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.

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.

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.

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.

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.

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.

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.

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.

Spiradenocarcinoma, cylindrocarcinoma and spiradenocylindrocarcinoma: a clinicopathological study of nine cases.

AIMS: To elucidate diagnostic criteria for spiradenocarcinoma, cylindrocarcinoma and spiradenocylindrocarcinoma, and to emphasize correlations between clinical behaviour and variable morphological patterns. METHODS AND RESULTS: We investigated the clinicopathological and immunophenotypic features of nine cases. There were five men and four women, with ages ranging from 58 years to 82 years. The tumour size varied from 10 mm to 50 mm. The head and neck were most commonly involved. Three cases of spiradenocarcinoma and three cases of cylindrocarcinoma showed a salivary gland-type basal cell adenocarcinoma-like pattern, low-grade (BCAC-LG) and/or high grade (BCAC-HG). The remaining three cases of spiradenocarcinoma showed adenocarcinoma in situ, with invasive adenocarcinoma being seen in one of these cases. PAS staining revealed loss of the PAS-positive hyaline sheath in malignant zones of cylindrocarcinoma. p53 staining was variably positive in the malignant components of all cases. Follow-up was available for all patients, ranging from 5 months to 107 months. Two patients died of disease, one experienced recurrence, and one died of an unrelated cause. CONCLUSIONS: Patients with BCAC-LG have a better prognosis. BCAC-HG is more likely to be found in cylindrocarcinoma, and its clinical behaviour seems to be more aggressive. Close follow-up for early detection of recurrence and metastases is strongly recommended.

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.

[Cutaneous regressing/regressed malignant melanoma: a clinicopathologic analysis of 8 cases].

OBJECTIVE: To study the clinicopathologic features and differential diagnosis of cutaneous regressing/regressed melanoma. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Influence of obesity on clinicopathological characteristics in patients with clinically localized prostate cancer].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Basal cell carcinoma of the scrotum: clinicopathologic analysis of 10 cases.

BACKGROUND: Basal cell carcinoma (BCC) located on the scrotum is rare. OBJECTIVE: To analyze clinical and pathologic features, discuss therapeutic strategies, and identify prognostic factors of scrotal BCC in Chinese patients. MATERIALS AND METHODS: Between 2000 and 2010, 10 patients with scrotal BCC were diagnosed and treated at our institution. A review was performed using the clinical records and dermatopathologic slides of these patients. RESULTS: The median patient age was 70. Skin lesions presented as red nodules and brownish plaques. All patients were treated using wide excision without adjuvant therapy. After an average follow-up of 47 months, eight patients were in good health without any relapse. One patient developed left inguinal lymph node metastasis at 21 months that was successfully treated using bilateral inguinal lymphadenectomy. One patient developed bilateral pulmonary metastasis at 48 months and was palliatively treated with chemotherapy. The clinical and histopathologic risk factors predisposing to metastasis were large primary neoplasms; a long period of misdiagnosis; and infiltrating, morpheaform, spiky, irregular outline pathologic patterns. CONCLUSIONS: BCC of the scrotum is rare. It can metastasize after a long period of initial therapy. Long-term surveillance including a complete metastatic examination is recommended for these patients.

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.

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.

[Cutaneous anaplastic large cell lymphoma: clinicopathologic, immunohistochemical and prognostic study of 44 cases].

OBJECTIVE: To study the clinicopathologic features, immunophenotype and prognosis of primary cutaneous anaplastic large cell lymphoma (CALCL). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Neutrophil/eosinophil-rich type of primary cutaneous anaplastic large cell lymphoma: a clinicopathological, immunophenotypic and molecular study of nine cases.

AIMS: To elucidate the clinicopathological, immunophenotypic and molecular features of neutrophil/eosinophil-rich primary cutaneous anaplastic large cell lymphoma (CALCL), and to emphasize the cutaneous manifestations, differential diagnosis and prognosis of this peculiar entity. METHODS AND RESULTS: We described the clinical presentations, histopathology, immunophenotype, molecular features and follow-up courses of nine neutrophil/eosinophil-rich CALCL cases. Various clinical lesions including multiple nodules, plaques and solitary exophytic masses with or without ulceration or crusting were noted in nine patients. Two patients died of disease progression, with one developing multiple lymph node involvement. Histologically, cohesive sheets or small clusters of neoplastic cells were admixed with large numbers of neutrophils and/or eosinophils, representing 10-40% of cells per high-power field. All nine cases showed T-cell phenotypes. The frequency of rearranged TCRB, TCRG and TCRD genes in six cases with available paraffin-embedded tissue was 100%, 83% and 33%, respectively. CONCLUSIONS: Neutrophil/eosinophil-rich CALCL should be differentiated from various infectious and non-infectious diseases, especially from non-neoplastic cutaneous CD30+ infiltrates rich in neutrophils and eosinophils. Precise correlation of clinical presentation, morphological features, phenotypic and molecular analysis can help to establish the correct diagnosis. Whether this rare variant has a significantly different prognosis from classical CALCL needs further investigation.