Feasibility of endoscopic submucosal dissection: a new technique for en bloc resection of a large superficial tumor in the colon and rectum.

Endoscopic submucosal dissection (ESD) is a promising procedure that enables en bloc resection of large superficial tumors in the upper gastrointestinal tract. On the other hand, ESD in the colon and rectum is technically difficult to perform because of its anatomical features. At our institution, 137 consecutive superficial colorectal tumors larger than 20 mm in diameter in 137 patients were treated by ESD between April 2007 and October 2010, and 132 lesions were successfully resected. The average procedure time was 79.2 minutes, and the rate of en bloc resection was 89.1% (122/137). The rate of complete resection, defined as en bloc resection with tumor-free lateral and vertical margins, was 85.4% (117/137). The rate of perforation was 3.6% (5/137). Colorectal ESD achieved a high rate of en bloc resection and complete resection and is applicable in the colorectum.

Clinical course of abducens nerve palsy associated with skull base tumours.

BACKGROUND: The clinical course of abducens nerve palsy associated with skull base tumour is rarely reported. In this study, we examined the post-operative course of abducens nerve palsies associated with various skull base tumours. METHOD: Between January 2003 and December 2006, 240 patients with various skull base tumours underwent surgery at Kyushu University Hospital. Among them, nine patients presented with abducens nerve palsies (ten nerves) following surgery. The conditions included two pituitary adenomas, two trigeminal schwannomas and five meningiomas. We evaluated the function of the abducens nerves in these patients on admission, at discharge, and periodically in the outpatient clinic. FINDINGS: Four of the abducens nerve palsies already existed prior to surgery, and six of them developed post-operatively. In the four patients with pituitary adenomas and trigeminal schwannomas, all nerves were anatomically preserved and showed complete recovery of function within 6 months after surgery. In contrast, only two of the six palsies in patients with skull base meningiomas showed complete recovery. In three patients with petro-clival meningiomas, the abducens nerves were completely transected during surgery, and one was reconstructed using fibrin glue. This patient remarkably recovered from the abducens nerve palsy within 2 years. CONCLUSIONS: The abducens nerve palsies in pituitary adenomas and trigeminal schwannomas showed a better clinical course compared to those in skull base meningiomas. The abducens nerve palsies that occur with skull base meningiomas are less likely to recover. Nevertheless, it is important to preserve the nerves and to perform surgical repair if the nerve is transected.

Performance evaluation of radiologists with artificial neural network for differential diagnosis of intra-axial cerebral tumors on MR images.

BACKGROUND AND PURPOSE: Previous studies have suggested that use of an artificial neural network (ANN) system is beneficial for radiological diagnosis. Our purposes in this study were to construct an ANN for the differential diagnosis of intra-axial cerebral tumors on MR images and to evaluate the effect of ANN outputs on radiologists' diagnostic performance. MATERIALS AND METHODS: We collected MR images of 126 patients with intra-axial cerebral tumors (58 high-grade gliomas, 37 low-grade gliomas, 19 metastatic tumors, and 12 malignant lymphomas). We constructed a single 3-layer feed-forward ANN with a Levenberg-Marquardt algorithm. The ANN was designed to differentiate among 4 categories of tumors (high-grade gliomas, low-grade gliomas, metastases, and malignant lymphomas) with use of 2 clinical parameters and 13 radiologic findings in MR images. Subjective ratings for the 13 radiologic findings were provided independently by 2 attending radiologists. All 126 cases were used for training and testing of the ANN based on a leave-one-out-by-case method. In the observer test, MR images were viewed by 9 radiologists, first without and then with ANN outputs. Each radiologist's performance was evaluated through a receiver operating characteristic (ROC) analysis on a continuous rating scale. RESULTS: The averaged area under the ROC curve for ANN alone was 0.949. The diagnostic performance of the 9 radiologists increased from 0.899 to 0.946 (P < .001) when they used ANN outputs. CONCLUSIONS: The ANN can provide useful output as a second opinion to improve radiologists' diagnostic performance in the differential diagnosis of intra-axial cerebral tumors seen on MR imaging.

Perfusion imaging of brain tumors using arterial spin-labeling: correlation with histopathologic vascular density.

