Rethinking The Cancer Diagnosis Gold Standard

oncologyoutlookRethinking the Cancer Diagnosis Gold StandardRethinking the Cancer Diagnosis Gold StandardRethinking the Cancer Diagnosis Gold StandardBy Kevin A. Hahn, DVM, Ph.D.Histopathology is a valued commodity in obtaining a diagnosis. Like gold, it is an elegant discipline left to the visual acuity and interpretation of the pathologist.Histopathology is a valued commodity in obtaining a diagnosis. Like gold, it is an elegant discipline left to the visual acuity and interpretation of the pathologist.

Why does histopathology continue to be considered the gold standard for a diagnosis? 

While pathology's roots are closely associated with the history and progress of medicine, in particular the detection, understanding and classification of diseases, why is it still considered the gold standard despite technological advances in our understanding of the subcellular and genetic levels of the body?

What is a "gold standard"? The term comes from the monetary system of many modern countries.  Gold is considered the true value of a country's currency. If a country will redeem any of its money in gold, it is said to be using the gold standard. 

Why Gold?
Gold is one of the oldest, most scarce known metals. It is considered an elegant and metal. It has a yellow aura or beauty; hence the use of the symbol Au in the table of elements.

Gold is still a valued commodity.

So too, histopathology is a valued commodity in obtaining a diagnosis. Like gold, it is an elegant discipline left to the visual acuity and interpretation of the pathologist. But is it time to abandon our gold standard of histopathology?

In cancer medicine we commonly refer to clinical staging an approach to define the extent of the cancer and to predict prognosis. Yet it is the histopathological appearance of the tumor (grade, mitotic index) that becomes our gold standard in developing a plan and predicting patient prognosis.

But consider that when we submit a biopsy for histopathological evaluation, less than 0.01 percent of the sample is actually viewed by the pathologist. The pathologist stakes her/his career on the diagnostic interpretation of this sample. 

Our clients place their trust in us as we, too, interpret the pathological description of the sample.

Cancer Overlooked
When a pathologist examines a histologic specimen, the reliable limit of detection is <1 cancer cell per 200 observed cells.
 
This means that true cancer cells are often overlooked because they do not exhibit the gold standard criteria of malignancy, such as nuclear or cytoplasmic pleomorphism, increased or abnormal appearing nucleoli, variable nuclear to cytoplasmic ratios, mitotic figures or other morphologic features.

Are there other methods available to us with greater confidence or accuracy? Should we abandon the gold standard of histopathology for another disciplinary science?

I tell most of my clients that we can arrive at an appropriate diagnosis of their pet's condition by means of clinical laboratory, imaging or pathology results. 

While there is a urine test that is suggestive for a diagnosis of bladder cancer in dogs, while an elevated amended insulin-to-glucose ratio is suggestive for a diagnosis of insulinoma, while an elevated periosteum with a sunburst osteoid production pattern on survey images is suggestive of osteosarcoma, time and again we refer to biopsy specimens and histologic examination as the diagnostic gold standard.

A New Standard?
If we are to find an alternative to the gold standard of histopathology, our first task is to find a feasible test. 

A CT scan may be quite useful in providing information about the nervous system, but may not be practical for most clients. A brain biopsy is an accurate test for diagnosing a primary cerebral tumor, but not necessarily practical either.

Our second task is to be sure the alternative test is likely to give us the correct answer it should be used in the proper population. Fungal serology in a dog with pulmonary masses is far more appropriate when performed in the proper geographic region of the country. 

From the sequencing of the canine genome come a multitude of new tests (microarrays, in situ tissue immunoflourescent antibody binding, PCR, flow cytometry) with increased sensitivity and specificity for obtaining a diagnosis. We can create genetic profiles from tiny skin biopsies. 

With the numerous advances in immunology and molecular biology over the past five to 10 years, why do we still consider histopathology the gold standard in diagnostic medicine? 

Because seeing is believing.

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Kevin A. Hahn, DVM, Ph.D., Dipl. ACVIM (Oncology), is director of Oncology Services at Gulf Coast Veterinary Specialists, Houston (www.gcvs.com/oncology) and is the oncology consultant for YourNetVet (www.yournetvet.com).

06-20-2007