Computed tomography features of acinar cell carcinoma of the pancreas.

PURPOSE: To report the computed tomography (CT) features of pancreatic acinar cell carcinoma (ACC) and identify CT features that may help discriminate between pancreatic ACC and pancreatic ductal adenocarcinoma (PDA). MATERIALS AND METHODS: The CT examinations of 20 patients (13 men, 7 women; mean age, 66.5±10.7 [SD] years; range: 51-88 years) with 20 histopathologically proven pancreatic ACC were reviewed. CT images were analyzed qualitatively and quantitatively and compared to those obtained in 20 patients with PDA. Comparisons were performed using univariate analysis with a conditional logistic regression model. RESULTS: Pancreatic ACC presented as an enhancing (20/20; 100%), oval (15/20; 75%), well-delineated (14/20; 70%) and purely solid (13/20; 65%) pancreatic mass with a mean diameter of 52.6±28.0 (SD) mm (range: 24-120mm) in association with visible lymph nodes (14/20; 70%). At univariate analysis, well-defined margins (Odds ratio [OR], 7.00; P=0.005), nondilated bile ducts (OR, 9.00; P=0.007), visible lymph nodes (OR, 4.33; P=0.028) and adjacent organ involvement (OR, 5.67; P=0.02) were the most discriminating CT features to differentiate pancreatic ACC from PDA. When present, lymph nodes were larger in patients with pancreatic ACC (14±4.8 [SD]; range: 7-25mm) than in those with PDA (8.8±4.1 [SD]; range: 5-15mm) (P=0.039). CONCLUSION: On CT, pancreatic ACC presents as an enhancing, predominantly oval and purely solid pancreatic mass that most frequently present with no bile duct dilatation, no visible lymph nodes, no adjacent organ involvement and larger visible lymph nodes compared to PDA.

MR imaging features of pancreatic acinar cell carcinoma.

PURPOSE: This study aimed to report the magnetic resonance imaging (MRI) features of acinar cell carcinoma (ACC) of the pancreas including diffusion-weighted MRI findings. MATERIALS AND METHODS: The MRI examinations of five patients (3 men, 2 women; median age, 61years) with histopathologically proven ACC of the pancreas were retrospectively reviewed. MR images were analyzed qualitatively (location, shape, homogeneity, signal intensity, vascular involvement and extrapancreatic extent of ACC) and quantitatively (tumor size, apparent diffusion coefficient [ADC] and normalized ADC of ACC). RESULTS: All ACC were visible on MRI, presenting as an oval pancreatic mass (5/5; 100%), with moderate and heterogeneous enhancement (5/5; 100%), with a median transverse diameter of 43mm (Q1, 35; Q3, 82mm; range: 30-91mm). Tumor capsule was visible in 4/5 ACC (80%) and Wirsung duct enlargement in 2/5 ACC (40%). On diffusion-weighted MRI, all ACC (5/5; 100%) were hyperintense on the 3 b value images. Median ADC value of ACC was 1.061×10-3mm2/s (Q1, 0.870×10-3mm2/s; Q3, 1.138×10-3mm2/s; range: 0.834-1.195×10-3mm2/s). Median normalized ADC ratio of ACC was 1.127 (Q1, 1.071; Q3, 1.237; range: 1.054-1.244). CONCLUSIONS: On MRI, ACC of the pancreas presents as a large, oval pancreatic mass with moderate and heterogeneous enhancement after intravenous administration of a gadolinium chelate, with restricted diffusion and a median ADC value of 1.061×10-3mm2/s on diffusion-weighted MRI. Further studies however are needed to confirm our findings obtained in a limited number of patients.

Anaplastic Kaposi's sarcoma: 5 cases of a rare and aggressive type of Kaposi's sarcoma.

