Primary leptomeningeal melanocytic neoplasms: A clinicopathologic, immunohistochemical, and molecular study of 12 cases.

This study investigated the clinicopathological, immunohistochemical, and molecular features of primary leptomeningeal melanocytic neoplasms (LMNs). Twelve LMN cases were retrospectively reviewed. We performed Fluorescence in-situ hybridization (including a 4-probe FISH assay with CDKN2A and MYC assay) and Next-Generation sequencing analyses on available cases. Histologically, 2 tumours were classified as melanocytomas (MC), 2 as intermediate-grade melanocytomas (IMC), and 8 as leptomeningeal melanomas (LMM). Two rare cases of LMM were associated with large plaque-like blue nevus. One MC case was associated with Ota. Ten cases (83.3%) showed melanocytic cells with benign features diffusely proliferating within the meninges. The Ki-67 in three categories differed (MC 0-1%, IMC 0-3%, LMM 3-10%). 57.1% of LMM cases (4/7) were positive for FISH. Nine of 10 tumours harboured activating hotspot mutations in GNAQ, GNA11, or PLCB4. Additional mutations of EIF1AX, SF3B1, or BAP1 were found in 40%, 30%, and 10% of tumours, respectively. During the follow-up (median = 43 months), 5 LMM patients experienced recurrence and/or metastasis, 3 of them died of the disease and the other 2 are alive with the tumour. Our study is by far the first cohort of LMN cases tested by FISH. In addition to morphological indicators including necrosis and mitotic figures, using a combination of Ki-67 and FISH helps to differentiate between IMC and LMM, especially in LMM cases with less pleomorphic features. SF3B1 mutation is first described in 2 cases of plaque-type blue nevus associated with LMM. Patients with SF3B1 mutation might be related to poor prognosis in LMN.

A deep learning model, NAFNet, predicts adverse pathology and recurrence in prostate cancer using MRIs.

We aimed to apply a potent deep learning network, NAFNet, to predict adverse pathology events and biochemical recurrence-free survival (bRFS) based on pre-treatment MRI imaging. 514 prostate cancer patients from six tertiary hospitals throughout China from 2017 and 2021 were included. A total of 367 patients from Fudan University Shanghai Cancer Center with whole-mount histopathology of radical prostatectomy specimens were assigned to the internal set, and cancer lesions were delineated with whole-mount pathology as the reference. The external test set included 147 patients with BCR data from five other institutes. The prediction model (NAFNet-classifier) and integrated nomogram (DL-nomogram) were constructed based on NAFNet. We then compared DL-nomogram with radiology score (PI-RADS), and clinical score (Cancer of the Prostate Risk Assessment score (CAPRA)). After training and validation in the internal set, ROC curves in the external test set showed that NAFNet-classifier alone outperformed ResNet50 in predicting adverse pathology. The DL-nomogram, including the NAFNet-classifier, clinical T stage and biopsy results, showed the highest AUC (0.915, 95% CI: 0.871-0.959) and accuracy (0.850) compared with the PI-RADS and CAPRA scores. Additionally, the DL-nomogram outperformed the CAPRA score with a higher C-index (0.732, P < 0.001) in predicting bRFS. Based on this newly-developed deep learning network, NAFNet, our DL-nomogram could accurately predict adverse pathology and poor prognosis, providing a potential AI tools in medical imaging risk stratification.

Combination of Androgen Deprivation Therapy with Radical Local Therapy Versus Androgen Deprivation Therapy Alone for Newly Diagnosed Oligometastatic Prostate Cancer: A Phase II Randomized Controlled Trial.

