Systemic modulation of stress and immune parameters in patients treated for prostate adenocarcinoma by intensity-modulated radiation therapy or stereotactic ablative body radiotherapy.

BACKGROUND: In this exploratory study, the impact of local irradiation on systemic changes in stress and immune parameters was investigated in eight patients treated with intensity-modulated radiation therapy (IMRT) or stereotactic ablative body radiotherapy (SABR) for prostate adenocarcinoma to gain deeper insights into how radiotherapy (RT) modulates the immune system. PATIENTS AND METHODS: RT-qPCR, flow cytometry, metabolomics, and antibody arrays were used to monitor a panel of stress- and immune-related parameters before RT, after the first fraction (SABR) or the first week of treatment (IMRT), after the last fraction, and 3 weeks later in the blood of IMRT (N = 4) or SABR (N = 4) patients. Effect size analysis was used for comparison of results at different timepoints. RESULTS: Several parameters were found to be differentially modulated in IMRT and SABR patients: the expression of TGFB1, IL1B, and CCL3 genes; the expression of HLA-DR on circulating monocytes; the abundance and ratio of phosphatidylcholine and lysophosphatidylcholine metabolites in plasma. More immune modulators in plasma were modulated during IMRT than SABR, with only two common proteins, namely GDF-15 and Tim­3. CONCLUSION: Locally delivered RT induces systemic modulation of the immune system in prostate adenocarcinoma patients. IMRT and SABR appear to specifically affect distinct immune components.

Intramedullary spinal schistosomiasis: A case report and review of the literature.

INTRODUCTION: Spinal cord schistosomiasis is an extremely rare entity presenting with a wide range of neurological symptoms. The early diagnosis and treatment can improve neurological outcome. Histopathological examination is the gold standard for establishing the diagnosis of spinal schistosomiasis, revealing schistosoma eggs. CASE REPORT: We report a case of a 13-year-old male, from Mauritania, with a history of drinking unsafe water, presenting with an acute urinary retention and gait disturbances evolving for 1 month. His clinical examination found an incomplete conus medullary syndrome made up of urinary retention, lively patellar reflexes on the right, ataxia when walking on the same side and indifferent cutaneous planter reflex. The magnetic resonance imaging (MRI) on dorsal spine revealed an enhancing mass involving the conus medullaris in the L1-L2 region suggestive of an arteriovenous malformation or a cavernoma. The resection tissue specimens for diagnosis were fixed with 10 % buffered formalin. The slides were stained with haematoxylin-eosin staining for light microscopy. The diagnosis of schistosomiasis spinal cord was retained. The child has been treated with oral praziquantel 25 mg/kg. DISCUSSION: Diagnosis of schistosomiasis is based on a combination of clinical evaluation, imaging studies, and laboratory tests. However, definitive diagnosis typically requires histopathological examination of spinal cord lesions obtained through biopsy. Differential diagnosis is broad, including an acute vascular event and/or tumor, especially in children from endemic areas for schistosomiasis. CONCLUSION: Schistosomiasis infection should be suspected when encountering medullary lesion associated to peripheral hypereosinophilia. Surgical excision combined with praziquantel may help improve neurological deficits.

Congenital cervical choristoma of the neck mimicking cystic lymphangioma.

INTRODUCTION: Choristoma is a mass presenting normal histology, but in an abnormal location. Cystic choristoma is rarely reported in the head and neck region. Neonatal cystic masses in the neck suggest usually correspond to a diagnosis of cystic lymphangioma. CASE REPORT: We report a case of a congenital cystic choristoma of the neck clinically and radiologically mimicking cystic lymphangioma. DISCUSSION: Congenital cystic choristoma is an extremely rare lesion, essentially described in neonates, composed of various types of tissues. The diagnosis of congenital cystic choristoma may be suggested on imaging and must be confirmed by histopathological examination. Treatment consists of complete surgical resection.

Myocardial lysis in a fetus induced by maternal paraphenylenediamine poisoning following an intentional ingestion to induce abortion.

