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M Younes

Publications and source records attributed to M Younes.

At least 37 records · Page 2Linked to original sources
PubMed2000

Fas ligand expression in esophageal carcinomas and their lymph node metastases.

BACKGROUND: Although esophageal adenocarcinomas (EADCA) have been shown to have substantially reduced or absent Fas expression, the status of Fas ligand (FasL) in these tumors, especially adenocarcinomas, is largely unknown. METHODS: Using immunohistochemistry, the authors investigated FasL expression in sections of formalin fixed, paraffin embedded tissue from 13 EADCA. They also studied sections of 15 esophageal squamous cell carcinomas (ESCCA) and of lymph node metastases from 7 EADCA and 4 ESCCA. The percentage of FasL positive cells in each tumor was recorded. FasL expression in EADCA was compared with that in ESCCA and with lymph node status. Statistical analysis was performed using the Fisher exact test. RESULTS: No specific staining pattern was seen in adenocarcinomas. In ESCCA, FasL was often located in the cells at the periphery of tumor nests. All (100%) of EADCA showed FasL expression in greater than 25% of the cancer cells, and all were associated with lymph node metastasis. Fifty-three percent of ESCCA showed FasL expression in greater than 25% of the cancer cells and 33% had lymph node metastasis. Expression of FasL in greater than 25% of tumor cells was associated with a significantly higher incidence of lymph node metastasis (P=0.0001). All lymph node metastases from esophageal carcinomas showed FasL immunoreactivity in greater than 50% of the metastatic tumor cells. CONCLUSIONS: FasL expression in greater than 25% of cancer cells correlates with a high incidence of lymph node metastasis in esophageal carcinomas. All cancer metastases in lymph nodes express FasL in >50% of the cells. These findings indicate that FasL plays an important role in the immune evasion and metastasis of esophageal carcinomas.

Adenocarcinoma↗
PubMed2000

Pesticides in drinking water--a case study.

Pesticides occupy a unique position among chemicals found in drinking water, since they are deliberately used to control pests in agriculture and public health. They comprise a variety of compounds of various chemical properties (many of which being persistent in the environment), toxic potential, and mechanism of action. Safety assessment for drinking water is conducted by allocating health-based guidelines for exposure through this environmental medium. The tolerable daily intake (TDI) approach is used by WHO in the case of pesticides with assumed thresholds of effect, while low-dose extrapolation is used in the case of non-threshold carcinogens. Risk management, however, can also be based on the precautionary principle. Risk assessment evaluates the risk emanating from a given exposure on the basis of all available data.

Humans↗
PubMed2000

Barrett's esophagus.

Barrett's esophagus occurs more frequently than previously anticipated. Detection of Barrett's esophagus is by endoscopic biopsy in which normal squamous epithelium of the esophagus is replaced by a specialized columnar epithelium of any length. Patients with more than five years of gastroesophageal reflux symptoms, particularly those 50 years of age or older, should have upper endoscopy to detect Barrett's esophagus. With recognition of Barrett's esophagus as a premalignant lesion, the crucial issue is surveillance for detection of dysplasia. Although the natural history of dysplasia is incompletely defined, it is clear that patients with dysplasia have a higher risk for adenocarcinoma than those without dysplasia. Dysplasia is not the ideal marker for selecting patients at high risk for adenocarcinoma, however; recent studies have shown that p53 protein accumulation appears to be earlier and more specific/sensitive marker of malignant potential in Barrett's esophagus. Management of Barrett's esophagus often involves a multidisciplinary evaluation and its current status is reviewed.

Barrett Esophagus↗
PubMed2000

Decreased expression of Fas (CD95/APO1) associated with goblet cell metaplasia in Barrett's esophagus.

