Vibration-controlled transient elastography for noninvasive evaluation of liver steatosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) refers to a large spectrum of liver disorders and is the most common cause of metabolic liver disease. The current gold standard for diagnosing NAFLD is liver biopsy, which can lead to severe complications. PURPOSE: Among the noninvasive diagnostic options, we chose to use a FibroScan and developed an algorithm applying the Voigt rheological model to assess the viscoelastic properties of the liver and evaluate its performance for the diagnosis of steatosis. METHODS: Twenty-two healthy volunteers and 20 patients with steatosis were included. For each subject, we used a modified FibroScan, whose data had been processed by our algorithm to separate the two viscoelastic components, stiffness µ, and viscosity η. The liver elasticity µFibroscan measured by the FibroScan was also recorded. Mann-Whitney tests and receiver operating characteristics (ROCs) curve analyses were performed to compare the parameters between the two groups, and Pearson's correlation coefficients were used to assess the correlations between the parameters. RESULTS: We found a good correlation between η and µFibroscan (r = 0.75), and poor correlations between µ and both η and µFibroscan (r = 0.33 and r = 0.03, respectively). We also showed that η and µFibroscan were higher in patients with steatosis compared to healthy volunteers, with area under the ROCs (AUROC) curve at 0.814 and 0.891, respectively. Conversely, µ was not different between the two groups (AUROC = 0.557). CONCLUSIONS: Our novel method successfully separated the two viscoelastic properties of the liver, of which the parameter η is a sensitive indicator for steatosis.

[A rare case of appendiceal mucinous tumor with myxoglobulosis]. / Un cas rare de tumeur mucineuse appendiculaire avec myxoglobulose.

Myxoglobulosis is a rare macroscopic form (<1%) of appendiceal mucocele characterized by opaque mucin beads. This entity, still unknown in clinical practice, can only be confirmed by anatomopathological examination. Many histological diagnoses that may impact the prognosis of patients should be discussed in the presence of myxoglobulosis, including neoplastic causes. We report the rare case of myxoglobulosis, whose histopathological management concluded the diagnosis of low-grade appendicular mucinous neoplasm.

Natural history of liver adenomatosis: A long-term observational study.

BACKGROUND & AIMS: Liver adenomatosis (LA) is characterized by the presence of at least 10 hepatocellular adenomas (HCAs), but the natural history of this rare liver disorder remains unclear. Thus, we aimed to reappraise the natural history and the risk of complications in a cohort of patients with at least 10 HCAs. METHODS: We analyzed the natural history of 40 patients with LA, excluding glycogen storage disorders, in a monocentric cohort. Pathological examination was performed, with immunostaining and molecular biology carried out on surgical specimens or liver biopsies. RESULTS: Forty patients (36 female) were included with a median follow-up of 10.6 (1.9-26.1) years. Six (15%) patients had familial LA, all with germline HNF1A mutations. Median age at diagnosis was 39 (9-55) years. Thirty-three (94%) women had a history of oral contraception, and 29 (81%) women had a pregnancy before LA diagnosis. Overall, thirty-seven (93%) patients underwent surgery at diagnosis. Classification of HCAs showed 46% of patients with HNF1A-mutated HCA, 31% with inflammatory HCA, 3% with sonic hedgehog HCA, 8% with unclassified HCA. Only 15% of the patients demonstrated a "mixed LA" with different HCA subtypes. Hepatic complications were identified in 7 patients: 1 patient (3%) died from recurrent hepatocellular carcinoma after liver transplantation; 6 (15%) had hemorrhages, of which 5 occurred at diagnosis, with 1 fatal case during pregnancy, and 2 occurred in male patients with familial LA. Four patients (10%) had repeated liver resections. Finally, 4 (10%) patients developed extrahepatic malignancies during follow-up. CONCLUSIONS: The diversity in HCA subtypes, as well as the occurrence of bleeding and malignant transformation during long-term follow-up, underline the heterogeneous nature of LA, justifying close and specific management. In patients with germline HNF1A mutation, familial LA occurred equally frequently in males and females, with a higher rate of bleeding in male patients. LAY SUMMARY: Liver adenomatosis is a rare disease characterized by the presence of 10 or more hepatocellular adenomas that may rarely be of genetic origin. Patients with liver adenomatosis have multiple adenomas of different subtypes, with a risk of bleeding and malignant transformation that justify a specific management and follow-up.

Revisiting the role of the pathological grading in pediatric adrenal cortical tumors: results from a national cohort study with pathological review.