The acute toxicity of paraphenylenediamine (PPD) has been associated with several histopathological changes. In humans, acute PPD poisoning is known to cause rhabdomyolisis and particularly myocardial lysis. However, its toxicity for the fetus has never been reported in the literature. We report a case of myocardial lysis in a fetus expelled by a 22-year-old mother after apparent ingestion of an unknown amount of PPD. The patient was admitted to our intensive care unit with acute onset of respiratory distress and rhabdomyolysis. The pelvic ultrasonography on admission showed a normally progressing pregnancy of 23-24 weeks. On day 9 post-ingestion, the patient spontaneously expelled a non-viable fetus. The fetal examination did not show any external or macroscopic abnormalities. However, the histopathological exam showed an important heart and lung congestion. There was also some interstitial edema and inflammation at the base of the lingua, in addition to a chorionic villus thrombosis and abruptio placentae. The histopathology of the myocardium showed lysis of the cardiac muscle. This observation suggests that the PPD was most likely responsible for the myocardial injury in the fetus.

[Pulmonary alveolar microlithiasis: report of four cases]. / La microlithiase alvéolaire pulmonaire: à propos de quatre cas.

INTRODUCTION: Pulmonary alveolar microlithiasis is a rare disease characterised by the formation and deposition of calcium phosphate microliths in the lung. It is an autosomal recessive disorder, for which mutation in the SLC34A2 gene was recently found to be responsible for the disease. OBSERVATIONS: We report on four cases of pulmonary alveolar microlithiasis. Three patients were asymptomatic. The diagnosis was made after histological confirmation in three patients. The outcome was marked by the death of one patient. CONCLUSION: Pulmonary alveolar microlithiasis is a rare disease. Diagnosis is made with high-resolution computed tomography, which exhibits the calcic character and distribution of the lesions, thus avoiding the need to perform lung biopsy. We suggest that a literature review be performed.

An atypical odontogenic myxoma.

INTRODUCTION: Odontogenic myxoma is an uncommon tumor of the jaws, benign but locally invasive. It arises from the mesenchymal portion of the tooth germ. It has a variable non-specific clinical and radiological appearance, and may be confused with other lesions of the jaws. CASE REPORT: A patient aged 50 presented for a periodontal treatment. After routine retroalveolar X-rays, we noted a small limited radiolucency between the left mandibular canine and the left mandibular first premolar. There were no clinical symptoms. Histology after enucleation of the lesion revealed the diagnosis of odontogenic myxoma. DISCUSSION: Odontogenic myxoma is a relatively rare benign neoplasia. It is locally aggressive, inducing important facial deformation and tooth displacement. The lesion often grows without symptoms and presents as a painless swelling. The radiographic features are variable, it appears as a unilocular or multilocular radiolucency, and the diagnosis is therefore not easy. The case reported is an atypical presentation of odontogenic myxoma because of the small size of the lesion, the radiographic features, and the early detection and management.

[Renal failure in sarcoidosis: case report]. / Sarcoïdose et insuffisance rénale: à propos de deux cas.

Renal involvement in sarcoidosis is rare and more often related to calcium metabolism disorders or granulomatous interstitial nephritis, glomerulonephritis is exceptional. The two cases of renal failure reported in this article illustrate the gravity of this complication, whose treatment remains difficult.

The acute regulation of mineralocorticoid biosynthesis: scenarios for the StAR system.

The zona glomerulosa cell of the adrenal cortex produces mineralocorticoids in response to physiological stimuli (angiotensin II and extracellular K(+)) activating the Ca(2+) messenger system. The mechanisms underlying the generation of the Ca(2+) signal have been analyzed extensively and recent developments have contributed to bridging the gap between intracellular signals and activation of the biological function. This article summarizes the current knowledge on the intracellular targets of the Ca(2+) messenger, obtained mainly in bovine glomerulosa cells. Ca(2+) appears to exert a dual effect, both at the intramitochondrial level and at the nuclear level, where it activates steroidogenic acute regulatory protein (StAR) gene transcription.

