Kemal Kosemehmetoglu

TLE1 expression is not specific for synovial sarcoma: a whole section study of 163 soft tissue and bone neoplasms

TLE1, a transcriptional repressor essential in hematopoiesis, neuronal differentiation and terminal epithelial differentiation, has recently been shown in a single tissue microarray study to be a highly sensitive and relatively specific marker of synovial sarcomas. Expression of TLE1 has not, however, been studied in standard sections of soft tissue and bone tumors. We investigated TLE1 expression in a large series of well-characterized mesenchymal tumors, to more fully characterize the range of TLE1 expression. Standard sections of 163 bone and soft tissue tumors were immunostained for TLE1 (sc-9121, 1:100; Santa Cruz Biochemicals) using the Dako Dual Envision+ detection system. Nuclear positivity was scored as negative (<5% of cell positive), 1+ (5–25% of cells positive), 2+ (25–50% of cells positive), and 3+ (>50% of cells positive). Overall, TLE1 was expressed by 18 of 20 (90%) of synovial sarcoma, with 16 cases (89%) showing 2–3+ positivity. However, TLE1 expression was also seen in 53 of 143 (37%) non-synovial sarcoma, with 36 such cases (25%) showing 2–3+ positivity. TLE1 expression was commonly seen in peripheral nerve sheath tumors, including 33% of neurofibromas, 100% of schwannomas, and 30% of malignant peripheral nerve sheath tumors. Among non-neoplastic tissues, nuclear TLE1 expression was variably present in basal keratinocytes, adipocytes, perineurial cells, endothelial cells and mesothelial cells. Our study confirms the excellent sensitivity of TLE1 for synovial sarcoma. However, TLE1 expression is by no means specific for synovial sarcoma, being present in a number of tumors, which enter its differential diagnosis, in particular tumors of peripheral nerve sheath origin. Heterogeneity of TLE1 expression likely explains the differences between the present standard section study and the earlier TMA study. TLE1 may be of value in the differential diagnosis of synovial sarcoma, but should be used only in the context of a panel of antibodies. Morphology, ancillary immunohistochemistry for traditional markers such as cytokeratins and CD34, and molecular confirmation of synovial sarcoma-associated fusion genes should remain the ‘gold standards’ for this diagnosis.

Clear cell sarcoma of tendons and aponeuroses, and osteoclast-rich tumour of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts: a review and update

Clear cell sarcoma (CCS) is a rare, distinctive soft tissue neoplasm, typically occurring in the distal extremities of young adult patients. Although CCS shows melanocytic differentiation, it is now clear that it is clinicopathologically and genetically distinct from conventional malignant melanoma. The ‘osteoclast-rich tumour of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts’ is an extraordinarily rare gastrointestinal neoplasm that shares some features of CCS, but differs from it in other ways. The historical, histopathological, ultrastructural, immunohistochemical and genetic aspects of these two tumours are reviewed in this article.

Lamotrigine attenuates cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits.

BACKGROUND Increasing evidence implicates voltage-dependent sodium and potassium channels, in addition to calcium channels of various types, in the pathophysiological development of cerebral vasospasm. This study investigated the ability of LTG, an antiepileptic drug with multi-ion channel inhibition properties, to prevent cerebral vasospasm and subsequent neural ischemia in a rabbit model of SAH. METHODS Thirty-five New Zealand white rabbits were assigned to 1 of 3 groups: (1) control (no SAH, saline injection); (2) SAH alone; (3) SAH + LTG, 20 mg/kg daily. Animals were killed 72 hours after SAH, then basilar artery lumen areas and arterial wall thickness were measured in all groups. The histological sections of the CA1 and CA3 regions and dentate gyri of the hippocampi were evaluated semiquantitatively for neural tissue degeneration. RESULTS In the SAH group, the mean luminal cross-sectional area of the basilar artery was reduced by 62% after SAH as compared with the non-SAH controls (P < .0001). After SAH, the vasospastic response was attenuated by 36% in animals treated with 20 mg/kg of LTG compared with the SAH group (P < .005). The mean luminal cross-sectional areas of the basilar artery were 279000 +/- 27000 microm(2) in the control group, 173000 +/- 17600 microm(2) in the SAH group, and 236000 +/- 10000 microm(2) in the SAH + LTG group. The differences between the SAH group and the LTG-treated group were statistically significant (P < .0001). Histological examination was done in 12 control, 12 SAH, and 9 SAH + LTG-treated animals. The mean degeneration score for the control group and SAH + LTG group was statistically significant (P = .012). The difference between the SAH group and SAH+ LTG group was also statistically significant (P = .006). CONCLUSIONS These findings demonstrate that oral administration of LTG has marked neuroprotective effect and significantly attenuates cerebral vasospasm after SAH, thus providing additional support for the role of non-L-type calcium channels and voltage-dependent sodium channels in vasospasm.

