Clinical Characteristics of Recurrent Juvenile Nasopharyngeal Angiofibroma (JNA) After Radiation Therapy.

Juvenile nasopharyngeal angiofibroma (JNA) is a benign vascular tumor occurring in young males. Treatment of JNA is a complex procedure, especially in advanced cases with a high risk of major complications. We report the clinical, radiological and histological specialties of a rare case of recurrent JNA 3 years after radiation therapy in an 18-year-old boy. The patient underwent endoscopy assisted partial midfacial degloving approach. This treatment has been shown to be effective in advanced JNAs with minor morbidity.

An unusual mass of nasal cavity: recurrent glomangiopericytoma.

Hemangiopericytomas are rare tumors of sinonasal region. In this article, we described a case of recurrent mass in right nasal cavity which presented with nasal obstruction and intermittent epistaxis. Patient had a surgical history on the same nasal region without any histopathological document. Abnormal bleeding was observed during surgery and mass was partially removed for histopathological investigation. The result was glomangiopericytoma of the sinonasal region. Although extended surgery was recommended to the patient including preoperative and perioperative measures for bleeding problem, patient preferred to follow-up rather than removal. The clinical progress and review of glomangiopericytoma have also been discussed.

Cyclin A and cyclin B1 overexpression in differentiated thyroid carcinoma.

Approximately 30% of patients with thyroid nodules have indeterminate or suspicious fine-needle aspiration (FNA) biopsy results. These patients usually undergo thyroidectomy because of cancer risk. Our aim was to determine diagnostic value of cyclin A and cyclin B1 immunohistochemistry added to routine cytology and their expression on histological sections. We studied the expression of cyclin A and cyclin B1 in FNA biopsies and resection specimens of 168 indeterminate or suspicious FNA biopsy results retrospectively at an academic hospital using immunohistochemistry. Malignant histopathology consisted 64 of resection specimens (58 papillary, 4 follicular, 1 medullary, and 1 Hürthle cell carcinoma). Cyclin A was overexpressed in 51.5% of malignant cases in contrast to 31.7% of 104 benign pathology specimens (P = 0.025). Cyclin B1 was positive in 39.1% of malignant specimens in contrast to 15.4% of benign cases (P = 0.001). Cyclin A overexpression was not linked to cyclin B1 overexpression. No association was found between overexpression of cyclin A, cyclin B1 and age, thyroiditis, multifocality, tumor size, extra-thyroidal extension, capsule infiltration, lymph node and distant organ metastases and TNM stage in malignant cases. Female patients with thyroid carcinoma overexpressed significantly more cyclin B1 than male patients (P = 0.015). Retrospective analysis of cyclin A and cyclin B1 in FNA biopsies yielded negative results for both benign and malignant cases. In conclusion, cyclin A and cyclin B1 are useful markers in the distinction of benign and malignant thyroid tumors and can increase diagnostic accuracy.

Morphological evaluation of parathyroid adenomas and immunohistochemical analysis of PCNA and Ki-67 proliferation markers.

OBJECTIVE: Parathyroid adenomas are the most common cause of primary hyperparathyroidism. Biological studies have shown that parathyroid adenomas are monoclonal proliferations. Up to date, five cell types have been identified in normal parathyroid tissues; chief cells, vacuolated chief cells, dark chief cells, oxyphil cells and transitional oxyphil cells. Most parathyroid adenomas are predominantly composed of chief cells. In this study, we aimed to indicate the relationship between the predominant cell type in parathyroid adenomas and proliferating cell nuclear antigen, Ki-67 antigen, and serum parathormone levels and the gland weight. MATERIAL AND METHOD: 15 cases who had a diagnosis of parathyroid adenomas were included in the study. Histopathologically, the predominant cell type was determined in all the cases. Paraffin blocks were immunohistochemically stained with proliferating cell nuclear antigen and Ki-67. RESULTS: The average parathormone level of the cases was 239.52 ± 36.61 pg/ml before surgery. Mean gland weight was 1.69 ± 0.49 g. Two of the cases showed atypical adenoma characteristics. The predominant cell type was vacuolated chief cell. Immunohistochemical investigation showed that the mean average Ki-67 index value was 4.26 ± 0.86%. The mean proliferating cell nuclear antigen index was 93.20± 45.72/10³. There was a meaningful relationship between gland weights and serum parathormone levels. There was no meaningful relationship between predominant cell types and serum parathormone levels, proliferating cell nuclear antigen index, and Ki-67 index. The chief cell was identified as the predominant cell type. CONCLUSION: It can be concluded that parathyroid adenomas come into existence as a result of neoplastic proliferation of chief cells, especially vacuolated chief cells.

