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Focuses on acute renal failure and hematuria in marathon runners, examining the role of glomerular bleeding in tublar injury in the risk of renal failure in runners and referencing the case report of a 46-year-old male marathon runner. Details on the symptoms the runner presented; Factors which contributed to the onset of renal failure; Information on the tests conducted on the patient; Treatment administered to the patient.

Denial of pregnancy is a rare psychic process associated with an increased risk of infant death. Forensic examinations to determine viability at birth can heavily influence the legal proceedings in cases of clandestine deliveries that result in the death of the infant. A 32-year-old woman who experienced a denial of pregnancy up to 30 weeks of amenorrhea reported giving birth at home at an estimated term of 35 weeks of amenorrhea. No one witnessed the delivery. She claimed the infant was stillborn. Forensic examinations revealed characteristic features of a live born infant. The mother tested positive for mifepristone. Mifepristone is an anti-progestin drug used for early abortion and to induce labor in cases of in-utero fetal death in later pregnancy. Even if mifepristone crosses the placenta, it has no direct toxic effect on the fetus. Our observations suggest premature live birth caused by mifepristone, followed by asphyxia due to meconium inhalation syndrome associated with lung immaturity especially since the birth occurred at home and no medical care was provided after the birth. The tragic outcome of this clinical case calls for vigilance and global management, including the psychiatric care of parturients in the context of late discovery of pregnancy. In France, this situation showed a legal gap between the consideration of the fetus and laws concerning abortion. To our knowledge, in France, this case has allowed the court to set a legal precedent as a similar case had never been reported elsewhere., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Aortitis is a group of disorders characterized by the inflammation of the aorta. The large-vessel vasculitides are the most common causes of aortitis. Aortitis long-term outcomes are not well known., Objectives: The purpose of this study was to assess the long-term outcome and prognosis of noninfectious surgical thoracic aortitis., Methods: This was a retrospective multicenter study of 5,666 patients with thoracic aorta surgery including 217 (3.8%) with noninfectious thoracic aortitis (118 clinically isolated aortitis, 57 giant cells arteritis, 21 Takayasu arteritis, and 21 with various systemic autoimmune disorders). Factors associated with vascular complications and a second vascular procedure were assessed by multivariable analysis., Results: Indications for aortic surgery were asymptomatic aneurysm with a critical size (n = 152 [70%]), aortic dissection (n = 28 [13%]), and symptomatic aortic aneurysm (n = 30 [14%]). The 10-year cumulative incidence of vascular complication and second vascular procedure was 82.1% (95% CI: 67.6%-90.6%), and 42.6% (95% CI: 28.4%-56.1%), respectively. Aortic arch aortitis (HR: 2.08; 95% CI: 1.26-3.44; P = 0.005) was independently associated with vascular complications. Descending thoracic aortitis (HR: 2.35; 95% CI: 1.11-4.96; P = 0.031) and aortic dissection (HR: 3.08; 95% CI: 1.61-5.90; P = 0.002) were independently associated with a second vascular procedure, while treatment with statins after aortitis diagnosis (HR: 0.47; 95% CI: 0.24-0.90; P = 0.028) decreased it. After a median follow-up of 3.9 years, 19 (16.1%) clinically isolated aortitis patients developed features of a systemic inflammatory disease and 35 (16%) patients had died., Conclusions: This multicenter study shows that 82% of noninfectious surgical thoracic aortitis patients will experience a vascular complication within 10 years. We pointed out specific characteristics that identified those at highest risk for subsequent vascular complications and second vascular procedures., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Primary heart neoplasms are rare and poorly known by general pathologists. However, they are not exceptionally encountered in pathology laboratories having a recruitment of cardiac surgery specimens. About 80 % of them are benign tumors and 20 % are malignant tumors. Some tumors are specific to the heart or have characteristics when they grow in the heart, including myxoma and papillary fibroelastoma. The classification currently in use is the 4th edition of the WHO classification of heart tumors published in 2015, which takes into account the evolution of knowledge in the field of sarcomas, but which does not yet recognize cardiac intimal sarcoma. recently individualized in its intracardiac location., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Apolipoprotein A1 amyloidosis (ApoAI) results from specific mutations in the APOA1 gene causing abnormal accumulation of amyloid fibrils in diverse tissues. The kidney is a prominent target tissue in ApoAI amyloidosis with a remarkable selectivity for the renal medulla. Here, we investigated six French families with ApoAI Glu34Lys, p.His179Profs∗47, and a novel p.Thr185Alafs∗41 variant revealing unprecedented clinical association of a glomerular with a retinal disease. Comprehensive clinicopathological, molecular and proteomics studies of numerous affected tissues ensured the correlation between clinical manifestations, including novel unrecognized phenotypes, and apoA-I amyloid deposition. These ophthalmic manifestations stemmed from apoA-I amyloid deposition, highlighting that the retina is a previously unrecognized tissue affected by ApoAI amyloidosis. Our study provides the first molecular evidence that a significant fraction of ApoAI amyloidosis cases with no family history result from spontaneous neomutations rather than variable disease penetrance. Finally, successful hepatorenal transplantation resulted in a life- and vision-saving measure for a 32-year-old man with a hitherto unreported severe ApoAI amyloidosis caused by the very rare Glu34Lys variant. Our findings reveal new modes of occurrence and expand the clinical spectrum of ApoAI amyloidosis. The awareness of glomerular and ocular manifestations in ApoAI amyloidosis should enable earlier diagnosis and avoid misdiagnosis with other forms of renal amyloidosis. Thus, documented apoA-I amyloid deposition in the retina offers new biological information about this disease and may change organ transplantation practice to reduce retinal damage in patients with ApoAI amyloidosis., (Published by Elsevier Inc.)