The prognosis of malignant pediatric adrenocortical tumors is closely related to disease stage, which is used to guide perioperative treatment recommendations. However, current scoring systems are inadequate to distinguish between benign and malignant adrenocortical tumors. Robust microscopic prognostic features that could help determine perioperative therapy are also lacking. The aim of this national study was to review the prognostic value of the Wieneke scoring criteria and Ki67 labeling index in unselected pediatric adrenocortical tumors. Using strict definitions previously defined by expert pathologists, a Wieneke score was re-attributed to each tumor after an independent and centralized review. In addition, Ki67 proliferation index was performed and reviewed for each case. A total of 95 cases were selected; all were treated between 2000 and 2018 and had histopathologic material and sufficient outcome-related information available. Localized disease was found in 88% of patients. Among those with advanced disease, 6% had tumor extension into adjacent organs and 5% had metastases at diagnosis. Median follow-up was 5 years and 3 months. The 5-year PFS was 82%, 95% CI [73%-91%]. Tumor stage significantly correlated with PFS (p < 0.0001). Tumor weight up to 200 g, extra-adrenal extension and initial non-complete surgical resection were statistically associated with worse outcomes. No recurrences nor metastases occurred when the Ki67 index was < 15%. Up to two of the following five factors including tumor necrosis, adrenal capsular invasion, venous invasion, mitotic count > 15/20 high-power fields, and Ki67 index > 15%, significantly correlated with worse outcomes. We propose a pathological scoring system incorporating the Ki67 index as part of a two-step approach after disease staging to guide adjuvant treatment in pediatric adrenocortical tumors, especially after incomplete resection. These results should be validated in an independent cohort.

Ten-year experience of transjugular intrahepatic portosystemic shunt for noncirrhotic portal hypertension.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is considered to be well suited for the treatment of noncirrhotic portal hypertension (NCPHT) because of a usually severe portal hypertension (PHT) and a mild liver failure, but very less data are available. PATIENTS AND METHODS: Records of patients referred for TIPS between 2004 and 2015 for NCPHT were reviewed. No patient should have clinical or biological or histological features of cirrhosis. RESULTS: Twenty-five patients with a wide variety of histological lesions (sinusoidal dilatations, granulomatosis, regenerative nodular hyperplasia, obliterative portal venopathy, or subnormal liver) and a wide variety of associated diseases (thrombophilia, sarcoidosis, common variable immunodeficiency, scleroderma, Castleman's disease, early primitive biliary cirrhosis, congenital liver fibrosis, chemotherapy, purinethol intake, and congenital varices) were included. Two complications occurred during the procedure: one periprosthetic hematoma and the other misposition of a covered stent. During the first month, two other patients had an early thrombosis, another had induced encephalopathy, and one died of early rebleeding. Two of these complications occurred in patients with cavernoma. With a mean follow-up of 39 months, 10 patients experienced at least one episode of spontaneous encephalopathy, with three of these patients requiring a stent reduction. Five patients had a recurrence of their initial symptoms, and one had an asymptomatic hemodynamic dysfunction. CONCLUSION: TIPS is effective in NCPHT but can be technically difficult, especially in the case of cavernoma. Good liver function does not prevent the occurrence of long-term encephalopathy.

Diagnostic performance of contrast-enhanced CT-scan in sinusoidal obstruction syndrome induced by chemotherapy of colorectal liver metastases: Radio-pathological correlation.

PURPOSE: Sinusoidal obstruction syndrome (SOS) is a likely side effect of colorectal liver metastases (CRLM) chemotherapy. This study aimed to assess computed tomography scan (CT-scan) performance for SOS diagnosis for patients receiving neoadjuvant chemotherapy (NC) prior to CRLM surgery, comparing obtained results with pathological gold standard. METHODS: Preoperative CT-scans of 67 patients who had received a NC prior to liver resection for CRLM from 2011 to 2016 were retrospectively analysed. Positive diagnosis and severity of SOS were established after consensual review of the slides by three pathologists. Preoperative CT-scans were separately interpreted by two radiologists and evocative signs of SOS were sought, defined according to a literature review and operators experience. In order to identify SOS predictors, univariate analysis and multivariate logistic regression were used to study CT-scan signs and pathological results correlation. RESULTS: Twenty-nine patient (43%) had an SOS, 22 (33%) were low-grade and 7 (10%) were high-grade. All patient had received a median of 6 cures (3-27) containing Oxaliplatin for 53 (79%) of them. In univariate analysis, hepatic heterogeneity (p<0.001), puddle-like or micronodular appearance (p<0.001), peripheral distribution of heterogeneity (p=0.085), clover-like sign (p=0.02), splenomegaly (p=0.0026), spleen volume increase ≥30% (p=0.04) or splenic length increase ≥15% (p=0.04), as well as the subjective impression of the observer (P<0.001) were significantly associated with SOS diagnosis. In multivariate analysis, clover-like sign (OR 1.87, 95% CI 1.18-2.95, p=0.0081), increase in spleen volume ≥30% (OR 1.29, 95% CI 1.01-1.64, p=0.04), and the peripheral distribution of heterogeneity (OR 1.53, 95% CI 1.21-1.94, p<0.001) were independent SOS predictors. The area under the ROC curve was 0.804. The inter-observer agreement for SOS diagnosis was moderate (Kappa=0.546). CONCLUSION: CT-scan can detect suggestive signs of SOS in patients receiving chemotherapy for CRLM. By integrating clinical and biological information into CT-scan data, it may be fruitful to create a positive diagnostic and severity score for chemotherapy-induced SOS.

