The use of the Bethesda terminology in thyroid fine-needle aspiration results in a lower rate of surgery for nonmalignant nodules: a report from a reference center in Turkey.

The Bethesda system (BS) for reporting thyroid fine-needle aspiration (FNA), which classifies nodules as nondiagnostic (ND), benign (B), atypia/follicular lesion of undetermined significance (AUS/FLUS), suspicious for follicular neoplasm (SFN/FN), suspicious for malignancy (SFM), or malignant (M), uses clinically valuable management guidelines. The authors employed a similar in-house classification system (IS) for thyroid FNAs, using the categories of ND, B, suspicious follicular cells (SFC), follicular lesion/neoplasm (FL/FN), SFM, and M. The authors compared IS and BS, and assessed the utility of BS in clinical practice. A total of 581 nodules with cytological/histological follow-up were examined and indeterminate lesions by BS were reclassified. The sensitivity and specificity for malignancy using IS were similar to that of BS (77% vs 99%). However, when SFN/FN and SFM were both considered positive, the results for IS and BS were as follows: sensitivity, 85% versus 85%; specificity, 87% versus 94%; and diagnostic accuracy, 86% versus 90%, respectively. Discrepancies between cytological and histological data were evident in 35 cases among all categories of BS except AUS/FLUS. The rate of surgery for nonmalignant nodules was lesser (20% vs 9%) by BS. Among 34 AUS/FLUS cases with follow-up data, hypocellularity was the case in 11 (46%) nonneoplastic and 10 (100%) neoplastic nodules. The use of BS results in a lower rate of surgery for nonmalignant nodules even though patients with borderline cytopathologic features are still encountered. AUS/FLUS category can be separated into subgroups according to the factors causing difficulties in the interpretation. There is a need of accumulation of AUS/FLUS cases to do further evaluations and studies.

Colonic necrosis and perforation due to calcium polystyrene sulfonate in a uraemic patient: a case report.

Sodium or calcium polystyrene sulfonate (Kayexalate or analog) is an ion-exchange resin commonly used to treat hyperkalaemia in patients with chronic kidney disease. It is known to cause digestive complications, such as nausea, vomiting and constipation. Although rare, colonic necrosis and perforation are very severe complications associated with the medication. In this case report, we present a case of calcium polystyrene sulfonate-induced colonic necrosis and perforation to remind clinicians of this rare, but dangerous, toxicity associated with this commonly used medication.

Anti-CD10 (56C6) is expressed variably in adrenocortical tumors and cannot be used to discriminate clear cell renal cell carcinomas.

In the evaluation of retroperitoneal masses, the practicing pathologist faces a dilemma when making a diagnosis based on histology given the often overlapping morphologic appearances of the adrenocortical carcinoma, renal cell carcinoma (RCC), and hepatocellular carcinoma (HCC). CD10 is expressed in a membranous fashion in the vast majority of clear cell RCCs; therefore, it is widely used for distinction from its mimics. However, its expression is not well-investigated in adrenal cortical tumors. We examined CD10 expression in 47 surgically resected adrenocortical tumors (26 adenomas and 21 carcinomas) and compared with 20 clear cell RCCs and 25 HCCs. Twenty HCCs (80%), 18 RCCs (90%), 11 adrenocortical carcinomas (52%), and 18 adrenocortical adenomas (69%) were positive for CD10. HCCs were characterized by a canalicular staining, and clear cell RCCs exhibited membranous or mixed membranous-cytoplasmic staining. Adrenocortical tumors displayed mainly cytoplasmic staining. Four adrenocortical carcinomas and one adenoma also displayed the membranous staining pattern. Despite the relatively small number of samples, our preliminary results revealed that adrenocortical tumors may express CD10 (Clone: 56C6). The most important point from this paper is the fact that anti-CD10 expression has not been previously reported in adrenocortical carcinomas. This suggests that CD10 does not seem to be a useful marker for discriminating clear cell RCCs from adrenocortical tumors since CD10 expression does not rule out the possibility of adrenocortical tumors. This feature should be kept in mind when constructing an antibody panel for an epithelial tumor that involves the adrenal gland and kidney, especially in small biopsy specimens.

Does HepPar-1 immunoexpression have a role in differential diagnosis of periampullary cancer?