Background: IgA nephropathy (IgAN) often follows infections and features IgA mesangial deposition. Polymeric IgA deposits in the mesangium seem to have varied pathogenic potential, but understanding their pathogenicity remains a challenge. Most mesangial IgA1 in human IgAN has a hypogalactosylated hinge region, but it is unclear whether this is required for IgA deposition. Another important question is the role of adaptive IgA responses and high-affinity mature IgA antibodies and whether low-affinity IgA produced by innate-like B cells might also yield mesangial deposits., Methods: To explore the effects of specific qualitative variations in IgA and whether altered affinity maturation can influence IgA mesangial deposition and activate complement, we used several transgenic human IgA1-producing models with IgA deposition, including one lacking the DNA-editing enzyme activation-induced cytidine deaminase (AID), which is required in affinity maturation. Also, to explore the potential role of the IgA receptor CD89 in glomerular inflammation, we used a model that expresses CD89 in a pattern observed in humans., Results: We found that human IgA induced glomerular damage independent of CD89. When comparing mice able to produce high-affinity IgA antibodies with mice lacking AID-enabled Ig affinity maturation, we found that IgA deposition and complement activation significantly increased and led to IgAN pathogenesis, although without significant proteinuria or hematuria. We also observed that hinge hypoglycosylation was not mandatory for IgA deposition., Conclusions: In a mouse model of IgAN, compared with high-affinity IgA, low-affinity innate-like IgA, formed in the absence of normal antigen-driven maturation, was more readily involved in IgA glomerular deposition with pathogenic effects., (Copyright © 2019 by the American Society of Nephrology.)