Atrial natriuretic peptide inhibits calcium-induced steroidogenic acute regulatory protein gene transcription in adrenal glomerulosa cells.

Atrial natriuretic peptide (ANP) is a potent inhibitor of mineralocorticoid synthesis induced in adrenal glomerulosa cells by physiological agonists activating the calcium messenger system, such as angiotensin II (Ang II) and potassium ion (K+). While the role of calcium in mediating Ang II- and K(+)-induced aldosterone production is clearly established, the mechanisms leading to blockade of this steroidogenic response by ANP remain obscure. We have used bovine adrenal zona glomerulosa cells in primary culture, in which an activation of the calcium messenger system was mimicked by a 2-h exposure to an intracellular high-calcium clamp. The effect of ANP was studied on the following parameters of the steroidogenic pathway: 1) pregnenolone and aldosterone production; 2) changes in cytosolic ([Ca2+]c) and mitochondrial ([Ca2+]m) Ca2+ concentrations, as assessed with targeted recombinant aequorin; 3) cholesterol content in outer mitochondrial membranes (OM), contact sites (CS), and inner membranes (IM); 4) steroidogenic acute regulatory (StAR) protein import into mitochondria by Western blot analysis; 5) StAR protein synthesis, as determined by [35S]methionine incorporation, immunoprecipitation, and SDS-PAGE; 6) StAR mRNA levels by Northern blot analysis with a StAR cDNA; 7) StAR gene transcription by nuclear run-on analysis. While clamping Ca2+ at 950 nM raised pregnenolone output 3.5-fold and aldosterone output 3-fold, ANP prevented these responses with an IC50 of 1 nM and a maximal effect of 90% inhibition at 10 nM. In contrast, ANP did not affect the [Ca2+]c or [Ca2+]m changes occurring under Ca2+ clamp or Ang II stimulation in glomerulosa cells. The accumulation of cholesterol content in CS (139.7 +/- 10.7% of control) observed under high-Ca2+ clamp was prevented by 10 nM ANP (92.4 +/- 4% of control). Similarly, while Ca2+ induced a marked accumulation of StAR protein in mitochondria of glomerulosa cells to 218 +/- 44% (n = 3) of controls, the presence of ANP led to a blockade of StAR protein mitochondrial import (113.3 +/- 15.0%). This effect was due to a complete suppression of the increased [35S]methionine incorporation into StAR protein that occurred under Ca2+ clamp (94.5 +/- 12.8% vs. 167.5 +/- 17.3%, n = 3). Furthermore, while the high-Ca2+ clamp significantly increased StAR mRNA levels to 188.5 +/- 8.4 of controls (n = 4), ANP completely prevented this response. Nuclear run-on analysis showed that increases in intracellular Ca2+ resulted in transcriptional induction of the StAR gene and that ANP inhibited this process. These results demonstrate that Ca2+ exerts a transcriptional control on StAR protein expression and that ANP appears to elicit its inhibitory effect on aldosterone biosynthesis by acting as a negative physiological regulator of StAR gene expression.

Characterization of the 3 beta-hydroxysteroid dehydrogenase activity associated with bovine adrenocortical mitochondria.

