Risk Factors for Dropout From the Liver Transplant Waiting List of Hepatocellular Carcinoma Patients Under Locoregional Treatment.

BACKGROUND: In new organ allocation policy, patients with hepatocellular carcinoma (HCC) experience a 6-month delay in being granted Model for End-Stage Liver Disease exception points. However, it may not be fair for patients at risk of early progression of HCC. METHODS: All patients who were diagnosed as United Network for Organ Sharing (UNOS) stage 1 or 2 of HCC between January 2004 and December 2012 were included. Patients who received surgical resection or liver transplant (LT) as a primary treatment and who did not receive any treatment for HCC were excluded. Patients with baseline Model for End-Stage Liver Disease score ≥22 were also excluded because they have a higher chance of receiving LT. Patients who developed extrahepatic progression within 1 year were considered as high-risk for early recurrence after LT. RESULTS: A total of 586 patients were included. Mean (SD) age was 59.9 (10.3) years and 409 patients (69.8%) were men. The cumulative incidence of estimated dropout was 8.9% at 6 months; size of the maximum nodule (≥3 cm) and nonachievement of complete response were independent factors. Extrahepatic progression developed in 16 patients (2.7%) within 1 year; size of the maximum nodule (4 cm) and alpha-fetoprotein level (>100 ng/mL) were independent predictors. CONCLUSIONS: The estimated dropout rate from the waiting list within 6 months was 8.9%. Advantage points might be needed for patients with maximum nodule size ≥3 cm or those with noncomplete response. However, in patients with maximum nodule size ≥4 cm or alpha-fetoprotein level >100 ng/mL, caution is needed.

Intraoperative neuromonitoring for surgical training in thyroid surgery: its routine use allows a safe operation instead of lack of experienced mentoring.

BACKGROUND: The aim of the present study was to evaluate the influence of intraoperative neuromonitoring (NM) on surgical training. The results of thyroidectomy performed by inexperienced surgeons under the supervision of a consultant surgeon without intraoperative neuromonitoring (ioNM) were compared to those of the operations performed without experienced assistance but under neuromonitoring control. MATERIALS AND METHODS: The study included the thyroid operations performed in our Department between 2005 and 2012. Among them, residents or fellows performed 1,116 procedures. Seven hundred sixty-five operations were conducted without neuromonitoring (NV group) and 351 with NM group. In the NV group 375 unilateral and 390 bilateral operations were performed. In the NM group 149 unilateral and 202 bilateral operations were performed. Primary end point of the study was the incidence of postoperative recurrent laryngeal nerve palsy. A secondary end point was the impact of ioNM on operating time and operative strategy. RESULTS: The incidence of recurrent laryngeal nerve (RLN) palsy was 2.6 % in the NV group and 2.7 % in the NM group [p = ns]. One case of bilateral RLN palsy was observed in the NV group. The operative time was longer in the NM group for both lobectomy and total thyroidectomy (50 vs. 56 min and 76 vs. 81 min, respectively; p < 0.05). CONCLUSIONS: The routine use of intermittent intraoperative neuromonitoring during thyroid operations does not reduce the incidence of RLN palsy. Nevertheless, it allows inexperienced surgeons to perform a safe operation with a complication rate comparable to that obtained under supervision of an experienced surgeon. Moreover, ioNM could avoid the unfortunate occurrence of a bilateral RLN palsy.

Clinical significance of CD151 overexpression in subtypes of invasive breast cancer.

BACKGROUND: CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated. METHODS AND RESULTS: The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (P<0.001) and disease-free survival (P=0.02), and stage II and III patients with CD151 overexpression demonstrated substantially poorer OS (P=0.0474 and 0.0169). In the five subtypes analyses, CD151 overexpression retained its adverse impact on OS in the Luminal A (P=0.0105) and quintuple-negative breast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer. CONCLUSION: CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer.

Improvement of type 2 diabetes mellitus in obese and non-obese patients after the duodenal switch operation.

