Rita Wilson’s recent announcement of her experience with an early breast lesion emphasizes both the importance, and the limitations, of the pathologist in the evaluation of a breast biopsy. As laypeople, we assume that a pathologist can look at a piece of tissue and easily tell whether it is cancer or not. The truth is that there is some art as well as science in diagnosis. To evaluate a biopsy, the tissue that is removed is cut up into small pieces and fixed in formalin to preserve it. It is then dehydrated and fixed in paraffin so that it can be sliced into slivers in a machine similar to the one used to slice ham. Each sliver is put on a glass slide, the paraffin is melted, and the slide is stained so that the pathologist can look at it under the microscope. Through the microscope, the pathologist then looks at cells of different types and tries to discern the presence or absence of cancer cells. This is determined by how the cells look and whether they are where they should be according to the structure of healthy breast tissue. For example, the breast has lobules that have the capacity to make both milk and ducts, which are there to carry the milk to the nipple. The pathologist is seeking to identify whether the ductal cells are presence only in the milk duct or invading into the surrounding tissue. This process of identifying potentially malignant cells by their presence in environments where they do not belong is not unlike the profession of psychiatry, in that the psychiatrist is tasked with determining whether a person is clearly psychotic, merely neurotic, or just a little odd by evaluating whether their behavior is appropriate to the setting. For example, a person singing and dancing on a table at a party may be acting somewhat inappropriately, but is probably not psychotic. That same person singing and dancing on a table in the library may need therapy. Determining whether the person’s presence and behavior is appropriate to the setting is key to determining whether they should be diagnosed as mentally ill or not. Often the answer depends on who is doing the evaluation. With this background, let’s examine what LCIS and PLCIS actually represent. LCIS is lobular carcinoma in situ, which is commonly understood as abnormal-looking cells contained within a lobule. We know from long-term studies that this finding can indicate a higher risk for breast cancer in either breast of about 1 percent per year, maxing out at a 30 percent lifetime risk. The current options for treating LCIS are watchful waiting with close monitoring, hormonal drugs for prevention (tamoxifen), or bilateral prophylactic mastectomies. More recently, pathologists have noted that some LCIS is more “funny-looking” than average, and this is termed pleomorphic lobular carcinoma in situ (PLCIS), with pleomorphic meaning “different shapes.” Although we don’t yet have long-term follow up on many women with this situation, there is a suggestion that PLCIS may be more likely to become cancerous than the usual kind of LCIS. According to the media report of Ms. Wilson’s announcement, she was diagnosed with LCIS some time ago and was appropriately monitored. She then developed a lesion, which was biopsied and at first reported as LCIS. A second opinion reported PLCIS. On this basis, Ms. Wilson underwent bilateral mastectomies where they found area that indeed showed these abnormal appearing cells outside of a lobule, which was therefore termed invasive. The takeaway message from Ms. Wilson’s situation is this: Individuals read pathology slides. And the diagnosis is often in the eye of the beholder. We encourage second opinions about treatment, but most people don’t realize that when they ask for a second opinion on the diagnosis, the opinion should be based on examination of the actual biopsy slides, not simply the original pathology report. Some cases are clear-cut but if there is any question, the more eyes looking at the tissue, the more accurate the diagnosis, and the more confident a woman can feel in the decisions she makes. Too often, celebrities who publicly share their health stories leave out key information, which in turn can cause confusion and sometimes stimulate people to take action that may not be necessary or advised. We applaud Ms. Wilson’s willingness to include the details of her specific situation so that other women can better understand the rationale that drove her personal treatment decision.

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We combat the disparities that exist in research by challenging the scientific community to launch studies that are as inclusive and diverse as the people that breast cancer affects.

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