Childhood pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease. Its pulmonary histopathology, according to comprehensive clinical-radiological findings and BRAF V600E mutation status, has not yet been thoroughly documented. From the 167 childhood PLCH cases entered in the French National Histiocytosis Registry (1983-2016), we retrieved lung biopsies from a consecutive retrospective series of 17 patients, diagnosed when they were 2 weeks to 16 years old (median, 9.4 years), and report the clinical and histopathological findings herein. Histological analyses of biopsies (16 surgical and 1 postmortem) found the following features, alone or associated: Langerhans cell (LC) nodules with cavitation (9/17), cysts (14/17), fibrotic scars (2/17), peribronchiolar topographic distribution of the lesions (10/17), and accessory changes, like stretch emphysema (7/17). Those characteristics closely resemble those describing adult PLCH. However, unusual findings observed were 2 large nodules and a diffuse interstitial LC infiltrate. BRAF V600E mutation was detected in 4 of 12 samples tested, notably in the 3 with unusual features. In conclusion, childhood PLCH mostly shares the common histology features already described in adult PLCH, regardless of age. Because smoking is considered the major trigger in PLCH pathogenesis, the findings based on this series suggest other inducers of bronchiolar LC recruitment, especially in very young patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We report the case of a girl of 5 and a half months admitted for discomfort and consciousness loss at home and supported on sudden infant death protocol. Workup was negative. Autopsy showed only signs of asphyxia. Microscopic examination of the pancreas showed hypertrophic beta cells of Langerhans islets, explaining death linked to severe hypoglycemia by inappropriate insulin hypersecretion. This observation highlights the importance of the management of sudden infant unexpected death according to the protocol of the National Health Authority, which includes an autopsy with complete sampling, which in this case resulted in a diagnosis of unknown disease the lifetime of the child., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The aim of this article is to illustrate the importance of N-butane determination in postmortem samples through a case report and to propose actions and precautions to be taken into consideration when butane is suspected to be involved in cases of death. The case concerns a 15-year-old boy found dead after sniffing a cigarette lighter refill. Toxicological investigation revealed the presence of butane in the heart and femoral blood (1280 and 1170 μg/L, respectively), in the gastric contents (326 μg/L), and in the liver (1010 μg/kg) and lung tissues (210 μg/kg). Propane was present only in the blood samples at concentrations tenfolds lower.Butane can be involved in three kinds of fatalities: deliberate inhalations including volatile substance abuse (VSA), involuntary exposure, and homicides. A fatal outcome of butane inhalation can be caused by asphyxia and/or cardiac arrhythmia. In the context where butane exposure is evidenced by non-toxicological investigations, the usefulness of the determination of butane in postmortem samples is often questionable. However, it is admitted that butane-related deaths are generally underreported. Several difficulties including sample handling and storage, substantial variation in tissue concentrations, and lack of a lethal threshold make the interpretation of butane results challenging. In our opinion, systematic toxicological methods should be developed in order to analyze butane, at least when it concerns a typical VSA victim, even when butane is not actually suspected to be the cause of death.

Postmortem investigation often reveals various conditions, which may or may not have played a part in the death of the individual. The case of a 32-year-old woman is reported, with a long history of drug addiction. She was found dead in her bed. The autopsy revealed diffuse pulmonary edema with congestion of the lungs, brain, liver, and spleen. Microscopic examination of the lungs showed multiple intra-alveolar and interstitial foamy macrophages and extracellular fat droplets surrounded by polynuclear giant cells. Death was attributed to acute polydrug intoxication. As microscopic examination had revealed severe pulmonary lesions, lipoid pneumonia was considered as a contributing factor to death. Lipoid pneumonia is an uncommon entity with the characteristic radiograph features and histologic findings of alveoli filled with vacuolated, lipid-laden histiocytes. It can be either exogenous or endogenous in cause, based on the source of the lipid. Exogenous lipoid pneumonia usually results from aspiration or inhalation of fat-like material, such as mineral oil or petroleum-based lubricants and decongestants, resulting in pulmonary inflammatory reactions., (© 2014 American Academy of Forensic Sciences.)

Background: It remains presently unclear whether disease progression in colorectal carcinoma (CRC), from early, to invasive and metastatic forms, is associated to a gradual increase in genetic instability and to a scheme of sequentially occurring Copy Number Alterations (CNAs)., Methods: In this work we set to determine the existence of such links between CRC progression and genetic instability and searched for associations with patient outcome. To this aim we analyzed a set of 162 Chromosomal Instable (CIN) CRCs comprising 131 primary carcinomas evenly distributed through stage 1 to 4, 31 metastases and 14 adenomas by array-CGH. CNA profiles were established according to disease stage and compared. We, also, asked whether the level of genomic instability was correlated to disease outcome in stage 2 and 3 CRCs. Two metrics of chromosomal instability were used; (i) Global Genomic Index (GGI), corresponding to the fraction of the genome involved in CNA, (ii) number of breakpoints (nbBP)., Results: Stage 1, 2, 3 and 4 tumors did not differ significantly at the level of their CNA profiles precluding the conventional definition of a progression scheme based on increasing levels of genetic instability. Combining GGI and nbBP,we classified genomic profiles into 5 groups presenting distinct patterns of chromosomal instability and defined two risk classes of tumors, showing strong differences in outcome and hazard risk (RFS: p = 0.012, HR = 3; OS: p < 0.001, HR = 9.7). While tumors of the high risk group were characterized by frequent fractional CNAs, low risk tumors presented predominantly whole chromosomal arm CNAs. Searching for CNAs correlating with negative outcome we found that losses at 16p13.3 and 19q13.3 observed in 10% (7/72) of stage 2-3 tumors showed strong association with early relapse (p < 0.001) and death (p < 0.007, p < 0.016). Both events showed frequent co-occurrence (p < 1x10-8) and could, therefore, mark for stage 2-3 CRC susceptible to negative outcome., Conclusions: Our data show that CRC disease progression from stage 1 to stage 4 is not paralleled by increased levels of genetic instability. However, they suggest that stage 2-3 CRC with elevated genetic instability and particularly profiles with fractional CNA represent a subset of aggressive tumors.