Introduction. Type 2 diabetes mellitus (T2DM) is one of the most important obesity-related comorbidities. This study was undertaken to characterise the effect of the biliopancreatic diversion with duodenal switch (BPD-DS) in morbidly obese and nonmorbidly obese diabetic patients. Methods. Outcome of 74 obese diabetic patients after BPD-DS and 16 non-obese diabetic patients after BPD or gastric bypass surgery was evaluated. Insulin usage, HbA(1c)-levels, and index of HOMA-IR (homeostasis model assessment of insulin resistence) were measured. Results. A substantial fraction of patients is free of insulin and shows an improved insulin sensitivity early after the operation, another fraction gets free of insulin in a 12-month period after the operation and a small fraction of long-term insulin users will not get free of insulin but nevertheless shows an improved metabolic status (less insulin needed, normal HbA(1c)-levels). Conclusion. BPD-DS leads to an improvement of T2DM in obese and non-obese patients. Nevertheless, more data is needed to clarify indications and mechanisms of action and to adjust our operation techniques to the needs of non-obese diabetic patients.

Clinical relevance of TNM staging system according to breast cancer subtypes.

BACKGROUND: There has been reported that the association between nodal spread and tumor size was disrupted in triple-negative breast cancer (TNBC) and it showed characteristically early relapse. The TNM (tumor-node-metastasis) staging system might not be equally effective as a prognostic indicator for all subtypes. The aim of our study was to evaluate the usefulness of the staging according to subtypes. PATIENTS AND METHODS: We conducted a retrospective analysis of invasive breast cancer patients who received curative surgery at Samsung Medical Center from 2000 to 2004. Relapse-free survivals (RFS) by stage were analyzed. RESULTS: Thousand eight hundred and seventy-nine patients who were available clinicopathologic data were included. These patients were divided into three subtypes: hormone receptor (HR)+, human epidermal growth factor receptor 2+, and triple negative groups. As the stage became more advanced, the slope of each stage of the RFS curves of patients with HR+ and HER2+ steadily increased. In contrast, RFS curves intermingled and showed overlap from stage 1 to 3A in TNBC patients. There was only wide separation of RFS curves between stage 1-3A and 3B-3C in TNBC. CONCLUSIONS: The current TNM staging system might not be enough for encompassing the tumor biology and for predicting outcomes to make therapeutic decisions for all BCs, especially for TNBC patients.

Thymidine synthase, thymidine phosphorylase, and excision repair cross-complementation group 1 expression as predictive markers of capecitabine plus cisplatin chemotherapy as first-line treatment for patients with advanced oesophageal squamous cell carcinoma.

BACKGROUND: Our purpose was to evaluate thymidine synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementation group 1 (ERCC1) expression as biomarkers for capecitabine and cisplatin (XP) combination chemotherapy in patients with metastatic oesophageal squamous cell cancer. METHOD: A total of 113 patients with metastatic oesophageal squamous cell cancer were treated with XP chemotherapy at the Samsung Medical Center between 2003 and 2007, of whom 72 had available clinical data and paraffin blocks for immunohistochemistry of TS, TP, and ERCC1. RESULTS: The median age of the 72 patients was 62 years. The overall response rate (RR) was 51.4%. The median progression-free survival (PFS) and overall survival (OS) were 4.2 and 12.0 months, respectively. High expression of TS and TP was associated with a higher RR than was low expression of TS and TP (54.1 vs 40.5%, P=0.022). Strong ERCC1 expression and a low TS score were identified as unfavourable independent risk factors for PFS (HR 10.71, 95% confidence interval (CI) 2.1-54.7, P=0.004 for strong ERCC1 expression; and HR 2.9, 95% CI 1.0-7.9, P=0.044 for low TS score). Strong ERCC1 expression was identified as an unfavourable independent risk factor for OS (HR 3.73, 95% CI 1.39-10.0, P=0.009). CONCLUSION: These data indicate that expression of TS, TP, and ERCC1 may be predictive markers for response and survival in patients with metastatic oesophageal squamous cell cancer receiving XP chemotherapy.

Herpes simplex virus pneumonia: high-resolution CT findings.