Fas ligand (FasL) has been shown to induce apoptosis in cells expressing its receptor Fas. We have recently shown that Fas ligand is overexpressed in all cases of Barrett's metaplasia (BM) with dysplasia and esophageal adenocarcinomas, and in a few cases of BM negative with dysplasia. The aim of this work was to determine the status of Fas expression in BM with and without dysplasia or carcinoma. Formalin-fixed and paraffin-embedded tissue sections from esophageal biopsies and esophagectomy specimens with BM, with and without dysplasia and carcinoma, were immunostained for Fas and FasL using the immunoperoxidase technique. The percentage of positive cells in each case was evaluated and compared with the degree of dysplasia. When Fas expression was assessed in glands with goblet cell metaplasia, Fas immunoreactivity was either undetected or present in less than 10% of the cells in 85% of the cases, and only 1 (4%) of the 28 cases examined showed Fas immunoreactivity in more than 25% of the cells. When we compared Fas expression in goblet cell-containing glands with glands of gastric cardia phenotype, we found that in the 26 cases of BM with or without dysplasia Fas was completely undetectable in goblet cell-containing glands in 15 (58%) of the cases but was undetectable in only 3 (12%) of the glands with gastric cardia phenotype (P = .002). Fas is usually undetectable or is expressed at a low level in BM with or without dysplasia or carcinoma. Fas expression in goblet cell-containing glands is less frequent than in glands with gastric cardia phenotype in the same specimens. BM with dysplasia or carcinoma overexpress FasL, so decreased Fas expression may protect BM with dysplasia and carcinoma from self-destruction while allowing them to evade immune surveillance.

Adenocarcinoma↗
PubMed2000

Relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 overexpression in Barrett metaplasia.

BACKGROUND: There is a need for molecular markers of malignant progression in Barrett metaplasia (BM). The aim of this study is to determine the relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 in BM. METHODS: Sections of esophageal biopsy specimens from 120 patients with BM were evaluated for dysplasia, p53 protein, and Glut1 expression by immunohistochemistry, and DNA ploidy by Feulgen stain and image analysis. In cases with diploid DNA histograms, the percentage cells in the G0G1 and G2M phases of the cell cycle were determined. RESULTS: Of 108 diploid cases 19 (28%) of 69 cases with G0G1 > or = 90% or G2M > or = 8.33% were p53-positive, in contrast to only 1 (3%) of 39 cases with lower G0G1 or G2M (P = 0.0008). Of 32 p53-positive cases 11 (32%) were aneuploid, in contrast to none (0%) of 88 p53-negative cases (P < 0.0001). Ten (91%) of 11 aneuploid cases were high-grade dysplasial adenocarcinoma (HGD/CA), compared with only 1 (1%) of 109 diploid cases (P < 0.0001). Five (45%) of 11 cases with HGD/CA were Glut1-positive, in contrast to none (0%) of 109 cases without HGD/CA (P < 0.0001). CONCLUSIONS: Our data strongly suggest that in BM, after oxidative DNA damage, as a result of gastroesophageal reflux, there is an increase in the percentage of cells in the G0G1 or G2M phases of the cell cycle to enable repair of damaged DNA; in some of these cases this is followed sequentially by p53 gene mutation and protein accumulation, DNA aneuploidy, HGD, and CA with or without Glut1 overexpression. These events can be detected in routinely processed biopsy samples.

Adenocarcinoma↗
PubMed2000

Optimized cyclin D1 immunoperoxidase staining in mantle cell lymphoma.

Mantle cell lymphoma (MCL) has a worse prognosis than MALT lymphoma (MALTL). Distinction between MCL and MALTL on purely morphologic grounds can be difficult. Cyclin D1 (PRAD1/bcl1) is overexpressed in MCL as a result of a t(11:14) gene rearrangement, which leads to overexpression of cyclin D1 mRNA and protein. The immunohistochemical detection of cyclin D1 in MCL has been reported by several authors to be highly specific with sensitivity ranging from 70%-100%, but diagnostic laboratories have reported difficulty in finding a reliable method for cyclin D1 immunostaining. The aim of this study was to evaluate and optimize a method for detection of cyclin D1 by paraffin section immunoperoxidase staining. Sections of routinely processed tissue from five MCL and one splenic marginal zone lymphoma (MZL) were immunostained using a mixture of two primary monoclonal antibodies and a standard avidin-streptavidin method. Antigen retrieval was performed using 1) steam heat in citrate buffer, 2) as in "1" followed by sonication for one minute, and 3) as in "2" followed by enzymatic digestion. All the above were repeated, with the additional use of catalyzed signal amplification (CSA). Later, sections of the same cases, plus three MALTL were immunostained as in "2". Steam heat antigen retrieval alone produced the best results. All MCL showed positive nuclear staining while the MZL and all MALTL were negative. Sonication did not enhance staining noticeably, whereas enzymatic digestion produced cytoplasmic staining. CSA increased background staining with no significant gain in nuclear stain intensity. We conclude that cyclin D1 immunostaining of formalin-fixed, paraffin-embedded tissue can be reliably achieved by heat induces antigen retrieval and a cocktail of two monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed2000