The enzymatic activity of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD/I) constitutes an essential step in the biosynthesis of active steroid hormones such as progesterone, mineralo- and gluco-corticoids, estrogens, and androgens. Its subcellular localization in steroidogenic tissues is usually considered to be mainly microsomal; however, 3 beta HSD/I activity is also present in mitochondrial preparations. In the present study, the distribution of 3 beta HSD/I in bovine adrenocortical subcellular preparations has been reexamined, and the catalytic properties of the enzyme present in the various cell compartments have been characterized. About 30% of the total 3 beta HSD/I was found to remain tightly associated with highly purified mitochondrial preparations. The preferred substrate of the mitochondrial enzyme was pregnenolone. Examination of submitochondrial preparations revealed that 3 beta HSD/I was associated with both the inner membrane and a particulate fraction that sediments in a density gradient between inner and outer membranes. The specific activity of the enzyme was at its highest in this intermediate density fraction, which exhibited the properties of mitochondrial intermembrane contact sites. Taken together, these observations suggest that these contact sites may represent a supramolecular organization of biological significance in adrenocortical cell steroidogenic functions. Such intermembrane fusion sites would facilitate the access of cholesterol to the inner membrane in which cholesterol side-chain cleavage cytochrome P-450 is located as well as the rapid transformation of its reaction product (i.e. pregnenolone) to progesterone by 3 beta HSD/I. Such a submitochondrial organization opens new possibilities in the understanding of the regulation of adrenocortical differentiated functions.

Decreased expression of steroidogenic acute regulatory protein: a novel mechanism participating in the leptin-induced inhibition of glucocorticoid biosynthesis.

The adipocyte-derived hormone leptin is a central modulator of food intake, metabolism and neuroendocrine functions. It is also involved in a physiological loop linking the activity of the hypothalamo-pituitary-adrenal axis and adipose tissue. At the adrenal level, leptin has been shown to antagonize the effects of ACTH on glucocorticoid biosynthesis by decreasing the expression of various enzymes of the steroid biosynthetic pathway. The steroidogenic acute regulatory protein regulates cholesterol delivery to the P450(scc) enzyme, a process that is rate limiting in steroid hormone biosynthesis. We have demonstrated here that leptin significantly inhibits the expression of steroidogenic acute regulatory protein in primary cultures of rat adrenocortical cells. This inhibition was observed at both the protein and mRNA levels. In contrast, leptin was not found to interfere with the expression of the cytosolic enzyme cholesterol ester hydrolase or with that of the mitochondrial enzyme P450(scc). In addition, we observed the anticipated stimulation of cAMP production by ACTH in the presence of leptin, suggesting that it does not interfere with intracellular ACTH signaling. In summary, our data provide evidence that the interplay existing between leptin and ACTH in vivo is mediated at least partially via a direct and opposite modulation of steroidogenic acute regulatory protein, a key factor in the adrenal steroid biosynthetic pathway. This effect of leptin could also be relevant to other steroidogenic tissues.

Angiotensin II promotes selective uptake of high density lipoprotein cholesterol esters in bovine adrenal glomerulosa and human adrenocortical carcinoma cells through induction of scavenger receptor class B type I.

Angiotensin II is one of the main physiological regulators of aldosterone biosynthesis in the zona glomerulosa of the adrenal cortex. The hormone stimulates intracellular cholesterol mobilization to the mitochondrion for steroid biosynthesis. Here we have examined whether angiotensin II also modulates exogenous lipoprotein cholesterol ester supply to the steroidogenic machinery and whether this control is exerted on the selective transport of high density lipoprotein-derived cholesterol ester to intracellular lipid droplets through the scavenger receptor class B type I. In bovine adrenal glomerulosa and human NCI H295R adrenocortical carcinoma cells, high density lipoprotein stimulated steroid production. Angiotensin II pretreatment for 24 h potentiated this response. Fluorescence microscopy of cellular uptake of reconstituted high density lipoprotein containing a fluorescent cholesterol ester revealed an initial, time-dependent narrow labeling of the cell membrane followed by an intense accumulation of the fluorescent cholesterol ester within lipid droplets. At all time points, labeling was more pronounced in cells that had been treated for 24 h with angiotensin II. Fluorescence incorporation into cells was prevented by a monoclonal antibody directed against apolipoprotein A-I. Upon quantitative fluorometric determination, cholesterol ester uptake in angiotensin II-treated bovine cells was increased to 175 +/- 15% of controls after 2 h and to 260 +/- 10% after 4 h of exposure to fluorescent high density lipoprotein. The amount of scavenger receptor class B type I protein detected in cells treated with angiotensin II for 24 h reached 203 +/- 12% of that measured in control cells (n = 3, P < 0.01). In contrast, low density lipoprotein receptors were only minimally affected by angiotensin II treatment. This increase in scavenger receptor class B type I protein was associated with a 3-fold induction of scavenger receptor class B type I mRNA, which could be prevented by actinomycin D but not by cycloheximide. Similar results were obtained in the human adenocarcinoma cell line H295R. These observations show that angiotensin II regulates the scavenger receptor class B type I-mediated selective transport of lipoprotein cholesterol ester across the cell membrane as a major source of precursor for mineralocorticoid biosynthesis in both human and bovine adrenal cells.