Immunohistochemical and morphologic findings in columnar cell lesions of the breast.

BACKGROUND: Columnar cell lesions (CCLs) with or without atypia frequently coexist with invasive or in situ breast carcinomas. In this study, 39 mastectomy specimens containing CCLs coexisting with invasive carcinomas were retrospectively analyzed for cellular characteristics and structural pattern of CCL neighboring the tumor. MATERIALS AND METHODS: The expression of estrogen receptor (ER), progesterone receptor (PR), and p53 antibodies in CCL and coexisting invasive tumors, type of invasive tumor, histopathologic grade, and presence of atypia in CCL have been studied. RESULTS: Sixteen (41%) of all CCLs were with atypia, whereas 23 (59%) of them were without atypia. No correlations were found between the presence of CCLs with atypia and either the morphologic type of carcinoma or histopathologic grade of the tumors. Presence of atypia in the CCL was not correlated with the expression of p53 in the invasive tumors. CCLs without atypia dominated in Grade III tumors. The percentages of CCLs without atypia were also higher in both ER (-) and PR (-) tumors. CONCLUSIONS: CCL with atypia is generally considered to be a precursor of invasive carcinoma; however, in our study, CCLs without atypia more frequently coexisted with breast carcinoma.

HER-2/neu gene codon 655 (Ile/Val) polymorphism in breast carcinoma patients.

Amplification and/or overexpression of HER-2/neu has been reported to be associated with poor prognosis in breast cancer. One single-nucleotide polymorphism at codon 655 indicates a guanine-to-adenine substitution (Ile655Val) in the transmembrane domain-coding region of the HER-2/neu gene reported to be associated with increased risk of breast cancer. However, several studies have shown that this association is controversial. In this study, we aimed to evaluate the association between HER-2 codon 655 polymorphisms and breast cancer risk in breast cancer patients. We analyzed the HER-2 codon 655 polymorphisms in paraffin block sections from 58 breast cancer patients and 55 control subjects and evaluated the association of the polymorphic alleles with breast cancer. Following DNA isolation, polymerase chain reaction-restriction fragment length polymorphism analysis was carried out. The polymorphic Val allele was detected in 12.1% of the patients and in 17.3% of the control subjects. When the results of the study were evaluated, no statistically significant correlation was found between HER-2/neu codon 655 polymorphism and breast cancer.

Intravenous lipoleiomyomatosis of uterus with cardiac extension: a case report.

A case of intravenous leiomyomatosis (IVL) with histological features of a lipoleiomyoma (intravenous lipoleiomyoma) in a 48-year-old woman is reported. The patient, with the tumor located in the uterus and extended up on the right side of the heart through the inferior vena cava, was diagnosed as having a cardiac mass. She displayed symptoms of dyspnea, chest pain due to the cardiac mass, as well as pelvic pain and dysmenorrhea. She underwent cardiac surgery because of a right atrial mass, and the histopathological diagnosis was leiomyoma without the knowledge of a uterine mass. Afterwards, a right adnexial mass was detected in the pelvis, and a total hysterectomy-bilateral salpingo-oophorectomy was performed for the adnexial mass, which was also diagnosed as leiomyoma. In this case report, we describe an intravenous lipoleiomyomatosis of the uterus which, at the initial clinical presentation, showed cardiovascular symptoms. We emphasize the histopathological features and the differential diagnosis of this rare tumor in the light of the literature.

Steroid-resistant acute rejections after liver transplant.