BACKGROUND: Previous studies suggested that men with metastatic prostate cancer might benefit from local treatment of the primary tumor. OBJECTIVE: To determine whether radical local therapy (RLT) improves survival for men with oligometastatic prostate cancer (OMPCa). DESIGN, SETTING, AND PARTICIPANTS: This open-label randomized controlled trial included patients with newly diagnosed OMPCa defined as five or fewer bone or extrapelvic lymph node metastases and no visceral metastases. INTERVENTION: Patients were randomly allocated to androgen deprivation therapy (ADT) or ADT and RLT. Men allocated RLT received either cytoreductive radical prostatectomy (RP) or prostate radiation therapy (RT) with a radical dose schedule. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was radiographic progression-free survival (rPFS). Secondary outcomes were overall survival (OS) and prostate-specific antigen (PSA) progression-free survival. RESULTS AND LIMITATIONS: Between September 2015 and March 2019, 200 patients were randomized, with 100 men allocated to each group. The median age was 68 yr and the median PSA at diagnosis was 99 ng/ml. In the study group, 96 patients underwent RLT (85 RP and 11 RT). In the control group, 17 patients eventually received RLT (15 RP and two RT). All patients were included for an intention-to-treat analysis. After a median follow-up of -48 mo, the median rPFS was not reached in the study group and was 40 mo in the control group (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.27-0.70; p = 0.001). The 3-yr OS rate was 88% for the study group and 70% for the control group (HR 0.44, 95% CI 0.24-0.81; p = 0.008). CONCLUSIONS: Men with newly diagnosed OMPCa who received ADT plus RLT (mainly prostatectomy) had significantly higher rates of rPFS and OS than those who received ADT alone. PATIENT SUMMARY: This study investigated the effect of radical local therapy (RLT) of the primary tumor on survival in patents with oligometastatic prostate cancer. In our group, RLT improved radiographic progression-free and overall survival.

Primary cutaneous adenoid cystic carcinoma: a clinicopathologic, immunohistochemical, and fluorescence in-situ hybridisation study of 13 cases.

AIMS: This study aimed to investigate the clinical, histological, immunohistochemical and chromosomal features of primary cutaneous adenoid cystic carcinoma (PCACC). METHODS AND RESULTS: We retrospectively analysed 13 cases identified on their clinicopathological features and performed fluorescence in-situ hybridisation (FISH) on six available cases. Head and neck (46.2%) were most commonly involved. The median age was 53 years, with a male predilection. Histologically, tumours were classified as grades 1 (eight), 2 (four) and 3 with high-grade transformation (HGT) (one). The HGT component was demonstrated as poorly differentiated carcinoma with multifocal necrosis and myoepithelial differentiation. Patients with one of the following factors: longest diameter of the lesion (≥ 1 cm), involvement of subcutaneous fat tissue and widely infiltrative border had a relatively higher rate of local recurrence, distant metastasis and death. Five of six cases were confirmed to have MYB translocation, while nuclear staining for MYB proto-oncogene, transcription factor (MYB) protein was found in four cases. During the follow-up (median = 64 months), two patients experienced local recurrences. One patient, who was classified as grade III PCACC with HGT, developed multiple metastases and died of disease. Another patient was alive with multiple metastases. CONCLUSIONS: This is the largest single-institution study, to our knowledge, of PCACC in an Asian population. We describe the first case of scalp PCACC with HGT, which is the only death case in our series. PCACC tends to recur locally and has metastatic potential. PCACC with HGT has a poor prognosis.

Prognostic value of PTEN in de novo diagnosed metastatic prostate cancer.

The purpose of our study is to investigate the prognostic value of phosphatase and tensin homolog on chromosome 10 (PTEN) expression in patients with de novo metastatic castration naïve prostate cancer (mCNPC). A total of 205 patients with mCNPC at Fudan University Shanghai Cancer Center (Shanghai, China) were retrospectively examined. Immunohistochemical staining of PTEN was performed on prostate biopsy samples of these patients. Associations among clinicopathological features, patient survival and PTEN protein expression were analyzed. PTEN loss occurred in 58 of 205 (28.3%) patients. Loss of PTEN was significantly correlated with high metastatic volume (P = 0.017). No association between PTEN expression and Gleason score was observed. Patients with PTEN loss had significantly shorter progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001) compared with patients with intact PTEN expression. Multivariate analysis showed that elevated alkaline phosphatase, high metastatic volume and PTEN loss were independent poor prognostic factors for PFS. The Eastern Cooperative Oncology Group performance status (ECOG PS)#8805; 2 and PTEN loss were independent poor prognostic factors for OS. The adjusted hazard ratio of PTEN loss for PFS and OS was 1.67 (95% confidence interval [CI]: 1.14-2.43, P = 0.008) and 1.95 (95% CI: 1.23-3.10, P = 0.005), respectively. PTEN loss was also significantly associated with shorter PFS (P = 0.025) and OS (P < 0.001) in patients with low-volume metastatic disease. Our data showed that PTEN loss is an independent predictor for shorter PFS and OS in patients with de novo mCNPC.