The purpose of this study was to evaluate the high-resolution computed tomographic (HRCT) findings of five adult patients (either immunocompromised or immunocompetent) with herpes simplex virus (HSV) pneumonia. We retrospectively assessed HRCT images of 5 patients (all male patients, age range 39-70 years; mean 62 years) with HSV pneumonia. The specific pathological findings that allowed for a definite diagnosis of HSV pneumonia included the presence of intranuclear inclusion bodies on haematoxylin and eosin staining, or positive immunohistochemical staining. High-resolution CT scans (HiSpeed Advantage or LightSpeed QX/i, GE Healthcare) using 1- or 1.25-mm collimation at 10-mm intervals without intravenous contrast medium injection were assessed, in particular for the presence and distribution of parenchymal abnormalities including ground-glass attenuation, airspace consolidation, nodules and interlobular septal thickening. In two patients, pathological specimens were obtained from open lung biopsy or bronchoscopic biopsy, and were correlated with HRCT findings. Three HRCT patterns of pulmonary abnormalities were identified in our series of HSV pneumonia: predominant areas of diffuse or multifocal ground-glass attenuation, predominant areas of multifocal peribronchial consolidations, and a mixed pattern of both. Histopathologically, areas of ground-glass attenuation seen on HRCT corresponded to diffuse alveolar damage in one patient who underwent open lung biopsy. No specific differences in HRCT findings were seen between the immunocompromised and the immunocompetent patients. In patients suspected of having an acute lower respiratory infection, whether immunocompromised or immunocompetent, a possibility of HSV pneumonia can be included in differential diagnoses when diffuse or multifocal areas of ground-glass attenuation and/or consolidations are seen on HRCT.

Neuroprotective effects of an alkaloid-free ethyl acetate extract from the root of Sophora flavescens Ait. against focal cerebral ischemia in rats.

Large amounts of brain nitric oxide are produced over several hours after a stroke. This probably causes DNA strand nicks, nitration of cytosolic components of neurons, and ultimately neuronal death. Oxymatrine and matrine are two major alkaloids of the Chinese herb Sophora flavescens Ait. (Leguminosae); they have been demonstrated to inhibit liver injury during warm ischemia and reperfusion and to induce apoptosis, respectively, in vivo and in vitro. However, the neuroprotective efficacy of the EtOAc extract of S. flavescens (ESF) without the alkaloids has not been explored. This study investigated the inhibitory efficacy of ESF, which contain two major flavonoids kurarinone (45.5%) and sophoraflavone G (14.7%), in focal cerebral ischemia. Focal cerebral ischemia was induced using the middle cerebral artery occlusion (MCAO) method. After 1.5h of MCAO and 24h of reperfusion, the extent of neurological deficits and the infarct volume were measured in Sprague-Dawley rats. Compared with carnosine (50mg/kg), as positive control ESF (20mg/kg) significantly reduced infarct volume and neurological deficits. Treatment of human SH-SY5Y cells with sodium nitroprusside (SNP), a nitric oxide donor, decreased cell viability by causing apoptosis-like cell death. ESF significantly inhibited caspase-3-like enzyme activity and DNA fragmentation. The level of active caspase-3 was maximal 6h after SNP treatment. However, active caspase-3 and apoptosis were dose-dependently inhibited by ESF treatment. Flow cytometry analysis showed that ESF significantly inhibited cell apoptosis (p<0.05) and reduced the apoptotic index by 79.9% (p<0.01). These results indicate that ESF is neuroprotective in focal cerebral ischemia and the flavonoids in ESF might be responsible for its neuroprotective activity in rats, alone or in part.

Glutamine induces heat-shock protein-70 and glutathione expression and attenuates ischemic damage in rat islets.

