COMMENTARY

Two Truths and a Lie About Pathology

Benjamin Mazer, MD, MBA

Disclosures

October 08, 2019

Pathologists are sometimes referred to as "the doctor's doctor," but I've noticed that our "patients,"—oncologists, surgeons, and other physicians—often don't make appointments with us.

It turns out I'm not alone. A study recently published in the Journal of General Internal Medicine surveyed internal medicine residents and attending physicians about how often they collaborated with pathologists. For both outpatient and inpatient care, the majority of respondents rarely or never communicated with pathologists.

Because most patients receive care either directly (through a tissue biopsy diagnosis) or indirectly (through oversight of clinical labs and blood banks) from a pathologist, this lack of communication is disheartening and dangerous.

Poor collaboration between pathologists and clinicians means both small misunderstandings and large misconceptions, and as pathologists diagnose nearly all cancers, the stakes couldn't be higher.

In the hope of encouraging more collaboration, here are some misunderstood "truths" about pathology I've heard from my clinical colleagues, and one very common "lie."

There are no "malignant cells."

This "truth" may surprise any oncologist who's read a pathology report announcing a specimen "positive for malignant cells": Cancer can't be diagnosed from cells alone. Pathologists also draw on epidemiology, historical observation, and expert judgment to make the call. Surgical pathologist Juan Rosai, MD, spoke for many of us when he declared that "the division of tumors into benign and malignant is inadequate to express the almost infinite variety that exists in human neoplasia."

Even expert oncologists can get confused by this. A recent editorial published in JAMA Oncology discussing the controversy of low-grade thyroid tumors ignored this subtlety, stating that "[a] cancer is a cancer, whether it is called a nodule, mass, tumor, neoplasm, or cancer. If there are malignant cells in the specimen, it is a cancer." Since malignancy and cancer are synonyms, telling us malignant cells are cancer is meaningless.

A cancer, it happens, is not always a cancer. In the field of thyroid tumors, one common type of thyroid cancer has recently been downgraded by removing cancer (carcinoma) from its name. In breast pathology, "lobular carcinoma in situ" is now confusingly staged as benign despite retaining the "carcinoma" name. What was cancer yesterday is not cancer today.

Disagreements may mean the difference between active surveillance and aggressive treatment.

These changes are a response to the epidemic of cancer overdiagnosis occurring in thyroid, breast, prostate, melanoma, and other cancers. There is a misconception even among physicians that overdiagnosis means misdiagnosis, but that couldn't be further from the truth. If a dozen pathologists all agree that a tumor's diagnosis is "papillary thyroid microcarcinoma," for example, it's still likely that the tumor is being overdiagnosed: this common, indolent "cancer" was never destined to harm the patient.

When we rigidly label tumors as either benign or malignant, we only exacerbate this problem, as cancers exhibit a wide spectrum of aggressiveness. Our profession's long-standing fear of undertreating anything called "cancer" has hampered our ability to develop a similar spectrum of interventions. Pathologists and oncologists can better work together by ensuring that patients explicitly understand the risks any given tumor poses to their health and, eventually, by developing multiple evidence-based surveillance or treatment options that allow patients to tailor treatment to their individual view of these risks.

The best laboratory test is a second opinion.

Although some tumors can be definitively diagnosed, others cause diagnostic uncertainty. When a pathologist makes a cancer diagnosis, he or she relies on both technical skill and clinical judgment. Some malignant features are subtle and hard to spot, whereas others are simply ambiguous. Miniscule cancers that have metastasized to a lymph node or spread single-file through a stomach, for example, can sometimes appear in a lone microscopic field or mimic benign changes. This game of pathologic "Where's Waldo?" gets easier as a pathologist gains more experience.

Subspecialists who see the same tumors over and over again may have more developed technical expertise, just as a surgeon who has performed many surgeries likely operates with more finesse. Some rare tumors may only come across a general pathologist's desk once in a career, and whether or not the pathologist has seen it before can be the deciding factor in a correct diagnosis. The New York Times Magazine even recently published a story about a subspecialty National Institutes of Health pathologist confirming a rare lymphoma diagnosis after other conscientious pathologists came up short. Even common cancers undergo revisions to their grading and staging, and subspecialists may be more familiar with these ever-changing nuances.

