Jennifer Gordetsky

Utility of PTEN and ERG immunostaining for distinguishing high-grade PIN from Intraductal Carcinoma of the Prostate on Needle Biopsy

Intraductal carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to resolve this differential diagnosis. Here, we tested whether these markers are diagnostically useful in the needle biopsy setting. Separate or combined immunostains were applied to biopsies containing morphologically identified intraductal carcinoma, PIN, or borderline intraductal proliferations more concerning than PIN but falling short of morphologic criteria for intraductal carcinoma. Intraductal carcinoma occurring with concurrent invasive tumor showed the highest rate of PTEN loss, with 76% (38/50) lacking PTEN and 58% (29/50) expressing ERG. Of biopsies containing isolated intraductal carcinoma, 61% (20/33) showed PTEN loss and 30% (10/33) expressed ERG. Of the borderline intraductal proliferations, 52% (11/21) showed PTEN loss and 27% (4/15) expressed ERG. Of the borderline cases with PTEN loss, 64% (7/11) had carcinoma in a subsequent needle biopsy specimen, compared with 50% (5/10) of PTEN-intact cases. In contrast, none of the PIN cases showed PTEN loss or ERG expression (0/19). On needle biopsy, PTEN loss is common in morphologically identified intraductal carcinoma yet is very rare in high-grade PIN. Borderline intraductal proliferations, especially those with PTEN loss, have a high rate of carcinoma on resampling. If confirmed in larger prospective studies, these results suggest that PTEN and ERG immunostaining may provide a useful ancillary assay to distinguish intraductal carcinoma from high-grade PIN in this setting.

Grading of prostatic adenocarcinoma: current state and prognostic implications

BackgroundDespite significant changes in the clinical and histologic diagnosis of prostate cancer, the Gleason grading system remains one of the most powerful prognostic predictors in prostate cancer. The correct diagnosis and grading of prostate cancer is crucial for a patient’s prognosis and therapeutic options. However, this system has undergone significant revisions and continues to have deficiencies that can potentially impact patient care.Main BodyWe describe the current state of grading prostate cancer, focusing on the current guidelines for the Gleason grading system and recent changes from the 2014 International Society of Urological Pathology Consensus Conference on Gleason Grading of Prostatic Carcinoma. We also explore the limitations of the current Gleason grading system and present a validated alternative to the Gleason score. The new grading system initially described in 2013 in a study from Johns Hopkins Hospital and then validated in a multi-institutional study, includes five distinct Grade Groups based on the modified Gleason score groups. Grade Group 1 = Gleason score ≤6, Grade Group 2 = Gleason score 3 + 4 = 7, Grade Group 3 = Gleason score 4 + 3 = 7, Grade Group 4 = Gleason score 8, Grade Group 5 = Gleason scores 9 and 10.ConclusionAs this new grading system is simpler and more accurately reflects prostate cancer biology, it is recommended by the World Health Organization (WHO) to be used in conjunction with Gleason grading.

Frozen section assessment in testicular and paratesticular lesions suspicious for malignancy: its role in preventing unnecessary orchiectomy

To investigate the role of frozen section assessment in sparing unnecessary orchiectomy for suspected lesions, we retrospectively reviewed intraoperative testicular and paratesticular frozen section assessments performed at our institution between the years 1993 and 2010. Frozen section assessments were performed on 45 testicular lesions (age, 5-60 [mean, 32.2] years; lesion size, 0.5-9.7 [mean, 2.1] cm) and 20 paratesticular lesions (age, 26-76 [mean, 43.5] years; lesion size, 0.4-11.0 [mean, 2.8] cm) before the decision to complete radical orchiectomy. Benign/malignant frozen section assessment diagnoses were reported in 26/19 testicular cases and 17/3 paratesticular cases, respectively. Of the 26 benign testicular frozen section assessments, 5 cases resulted in orchiectomy, where permanent diagnoses included epidermoid cyst, large cell calcifying Sertoli cell tumor, fibrous pseudotumor, abscesses, and sarcoidosis, caused by a concern for potential malignancy or questionable viability of the testicles. Of the 19 malignant testicular frozen section assessments, orchiectomy was performed in 16 cases with germ cell tumor, but not in the remaining 3 cases with lymphoma. Of the 17 benign paratesticular frozen section assessments, 2 cases, both fibrous pseudotumors, resulted in orchiectomy. There were statistically significant differences in the size of the testicular (P < .001) or paratesticular (P < .001) lesions between benign and malignant frozen section assessments. Thus, in 36 (83.7%) of 43 cases with benign frozen section assessments, in addition to all 3 cases of lymphoma, orchiectomy was successfully avoided. These results suggest that frozen section assessment is useful for permitting testicular preservation, especially in men with small, nonpalpable, incidentally found masses as well as other benign lesions where a clinical diagnosis of malignancy is in doubt.