Effects of inspiratory flow on diaphragmatic motor output in normal subjects.

Increasing inspiratory flow (V) has been shown to shorten neural inspiratory time (TI(n)) in normal subjects breathing on a mechanical ventilator, but the effect of V on respiratory motor output before inspiratory termination has not previously been studied in humans. While breathing spontaneously on a mechanical ventilator, eight normal subjects were intermittently exposed to 200-ms-duration positive pressure pulses of different amplitudes at the onset of inspiration. Based on the increase in V above control breaths (DeltaV), trials were grouped into small, medium, and large groups (mean DeltaV: 0.51, 1.11, and 1.65 l/s, respectively). We measured TI(n), transdiaphragmatic pressure (Pdi), and electrical activity (electromyogram) of the diaphragm (EMGdi). Transient increases in V caused shortening of TI(n) from 1.34 to 1.10 (not significant), 1.55 to 1.11 (P < 0.005), and 1.58 to 1.17 s (P < 0. 005) in the small, medium, and large DeltaV groups, respectively. EMGdi measured at end TI(n) of the pulse breaths was 131 (P < 0.05), 142, and 155% (P < 0.05) of the EMGdi of the control breaths at an identical time point in the small, medium, and large trials, respectively. The latency of the excitation was 126 +/- 42 (SD) ms, consistent with a reflex effect. Increasing V had two countervailing effects on Pdi: 1) a depressant mechanical effect due primarily to the force-length (11.2 cmH(2)O/l) relation of the diaphragm, and 2) an increase in diaphragm activation. For the eight subjects, mean peak Pdi did not change significantly, but there was significant intersubject variability, reflecting variability in the strength of the excitation reflex. We conclude that increasing inspiratory V causes a graded facilitation of EMGdi, which serves to counteract the negative effect of the force-length relation on Pdi.

Adult↗
PubMed1999

Powerful respiratory stimulation by thin muscle afferents.

The ventilatory responses to electrical stimulation of phrenic afferents were examined in spontaneously breathing dogs at different levels of sodium pentobarbital anesthesia. High intensity stimulation (activation of all the afferents, including thin fibers) increased ventilation (V(E)). The increase in V(E) was comparable to that of breathing 10% CO2 and was inversely related to anesthesia level. Under light anesthesia, V(E) increased to 282+/-36% of the control value when the phrenic nerve was stimulated at 130 times the twitch threshold (n = 15; P < 0.01). The increase in V(E) was due to increases in breathing rate (193+/-19%) and tidal volume (V(T)) (143+/-8%). On the other hand, inspiratory time (T(I)) decreased. Thus, average airflow rate (V(T)/T(I)) increased to 204+/-23%. After administration of 20 and 40% of the initial dose of pentobarbital, V(E) response was attenuated to 157+/-21 and 121+/-4%, respectively. We conclude that thin muscle afferents are capable of eliciting pronounced ventilatory stimulation. The small responses observed earlier were likely due to depth of anesthesia.

Anesthesia↗
PubMed1999

Background to the ADI/TDI/PTWI.