Recurrent primary cutaneous mucinous carcinoma with neuroendocrine differentiation: case report and review of the literature.

We report the case of a 60-year-old woman presenting with primary cutaneous mucinous carcinoma (PCMC) with neuroendocrine differentiation, revealed by neuroendocrine tumor lymph node metastasis 7 years before identification of the skin tumor. Only five cases of PCMC with neuroendocrine differentiation have been reported to date. The frequency of this neuroendocrine component may be underestimated, as it can require immunohistochemistry for identification, rather than being obvious on initial histopathologic examination. In the case presented here, the prominent neuroendocrine component displayed the morphological features of a well-differentiated neuroendocrine tumor with expression of common neuroendocrine markers, strong expression of estrogen and progesterone receptors and low Ki67 proliferation index (5%). This case shows that not all primary cutaneous neuroendocrine carcinomas are Merkel cell carcinomas (MCCs). In addition to rare primary cutaneous carcinoid tumors, the diagnosis of PCMC with neuroendocrine differentiation must be considered, particularly when confronted by a mucinous tumor or lymph node metastases of neuroendocrine carcinoma of unknown origin. On the basis of this case, identification of a neuroendocrine component in a PCMC might be an adverse prognostic indicator of recurrence or of lymph node metastasis and should support wider excision margins of the tumor.

MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone.

Low-grade osteosarcoma is a rare malignancy that may be subdivided into two main subgroups on the basis of location in relation to the bone cortex, that is, parosteal osteosarcoma and low-grade central osteosarcoma. Their histological appearance is quite similar and characterized by spindle cell stroma with low-to-moderate cellularity and well-differentiated anastomosing bone trabeculae. Low-grade osteosarcomas have a simple genetic profile with supernumerary ring chromosomes comprising amplification of chromosome 12q13-15, including the cyclin-dependent kinase 4 (CDK4) and murine double-minute type 2 (MDM2) gene region. Low-grade osteosarcoma can be confused with fibrous and fibro-osseous lesions such as fibromatosis and fibrous dysplasia on radiological and histological findings. We investigated MDM2-CDK4 immunohistochemical expression in a series of 72 low-grade osteosarcomas and 107 fibrous or fibro-osseous lesions of the bone or paraosseous soft tissue. The MDM2-CDK4 amplification status of low-grade osteosarcoma was also evaluated by comparative genomic hybridization array in 18 cases, and the MDM2 amplification status was evaluated by fluorescence in situ hybridization or quantitative real-time polymerase chain reaction in 31 cases of benign fibrous and fibro-osseous lesions. MDM2-CDK4 immunostaining and MDM2 amplification by fluorescence in situ hybridization or quantitative real-time polymerase chain reaction were investigated in a control group of 23 cases of primary high-grade bone sarcoma, including 20 conventional high-grade osteosarcomas, two pleomorphic spindle cell sarcomas/malignant fibrous histiocytomas and one leiomyosarcoma. The results showed that MDM2 and/or CDK4 immunoreactivity was present in 89% of low-grade osteosarcoma specimens. All benign fibrous and fibro-osseous lesions and the tumors of the control group were negative for MDM2 and CDK4. These results were consistent with the MDM2 and CDK4 amplification results. In conclusion, immunohistochemical expression of MDM2 and CDK4 is specific and provides sensitive markers for the diagnosis of low-grade osteosarcomas, helping to differentiate them from benign fibrous and fibro-osseous lesions, particularly in cases with atypical radio-clinical presentation and/or limited biopsy samples.

