Lydia Deschamps

Telangiectatic adenoma: An entity associated with increased body mass index and inflammation

What were previously called telangiectatic focal nodular hyperplasias are in fact true adenomas with telangiectatic features (TAs) without overt characterized genetic abnormalities. The aim of our study was to review a surgical series of TAs in order to describe clinical, biological, and radiological findings of these lesions and to evaluate their outcomes. From January 1996 to November 2005, 284 patients with benign hepatocellular nodules underwent surgical resection at Beaujon Hospital. Among them, 32 TAs from 27 patients were diagnosed. Ninety‐two percent of the patients were women. Mean age was 38 years (range 17–63). Mean body mass index was 28 (range 18–49), with 16 patients being overweight. Symptoms revealed lesions in 10 patients. In 13 patients, TA was associated with another benign liver lesion. Mean size of the TAs was 5 cm (range 1–17 cm). Histological analysis showed cellular atypias in 6 cases (19%), steatosis in 17 cases (53%), vascular changes in 19 cases (59%), and significant inflammatory infiltrate in 29 cases (91%). In 1 case, the TA had foci of well‐differentiated hepatocellular carcinoma. In 18 of the 26 cases (69%), adjacent liver showed significant steatosis. Serum biomarkers of inflammation were increased in 90% of patients (19 of 22). After surgical resection, inflammatory marker levels returned to normal values in all patients tested. Conclusion: This study has shown that TAs occur in a characteristic background of overweight patients and are often associated with a biological inflammatory syndrome. Moreover, a TA may progress to malignancy. (HEPATOLOGY 2007;46:140–146.)

Overexpression of the Oxygen Sensors PHD-1, PHD-2, PHD-3, and FIH Is Associated with Tumor Aggressiveness in Pancreatic Endocrine Tumors

Purpose: Tumor hypoxia is associated with poor prognosis and resistance to treatment. Our aim was to assess the expression of proteins that act as cellular oxygen sensors, directly regulating the hypoxia inducible factor (HIF) pathway, i.e., prolyl hydroxylase domain proteins (PHD)-1, PHD-2, PHD-3, and FIH in pancreatic endocrine tumors (PET). Experimental Design: Immunohistochemical expression of these markers was examined in 109 PET included in tissue microarrays and representing various stages of tumorigenesis. The results were correlated with histoprognostic factors including Ki-67 index, presence of a fibrotic focus, and microvascular density (MVD). Results: The cytoplasmic and nuclear expressions of the three PHD isoforms were associated, and their expression was significantly higher in aggressive PETS, malignant, with lymph node metastases or with lower MVD. High nuclear expression of the three isoforms highly correlated with HIF-1α nuclear expression (P = 0.02, 0.003, and 0.006, respectively). Moreover, high nuclear PHD-1 or PHD-3 expression was associated with a poorer survival (P = 0.01). Cytoplasmic FIH was significantly higher in malignant PETs (P = 0.05) and in PETs with lymph node metastases (P = 0.02), and its expression correlated positively with those of cytoplasmic PHD isoforms (P < 0001). FIH stromal expression was found in 23% of PETs and correlated with higher FIH nuclear expression (P = 0.0004) and poorer disease-free survival (P = 0.0018). Conclusion: HIF regulatory proteins are highly expressed in PET and their expression is correlated with tumor metastases, tumor recurrence, and prognosis. These molecules that play an important role in the control of hypoxia-induced genes may have a function in the regulation of cellular proliferation and differentiation during endocrine tumorigenesis.

Heterogeneity of tumor prognostic markers: a reproducibility study applied to liver metastases of pancreatic endocrine tumors

Liver biopsy of metastatic pancreatic endocrine tumors allows confirmation of the diagnosis and assessment of prognosis. However, sampling variability is a potential limitation. Our aim was to use the tissue microarray technique to assess the heterogeneity of three prognostic markers, ie, MIB-1 proliferation index, microvascular density and somatostatin receptor type 2, inside single or between synchronous or metachronous liver metastases of pancreatic endocrine tumors. Tissue microarrays were constructed, which included core biopsies taken from surgically resected liver metastases in 29 patients. MIB-1, microvascular density and somatostatin receptor type 2 were evaluated after immunostaining. The heterogeneity was highlighted by the calculation of the reproducibility of the values of two cores randomly selected among all the cores studied. For quantitative variables, it was assessed by the intraclass correlation coefficient and by a Bland–Altman approach. For qualitative variables, observed agreement and weighted κ were given. A total of 184 liver metastases were analyzed. For MIB-1, the intraclass correlation coefficients were 0.63, 0.69 and 0.67 and for microvascular density, the intraclass correlation coefficients were 0.48, 0.60 and 0.00, respectively, in single, synchronous and metachronous liver metastases. The variability increased for higher mean values of microvascular density. For somatostatin receptor type 2, the observed agreements were 91% (κ=0.81), 69% (κ=0.49) and 79% (κ=0.68) in single, synchronous and metachronous liver metastases, respectively. In conclusion, tissue microarray analysis identifies heterogeneity of protein expression in pancreatic endocrine metastases, which depends on the marker tested. The reproducibility is better for MIB-1 and somatostatin receptor type 2 than for microvascular density. Sampling variability should be taken into consideration as a potential limitation to the assessment of prognostic and therapeutic markers in biopsy samples from metastatic pancreatic endocrine tumors.