BACKGROUND: Anaplastic Kaposi's sarcoma (KS) is a rare form of KS characterized clinically by the development of a tumour mass with unusual local aggressiveness and histologically by a specific architecture and cytological morphology. A very small number of limited series in endemic countries have established characteristics common to these anaplastic forms of KS. We present five patients with an anaplastic form in a context of KS ongoing for several years in a non-endemic country. MATERIALS AND METHODS: We collected 5 cases of anaplastic KS followed in our department over a period of 20years. We describe the main developmental, clinical, virological and histological features. RESULTS: The cases involved 4 men and 1 woman whose mean age at diagnosis of anaplastic KD was 70years, with an average time of 25years between initial diagnosis of KD and anaplastic transformation. Our patients were all treated with chemotherapy and/or radiotherapy (RT) prior to diagnosis of anaplastic transformation. All patients had a tumour mass of the lower limbs developing in classically indolent KS with associated chronic lymphoedema. Progression was very aggressive locally with deep invasion of the soft tissues as well as osteoarticular involvement, without visceral dissemination. At present, three patients are dead, one patient is showing partial response, and one patient is in locoregional progression. Diagnosis of the disease was based on histopathological findings. The tumour cells were undifferentiated, pseudo-cohesive, and chiefly organized in sheets. The mitotic count was high (27 mitoses per 10 fields at high magnification). Necrosis was constant. DISCUSSION: To our knowledge, this is the first series describing anaplastic Kaposi's sarcoma in a non-endemic country. The severity of the prognosis, despite the absence of visceral dissemination, is related to the local aggressiveness of anaplastic KS and to its resistance to radiotherapy and chemotherapy, with amputation being required in certain cases.

Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016

Tumor budding is a well-established independent prognostic factor in colorectal cancer but a standardized method for its assessment has been lacking. The primary aim of the International Tumor Budding Consensus Conference (ITBCC) was to reach agreement on an international, evidence-based standardized scoring system for tumor budding in colorectal cancer. The ITBCC included nine sessions with presentations, a pre-meeting survey and an e-book covering the key publications on tumor budding in colorectal cancer. The 'Grading of Recommendation Assessment, Development and Evaluation' method was used to determine the strength of recommendations and quality of evidence. The following 10 statements achieved consensus: tumor budding is defined as a single tumor cell or a cell cluster consisting of four tumor cells or less (22/22, 100%). Tumor budding is an independent predictor of lymph node metastases in pT1 colorectal cancer (23/23, 100%). Tumor budding is an independent predictor of survival in stage II colorectal cancer (23/23, 100%). Tumor budding should be taken into account along with other clinicopathological features in a multidisciplinary setting (23/23, 100%). Tumor budding is counted on H&E (19/22, 86%). Intratumoral budding exists in colorectal cancer and has been shown to be related to lymph node metastasis (22/22, 100%). Tumor budding is assessed in one hotspot (in a field measuring 0.785 mm2) at the invasive front (22/22, 100%). A three-tier system should be used along with the budding count in order to facilitate risk stratification in colorectal cancer (23/23, 100%). Tumor budding and tumor grade are not the same (23/23, 100%). Tumor budding should be included in guidelines/protocols for colorectal cancer reporting (23/23, 100%). Members of the ITBCC were able to reach strong consensus on a single international, evidence-based method for tumor budding assessment and reporting. It is proposed that this method be incorporated into colorectal cancer guidelines/protocols and staging systems.

Self-assembling peptide matrix for the prevention of esophageal stricture after endoscopic resection: a randomized controlled trial in a porcine model.

Esophageal stricture formation after extensive endoscopic resection remains a major limitation of endoscopic therapy for early esophageal neoplasia. This study assessed a recently developed self-assembling peptide (SAP) matrix as a wound dressing after endoscopic resection for the prevention of esophageal stricture. Ten pigs were randomly assigned to the SAP or the control group after undergoing a 5-cm-long circumferential endoscopic submucosal dissection of the lower esophagus. Esophageal diameter on endoscopy and esophagogram, weight variation, and histological measurements of fibrosis, granulation tissue, and neoepithelium were assessed in each animal. The rate of esophageal stricture at day 14 was 40% in the SAP-treated group versus 100% in the control group (P = 0.2). Median interquartile range (IQR) esophageal diameter at day 14 was 8 mm (2.5-9) in the SAP-treated group versus 4 mm (3-4) in the control group (P = 0.13). The median (IQR) stricture indexes on esophagograms at day 14 were 0.32 (0.14-0.48) and 0.26 (0.14-0.33) in the SAP-treated and control groups, respectively (P = 0.42). Median (IQR) weight variation during the study was +0.2 (-7.4; +1.8) and -3.8 (-5.4; +0.6) in the SAP-treated and control groups, respectively (P = 0.9). Fibrosis, granulation tissue, and neoepithelium were not significantly different between the groups. The application of SAP matrix on esophageal wounds after a circumferential endoscopic submucosal dissection delayed the onset of esophageal stricture in a porcine model.