BACKGROUND: The transplantation of isolated islets is believed to be an attractive approach for cure of diabetes mellitus. Heat-shock protein (HSP70), which plays a vital role in cellular protection, has been detected in various tissues subjected to stress. Glutamine (GLN) is an important cellular fuel and an essential precursor for the antioxidant glutathione (GSH). It is believed to enhance cellular survival against a variety of stressful stimuli through HSP70. Thus, we performed this study to examine the hypothesis that preoperative GLN administration induces HSP70 and GSH expression before islet transplantation attenuating ischemic damage to rat islets. METHODS: Adult male Sprague-Dawley (SD) rats were randomly divided into two groups according to the administration of GLN after islet isolation. Group A served as the controls, receiving no GLN. Group B islet cells were cultured with L-GLN (10 mmol/L) supplementation for 24 hours. The GSH levels were measured in islet cells. Both HSP70 and proteins related to apoptosis were analyzed in islet cells by Western blots. Isolated rat islets were cultured with interleukin (IL)-1beta. Nitrite production was measured using the Griess reagent. RESULTS: The GSH levels were significantly elevated in the glutamine-treated group. HSP70 expression in islets treated with GLN was markedly stronger compared with the control group. The basal Bcl-2 expression was markedly increased by GLN treatment. The GLN-treated group showed attenuated IL-1beta-induced injury in association with NO production. CONCLUSION: These results suggested that preoperative GLN administration induced HSP70 and GSH expressions before islet transplantation, thus attenuating IL-1beta-induced injury in association with NO production and apoptosis, which might be potential tool to mitigate the ischemic damage to islet cells and the early inflammation at the site of implantation through a self-protective mechanism.

Evaluation of ER and Ki-67 proliferation index as prognostic factors for survival following neoadjuvant chemotherapy with doxorubicin/docetaxel for locally advanced breast cancer.

BACKGROUND: The aim of the study was to identify reliable predictive biological markers for treatment outcome following neoadjuvant adriamycin/docetaxel (AT) chemotherapy in locally advanced breast cancer patients. MATERIALS AND METHODS: This study was a phase II study on AT neoadjuvant chemotherapy in locally advanced breast cancer patients. Patients received 50 mg/m(2) of doxorubicin intravenously (IV) over 15 min followed by docetaxel 75 mg/m(2) infused over 1 h, repeated every 3 weeks for three cycles. Surgery was performed within 3-4 weeks following the last cycle of chemotherapy. We analyzed the pre-treatment and post-treatment expression levels of ER, PgR, HER-2, Ki-67 proliferation index, and p53 and examined the correlation between the markers and clinical parameters with treatment response, overall survival and relapse-free survival following neoadjuvant treatment. RESULTS: From July 2001 to September 2004, 61 patients were enrolled. The meaningful parameters adversely influencing survival were post-treatment ER(-) status (P = 0.013) and post-treatment Ki-67 index above 1.0% (P = 0.013). At the multivariate level, the post-treatment Ki-67 proliferation index < or = 1.0 was the only meaningful prognostic factor for better survival (P = 0.033). Notably, tumors with Ki-67 index < or = 1.0 were more likely to express ER with statistical significance (P = 0.002). Tumors with ER(+) and Ki-67 index < or = 1.0 showed the highest survival rate, followed by ER(+) and Ki-67 index > 1.0%, ER(-) and Ki-67 < or = 1.0%, and ER(-) and Ki-67 > 1.0% with the worst survival (P = 0.033). CONCLUSION: Collectively, post-treatment ER status and Ki-67 proliferation index were prognostic of overall survival following neoadjuvant AT chemotherapy.

Spinal epidural hemangiomas: various types of MR imaging features with histopathologic correlation.

BACKGROUND AND PURPOSE: Because of the high vascularization of hemangiomas, preoperative misinterpretation may result in unexpected intraoperative hemorrhage and incomplete resection, which results in the persistence of clinical symptoms or recurrence. Our purpose was to analyze various MR imaging features of a spinal epidural hemangioma with histopathologic correlation. MATERIALS AND METHODS: After searching through the pathology data bases in 3 hospitals, we included 14 patients (9 male and 5 female; mean age, 38 years; age range, 2-62 years) with spinal epidural hemangiomas confirmed by surgical resection after MR imaging. Three radiologists reviewed the MR imaging in consensus and categorized the features into subtypes on the basis of histopathologic findings. RESULTS: We categorized the MR imaging features as follows: type A for a cystlike mass with T1 hyperintensity (2 cases, arteriovenous type with an organized hematoma), type B for a cystlike mass with T1 isointensity (3 cases, venous type), type C for a solid hypervascular mass (7 cases, cavernous type), and type D for an epidural hematoma (2 cases, cavernous type with hematoma). Types A and B had frequent single segmental involvement (4/5), whereas types C and D had multisegmental involvement in all. Regardless of MR types, lobular contour (8/14) and a rim of low T2 signal intensity (8/14) of the mass were common. T1 hyperintensity of the mass was occasionally seen (5/14). CONCLUSIONS: Spinal epidural hemangiomas can have various MR imaging features according to their different histopathologic backgrounds. In addition to common features such as solid hypervascularity, lobular contour, and a rim of low T2 signal intensity, T1 hyperintensity or multisegmental involvement may also be a clue in the differential diagnosis of a spinal epidural hemangioma.