Leflunomide prevents vasospasm secondary to subarachnoid haemorrhage

SummaryBackground. Though cerebral vasospasm is one of the most serious complications of subarachnoid haemorrhage (SAH), its complex pathogenesis is poorly understood and available clinical treatment options are unsatisfactory. This study was designed to examine the efficacy of leflunomide, an immunomodulatory agent with inhibitory properties, on vascular smooth muscle cell proliferation and inflammation in a rabbit cerebral vasospasm model. Methods. Twenty-two adult New-Zealand rabbits were assigned to 4 groups: control, SAH, SAH plus vehicle, SAH plus leflunomide. Subarachnoid haemorrhage was induced by administration of 1 ml of fresh unheparinised autologous arterial blood into the cisterna magna. Oral leflunomide (2 mg/kg) or vehicle treatment was started 12 h after the induction of subarachnoid haemorrhage and administered once a day. Three days later, the animals were sacrificed and the basilar artery was examined histologically for the lumen area and the thickness of the vessel wall. Inflammatory reaction was also examined by counting white blood cells within the vessel wall by means of light microscopic examination using haematoxylin and eosin staining. Findings. Severe and moderate vasospasms were detected in the basilar artery of the SAH and SAH plus vehicle treated groups, respectively. Leflunomide effectively reduced the vasospasm of the basilar artery. Compared to the vehicle treated group, leflunomide significantly reduced the lumen area (p < 0.01) and hyperplasia of the vessel wall (p < 0.01). Although inflammatory response within the vessel wall was reduced in the leflunomide treated group, no statistical significance was found between groups (p = 0.07). Conclusion. This study demonstrates for the first time that leflunomide treatment attenuates cerebral vasospasm in a rabbit SAH model while inflammatory reaction in the vessel wall is not affected. Although further studies are needed to reveal its molecular mechanisms in relieving vasospasm, leflunomide may provide a therapeutic potential for human cerebral vasospasm induced by SAH.

Intra-articular epithelioid sarcoma showing mixed classic and proximal-type features: report of 2 cases, with immunohistochemical and molecular cytogenetic INI-1 study.

Epithelioid sarcoma, a rare sarcoma with epithelial differentiation, most often occurs in the distal extremities; however, it may occur in essentially any location. With the recent recognition that the loss of expression of the tumor-suppressor gene INI-1 may be associated with epithelioid sarcoma, it has become clear that epithelioid sarcoma may occur in previously unsuspected locations such as bone. Only 2 cases of intra-articular epithelioid sarcoma have been previously reported. We retrieved 2 intra-articular cases coded as epithelioid sarcoma from our archives. Both expressed cytokeratins (AE1/AE3 and OSCAR), CD34, vimentin, and epithelial membrane antigen, and showed complete loss of expression of INI-1. Fluorescence in situ hybridization was performed on formalin-fixed, paraffin-embedded sections by using a laboratory-developed dual-color probe containing INI1 (CTD-2511E13 and CTD-2034E7) (22q11.2) (OR) and PANX2 (RPCI3-402G11) (22q13.33) (GR) probes as control. Both cases occurred in a clearly intra-articular location in the knee. Case 1 was that of a 19-year-old man with a long-standing history of pain and limited joint function. This patient was disease free after amputation. Case 2 was that of a 60-year-old woman. Follow-up information available for this patient showed bilateral subpleural metastases. Morphologically, case 1 showed features of proximal-type epithelioid sarcoma, whereas case 2 showed mixed features of classic and proximal-type epithelioid sarcoma. Immunohistochemistry showed complete loss of INI-1 protein in both cases; fluorescence in situ hybridization analyses were negative for INI-1 gene deletion. Herein, we have reported 2 cases of intra-articular epithelioid sarcoma, showing morphologic and immunohistochemical features identical to those of epithelioid sarcoma in conventional locations, including loss of INI-1 expression. Intra-articular epithelioid sarcoma should be distinguished from malignant pigmented villonodular synovitis and from carcinoma metastatic to the synovium. Improved recognition of this rare clinical presentation should allow for better understanding of its unique features.

