ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Fibroma , Heart Neoplasms , Myxoma , Sarcoma , Soft Tissue Neoplasms , HumansABSTRACT
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.
Subject(s)
Amyloidosis, Familial , Amyloidosis , Kidney Diseases , Adult , Amyloidosis/diagnosis , Amyloidosis/genetics , Amyloidosis, Familial/genetics , Apolipoprotein A-I/genetics , Humans , Kidney Diseases/diagnosis , Kidney Diseases/genetics , Male , RetinaABSTRACT
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.
Subject(s)
Antibody Affinity , Glomerular Mesangium/metabolism , Glomerulonephritis, IGA/etiology , Immunoglobulin A/metabolism , Animals , Antigens, CD/physiology , Complement Activation , Cytidine Deaminase/physiology , Glomerular Mesangium/pathology , Glomerulonephritis, IGA/immunology , Glycosylation , Humans , Immunoglobulin A/toxicity , Mice , Receptors, Fc/physiologyABSTRACT
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.
Subject(s)
Congenital Hyperinsulinism/complications , Sudden Infant Death/etiology , Autopsy , Congenital Hyperinsulinism/diagnosis , Congenital Hyperinsulinism/pathology , Delayed Diagnosis , Diagnosis, Differential , Female , Hemorrhage/etiology , Humans , Hyperplasia , Infant , Islets of Langerhans/pathology , Vomiting/etiologyABSTRACT
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.
Subject(s)
Butanes/analysis , Butanes/poisoning , Inhalant Abuse , Adolescent , Chromatography, Liquid , Death, Sudden/etiology , Forensic Toxicology , Humans , Male , Mass Spectrometry , Propane/bloodABSTRACT
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.
Subject(s)
Chromosomal Instability/genetics , Colorectal Neoplasms/genetics , Neoplasm Recurrence, Local/genetics , Prognosis , Adult , Aged , Carcinoma in Situ/genetics , Chromosome Breakpoints , Colorectal Neoplasms/pathology , Comparative Genomic Hybridization , Disease Progression , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/pathology , Treatment OutcomeABSTRACT
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.
Subject(s)
Colorectal Neoplasms/genetics , ErbB Receptors/antagonists & inhibitors , Gene Amplification , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Humans , Proto-Oncogene Proteins p21(ras) , Retrospective StudiesABSTRACT
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.
Subject(s)
Adenoma/diagnosis , Incidental Findings , Pancreatic Neoplasms/diagnosis , Adenoma/surgery , Aged , Biomarkers, Tumor/analysis , Diabetes Mellitus, Type 2/complications , Fibromatosis, Aggressive/blood , Fibromatosis, Aggressive/surgery , Humans , Hyperplasia , Male , Middle Aged , Neoplasm Proteins/analysis , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/surgery , Pancreatic Neoplasms/surgery , Pancreatitis, Chronic/complications , Splenectomy , Splenomegaly/etiologyABSTRACT
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.
Subject(s)
Aortic Dissection , Aortitis , Cardiovascular Diseases , Humans , Aortitis/epidemiology , Prognosis , Aorta , Inflammation , Aortic Dissection/diagnosis , Aortic Dissection/epidemiology , Aortic Dissection/surgeryABSTRACT
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.
Subject(s)
Immunosuppressive Agents/adverse effects , Kidney Glomerulus/metabolism , Kidney Glomerulus/pathology , Proteinuria/diagnosis , Sirolimus/adverse effects , Vascular Endothelial Growth Factor A/metabolism , Adult , Cyclosporine/therapeutic use , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Image Processing, Computer-Assisted , Immunoenzyme Techniques , Kidney Transplantation/adverse effects , Male , Middle Aged , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Prognosis , Prospective Studies , Proteinuria/etiology , Proteinuria/metabolismABSTRACT
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.
Subject(s)
Antirheumatic Agents/adverse effects , Arthritis, Juvenile/drug therapy , Inflammatory Bowel Diseases/chemically induced , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adolescent , Arthritis, Juvenile/physiopathology , Child , Child, Preschool , Female , France , Humans , Inflammatory Bowel Diseases/physiopathology , Male , Retrospective Studies , Surveys and Questionnaires , Time Factors , Tumor Necrosis Factor-alpha/adverse effectsSubject(s)
Anatomy/history , Faculty, Medical/history , France , History, 20th Century , History, 21st CenturyABSTRACT
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.
Subject(s)
Carcinoma, Squamous Cell/diagnostic imaging , Fluorodeoxyglucose F18 , Head and Neck Neoplasms/diagnostic imaging , 4-Nitroquinoline-1-oxide/administration & dosage , Animals , Carcinoma, Squamous Cell/chemically induced , Head and Neck Neoplasms/chemically induced , Male , Mouth Neoplasms/chemically induced , Mouth Neoplasms/diagnostic imaging , Positron-Emission Tomography , Rats , Rats, Sprague-Dawley , Tomography, X-Ray ComputedABSTRACT
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.
Subject(s)
Colonic Polyps/pathology , Intestinal Polyposis/pathology , Aged , Humans , Lipoma/pathology , MaleABSTRACT
Childhood pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease. Its pulmonary histopathology, according to comprehensive clinical-radiological findings and BRAFV600E 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. BRAFV600E 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.
Subject(s)
Histiocytosis, Langerhans-Cell/genetics , Histiocytosis, Langerhans-Cell/pathology , Lung Diseases/genetics , Lung Diseases/pathology , Proto-Oncogene Proteins B-raf/genetics , Adolescent , Child , Child, Preschool , Cohort Studies , Female , France , Humans , Infant , Infant, Newborn , Male , Mutation , Retrospective StudiesABSTRACT
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.
Subject(s)
Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/pathology , 4-Nitroquinoline-1-oxide , Animals , Carcinogens , Carcinoma, Squamous Cell/chemically induced , Disease Models, Animal , Fluorodeoxyglucose F18/pharmacology , Head and Neck Neoplasms/chemically induced , Male , Neoplasm Transplantation , Positron-Emission Tomography/methods , Radiopharmaceuticals/pharmacology , Rats , Rats, Sprague-Dawley , Time Factors , Tomography, X-Ray Computed/methodsABSTRACT
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.
Subject(s)
Carcinoma/pathology , Kidney Neoplasms/pathology , Kidney Tubules, Collecting/pathology , Adult , Aged , Aged, 80 and over , Humans , Immunohistochemistry , Kidney Diseases, Cystic/pathology , Male , Middle AgedABSTRACT
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.