BACKGROUND AND PURPOSE: We investigated the relationship between tumor blood-flow measurement based on perfusion imaging by arterial spin-labeling (ASL-PI) and histopathologic findings in brain tumors. MATERIALS AND METHODS: We used ASL-PI to examine 35 patients with brain tumors, including 11 gliomas, 9 meningiomas, 9 schwannomas, 1 diffuse large B-cell lymphoma, 4 hemangioblastomas, and 1 metastatic brain tumor. As an index of tumor perfusion, the relative signal intensity (SI) of each tumor (%Signal intensity) was determined as a percentage of the maximal SI within the tumor per averaged SI within normal cerebral gray matter on ASL-PI. Relative vascular attenuation (%Vessel) was determined as the total microvessel area per the entire tissue area on CD-34-immunostained histopathologic specimens. MIB1 indices of gliomas were also calculated. The differences in %Signal intensity among different histopathologic types and between high- and low-grade gliomas were compared. In addition, the correlations between %Signal intensity and %Vessel or MIB1 index were evaluated in gliomas. RESULTS: Statistically significant differences in %Signal intensity were observed between hemangioblastomas versus gliomas (P < .005), meningiomas (P < .05), and schwannomas (P < .005). Among gliomas, %Signal intensity was significantly higher for high-grade than for low-grade tumors (P < .05). Correlation analyses revealed significant positive correlations between %Signal intensity and %Vessel in 35 patients, including all 6 histopathologic types (rs = 0.782, P < .00005) and in gliomas (rs = 0.773, P < .05). In addition, in gliomas, %Signal intensity and MIB1 index were significantly positively correlated (rs = 0.700, P < .05). CONCLUSION: ASL-PI may predict histopathologic vascular densities of brain tumors and may be useful in distinguishing between high- and low-grade gliomas and in differentiating hemangioblastomas from other brain tumors.

A case of intracranial hypoglossal neurinoma without hypoglossal nerve palsy: operative view of the preserved rostral trunk.

Hypoglossal neurinomas usually manifest with hemiatrophy and weakness of the tongue. A rare case of intracranial hypoglossal neurinoma without preoperative hypoglossal nerve dysfunction and its operative view are presented. A 36-year-old female who presented with headaches and vertigo was admitted to our hospital. The neurological examination revealed bilateral papilledema and mild truncal ataxia, although weakness and atrophy of the tongue were not observed. Magnetic resonance and computed tomography images demonstrated a large foramen magnum tumor without enlargement of the hypoglossal canal. Total removal of the tumor was performed via a lateral suboccipital craniotomy and C1 partial laminectomy. During the operation, two trunks were observed for the hypoglossal nerve at the entrance of the hypoglossal canal. The tumor arose from the caudal trunk, while the intact rostral trunk entered the hypoglossal canal normally. The tumor only developed intracranially, and since the rostral trunk of the hypoglossal nerve was intact, the patient did not present with hypoglossal nerve palsy preoperatively.

Esophageal atresia with double tracheoesophageal fistula--a case report and review of the literature.

Esophageal atresia with double tracheoesophageal fistula (TEF) is a very rare anomaly, and the accurate preoperative diagnosis of proximal TEF is very difficult. This paper describes a baby girl who presented with esophageal atresia with double, proximal, and distal TEF. The distal TEF was diagnosed before operation, whereas the proximal TEF was found intraoperatively. Overlooking the presence of proximal TEF can lead to increased morbidity and mortality due to severe respiratory infection and the necessity of a second operation. Great care must therefore be taken to not overlook the presence of proximal TEF in patients with this anomaly.

Spatio-temporal analysis by voltage topography of ictal electroencephalogram on MR surface anatomy scan for the localization of epileptogenic areas.

A 15-year-old girl developed intractable epilepsy following a right transcallosal resection of the intraventricular teratoma. Magnetic resonance (MR) imaging showed a T (2)-prolonged subcortical lesion in the right frontal lobe as well as a residual intraventricular tumor. The integration of the voltage topography of ictal onset activities of the scalp-recorded electroencephalogram (EEG) and a surface anatomy scan of MR images clearly revealed the epileptogenic area on the cortex above the subcortical lesion, with the propagation pattern towards the frontopolar area. Excision of the epileptogenic cortex and underlying gliosis resulted in a successful cessation of the epilepsy. This non-invasive EEG technique provided useful information that accurately localized the epileptogenic area on a large structural abnormality without invasive intracranial electrocorticographic monitoring.

The effect of a prenatal androgen disruptor, vinclozolin, on gubernacular migration and testicular descent in rats.