Intralesional curettage and cementation for low-grade chondrosarcoma of long bones: retrospective study and literature review

BackgroundVarious treatment strategies for low-grade chondrosarcomas with variable outcomes have been reported in the literature. The aim of this study was to assess the oncological and functional outcomes associated with intralesional curettage followed by adjuvant therapy comprising high-speed burring, thermal cauterization, and bone cementation with polymethylmethacrylate.MethodsWe performed a retrospective review of 21 consecutive patients with intramedullary low-grade chondrosarcoma of long bones treated by intralesional curettage and adjuvant therapy comprising high-speed burring, thermal cauterization, and cementation at our institution from 2007 to 2012.ResultsThe average age of the patients was 48.7 (range, 18–71) years. There were 7 male and 14 female patients. The mean follow-up period was 58.4 (range, 26–85) months after surgery. The treated lesions were located in the proximal humerus (n =10), proximal tibia (n =6), and distal femur (n =5). At the average follow-up time point of 58.4 (range, 26–85) months, no patient had developed local recurrence and no distant metastases were observed. The average Musculoskeletal Tumor Society score among all 21 patients was 95% (84–100).ConclusionsThe combination of intralesional curettage, application of high-speed burring, thermal cauterization, and cementation is an effective treatment strategy for low-grade intramedullary chondrosarcoma of long bones. Excellent oncological and functional results can be obtained.

Uterine tumors resembling ovarian sex cord-stromal tumors: synchronous uterine tumors resembling ovarian sex cord-stromal tumors and ovarian sex cord tumor

Uterine tumors resembling ovarian sex cord-stromal tumors (UTROSCTs) are very rare. In this article, we present 3 cases that manifest classical histomorphological features alongside diverse immunohistochemical findings. As a distinctive finding, one of the patients had UTROSCT in the uterus and an ovarian sex cord tumor, called granulosa cell tumor, in the left ovary, simultaneously. Problems in diagnosing such pathologic condition generally arise because of the variable histologic picture of UTROSCT and may cause problems for general and other nongynecologic surgical pathologists. Immunohistochemically, these tumors express different markers that indicate their polyphenotypic origins.

Indian ink vs tissue marking dye: a quantitative comparison of two widely used macroscopical staining tool

The evaluation of the surgical margins is a major concern in surgical pathology, and marking of surgical margins with substances such as alcian blue, Tipp-ex, artists pigments, colored gelatin, starch, erythrocyte layers, etc. was recommended for this purpose; Indian ink and tissue marking dyes are widely used. As there is no systematic study comparing tissue marking dyes and Indian ink as the most common substances used for the purpose, this study was conducted to compare the two. Penetration into the tissue, brightness under the microscope, the spreading area of one drop of dye on tissue paper, the intensity of colors, and unit price were compared for each of the five colors of Rotrings Indian ink and Thermo–Shandons tissue marking dyes, applied on reduction mammoplasty specimens. Rotrings Indian ink is proved to be just as effective as Thermo–Shandons tissue marking dye and bares the majority of the characteristics of a perfect staining substance, which are easily applied, quickly fixed, durable and cheap, contain no potential contaminants, be work safe, would not smudge/stain surrounding tissues, and look bright under the microscope without obscuring the view.

Metanephric adenoma in a 6-year-old child with hemihypertrophy.

Metanephric adenoma (MA) is a renal tumor that is rarely diagnosed in children. Although it is considered benign and to have a good prognosis, the diagnosis of MA is challenging because of histopathologic and radiologic similarities to Wilms tumor. In this case report, we present a 6-year-old girl, with a renal mass and right hemihypertrophy, who was previously diagnosed as Wilms tumor on a fine-needle biopsy and diagnosed as MA after nephroureterectomy. The differentiation between Wilms tumor and metanephric adenoma is also discussed.

Papillary carcinoma with diffuse papillomatosis of gallbladder and cystic duct.

Biliary papillomatosis and papillary carcinoma are rare tumors of biliary tract; and because of their morphologic similarities, papillomatosis-papillary carcinoma sequel has been proposed. We report an unusual case of polypoid minimally invasive papillary carcinoma located at the junction between cystic and common bile ducts, complicated with biliary papillomatosis of gallbladder and cystic duct, showing focal areas of malignant change. Intrahepatic ducts, hepatic ducts, and distal common bile duct were spared. Both papillomatosis and papillary carcinoma showed areas of high p53 and p21 expression with high proliferative index. Patient is still alive for 4 years without evidence of disease after modified Whipple operation. Possible pathogenetic mechanisms are further discussed.