High IL-23+ cells infiltration correlates with worse clinical outcomes and abiraterone effectiveness in patients with prostate cancer.

Individualized treatment of prostate cancer depends on an accurate stratification of patients who are sensitive to various treatments. Interleukin-23 (IL-23) was reported to play a significant role in prostate cancer. Here, we aimed to explore the clinical value of IL-23-secreting (IL-23+) cells in prostate cancer patients. We evaluated interleukin-23A (IL-23A) expression in The Cancer Genome Atlas database and retrospectively enrolled 179 treatment-naïve metastatic prostate cancer patients diagnosed in our institute between June 2012 and December 2014. IL-23+ cells were stained and evaluated via immunohistochemistry. Further, survival and multivariate Cox regression analyses were conducted to explore the prognostic value of IL-23+ cells. We found that IL-23A expression correlated with disease progression, while IL-23+ cells were clearly stained within prostate cancer tissue. Patients with higher Gleason scores and multiple metastatic lesions tended to have more IL-23+ cell infiltration. Further analyses showed that patients with higher levels of IL-23+ cells had significantly worse overall survival (hazard ratio [HR] = 2.996, 95% confidence interval [95% CI]: 1.812-4.955; P = 0.001) and a higher risk of developing castration resistance (HR = 2.725, 95% CI: 1.865-3.981; P = 0.001). Moreover, subgroup analyses showed that when patients progressed to a castration-resistant status, the prognostic value of IL-23+ cells was observed only in patients treated with abiraterone instead of docetaxel. Therefore, we showed that high IL-23+ cell infiltration is an independent prognosticator in patients with metastatic prostate cancer. IL-23+ cell infiltration may correlate with abiraterone effectiveness in castration-resistant prostate cancer patients.

Preferentially expressed antigen in melanoma immunohistochemistry as an adjunct for differential diagnosis in acral lentiginous melanoma and acral nevi.

Preferentially expressed antigen in melanoma (PRAME) has shown promising utility in distinguishing benign melanocytic lesions from melanomas, but knowledge of its expression pattern in acral lentiginous melanoma (ALM) and acral nevi (ANs) is limited. Immunohistochemical expression of PRAME was examined in 75 ALMs and 34 ANs. The clinical and histopathologic characteristics of patients with ALM were collected. PRAME was immunoreactive in 89.3% (67/75) of ALMs, but entirely negative in 94.1% (32/34) of ANs. When staining at least 50% of lesional melanocytes was determined as positivity, the sensitivity and specificity of PRAME for distinguishing ALM from ANs were 69.3% and 100%, respectively. Seventy-one cases of ALMs had tumor cells in the epidermis; 71.8% (51/71) of them showed positive for PRAME. By contrast, 61 ALMs had tumor cells in the dermis; 65.6% (40/61) exhibited positive expression. Twenty-nine of 39 (74.4%) epithelioid cell ALMs were observed to be positive for PRAME. By comparison, 63.8% (23/36) of ALMs with spindle tumor cells were positive for PRAME. However, PRAME positive expression was not associated with any clinical and histopathologic characteristics of patients with ALM, including Breslow thickness, ulcer, cytomorphology, lymph node metastasis, or tumor-infiltrated lymphocytes (TILs). Nevertheless, we observed that 82.6% (19/23) of ALMs with lymph node involvement at diagnosis expressed PRAME, compared with 57.6% (20/35) of those without. In summary, PRAME immunohistochemistry can serve as a helpful adjunct in the differential diagnosis of ALMs and ANs with good sensitivity and high specificity. Additionally, PRAME tends to have a higher positive rate in epidermal melanocytes than in the dermis and is inclined to express in epithelioid cells than in spindle cells of ALMs.

Clinicopathological, immunohistochemical and fluorescence in-situ hybridisation features of early subungual melanoma: an analysis of 65 cases.