BACKGROUND/PURPOSE: Androgen has been shown to regulate inguinoscrotal testicular descent. This study aims to clarify the effect of one of the major endocrine disrupters, vinclozolin (V), on both gubernacular migration and inguinoscrotal testicular descent in rats. METHODS: Time-pregnant rats were segregated into 2 groups. In group I, the rats were administered 200 mg/kg/d of V by gavage on days 15 to 18 of gestation. In group II, the rats were administered the same volume of solvent and were used as controls. At birth, the anogenital distance was measured in pups, and gubernacular migration was examined at 10 days of age in some of male offspring. Next, the incidence of testicular descent and the growth of external genitalia were investigated in the remaining male offspring at 60 days of age. The chi2 test was used for statistical analysis of the results. RESULTS: At birth, the anogenital distance (AGD) index decreased significantly more in group I than in group II in male offspring. However, there was no significant difference in the AGD index between the 2 groups in the female offspring. At 10 days of age, an aberrant migration of the gubernaculum was found in the 51.5% of V-treated rats in group I. At 60 days of age, the incidence of cryptorchidism was 57.7% in group I and 0% in group II (P <.05). In addition, hypospadias with cleft phallus and pseudo vagina with a blind pouch also were observed in some of the V-treated rats. CONCLUSIONS: Prenatal administration with V thus caused intrauterine defects, which resulted in testicular maldescent caused by the induction of an aberrant migration of the gubernaculum associated with an abnormal extension of the processus vaginalis, and this may have been caused by the antiandrogenic effect of V in utero.

Short-time exposure to vinclozolin in utero induces testicular maldescent associated with a spinal nucleus alteration of the genitofemoral nerve in rats.

BACKGROUND/PURPOSE: Vinclozolin (V), a known antiandrogen, has been used widely to protect fruits, vegetables, and turf from fungus damage. The aim of this study was to clarify the effect of V on both the development of the spinal cord nucleus and testicular descent in rats. METHODS: Pregnant rats were administered 200 mg/kg/d of V from day 16 to 18 of gestation. At 5 days of age, the genitofemoral nerve (GFN) of male pups was identified on the psoas muscle, and diamidinophenyl indole was applied to the proximal cut end of the GFN. Forty-eight hours later, the T11 to L4 level of the spinal cord was removed, and 30-microm frozen serial sections were made. Next, the spinal nuclei labeled in a retrograde fashion by diamidinophenyl indole (DAPI) were examined with a fluorescence microscope. Additional male pups survived until 60 days of age to evaluate the position of the testes. RESULTS: The size of the DAPI-labeled spinal nuclei were smaller in the V-treated rats than in the control rats. The average number of the DAPI-labeled spinal nuclei decreased significantly more in the V-treated rats (176+/-33) than in the controls (247+/- 21; P <.05) during the newborn period. At 60 days of age, 15 of the 26 male rats showed either unilateral or bilateral undescended testes in the V-treated rats. The incidence of cryptorchidism was also significantly higher in the V-treated rats (57.7%) than in the controls (0%; P <.05). CONCLUSIONS: The antiandrogenic effect of the prenatal administration of V inhibited the development of the GFN nucleus in the spinal cord and induced testicular maldescent in rats. These results support the hypothesis that androgens regulate the descent of the testis through GFN development.

Vascular endothelial growth factor in chronic subdural haematomas.

OBJECTIVE: To elucidate molecular aspects of the mechanisms of expansion of chronic subdural haematomas (CSH), we examined the expression of two representative angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in CSH. METHODS: We quantified VEGF and bFGF in haematoma fluid and serum of 20 patients with CSH using an enzyme-linked immunosorbent assay. Mean concentrations of VEGF in the haematoma fluid (10277 pg/ml) and in serum, (355 pg/ml) were much greater than those of bFGF (haematoma, 3.04 pg/ml; serum, 4.74 pg/ml). Surgical specimens, including dura and the outer membrane of the CSH were analysed by in situ hybridisation to detect VEGF mRNA. Macrophages and vascular endothelial cells in the outer membrane over expressed VEGF mRNA. CONCLUSIONS: Enhanced production of VEGF by macrophages and vascular endothelial cells in the outer membrane is thought to be pathogenetically important in CSH.

[A case of tuberculous endometritis detected by cytology of mass screening for gynecologic cancer].

