Histopathologic False-positive Diagnoses of Prostate Cancer in the Age of Immunohistochemistry

Abstract

There are few studies into the rate and causes of histopathologic false-positive diagnosis of prostate cancer. Only 2 of these, including a previous one from our group, incorporate survival data. In addition, in none of the previous studies had immunohistochemistry (IHC) been originally requested on any of the misdiagnosed cases. Diagnostic biopsies (n=1080) and transurethral resection of prostate specimens (n=314) from 1394 men with clinically localized prostate cancer diagnosed in the United Kingdom but treated conservatively between 1990 and 2003 were reviewed by a panel of 3 genitourinary pathologists. Thirty-five cases were excluded for being potentially incomplete. Of the remaining 1359, 30 (2.2%) were reassigned to a nonmalignant category (26 benign and 4 suspicious for malignancy). IHC had been originally performed on 7 of these. The reasons for the errors were recorded on each case: adenosis (19), partial atrophy (3), prostatic intraepithelial neoplasia (2), seminal vesicle epithelium (1), and hyperplasia (1). Follow-up of these men revealed only one prostate cancer-related death, possibly due to unsampled tumor. In conclusion, a relatively small number of prostate cancer mimics were responsible for a large proportion of the false-positive prostate cancer diagnoses and the use of IHC did not prevent the overcall of benign entities as cancer in approximately a quarter of these cases. Targeting these mimics at educational events and raising awareness of the pitfalls in the interpretation of IHC in prostate cancer diagnosis, emphasizing that glands within a suspicious focus should be treated as a whole rather than individually, may be beneficial in lowering the rate of false-positive diagnosis.

Figures

Figure 1

Adenosis. Core biopsy. H&E. Small tightly-packed acini with mild atypia.

Figure 2

Adenosis. Core biopsy. 34BE12 immunostain performed originally demonstrates a discontinuous basal cell layer with occasional acini lacking basal cells in this section.

Figure 3

Partial atrophy. Core biopsy. H&E. Disorganized acini of different size and shape with no significant atypia and no typical features of atrophy.

Figure 4

Partial atrophy. Core biopsy. 34BE12 immunostain performed originally demonstrates a continuous basal cell layer.

Figure 5

Adenosis. Core biopsy. H&E. Note fading staining. Dense area combining small and medium-sized acini with no significant atypia.

Figure 6

Adenosis. Core biopsy. 34BE12 immunostain performed originally. Staining has failed and appears to highlight nuclei of luminal epithelial cells whilst it is completely negative in other areas.

Figure 7

Sclerosing adenosis. TURP. H&E. Small round acini embedded in a richly cellular stroma.

Figure 8

Seminal vesicle epithelium. Core biopsy. H&E. Marked nuclear atypia and intracytoplasmic pigment.