AIMS: Very limited data are available concerning the clinicopathological and molecular features of early subungual melanoma (SM), especially with regard to the Asian population. The aim of this study was to investigate the clinical, histological, immunohistochemical and chromosomal features of early SM. METHODS AND RESULTS: Fifty-two in-situ and 13 thin (Breslow thickness ≤1.0 mm) SM cases were retrospectively reviewed. All patients presented with longitudinal melanonychia involving a single digit, and the thumb was the most affected digit (35 of 65, 53.8%). Microscopically, most cases showed small to medium nuclear enlargement (58 of 65) and mild to moderate nuclear atypia (57 of 65). Hyperchromatism and irregular contours of nuclei were persistent features in all cases. The variation of melanocyte count (the number of melanocytes per mm dermal-epithelial junction) ranged from 31 to 255. Intra-epithelial mitoses were identified in 34 cases (52.3%). Statistically, features of in-situ lesions including higher melanocyte count (>70), presence of multinucleated melanocytes, inflammatory infiltrate and cutaneous adnexal extension, were associated with early invasion. Melan-A, human melanoma B (HMB)45, mouse monoclonal melanoma antibody (PNL2) and SOX10 antibodies (>95.0%) showed superior diagnostic sensitivity to S-100 protein (83.1%). Fluorescence in-situ hybridisation (FISH) results were positive in 15 of 23 successfully analysed cases. CONCLUSIONS: To the best of our knowledge, this is the largest single-institution study of early SM in an Asian population, and the largest cohort tested by FISH. Early SM mainly showed small to medium nuclear enlargement and mild to moderate nuclear atypia. High melanocyte count, hyperchromatism and irregular contours of nuclei and intra-epithelial mitoses are crucial diagnostic parameters. Immunohistochemistry, especially SOX10 staining, and FISH analysis are valuable in the diagnosis of SM.

Nevus cell aggregates massively occupying parenchyma of an external iliac lymph node: A case report and review of the literature.

We report a case of nevus cell aggregates (NCAs) in an external iliac lymph node from a patient with a compound congenital nevus in the corresponding drainage skin. Melanocytes in parenchyma were in band, nest-like or nodular fashion, and partly continuous with those in capsule and trabeculae. The largest nodule in parenchyma measured 6.5 mm. Melanocytes mostly exhibited benign appearance identical to cutaneous nevus. A few regions abundant in cells displayed atypical features, including increased nucleo-cytoplasmic ratio, small nucleoli, and occasional mitotic figures. Immunohistochemistry showed that melanocytes stained positive for p16, but negative for HMB-45 and nestin. Ki-67 labeling was less than 1% and reticulin mainly surrounded individual melanocytes. Besides, Vysis melanoma fluorescence in situ hybridization (FISH) plus another 2 probes targeting 9p21(CDKN2A) and 8q24(MYC) showed normal results. The patient is alive without malignant tumor after 52-month follow up. Our case provides a new evidence for the existence of intraparenchymal NCAs in deep lymph node and indicates that melanocytes with some atypical features can occur in nodal nevi. Nevus cells in parenchyma connected to those in capsule and trabeculae are a significant clue to distinguish nodal nevi from metastatic melanomas. Additionally, immunohistochemistry and FISH assay are useful in differential diagnosis.

Clinicopathological diversity and outcome of longitudinal melanonychia in children and adolescents: analysis of 35 cases identified by excision specimens.

AIMS: Longitudinal melanonychia in paediatric patients often represents a difficult diagnostic challenge, and studies emphasising its clinical and histopathological features are limited due to its low incidence in childhood. METHODS AND RESULTS: We retrospectively analysed 35 paediatric cases identified by excision specimens on their clinicopathological features, and performed fluorescence in-situ hybridisation on 13 available cases. Fingernails (77.1%) were more likely to be affected. Total melanonychia and Hutchinson's sign were observed in 10 (28.6%) and 14 (40.0%) cases, respectively. Nail dystrophy at diagnosis was present in five cases. After complete excision of the lesions, four patients relapsed during follow-up (mean = 38 months). Seventeen cases were diagnosed as lentigines and 18 as naevi, among which 11 cases were categorised as lentigines/naevi with atypical melanocytic hyperplasia. Mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and peri-ungual skin involvement were found in 25.7% (9 of 35), 40.0% (14 of 35), 40.0% (14 of 35) and 40.0% (14 of 35) of cases, respectively. Thirteen cases tested by fluorescence in-situ hybridisation showed no copy number aberration at the probed loci. There was a statistically significant difference in the following features between patients aged less and more than 10 years (P < 0.05): cytomorphology, mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and melanocyte count. CONCLUSIONS: Some concerning clinicopathological characteristics, which are signs indicative of melanoma in adults, are not uncommon in paediatric longitudinal melanonychia, especially in patients aged ≤ 10 years. Owing to the extremely low incidence of melanoma in paediatric longitudinal melanonychia, in most circumstances a more conservative clinical management strategy should be adopted.