AIMS: Histological subtyping of periampullary carcinomas is considered as a criterion for prognosis and therapeutic implications of these tumours. We assessed the immunoexpression rates of HepPar-1, CDX2 and MUC2 antibodies in different subtypes of periampullary adenocarcinomas (PAC), intestinal and pancreatobiliary, in order to assess their impact on differential diagnosis of this group of cancers. The expression of antibodies was also measured in ductal adenocarcinoma of the pancreatic head (DAPH). METHODS: Sixty-five patients with PAC and DAPH who underwent pancreatic Whipple resection constituted the study cohort. Of these, 46 (71%) had PAC, and 19 (29%) had DAPH. Among PACs, 20 (44%) were intestinal and 26 (56%) were pancreatobiliary type. RESULTS: HepPar-1 immunoreactivity was detected in 18 (39%) of all PACs. The rate of HepPar-1 expression was significantly higher in intestinal type PAC (75%) than it was in pancreatobiliary type (12%). The sensitivity, specificity, and accuracy of HepPar-1 immunoexpression for diagnosing intestinal type PAC were 75% , 89%, and 83%, respectively. Similarly, the rates of both CDX2 and MUC2 expressions were significantly higher in intestinal type PAC (80%) than they were in pancreatobiliary type (8%). The sensitivity, specificity, and accuracy of both CDX2 and MUC2 immunoexpressions for intestinal type PAC were 80%, 92%, and 87%, respectively. CONCLUSION: HepPar-1 antibody was found to be a highly sensitive and specific marker for distinguishing intestinal type from pancreatobiliary type among PACs. In addition to CDX2 and MUC2 antibodies, HepPar-1 immunoexpression seems to have a potential role in differential diagnosis of PACs.

Intraductal growth-type mucin-producing peripheral cholangiocarcinoma associated with biliary papillomatosis.

A 64-year-old woman with upper abdominal pain, nausea, and vomiting was admitted. The magnetic resonance imaging revealed marked dilation and "crowding" of the segment 4 bile ducts with an area suspicious for a stone or tumor. Ultrasonography-guided percutaneous transhepatic cholangiography revealed multiple filling defects in the segment 4 bile ducts, the left and common hepatic ducts. A left hepatectomy and cholecystectomy was performed. Dilated bile ducts containing mucinous material and a mass in the cystically dilated bile ducts of segment 4 were detected in the gross examination. It showed continuity within the surrounding dilated bile ducts. The dilated bile ducts of the segments 2 and 3 contained mucinous material without any apparent mass formation. Microscopically, the bile ducts were lined by biliary epithelium displaying simple and complex papillary structures with moderate to severe degree of dysplastic changes. The mass was composed of complex papillary structures filling the bile duct with a few foci of invasion. The papillary structures were composed of mucin-producing columnar cells as well as cells with oncocytic appearance. Patchy cytokeratin 7, cytokeratin 19, hepatocyte paraffin 1, MUC2, and CDX2 immunopositivities were observed. Biliary papillomatosis, mucin-producing intrahepatic cholangiocarcinoma, and intraductal papillary-type peripheral cholangiocarcinoma are in the same disease spectrum of papillary biliary neoplasm and termed as intraductal papillary neoplasm of the liver. Mucinous hypersecretion and signs of mucobilia are considered specific and should raise the suspicion of lesions in this spectrum.

The prognostic significance of angiogenesis and the effect of vascular endothelial growth factor on angiogenic process in Wilms' tumour.

AIMS: There is a subgroup of patients with Wilms' tumour (WT) having favourable clinicopathological features but adverse outcome. We aimed to investigate the prognostic significance of angiogenesis and whether it can be used for predicting which patients will fall into this category, and the possible role of vascular endothelial growth factor (VEGF) on angiogenesis in WT. METHODS: Tumours in nephrectomy specimens from 63 WT patients were investigated for neovascularisation and VEGF expression by immunohistochemistry. The endothelial cells were highlighted by anti-CD34 and anti-CD31, and the microvessels in the hot-spots were counted. Correlations between the microvessel density (MVD), VEGF expression, clinicopathological features and prognosis were studied. RESULTS: Among 21 patients with follow-up data, favourable histology was detected in 17, seven of which died of disease. Patients with highly vascular tumours showed significantly poorer prognosis than those with low vascular tumours. There was no significant relationship between angiogenesis and VEGF expression. VEGF immunostaining revealed various patterns in different components of WT. CONCLUSIONS: We suggest that high MVD can be used as an indicator of poor prognosis with WT patients displaying favourable histology and there might be some additional growth factors other than VEGF which may also be responsible for angiogenesis in WTs.

A case of inflammatory pseudotumor in the spleen.

