” he says. “But one day when you are dealing with it, or it’s your appendix, then you’d like to know that there’s some data upon which to base a recommendation.”

Those who question a conservative approach are making the assumption that a positive margin leaves tumor behind and increases risk of recurrence. Data from the study published in Archives suggest otherwise. Says Dr. Misdraji, above: “Even if you think that’s a shocking approach [to be conservative], that’s what the majority treatment approach is already.”

Now, there is. That study, so easily dismissed at the meeting, was recently published in an early online release in Archives of Pathology & Laboratory Medicine (www.archivesofpathology.org/doi/abs/10.5858/arpa.2014-0246-OA).

The retrospective study is small— 16 cases—but intriguing. It is, say its authors, the first data assembled to look at the implications of a positive margin in patients with LAMN. Or, as Dr. Misdraji puts it, “How alarmist should a pathologist be?” Should pathologists urge additional surgery or therapy in such cases? Or is a more conservative approach valid?

The paper is an effort to replace perception with evidence, says lead author Thomas Arnason, MD, attending anatomical pathologist, Queen Elizabeth II Health Sciences Centre, and assistant professor of pathology, Dalhousie University, Halifax, Nova Scotia.

“I think there’s an assumption in pathology, in general, that when you have a positive margin, it mandates further resection,” with the thought that disease will recur or spread if it’s present at the margin, says Dr. Arnason.
With this paper, the authors are suggesting otherwise. “In our experience, there is no evidence that will happen,” says Dr. Arnason.

As the paper notes, appendiceal adenomas and LAMNs that are confined to the appendix are cured by appendectomy. But when patients have positive margins, they may undergo cecal resection to reduce risk (or perceived risk) of recurrence or dissemination.

And why not? When Dr. Arnason and colleagues delivered the paper as a platform presentation at the USCAP annual meeting in March, one pathologist audience member responded with some degree of astonishment. (The comments were strong enough, Dr. Misdraji says, that they were addressed in the final paper.) The consequences of the tumor recurring as pseudomyxoma peritonei were so dire, the listener said, that the authors weren’t justified in suggesting conservative treatment, especially since cecectomy is a minimal procedure.