Alexandre Rouquette

Progressive Upregulation of PD-1 in Primary and Metastatic Melanomas Associated with Blunted TCR Signaling in Infiltrating T Lymphocytes

Programmed death-1 (PD-1) is involved in T-cell tolerance to self-antigens. For some cancers, it has been suggested that the expression of a ligand of PD-1, namely PD-L1, could contribute to tumor escape from immune destruction. Nevertheless, the relationship between PD-1 expression on tumor-infiltrating T lymphocytes (TILs), disease stage, and TIL responsiveness is still poorly documented. In this study, we show that freshly isolated CD4(+) and CD8(+) TILs express substantial levels of PD-1 in primary melanomas. The expression of PD-1 was further increased at later stages in distant cutaneous metastases, especially on CD8(+) TILs. The expression of PD-1 ligands was frequent only in metastases, on both tumor cells and tumor-derived myeloid cells. TILs isolated from these cutaneous tumors are poorly reactive ex vivo, with blunted calcium response and IFN-γ production after TCR stimulation. Surprisingly, in distinct parts of a primary melanoma, either invasive or regressing, we show that TILs similarly express PD-1 and remain dysfunctional. The expressions of PD-1 and PD-L1 in metastatic melanoma lesions could be considered as witnesses of an unsuccessful anti-tumoral immune response, but the direct involvement of PD-1 in the severity of the disease, and the importance of TILs in tumor regression, remain to be established.

Sarcoidosis Lung Nodules in Colorectal Cancer Follow-Up: Sarcoidosis or Not?

OBJECTIVE Sarcoidosis is a multisystem chronic granulomatous disease found predominantly in the lungs and lymph nodes. Its pathologic hallmark is the presence of noncaseating granulomas. Sarcoidosis is a chronic inflammatory condition that may increase the risk of cancer, yet at the same time, cancer can be associated with a sarcoid-like reaction. METHODS It is difficult to distinguish between sarcoidosis and sarcoid-like reactions because their imaging characteristics are identical. We report on 3 cases of sarcoidosis or sarcoid-like reactions in patients with colorectal cancer and highlight the diagnosis process. RESULTS Systemic symptoms observed in patients with sarcoidosis commonly can be masked or mimicked by symptoms related to the malignancy. Moreover, it is important to distinguish between the 2 entities to give patients adequate therapy. CONCLUSION Our cases focused on the usefulness of histologic proof in patients with cancer with sarcoidosis.

Acinar cell carcinoma: a possible diagnosis in patients without intrapancreatic tumour

BACKGROUND Acinar cell carcinomas of the pancreas are rare neoplasms. Usually diagnosed at an advanced stage, in general they are large solid pancreatic tumours with an average size of more than 10 cm. AIMS AND RESULTS We report 3 cases of acinar cell carcinomas involving the peripancreatic lymph nodes, the liver hilum and the colon respectively, without clinical or pathological evidence of pancreatic tumours. These highly cellular neoplasms showed a predominantly acinar cell differentiation intermingled with a ductal component, with intracellular or extracellular mucin production by at least 25% of tumour cells. In addition, one case showed endocrine differentiation. Diffuse immunoreactivity for acinar enzymes trypsin and chymotrypsin was present in all cases. CONCLUSION The occurrence of acinar cell carcinomas outside the pancreas underlines the notion that acinar cell carcinomas may originate in extrapancreatic sites and probably develop from heterotopic or metaplastic pancreatic foci present along the biliary tract.

Resection of Late Pulmonary Metastases from Pancreatic Adenocarcinoma: Is Surgery an Option?

ABSTRACT Patients with recurrences from pancreas adenocarcinoma have a poor survival rate despite new chemotherapy treatment options. Recurrences are mainly hepatic metastases or peritoneal dissemination and surgical treatment is not recommended. Late and single metachronous pulmonary recurrences are uncommon and may mimic primary lung carcinoma. We report two patients with late and unique pulmonary metastasis from pancreatic cancer. These two patients underwent surgical resection; three and five years later, they did not experience recurrences. Cases called for a surgical approach in late and unique pulmonary metastases from pancreatic cancer, and paved the way for a prolonged chemotherapy free period.