High prevalence of IgG4-related lymphoplasmacytic infiltrative disorder in 25 patients with orbital inflammation: a retrospective case series

Aims To evaluate retrospectively the prevalence of positive IgG4-immunostaining in orbital tissue of patients with idiopathic orbital inflammation and to compare the clinical, radiographic and pathologic features among patients with and without IgG4-positive cells. Patients and methods 25 patients with biopsy-proven idiopathic orbital inflammation examined from January 2006 through December 2011 were included. Immunohistochemistry with IgG and IgG4 immunostaining from biopsy specimens of all patients was performed. Tissue with more than 10 IgG4-positive plasma cells per high-power field and with a ratio of IgG4+/IgG+ plasma cells of more than 40% was scored as positive. Histopathologic features, demographic and clinical data, radiologic findings, treatment and follow-up information for each patient were analysed. Results Immunohistochemical staining showed 10 cases (40%) were IgG4 positive. The symptoms and signs included eyelid or periocular swelling/mass in all, pain (3/10), extraocular muscle restriction (3/10), proptosis (5/10) and/or decreased vision (4/10). Demographic and clinical findings of these patients did not differ from those with IgG4-negative cells. The presence of positive IgG4-immunostaining in orbital tissue was significantly associated with characteristic pathological features (more background fibrosis, lymphoid hyperplasia, plasma cells and phlebitis). Conclusions Finally, 40% of patients with biopsy-proven orbital inflammation were classified as IgG4-RD, with typical histological features, but without specific clinical or radiological findings.

Predictors of tumor response after preoperative chemoradiotherapy for rectal adenocarcinomas.

The ability to predict response after chemoradiotherapy in rectal adenocarcinoma may allow selecting patients to whom less invasive surgical treatment could be proposed. Tumor hypoxia has been implicated in the mechanisms of resistance to chemoradiotherapy in several malignancies. The aim was to identify morphological criteria and molecular markers of hypoxia associated with chemoradiotherapy response. Clinicopathologic data from 61 patients (35 male, 60.5 ± 10 years) undergoing rectal cancer resection after neoadjuvant chemoradiotherapy were collected. Pretreatment biopsies, available for 40 patients, were immunostained for hypoxia markers (carbonic anhydrase 9, glucose transporter 1, chemokine receptor 4) and microvascular density determination. Mean tumor size was 2.7 ± 1.6 cm. Twenty-one patients (34%) were considered as responders, that is, having significant or complete primary tumor regression without lymph node metastasis. Compared to other patients, responders had significantly more often flat tumors with or without ulceration (57% versus 18%, P = .01) and less vascular and/or neural invasions (9% versus 65%, P < .0001) or tumor necrosis (9% versus 41%, P < .01), respectively. Regarding pretreatment biopsies, carbonic anhydrase 9 expression was significantly lower in responders (7% versus 46%, P = .012). This study showed that tumor necrosis as an overexpression of carbonic anhydrase 9 was an effective molecular marker of postchemoradiotherapy response. This might suggest a key role of hypoxia in resistance mechanisms of chemoradiotherapy in rectal adenocarcinoma. This study highlighted the importance of predictive criteria to chemoradiotherapy response in proposing to selected patients an alternative treatment (eg, local resection) to more radical surgery.

Endocrine tumors of the appendix: a pathologic review.

CONTEXTnAlthough rare, appendiceal endocrine tumors are the most common neoplasms of the appendix. Pathologic analysis is important for guiding the management of patients.nnnOBJECTIVEnTo provide recent data that focus on the pathology of endocrine tumors of the appendix including classifications and guidelines for patient management.nnnDATA SOURCESnA review of the recent literature including TNM classifications and patient management guidelines.nnnCONCLUSIONSnAppendiceal endocrine tumors are separated into 2 main groups: classic endocrine tumors and goblet cell carcinoids. They can be classified according to World Health Organization and TNM classifications. Evaluation of their prognoses and risks of malignancy, according to these classifications, depends on several parameters including tumor size, proliferation rate, and infiltration of appendiceal wall and mesoappendix. Most patients with classic endocrine tumors of the appendix have a favorable prognosis. Indications for postappendectomy, complementary surgery, which are still controversial, especially for tumors between 1 and 2 cm, are presented and discussed. In contrast, in patients presenting with a goblet cell carcinoid, a right hemicolectomy after the initial appendectomy is considered the standard surgical intervention.