A 59-year-old male, was admitted to our hospital for a tumor of the pancreatic tail. Serum CEA and CA 19-9 levels were normal. Splenopancreasectomy found a desmoid tumour. A 69-year-old male was referred to our institution for chronic anemia and inflammatory syndrome with splenomegaly. Splenectomy showed an important splenic congestion and siderosis. Both patients had a type 2 diabetes mellitus. Furthermore, histological examination revealed pancreatic endocrine microadenomas. The two patients' postoperative course was unremarkable. Eleven and 24 months respectively after the diagnosis, the patients are alive and well, with no tumor recurrence., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

KRAS mutations are the most common oncogenic event in colorectal cancer (CRC) progression and their occurrence is associated with lack of response to anti epidermal growth factor receptor (EGFR) targeted therapies. Using preclinical models and patients' samples we recently reported that the emergence of KRAS mutations but also KRAS amplification is associated with acquired resistance to the EGFR inhibitors cetuximab or panitumumab. We reasoned that KRAS amplification may also be responsible for primary resistance to these agents. Furthermore, while the prevalence of KRAS mutations has been well established in CRC, little is known about the frequency of KRAS amplification in large CRC series. We performed a screening of 1,039 CRC samples to assess the prevalence of KRAS amplification in this tumor type and further evaluated the role of this genetic alteration on the sensitivity to anti EGFR therapies. We detected KRAS amplification in 7/1,039 (0.67%) and 1/102 evaluable CRC specimens and cell lines, respectively. KRAS amplification was mutually exclusive with KRAS mutations. Tumors or cell lines harboring this genetic lesion are not responsive to anti-EGFR inhibitors. Although KRAS amplification is an infrequent event in CRC, it might be responsible for precluding response to anti-EGFR treatment in a small proportion of patients., (Copyright © 2013 UICC.)

Phenotypic identification of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) subtypes using immunohistochemical markers has been developed from their molecular characteristics. Our objective was to evaluate the sensitivity of these markers in the definitive diagnosis of these lesions by core needle biopsies. A total of 239 needle biopsies paired with their surgical resection specimen (group A) or without an associated resection specimen (group B) were reviewed. Using a step-by-step algorithm after standard staining, appropriate immunostaining analyses were performed to determine the certainty of diagnosis of FNH, HNF1α-inactivated HCA, inflammatory HCA, β-catenin-activated HCA, or unclassified HCA. The diagnosis of FNH was certain or probable on routine stains in 53% of needle biopsies of group A, whereas after glutamine synthetase staining, the diagnosis was certain in 86.7% as compared with 100% on the corresponding surgical specimen (P=0.04). In needle biopsies of group A, the diagnosis of HCA was certain on routine stains in 58.6% as compared with 94.3% on surgical specimens. After specific immunostaining, diagnosis was established on biopsies with 74.3% certainty, including all HCA subtypes, with similar distribution in surgical specimens. For each "certain diagnosis" paired diagnostic test (biopsy and surgical specimen), a positive correlation was observed (P<0.001). No significant difference was observed between groups A and B for FNH (P=0.714) or for HCA subtypes (P=0.750). Compared with surgical specimens, immunohistochemical analysis performed on biopsies allowed the discrimination of FNH from HCA and the identification of HCA subtypes with good performance.

Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia frequently associated with clotting abnormalities and severe hemorrhagic diathesis. The disease is associated with a high incidence of early fatal hemorrhage. We report the sudden death of a 40-year-old male without significant medical history in which foul play had been initially suspected. A thorough postmortem investigation performed on the decedent lead to the diagnosis of APL. Cause of death was a cerebellar hematoma. Underlying APL should be considered in the differential diagnosis when unexplained bleeding is encountered in a decedent. This case emphasizes the value of routinely collecting bone marrow during an autopsy to enable accurate testing and diagnosis., (© 2012 American Academy of Forensic Sciences.)

Background: Sirolimus (SRL) is a potent immunosuppressant used in organ transplantation. It is known to decrease vascular endothelial growth factor (VEGF) synthesis, making it an interesting treatment option for transplant patients who develop Kaposi sarcoma or other malignant diseases. Because VEGF plays a key role in glomerular function and vascular remodelling, we determined the effect of SRL on renal VEGF expression., Methods: Using immunohistochemistry and quantitative image analysis, we examined renal VEGF expression in routine kidney biopsies performed at 1 year post-transplant in the CONCEPT study, a prospective randomized study comparing a cyclosporine (CsA)-based regimen to a SRL-based regimen in association with mycophenolate mofetil (MMF)., Results: A total of 74 patients were included in this substudy; 35 were randomized to the CsA group and 39 to the SRL group. Using continuous variables, the mean percentage of glomerular VEGF expression at Week 52 was significantly lower in the SRL group (14.7 ± 13%) compared to CsA group (21.2 ± 14%: P = 0.02). The percentage of glomerular VEGF expression at Week 52 was not influenced by recipient or donor age, gender, renal function, CsA dose, CsA blood level, SRL dose or SRL blood level. It was significantly lower in patients with a proteinuria over versus below 0.5 g/day (11.58 ± 7.9 versus 19.45 ± 15.53; P = 0.036)., Conclusions: There is emerging evidence that the VEGF system can play either a beneficial or a detrimental role depending on the specific pathologic situations. Therefore, modulating the renal VEGF axis by using an SRL-based regimen may influence the evolution of kidney injury associated with renal transplantation.

Background: The aim of this study was to assess, at the European level and using digital technology, the inter-pathologist reproducibility of the ISHLT 2004 system and to compare it with the 1990 system We also assessed the reproducibility of the morphologic criteria for diagnosis of antibody-mediated rejection detailed in the 2004 grading system., Methods: The hematoxylin-eosin-stained sections of 20 sets of endomyocardial biopsies were pre-selected and graded by two pathologists (A.A. and M.B.) and digitized using a telepathology digital pathology system (Aperio ImageScope System; for details refer to http://aperio.com/). Their diagnoses were considered the index diagnoses, which covered all grades of acute cellular rejection (ACR), early ischemic lesions, Quilty lesions, late ischemic lesions and (in the 2005 system) antibody-mediated rejection (AMR). Eighteen pathologists from 16 heart transplant centers in 7 European countries participated in the study. Inter-observer reproducibility was assessed using Fleiss's kappa and Krippendorff's alpha statistics., Results: The combined kappa value of all grades diagnosed by all 18 pathologists was 0.31 for the 1990 grading system and 0.39 for the 2005 grading system, with alpha statistics at 0.57 and 0.55, respectively. Kappa values by grade for 1990/2005, respectively, were: 0 = 0.52/0.51; 1A/1R = 0.24/0.36; 1B = 0.15; 2 = 0.13; 3A/2R = 0.29/0.29; 3B/3R = 0.13/0.23; and 4 = 0.18. For the 2 cases of AMR, 6 of 18 pathologists correctly suspected AMR on the hematoxylin-eosin slides, whereas, in each of 17 of the 18 AMR-negative cases a small percentage of pathologists (range 5% to 33%) overinterpreted the findings as suggestive for AMR., Conclusions: Reproducibility studies of cardiac biopsies by pathologists in different centers at the international level were feasible using digitized slides rather than conventional histology glass slides. There was a small improvement in interobserver agreement between pathologists of different European centers when moving from the 1990 ISHLT classification to the "new" 2005 ISHLT classification. Morphologic suspicion of AMR in the 2004 system on hematoxylin-eosin-stained slides only was poor, highlighting the need for better standardization of morphologic criteria for AMR. Ongoing educational programs are needed to ensure standardization of diagnosis of both acute cellular and antibody-mediated rejection., (2011 International Society for Heart and Lung Transplantation. All rights reserved.)