A case of an inflammatory pseudotumor of the spleen is presented. A 43-year-old woman was hospitalized for a detailed examination due to pancytopenia, which was diagnosed during an examination related to left upper quadrant abdominal pain. Physical examination revealed a 2 to 3 cm splenomegaly. Reticulocyte count was 4% and erythrocyte sedimentation rate was 55 mm/h. No other important findings were noted, except for an evident increase in myeloid series and megakaryocytes (more evident in erythroid series) on bone marrow aspiration and biopsy. Computed tomography (CT) scan revealed splenomegaly and a centrally located hypodense lesion with a 92 X 86 mm axial diameter in the spleen. With a hematologic malignancy prediagnosis, a splenectomy was performed on the patient because of pancytopenia and splenomegaly. An intrasplenic, centrally located, well-limited, capsulated lesion (9.5 x 11 x 10 cm in diameter) was discovered on macroscopic examination of the material. A cellular infiltration area was seen on microscopic examination. The spleen capsule was mildly fibrotically thickened. The lesion that separated from the spleen tissue consisted of diffusely proliferated fusiform fibroblasts, heterogenous inflammatory cells consisting mainly of plasma cells, lymphocytes, sparse neutrophils and vascular elements. No granuloma or multinuclear giant cells were detected. Pancytopenia improved on follow-up. The patient followed up for two years, is now healthy and has no complaints.

The diagnostic value of image guided percutaneous fine needle aspiration biopsy in equivocal mediastinal masses.

BACKGROUND AND AIMS: The aim of this study was to assess the diagnostic value of image guided percutaneous fine needle aspiration (FNA) biopsy in equivocal mediastinal masses. PATIENTS: Sixty-six patients with an equivocal mediastinal mass who underwent FNA biopsy between 1993 and 2003 were eligible for final analysis. The cytological and definitive diagnosis of masses were grouped as primary 22 (33%)-30 (46%) and secondary (metastatic) neoplasms 18 (27%)-18 (27%) and nonneoplastic lesions 20 (30%)-18 (27%) respectively. RESULTS: The diagnostic accuracy (95% C.I.) of FNA biopsy for primary mediastinal neoplasms, secondary neoplasms and nonneoplastic lesions were found to be 93.3 (83.8-98.2)%, 100 (95.1-100)%, 93.3 (83.8-98.2)%, respectively. CONCLUSION: Image guided percutaneous FNA biopsy is a safe and highly accurate diagnostic method for equivocal mediastinal masses.

Cell proliferation rate and telomerase activity in the differential diagnosis between benign and malignant mesothelial proliferations.

AIMS: The differential diagnosis of malignant mesothelioma (MM) from benign mesothelial lesions (BML) based on histopathological criteria is sometimes not satisfying and causes diagnostic problems for histopathologists. We aimed to investigate whether the immunohistochemically determined cell proliferation rate and telomerase activity, using Ki-67 and human telomerase reverse transcriptase (hTERT) immunohistochemistry, respectively, are useful in the differential diagnosis of MM from BML. METHODS: Sixty-six cases of MM (33 epithelioid, 30 biphasic and 3 sarcomatoid) and 22 cases of BML (15 reactive mesothelial proliferations and 7 fibrous pleuritis/pericarditis) were included in this study. We evaluated the proliferative activity by Ki-67 and telomerase activity by hTERT immunohistochemistries for each case. RESULTS: The mean value of the Ki-67 proliferation index (PI) in MMs was significantly higher than that of BMLs. Biphasic MMs have higher a Ki-67 PI than epithelioid and sarcomatoid types. Ki-67 immunohistochemistry has a sensitivity of 74%, specificity of 86% and positive predictive value of 94% in detecting MM. hTERT immunohistochemistry detected MM with sensitivity and specificity of 68%. CONCLUSION: As a result, being cheap and simple methods, Ki-67 and hTERT immunohistochemistries can be used in differentiating malignant and benign mesothelial lesions in routine formalin-fixed, paraffin-embedded material.

Can renal oncocytoma be differentiated from its renal mimics? The utility of anti-mitochondrial, caveolin 1, CD63 and cytokeratin 14 antibodies in the differential diagnosis.

