Cribriform prostate cancer: an aggressive pattern where definition and size matter

Recognition of cribriform growth pattern in prostate cancer is important for prognostic stratification and clinical decision making for many prostate cancer patients. However, as pathologists, we recognize that cribriform prostate cancer can take on many forms, and that not all morphologic variations that could potentially be considered as cribriform confer the same high–risk profile. Furthermore, a number of recent studies have shown that large cribriform glands is a more aggressive pattern and should be distinguished from small cribriform glands, though use of multiple different definitions to define size has made how to apply this distinction less clear. Here, we review the multiple patterns of cribriform architecture that one can encounter in prostate cancer and recent consensus definitions proposed for the diagnosis of cribriform prostate cancer. We highlight patterns of cribriform growth that have been shown to behave more aggressively, with a focus on size. Finally, we provide some practical considerations for reporting.     

Clinical utility of pathology data: prostate and kidney cancer

Cancer pathology reports can be complex due to multiple data elements, variability in terminology, and increasing recognition of emerging diagnostic entities. However, treatment may be significantly influenced by histologic subtype, histologic grade, and pathologic tumor stage. We review the clinical utility of pathology data for prostate and kidney cancers, with emphasis on main decision-making points. Key parameters that affect management of prostate cancer in the biopsy setting include Grade Group, percentage of pattern 4, and sometimes extent of involvement. Histologic subtypes mostly do not affect management, with exceptions of small cell carcinoma and sometimes cribriform/intraductal carcinoma. For renal cancer, histologic subtype, tumor grade, and tumor stage are important for prognostication. Confirming a diagnosis of renal cell carcinoma and recognition of clear cell, non-clear cell, and select other histologies are important in the metastatic setting for treatment selection.     

Incidence of intraductal carcinoma,multifocality and bilateral significant disease in radical prostatectomy specimens from Japan and United States

Significant differences, including epidemiologic, clinical, pathologic and genetic, exist between Asian and Caucasian prostate cancer. Detailed pathologic data are, however, scarce. We studied in detail and compared the pathological features of prostate cancer in radical prostatectomy specimens in 228 patients (117 Japan, 111 US). Japanese prostate cancer had a higher Gleason grade group (mean 2.67 vs. 2.42 US, P < 0.05), but lower pathological stage (72 % pT2 and 28 % pT3 vs 55 % pT2 and 45 % pT3 US, P < 0.05). Japanese cancer showed significantly more tumor foci (3.8 vs 2.9 US, P < 0.05), and higher incidence of bilateral significant disease (81.3 % vs. 66.7 % US, P < 0.05). The dominant tumor nodules in Japanese cases had higher Gleason grade group (mean 2.73 vs. 2.40 US, P < 0.05). The incidence of intraductal carcinoma was significantly higher in Japanese patients (35.3 % vs. 12.6 % US, P < 0.01), which was independent of Gleason score (7: 30.9 % Japan vs 11.8 % US, P < 0.01; ≥ 8: 87.5 % Japan vs 28.6 % US, P < 0.01) and tumor stage (pT2: 24.1 % Japan vs 6.6 % US, P < 0.01; pT3: 62.9 % Japan vs 20 % US, P < 0.01). These findings demonstrate distinct pathological features in prostate cancer between Japanese and Caucasian patients, and may have important diagnostic and therapeutic implications.     

Association of intraductal carcinoma of the prostate detected by initial histological specimen and neuroendocrine prostate cancer: A report of three cases

We present three cases of neuroendocrine prostate cancer (NEPC) and histologically investigate the association of intraductal carcinoma of the prostate (IDC-P) and NEPC. Case 1 was a 76-year-old man who had NEPC identified by repeated biopsy specimens when his prostate-specific antigen (PSA) level became elevated 8 years after the initiation of androgen deprivation therapy (ADT). Case 2 was a 70-year-old man who had NEPC detected when multiple bone metastases were found 3 years after the initiation of ADT. Case 3 was a 70-year-old man who was diagnosed with NEPC based on histological examination of transurethral resected specimens. The histological findings in these three cases showed mixed neuroendocrine carcinoma–acinar adenocarcinoma with various proportions of both components. In all three cases, the neuroendocrine carcinoma components were positive for synaptophysin and chromogranin A, whereas the adenocarcinoma components were positive for PSA and NKX3.1. When we retrospectively reviewed the initial hematoxylin and eosin-stained slides, IDC-P was detected in all three cases. Furthermore, we collected nine additional cases of NEPC and found that all six cases with initial biopsy specimens available had an IDC-P component. Detecting IDC-P on initial histological specimens of the prostate may predict transformation to NEPC.     