International scientific committees such as the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and the Joint FAO/WHO Meeting on Pesticide Residues (JMPR), regional scientific committees such as those of the European Union, and national regulatory agencies generally use the safety factor approach for establishing acceptable or tolerable intakes of substances that exhibit thresholds of toxicity. The acceptable daily intake (ADI) is used widely to describe "safe" levels of intake; other terms that are used are the reference dose (RfD) and tolerable intakes that are expressed on either a daily (TDI or tolerable daily intake) or weekly basis. JECFA uses the term PTWI, or provisional tolerable daily intake, for contaminants that may accumulate in the body. The weekly designation is used to stress the importance of limiting intake over a period of time for such substances. When using this approach no-observed-effect levels (NOELs) or no-observed-adverse-effect levels (NOAELs) are identified in the critical studies, to which appropriate safety or uncertainty factors are applied. Although the value of safety factors varies depending upon a number of factors, 100 is most often used, which is designed to account for interspecies and intraspecies variations. Within the framework of the IPCS project on harmonization of approaches to the assessment of risk from exposure to chemicals, issues relating to uncertainty and variability are being addressed with the aim of relying, whenever appropriate, on data-derived safety/uncertainty factors. The ILSI Europe ADI Task Force has, for the past few years, been considering the scientific basis for the safety factor, which will be discussed by other speakers in the workshop. The value of the NOAEL is dependent on the design of the study. Because of the expense and time required conduct many studies, doses are usually spread over wide intervals. Thus, the no-observed-adverse-effect level may be considerably less than a marginally effective dose. In addition, use traditionally has not been made of the dose-response relationship when establishing ADIs. Newer approaches such as the benchmark dose may provide ways of making use of dose-response information. It is unlikely that consumption at the level of the ADI will result in significant risk to the consumer because of the conservatisms that are built into it. It usually is based on long-term studies that are intended to mimic consumption over the lifetime of humans. The ADI is applied to "discretionary" chemicals (food additives, veterinary drugs, and pesticides) by JECFA and JMPR, which are relatively easy to control if safety problems are identified. On the other hand, when tolerable intakes are derived for contaminants that are present in the environment at high levels, the use of standard safety factors could result in discarding large portions of the food supply. Thus, it is very important that the basis for the tolerable intake is fully described so that informed judgments can be made about the health consequences of exceeding it.

Animals↗
PubMed1999

Specific issues in health risk assessment of endocrine disrupting chemicals and international activities.

Specific issues in health risk assessment of EDCs and correlated international activities thereof are discussed. Risk characterization is a synthesis of all information including hazard assessment, dose-response relationship, and exposure information to identify clearly the strengths and weaknesses of the database, the criteria applied to evaluation and validation of all aspects of methodology, and the conclusions reached from the review of scientific information. In the case of EDCs, new models need to be developed taking into account possible new kinds of information, e.g., effects of EDCs on gene activation in response to hormonal challenge or effects on receptor expression. Such models should also account for homeostatic adaptive responses and consider the possibility of having windows of exposure for given effects. Work to compile and harmonize the definitions and terms appropriate to endocrine disruption will be conducted within the joint IPCS/OECD project on harmonization of risk/hazard assessment terminology reviews. The ICPS is the process of preparing a "State of the Science" report, and is implementing a global inventory of ongoing research on ECDs.

Animals↗
PubMed1999

Overexpression of Fas ligand (FasL) during malignant transformation in the large bowel and in Barrett's metaplasia of the esophagus.

Esophageal and colorectal adenocarcinomas overexpress Fas ligand (FasL), which can protect them from immune surveillance. The aim of this work was to determine whether FasL expression, and therefore FasL-dependent immune evasion, occurs early during malignant transformation in Barrett's metaplasia (BM) of the esophagus, and in the large intestine. Sections of formalin-fixed and paraffin-embedded tissue from esophageal and large bowel biopsies and resection specimens were immunostained for FasL using standard immunoperoxidase technique. The percentage of positive cells was correlated with the degree of dysplasia in BM and with the size and villous architecture of colorectal adenomas. In BM, FasL was detected in 55% of cases negative for dysplasia, and was associated with inflammation in almost all positive cases. By contrast, all cases of BM (100%) with low- or high-grade dysplasia were FasL-positive. In the large intestine, 25% of small adenomas were negative for FasL, and FasL overexpression was significantly more frequent in larger adenomas and in adenomas with tubulovillous or villous morphology. Our results suggest that (1) FasL overexpression is acquired early during malignant transformation of BM and the large bowel and (2) FasL overexpression occurs relatively earlier during malignant progression of BM than the large bowel, probably as a result of the preceding repeated inflammation.