Uveal melanoma hepatic metastases mutation spectrum analysis using targeted next-generation sequencing of 400 cancer genes.

AIMS: Uveal melanoma (UM) is the most common malignant tumour of the eye. Diagnosis often occurs late in the course of disease, and prognosis is generally poor. Recently, recurrent somatic mutations were described, unravelling additional specific altered pathways in UM. Targeted next-generation sequencing (NGS) can now be applied to an accurate and fast identification of somatic mutations in cancer. The aim of the present study was to characterise the mutation pattern of five UM hepatic metastases with well-defined clinical and pathological features. METHODS: We analysed the UM mutation spectrum using targeted NGS on 409 cancer genes. RESULTS: Four previous reported genes were found to be recurrently mutated. All tumours presented mutually exclusive GNA11 or GNAQ missense mutations. BAP1 loss-of-function mutations were found in three UMs. SF3B1 missense mutations were found in the two UMs with no BAP1 mutations. We then searched for additional mutation targets. We identified the Arg505Cys mutation in the tumour suppressor FBXW7. The same mutation was previously described in different cancer types, and FBXW7 was recently reported to be mutated in UM exomes. CONCLUSIONS: Further studies are required to confirm FBXW7 implication in UM tumorigenesis. Elucidating the molecular mechanisms underlying UM tumorigenesis holds the promise for novel and effective targeted UM therapies.

A novel LKB1 isoform enhances AMPK metabolic activity and displays oncogenic properties.

The LKB1 tumor suppressor gene encodes a master kinase that coordinates the regulation of energetic metabolism and cell polarity. We now report the identification of a novel isoform of LKB1 (named ΔN-LKB1) that is generated through alternative transcription and internal initiation of translation of the LKB1 mRNA. The ΔN-LKB1 protein lacks the N-terminal region and a portion of the kinase domain. Although ΔN-LKB1 is catalytically inactive, it potentiates the stimulating effect of LKB1 on the AMP-activated protein kinase (AMPK) metabolic sensor through a direct interaction with the regulatory autoinhibitory domain of AMPK. In contrast, ΔN-LKB1 negatively interferes with the LKB1 polarizing activity. Finally, combining in vitro and in vivo approaches, we showed that ΔN-LKB1 has an intrinsic oncogenic property. ΔN-LKB1 is expressed solely in the lung cancer cell line, NCI-H460. Silencing of ΔN-LKB1 decreased the survival of NCI-H460 cells and inhibited their tumorigenicity when engrafted in nude mice. In conclusion, we have identified a novel LKB1 isoform that enhances the LKB1-controlled AMPK metabolic activity but inhibits LKB1-induced polarizing activity. Both the LKB1 tumor suppressor gene and the oncogene ΔN-LKB1 are expressed from the same locus and this may account for some of the paradoxical effects of LKB1 during tumorigenesis.

Endoscopic findings in Cowden syndrome.

Cowden syndrome is characterized by diffuse hamartomas involving the whole digestive tract. The gastrointestinal expression of the disease is inconstant, but hamartomatous polyposes are frequent. In a multicenter study we studied the endoscopic appearance of Cowden syndrome--as defined by fulfillment of international consortium criteria--in 10 patients. In 6 of the 10 patients the connection with Cowden syndrome was made retrospectively on the basis of the gastrointestinal endoscopic findings. All patients had upper and lower gastrointestinal tract involvement. Mean follow-up duration was 9.5 years (range: 2-26 years). Mean age was 37 years (range: 18-56 years). Polyps of the upper gastrointestinal tract were hamartomas, ganglioneuromas, lipomas, and adenomas. Diffuse glycogenic acanthosis was reported in nine patients. Besides the classical hamartomatous polyposis, diffuse macroscopic esophageal acanthosis and microscopic ganglioneuromatosis are other key findings associated with a diagnosis of Cowden syndrome. Physicians should be aware of these characteristics in order to diagnose Cowden syndrome early.

