thepathologist

"Focused on the Prostate since 1996"

The Pathologist's Role in the Processing and Interpretation of Your Biopsy Specimen

By Jonathan R. Oppenheimer, M.D., F.C.A.P.

From the patient's (and most urologists') perspective the pathologist and his lab is somewhat of a black box - in goes the specimen and out comes a diagnosis. In this article I will reveal some of the inner workings of this mysterious box and hopefully show how understanding your pathology reports may assist you in the diagnosis, prognosis, and treatment of prostate cancer.

What happens to the prostate samples your Urologist removes?

Immediately after obtaining the needle biopsy, the urologist places each of the tissue core samples into a small vial containing a liquid (usually 10% formalin) which acts as a "pickling" solution." The specimen is then sent to a laboratory directed by a pathologist, the physician who is the physician responsible for analyzing and diagnosing tissue specimens (blood, biopsies, prostates) that are sent to the lab by your urologist or surgeon.

After further chemical processing the fixed tissue is embedded in paraffin cubes or "blocks" which are then cut with a very sharp knife to create translucently thin sections which are stained with colored dyes and placed on glass slides for viewing under the microscope. Occasionally it is necessary to confirm or rule-out carcinoma (cancer) by applying special immunoperoxidase stains which look for a specific protein ( CK-903 or low molecular weight cytokeratin) which is present surrounding benign, but not malignant glands. If not obtained at first, these special studies may be performed on material that is still in the paraffin blocks. The laboratory must legally keep these blocks in storage for up to seven years.

Additional tests such as ploidy analysis (which measures the chromosomal content of malignant cells) and microvessel density (which is associated or afterwards from tissue remaining in the saved paraffin blocks. Ploidy analysis on prostatectomy specimens has been shown to be an important prognostic factor in predicting the spread of tumor outside the prostate and thus the chance of recurrence after surgery.

Making the Diagnosis (What goes on in your Pathologist's Head)

Fortunately, there are objective criteria which pathologists use to make the diagnosis of cancer, but these are most easily applied on the largest and most easily diagnosable lesions. Because most pathologists now practicing were trained before the current popularity of thin needle-core biopsies, many have never had formal training in the interpretation of such specimens, accounting for considerable variation in their ability to diagnose small lesions. Fortunately (for themselves as well as their patients) a pathologist learns to be conservative in his diagnoses. There is nothing more embarrassing (or costly to the pathologist) than making a diagnosis of cancer only to find that the subsequently removed prostate is free of disease. It is for this reason that a pathologist may undercall a lesion, choosing to words like "atypical," "suspicious," and "can't rule out", when he lacks the confidence to be definitive. A repeat biopsy may well provide the evidence necessary to make an unequivocal diagnosis, but may have been avoided if the original biopsy had been reviewed by someone with more experience. Caution is indeed the better part of valor and even the most expert of prostate pathologists must occasionally offer less than definitive diagnoses.

The same psychology that may lead a pathologist to hesitate in making a diagnosis of cancer may be responsible for the problem of undercalling the Gleason score when a definitive positive (cancer) diagnosis is made on a very small lesion. It has been my experience that most "2+2=4" biopsies sent to Johns Hopkins Hospital for evaluation are actually 3+3=6 biopsies that have been undergraded by a general pathologist. This phenomenon decreases the predictive value of such prognostic aids as Partin and Narayan Tables to predict pathologic stage based on pre-operative information (typically Gleason score, Clinical stage, and PSA level).

Another reason for sub-optimal diagnosis is the oversight of a microscopic focus of carcinoma which may represent the tip of the proverbial iceberg. Fortunately, the incidence of the misinterpretation of a benign entity as malignant is beginning to wane as such cases are getting wider publicity in pathologic circles. A much more common occurance is the failure to identify poor prognostic factors in malignant cases (factors such as extensive intravascular, extraprostatic, or perineural tumor involvement) leading to unnecessary radical surgery.