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.

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.

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.

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.

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.

Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primary liver tumors with beta-catenin mutations.

The Wnt/beta-catenin signaling pathway is activated in many human hepatocellular carcinomas (HCC). We tried to identify the genes involved in carcinogenesis and progression of HCC with beta-catenin mutations. We used PCR-based subtractive hybridization to compare gene expression between malignant and benign components of a human HCC occurring in pre-existing adenoma activated for beta-catenin. Two of the genes identified belong to the Regenerating gene (REG) family. They encode the Regenerating islet-derived 3 alpha (REG3A/HIP/PAP/REG-III) and 1 alpha (REG1A) proteins, both involved in liver and pancreatic regeneration and proliferation. Using siRNA directed against beta-catenin, we demonstrated that REG3A is a target of beta-catenin signaling in Huh7 hepatoma cells. The upregulation of REG3A and REG1A expression is significantly correlated to the beta-catenin status in 42 HCC and 28 hepatoblastomas characterized for their beta-catenin status. Thus, we report strong evidence that both genes are downstream targets of the Wnt pathway during liver tumorigenesis.

[A pancreatic pseudocyst associated with three simultaneous hemorragic complications]. / Un pseudo-kyste pancréatique responsable de trois complications hémorragiques simultanées.

The onset of secondary hemorrhagic complications with the development of pancreatic pseudocysts is rare but has a high mortality rate. Management of the hemorrhagic complications of pancreatic pseudocysts is surgical despite the contribution of arterial embolization. We report the observation of a 59-year-old patient who had presented an episode of acute pancreatitis 1 month before consulting for abdominal pain associated with an episode of melena. The CT showed a pancreatic pseudocyst complicated by an intracystic tear, a splenic artery aneurysm in the Wirsung canal, and rupture of the spleen. These three lesions were treated simultaneously with left splenopancreatectomy starting with the splenic vessels. The simultaneous onset of three hemorrhagic complications of a pseudocyst is exceptional and has never been described to our knowledge.

PML nuclear bodies are general targets for inflammation and cell proliferation.

Acute promyelocytic leukemia is associated with a t(15;17) translocation that generates a fusion product between PML and the retinoic acid receptor alpha. Recently, PML was shown to concentrate within subnuclear domains, referred to as nuclear bodies, that are disorganized in acute promyelocytic leukemia cells. This observation provided the first evidence that alteration of a nuclear structure may play a role in human pathogenesis. In an attempt to clarify the role of PML and, more generally, of the associated nuclear bodies, we used immunohistochemistry to explore the expression of PML in normal, inflammatory, and neoplastic human tissues. With the exception of endothelial cells and macrophages that contain a high amount of PML protein, a weak speckled labeling pattern was observed in the nucleus of all cell types analyzed. By contrast to normal tissues, the level of PML expression was considerably enhanced in inflammatory tissues, predominantly around the mononuclear cell infiltrate, as well as during either normal or pathological proliferative states, in particular in tumoral pathology. Surprisingly, in most hepatocellular carcinoma, a cytoplasmic delocalization of PML was observed. Finally, the number of PML nuclear bodies increased up to twice their normal value as quiescent cultured cells were stimulated to grow upon serum addition. Altogether these results strongly suggest that the PML-associated nuclear bodies are implicated both in the inflammatory process and in cell growth control.

The acute promyelocytic leukemia PML-RAR alpha protein induces hepatic preneoplastic and neoplastic lesions in transgenic mice.

The PML-RAR alpha hybrid protein generated by the t(15;17) translocation in acute promyelocytic leukemia (APL) is thought to play a central role in the oncogenic process. However, analysis of the oncogenic activity of the fusion protein in tissue culture assays or in mice has been hampered by its apparent toxicity in multiple murine cells. To circumvent this problem, we generated an inducible line of transgenic mice, MT135, in which the expression of PML-RAR alpha is driven by the metallothionein promoter. After 5 days zinc stimulation, 27 out of 54 mice developed hepatic preneoplasia and neoplasia including foci of basophilic hepatocytes, dysplasia and carcinoma with a significantly higher incidence of lesions in females than in males. The rapid onset of liver pathologies was dependent on overexpression of the transgene since it was not detected in noninduced transgenic animals of the same age. The PML-RAR alpha protein was always present in altered tissues at much higher levels than in the surrounding normal liver tissues. In addition, overexpression of PML-RAR alpha resulted in a strong proliferative response in the hepatocytes. We conclude that overexpression of PML-RAR alpha deregulates cell proliferation and can induce tumorigenic changes in vivo.