Phenotypes of circulating tumour cells predict time to castration resistance in metastatic castration-sensitive prostate cancer.

OBJECTIVES: To identify biomarkers that predict the response to standard androgen deprivation therapy (ADT) of patients newly diagnosed with metastatic castration-sensitive prostate cancer (CSPC) in order to improve therapeutic decision-making, and to investigate whether the characterization of baseline circulating tumour cells (CTCs) would predict the effective period of standard ADT. MATERIALS AND METHODS: The study included 108 patients newly diagnosed with high-volume metastatic CSPC. Enumeration and characterization of patients' baseline CTCs (CTCs+ and CTCs-, indicating detectable and undetectable CTCs, respectively) were performed using the CanPatrol technique, which detects markers of the epithelial to mesenchymal transition (EMT) in CTCs, and classifies CTCs into epithelial, biophenotypic and mesenchymal phenotypes. RESULTS: After a median follow-up of 24 months, 90 patients (83.3%) progressed to castration-resistant prostate cancer (CRPC), 93 patients (86.1%) had detectable CTCs, and the median number of CTCs was 4. The rate of progression to CRPC was significantly higher for patients with mesenchymal CTCs+ than for patients with CTCs+/mesenchymal CTCs- and CTCs- (93.1% vs 71.4% and 73.3%; P = 0.013). The median time to CRPC for patients with mesenchymal CTCs+ was significantly shorter than for those with CTCs+/mesenchymal CTCs- and CTCs- (10.5 months vs 18.0 and 14.0 months; P = 0.003). Multivariate Cox regression analysis suggested that the CTC phenotype was the only independent prognostic factor influencing the progression of disease from CSPC to CRPC. CONCLUSIONS: Characterization of baseline CTCs according to the EMT phenotype predicted the effective period of standard ADT for patients newly diagnosed with metastatic CSPC. These findings are important for counselling patients and designing clinical trials.

Clinical activity of abiraterone plus prednisone in docetaxel-naοve and docetaxel-resistant Chinese patients with metastatic castration-resistant prostate cancer.

This study investigated the clinical activity of abiraterone plus prednisone in docetaxel-naïve and docetaxel-resistant Chinese patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 146 patients with docetaxel-naïve group (103 cases) and docetaxel-resistant group (43 cases) were enrolled from the Shanghai Cancer Center (Shanghai, China) in this retrospective cohort study. The efficacy endpoints were prostate-specific antigen response rate, prostate-specific antigen progression-free survival, clinical/radiographic progression-free survival, and overall survival in response to abiraterone plus prednisone. Significantly higher prostate-specific antigen response rate was found in docetaxel-naïve group (54.4%, 56/103) compared to docetaxel-resistant group (34.9%, 15/43) (P = 0.047). In addition, significantly higher median prostate-specific antigen progression-free survival (14.0 vs 7.7 months, P = 0.005), clinical or radiographic progression-free survival (17.0 vs 12.5 months, P = 0.003), and overall survival (27.0 vs 18.0 months, P = 0.016) were found in docetaxel-naïve group compared to docetaxel-resistant group, respectively. The univariate and multivariate analyses indicated that lower albumin and visceral metastases were independent significant predictors for shorter overall survival. To sum up, our data suggested that abiraterone plus prednisone was efficient in both docetaxel-naïve and docetaxel-resistant Chinese patients. Moreover, higher PSA response rate and longer overall survival were observed in the docetaxel-naïve group, which suggested that abiraterone was more effective for docetaxel- naïve patients than for docetaxel failures.

PD-L1 expression in tumour-infiltrating lymphocytes is a poor prognostic factor for primary acral melanoma patients.

