High IL-23+ cells infiltration correlates with worse clinical outcomes and abiraterone effectiveness in patients with prostate cancer / 亚洲男科学杂志(英文版)

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.

Prognostic value of PTEN in de novo diagnosed metastatic prostate cancer / 亚洲男科学杂志(英文版)

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.

Influence of obesity on clinicopathological characteristics in patients with clinically localized prostate cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the influence of anthropometric measures of obesity, including body mass index (BMI), abdominal subcutaneous adipose tissue and visceral adipose tissue, on pathological characteristics in patients with clinically localized prostate cancer.</p><p><b>METHODS</b>From January 2006 to March 2013, the 413 patients of prostate cancer who received radical prostatectomy (RP) and their clinical and pathological data had been collected. The median age for the entire cohort was 68 years, which ranged from 48 to 78 years. All patients were diagnosed with prostate cancer before surgery and the Gleason score ranged from 4 to 10 (median 7). Anthropometric measures of abdominal adiposity including anterior abdominal fat, posterior abdominal fat and anteroposterior diameter were measured from the T2 weighted sagittal localization images of MRI scans and subcutaneous adipose tissue and the percentage of visceral adipose tissue were calculated. The patients' clinical and pathologic characteristics across BMI groups were compared used Student's t test for continuous variables or chi-squared test for categorical variables. Moreover, univariable and multivariable logistic regression models were used to address the influence of anthropometric measures of obesity on pathological outcomes.</p><p><b>RESULTS</b>The BMI ranged from 14.2 to 34.0 kg/m(2) and the median value was 23.8 kg/m(2). The abdominal subcutaneous adipose tissue ranged from 12.6 to 60.3 mm and the median value was 31.4 mm. The percentage of visceral adipose tissue ranged from 71.1% to 92.1% and the median value was 83.8%. In RP specimens, Gleason score ≥ 8 was observed in 141 patients (34.1%), pathological tumor stage was T3a in 69 patients (16.7%) and pathological tumor stage was T3b in 78 patients (18.9%). Positive surgical margin and lymph node involvement were observed in 71(17.2%) and 38(9.2%) patients, respectively. Although univariate analysis showed that BMI ≥ 25 kg/m(2) was associated with pathological Gleason score ≥ 8 (OR = 1.413, P = 0.035), this positive correlation disappeared in multivariate analysis(P = 0.095). In multivariate analysis, the percentage of visceral adipose tissue was significantly associated with pathological Gleason score (OR = 9.618, P = 0.000), extracapsular extension (OR = 6.750, P = 0.002) and seminal vesicle invasion (OR = 4.419, P = 0.007) after adjusting for patient age, PSA level, clinical stage and biopsy Gleason score.</p><p><b>CONCLUSIONS</b>Anthropometric measures of abdominal adiposity was more sophisticated than simple BMI to evaluate the risk of obesity with regard to the aggressiveness of prostate cancer. The percentage of visceral adipose tissue was an independent factor for pathological Gleason score, extracapsular extension and seminal vesicle invasion in RP specimens.</p>

Cutaneous regressing/regressed malignant melanoma: a clinicopathologic analysis of 8 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and differential diagnosis of cutaneous regressing/regressed melanoma.</p><p><b>METHODS</b>Histopathologic evaluation and immunohistochemical study by EnVision method were performed in 8 cases of cutaneous regressing/regressed melanoma. The clinical presentation, treatment and follow-up data were analyzed.</p><p><b>RESULTS</b>The age of the patients ranged from 40 to 69 years (mean 58 years). The male-to-female ratio was 3: 1. Tumors were located on the back (4 cases), sole of the foot (2 cases), ventral aspect of the toes (1 case), and the forearm (1 case). Clinically, 6 patients presented with progressive black mole of the skin, followed by subsequent focal hypopigmentation, even scarring. Two patients presented with multiple foci of dark-brown pigmentation. Microscopically, 3 cases were completely regressed malignant melanoma. Tumoral melanosis was found in 1 of 3 cases. The other 5 cases were melanoma with severe regression. The extent of regression ranged from 75% to 90%. The Breslow depth of the tumors ranged from 0.5 to 1.0 mm. Immunohistochemically, both metastatic and primary tumor cells were diffusely positive for S-100, HMB45 and Melan A, while melanophages were positive for CD68. Follow-up data were available in 8 patients, ranging from 8 to 27 months. Five patients were alive with no evidence of disease, 1 patient was alive with stable disease and 2 patients died of metastatic melanoma.</p><p><b>CONCLUSIONS</b>Correlation between clinical presentation and pathologic features is important for diagnosis of cutaneous regressing/regressed melanoma. Thin melanoma with extensive regression ( ≥ 75%) should not been regarded as low metastatic risk and wide excision combined with sentinel lymph node biopsy is recommended.</p>

