Impact of expert pathology review in skin adnexal carcinoma diagnosis: Analysis of 2573 patients from the French CARADERM network.

PURPOSE: To prospectively assess the impact of expert pathological review of skin adnexal carcinoma diagnosis in France. METHODS: From 2014 to 2019, 2573 samples from patients with newly diagnosed or suspected skin adnexal carcinomas were reviewed prospectively by expert pathologists through the national CARADERM (CAncers RAres DERMatologiques) network. Changes in diagnosis between referral and expert review were analysed regarding their potential impact on patient care or prognosis. RESULTS: The samples comprised 2205 newly diagnosed adnexal carcinomas, 129 benign adnexal tumours, 136 basal cell carcinomas, 74 squamous cell carcinomas, six cutaneous metastases and 13 other malignancies. There were 930 (42%) sweat gland carcinomas, of which porocarcinoma (261; 11.8%), microcystic adnexal carcinoma (125; 5.7%) and hidradenocarcinoma (109; 4.9%) were the most frequent subtypes; 778 (35%) hair follicle carcinomas, 238 (11%) sebaceous carcinomas and 212 (10%) extramammary Paget diseases/mammary-like anogenital gland adenocarcinomas. A diagnostic change between referral and expert review occurred in 503 (21.3%) patients, significantly higher for cases sent with a provisional diagnosis seeking an expert second opinion (45.7%) than for cases sent with a formal diagnosis (2.8%) (p < .0001). Sweat gland carcinomas were more prone to diagnostic discrepancies than other tumours (p < .0001), including 1.8% of patients with sweat gland carcinoma subtype misclassification with predicted clinical impact. Changes between benign and malignant conditions occurred in 117 samples (5% of patients). CONCLUSION: The study provides a unique description of the distribution of skin adnexal carcinomas and highlights the importance of expert review for these rare cancers. Optimal clinical management was impacted in a significant proportion of patients.

Prognostic value of microRNA expression pattern in upper tract urothelial carcinoma.

OBJECTIVE: To examine the microRNA (miRNA) expression pattern in tumour samples from patients with progressing and non-progressing upper tract urothelial carcinoma (UTUC) in order to identify putative miRNAs that may be used as prognostic markers. PATIENTS AND METHODS: We conducted a multicentre, retrospective study of formalin-fixed paraffin-embedded tissue samples from 150 patients with UTUC who had undergone radical nephroureterectomy. Global miRNA expression patterns were analysed in 18 selected samples from patients with UTUC using TaqMan arrays. The differential expression of five key miRNAs was validated by quantitative polymerase chain reaction in an independent cohort of 132 samples from patients with UTUC. Models to predict tumour progression and cancer-specific survival that included miRNA expression patterns were developed by Cox regression analysis. RESULTS: Twenty-six miRNAs were found to be aberrantly expressed between samples from patients with progressing and non-progressing UTUC and five of these were selected for subsequent studies. The regression analysis identified tumour stage and miR-31 and miR-149 expression as independently associated with tumour progression and tumour stage and miR-149 expression as independently associated with cancer-specific survival. The risk scores derived from these miRNA models were able to discriminate two groups with a highly significantly different probability of tumour progression (hazard ratio [HR] 4.78; P < 0.001) and death (HR 276; P = 0.004). CONCLUSIONS: There is a differential miRNA expression pattern between patients with progressing and non-progressing UTUC. The identification of new miRNAs associated with a high probability of tumour recurrence and cancer-specific survival in patients with UTUC and their combination in a robust, easy-to-use and reliable algorithm may help tailor treatment and surveillance strategies in these patients.

Assessment of human epidermal growth factor receptor 2 status in urothelial carcinoma of the upper urinary tract: a study using dual-color in situ hybridization and immunohistochemistry.