Among the epithelial renal tumours with eosinophilic cytoplasm, the main differential diagnostic problem arises between renal oncocytomas (ROs) and eosinophilic variants of chromophobe renal cell carcinomas (RCCs). We investigated the possible role of anti-mitochondrial (AMA), anti-caveolin 1 (CAV1), anti-CD63 (CD63) and anti-cytokeratin 14 (CK14) antibodies in the differential diagnosis of eosinophilic epithelial tumours and applied the Muller and Mowry modification of Hale's colloidal iron stain (HCI). Thirty-five ROs and 77 eosinophilic RCCs (27 chromophobe, 28 clear cell and 22 papillary RCCs) were included in this study. Apical and/or polar CD63 immunostaining (94%) and diffuse AMA (91%) and CAV1 (88%) immunostainings were the characteristics of ROs, whereas diffuse CD63 immunostaining (96%) and diffuse-peripheral AMA (96%) and CAV1 (92%) immunostainings were characteristic immunohistochemical features of eosinophilic chromophobe RCCs. We showed CK14 antibody not to be useful in the differential diagnosis of the eosinophilic epithelial renal tumours. The staining localisations with AMA, CAV1 and CD63 antibodies were significantly different between tumour groups. AMA had 96% sensitivity and 94% specificity, whereas CAV1 had 92% sensitivity and 97% specificity in diagnosing chromophobe RCCs. With HCI staining, ROs, showing apical and/or polar staining, could be differentiated from chromophobe RCCs, showing diffuse cytoplasmic staining. HCI had fairly low (69%) sensitivity and 100% specificity, whereas CD63 had 95% sensitivity and 100% specificity to diagnose ROs. We recommend using CD63 as the best marker of choice for distinguishing ROs from eosinophilic chromophobe RCCs when standard diagnostic criteria are not helpful.

Significance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomas.

Angiogenesis is a key process in tumour growth and metastasis, and Factor-VIII microvascular density has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to activated endothelial cells in tissues participating in angiogenesis, and we therefore wanted to compare the prognostic significance of CD105/endoglin to that of Factor-VIII. In a population-based endometrial carcinoma study with long (median 11.5 years) and complete patient follow-up, mean intratumour microvascular density (MVD) assessed using CD105/endoglin was investigated and compared with previous data for MVD assessed using Factor-VIII. MVD by CD105/endoglin was significantly correlated with MVD by Factor-VIII (p=0.001). However, tumours within the two groups defined by the upper and lower quartiles for CD105/endoglin-MVD were both significantly more often metastatic (FIGO-stage III/IV; p=0.03), with high tumour cell proliferation by Ki67 (p=0.007) and with reduced survival (p=0.036) as compared with the intermediate groups. In Cox regression analysis, CD105/endoglin-MVD showed independent prognostic influence when analysed together with patient age, FIGO stage, histologic subtype, histologic grade and Factor-VIII-MVD, while the latter lost its prognostic impact when CD105/endoglin was included. In the subgroup with high MVD, there was a tendency towards improved response to radiation therapy. In conclusion, CD105/endoglin-MVD is significantly associated with FIGO stage, tumour proliferation and prognosis in endometrial carcinoma, indicating that this is a better angiogenic marker in these tumours.

Impact of p53 and Ki-67 in predicting recurrence and progression of superficial (pTa and pT1) urothelial cell carcinomas of urinary bladder.

In predicting the aggressive behavior of bladder tumors, the histopathological characteristics of grade and invasive stage are of principal importance. However, for predicting tumor recurrence and progression, these are sufficient only to a limited extent, particularly in the case of superficial (pTa and pT1) urothelial cell carcinomas. New prognostic factors are therefore needed to avoid either insufficient or excessive treatment. In this retrospective study, we investigated the prognostic value of the p53 and Ki-67 immunoreactivity indices. The present study included 118 superficial urinary bladder tumors consisting of 58 recurrent and 60 non-recurrent cases. Twenty of the recurrent tumors progressed into a higher grade and/or invasive stage. Paraffin immunohistochemical analysis was carried out using anti-p53 and anti-Ki-67 antibodies on the initial tumor tissues. We concluded that there is a highly significant relationship between the p53 and Ki-67 immunoreactivities and the histological grade and pathological stage of the tumors (P < 0.0001). We observed a significant relationship between the presence of recurrence and progression and the p53 immunoreactivity index (P < 0.01 and P = 0.017, respectively) and Ki-67 immunoreactivity index (P < 0.0001 and P = 0.046, respectively). Positivity for p53 and Ki-67 can demonstrate the risk of recurrence (p53: sensitivity = 76%, specificity = 58%; Ki-67: sensitivity = 86%, specificity = 48%) and progression (p53: sensitivity = 80%, specificity = 46%; Ki-67: sensitivity = 85%, specificity = 36%; ). We believe that both of these immunohistochemical markers can be considered valuable in addition to classical histopathological prognostic parameters for predicting recurrence and progression risks.