Cutaneous anaplastic large cell lymphoma: clinicopathologic, immunohistochemical and prognostic study of 44 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype and prognosis of primary cutaneous anaplastic large cell lymphoma (CALCL).</p><p><b>METHODS</b>Histopathologic evaluation and immunohistochemical study by Envision method were carried out in 44 archival cases of CALCL. The clinical information and follow-up data were analyzed.</p><p><b>RESULTS</b>The patients presented with skin nodules, masses or plaques, sometimes associated with ulceration. The commonest sites of involvement were the extremities. Follow-up data were available in 39 patients. The overall survival rate was 87.2% (34/39). Disease relapses were detected in 46.2% (18/39) of the patients. Statistical analysis indicated that patients older than 50 years of age or with no less than two involved anatomic sites were more likely to have disease relapses (P < 0.05). Histologically, 31 cases were classified as common variant, 6 cases as small cell variant and 7 cases as neutrophil/eosinophil-rich variant. Immunohistochemical study showed that the rates of expression of CD30, CD45, CD45RO, CD43, CD3, cytotoxic protein and epithelial membrane antigen were 100% (44/44), 91.2% (31/34), 82.6% (19/23), 94.7% (18/19), 70.0% (28/40), 73.3% (22/30) and 31.8% (7/22), respectively. The CD4(+)/CD8(-), CD4(-)/CD8(+) and CD4(-)/CD8(-) immunophenotypes were found in 58.3% (21/36), 22.2% (8/36) and 19.4% (7/36) of the CALCL cases, respectively. Only one case (3.7%) expressed CD56.</p><p><b>CONCLUSIONS</b>CALCL is a form of low-grade primary cutaneous T-cell lymphoma with a wide spectrum of clinicopathologic pattern. Special variants of CALCL should not be confused with other types of cutaneous lymphomas and inflammatory lesions. CALCL patients older than 50 years of age or with no less than two involved anatomic sites are more likely to have disease relapses.</p>

MR imaging features of different renal cell carcinoma subtypes / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare and analyze the MRI features of different renal cell carcinoma (RCC) subtypes.</p><p><b>METHODS</b>The MR images of 81 surgically and pathologically confirmed renal cell carcinomas from 79 patients were reviewed retrospectively. The MR imaging features of lesions in plain scan, the degree and patterns of lesion enhancement (homogeneous, heterogeneous, peripheral), and tumor spreading patterns were analyzed. In order to evaluate the diagnostic validity of differentiating RCC subtypes using signal enhancement, receiver operating characteristic curves (ROC) were generated. The cutoff value of post-contrast signal intensity to noise ratios (SNR) of the tumor parenchyma were also generated in order to differentiate clear cell RCC from other subtypes.</p><p><b>RESULTS</b>Of the 81 lesions, 58 were clear cell carcinomas, 10 chromophobe cell carcinomas, 8 papillary cell carcinomas, and 5 unclassified RCC. All the chromophobe cell subtype tumors showed a homogeneous density (P < 0.05). The clear cell subtype tumors were likely heterogenous, and also showed heterogenous enhancement with mixed signal than other subtypes (P < 0.05). The cutoff value of SNR, which was used to differentiate clear cell subtype from the other subtypes, were 616 (corticomedullary phase), 579 (nephrographic phase) and 278 (excretory phase), retrospectively. The nephrographic phase is the most appropriate for differentiation, with a sensitivity of 62.1%, specificity of 91.3%, positive predictive value of 94.7%, negative predictive value of 48.8% and an accuracy value of 70.3%. No significant difference was found in tumor spreading patterns among all subtypes of RCC.</p><p><b>CONCLUSION</b>MR imaging features, particularly tumor heterogeneity and degree of enhancement are useful in differentiation of the renal cell carcinoma subtypes, and in choosing an individualized therapy.</p>