Factors predicting prostate cancer upgrading on magnetic resonance imaging–targeted biopsy in an active surveillance population

The objective of this study was to create a nomogram model integrating clinical and multiparametric magnetic resonance imaging (MP‐MRI)–based variables to predict prostate cancer upgrading in a population of active surveillance (AS) patients.

Expression of semenogelins I and II and its prognostic significance in human prostate cancer

Little is known about the role of semenogelins, seminal plasma proteins that play critical roles in semen clotting and subsequent liquefaction in the presence of zinc and prostate‐specific antigen, in human malignancies.

Initial Experience Using 99mTc-MIBI SPECT/CT for the Differentiation of Oncocytoma From Renal Cell Carcinoma

Purpose The differentiation of oncocytoma from renal cell carcinoma (RCC) remains a challenge with currently available cross-sectional imaging techniques. As a result, a large number of patients harboring a benign oncocytoma undergo unnecessary surgical resection. In this study, we explored the utility of 99mTc-MIBI SPECT/CT for the differentiation of these tumors based on the hypothesis that the large number of mitochondria in oncocytomas would lead to increased 99mTc-MIBI uptake. Patients and Methods In total, 6 patients (3 with oncocytoma and 3 with RCC) were imaged with 99mTc-MIBI SPECT/CT. Relative quantification was performed by measuring tumor-to-normal renal parenchyma background ratios. Results All 3 oncocytomas demonstrated radiotracer uptake near or above the normal renal parenchymal uptake (range of uptake ratios, 0.85–1.78). In contrast, the 3 RCCs were profoundly photopenic relative to renal background (range of uptake ratios, 0.21–0.31). Conclusions 99mTc-MIBI SPECT/CT appears to be of value in scintigraphically distinguishing benign renal oncocytoma from RCC.

Identifying additional lymph nodes in radical cystectomy lymphadenectomy specimens

Lymph node count has prognostic implications in bladder cancer patients who are treated with radical cystectomy. Lymph nodes that are too small to identify grossly can easily be missed, potentially leading to missed nodal metastases and inaccurate nodal counts, resulting in inaccurate prognoses. We investigated whether there is a benefit to submitting the entire lymph node packet for histological examination to identify additional lymph nodes. We prospectively assessed 61 pelvic lymphadenectomy specimens in 14 consecutive patients undergoing radical cystectomy. The specimens were placed in Carnoys solution overnight, then analyzed for lymph nodes. The residual tissue was entirely submitted to assess for additional lymph nodes. In 61 specimens, we identified 391 lymph nodes, ranging from 4–44 nodes per patient. We identified 238 (61%) lymph nodes with standard techniques and 153 (39%) lymph nodes in submitted residual tissue. The number of additional lymph nodes found in the residual tissue ranged from 0 to 26 (0–75%) per patient. These lymph nodes ranged in size from 0.05 to 1 cm. All additional lymph nodes were negative for metastatic disease. Submitting the entire specimen for histological examination allowed for identification of more lymph nodes in radical cystectomy pelvic lymphadenectomy specimens. However, as none of the additional lymph nodes contained metastatic disease, it is unclear if there is a clinical benefit in evaluating lymph nodes that are neither visible nor palpable in lymphadenectomy specimens.

Higher Prostate Cancer Grade Groups Are Detected in Patients Undergoing Multiparametric MRI-targeted Biopsy Compared With Standard Biopsy.