Dual subcellular localization of the 3 beta-hydroxysteroid dehydrogenase isomerase: characterization of the mitochondrial enzyme in the bovine adrenal cortex.

The enzyme 3 beta-hydroxysteroid dehydrogenase isomerase (3 beta-HSD/I) is an essential step in the biosynthesis of steroid such as progesterone, mineralo- and gluco-corticoids, estrogens and androgens in steroidogenic tissues. It is considered to be mainly localized in microsomes; however, 3 beta-HSD/I activity has also been described to be associated with mitochondrial preparations. In this study, we examined the subcellular distribution of 3 beta-HSD/I in bovine adrenocortical tissue and we characterized the catalytic properties of the enzyme present in the various cell compartments. About 30% of the total 3 beta-HSD/I activity was found to remain tightly associated with the purified mitochondrial pellet. The 3 beta-HSD/I and 3-ketoreductase activities were found in microsomes as well as in mitochondria. The 3 beta-HSD/I associated with the mitochondrial fraction did not require addition of exogenous NAD+. When the pyridine nucleotide was reduced following addition of substrates of the tricarboxylic acids cycle, the mitochondrial 3 beta-HSD/I activity decreased, suggesting that the enzyme utilizes NAD+ available from the matrix space. By contrast, the microsomal enzyme was inactive in the absence of exogenous NAD+. Submitochondrial fractionation disclosed that 3 beta-HSD/I was associated (i) with the inner membrane and (ii) with a particulate fraction sedimenting in a density gradient between inner and outer membranes. This fraction was characterized as contact sites between the two membranes. 3 beta-HSD/I specific activity was much higher in this fraction than in the inner mitochondrial membrane. Altogether, these observations suggest that these mitochondrial intermembrane contact sites may represent a special organization of functional significance, facilitating both the access of cholesterol to the inner membrane where cytochrome P-450scc is located and the rapid transformation of its product, pregnenolone, to progesterone, through 3 beta-HSD/I activity.

Organization of 3 beta-hydroxysteroid dehydrogenase/isomerase and cytochrome P450scc into a catalytically active molecular complex in bovine adrenocortical mitochondria.

We have previously reported the co-localization [Cherradi et al., Endocrinology 134 (1994) 1358-1364] of 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) and cytochrome P450scc (cyt. P450scc) in the inner membrane and in the intermembrane contact sites of adrenocortical mitochondria. This observation raises the question of a possible functional association between the two proteins. Isolated bovine adrenocortical mitochondria are able to convert cholesterol to progesterone without the need of exogenous cofactors. An association of 3 beta-HSD and cyt. P450scc is observed during the purification of 3 beta-HSD from mitochondria. The behaviour of 3 beta-HSD on a column of Heparin-Sepharose is modified by the presence of cyt. P450scc. Immunoprecipitations from mitochondria with either anti-cyt. P450scc or anti 3 beta-HSD antibodies result in a co-precipitation of the two proteins. Both proteins engaged in these immunocomplexes are catalytically active. The interaction was further demonstrated by the surface plasmon resonance method using purified components. An affinity demonstrated by the surface plasmon resonance method using purified components. An affinity constant of 0.12 microM between 3 beta-HSD and P450scc was obtained. These observations suggest that P450scc and 3 beta-HSD may associate into a molecular complex in the mitochondrial compartment and may constitute a functional steroidogenic unit, thus opening new possibilities in the regulation of the production of progesterone and its flow in the adrenocortical cell.