Tumeurs du haut appareil urinaire et syndrome de Lynch : doit-on proposer un dépistage systématique ?

OBJECTIVE The data describing the urologic extracolonic cancers associated with Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) are variable. The aim of our study was to establish the frequency of mutations in mismatch repair (MMR) genes in patients with upper urinary tract transitional cell carcinoma (UUT-TCC) and to evaluate the clinical benefits of a systematic screening. METHODS Specimen blocks were obtained from 146 patients treated for UUT-TCC in our center. Clinicopathological characteristics and survival data of patients were collected (median follow-up = 42.5 months). Immunohistochemistry was performed by tissue microarray (TMA), in order to detect mutations in mismatch repair genes. Results obtained after TMA analysis were confirmed at a molecular level by microsatellite instability (MSI) analysis. RESULTS Mutations in mismatch repair genes were detected in seven patients (4.8%) at immunohistochemistry screening, and confirmed by MSI analysis for five of them (3.4%). Clinicopathological characteristics and survival data did not differ significantly in patients with instability compared with patients without. After a median follow-up of 42.5 months, none of them experienced a new HNPCC manifestation. CONCLUSION The frequency of mutations in mismatch repair genes in UUT-TCC was very low, with a good accuracy of immunohistochemistry. Systematic screening should not be proposed in daily practice.

A new device to expedite endoscopic submucosal dissection procedures: a randomized animal study of efficacy and safety (with videos)

Background and study aims: Endoscopic submucosal dissection (ESD) is a recognized method for the curative treatment of superficial neoplasia, but its use is limited by lengthy procedures and the lack of versatility of existing knives. We developed a prototype ESD device with the ability to work as a needle, hook, or “scythe.” This new device was compared to regular ESD knives in a randomized animal study. Patients and methods: Eight pigs underwent two gastric ESD procedures each, similar in size and difficulty, one with a regular ESD device and the other with the new device. The order and location of each ESD, as well as the performing operator, were randomized. Primary judgment criterion was safety of procedures. Overall and submucosal dissection procedure times were measured. Time-to-surface ratios were measured and estimated for ESDs larger than those performed. Histopathology of the resected tissue and remaining stomach was done after each experiment. Results: No complications were observed throughout the study and all resections were completed en-bloc and uneventfully. The submucosal extension of resections was similar with both the standard and the new devices. A comparison of time-consumption between groups did not show statistically significant differences, but a dramatic reduction of procedure duration was observed in some procedures with the new device; based on observed data, a potential time-saving of up to 66 % was anticipated, with a relatively short learning curve. Conclusions: This new versatile device proved to be as safe as regular ESD knives, and seems likely to help reduce the duration of the procedure.

Tumeurs du haut appareil urinaire et syndrome de Lynch : doit-on proposer un dépistage systématique ?Should we systematically Screen for Lynch syndrome in Patients with upper urinary tract carcinoma?

OBJECTIVE The data describing the urologic extracolonic cancers associated with Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) are variable. The aim of our study was to establish the frequency of mutations in mismatch repair (MMR) genes in patients with upper urinary tract transitional cell carcinoma (UUT-TCC) and to evaluate the clinical benefits of a systematic screening. METHODS Specimen blocks were obtained from 146 patients treated for UUT-TCC in our center. Clinicopathological characteristics and survival data of patients were collected (median follow-up = 42.5 months). Immunohistochemistry was performed by tissue microarray (TMA), in order to detect mutations in mismatch repair genes. Results obtained after TMA analysis were confirmed at a molecular level by microsatellite instability (MSI) analysis. RESULTS Mutations in mismatch repair genes were detected in seven patients (4.8%) at immunohistochemistry screening, and confirmed by MSI analysis for five of them (3.4%). Clinicopathological characteristics and survival data did not differ significantly in patients with instability compared with patients without. After a median follow-up of 42.5 months, none of them experienced a new HNPCC manifestation. CONCLUSION The frequency of mutations in mismatch repair genes in UUT-TCC was very low, with a good accuracy of immunohistochemistry. Systematic screening should not be proposed in daily practice.