Adenocarcinoma↗
PubMed1999

The toxic and metabolic effects of 23 aliphatic alcohols in the isolated perfused rat liver.

We investigated the acute toxic and metabolic effects of 23-aliphatic alcohols (16 saturated and 7 unsaturated) in the isolated perfused rat liver at a concentration of 65.1 mmol/l (approximately 0.3% ethanol). The capacity of the straight chain primary alcohols (methanol, ethanol, 1-propanol, 1-butanol and 1-pentanol) to release the enzymes glutamate-pyruvate transaminase (GPT), lactate dehydrogenase (LDH) and glutamate dehydrogenase (GLDH) into the perfusate was strongly correlated with their carbon chain length. The secondary alcohols were less active in this respect whereas branching of the carbon chain did not consistently change alcohol toxicity. Unsaturation in the straight chain but not in the branched chain alcohols was accompanied by an increase in toxicity. An increased enzyme release was in general accompanied by, and correlated to, reductions in oxygen consumption, bile secretion, and perfusion flow of the isolated livers. Statistically significant correlations exist between parameters of alcohol-induced hepatotoxicity and the membrane/buffer partition coefficents of the alcohols. With the exception of methanol, all alcohols tested increased the lactate/pyruvate ratio of the perfusate, although this effect was not correlated to the degree of hepatic injury. Hepatic ATP concentrations decreased in most cases in line with hepatic injury and were particularly correlated with changes in oxygen consumption. Hepatic concentrations of reduced glutathione (GSH) were only diminished by the unsaturated alcohols, whereas an increase in hepatic oxidized glutathione (GSSG) occurred only with some of the saturated alcohols. Hepatic concentrations of malondialdehyde (MDA) increased after two saturated and three unsaturated alcohols but did not correlate with other parameters of hepatotoxicity. In conclusion, alcohol-induced hepatotoxicity is primarily due to membrane damage induced by the direct solvent properties of the alcohols. The consequences and relative contributions of alcohol metabolization to the overall hepatotoxicity of higher alcohols requires further study.

3,4-Methylenedioxyamphetamine↗
PubMed1999

Influence of hypoxia and hyperoxia on the cardiovascular and lethal effects of ethanol.

The mutual potentiation of the hepatotoxic effects of ethanol and hypoxia raised the question of whether such an interaction also occurs in the cardiovascular system. Therefore, anaesthetized rats were infused intravenously with ethanol (25 mg/kg x min.) over 90 min. to reach blood ethanol concentrations between 2.2 and 2.6 g/l and were ventilated artificially either with room air, 10% O2/90% N2 or 100% O2. Under normoxic conditions, ethanol produced a slow decrease of mean arterial blood pressure from 130 to 100 mmHg due to the decline in cardiac output and stroke volume (-20%) while heart rate and peripheral resistance remained unchanged. Hypoxia (arterial oxygen tension 35-38 mmHg) without ethanol produced immediate hypotension (-60 mmHg) without decreasing the cardiac output, i.e. by reducing peripheral resistance. In combination with ethanol, hypoxia produced an even stronger hypotension (-90 mmHg) due to reduction in both cardiac output and peripheral resistance. On the other hand, respiration with 100% O2 (arterial oxygen tension about 500 mmHg) elevated peripheral resistance, attenuated ethanol-induced cardiodepression and prevented ethanol-induced hypotension. The lethal doses of ethanol evaluated by infusing 75 mg/kg x min. ethanol until death amounted to 4.1 g/kg with 10% O2, to 5.5 g/kg with 20% O2 (room air) and to 6.9 g/kg with 100% O2. Thus decrease in vascular contractility induced by hypoxia combined with ethanol-induced cardiodepression may result in lethal cardiovascular failure. Hyperoxia, on the other hand, counteracts ethanol-induced cardiodepression and its acute toxicity by raising the vascular contractility.