AIMS: Programmed cell death protein 1-programmed death-ligand 1 (PD-L1) blockade immunotherapy has shown notable therapeutic benefit in metastatic melanoma, but the clinical relevance of PD-L1 expression remains unclear in melanoma, especially in acral melanoma, which is the most common subtype in Asians. The aim of this study was to evaluate the clinical effect of PD-L1 expression in primary acral melanoma. METHODS AND RESULTS: We used immunohistochemistry to evaluate PD-L1 expression in tumour cells and tumour-infiltrating lymphocytes (TILs), and analysed its associations with clinicopathological features and survival in 78 primary acral melanoma patients. We found that expression of PD-L1 in tumour cells and TILs occurred exclusively in a tumour-stroma interface pattern, consistent with the predominant pattern of TIL distribution. The presence of peritumoral TILs was also associated with high PD-L1 expression in tumour cells. Furthermore, PD-L1 expression in tumour cells and that in TILs showed a close relationship (Spearman's rho = 0.381, P = 0.001). However, neither PD-L1 expression in tumour cells nor that in TILs was significantly correlated with clinicopathological features. In univariate analysis, cases with PD-L1-positive TILs had significantly poorer survival than those with PD-L1-negative TILs (median disease-specific survival of 40.7 months versus 78.0 months; P = 0.008). In multivariate analysis, PD-L1 expression in TILs was an independent factor for poor prognosis (P = 0.032), whereas PD-L1 expression in tumour cells was not significantly correlated with survival in univariate analysis (P = 0.378) and multivariate analysis (P = 0.354). CONCLUSION: This is the first study to demonstrate that PD-L1 expression in TILs, but not that in tumour cells, is an independent predictor of poor prognosis in acral melanoma.

Chemokine Receptors CXCR4 and CXCR7 are Associated with Tumor Aggressiveness and Prognosis in Extramammary Paget Disease.

Chemokines are involved in many aspects of oncogenesis, including regulation of cancer cell growth, dissemination and host-tumor response. However, the potential of the chemokine receptors, CXCR4 and CXCR7, in serving as biomarkers in extramammary Paget's disease (EMPD) has been rarely examined. Expressions of CXCR4 and CXCR7 were evaluated in 92 EMPD specimens by immunohistochemistry. High expression of CXCR4 and CXCR7 were both correlated with regional lymph node metastasis and presence of lymphovascular invasion. High expression of CXCR7 also correlated with the depth of invasion. The prognostic value of these two chemokines were also investigated in progression-free survival (PFS) and cancer-specific survival (CSS). Both high expression of CXCR4 and CXCR7 were indicative of shorter PFS and CSS. In the combined prognostic model, concomitant high expression of CXCR4 and CXCR7 were suggestive of poor prognosis compared with the other two groups. In the multivariate analysis, depth of invasion, combined prognostic model and regional lymph node metastasis at diagnosis were the independent prognostic factors for EMPD patients for PFS, and the former two factors independently impacted CSS. Our results demonstrated that CXCR4 and CXCR7 can be used as prognostic biomarkers and prediction of aggressiveness of EMPD. Therapy targeting CXCR4 and CXCR7 may helpful to prevent EMPD progression and improve the prognosis of EMPD.

Syringocystadenocarcinoma papilliferum: Clinicopathologic analysis of 10 cases.

BACKGROUND: Syringocystadenocarcinoma papilliferum (SCACP) is an exceedingly rare cutaneous adnexal neoplasm. We aimed to investigate the clinicopathologic and immunophenotypic features of SCACP, and to discuss the prognosis of this rare entity. METHOD: We retrospectively collected clinical, pathological and follow-up data of 10 cases with SCACP. RESULTS: There were 8 males and 2 females, with ages ranging from 26 to 74 years. The chest was most frequently involved. Histologically, 1 case only showed SCACP in situ, 9 cases presented with variable invasive components of adenocarcinoma and/or squamous cell carcinoma in addition to areas of in situ. Apocrine differentiation with decapitation was evident in 4 cases and mucinous metaplasia was noted in 1 case. P63 was positive in invasive squamous cell carcinoma, while CK7 was variably positive in invasive adenocarcinoma. Regional lymph node metastasis was confirmed by pathological examination in 4 patients. Follow up was available for 9 patients, ranging from 3 to 112 months. Three patients died of the disease within 1 year after recurrences. CONCLUSIONS: Because of high rates of regional lymph node metastasis and mortality in our patients, clinical behavior of SCACP seems to be more aggressive than that previously reported.

Factors influencing biochemical recurrence in patients who have received salvage radiotherapy after radical prostatectomy: a systematic review and meta-analysis.