Close correlation between beta-catenin gene alterations and nuclear accumulation of the protein in human hepatocellular carcinomas.

Several lines of evidence indicate that beta-catenin acquires oncogenic activity when its intracellular concentration increases as a result of either mutation in the beta-catenin gene itself or inactivation of the adenomatous polyposis coli (APC) gene. In an attempt to elucidate the molecular mechanisms underlying hepatocellular carcinogenesis, we have studied the frequency of beta-catenin gene alterations in exon 3, a region known to represent a mutation hot spot, and its inappropriate protein expression by immunohistochemistry in 73 hepatocellular carcinomas (HCCs). The results were correlated with different clinical and pathological data, particularly with the presence or not of an associated cirrhosis. Fourteen (19%) HCCs showed beta-catenin gene alterations with missense mutations in nine cases and interstitial deletions in five cases. These genetic alterations were present in both cirrhotic and non-cirrhotic groups. By contrast, we did not find any beta-catenin gene alterations in the nine fibromellar carcinomas we examined. Nuclear accumulation of the protein was observed in 18 of them (25%). Remarkably, these included ten of the 14 tumors harboring somatic mutations in the beta-catenin gene (P < 0.001). Our results indicate that accumulation of beta-catenin resulting from genetic mutations is a frequent event in non-fibrolamellar type hepatocellular carcinoma. The close association between increased beta-catenin protein stability and mutation indicates that immunohistochemistry may be a powerful method for the detection of the mutated protein in future clinical practice.

Distinct chromosomal abnormality pattern in primary liver cancer of non-B, non-C patients.

To discriminate among the chromosomal abnormalities associated with the etiology of hepatocellular carcinoma (HCC), we performed a comparative genomic hybridization (CGH) analysis on 34 HCCs resected on non-cirrhotic livers from patients serologically negative for both hepatitis B (HBV) and C (HCV) viruses. The results were compared to those of a previous analysis of 50 HCCs selected on the basis of their positivity for HBV infection. The majority of the abnormalities found in the HBV positive cases (losses of chromosome arms 1p, 8p, 6q, 13q and 14q and gains of 1q, 8q, 6p and 17q) were similarly detected in the virus negative specimens. In contrast, a significant decrease (40% on average) was observed for losses at 4q, 16q and 17p in non-viral HCC samples, suggesting that these abnormalities are tightly associated with HBV infection. Thus, in addition to a common pathway towards malignancy, a subset of alterations may preferentially contribute to virus-induced carcinogenesis. In a parallel CGH study of 10 fibrolamellar carcinomas, a rare subtype of HCC, we found in six out of the seven informative cases, gains of chromosome arm 1q. This region, which is also preferentially amplified in non fibrolamellar tumors (58%), may contain an essential proto-oncogene commonly implicated in liver carcinogenesis.

Gene expression profiles of pancreatic cancer and stromal desmoplasia.

Gene expression studies were undertaken in normal pancreas and pancreatic adenocarcinomas to determine new candidate genes that can potentially be used as markers of the disease. The characteristic desmoplastic stromal reaction of pancreatic adenocarcinoma greatly hampers expression studies in this tumour type, and usually necessitates time-consuming tissue microdissection for enrichment of the tumour cell population. We show that fine needle aspiration of cancer provides a fast and efficient way of obtaining samples highly enriched in tumour cells with sufficient yields of RNA. Using Atlas cancer cDNA arrays with 588 cancer-related genes, we describe gene expression profiles of normal pancreas, bulk pancreatic tumour tissues and pancreatic tumour aspirates containing more than 95% tumour cells. Analysis of bulk tissue specimens revealed differentially expressed genes belonging predominantly to the stromal component of the tumour. This contrasted with the results obtained from tumour-cell enriched samples. Several genes already described in pancreatic cancer (caspase 8, TIMP1, CD9, IL-13) were also differentially expressed in our study. Furthermore, we found dysregulated expression of genes not previously associated with pancreatic adenocarcinoma, such as Rac 1, GLG1, NEDD5, RPL-13a, RPS9 and members of the Wnt5A gene family. In summary, we present a panel of genes newly identified in the pathogenesis of pancreatic adenocarcinoma and demonstrate that fine needle aspirates of the tumour mass are a convenient source of material for gene expression studies in tumours accompanied by desmoplastic reactions.