Anesthesia↗
PubMed1999

Medullary metastasis causing impairment of respiratory pressure output with intact respiratory rhythm.

We present an unusual case of weaning failure. A 67-yr-old man presented with confusion, hyponatremia, and hypercapnic respiratory failure that necessitated mechanical ventilation. CXR revealed a right hilar mass (non-small-cell carcinoma on biopsy). Level of consciousness improved with treatment of his hyponatremia. However, attempts at weaning were complicated by hypercapnia with no overt distress. Resistance and elastance were only slightly abnormal, excluding mechanics as a cause of respiratory failure. Maximal inspiratory pressure (MIP) and vital capacity (VC) were reduced at -15 cm H2O and 0.97 L, respectively. Limb muscle strength was well preserved, suggesting isolated respiratory muscle weakness. During a weaning trial respiratory rate increased from 7 to 40 breaths/min as PCO2 increased from 56 to 89 mm Hg, confirming an intact respiratory pacemaker and good response to CO2. However, spontaneous Pdi was only 1 to 2 cm H2O (< 20% of Pdimax) despite profound hypercapnia. The fact that the patient did not utilize a greater fraction of his pressure-generating capacity suggested preferential impairment of the automatic respiratory centers. MRI showed a large central metastatic lesion in the rostral medulla with only a thin rim of uninvolved tissue. This case illustrates the utility of relating the magnitude of spontaneous efforts to maximal voluntary efforts as a means of localizing the site of involvement in cases of respiratory muscle weakness. It also demonstrates that a large medullary mass lesion may selectively impair brainstem modulation of respiratory pressure output while sparing other medullary functions, and in particular the pacemaking function of the respiratory centers.

Aged↗
PubMed1999

Effect of ventilator flow rate on respiratory timing in normal humans.

Respiratory rate (RR) increases as a function of ventilator flow rate (V). We wished to determine whether this is due to a decrease in neural inspiratory time (T In), neural expiratory time (TEn), or both. To accomplish this, we ventilated 15 normal subjects in the assist, volume cycled mode. Ventilator flow rate was varied at random, at four breaths with each step, over the flow range from 0.8 (Vmin) to 2.5 (Vmax) L/s. V T was kept constant. The pressure developed by respiratory muscles (Pmus) was calculated with the equation of motion (Pmus = V. R + V. E - Paw, where R = resistance, V = volume, E = elastance, and Paw = airway pressure). Electromyography of the diaphragm (Edi) was also done in five subjects. TIn and TEn were determined from the Pmus or Edi waveform. TIn decreased progressively as a function of V, from 1.44 +/- 0.34 s at Vmin to 0.62 +/- 0.26 s at Vmax (p < 0.00001). Changes in TEn were inconsistent and not significant. TIn/Ttot decreased significantly (0.30 +/- 0.06 at Vmin to 0.18 +/- 0.09 at Vmax; p < 0. 00001). We conclude that TI is highly sensitive to ventilator flow, and that the RR response to V is primarily related to this T In response. Because an increase in V progressively reduces T In/Ttot, and this variable is an important determinant of inspiratory muscle energetics, we further conclude that inspiratory muscle energy expenditure is quite sensitive to V over the range from 0.8 to 2.5 L/s.

Adult↗
PubMed1999

Response of ventilator-dependent patients to different levels of pressure support and proportional assist.