Several studies have evaluated the risk factors influencing biochemical recurrence (BCR) of prostate cancer in patients receiving salvage radiotherapy (SRT) for BCR after radical prostatectomy (RP), but the results remain conflicting. In this study, we performed a meta-analysis to resolve this conflict. We searched the following databases: PubMed, Embase, and Web of Science using the following terms in "All fields": "salvage radiation therapy," "salvage IMRT," "S-IMRT," "salvage radiotherapy," "SRT," "radical prostatectomy," "RP," "biochemical recurrence," "BCR," "biochemical relapse." Eleven studies, with a total of 1383 patients, were included in our meta-analysis. Of all the variables, only Gleason score (GS) ≥7 (odds ratio [OR]: 3.82; 95% confidence interval [CI]: 2.60-5.64) and pathological tumor (pT) stage ≥3a (OR: 1.82; 95% CI: 1.36-2.42) were positively correlated with BCR. However, SRT combined with androgen deprivation therapy (ADT) (OR: 0.63; 95% CI: 0.44-0.90) and radiation therapy (RT) dose ≥64 Gy (OR: 0.35; 95% CI: 0.19-0.64) were negatively correlated with BCR. Perineural invasion (OR: 2.64; 95% CI: 1.11-6.26), preoperative prostate-specific antigen (PSA) ≥10 ng ml-1 (OR: 1.36; 95% CI: 0.94-1.96), positive surgical margin (OR: 0.92; 95% CI: 0.7-1.19), and seminal vesicle involvement (SVI) (OR: 1.09; 95% CI: 0.83-1.43) had no effect on BCR. Our meta-analysis indicated that pT stage, GS, RT dose, and SRT combined with ADT may influence BCR, while preoperative PSA, surgical margin, perineural invasion, and SVI have only a weak effect on BCR.

Relationship between circumcision and human papillomavirus infection: a systematic review and meta-analysis.

Male circumcision (MC) is reported to reduce human papillomavirus (HPV) prevalence in men. However, the efficacy remains imprecise. The aim of this study was to conduct a systematic review and meta-analysis to assess the relationship between MC and genital HPV infection and genital warts. PUBMED, EMBASE, and Web of Science were searched from inception to March 22, 2015. We identified 30 papers, including a total of 12149 circumcised and 12252 uncircumcised men who were evaluated for the association of circumcision with genital HPV or genital warts. Compared with men who were not circumcised, circumcised men may have had significantly reduced odds of genital HPV prevalence (odds ratio [OR]: 0.68; 95% confidence interval [95% CI]: 0.56-0.82). There was no significant association between MC and genital HPV acquisition of new infections (OR: 0.99; 95% CI: 0.62-1.60), genital HPV clearance (OR: 1.38; 95% CI: 0.96-1.97), and prevalence of genital warts (OR: 1.17; 95% CI: 0.63-2.17). This meta-analysis suggests that circumcision reduces the prevalence of genital HPV infections. However, no clear evidence was found that circumcision was associated with decreased HPV acquisition, increased HPV clearance, or decreased the prevalence of genital warts. More studies are required to evaluate adequately the effect of MC on the acquisition and clearance of HPV infections and prevalence of genital warts.

Primary invasive extramammary Paget disease on penoscrotum: a clinicopathological analysis of 41 cases.

To investigate the clinicopathological and immunohistochemical features and prognostic factors for invasive extramammary Paget disease (EMPD) on penoscrotum, we described the clinical presentations, histopathology, and follow-up courses of 41 cases. The age of the patients ranged from 42 to 84 years. All the patients were treated with wide surgical excision, and 14 were confirmed to have lymph node metastasis. During follow-up, 18 patients (43.9%) developed local or distant recurrence, and 13 patients (31.7%) died of the disease. Histologically, glandular formation with true lumina within the epidermis was found in 29 cases, and signet ring cells were seen in 11 cases. In invasive components, nodular/micronodular growth pattern, glandular formation, and strands/solid sheets existed in 95.1% (39/41), 43.9% (18/41), and 24.4% (10/41) of the cases, respectively. More than half of the cases had at least 2 different types of invasive growth pattern. CK7 was diffusely positive in all cases, whereas CK20 was focally positive in 8 cases. GCDFP-15 was expressed to a variable degree in 24 cases. Presence of strands/solid sheets, lymphovascular invasion, and perineural invasion in invasive EMPD were found to be correlated with higher lymph node metastatic rate. Univariate analysis revealed that patients with one of the following prognostic factors: delay in diagnosis more than 7.5 years, depth of invasion more than 1 mm, invasive pattern of strands/solid sheets, marked inflammation, lymphovascular invasion, and lymph node metastasis at diagnosis, had significantly shorter cancer-specific survival. We concluded that invasive EMPD is a rare malignant skin neoplasm with morphological diversity. Invasive pattern of strands/solid sheets is significantly associated with both lymph node metastasis and worse prognosis. Delay in diagnosis, depth of invasion, marked inflammation, lymphovascular invasion, and regional lymph node status are important prognostic factors.

