The Value of Pathology Review in Cancer Diagnosis

By Anthony M Magliocco MD

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Pathologists are amongst the most misunderstood of medical specialists.  They are perhaps one of the most important members of the cancer care team, especially now in the age of precision oncology.

Pathologists are MDs who have gone on to undergo focused and specialized training in a 4 yr residency in pathology in either anatomic or clinical pathology.  Anatomic pathology is the study of tissues and includes the subspecialties of surgical pathology, cytopathology, and autopsy pathology. Clinical pathology covers blood based testing and microbiology.

Some pathologists go on to further super subspecialize in focused areas such as cancer, or research. When a surgeon or radiologist removes a tissue specimen from a lesion it is sent to the pathologist for review. This involves examining the specimen carefully and selecting regions for further microscopic examination.  This process involves “fixing” the specimen in formalin, removing the water from it, and embedding it in paraffin. Then thin slices are made to put the tissue on a glass slide for staining and further evaluation by the pathologist. The pathologist may also use advanced diagnostic methods such as immunohistochemistry or molecular analysis to further characterize the tissue.

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Image of high grade breast cancer with mitotic figures

Essentially, pathologists are often the first physicians to make a diagnosis of cancer in a patient and pathologists then perform the key further anlaysis to enable an oncologist to select the right treatment for a patient.

Taking breast cancer as an example, a pathologists role is to make the diagnosis of breast cancer, describe what histological type of cancer it might be- ie ductal or lobular. The pathologist must also evaluate the “grade” of the specimen which gives information of how biologically aggressive it might be, and whether the surgical margins and regional lymph nodes contain metastatic disease. This examination is critical to determine if further surgery is necessary or if other therapy such as endocrine therapy chemotherapy or a targeted therapy such as Trastuzumab.

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breast cancer with HER2 amplification a feature for selecting Trastuzumab

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As the treatments for breast cancer grow, and our knowledge increases we now know that breast cancer is a complicated disease with many subtypes and important features that help guide therapy. Consequently, the demands on pathologists are increasing this also means that non- specialist pathologists may have challenges keeping up with new advances in specialty areas of testing and treatment.

Consequently large cancer centers generally have a policy for all pathology to be reviewed by an expert cancer center subspecialist or team of subspecialists prior to selecting and initiating treatment.

This pathology review frequently adds new information to a case, or actually changes the diagnosis resulting in a change to the treatment plan. In some cases as many as 20% of community pathology diagnoses are changed or amended by central subspecialist pathologist review.

Consequently, a second opinion from a pathologist can be very valuable for a patient and their oncologist to ensure that the treatment course is the most appropriate for the condition.

Having the correct diagnosis and the complete biomarker profile of a cancer is essential to ensure that the most effective therapy is being used and the best chance for a good outcome is achieved.

 

 

 

 

 

 

TRIPLE NEGATIVE BREAST CANCER IS OVER DIAGNOSED

By Dr. Anthony Magliocco

Getting a second opinion for a cancer diagnosis is highly recommended, but even more so if you face triple negative breast cancer, which can be aggressive and difficult to treat.

A new study led by Moffitt Cancer Center pathologist Dr. Marilin Rosa shows that triple negative breast cancer may be frequently overdiagnosed and reclassified after expert review and biomarker retesting. Moffitt investigators presented the data at the 2018 United States & Canadian Academy of Pathology Annual Meeting in Vancouver.

Researchers reviewed over 560 cases of breast cancer referred to Moffitt and found that 113 were initially classified as triple negative by external evaluation. After biomarker retesting, about 28 percent of the triple negative cases were reclassified as hormone receptor positive.

Moffitt’s study demonstrates the value of biomarker retesting for triple negative breast cancers before selecting an appropriate treatment plan. A second opinion that changes your diagnosis can have a huge impact on survival.

In triple negative breast cancer, the three most common types of receptors known to fuel most breast cancer growth — estrogen, progesterone and the HER-2 gene — are not present. This makes common treatments such as hormone therapy and drugs that target the three missing receptors ineffective.

Up to 20 percent of breast cancer diagnoses are triple negative and are more likely to affect younger patients, blacks, Hispanics and those with a BRCA1 gene mutation. This disease is also more likely to spread and recur.

The takeaway: Having an accurate cancer diagnosis is critical to planning appropriate treatment. If you are diagnosed with triple negative breast cancer, consider getting a second opinion before starting a treatment plan.