Pulmonary cavitary mass containing a mural nodule: differential diagnosis between intracavitary aspergilloma and cavitating lung cancer on contrast-enhanced computed tomography.

AIM: The objective of this study was to identify whether there were any significant differences in the computed tomography (CT) findings of an intracavitary aspergilloma and a cavitating lung cancer containing a mural nodule. MATERIALS AND METHODS: The CT and histopathological findings of 12 patients (male:female ratio 3:9; aged 51-76 years) with cavitating lung cancer containing a mural nodule and 26 patients (male:female ratio 14:12; aged 29-72 years) with intracavitary aspergilloma were retrospectively reviewed. RESULTS: The mural nodules within cavitating lung cancer were more enhanced (p<0.001) and showed a nondependent location more frequently (p=0.012) than those of intracavitary aspergillomas. The cavitary walls were thicker in cavitating lung cancer (mean 5.8mm thick) than those in intracavitary aspergillomas (mean 2.6mm thick; p=0.035). Adjacent bronchiectasis and volume decrease of the involved lobe were observed more frequently in intracavitary aspergillomas than in cavitating lung cancers (p<0.001 and p=0.008, respectively). CONCLUSION: Whether a mural nodule within a cavitary lesion is contrast-enhanced or not is one of the most important features in making a differential diagnosis between an intracavitary aspergilloma and a cavitating lung cancer. Assessment of dependent location of a mural nodule within the cavity and wall thickness of the cavity itself can also be helpful for differentiation.

Fine needle aspiration cytology of solitary fibrous tumours of the pleura.

OBJECTIVE: To analyse fine needle aspirates from solitary fibrous tumour (SFT) of the pleura and to elucidate the cytological features unique to these tumours and differential diagnostic findings of benign and malignant SFTs. METHODS: Fine needle aspiration (FNA) cytology slides from eight cases of SFT of the pleura, including six benign and two malignant SFTs, were reviewed. The subsequent histological slides were also examined. RESULTS: Cytological diagnoses from six histologically proven cases of benign SFTs were low-grade sarcoma (one), non-small cell carcinoma (one), malignant tumour (1) and benign (three). Two cases of malignant SFTs were cytologically diagnosed as malignancy. The aspirates showed a varying degree of cellularity. Most smears were composed of single, scattered fusiform cells, and irregular loose aggregates of oval to spindle cells intimately admixed with dense collagenous stroma. Two malignant SFTs had a greater number of cells in clusters, and displayed mitotic activity, without significant cytological atypia. CONCLUSIONS: The diagnosis of SFT may be suggested by a combination of cytological and radiological findings. The precise determination of malignancy for SFT, however, is not usually straightforward on the basis of cytological features alone. The findings of highly cellular clusters and mitotic activity in the FNA cytological smear can help differentiate malignant from benign SFTs.

Benign localized fibrous tumour of the pleura: CT features with histopathological correlations.

AIM: To assess the CT features of benign localized fibrous tumour of the pleura, with histopathological correlations. MATERIALS AND METHODS: CT and histopathological findings of 18 patients with surgically resected benign localized fibrous tumour of the pleura were retrospectively assessed. RESULTS: Tumours were pleura or fissure based, semilunar, lentiform or oval in shape, classified according to their homogeneous, slightly heterogeneous or heterogeneous enhancement pattern. Of the 18 tumours, 5 (28%) demonstrated > or = 55 HU increment or higher attenuation than muscles on contrast-enhanced CT, and histopathologically showed a haemangiopericytoma-like pattern with rich vascularity. CONCLUSION: CT analysis of the shape of a mass and the enhancement pattern can be helpful in the diagnosis of benign localized fibrous tumour of the pleura.