OBJECTIVES: Liver transplant is the definitive treatment for the end-stage liver disease. Although effective immunosuppressants are available, steroid-resistant acute rejection can be encountered. MATERIALS AND METHODS: Between September 2001 and April 2010, 285 adult and pediatric liver transplants were done on 279 patients from deceased donors and living-related donors at our center. All patients received tacrolimus-based immunosuppressive therapy. Steroids were tapered in 3 months. Liver biopsy was done to confirm acute rejection after vascular or biliary complications had been excluded. High-dose steroids were administered for acute rejections. If there was no response to steroids, acute rejection was defined as steroid-resistant acute rejection. After confirming steroid-resistant acute rejection by a second biopsy, antithymocyte globulin was given to patients until liver functions return to normal level with ganciclovir prophylaxis. RESULTS: Acute rejection was detected in 87 liver transplants (30.5%). Steroid-resistant acute rejections were detected in 12 of 87 patients (7 male, 5 female; 8 pediatric, 4 adult patients; mean age, 16.08 +/- 12.1 years) (13.7%). Mean time from transplant to steroid-resistant acute rejection was 73.58 +/- 59.24 days (range, 20-181 days). The predominant cause of liver disease before liver transplant in patients who had steroid-resistant acute rejection was fulminant hepatic failure. Steroid-resistant acute rejection therapy was successful in 10 of 12 patients (83.3%). Two patients did not respond to therapy; therefore, they advanced to chronic rejection. Adverse effects due to cytokine release were the most frequently encountered reactions in the early period of antithymocyte globulin treatment. The mean follow-ups after steroid-resistant acute rejection treatment were 38.2 +/- 26 months (range, 2-85 months). We did not encounter any serious reaction, serious infection, or long-term adverse effect after antithymocyte globulin treatment. CONCLUSIONS: According to our experience, antithymocyte globulin can be considered as a good therapeutic option in steroid-resistant acute rejection with acceptable adverse effects.

Immunohistochemical FHIT expression still exists in early lesions of basal cell carcinoma.

In this study, we evaluated the expression of Fragile Histidine Triad (FHIT) in basal cell carcinoma (BCC). The FHIT locus was found to be altered in numerous types of cancer [6,7,18,20,22,25,26]. However, we found only one study dealing with FHIT expression in BCC [11]. In our study, we used immunohistochemical methods for the evaluation of FHIT expression in tissue samples of 42 BCC cases. The control group was formed by intradermal melanocytic nevi (IMN). Ki-67 labeling index was used to compare cellular proliferation of BCC with internal and external controls. The study group was further separated into two subgroups, according to the intensity of FHIT staining. The Ki-67 indexes of these subgroups were also compared with each other. As a primary result, there was no significant decrease in FHIT expression in early lesions of BCC. As a second finding, there was no correlation between the intensity of FHIT staining and Ki-67 labeling index. As a third finding, there was no difference in Ki-67 labeling index between early lesions of BCC and non-neoplastic epidermis. The results were unexpected, since FHIT expression has been reported to be lost in an above mentioned study [11]. We concluded that FHIT expression remains to be positive, at least in early lesions of BCC.

Management of elderly patients with advanced non-small cell lung cancer in Turkey.

OBJECTIVE: Non-small cell lung cancer is a disease that affects the elderly. However, most patients older than 70 years are less likely to receive standard therapy than their younger counterparts and the aim of the present study was to determine age-dependent variation in efficacy. SUBJECTS AND METHODS: Between 2004-2008, 40 consecutive patients older than 70 years received treatment for advanced non-small cell lung cancer. All were evaluated for response and toxicity. Chemotherapy was either with cisplatin or carboplatin and double or single agents (vinorelbine, gemcitabine). Docetaxel was used as a second line therapy in selected cases. Patients were grouped according to age: group 1 (70-74 years), group 2 (>or= 75 years). RESULTS: Except for 4 cases, all received chemotherapy, and 61 % were given a cisplatin-containing regimen. Second-line therapy was given to 42.5% and grades 3-4 neutropenia was seen in 17 (42.5%). Only one patient died due to neutropenic fever. Nephrotoxicity was observed in 2 (5%) and one underwent hemodialysis. Overall survival was 10 months, with median survival periods for groups 1 and 2 of 13 and 10 months, respectively (p> 0.05). No differences were found regarding type of chemotherapy administered or adverse events between the 2 groups. CONCLUSION: Patients older than 75 years appear to deserve the same standard therapy for non-small cell lung cancer as that given to younger cases.

p53 expression in pterygium in two climatic regions in Turkey.

PURPOSE: To assess accumulation of p53 protein in samples of primary pterygium from people living in two different climatic regions in Turkey. MATERIALS AND METHODS: Group 1 included 101 pterygium specimens from people in Adana located in southern Turkey. Group 2 included 39 pterygium specimens from people in Ankara, located in the middle of Turkey. Climatic conditions throughout the year are sunnier and warmer in Adana than they are in Ankara. The control group (Group 3) included 30 specimens of conjunctiva that had been excised during cataract surgery from 30 patients without pterygium. The pterygial specimens and control conjunctiva were studied by immunohistochemistry using antibodies against p53 protein. Pearson's chi-square test was used to compare the p53 immunoreactivity. RESULTS: The p53 immunoreactivity in Groups 1 and 2 was greater than it was in the control group ( P 0.001). There were no differences in p53 immunoreactivity between Groups 1 and 2 ( P= 0.060). CONCLUSION: The p53 immunoreactivity was not correlated with ultraviolet irradiation exposure. The p53 immunoreactivity in our pterygium specimens suggests that pterygium could be a result of uncontrolled cell proliferation.