Purification and characterization of 3 beta-hydroxysteroid-dehydrogenase/isomerase from bovine adrenal cortex.

The formation of 4-ene-3-ketosteroids from 3 beta-hydroxy-5-ene precursors is an obligatory step in the biosynthesis of hormonal steroids such as glucocorticoids, mineralocorticoids, estrogens and androgens. In the adrenal cortex, pregnenolone, 17 alpha-hydroxy-pregnenolone and dehydroisoandrosterone are converted to progesterone, 17 alpha-hydroxy-progesterone and androstenedione, respectively, by the enzymatic system 3 beta-hydroxy-5-ene steroid dehydrogenase and 3-keto-5-ene steroid isomerase (3 beta-HSD/I). The present work reports a two step purification procedure which yields an homogenous preparation of 3 beta-HSD/I from bovine adrenal cortex. It uses solubilization of the microsomal proteins followed by two chromatographic steps, i.e. DEAE-cellulose and heparine-sepharose columns. The enzyme was obtained as an homogeneous protein exhibiting an apparent molecular size of 45 kDa upon SDS-gel electrophoresis and of 81 kDa upon gel filtration. The purified enzyme exhibits both the 5-ene-3 beta-ol steroid dehydrogenase and isomerase activities in contrast to previous work using a more complex procedure which yielded a final preparation having lost its isomerase activity [Hiwatashi et al., Biochem. J. 98 (1985) 1519-1525]. N-terminal aminoacid (29 residues) sequence of the purified protein was determined and was found identical to that predicted from the nucleic acid sequence of the recently identified enzyme cDNA [Zhas et al. FEBS Lett. 259 (1989) 153-157].

[Clear cell sarcoma of the kidney. A study of 13 cases]. / Sarcome rénal à cellules claires. A propos d'une série de 13 cas.

UNLABELLED: Clear cell sarcoma of the kidney (CCSK) also called a "bone-metastasizing renal tumor of childhood" is the second common pediatric renal neoplasm. This tumor is associated with a higher rate of relapse and a wider distribution of metastases than Wilms' tumor. PATIENTS AND METHODS: We have reviewed records of 13 cases of CCSK among 277 renal tumors (5%) diagnosed at the children's hospital of Rabat between 1990 and 2002. RESULTS: The median age at diagnosis was 14 months (5 months-9 years). The male to female ratio was 5.5:1.00. Abdominal mass, usually the first physical finding, was associated with hematuria in four cases. No congenital malformation syndrome or familial Wilms' tumor were observed. Imaging studies found out seven right and six left intrarenal processes. Preoperative chemotherapy was given according to the SIOP9, SIOP93-01 and GFAOP 98 protocols. Twelve of 13 children underwent nephrectomy. Tumor measurements varied through 450-3450 g and 7-26 cm. The classic morphologic pattern was seen in nine cases (69%). The distribution local stage was I: three cases; II: three cases; III: six cases; IV: one case. Postoperative chemotherapy and radiotherapy (21 600-30 600 cGy) was done in 10 cases. With a median follow up of 44 months, four patients showed bone metastases (31%), four are alive in CR, four are lost for follow up and five died. CONCLUSION: CCSK remains the pediatric renal tumor most frequently misdiagnosed. Its aggressiveness and its ability to give bone metastases need to recognize early this diagnosis for an adapted treatment.

[Benign granular cell anal tumor]. / Tumeur anale bénigne à cellules granuleuses.

INTRODUCTION: Granular cell tumors (GCT) are rarely located in the perianal area. OBSERVATION: Over the past 3 years, a 56 year-old man presented a papule of the right margin of the anus that had progressively increased in size (1.5 cm). Cell proliferation was located in the dermis and strongly expressed the S100 protein. It was covered by a pseudo-epitheliomatous hyperplasia of the overlying epidermis. Forty months after local surgical excision, there was no sign of recurrence. COMMENTS: Granular cell tumors are rare and usually benign. When cutaneous or mucosal, the pseudo-epitheliomatous hyperplasia of the overlying epithelium may, on superficial samples, be mistakenly diagnosed as squamous cell carcinomas. Malignant GCT may, histologically, appear identical to a benign GCT and only the appearance of metastases (generally after local recurrence) permits the subsequent diagnosis of malignancy.