A 55-year-old infertile woman was referred to our clinic for further investigation on extragenital tuberculosis, as tuberculous endometritis was strongly suspected by cytology of her vaginal smear carried out on the occasion of the mass examination for gynecologic cancer screening. Her vaginal smear revealed epithelioid cell clusters which are characteristic for tuberculosis, and cultures of her vaginal discharge were positive for M. tuberculosis consecutively. Moreover, she was exposed for tuberculosis infection from her father who died of active pulmonary tuberculosis when she was ten years old. Her tuberculin test was strongly positive, and her chest radiography showed no abnormality, but a small nodular shadow evaluated as primary focus of tuberculosis located beneath the pleura of the right lower lung field was confirmed by chest CT. In addition, calcification of her para-aortic abdominal lymphnode was detected by simple abdominal X-ray. Based on these data, she was diagnosed as tuberculous endometritis via abdominal cavity, and three antituberculous drugs, namely RFP, INH and EB, were administrated. The mycobacterial cultures of vaginal discharge converted to negative, and chemotherapy was terminated after 9 months treatment. A risk factor leading to the onset of gynecologic tuberculosis, in this case was an exposure to infection from her father. In order to evaluate risk factors relating to the development of gynecologic tuberculosis, bibliographic studies were made on 19 cases of tuberculous endometrites reported recently in Japan regarding their age, its pathogenesis and immuno-suppressive conditions, and the summarized results were as follows. 1. approximately 80% of them were elderly, namely 79% were above 50 years, 63% above 60 years, and 26% above 70 years. 2. 50% of them were caused by endogenous reactivation. 3. 25% of them were immuno-compromised host. It can be concluded that more than 70% of the patients with tuberculous endometritis had risk factors on the host side to develop tuberculosis.

Inhibition of FGF-2-mediated chemotaxis of murine brain capillary endothelial cells by cyclic RGDfV peptide through blocking the redistribution of c-Src into focal adhesions.

The alpha(v)beta(3) integrin is essential for fibroblast growth factor (FGF)-induced angiogenesis in vivo. However, the role of this integrin in FGF-2-mediated cellular responses by cultured endothelial cells is largely unknown. Cyclic RGDfV (cRGDfV) peptide is widely used to inhibit the binding of alpha(v)beta(3) integrin to vitronectin. To investigate the role of this integrin in FGF-2-mediated cellular responses, we used immortalized murine brain capillary endothelial cells, denoted IBE cells. Because IBE cells proliferate and migrate in response to FGF-2-treatment, when cultured on fibronectin-coated surface, we first examined the inhibitory activity of this peptide on the binding of alpha(v)beta(3) integrin to fibronectin as well as vitronectin. Solid phase binding assay revealed that cRGDfV peptide strongly inhibited the binding of purified alpha(v)beta(3) integrin to vitonectin- and fibronectin-coated plastic surfaces at a concentration of 50 microM. cRGDfV peptide at 50 microM inhibited spreading as well as adhesion of IBE cells on vitronectin-coated plastic surface but not on fibronectin. On fibronectin-coated substrata, cRGDfV at 50 microM attenuated FGF-2-mediated chemotaxis, but not FGF-2-induced proliferation, of IBE cells. We have previously demonstrated that mitogen-activated protein kinase (MAPK) activation within focal adhesions through c-Src activity was involved in FGF-2-induced chemotaxis of IBE cells. Treatment of cells with cRGDfV peptide was associated with reduced c-Src activity without tyrosine dephosphorylation. Immunofluorescent staining showed that cRGDfV inhibited redistribution of c-Src into focal adhesions. MAPK activation by FGF-2 within focal adhesions was also attenuated in the presence of cRGDfV peptide. Our results indicated that cRGDfV peptide inhibited redistribution of c-Src into focal adhesions, leading to impaired MAPK activation within focal adhesions and motility in FGF-2-treated endothelial cells.

Cyclooxygenase-2 expression in human gliomas: prognostic significance and molecular correlations.

Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin H synthase, has been implicated in the growth and progression of a variety of human cancers. Although COX-2 overexpression has been observed in human gliomas, the prognostic or clinical relevance of this overexpression has not been investigated to date. In addition, no study has analyzed the relationship between COX-2 expression and other molecular alterations in gliomas. Consequently, we examined COX-2 expression by immunohistochemistry in tumor specimens from 66 patients with low- and high-grade astrocytomas and correlated the percentage of COX-2 expression with patient survival. We also analyzed the relative importance of COX-2 expression in comparison with other clinicopathological features (age and tumor grade) and other molecular alterations commonly found in gliomas (high MIB-1 level, p53 alteration, loss of retinoblastoma (Rb) protein or p16, and high bcl-2 level). Kaplan-Meier analyses demonstrated that high COX-2 expression (>50% of cells stained positive) correlated with poor survival for the study group as a whole (P < 0.0001) and for those with glioblastoma multiforme in particular (P < 0.03). Cox regression analyses demonstrated that COX-2 expression was the strongest predictor of outcome, independent of all other variables. In addition, high COX-2 expression correlated with increasing histological grade but did not correlate with positive p53 immunostaining, bcl-2 expression, loss of p16 or retinoblastoma protein expression, or high MIB-1 expression. These findings indicate that high COX-2 expression in tumor cells is associated with clinically more aggressive gliomas and is a strong predictor of poor survival.

The biological effect of phthalate esters on transabdominal migration of the testis in fetal rats in comparison with the antiandrogen flutamide.

Phthalate esters are commonly used as plasticizers for polyvinyl chloride and are known to be hormone-disrupting chemicals. We previously reported that mono-n-butyl phthalate (MBP) administered to rat fetuses induced cryptorchidism postnatally. The aim of this study was to investigate the biological effect of MBP on the transabdominal migration of the testis in prenatal rats by comparing this with the prenatal effect of the antiandrogen flutamide on testicular descent. Time-pregnant Wistar King A rats were divided into three groups: group I rats (N = 3) were administered MBP 0.3 g/day by gavage from gestational days 15 to 18; group II rats (N = 3) were injected with flutamide (30 mg/day) from gestational days 15 to 18; group III rats (N = 3) were administered solvent as controls. On the 19th gestational day, all rats underwent a cesarean section and the male fetuses were dissected to examine the position of the testis, which was significantly higher in the abdominal cavity in the MBP-treated rats than in either the flutamide-treated or control rats. No significant difference was observed in the position of the testis between the flutamide-treated and control rat fetuses. Our findings suggest that maternal MBP prevented transabdominal migration of the testis in prenatal rats, which may not have been due to either an antiandrogenic or estrogenic effect of MBP, but to a direct toxic effect of MBP on the testis.

The role of mitogen-activated protein kinase activation within focal adhesions in chemotaxis toward FGF-2 by murine brain capillary endothelial cells.

Fibroblast growth factors (FGFs) regulate a number of angiogenic cellular responses such as migration of endothelial cells. To examine the role of mitogen-activated protein kinase (MAPK) in endothelial cell migration, chemotaxis toward FGF-2 was determined in murine brain capillary endothelial cells, denoted IBE cells. PD98059, a specific inhibitor for MAPK/Erk kinase, inhibited FGF-2-induced chemotaxis of IBE cells. It has been reported that c-Src tyrosine kinase phosphorylates focal adhesion kinase at tyrosine 925 within focal adhesions, which in turn creates the binding site for Grb2, leading to MAPK activation. The Src family tyrosine kinase inhibitor, PP1, as well as overexpression of kinase-inactive c-Src, attenuated chemotaxis toward FGF-2. To investigate the signaling events involved in FGF-2-induced chemotaxis, MAPK activation was monitored in IBE cells by indirect immunofluorescence staining. Activated MAPK was initially observed in the cytoplasm and gradually moved into nuclei. A fraction of MAPK was activated by FGF-2 within focal adhesions, where FGF receptor-1 and Src family kinases were also colocalized. MAPK activation within focal adhesions was remarkably decreased in kinase-inactive c-Src-expressing IBE cells. Our data suggest that activation of MAPK by FGF-2 within focal adhesions may depend on c-Src activity and is crucial for FGF-2-induced migration of IBE cells.

Comparative studies of fertility and histologic development of contralateral scrotal testes in two rat models of unilateral cryptorchidism.