Induction of apoptosis of rabbit corneal endothelial cells by preservative-free lidocaine hydrochloride 2%, ropivacaine 1%, or levobupivacaine 0.75%.

PURPOSE: To determine and compare the amount of apoptosis and changes in rabbit corneal endothelial cell morphology after intracameral administration of different anesthetic agents. SETTING: Department of Ophthalmology, Baskent University Medical Faculty, Ankara, Turkey. METHODS: Right eyes of 64 Vienna white rabbits were injected intracamerally with preservative-free lidocaine hydrochloride 2%, ropivacaine 1%, levobupivacaine 0.75%, or fortified balanced salt solution (BSS Plus) (control). Animals were humanely killed 1 day or 7 days later. Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling was used to detect apoptosis. Corneal endothelial cells and apoptotic cells were counted by light microscopy. The morphologic appearance was determined by transmission electron microscopy (TEM). RESULTS: Apoptotic cell density was high in the anesthetic groups on day 1 (P<.01); there was no significant difference between groups at 7 days. Apoptotic cell density declined significantly between 1 day and 7 days in the anesthetic groups (P<.05) but not in the control group. There was no difference in endothelial cell density between the 4 groups at 1 or 7 days. All anesthetic groups showed degenerative changes on TEM, with the least change in the preservative-free lidocaine hydrochloride 2% group. CONCLUSIONS: Intracameral injections of preservative-free lidocaine, ropivacaine, and levobupivacaine induced significantly more apoptotic endothelial cell loss than BSS Plus and led to morphologic changes in the corneal endothelial cells in the early period. This effect was temporary, with recovery by 7 days. Considering the limited proliferative capacity in human eyes, the induced apoptosis might result in the permanent cell loss and enlargement in human corneal endothelium.

Fulminant hepatic failure in children: etiology, histopathology and MDCT findings.

INTRODUCTION: The purpose of this study is to determine the etiologies, histopathology and MDCT findings of children with fulminant hepatic failure admitted to our institution. MATERIALS AND METHODS: Between June 2004 and November 2006, 15 children with fulminant hepatic failure who underwent MDCT were included retrospectively in this study. Twelve patients had liver biopsies. The patients were divided into three groups as hyperacute (Group I), acute (Group II) and subacute (Group III) depending on onset of hepatic encephalopathy. RESULTS: Hepatitis A in 4 patients, non-A, non-E hepatitis in 4; mushroom poisoning in 3; fulminant Wilson's disease in 2; autoimmune hepatitis in 1; and both hepatitis B and toxic hepatitis (with leflunomide treatment) in 1 patient were detected. MDCT of all three groups revealed diffuse reduction in hepatic attenuation in 11 patients; ascites in 9; periportal edema in 6; edema of gallbladder wall in 6; splenomegaly in 6; heterogeneous hepatic parenchyma in 6; hepatomegaly in 3; irregular contours of liver in 2; multiple micronodules in 1 and necrotic areas and regeneration in liver parenchyma in 2 patients. Histopathologic evaluation of liver biopsies showed massive hepatic necrosis, inflammatory cell infiltration and ductular proliferation in 8 patients, periportal edema in 6, edema of gallbladder wall in 5, regenerating nodules and fibrous septa consistent with cirrhotic pattern in 2, and regenerating nodules and necrotic areas in 2 patients. CONCLUSION: The most common MDCT findings in fulminant hepatic failure were diffuse reduction in hepatic attenuation and ascites. Massive hepatic necrosis was the most common histopathologic finding.

Pap smear findings in chronic renal failure patients compared with the normal population according to Bethesda 2001.

Dialysis remains the most common treatment for end-stage renal disease (ESRD). Although the increased risk of cancer after renal transplant is well documented, there is less certainty about the risk of cancer in patients treated only with dialysis. From 1997 to 2002, 262 ESRD patients received a Pap test at Baskent University. The smears of 149 patients who had ESRD for more than 9 months were compared with the smears of 150 otherwise healthy patients. All of the Pap smears were re-examined according to Bethesda 2001 criteria. The mean age of the patients was 42.88 years. Regarding micro-organisms, no statistically significant difference between the groups were observed. In 36 Pap smears, a shift in flora suggestive of bacterial vaginosis was detected. There were statistically significant differences between the groups. When age was considered as a marker of atrophy, atrophy in patients younger than 50 years was statistically different between the groups. Also, we determined that the shift in flora suggestive of bacterial vaginosis and atrophy in patients aged younger than 50 years did not depend on the length of hemodialysis. Of 13 patients (4.3%) who had epithelial cell abnormalities there were not statistically significant differences between the groups. In conclusion, according to our study, CRF seems not to be a predictive factor for cervical cancer. Shift in flora suggestive of bacterial vaginosis and atrophy in patients aged younger than 50 years might be the natural effects of uremia, and they appear not to be dependent on the length of the hemodialysis period.