Esophageal lichen planus: a series of eight cases including a patient with esophageal verrucous carcinoma. A case series.

Esophageal lichen planus is a rare condition. Its risk of malignant transformation is unknown. We report a series of eight patients with esophageal lichen planus referred to our unit between 1990 and 2005. Clinical, endoscopic, radiological and histological data of these patients were retrospectively reviewed. Seven patients were women. All patients had oral lichen planus. Endoscopic lesions were located in the upper third of the esophagus in seven patients and in the mid third in two patients. Five patients had esophageal stricture. Seven patients had peeling, friable esophageal mucosa. Histological examination of esophageal biopsies found characteristic features of lichen planus in two patients and nonspecific changes in five patients. All patients received corticosteroids. Patients with stricture underwent esophageal dilation. Esophageal perforation after dilation occurred in one patient. Corticosteroids improved dysphagia in all patients; steroid dependence occurred in two patients with stricture. One patient had an esophageal verrucous carcinoma, which was treated with radiotherapy and chemotherapy. Upper endoscopy should be performed in patients with mucosal lichen planus presenting with dysphagia to assess esophageal involvement. Esophageal strictures are frequent and require dilation. Corticosteroids are the first-line treatment, but steroid dependence may occur. Cancer can arise on esophageal lichen planus and justifies endoscopic follow-up.

Osteomalacia revealing celiac disease and primary biliary cirrhosis-related Fanconi syndrome in a patient with systemic sclerosis.

Systemic sclerosis (SSc) may affect the gastrointestinal tract and cause very rarely malabsorption syndrome related to bacterial overgrowth. Malabsorption syndrome may be responsible for weight loss, diarrhea, osteomalacia, and iron and vitamins deficiency. We report the case of a SSc patient who developed osteomalacia caused by the combination of two exceptional conditions in the setting of SSc: celiac disease (CD) and primary biliary cirrhosis (PBC)-related Fanconi syndrome. Oral prednisone with angiotensin-converting enzyme inhibitors, was initiated because of active lesions of tubulitis, and led to the complete regression of bone pains, and by the improvement of renal function and regression of the features of proximal tubulopathy. Thus, in the presence of vitamin deficiencies in a patient with SSc, together with a search for malabsorption syndrome secondary to bacterial overgrowth, CD and/or PBC-associated Fanconi syndrome should be investigated.

Massive postoperative ascites following pancreatic cysts fenestration in a patient with von Hippel-Lindau disease.

Pancreatic lesions in von Hippel Lindau disease (VHLD) are frequent and mainly consist of cystic lesions, which should not be resected because of their benign evolution. Solid lesions, mostly pancreatic endocrine tumors (PET), are rare and usually occur in combination with cystic lesions. We report a case of a patient with VHLD who underwent PET enucleation in a polycystic pancreas requiring fenestration of multiple adjacent cysts, to ensure complete resection with free resection margins. The postoperative course was complicated by massive ascitic fluid effusion, probably related to pancreatic-cyst fenestration. Although this complication is well-known after liver-cyst fenestration, it has not been reported after pancreatic-cyst fenestration. This observation emphasizes that morbidity from surrounding pancreatic polycystic disease should not be underestimated in pancreatic surgery for VHLD.

Endoscopic resection of a large Brunner's gland hamartoma.

Brunner's Gland Hamartoma (BGH) is a benign tumor of the duodenum that can lead to gastrointestinal bleeding and intestinal obstruction. Endoscopic resection has seldom been reported. We describe the case of a duodenal obstruction caused by a large BGH (6 cm x 4 cm). We report a 57-year-old woman hospitalized for tarry stools, weight loss and anorexia. Endoscopy revealed a large BGH (6 cm x 4 cm). Endoscopic ultrasound (EUS) revealed a submucosal duodenal tumor. In this paper, we report a case of large hyperplasia of BGH, successfully treated by endoscopic technique.