Fertility and the development of the contralateral scrotal testis in patients with unilateral cryptorchidism (UCO) remain controversial. This study investigated these controversies in two different UCO rat models using 43 Wistar King A rats. The animals were divided into three groups: I: an endocrinologic model of UCO was obtained by injecting pregnant dams with flutamide 100 mg/kg per day on days 15-17 of gestation (n = 12); II (n = 21): a mechanical model of UCO was obtained by extra-abdominal fixation of the gubernaculum in the neonatal period, III (n = 10): non-treated rats were used as controls. At the age of 90 days, 5 rats from each group were segregated into individual cages and housed with two virgin adult females for 2 weeks. The occurrence of pregnancy and litter sizes were counted in order to study fertility. All the animals were then weighed and killed. The occurrence of testicular descent, growth of the external genitalia, and epididymal development were examined. Morphologic and histologic evaluations were performed in the cryptorchid and contralateral testes. In the endocrinologic model (group I) the 10 female rats failed to show any offspring (0%), while in the mechanical model (group II) 9 out of 10 rats had offspring (90%, P < 0.001); 10 out of 10 control rats showed offspring. All of the rats in groups I and II had UCO, and the undescended testes were located in the superficial inguinal position, while the contralateral and control testes descended into the scrotum. Hypospadias and a small epididymis were frequently noted in the flutamide-treated rats. Testicular weight, seminiferous tubular diameter, and spermatogenesis were all significantly reduced in the undescended testes (UDT) compared to the contralateral and control testes. Moreover, the development of the contralateral testis was inhibited in group I compared to groups II and III. Our observations showed that short-term exposure to flutamide in utero induced significantly reduced fertility and degenerated contralateral scrotal testes in UCO rats compared to mechanically-induced UCO rats by early adulthood. It is suggested that fertility potential and testicular development in unilateral UDT may be partially due to the factors that induce testicular maldescent, especially in cases due to intrauterine hormonal abnormalities. These cases may show inhibited fertility and testicular development even after orchiopexy.

The specific expression of three novel splice variant forms of human metalloprotease-like disintegrin-like cysteine-rich protein 2 gene inBrain tissues and gliomas.

We have previously identified 67 exons on a yeast artificial chromosome contig spanning 1.5 Mb around the multidrug resistance 1 gene region of human chromosome 7q21.1. In this study, we identified three novel cytoplasmic variants (MDC2-gamma, MDC2-delta, and MDC2-epsilon) of the human metalloprotease-like disintegrin-like cysteine-rich protein 2 (MDC2) among these exons by screening a human brain cDNA library and also by using a reverse transcription polymerase chain reaction. Genomic sequence analysis strongly supported the idea that the variations in the cytoplasmic domain were generated by alternative splicing. The expression of MDC2 variant forms in human brain tissue and gliomas was examined by reverse transcription polymerase chain reaction and RNase protection assay. MDC2-epsilon was expressed only in the cortical and hippocampal regions in human brain, but not in gliomas. In contrast, MDC2-gamma was a major form expressed in human gliomas. Specific expression of these cytoplasmic variants of MDC2 in human brain and its malignancies is discussed.

Relationship between flow cytometric DNA ploidy and nuclear grade with endocrine dysfunction in adrenal cortical adenomas.

OBJECTIVES: To determine the relationship among the DNA ploidy, histopathologic features, and clinical syndrome in adrenal cortical adenomas, because the cells often show variability in nuclear size and configuration. METHODS: Our study included 44 adenomas associated with primary aldosteronism and 23 adenomas associated with Cushing syndrome. Normal adrenal glands from patients with renal carcinoma served as the controls. Paraffin-embedded tissues were examined for DNA content by flow cytometry. The mean percentage of G(2)/M (4C%) of the control samples was 3.8%. Tetraploid was represented by a histogram with both a 4C peak greater than 9% (mean + 2.4 SD of control samples) and a small 8C peak. RESULTS: Flow cytometric analysis revealed diploidy in 30, tetraploidy in 27, and aneuploidy in 8 of the 67 adenomas; 2 adenomas could not be classified. All 17 normal adrenal glands showed diploidy. A significant relationship was noted between DNA ploidy and the clinical syndrome (ie, a larger proportion of adenomas with primary aldosteronism had a tetraploid DNA histogram compared with adenomas with Cushing syndrome, P <0. 0001). Adenomas with primary aldosteronism had a significantly higher nuclear grade (III or IV) than did tumors with Cushing syndrome (P = 0.033). A significant relationship was also observed between DNA ploidy and nuclear grade in 57 euploid tumors, with tetraploid tumors often showing the highest nuclear grade (P = 0. 037). CONCLUSIONS: Our results have demonstrated that adrenal cortical adenomas associated with primary aldosteronism often reveal severe nuclear pleomorphism, indicating that nuclear pleomorphism might be due to a tetraploid stemline.