Objectives: To identify juvenile idiopathic arthritis (JIA) patients who developed IBD during treatment with anti-TNF-alpha agents and better characterize the IBD clinical and pathological presentation., Methods: A retrospective French multicentre study included patients with a diagnosis of JIA according to the ILAR criteria who developed IBD while under anti-TNF-alpha therapy before 18 years of age. Intestinal biopsies were collected and reviewed by the same pathologist., Results: Eight patients were included. They had been treated with etanercept from 11 to 78 months before IBD onset. Gastro-intestinal symptoms included abdominal pain (six patients), diarrhoea (four patients), anorexia (four patients), anal abscess (three patients) and oral ulcers (one patient). Five patients presented with Crohn's disease (CD) and three with indeterminate IBD, of whom four had severe pancolitis. Clinical remission of IBD was obtained in all patients after discontinuation of etanercept and initiation of IBD-specific therapy, including infliximab in six patients., Conclusion: IBD must be suspected in JIA patients treated with etanercept who develop intestinal symptoms, including anal abscess. This series raises the possibility of a relationship between etanercept therapy and the occurrence of IBD in a subset of patients with JIA.

Lipomatous polyposis of the colon is a rare affection, with about 10 published cases. This affection is characterized by a great number of polyps which can reach several hundreds, of diffuse location on the entire length of the colon, with a higher density on the left colon and the sigmoid. The size of polyps varies from 1 to 10 cm. When they are voluminous, they can be cause of obstruction, ulceration or bleeding. We report a case of colonic lipomatous polyposis, associated with an ileocolic lipomatous, an ileocolic diverticulosis and adenomatous polyps in a 70-year-old man.

Objectives: To explain the high incidence of misdiagnosis of angiomyolipoma (AML) prior to surgery., Materials and Methods: Between 1989 and 2007, 2,657 patients were operated for a renal tumor at Dupuytren hospital in Limoges and at Cochin hospital in Paris. In 85 cases (3.2%), tumors were AMLs on pathology. The group of patients in which the diagnosis was done preoperatively was compared to the one in which the diagnosis was missed., Results: Mean age of patients was 57-years-old and the sex-ratio was five women for one man. The mean size of AMLs was 5.4 cm. The patients were symptomatic in 46% of cases (39/85). The diagnosis of AML was ignored preoperatively in 62 patients (73%). In multivariate analysis, the small size of the AML, low proportion of fat and male sex were significantly associated with misdiagnosis of AML (p<0.001, p<0.018 and p<0.008, respectively)., Conclusions: The incidence of misdiagnosis of AML preoperatively is high. The diagnosis seems particularly difficult when the tumor is small or contains a small proportion of fat. In addition, this study highlights that the diagnosis of AML is frequently ignored in men. The increased resolution of CTscan and the use of preoperative biopsies for tumors less than 4 cm could be helpful to decrease the incidence of useless surgery of AMLs.

Purpose: The aim of this study was to demonstrate the ability to use human clinical positron emission tomography/computed tomography (PET/CT) to detect and investigate head and neck cancers chemically induced by 4-nitroquinoline-1-oxide (4-NQO) in a rat model., Study Design: The study design was prospective animal research., Procedures: A head and neck squamous cell carcinoma was established in 20 immunocompetent rats, who drank a 4-NQO solution during 16 weeks. 2-Deoxy-2-[F-18]fluoro-D: -glucose (FDG)-PET/CT was performed for five of them, 34 weeks after the start of the experiment to characterize the tumors. A day following the FDG-PET/CT, rats were euthanized and pathological features were evaluated by hematoxylin-eosin staining., Results: All rats had head and neck tumor at various locations at 34 weeks. Among the five rats selected for having FDG-PET/CT, the clinical examination detected exophytic tumors grown in the oral cavity for three of them (one on the inferior lip, one on the hard palate, and one on the internal side of the cheek). FDG-PET/CT confirmed the presence of those tumors and detected ones located on the base of tongue for three of them. Tumor extensions were characterized and tumor metabolic volumes were measured. The smallest lesion detected measured 3 x 3 x 4 mm. Pathologic examination using hematoxylin-eosin staining confirmed squamous cell carcinoma., Conclusions: This study demonstrated that FDG-PET/CT is a feasible examination to detect occult primary tumors in rat models. It is useful to follow tumor progression and evaluate therapeutics efficacy.