Frequency of genetic aberrations in mucosa-associated lymphoid tissue lymphoma of different sites / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the frequency of certain specific genetic aberrations, including t (11; 18)/API2-MALT1, t (1; 14)/IgH-bcl-10 and t (14; 18)/IgH-MALT1, in mucosa-associated lymphoid tissue (MALT) lymphoma of different sites.</p><p><b>METHODS</b>One hundred and ninety-six cases of MALT lymphoma from Cancer Hospital of Fudan University were enrolled into the study. The samples consisted of MALT lymphomas from stomach (53 cases, including 44 cases of low-grade MALT lymphoma and 9 cases of MALT lymphoma with diffuse large B-cell lymphoma component), ocular adnexa (50 cases), salivary gland (20 cases), lung (20 cases), intestine (17 cases), skin (17 cases), liver (8 cases), thyroid (5 cases) and other sites (2 cases from tongue, 1 case from pancreas, 1 case from larynx, 1 case from vocal cords and 1 case from kidney). Fluorescence in-situ hybridization for API2-MALT1 fusion gene, bcl-10, MALT1 and IgH genes was performed on paraffin sections.</p><p><b>RESULTS</b>Among the 196 cases of MALT lymphoma, 25 cases (12.8%) possessed API2-MALT1 fusion gene. The positive rates in various sites were significantly different (P = 0.002), as follows: 45.0% (9/20) in lung, 22.7% (10/44) in stomach (without large cell component), 15.0% (3/20) in salivary gland, 2 of 17 cases in intestine and 2.0% (1/50) in ocular adnexa. The fusion gene was not detected in the 9 cases of gastric MALT lymphoma with large cell transformation. It was also negative in the MALT lymphomas from skin, thyroid and other sites. One of the pulmonary MALT lymphoma cases showed simultaneous aberrations of IgH and MALT1 genes, such as t (14; 18)/IgH-MALT1. Two of the gastric MALT lymphoma cases without large cell transformation and one of the pulmonary MALT lymphoma cases showed aberrations in both IgH and bcl-10 genes, such as t (1; 14)/IgH-bcl-10. Six cases of MALT lymphoma, including 2 cases from salivary gland, 2 cases from liver, 1 case from thyroid and 1 case from stomach (large cell transformation), showed trisomy 18. On the other hand, 3 cases, including 2 cases from stomach and 1 case from intestine, showed MALT1 gene amplification.</p><p><b>CONCLUSIONS</b>In general, specific genetic aberrations have a relatively low frequency of occurrence in MALT lymphomas. The positive rates however show a remarkable difference in tumors of different anatomic sites. This phenomenon may suggest that MALT lymphomas in different sites, though sharing similar morphologic features, may have a divergent tumorgenesis.</p>

Individualized prostate biopsy strategy for Chinese patients with different prostate-specific antigen levels / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To evaluate the best individualized prostate biopsy strategies for Chinese patients with suspected prostate cancer.</p><p><b>METHODS</b>The present study included 221 Chinese patients who underwent transrectal ultrasound guided prostate biopsies for the first time. All patients underwent the same 10-core biopsy protocol. In addition to the Hodge sextant technique, four more biopsies were obtained from the base and middle regions of bilateral peripheral zones. The differences between 10-core and sextant strategies in cancer detection among patients with different prostate specific antigen (PSA) levels were evaluated. The relationship between PSA level, number of positive biopsy cores and organ-confined cancer rate in prostate cancer patients was also analyzed.</p><p><b>RESULTS</b>The overall prostate cancer detection rate was 40.7% in the 221 patients. The 10-core strategy increased cancer detection by 6.67% (6/90) in our patients (P < 0.05). The increased cancer detection rates decreased significantly when the patient PSA level increased from 0-20 ng/mL to 20.1-50 ng/mL and > 50 ng/mL (P < 0.01). The number of positive biopsy cores in prostate cancer patients increased significantly with increasing patient PSA level (P < 0.01). The rate of organ-confined prostate cancer decreased significantly with increasing patient PSA level (P < 0.01).</p><p><b>CONCLUSION</b>The extended 10-core strategy is recommended for Chinese patients with PSA = or < 20 ng/mL and the sextant strategy is recommended for those with PSA > 50 ng/mL. For patients with PSA ranging from 20.1 ng/mL to 50 ng/mL, the 10-core strategy should be applied in patients with life expectancy = or > 10 years and the sextant strategy should be applied in those with life expectancy < 10 years.</p>

Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To investigate human epidermal growth factor receptor type 2 (HER2) protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors.</p><p><b>METHODS</b>Immunohistochemistry (IHC) was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transurethral resection of the prostate (TURP). HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores >or=2+ were investigated for HER2 gene amplification status by fluorescent in situ hybridization (FISH).</p><p><b>RESULTS</b>Of the 104 prostate biopsy specimens, HER2 protein expression was 0, 1+, 2+ and 3+ in 49 (47.1%), 45 (43.3%), 8 (7.7%) and 2 (1.9%) cases, respectively. There was a significant association between HER2 expression and Gleason score (P = 0.026). HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores >or= 2+ showed HER2 gene amplification. Patients with HER2 scores >or= 2+ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 (P = 0.004) and 1+ (P = 0.034). Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death (P = 0.039).</p><p><b>CONCLUSION</b>An HER2 IHC score >or= 2+ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.</p>