AIM: Upper urinary tract urothelial carcinoma (UUTUC) is an uncommon neoplasm frequently discovered at a high-stage disease. The prognosis of disseminated UUTUCs is poor despite the use of platinum-based chemotherapy. The aim of the study was to evaluate HER2 overexpression and amplification in a series of 83 UUTUCs. MATERIALS AND METHODS: All tumors were formalin fixed. TNM stage, grade, lymphovascular invasion, surgical margins, morphologic variants were reviewed by 2 pathologists. All tumors were immunostained with anti-HER2 antibody. HER2 gene amplification was determined by dual-color in situ hybridization. Gene amplification was defined by an HER2/CEN 17 ratio >2.2. RESULTS: HER2 immunostaining was observed in 33/83 tumors. Twelve cases were 2+ score and 2 cases were 3+ score. HER2 in situ hybridization was evaluable in 75/83 cases. Amplification was observed in 6 (7%) cases. All amplified tumors were of high grade and 4/6 were stage pT3. A strong correlation between HER2 overexpression and amplification was noted (P<0.0001). HER2 overexpression and amplification were correlated with the pN+ stage but not with specific survival or recurrence. CONCLUSIONS: These results suggest that HER2 amplification is a rare event in UUTUC but may be of interest for targeted therapy in selected high-grade and high-stage tumors.

Small cell carcinoma of the upper urinary tract (UUT-SCC): report of a rare entity and systematic review of the literature.

BACKGROUND: Primary small cell carcinoma of the upper urinary tract (UUT-SCC) is an extremely uncommon disease. The current knowledge of these rare tumors is mainly based on case reports or small series. METHODS: We reported two cases and performed a systematic literature search from 1970 to 2010 for articles on UUT-SCC. Overall, 40 patients with UUT-SCC were reviewed, a database was generated to analyze clinical characteristics, pathological features and therapy outcomes and to attempt in identifying prognostic factors. RESULTS: For the 39 cases with available data, median age was 66.5 years and male-female ratio was 2:1. An Asian ethnic background was more common (59%). Surgery was the standard treatment given to all patients. In 67% of cases, SCC coexisted with another malignant component, including urothelial carcinoma in 62% of patients. Overall median survival was 15 months and the 1-, 2- and 3-year survival rates were 58.4%, 38.1% and 23.8%, respectively. Of all cases, 53.8% developed detectable metastasis in a median delay of 13 months. Pathological stage was the only significant prognostic factor found (p=0.01). Patients who received adjuvant chemotherapy seem to have a higher median survival comparatively to those who did not receive chemotherapy but this was not statistically significant (24 vs. 12 months, p=0.56). CONCLUSIONS: UUT-SCC is an extremely rare tumor characterized by an aggressive clinical course. Local or distant metastases are frequent and survival is poor. Pathological stage appeared to be a prognostic factor for overall survival.

[Congenital pulmonary alveolar proteinosis related to a surfactant protein B deficiency: report of two cases]. / Protéinose alvéolaire pulmonaire congénitale en rapport avec un déficit en protéine B du surfactant : à propos de deux observations.

Congenital pulmonary alveolar proteinosis is an uncommon affection, distinct from adult's alveolar proteinosis by its clinical, pathological, etiological and evolutive characteristics. We report two cases of congenital alveolar proteinosis related to a surfactant protein B deficiency. Clinical presentations were similar: the two children were full-term newborns and had swiftly developed respiratory distress. Chest radiography demonstrated bilateral alveolar syndrome. Echocardiography was normal. There was no sign of infection. The two children died respectively at three weeks and two months of life. Lung biopsy showed lesions of alveolar proteinosis in the two cases. Both children were homozygotes for the 121ins2 mutation of the SFTPB gene. Diagnosis of surfactant protein B deficiency must be suspected in congenital alveolar proteinosis. It can be confirmed by the absence of detection of the surfactant B protein by immunohistochemistry on fixed and paraffin-embedded lung tissue or by western blot on bronchoalveolar fluid and by the absence of mRNA by RT-PCR. We report the value of molecular diagnosis for genetic counseling and the possibility of early prenatal diagnosis by trophoblast biopsy.