The ventilator's response to the patient's effort is quite different in proportional assist ventilation (PAV) and pressure support ventilation (PSV). We wished to determine whether this results in different ventilatory and breathing pattern responses to alterations in level of support and, if so, whether there are any gas exchange consequences. Fourteen patients were studied. Average elastance (E) was 22.8 (range, 14 -36) cm H2O/L and average resistance (R) was 15. 7 (range, 9-21) cm H2O/L/s. The highest PSV support (PSVmax) was that associated with a tidal volume (VT) of 10 ml/kg (20.4 +/- 3.2 cm H2O), and the highest level of PAV assist (PAVmax) was 78 +/- 7% of E and 76 +/- 7% of R. Level of assist was decreased in steps to the lowest tolerable level (PSVmin, PAVmin). Minute ventilation, VT, ventilator rate (RRvent), and arterial gas tensions were measured at each level. We also determined the patient's respiratory rate (RRpat) by adding the number of ineffective efforts (DeltaRR) to RRvent. There was no difference between PSVmin and PAVmin in any of the variables. At PSVmax, VT was significantly higher (0.90 +/- 0.30 versus 0.51 +/- 0.16 L) and RRvent was significantly lower (13.2 +/- 3.9 versus 27.6 +/- 10.5 min-1) than at PAVmax. The difference in RRvent was largely related to a progressive increase in ineffective efforts on PSV as level increased (DeltaRR 12.1 +/- 10.1 vs 1.4 +/- 2.1 with PAVmax); there was no significant difference in RRpat. The differences in breathing pattern had no consequence on arterial blood gas tensions. We conclude that substantial differences in breathing pattern may occur between PSV and PAV and that these are largely artifactual and related to different patient-ventilator interactions.

Aged↗
PubMed1998

Adult mesoblastic nephroma: expansion of the morphologic spectrum and review of literature.

Mesoblastic nephroma (MN) is a distinctive tumor that is seen mostly in early infancy and that consists of classic and cellular (atypical) variants. Mesoblastic nephroma rarely occurs in adulthood, but MN in this age group still is poorly characterized because there are only 17 reported cases. We describe five additional cases of adult MN, including one case of the cellular variant, characterize the immunohistochemical profiles in detail, and critically review the previously reported cases. The collective data obtained from these 22 cases of adult MN showed that the patients predominantly were women (20 cases), ranging in age from 19 to 78 years, who were asymptomatic (5 cases) or had nonspecific signs and symptoms referable to a renal mass. Twenty tumors were classified as classic and 2 as cellular. The tumors were 2-24 cm, well circumscribed, and partially encapsulated and displayed a solid/ cystic cut surface, with a predominantly solid component in most tumors. One tumor, however, was almost purely cystic. Most tumors extended to the renal sinus. and some appeared entirely intrapelvic on imaging studies; however, gross and microscopic evaluation did not show destructive invasion of the pelvic wall. Extension of the tumor beyond the renal capsule has not been described. Each tumor was composed of epithelial and stromal components both. The epithelial component, which displayed no difference between the classic and cellular variants, was composed of isolated or clustered tubules and cysts lined by a benign epithelium with a wide range of cytologic differentiation. The stromal cells were composed of fibroblasts, myofibroblasts, and smooth muscle cells in various combinations. Stromal cellularity was low for the classic variant but high for the cellular variant. Hemorrhage, necrosis, and high mitotic index were noted in the stroma of the cellular, but not in the classic variant. Immunohistochemical study applied to the five current cases and seven normal control kidneys confirmed the presence of fibroblasts, myofibroblasts, smooth muscle cells, and prominent vessels in the stroma of each tumor. Most cysts and tubules within the tumors had a distinctive immunohistochemical profile, similar to that of collecting duct but different from those of other portions of the nephron in the normal control kidneys. After total or partial nephrectomy, without adjuvant chemotherapy or radiotherapy, 19 patients, including the 2 with cellular MN, were alive and well at 8-months to 48-years follow-up. Follow-up was not available in two patients. The remaining patient had recurrence at the surgical site 24 years after nephrectomy. Adult MN displays a distinctive morphologic spectrum that parallels that of its pediatric congener. It probably is a benign tumor that can be treated successfully by complete excision. The collecting duct differentiation expressed by most tubules and cysts of adult MN implies ureteric bud, which is the exclusive embryologic origin of collecting duct, as an important element in the histogenesis of this rare but fascinating type of tumor.

Adult↗