Neoadjuvant hormonal therapy for low-risk prostate cancer induces biochemical recurrence after radical prostatectomy via increased lymphangiogenesis-related parameters

Background: The effects of neoadjuvant hormonal therapy (NHT) on pathological features and lymphangiogenesis in patients with prostate cancer (PCa) for each pre-operative risk classification are unclear. Methods: To clarify the anti-cancer effects of NHT, we investigated 153 patients (non-NHT group?=?80 and NHT group?=?73) who underwent radical prostatectomy (RP) in Nagasaki University Hospital. Lymph vessel density and area (evaluated by D2-40-positive vessels), vascular endothelial growth factor (VEGF)-C and VEGF-D expressions, and biochemical recurrence (BCR)-free survival were compared between these two groups for each D\u27Amico risk classification (low?=?33, intermediate?=?58, high?=?62 patients). Results: In low-risk PCa patients, the risks of lymph vessel invasion and BCR were significantly higher in the NHT group than in the non-NHT group (P?=?0.040 and 0.022, respectively). Such significant difference was not seen in the intermediate- or high-risk PCa groups. Lymph vessel density of the peri-tumoral and intra-tumoral areas and the lymph vessel area were significantly higher (P?<?0.001) in the NHT group than in the non-NHT group in low-risk PCa. In regard to the expression of VEGF-C or VEGF-D, significant difference was not detected in low-risk PCa. Conclusions: NHT stimulated cancer cell progression and BCR via up-regulation of lymphangiogenesis-related parameters in patients with low-risk PCa. Although VEGF-C and VEGF-D expressions were not changed by NHT, lymph vessel density and area were increased in low-risk PCa patients. We suggest that NHT for patients with low-risk PCa may have a high risk for BCR after RP

Ciliated muconodular papillary tumors of the lung with KRAS/BRAF/AKT1 mutation

Background: Ciliated muconodular papillary tumors (CMPTs) are newly recognized rare peripheral lung nodules that are histologically characterized by ciliated columnar, goblet, and basal cells. Although recent studies have shown that CMPTs constitute a neoplastic disease, the complete histogenesis of CMPTs is not fully understood and molecular data are limited. Methods: We reviewed four cases of CMPT and performed immunohistochemical and genomic analyses to establish CMPT profiles. Results: All cases were positive for hepatocyte nuclear factor-4α and mucin 5B and negative for programmed death ligand 1 expression, as determined by immunohistochemistry. The genetic analysis revealed three pathogenic mutations (BRAF V600E, AKT1 E17K, and KRAS G12D), with the KRAS mutation reported here for the first time. Conclusion: Histological and genetic profiles indicate that CMPTs are likely neoplastic and exhibit features similar to mucinous adenocarcinoma. This suggests that some CMPTs may be a precursor lesion of mucinous adenocarcinoma

Classic Chromophobe Renal Cell Carcinoma Incur a Larger Number of Chromosomal Losses Than Seen in the Eosinophilic Subtype

Chromophobe renal cell carcinoma (chRCC) is a renal tumor subtype with a good prognosis, characterized by multiple chromosomal copy number variations (CNV). The World Health Organization (WHO) chRCC classification guidelines define a classic and an eosinophilic variant. Large cells with reticular cytoplasm and prominent cell membranes (pale cells) are characteristic for classic chRCC. Classic and eosinophilic variants were defined in 42 Swiss chRCCs, 119 Japanese chRCCs and in whole-slide digital images of 66 chRCCs from the Cancer Genome Atlas (TCGA) kidney chromophobe (KICH) dataset. 32 of 42 (76.2%) Swiss chRCCs, 90 of 119 (75.6%) Japanese chRCCs and 53 of 66 (80.3%) TCGA-KICH were classic chRCCs. There was no survival difference between eosinophilic and classic chRCC in all three cohorts. To identify a genotype/phenotype correlation, we performed a genome-wide CNV analysis using Affymetrix OncoScan$^{®}$ CNV Assay (Affymetrix/Thermo Fisher Scientific, Waltham, MA, USA) in 33 Swiss chRCCs. TCGA-KICH subtypes were compared with TCGA CNV data. In the combined Swiss and TCGA-KICH cohorts, losses of chromosome 1, 2, 6, 10, 13, and 17 were significantly more frequent in classic chRCC (p < 0.05, each), suggesting that classic chRCC are characterized by higher chromosomal instability. This molecular difference justifies the definition of two chRCC variants. Absence of pale cells could be used as main histological criterion to define the eosinophilic variant of chRCC

Increased aPKC Expression Correlates with Prostatic Adenocarcinoma Gleason Score and Tumor Stage in the Japanese Population

Background. Levels of the protein kinase aPKC have been previously correlated with prostate cancer prognosis in a British cohort. However, prostate cancer incidence and progression rates, as well as genetic changes in this disease, show strong ethnic variance, particularly in Asian populations. Objective. The aim of this study was to validate association of aPKC expression with prostatic adenocarcinoma stages in a Japanese cohort. Methods. Tissue microarrays consisting of 142 malignant prostate cancer cases and 21 benign prostate tissues were subject to immunohistological staining for aPKC. aPKC staining intensity was scored by three independent pathologists and categorized as absent (0), dim (1+), intermediate (2+), and bright (3+). aPKC staining intensities were correlated with Gleason score and tumor stage. Results. Increased aPKC staining was observed in malignant prostate cancer, in comparison to benign tissue. Additionally, aPKC staining levels correlated with Gleason score and tumor stage. Our results extend the association of aPKC with prostate cancer to a Japanese population and establish the suitability of aPKC as a universal prostate cancer biomarker that performs consistently across ethnicities