Pathologists can be stereotyped by other physicians as introverted and antisocial.

In contrast, many pathologic diagnoses lack decisive criteria, so pathologists may give different weight to the same observations, and no one is wrong. This issue was brought into focus recently when a study published in the BMJ showed that even expert pathologists often disagreed about whether a skin tumor represented a benign mole or a malignant melanoma: two seemingly opposite diagnoses. As there isn't yet a single microscopic finding that clinches a melanoma diagnosis, expert opinions differ. The same dilemmas also affect the grading of prostate cancer. Expert pathologists can disagree about whether a tumor is Gleason grade 3 or grade 4, which may mean the difference between active surveillance and aggressive treatment.

Figure. One cancer, two diagnoses: Even experts were split on this prostate cancer. Is this crowded and tangentially sectioned Gleason grade 3, meaning the patient can safely avoid treatment, or the poorly formed glands of an aggressive grade 4, which may result in surgery or radiation?

Oncologists can sometimes be eager to try out the latest, technologically advanced testing methods when the underlying pathologic diagnosis is debatable, and a change in diagnosis will influence patient care more than anything else. Another study of melanocytic lesions, for example, showed that a second pathologist opinion changed the diagnosis in a way that would alter treatment about 15% of the time.

A second opinion is easy to get—slides and tissue blocks can be mailed to different pathology practices—and some institutions now require an in-house pathologist to review an outside diagnosis before treatment is started. Second opinions can avert both diagnostic error and alert treating physicians to any ambiguity in the interpretation. Some oncologists or surgeons may be reluctant to cast doubt about a life-altering diagnosis, but a second opinion from a pathologist should be viewed, similar to any other expert consultation, as a chance for fresh eyes to examine a case and for a patient's care team to gain another valuable member.

And a lie: Pathologists can't help you talk to patients.

Pathologists can be stereotyped by other physicians as introverted and antisocial. This has not been my experience, as I've witnessed most communicate with ease. The increasing use of multidisciplinary "tumor boards" is one way that oncologists and surgeons are seeing firsthand the ability of pathologists to relay diagnostic insight, particularly when we take on an essential role in these meetings.

Although the majority of our communication is to physicians and laboratory staff, patients are increasingly seeking us out, now that they have easier access to medical records and online information. Some pathologists have even responded by setting up consultation programs for patients. Similar to other pathologists, I know of scared patients who were reluctant to undergo aggressive treatment until they were able to see their cancer firsthand under the microscope with a pathologist. Trust was built quickly in these intimate interactions.

I also know of inconsequential diagnostic comments within pathology reports that burdened patients with silent worry until they were explained away by a pathologist.

Most of our diagnoses, however, continue to be communicated by oncologists and surgeons. These physicians can struggle to describe our findings accurately. I have seen instances in which clinicians were falsely reassured by a pathologist's circumspect language; for example, interpreting the statement that the pathologist "cannot rule out an underlying invasive cancer" as empty boilerplate rather than a conscious warning that they are concerned by this possibility. Patients in these cases may have dangerously missed out on a follow-up biopsy.

Pathologists, for their part, work to write reports for many audiences at once: oncologists, surgeons, other pathologists, patients, and even researchers. This creates feedback loops of miscommunication, in which sometimes no one is speaking directly to each other and errors remain uncorrected.

Even in my short time in training, I have known surgeons quietly confused by a pathologist's jargon, unsure of whether the patient needs an operation or can avoid one. I don't know if it is pride, lack of time, or a false belief that pathologists cannot effectively communicate, but these types of questions should be asked openly and formally, rather than whispered in hallways among trainees.

Miscommunication in healthcare can be dire, and it's a particular shame when a simple phone call or face-to-face meeting with a pathologist could have prevented it. More active engagement with pathologists at tumor boards is one easy way to increase pathologist-oncologist communication, but clinicians should also consider working with pathologists to set up pathology report review sessions for interested patients. As patients become more invested in the details of these complex documents, pathologists may be best equipped to explain many of their idiosyncrasies.

Despite being the "doctor's doctor," pathologists' work is often mysterious to other physicians. Whether it comes to the true nature of malignancy or the judgment inherent in our diagnoses, there are a number of silently held assumptions about pathology. Only by openly discussing these assumptions can we replace them with reality.

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