Perineural invasion on biopsy is associated with upstaging at radical prostatectomy in Gleason score 3 + 4 = 7 prostate cancer

This study assesses if perineural invasion (PNI) detected on biopsy with Gleason score (GS) 3 + 4 = 7 prostate cancer (PCa) is associated with upstaging/upgrading of disease after radical prostatectomy (RP). 154 patients with GS 3 + 4 = 7 PCa diagnosed from biopsy who underwent RP were assessed for PNI. The percentage of biopsy sites with PNI (%PNI) was also calculated. Pattern 4 morphologies (ill‐defined glands [IDG], fused, cribriform, and glomerulations) were also assessed. Clinical information, GS and stage after RP were retrieved from the medical records. 45 % (69/154) of patients were upstaged (≥pT3) and 29 % (44/154) were upgraded to GS >3 + 4 = 7 after RP. 37 % (57/154) of patients had PNI which was associated with upstaging (RR 1.4; P = 0.04) but not upgrading (RR 0.9; P = 0.7). There was higher %PNI in upstaged patients (12.1 % ± 1.8 vs. 7.1 % ± 1.5, P = 0.03) with a significant correlation between %PNI and ≥pT3 (r = 0.178, P = 0.027). After multivariate analysis, only cribriform formations were significantly associated with upstaging (P = 0.009). The presence of PNI in biopsies with GS 3 + 4 = 7 PCa is associated with upstaging at RP but is a weaker predictor of ≥pT3 disease than cribriform morphology.     

CtBP2 overexpression is associated with tumorigenesis and poor clinical outcome of prostate cancer

Introduction

The aim of the study was to evaluate the expression of CtBP2 in prostate cancer and to determine its relationship with clinicopathologic parameters.

Material and methods

The expression of CtBP2 in 119 prostate cancer tissues and 41 normal tissues was examined by qPCR and Western blot analysis, and the results were correlated with clinicopathologic parameters.

Results

CtBP2 expression in prostate cancer tissues was higher than that in normal samples. CtBP2 overexpression was closely correlated with serum prostatic specific antigen (PSA) (p = 0.018), advanced tumor stage (T3) (p = 0.025), higher Gleason scores (p = 0.019), positive extraprostatic extension (p = 0.012), positive vascular invasion (p = 0.011) and perineural invasion (p = 0.035). However, no significant association was found between CtBP2 abnormal expression and other parameters, including age (p = 0.776), positive lymph node (p = 0.872) and positive surgical margin (p = 0.37). Moreover, CtBP2 overexpression was significantly associated with poor clinical outcome of prostate cancer (p = 0.0168).

Conclusions

CtBP2 is overexpressed in prostate cancer, and its increased expression is closely associated with tumor progression and the outcome of prostate cancer.     

Quantification of extraprostatic extension in prostate cancer: different parameters correlated to biochemical recurrence after radical prostatectomy

AIMS: Different methods to substage extraprostatic extension (EPE) were correlated with biochemical recurrence (BCR) after radical prostatectomy (RP). Methods and results: A total of 157 consecutive RP specimens with EPE were completely embedded. Twenty-three patients with adjuvant therapy or detectable postoperative PSA levels were excluded, leaving 134 patients for BCR analysis. Data were analysed using Kaplan-Meier survival and Cox regression analyses. In univariate analysis, maximal radial distance (RD) was associated with BCR as continuous (P = 0.006) and dichotomous (P = 0.002) parameters. In multivariate analysis, independent predictors of BCR were preoperative prostate-specific antigen (PSA) (P = 0.006), Gleason score (P = 0.001), positive surgical margins (P = 0.005), maximal RD dichotomized at 0.6 mm [= one high-power field (HPF)]; hazard ratio (HR) 3.4; 95% confidence interval (CI) 1.48-7.85; P = 0.004), total RD (P = 0.009) and EPE quantification according to Epstein (P = 0.002) and to Wheeler (P = 0.004). The 5-year risk of BCR was 20% (95% CI 0.65-0.94) in patients with RD ≤ 0.6 mm and 47% (95% CI: 0.41-0.65) with RD > 0.6 mm. The restriction of focal EPE in no more than two slides (Epstein and Wheeler) gave no better results. CONCLUSIONS: Maximal RD dichotomized at one HPF is an objective method to subdivide EPE and a strong, independent predictor for BCR after RP. Its use is recommended for substaging pT3a in future TNM classifications.     

Formation of intracellular lumina in human prostate carcinoma (DU145) cells,maturation into signet cells,and the cribriform morphology of tumors

The intracellular or intracytoplasmic lumen (IL) is an enigmatic histological structure that occurs in various tumor cells. A reassessment of diverse ILs fine-structure micrographs obtained out of previous studies encompassing the human prostate carcinoma (DU145) cell line and xenotransplanted carcinomas enabled us to propose aspects of ILs development in cancer cells: a combination of altered expressions in intercellular contacts and their cytoskeletal components would favor a disarray of self-apical polarity orientation; those defects, associated with a local, entwined enriched membranous structures growing as microvilli-like formations out of a disrupted endoplasm and trans-Golgi sorting, create ILs in cells’ perikarya. These misplaced intracytoplasmic domains can become enlarged through spaces made between the finger-like structures by accruing membranes of coalescent intracytoplasmic vesicles then adding microvilli and glycocalyx to constitute ILs. Cationic mucins added with or without a progressive or total loss of microvilli and content generate signet or ring cell, while ILs enlarge. Variable build-ups of these cells’ populations in carcinomas result in architectural mix-up of adjacent cells around these voids, misconstrued as new lumen, and establish a “cribriform” tumor pattern that often implies a poor cancer prognosis. Alternatively, cytotoxic changes caused by anticancer pro-oxidant treatment favor membrane alterations and exaggerate the ILs in xenotransplants into intracellular crypts that accompany other tumor degenerative changes.