[BRAF V600E mutation in papillary thyroid carcinoma: prevalence and detection in fine needle aspiration specimens]. / Mutation BRAF V600E et carcinomes papillaires de la thyroïde : prévalence et faisabilité de la détection sur produits de cytoponction.

UNLABELLED: BRAF V600E mutation in papillary thyroid carcinoma (PTC): prevalence and detection in fine needle aspiration (FNA) specimens. BACKGROUND AND OBJECTIVE: The activating mutation of the BRAF gene, T1799A, is the most common and specific genetic alteration in PTC. In the present study, our aims were to confirm these data and investigate the feasibility of BRAF mutation detection in FNA specimens. METHODS: In a retrospective study, we examined paraffin-embedded surgical samples of 57 PTC and 51 non-PTC thyroid tumors for the presence of BRAF mutation by dideoxy sequencing. We analyzed thyroid aspirates (drop and washed-out solution) and smears from 31 patients who underwent thyroidectomy, before intraoperative frozen sections, and 25 archival thyroid FNA smears. RESULTS: The BRAF mutation was present in 58 % of PTC. Among non-PTC thyroid tumors, only one medullary thyroid carcinoma contained the BRAF mutation. BRAF mutation was correctly detected from the FNA-derived materials. Considering the search of BRAF mutation in preoperative FNA smears, the diagnosis of PTC would have been affirmed in 31 % (4/13) of indeterminate and suspicious FNA. CONCLUSION: BRAF mutation detection in FNA specimens is feasible and could be used as an adjunct tool for preoperative diagnosis of PTC classified as indeterminate and suspicious with conventional cytology (categories 3, 4 and 5 according to NCI/Bethesda 2008 terminology).

Primary neuroendocrine tumor of the sacrum: case report and review of the literature.

Primary carcinoid tumor (well-differentiated neuroendocrine tumor) of the bone involving the sacrum is extremely rare. We report the case of a 72-year-old man who presented with a 20-year history of intermittent low back pain and was found to have an intraosseous sacral mass on imaging. A needle biopsy revealed that this lesion was a well-differentiated neuroendocrine tumor. Workup did not show any primary tumor or other metastatic disease. There was no associated tailgut cyst or sacrococcygeal teratoma. The lesion was treated with radiation therapy because a surgical approach was rejected. The patient is free of metastatic disease after 28 years evolution of the lesion, retrospectively seen to be present on a conventional radiography performed in 1980. A review of the literature revealed 20 case reports of neuroendocrine tumors arising from the presacral region (with or without associated tailgut cyst or sacrococcygeal teratoma) and sometimes extending to the sacrum. One additional case was located within the neural canal and involved the sacrum, the presacral region, and the rectal wall. Our case is the only tumor arising primarily from the sacrum. The long evolution of this lesion without any other location makes metastatic disease very improbable and this case appears to be a unique example of primary intraosseous sacral carcinoid tumor.

[Hodgkin's disease variant of Richter's syndrome. Two cases and literature review]. / Syndrome de Richter de type pseudohodgkinien. A propos de deux cas et revue de la littérature.

We report the clinical and immunohistological features of two cases of chronic lymphocytic leukaemia (CLL) with Hodgkin's transformation. These cases occurred in a 70-year-old man with a three-year history of CLL and in a 76-year-old man with a few months history of CLL. Microscopic examination showed the presence of large tumor cells with the morphological and immunophenotypic features of classical Hodgkin and Reed-Sternberg (R-S) cells, in a background of otherwise typical B-CLL. The transformation of CLL into large B cell lymphoma (Richter's syndrome) is a well-documented phenomenon. Only rarely does CLL transform into Hodgkin's lymphoma, but this diagnosis is often easy and offers few differential diagnoses. The major points of interest lie in the pathogenetic relationship between CLL and Hodgkin's disease, and in the potential clinical implications of this peculiar condition. Literature on the subject indicates that identical IgH gene rearrangements in micromanipulated R-S and CLL cells have been identified in 7/12 cases. In these patients, the R-S and CLL cells belong to the same clonal population, suggesting a progression from the underlying CLL cells. This group appears to have a poor prognosis, identical to classical Richter's syndrome. In other cases, the R-S cells were often Epstein-Barr virus (EBV) positive and did not share the clonal rearrangements identified in CLL cells, suggesting that Hodgkin's disease in these patients could represent a second malignancy, EBV-related and favored by immunosuppression, associated with a better prognosis.