Sarcoidosis of the prostate

A 55‐year‐old African‐American man with clinical stage T1c prostate cancer underwent prostatectomy. Non‐caseating, epithelioid granulomata adjacent to the anterior fibromuscular stroma were found incidentally. The granulomata included Langhans giant cells with rare conchoidal bodies. The distribution of the granulomata was not that of non‐specific granulomatous prostatitis centred around ducts and glands. By immunohistochemistry, the epithelioid cells were positive for angiotensin‐converting enzyme. The histological appearance suggested sarcoidosis, which was confirmed by the clinical history. Four years earlier, the patient had been treated for sarcoidosis

Common benign mimics of prostate cancer

A challenge in the diagnosis of prostate pathology is the numerous benign mimics of prostatic adenocarcinoma. Most of these lesions have no clinical significance but may be misinterpreted as cancer in biopsy specimens. In this review we describe the features of some of the more common benign mimics and discuss how they can be distinguished from carcinoma. The diagnostic entities most commonly associated with a false positive diagnosis of cancer are the atrophic group of lesions that include simple atrophy, partial atrophy and post-atrophic hyperplasia. Benign proliferations exhibit architectural atypia, often with closely packed small glands, but with no or little nuclear atypia. The most common diagnostic pitfall of this group is adenosis, which may have an even more atypical architecture than some cancers. A common denominator of atrophy and benign proliferations is that they consist of small glands that may have a patchy or absent basal cell layer, which adds to the diagnostic difficulties. Amongst hyperplastic and metaplastic lesions, basal cell hyperplasia may be misinterpreted as cancer because of its dark basophilic glands that sometimes display a certain degree of nuclear atypia and occasionally exhibit a pseudoinfiltrative pattern. The most important extraprostatic anatomical structure causing diagnostic difficulties is the seminal vesicle. The closely clustered small glands and often strikingly atypical nuclei of seminal vesicle epithelium may be misinterpreted as cancer. Awareness of these mimics is of paramount importance for the practicing pathologist as a false positive diagnosis of prostate cancer may lead to unnecessary radical therapy

Inflammatory cytokine and chemokine expression in sympathetic ophthalmia: a pilot study

Sympathetic ophthalmia is a bilateral uveitis that develops after penetrating injury to one eye. This study aimed to identify the inflammatory cellular sub-phenotypes and expression of pertinent inflammatory cytokines/chemokines in sympathetic ophthalmia (SO). Dalen-Fuchs nodules (DFN), granulomas, and non-granulomatous foci of inflammation were micro-dissected from 15 cases. RNA was extracted, and quantitative PCR was performed to measure IL-17, IL-18, IL-23, IFN-γ, CCL19, CXCL11, CCL17, and CCL22 transcripts. Immunohistochemical methods were used to characterize CD3, CD4, CD8, CD20, CD68, and CD163 expression. Non-granulomatous lymphocytes were predominantly CD3-positive and expressed more IFN-γ than cells within granulomas, consistent with Th1 cells. In contrast, granulomas and DFN contained mainly CD68+, CD163+/- and expressed more IL-17, IL-18, IL-23, CCL19, and CXCL11 than non-granulomatous cells. Our data indicate for the first time that M1 macrophages are the predominant inflammatory cells within granulomas and DFN of SO. We further observed high levels of IL-17 within granulomas and the presence of Th1 and M1 cells

Benign mimics of prostate cancer

The histopathological diagnosis of prostatic adenocarcinoma is challenged by the existence of numerous benign mimics. Most of these lesions have no clinical significance and many do not need to be reported. Their clinical relevance lies in the risk that they are misinterpreted as cancer. This review presents the histopathological features of benign mimics and discusses their distinction from cancer. The lesions that are most often misdiagnosed as cancer are atrophy and its variants, including simple atrophy, partial atrophy and post-atrophic hyperplasia. Benign proliferations are a group of lesions with crowded small glands with no or little nuclear atypia. The most problematic entity of this group is adenosis, which may have a more alarming architecture than some cancers. A diagnostic problem with atrophy and several of the benign proliferations is that the glands often have a discontinuous or absent basal cell layer. Hyperplastic and metaplastic lesions include basal cell hyperplasia. Basal cell hyperplasia may especially mimic prostate cancer with its small dark glands, variable nuclear atypia and a pseudoinfiltrative pattern, which may be present. The anatomical structure that most often causes diagnostic problems is the seminal vesicle. The mucosa of the seminal vesicle contains small acini, often with very pronounced nuclear atypia that may be misinterpreted as cancer. Pathologists need to be familiar with these mimics, as a false positive diagnosis of prostate cancer may lead to unnecessary radical treatment