Relationship between p53-associated proteins and estrogen receptor status in ovarian serous neoplasms.

We studied the immunoexpression of p14ARF, MDM2, and p53, in addition to relationships between those protein expressions and estrogen receptor (ER)alpha in ovarian serous tumors including benign (n= 23), borderline (n= 41), and malignant (n= 94). The aberrant expressions of p14ARF, MDM2, and p53 were observed in 19.6% (31/158), 47.5% (75/158), and 39.9% (63/158) of cases, respectively. The expression of MDM2 was significantly higher in borderline tumors compared to benign (P= 0.04) and malignant (P < 0.01) tumors. p53 expression in borderline tumors was uncommon, and p14ARF expression loss was mainly observed in carcinomas. Altered expression of p14ARF, MDM2, and p53 shows significant relationship with stage. Overexpression of MDM2 (P= 0.01) and loss of p14ARF expression (P= 0.04) were significantly associated with ER expression. Our results suggest that alteration of p14ARF-MDM2-p53 pathway proteins may contribute significantly to the tumorigenesis of ovarian serous neoplasms, and ER is involved in cellular regulation of p14ARF-MDM2-p53 pathway in ovarian serous neoplasms.

NK and NK-like T-cell lymphoma in extranasal sites: a comparative clinicopathological study according to site and EBV status.

AIMS: To analyse the clinicopathological findings of extranasal CD56+ cytotoxic T- or NK-cell lymphomas in different organs and to compare Epstein-Barr virus (EBV)+ and EBV- lymphoma of non-blastoid cytomorphology. METHODS AND RESULTS: Fifty-one cases of cCD3+ T-cell intracellular antigen (TIA-1)+ CD56+ lymphomas of extranodal/extranasal origin were included in the study. The primary sites of the CD56+ tumours were soft tissue (n = 10), the gastrointestinal (GI) tract (n = 13), the skin (n = 15), upper aerodigestive tract excluding nasal and nasopharyngeal regions (n = 11), the testis (n = 1), and parotid gland (n = 1). TCR gene rearrangement was detected in seven of 47 cases examined (16%). EBV was positive in 39 of 51 cases (76%). The positive rate of EBV was higher in tumours of soft tissue (80%), GI tract (92%), and skin (80%), and lowest in the upper aerodigestive tract excluding the nasal and nasopharyngeal region (50%). Tumours of the soft tissue and the upper aerodigestive tract tended to present with localized disease (P = 0.002). The 2-year survival rate was lowest for tumours of the GI tract (P = 0.0256). EBV- TCR- lymphoma showed less necrosis (P = 0.0133) and a better 2-year survival rate (P = 0.0066) than EBV+ TCR- lymphoma. Patients with EBV+ TCR+ lymphomas tended to present with localized disease, more often than EBV+ TCR- lymphoma (P = 0.0186). Significant prognostic factors in all CD56+ lymphomas were the site (P = 0.0256), EBV status (P = 0.0026), necrosis with or without perforation (P = 0.0338) and the presence of pleomorphic large tumour cells (P = 0.0428). Cox's regression analysis adjusting for other pathological parameters showed EBV status to be the only independent prognostic factor (P = 0.018). CONCLUSIONS: Extranodal CD56+ EBV- lymphoma at extranasal sites is a clinically less aggressive malignancy and displays less necrosis than CD56+ EBV+ lymphoma. Because CD56+ EBV+ TCR+ lymphomas show similar pathological and clinical findings to CD56+ EBV+ TCR- lymphomas, nasal-type NK/T-cell lymphomas at extranasal sites should be diagnosed as such on the basis of EBV+, cytotoxic T or NK phenotype irrespective of the genotype determined by molecular study.

Coexpression of Bcl-6 and CD10 in diffuse large B-cell lymphomas: significance of Bcl-6 expression patterns in identifying germinal center B-cell lymphoma.