[Pleuropulmonary blastoma: possible interest of neoadjuvant chemotherapy. A case report]. / Blastome pleuropulmonaire: intérêt possible d'une chimiothérapie néoadjuvante. A propos d'un cas.

Pleuropulmonary blastoma is a very exceptional anatomoclinical and histological entity recently distinguished from adult pneumoblastoma. This tumor, observed in children aged less than 15, can involve the lung, the pleura, or the mediastinum and is characterized by a very poor prognosis. We report the case of a 4-year-old girl who developed pleuropulmonary blastoma which was discovered in a context of respiratory distress. Standard chest x-ray revealed an opacity covering the entire left lung. Histology and immunohistology led to the diagnosis of pleuropulmonary blastoma with several components: blastematous, malignant mesenchymatous with pluridirectional differentiation, and benign epithelial tissue. Treatment consisted in preoperative chemotherapy and radiotherapy to reduce tumor volume. This neoadjuvant treatment is not widely reported and its relatively favorable result allowed tumor resection. This approach might be useful in similar cases.

[Chondromyxoid fibroma of bone: a rare benign bone tumor in children]. / Le fibrome chondromyxoïde de l'os: une tumeur osseuse rare de l'enfant.

Chondromyxoid fibroma is a rare benign tumor that is typically found in the metaphyseal ends of long tubular bones, such as the tibia. The radiographic appearances are those of a single, lytic lesion with lobulated margins, septations, cortical expansion and a sclerotic rim. The classic histological feature of a chondromyxoid fibroma is stellate or spindle-shaped cells arranged in lobules in a myxoid or chondroid background. Two cases are presented here: 8, and 12-year-old patients, both with lesions in the proximal tibia. The first case showed an unusual feature: it was diaphyseal chondromyxoid fibroma. In the second case, the lesion was metaphyso-diaphyseal. The differential diagnosis includes chondroblastoma, myxoma, aneurysmal cyst as well as chondrosarcoma. A surgical conservative treatment with complete excision is recommended even in case of recurrence.

Serum miR-483-5p and miR-195 are predictive of recurrence risk in adrenocortical cancer patients.

Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Local and distant recurrences occur in a subset of tumors classified as 'aggressive' ACC (aACC), as opposed to 'non-aggressive' ACC (naACC). In this study, we investigated whether tissue and serum microRNAs (miRNAs) are predictive of ACC prognosis. Tissue miRNA expression profiles were determined using microarrays in a test series of six adrenocortical adenomas (ACAs), six naACCs, and six aACCs. Eight miRNAs were selected for further validation by quantitative RT-PCR (ten ACAs, nine naACCs, nine aACCs, and three normal adrenals). Serum levels of five miRNAs were measured in samples from 56 subjects (19 healthy controls (HC), 14 ACA, nine naACC, and 14 aACC patients). MiR-195 and miR-335 levels were significantly decreased in both tumor and serum samples of ACC patients relative to ACA patients or HC. MiR-139-5p and miR-376a levels were significantly increased in aACC compared with naACC patients in tumor samples only. Tissue miR-483-5p was markedly upregulated in a majority of ACC compared with ACA patients or HC, but most importantly, serum miR-483-5p was detected only in aACC patients. High circulating levels of miR-483-5p or low circulating levels of miR-195 were associated with both shorter recurrence-free survival (P=0.0004 and P=0.0014 respectively) and shorter overall survival (P=0.0005 and P=0.0086 respectively). In conclusion, this study reports for the first time that circulating miR-483-5p and miR-195 are promising noninvasive biomarkers with a highly specific prognostic value for the clinical outcome of ACC patients.