Total colonic polyp diameter: a marker for the risk of malignancy?

BACKGROUND/AIMS: The correlation of the risk of malignancy with the sum of the diameters of small colonic polyps is unknown, and data regarding this topic are lacking. In this study, the relationship between the sum of the diameters of the total number of colonic polyps and poor histopathologic characteristics was examined. METHODS: A total of 920 neoplastic colon polyps were evaluated in 480 patients. The "total polyp diameter" (i.e. the sum of all polyp diameters identified during colonoscopy), which was calculated in each patient by adding the diameter of each polyp to a sum, was categorized as "small" (<10mm in diameter) or "large" (> or =10mm in diameter). The polyps were further categorized by histopathologic component as "unfavorable" or "favorable" and were divided into 2 groups: group 1 (those identified as carci noma, carcinoma in situ, villous adenoma, and tubulovillous adenoma with a villous component of more than 25%) and group 2 (mixed adenomatous polyps with various degrees of hyperplastic or inflammatory components and adenomas with a tubular component of more than 75%). RESULTS: Large polyps that had a total diameter greater than or equal to 10mm tended to have poor histopathologic characteristics (p<0.05). Polyps generally tended to localize in the left portion of the colon, and malignant polyps or those at risk for malignancy in particular tended to localize in the left colon (p<0.05). CONCLUSIONS: Polypectomy is recommended for patients in whom the sum of the diameter of all colonic polyps exceeds 10mm.

Pediatric liver transplant: results of a single center.

OBJECTIVES: Liver transplant in the pediatric population has become an accepted treatment modality for children with end-stage liver disease. In this study, we analyze our experiences with pediatric liver transplant at our center. MATERIALS AND METHODS: Since September 2001, 8 deceased-donor and 96 living-donor liver transplants have been done in 101 children (mean age, 6.7 +/- 5.5 years; range, 2 months to 17 years). The children's charts were reviewed retrospectively. RESULTS: Indications for liver transplant were cholestatic liver disease (n=17), biliary atresia (n=24), Wilson's disease (n=16), fulminant liver failure (n=18), hepatic tumor (n=13), and other (n=13). The median pediatric end-stage liver disease score was 23.1 +/- 11.1 (range, -8 to 48). The median follow-up was 24.2 +/- 19.4 months (range, 1-77 months). Three children underwent retransplant. The main complications were infections (25.9%) and surgical complications (39.5%) (including biliary complications and vascular problems). The incidence of acute cellular rejection was 42.3%. Sixteen children died during follow-up, and, at the time of this writing, the remaining 85 children (85%) were alive with good graft functioning, showing patient survival rates of 90%, 85%, and 83% at 6, 12, and 36 months, respectively. CONCLUSIONS: In conclusion, the overall outcomes of pediatric liver transplantation at our center are quite promising.

Diagnostic accuracy of fine-needle aspiration cytology of palpable breast masses: an SROC curve with fixed and random effects linear meta-regression models.

We used various meta-analytic methods to compare 25 studies describing fine-needle aspiration (FNA) cytologic analyses performed from 1984 to 2007 on palpable breast masses. We found that in the 25 studies examined, the sensitivity ranged from 78% to 100%, the specificity ranged from 76% to 100%, and the diagnostic odds ratio (DOR) ranged from 15.83 to 33 198. The overall diagnostic accuracy was found to be as follows: 0.93 (95% CI: 0.92-0.94) for sensitivity, 0.98 (95% CI: 0.97-0.98) for specificity, and 505.209 (95% CI: 273.08-934.95) for the DOR. The overall diagnostic accuracy according to the results of summary receiving operating characteristic (SROC) curve analysis was 0.95 +/- 0.0032, and the overall weighted area under the (receiving operating characteristic [ROC]) curve (AUC) was 0.99 +/- 0.0014. The DOR values did not show a large variation in the various positivity threshold values. However, the results of those studies had some heterogeneity. The four covariates that were added to the standard SROC model to evaluate variations in the results of the studies were the year of publication, the number of aspirations, the percentage of insufficient material, and the study design. The relative diagnostic accuracy of studies performed after 1990 was 3.98 times higher than that of studies performed before 1990. The relative DOR (RDOR) value was also found to be statistically significant (95% CI: 1.22-13.02). That result may be attributed to the technologic improvements in diagnostic tools over the years. Although it was not statistically significant, an increase in the number of aspirations caused an increase in the RDOR of the FNA cytology (95% CI: 0.52-8.11). In contrast, increasing the percent of insufficient material caused a statistically insignificant but clinically significant decrease in the RDOR of FNA (RDOR = 0.79, 95% CI: 0.21-2.98). In conclusion, our meta-analysis has shown that FNA cytologic analysis of palpable breast masses is highly accurate in the diagnostic differentiation of benign from malignant tumors.