Most follicular lymphomas (FLs) transform to diffuse lymphoma eventually, comprising a significant proportion of diffuse large B-cell lymphoma (DLBCL). Judging by bcl-2 rearrangement (bcl-2R), one third of DLBCLs are believed to be of FL derivation in the Western population. However, bcl-2R is not specific and is not detectable in every case of FL. In East Asia, FL is uncommon but DLBCL is not. The proportion of tumors of FL origin in DLBCL is not known in this region. The coexpression of Bcl-6 and CD10 proteins, a reliable marker to identify germinal center (GC) B-cell lymphoma including FL, was analyzed in primary nodal DLBCLs (n = 104) diagnosed at major hospitals in Seoul during a recent 2-year period, along with well-defined cases (n = 17) of nodal FL as controls. Bcl-2 protein expression (n = 77) was also studied along with bcl-2R (n = 64), by polymerase chain reaction. Formalin-fixed archival specimens were used in all these assays. The Bcl-6/CD10 coexpression was observed in 35 DLBCLs (34%) and 14 FLs (82%), and most of them showed a pattern of Bcl-6 expression similar to that of the GC. Bcl-2 expression or bcl-2R did not correlate with Bcl-6/CD10 coexpression. Histologically, compartmentalizing sclerosis was associated with a high rate of the coexpression (8 of 10). In conclusion, to detect GC B-cell lymphoma in routine biopsy specimens, a pattern of Bcl-6 staining similar to the GC must be identified. Bcl-6+/CD10+ GC B-cell lymphomas thus defined comprised one third of primary nodal DLBCLs in Korea. The incidence rate is similar to that in the West. The reasons for the discrepancy between the incidence of GC B-cell lymphoma and the paucity of the follicular pattern in East Asian subjects warrant further studies.

Immunoexpression of inhibin alpha-subunit in adrenal neoplasms.

Inhibin normally is produced by ovarian granulosa cells and testicular Sertoli cells. Extragonadal inhibin expression also has been detected in the placenta, pituitary gland, and liver. It may be difficult to make a distinction between adrenal cortical tumors, pheochromocytoma, and metastatic carcinomas including renal cell and hepatocellular carcinoma. Immunohistochemical expression of inhibin alpha-subunit was evaluated to determine whether any usefulness of immunostaining could be found for inhibin alpha-subunit in the differential diagnosis of adrenal glandular lesions. The authors performed immunostaining against inhibin alpha-subunit on 5 cases of normal adrenal gland, 1 case of adrenal cortical hyperplasia, 25 cases of adrenal cortical adenoma, 6 cases of adrenal cortical carcinoma, 21 cases of pheochromocytoma, 8 cases of metastatic carcinoma, and 10 cases of primary renal cell carcinoma. Normal adrenal gland showed a strong immunoreactivity against inhibin alpha-subunit, especially in the inner layer of the adrenal cortex, representing the zona reticularis, but adrenal medulla was negative for inhibin alpha-subunit. Adrenal cortical hyperplasia associated with Cushing's syndrome showed a strong, diffuse immunoreactivity for inhibin alpha-subunit. Immunoreactivity against the inhibin alpha-subunit was identified in all cases of adrenal cortical adenoma and carcinoma, especially in the adrenal cortical neoplasm with Cushing's syndrome, which showed a strong reactivity. However, immunoreactivity was absent in two metastatic carcinomas from the liver and colon and most of the pheochromocytomas, except three cases with weak focal positivity for inhibin alpha-subunit. Four cases of metastatic renal cell carcinoma and 10 cases of primary renal cell carcinoma revealed no immunoreactivity. Metastatic adenocarcinoma from the prostate showed a weak immunoreactivity for inhibin alpha-subunit. Metastatic hepatoblastoma was negative against inhibin alpha-subunit with endogenous biotin blocking. Immunoexpression for inhibin alpha-subunit is useful for making distinction between adrenal cortical tumors, pheochromocytoma, and metastatic carcinoma. Inhibin alpha-subunit may be valuable as part of a diagnostic immunohistochemical panel in adrenal glandular lesions.