High Grade Prostatic Intraepithelial Neoplasia (HGPIN)

High Grade Prostatic Intraepithelial Neoplasia (HGPIN):
Common questions asked about HGPIN are :
-How do we as pathologists make these diagnoses?
-What do they mean for the patient in terms of cancer risk?
-What is/are the optimal strategies for follow-up so that if cancer does eventually develop it is caught at an early, curable stage?

Pathology criteria for diagnosis of HGPIN:

-Architecturally benign acini/ducts lined by atypical cells.
-These cells show large nuclei and prominent nucleoli (cytologic features of carcinoma).
-Generally at least 10% of the luminal cells should show these features to make the diagnosis.


Diagnosis of HGPIN has been shown to be reproducible. Low grade prostatic intraepithelial neoplasia has poor reproducibility (even among experts), ill defined diagnostic criteria, and no true clinical relevance. It is for these reasons that I do not personally diagnose LGPIN.

Risk of subsequent cancer:

-In previous studies the risk of carcinoma on follow-up biopsy for a HGPIN diagnosis has been reported to be as high as 50%, however, when the data is based on series with increased case numbers, this decrease to around 25%.

-Number of cores with high grade PIN predicts risk of subsequent cancer (1 core-30%, 3 cores-40%, 4+ cores-75%).In addition, morphologic patterns of HGPIN (i.e. flat, tufted, micropapillary, cribriform) have not been shown to be predictive of subsequent carcinoma.

Follow up strategy for patients with HGPIN:

Although there have been several follow-up strategies for patients with a diagnosis of HGPIN, many recommend re-biopsy within 3-6 months. One protocol includes biopsies at 3-6 months for 2 years, followed by yearly biopsies for life.
In a recent study, recommendation was made that in the absence of other clinical indicators worrisome for cancer, men do not need a routine repeat biopsy within a year following a HGPIN diagnosis. As the natural history of HGPIN in any given patient is not known, the decision to take additional biopsies past 1 year is best made on a patient by patient basis with a frank discussion between the physician and patient.

Various studies have shown that in patients with prior diagnosis of HGPIN, cancer is often diagnosed in adjacent sites and even within the contralateral lobe. It is for this reason that when re-biopsy is performed for HGPIN sampling should be concentrated in the region of the previous HGPIN with the rest of the gland sampled so as not to miss small foci of cancer. Specimens should be meticulously labeled as to site (in addition to patient identification) and optimally no more than 2 cores should be submitted per container.

Summary:

1. HGPIN is characterized by architecturally benign glands lined by cells which are morphologically similar to prostate cancer, and is the putative precursor of prostate cancer.

2. Unlike HGPIN the diagnosis of LGPIN is not reproducible and carries no clinical significance.

3. While earlier reports described the risk of cancer following a diagnosis of HGPIN as high as 50%, more current reviews suggest that the risk may be much lower.

4. Men with a diagnosis of HGPIN (especially those with HGPIN focally) may not need re-biopsy for up to one year after initial diagnosis. Repeat biopsies should concentrate on the area of previous HGPIN, but also include sampling of the entire gland.
(Thanks to Dr.Dharam Ramnani for allowing to use the above images for this site.)
References:
1. Epstein JI, Herawi M. Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: implications for patient care. The Journal of Urology 2006; 175: 820-834.
2. Bishara T, Ramnani DM, Epstein JI. High grade prostatic intraepithelial neoplasia on needle biopsy risk of cancer on repeat biopsy related to number of involved cores and morphologic pattern. The American Journal of Surgical Pathology 2004; 28: 629-633.
3. Bostwick DG, Qian J. High-grade prostatic intraepithelial neoplasia. Modern Pathology 2004; 17: 360-379.