Recent studies have suggested that multiparametric magnetic resonance imaging (MRI)/ultrasound (US) fusion–guided prostate biopsy can detect more clinically significant prostate cancers, which could impact patient management. As many of the studies evaluating MRI/US fusion–guided prostate biopsy were conducted in specialized quaternary care centers, the question remains whether this technology is transferable to general practice. Our study assesses the diagnostic ability of MRI/US fusion–guided prostate biopsy compared with standard biopsy in the new era of prostate cancer Grade Grouping. We reviewed our prostate biopsy database evaluating men who underwent MRI/US fusion–guided prostate biopsy with concurrent standard 12-core extended-sextant biopsy. Patient demographics and pathologic findings were reviewed. All patient biopsies were performed by 1 of 2 urologic oncologists. Tumors were given a Grade Group for each biopsy based on the core with the highest grade in each case. A total of 191 patients underwent MRI/US fusion–guided biopsy with concurrent 12-core extended sextant biopsy, with a cancer detection rate of 56%. The average number of biopsy cores obtained via the targeted approach was significantly less than those obtained by standard biopsy, 4.8 cores versus 12 cores, respectively, P<0.001. There was no difference in cancer detection between targeted and standard biopsy, 41.4% and 49.2%, respectively, P=0.15. However, when comparing the 2 techniques, the degree of detection of ≥Grade Group 3 tumors significantly favored targeted biopsy over standard biopsy (P=0.009). MRI/US fusion–guided prostate biopsy is equivalent to the standard-of-care 12-core biopsy in terms of cancer detection and superior in detecting higher grade disease.

Seminal plasma proteins in prostatic carcinoma: increased nuclear semenogelin I expression is a predictor of biochemical recurrence after radical prostatectomy

Semenogelins and eppin are seminal plasma proteins that form a complex and inhibit sperm motility. However, the role of these proteins in prostate cancer is poorly understood. We immunohistochemically stained for semenogelins I and II and eppin in 291 radical prostatectomy specimens. We then evaluated the association between their expressions in nuclei, cytoplasms, or intraluminal secretions of benign/high-grade prostatic intraepithelial neoplasia/carcinoma cells and clinicopathologic profile available for our patient cohort. Stains were positive in 32%/77%/84% (nuclear semenogelin I), 87%/94%/84% (nuclear semenogelin II), 56%/64%/37% (nuclear eppin), 7%/15%/11% (cytoplasmic semenogelin I), 6%/11%/9% (cytoplasmic semenogelin II), 68%/74%/95% (cytoplasmic eppin), 97%/98%/13% (secreted semenogelin I), 98%/97%/11% (secreted semenogelin II), and 97%/98%/48% (secreted eppin) of benign/prostatic intraepithelial neoplasia/carcinoma, respectively. The levels of nuclear semenogelin I/cytoplasmic eppin were significantly higher in carcinoma than in benign (P<.001/P<.001) or prostatic intraepithelial neoplasia (P<.001/P<.001) and in prostatic intraepithelial neoplasia than in benign (P<.001/P=.006). Significantly higher nuclear semenogelin II expression was found in prostatic intraepithelial neoplasia than in benign (P<.001) or carcinoma (P<.001). Significantly lower nuclear eppin expression was seen in carcinoma than in benign (P<.001) or prostatic intraepithelial neoplasia (P<.001). Secreted semenogelin I, secreted semenogelin II, and secreted eppin were all significantly lower in carcinoma than in benign (P<.001) or prostatic intraepithelial neoplasia (P<.001). There were no statistically significant correlations between each stain and clinicopathologic features except significantly lower nuclear eppin expression in Gleason score 8 or higher tumors. Kaplan-Meier and log-rank tests further revealed that patients with nuclear semenogelin I-positive tumor had a significantly higher risk for biochemical recurrence (P=.046). Multivariate Cox model showed a trend toward significance (P=.093) in nuclear semenogelin I positivity as an independent predictor for recurrence. These results suggest that nuclear semenogelin I expression could be a reliable prognosticator in men who undergo radical prostatectomy.

Redefining abnormal follicle-stimulating hormone in the male infertility population.

Study Type – Diagnostic (validating cohort)