Combination of circulating tumor cell enumeration and tumor marker detection in predicting prognosis and treatment effect in metastatic castration-resistant prostate cancer.

Although circulating tumor cell (CTC) enumeration in peripheral blood has already been validated as a reliable biomarker in predicting prognosis in metastatic castration-resistant prostate cancer (mCRPC), patients with favorable CTC counts (CTC < 5/7.5 ml) still experience various survival times. Assays that can reduce patients' risks are urgently needed. In this study, we set up a real-time quantitative polymerase chain reaction (RT-qPCR) method to detect epithelial-mesenchymal transition (EMT) and stem cell gene expression status in peripheral blood to validate whether they could complement CTC enumeration. From January 2013 to June 2014 we collected peripheral blood from 70 mCRPC patients and enumerated CTC in these blood samples using CellSearch system. At the same time, stem cell-related genes (ABCG2, PROM1 and PSCA) and EMT-related genes (TWIST1 and vimentin) were detected in these peripheral blood samples using an RT-qPCR assay. Patient overall survival (OS) and treatment methods were recorded in the follow-up. For patients who received first-line chemotherapy, docetaxel plus prednisone, PSA progression-free survival (PSA-PFS) and PSA response rate were recorded. At the time of analysis, 35 patients had died of prostate cancer with a median follow-up of 16.0 months. Unfavorable CTC enumerations (CTC ≥5/7.5 ml) were predictive of shorter OS (p = 0.01). Also, positive stem cell gene expression indicated poor prognosis in mCRPC patients (p = 0.01). However, EMT gene expression status failed to show any prognostic value in OS (p = 0.78). A multivariate analysis indicated that serum albumin (p = 0.04), ECOG performance status (p < 0.01), CTC enumeration (p = 0.02) and stem cell gene expression status (p = 0.01) were independent prognostic factors for OS. For the 40 patients categorized into the favorable CTC enumeration group, positive stem cell gene expression also suggested poor prognosis (p < 0.01). A combined prognostic model consisting of stem cell gene expression and CTC enumeration increased the concordance probability estimated value from 0.716 to 0.889 in comparison with CTC enumeration alone. For patients who received docetaxel plus prednisone as first-line chemotherapy, positive stem cell gene expression suggested a poor PSA-PFS (p = 0.01) and a low PSA response rate (p = 0.008). However, CTC enumeration and EMT gene expression status did not affect PSA-PFS or PSA response rates. As a result, detection of peripheral blood stem cell gene expression could complement CTC enumeration in predicting OS and docetaxel-based treatment effects in mCRPC patients.

Primary invasive carcinoma associated with penoscrotal extramammary Paget's disease: a clinicopathological analysis of 56 cases.

OBJECTIVES: To investigate the clinicopathological features, therapeutic strategies, and prognostic factors of patients with penoscrotal invasive extramammary Paget's disease (EMPD). PATIENTS AND METHODS: We retrospectively collected clinical, pathological, and follow-up data of 56 men with invasive penoscrotal EMPD. Histopathological features of the primary skin lesion including tumour size, surgical margin status, depth of invasion and lymphovascular invasion were examined. RESULTS: The median age was 67 years and median longest diameter of lesion was 5 cm. All patients were treated with wide surgical excision and 22 patients with clinically positive regional lymph nodes underwent therapeutic regional lymph node dissection. At the end of the study, 44.6% of patients developed distant metastasis and 39.3% of patients had died from disease. Univariate analysis showed that patients with one of the following poor prognostic factors: depth of invasion of lower dermis or deeper, presence of lymphovascular invasion and regional lymph node metastasis at diagnosis, had significantly shorter cancer-specific survival time. Multivariate analysis found that depth of invasion was the only independent prognostic factor. CONCLUSION: The prognosis of invasive EMPD is significantly associated with depth of invasion, lymphovascular invasion and regional lymph node status. More aggressive therapy and more rigorous follow-up should be recommended for patients with these poor prognostic factors.