Cutaneous Rosai-Dorfman disease / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic feature, immunophenotype and differential diagnosis of cutaneous Rosai-Dorfman disease (CRDD).</p><p><b>METHODS</b>Clinical manifestation, morphologic features and immunohistochemical staining were studied in 8 cases of CRDD.</p><p><b>RESULTS</b>All 8 patients presented with multiple papules, nodules and/or coalescent patches or plaques distributing over the extremities or trunk, without lymphadenopathy or other systemic abnormalities. Microscopically, the lesions were located intradermally and/or subcutaneously. CRDD was characterized by the presence of S-100 positive histiocytic cells exhibiting emperipolesis, accompanying with infiltration of mixed inflammatory cells. Fibrosis, somewhere in vague storiform pattern due to stromal responses, with distribution of individual neutrophil microabscess was seen in cases with a long course of illness. Dilated vascular spaces in dermis containing numerous large typical histiocytes were seen in 2 cases.</p><p><b>CONCLUSIONS</b>CRDD is a benign, persistent proliferative disease of histiocytes. Systemic involvement is rare, outcome favorable. It should be differentiated from other types of histiocytosis, dermatofibrosarcoma protuberans, xanthoma and lymphoproliferative disorders. Immunohistochemical staining for S-100 protein and CD68 is helpful in making a correct diagnosis.</p>

A clinicopathological study of perianal Paget's disease associated with internal rectal adenocarcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features and the immunohistochemical phenotype of perianal Paget's disease (PPD) associated with internal anorectal adenocarcinoma, with emphasis on the histogenesis of Paget's cells.</p><p><b>METHODS</b>The clinical and pathologic features of three cases of PPD with rectal adenocarcinoma were investigated. Periodic-acid-Schiff (PAS), alcian-blue and mucicarmine staining with and without diastase digestion were performed. The immunohistochemical study was performed on selected sections by a panel of antibodies including carcinoembryonic antigen (CEA), CK7, CK8, CK10/13, CK20 and gross cystic disease fluid protein 15 (GCDFP15).</p><p><b>RESULTS</b>All three cases occurred in middle to old age male patients complaining of anal bleeding. Digital physical examination revealed ulcerated or cauliflower-like masses in the anus just distal to the dentate line. Perianal skin erythematous patches were found in two cases, and small discrete granules in one case. Histologically, the anorectal neoplasm was either a moderately or poorly differentiated adenocarcinoma. Two types of Paget's cells were noted, namely the classical type characterized by a polygonal shape with vesicular nuclei and abundant pale cytoplasm, and the signet ring type characterized by eccentrically displaced nucleus. Both the rectal adenocarcinoma cells and Paget's cells showed strong positivity for PAS, AB and mucicarmine, which were resistant to the diastase digestion. Immunohistochemically, they were both positive for CEA, CK7, CK8 and CK20, but negative for CK10/13 and GCDFP15.</p><p><b>CONCLUSIONS</b>The CK20(+)-GCDFP15(-) type Paget's cells in PPD were derived from the direct intraepithelial Pagetoid spread of anorectal adenocarcinomas. PPD was more frequently associated with internal carcinomas than any other type of extramammary Paget's disease. It is recommended that clinicians should carefully examine the anus or rectum in the presence of PPD to ascertain if it is associated with an internal carcinoma.</p>

Metastatic cystic squamous cell carcinoma in the neck mistaken as primary branchial cleft carcinoma: a report of 4 cases / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To raise the vigilance not to believe easily the diagnosis of a primary branchial cleft carcinoma.</p><p><b>METHODS</b>Four cases of cystic metastatic squamous cell carcinoma in the neck misdiagnosed as branchiogenic carcinoma from 1993 to 2002 in our hospital were analyzed retrospectively.</p><p><b>RESULTS</b>The primary sites of these 4 cases were later discovered, 2 in the aryepiglottic fold, 1 in faucial tonsil and 1 in the skin of the head, respectively. The discovery of the primary sites ranged from the day of initial surgery to 41 months.</p><p><b>CONCLUSION</b>None of the cases reviewed in this study was a branchiogenic carcinoma. Therefore, the diagnosis of a primary branchial cleft carcinoma requires the fulfillment of strict criteria both clinically and pathologically.</p>