A distinctive tumor described under the terms Bellini duct carcinoma and low-grade collecting duct carcinoma has been referred to by us and others as tubulocystic carcinoma. This renal cell carcinoma subtype is not recognized in the World Health Organization 2004 classification. Herein, we present a detailed study of 31 cases to further characterize this rare subtype of renal cell carcinoma. The tumor occurred in adults (mean age, 54 years) with a strong male predominance (7:1). Grossly, the tumors ranged from 0.7 to 17 cm, and exhibited a spongy or "bubble wrap" appearance reflecting the microscopic presence of variably sized cystically dilated tubules lined by a single layer of epithelium. The lining varied with a cuboidal, flat, and hobnail cell appearance, and the neoplastic cells had abundant eosinophilic cytoplasm and enlarged nuclei with prominent nucleoli. The cysts were closely spaced with an intervening variably fibrotic stroma. Immunohistochemistry and ultrastructural examination showed features of proximal convoluted tubules (Pax 2 immunoreactivity and short microvilli with brush border organization) and distal nephron (kidney-specific cadherin immunoreactivity and cytoplasmic interdigitation). Gene expression profiling showed that tubulocystic carcinoma displayed a unique molecular signature. Twenty-four tumors were stage pT1, 4 stage pT2, and 3 stage pT3. Disease progression (median follow-up of 56 months) occurred in 3 patients; 1 with local recurrence, and 2 with distant metastasis to bone and liver. In light of the distinctive clinicopathologic features and a low but definite metastatic potential, this unique subtype of renal cell carcinoma deserves formal recognition in the contemporary classification of renal neoplasms.

Aim: To develop and characterize by imaging and pathological examination a new immunocompetent rat model of head and neck squamous cell carcinoma (HNSCC)., Study Design: Prospective animal research., Materials and Methods: Frozen specimens of HNSCC induced chemically by 4-nitroquinoline 1 oxide (4-NQO) in Sprague Dawley rats were used for the first graft. Serial allografts were then performed with fresh specimens of tumor in twenty-five Sprague Dawley rats. A specimen of tumor (100 mm3) was picked up by head and neck dissection during an autopsy. The graft was performed in a subcutaneous manner, in the ventral part of the neck, using an incision of 4 mm, through the masseter muscle. Tumors were clinically measured once a week and volumes were calculated. 2-[18F]Fluoro-2-deoxy-D-glucose positron emission tomography coupled with computed tomography (FDG-PET/CT) was performed on days 14 and 30 after the graft. Rats were euthanized and pathological features were assessed using hematoxylin-eosin (HE) staining and immunohistochemistry markers to characterize the tumor., Results: An 80% take rate was achieved using fresh tumor specimens. Tumors grew rapidly; the mean tumoral volume was 1.013 cm3 on day 14 and 7.994 cm3 on day 30. FDG-PET/CT imaging targeted regions of metabolically active tumor. It showed a uniform uptake of 18F-FDG on day 14 and a large area of central necrosis on day 30. Pathological examinations showed a typical squamous cell carcinoma, with similar immunohistochemical analyses to the human squamous cell carcinoma., Conclusion: We propose a new allograft HNSCC rat model which is easily reproducible and rapidly obtained in comparison to that induced chemically with 4-NQO. This model was developed in immunocompetent rats, with similar conditions to human carcinogenesis and could be used for testing new therapeutics.

Hereditary non polyposis colorectal cancer or Lynch syndrome is due to germline mutation of one the DNA mismatch repair genes. This mutation is associated with an unstable phenotype in tumor DNA characterized by new microsatellite alleles that are absent in matching normal DNA. Besides the Bethesda reference panel, a new panel of 5 mononucleotide microsatellites (BAT25, BAT26, NR21, NR24, NR27) has been proposed, which is more sensitive and faster to use in a multiplex PCR assay. In tumor cells, immunohistochemistry detects the loss of expression of either MLH1, MSH2, MSH6 or PMS2 protein, corresponding to the mutated gene. Immunohistochemistry guides germline analysis, except for MLH1 extinction which may correspond to either MLH1 germline mutation or methylation of MLH1 promoter resulting in inactivation. The latter is mostly due to aging and is often associated to the V600E BRAF gene mutation in tumor DNA. Combination of these 3 somatic analyses should reduce indications of germline mutation analysis in Lynch syndrome.