VEGF, COX-2, and PCNA expression in renal cell carcinoma subtypes and their prognostic value.

OBJECTIVE: To evaluate the prognostic value of new markers such as VEGF (vascular endothelial growth factor), COX-2 (cyclooxygenase-2), and PCNA (proliferating cell nuclear antigen) and review their differences in expression by histological subtype in patients with renal cell carcinoma (RCC). METHODS: About 99 patients who underwent radical (n = 79) or partial nephrectomy (n = 20) were included in this study. Histopathological specimens from the subjects were retrospectively analyzed immunohistochemically for the presence of VEGF, COX-2, or PCNA. RESULTS: Mean staining ratios for VEGF, COX-2, and PCNA were 16.5, 16.8, and 31%, respectively. Correlations were evaluated among these three prognostic factors. There was no correlation between PCNA and VEGF (P = .068), but there were significant correlations between COX-2 and both PCNA and VEGF (P = .005 and P = .000, respectively). A significant correlation was found between the expression of VEGF and both pathologic stage and vascular invasion (P = .018 and P = .025, respectively). In addition, patients with conventional RCC had significantly lower VEGF and COX-2 levels than those with papillary RCC (P < .012). CONCLUSIONS: It is obvious that prognostic factors such as VEGF, COX-2, and PCNA may vary depending on histological subtype. The level of expression of these factors together with histological subtype may provide valuable predictive information about the outcome of treatment.

Liver transplant in an infant with bilateral cystic neuroblastoma complicated by hepatic metastases and life-threatening consumption coagulopathy.

Here we report a patient with stage-4 bilateral cystic adrenal neuroblastomas with disseminated liver metastases and consumption coagulopathy who underwent liver transplant. Our patient was initially diagnosed with infantile hepatic hemangioendothelioma and bleeding into the adrenal glands secondary to consumption coagulopathy (Kasabach-Merritt syndrome). Liver transplant was performed as a life-saving procedure under this diagnosis. We discuss this unique patient because of the diagnostic pitfalls of this rare disease and the successful clinical outcome after LT and subsequent chemotherapy for neuroblastoma.

Hepatic parenchymal changes and histologic eosinophilia as predictors of subsequent acute liver allograft rejection.

During the first episode of acute cellular rejection (ACR) after liver transplantation, centrilobular changes in liver biopsy specimens may be possible indicators of subsequent episodes of ACR, early chronic rejection, or acute graft loss. The purpose of this study was to identify differences between the histopathological findings in liver biopsy specimens obtained during the first rejection episode in patients who subsequently developed further episodes of ACR and those who did not. The histopathological findings in 22 patients who had a single episode of acute rejection (group 1) were compared with those in 23 patients who had multiple episodes of acute rejection (group 2). Only the first liver biopsy samples of the latter group were taken into consideration. We assessed the predictive value of centrilobular necrosis, central vein endothelialitis, pericentral inflammation, hepatocellular ballooning, cholestasis, hepatocellular apoptosis, lobular inflammation, the degree of portal eosinophilia, and characteristic portal tract features in poor responders to antirejection treatment. The time to the first episode of ACR and the rejection activity index were similar in patients in both groups. Hepatocellular apoptosis, hepatocellular ballooning, and central vein endothelialitis were common features of both groups. The incidences of pericentral inflammation, centrilobular necrosis, and portal eosinophilia were significantly higher in patients in group 2 than in those in group 1 (P < 0.05). Patients with pericentral inflammation, centrilobular necrosis, and marked portal eosinophilia during an initial episode of acute rejection may be more likely to develop subsequent episodes of ACR.