Mixed Endocrine Somatostatinoma of the Ampulla of Vater Associated with a Neurofibromatosis Type 1: A Case Report and Review of the Literature

CONTEXTnMixed endocrine tumors are double neoplasms with both glandular and endocrine components; these tumors are rare, especially those arising in the ampulla of Vater. Ampullary somatostatinomas are classically associated with neurofibromatosis type 1. We herein describe the first reported case of a mixed endocrine somatostatinoma of the ampulla of Vater associated with neurofibromatosis type 1; we also present a review of the literature of the 7 mixed endocrine tumors of the ampulla which have been reported so far.nnnCASE REPORTnA 49-year-old woman presented with atypical abdominal pain. Endoscopic examination revealed a tumor involving the ampulla of Vater and a CT scan identified stenoses of both the distal common bile duct and the main pancreatic duct. A pancreaticoduodenectomy was performed and pathological examination revealed two tumor components, exocrine (high grade adenoma with infiltrative adenocarcinoma) and endocrine (expressing somatostatin hormone) with lymph node metastases originating from both types. The patient was treated with adjuvant chemotherapy and has had no recurrence for 3 years.nnnDISCUSSIONnIn ampullary somatostatinomas, psammoma bodies are pathognomonic and chromogranin A is rarely expressed: these features should alert the pathologist to an association with neurofibromatosis type 1. The management of patients with mixed tumors is challenging. The treatment of choice is surgery, and adjuvant chemotherapy should be adapted to the most aggressive component, i.e. the exocrine one.nnnCONCLUSIONnBecause of their rarity, the diagnosis of ampullary mixed endocrine tumors is difficult. Our case points out the characteristic features of these neoplasms and their possible association with neurofibromatosis type 1.

Pancreatocolonic fistula complicating noninvasive intraductal papillary mucinous tumor of the pancreas

Intraductal papillary mucinous tumors (IPMT) of the pancreas are a distinct clinicopathological entity that is increasingly recognized and whose natural history and clinical presentation are now better understood. Nevertheless, only rare cases of pancreatobiliary or pancreatodigestive fistulas complicating IPMT have been described so far and their clinicopathological significance and association with cancer remain controversial. We report a case of pancreatocolonic fistula complicating a noninvasive IPMT, and review the published literature. Unlike previous reports, IPMT complicated by fistula in nearby organs does not seem to be more often associated with invasive carcinoma: frequency is comparable in resected IPMT with or without internal fistula. Since fistulas are not a reliable clinicopathological predictor of invasive malignancy, en-bloc resection should not be routinely performed especially if extended resection increases the immediate risks or the long-term risks of surgery.

Macrophage CD31 Signaling in Dissecting Aortic Aneurysm

BACKGROUNDnThe authors recently found that a CD31 agonist peptide reaches macrophages in injured aortas and exerts beneficial effects on apolipoprotein E-knockout (Apo E-/-) mice subjected to angiotensin (Ang) II infusion, a model of experimental acute aortic dissection and intramural hematoma (ADIM).nnnOBJECTIVESnThe purpose of this study was to evaluate the therapeutic potential of a drug-suitable agonist peptide in experimental ADIM.nnnMETHODSnP8RI, a retro-inverso sequence of the best candidate identified by functional inxa0vitro screening of a peptide library, passed an absorption, distribution, metabolism, excretion and toxicology analysis. Apo E-/- mice (male, 28-week-old) implanted with Ang II-releasing pumps received P8RI (2.5xa0mg/kg/day) or vehicle from day 14 (nxa0=xa010/group). Leukocytes were analyzed by flow cytometry. Healing features of human and mouse dissected aortic segments were assessed by histology and immunofluorescence. The effect of CD31 on macrophages was evaluated using cells from CD31-/- mice and P8RI, inxa0vitro.nnnRESULTSnHuman and experimental ADIM were characterized by the infiltration of proinflammatory macrophages. Thexa0absence of CD31 enhanced the proinflammatory polarization of macrophages, whereas the CD31 agonist P8RI favored reparative macrophages both inxa0vitro and inxa0vivo. The administration of P8RI after the occurrence of ADIM prevented aneurysmal transformation by promoting the resolution of intramural hematoma and the production of collagen in dissected aortas inxa0vivo, associated with enrichment of M2 macrophages at the site of injury.nnnCONCLUSIONSnCD31 signaling promotes the switching of proinflammatory macrophages to the reparative phenotype and favors the healing of experimental dissected aortas. Treatment with a drug-suitable CD31 agonist may facilitate the clinical management of ADIM.

A rare fungal infection: Phaehyphomycosis due to Veronaea botryosa and review of literature

We report a rare case of phaehyphomycosis in a 71-year-old heart transplant recipient Togo native patient. Four months after the transplant, he presented painless nodules on the right heel with superficial ulceration. The polyphasic identification uncovered a rare cause of phaehyphomycose: V. botryosa. The treatment combined surgical excision of the lesions and anti-fungal therapy with posaconazole. We discussed eleven reported cases in literature since 1990.