Background: In an orthotopic rat osteosarcoma model, histological and molecular findings were compared with the results of non-invasive imaging methods to assess disease progression at the primary site, the pattern of metastatic dissemination and the chemoresistance phenotype., Materials and Methods: Primary tumor engraftment, vascularization, growth and metastatic spread were evaluated using 18FDG tomoscintigraphy. Bone neoformation in the primary tumor and metastasis was determined using 18FNa confirmed by classical histological studies. Chemoresistance phenotype was assessed by analysis of MDR1 and MRP1 genes expression compared to 99mTc MIBI imaging., Results: 99mTc MIBI imaging correlated with the overexpression of the MDR1 and MRP1 genes. 18FDG, 18FNa and 99mTc tomoscintigraphies revealed that the pattern of vascularization, bone neoformation and hematogeneous metastatic dissemination in our animal model mimics its human counterpart., Conclusion: Multimodality, non-invasive imaging is a valid surrogate marker of histological and molecular characteristics in an orthotopic osteosarcoma model in immunocompetent rats; it allows extensive in vivo follow-up of osteosarcoma, including longitudinal analysis of chemoresistance.

Tubulocystic carcinoma is a tumor entity, which is not yet included in the WHO-classification of renal tumors. We report a series of 11 cases of this tumor, 6 of which were examined in by immunohistochemistry using a panel of five antibodies (CK7, CK34betaE12, CK19, CD10 and P504S). All patients were men. Each had renal tumor stage of pT1N0M0, with a diameter of 1.7 to 7 cm (mean, 3.3 cm). None of the patients presented with recurrence or metastases. Grossly, tumors were microcystic masses with a bubble-wrap appearance. Histological features included cysts and small tubules, separated by delicate septa and lined by flat to columnar or hobnail cells. The cyst and tubule epithelium showed immunohistochemical characteristics of both proximal and distal tubules. Tubulocystic carcinoma is a distinctive kidney tumor, with noteworthy macroscopic and microscopic characteristics, which can be distinguished from other cystic kidney tumors, including cystic nephroma, multilocular cystic renal cell carcinoma and some solid tumors with extensive cystic changes. More cases are needed to ascertain its prognosis. Tubulocystic carcinoma should be considered as a new subtype of renal cell carcinoma in the next revision of the WHO classification.

Tumor progression depends on the angiogenic switch. In this review, we recapitulate the molecular mechanisms involved in this angiogenic switch. The rat osteosarcoma model employed would permit further studies in the sequential events leading to initial recruitment of blood vessels and could lead to development of an angiogenesis-based panel of circulating blood cells (endothelial cells, endothelial progenitor cells and accessory cells) that can be quantified and used to detect microscopic tumors or to follow the efficacy of antiangiogenic therapy. Such a result would lead to the possibility of early therapy in cancer progression.

Prostatic sarcomas are very rare tumours with a very poor prognosis. They may coexist with prostatic adenocarcinoma, in which case they are only diagnosed on histological examination of the operative specimen with identification of sarcoma on immunohistochemical analysis. Due to their rapidly invasive potential, they must be detect early in the course, particularly in young subjects. Certain clinical signs, such as obstructive urinary symptoms in a young man or rectal symptoms in an elderly man are suggestive of sarcoma. In this article, the authors report two cases of prostatic sarcoma surgically treated and present a review of the literature on this disease.

Several genes have been involved in drug resistance but none are currently used in the drug decision process. To address this problem, mRNA levels were measured for the 5-fluorouracil metabolism-related genes, thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase in tumor samples of 40 patients with synchronous metastatic colon cancer by quantitative RT-PCR. Drug response and overall survival were also obtained for each patient. A logistic regression model was defined to calculate a response predicting score (RPS) with gene expression levels. This RPS split responders from nonresponders as, at the best statistical threshold (0.35), the area of receiver operating characteristic (ROC) curve established with this method was 0.82 and sensitivity and specificity were respectively 100% and 65.4%. Furthermore patients with scores above 0.35 tended to have better overall survival than those with a score less than 0.35 (p = 0.09).