Handan Zeren

PCNA and Ki-67 in central nervous system tumors: correlation with the histological type and grade.

Determination of proteins in the control of proliferation in normal cells helps a better understanding of cellular transformation and proliferation mechanisms. Measurement of proliferative activity is important in determining the tumor grade, recurrence span and malignancy. Proliferating cell nuclear antigen (PCNA) and Ki-67 are two of the nuclear markers used to demonstrate the proliferative phase of the cell cycle.In the present study, 63 central nervous system (CNS) tumors of various histologic types, diagnosed in Çukurova University Medical Faculty, Department of Pathology and graded according to WHO grading system were examined for PCNA and Ki-67 monoclonal antibodies using immunohistochemistry. Results were analyzed with statistical methods. Distribution of PCNA and Ki-67 LI (labeling index) values were determined for different tumor types. The highest PCNA and Ki-67 LI values were detected in medulloblastoma, malignant meningioma, primitive neuroectodermal tumor (PNET) and glioblastoma (GBM) groups, while pilocytic astrocytoma, meningioma, craniopharyngioma and oligodendroglioma showed the lowest values.In such tumors, the correlation between the increasing grade and PCNA and Ki-67 LI values were statistically significant. A correlation between the clinical outcome and Ki-67 and PCNA LI values was also detected.Conclusively, both markers can be used to evaluate the tumor grade and to asses the possibility of recurrence and malignancy in CNS tumors.

EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors.

Background: Malignant pleural mesothelioma (MPM) is an asbestos related tumour difficult to detect early and treat effectively. Asbestos causes genetic modifications and cell signalling events that favour the resistance of MPM to apoptosis and chemotherapy. Only a small number of patients, approximately 10%, survive more than 3 years. The aim of our study was to assess possible differences within signalling pathways between short term survivors (survival <3 years; STS) and long term survivors (survival >3 years; LTS) of MPM. Methods: 37 antibodies detecting proteins engaged in cell signalling pathways, enforcing proliferation, antiapoptosis, angiogenesis and other cellular activities were investigated by tissue microarray (TMA) technology. Results: Epidermal growth factor receptor (EGFR) was expressed stronger in LTS whereas platelet derived growth factor receptor (PDGFR) signalling was more abundant in STS. Expression of TIE2/Tek, a receptor for tyrosine kinases involved in angiogenesis, was differentially regulated via PDGFR and thus is more important in STS. Antiapoptosis was upregulated in STS by signal transducer and activator of transcription 1 (STAT1)–survivin and related molecules, but not in LTS. Our study provides novel insights into the regulatory mechanisms of signalling pathways in MPM, which differentially promote tumour growth in LTS and STS. Conclusion: We have demonstrated that small scale proteomics can be carried out by powerful linkage of TMA, immunohistochemistry and statistical methods to identify proteins which might be relevant targets for therapeutic intervention.

Antrochoanal polyp: a transmission electron and light microscopic study

Antrochoanal polyp (ACP) is a soft tissue mass originating from the maxillary antrum, emerging from the ostium and extending to the choana through the nasal cavity. Our aim was to investigate the light microscopic and ultrastructural features of ACP and to compare these with nasal polyps originating from the middle meatus (MMP). Seven ACP and seven MMP specimens were evaluated by transmission electron microscopy (TEM) and light microscopy. TEM examination showed epithelial cells with intact cilia covering both polyps. In some MMP cases, degeneration of the epithelium associated with some cilia loss was noted. Goblet cell hyperplasia was more prominent in MMP cases. Degeneration and partial destruction of the endothelial cells of the blood vessels were common findings in ACP cases; however, in the MMP group, endothelial cells were mostly intact with a few aggregates of ribosomes, and intact cell junctions were noted. Light microscopic examination revealed that inflammatory cells in the ACP group were numerous. However, eosinophils were predominant in MMP cases. Squamous metaplasia of the surface epithelium was detected in five ACP cases, but in none of the MMP cases. Basement membrane thickening was detected in two cases of the ACP and in four cases of the MMP group. There was a statistically significant difference between the two groups for inflammatory cells, eosinophilic cell infiltration, squamous cell metaplasia, endothelial cell destruction and goblet cell metaplasia. In conclusion, the low number of eosinophils, the high number of other inflammatory cells, the normal appearing basement membrane and intact and normal surface epithelium may reveal that the etiology of ACP might arise from chronic inflammatory processes rather than allergy. The destruction of the endothelium may be considered as a further sign of chronic inflammation.

Intravenous leiomyomatosis extending into the right ventricle after subtotal hysterectomy

A case of intravenous leiomyomatosis with extension into the right ventricle is described. A tumor in the inferior vena cava was detected three years after a subtotal hysterectomy had been performed for a myomatous uterus but was misdiagnosed as a thrombus. The tumor enlarged and intruded into the right ventricle for which she underwent surgery. The correct diagnosis was made during the surgery, therefore a two-stage resection was planned. Surgical resection is the best treatment for intracardiac extension of intravenous leiomyoma. We recommend iliac venotomy to remove the ilio-caval portion of the tumor in both stages of operations.

Maspin overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human ovarian carcinoma

The vascular endothelial growth factor (VEGF) family, including VEGFA, VEGFC, and VEGFD, plays an essential role in the angiogenesis of both pathologic and nonpathologic conditions. Maspin belongs to the serpin superfamily and has been identified as a tumor suppressor because it inhibits motility, invasion, and angiogenesis. Few studies have compared maspin with VEGF in ovarian carcinoma. Therefore, we investigated the expression and correlation of maspin, VEGFA, VEGFC, and VEGFD with the tumorigenesis of the ovary and clinicopathologic variables. Using immunohistochemistry, we examined maspin, VEGFA, VEGFC, and VEGFD expression in 60 ovarian carcinoma tissues (35 serous papillary carcinomas, 18 endometrioid carcinomas, and 7 primary ovarian mucinous carcinomas). Staining of cells was scored as +2 if more than 50% of the cells were positive, as +1 if less than 50% of the cells were positive, and as negative if none of the cells stained positive. Overexpression of maspin, VEGFC, and VEGFD was significantly associated with high tumor grade (P<.001, P=.004, P<.001, respectively), clinical stage (P=.002, .01, and .001, respectively), the presence of ascites (P<.001, P=.03, and P=.001, respectively), and the presence of metastatic lymph nodes (P=.002, P<.001, and P<.001, respectively). Maspin was correlated with VEGFA (P=.01), VEGFC (P<.001), and VEGFD (P<.001). The VEGFA score was positively correlated with high tumor grade (P=.04), lymphovascular space invasion (LVSI) (P<.001), International Federation of Gynecology and Obstetrics (FIGO) stage (P=.009), maspin, VEGFC (P=.003), and VEGFD (P=.003), but it was not correlated with the presence of ascites and metastatic lymph nodes. Maspin, VEGFC, and VEGFD are expressed in ovarian tumors with a poor prognostic parameters, and seem to play a role in ovarian cancer angiogenesis, progression, and lymph node metastases. Our results indicate that in contrast to most other carcinomas, maspin expression is directly associated with the biological aggressiveness of ovarian carcinoma. These results may offer new insights regarding the role of maspin in ovarian cancer and might also affect the diagnosis and treatment strategies.

Huge bilateral pulmonary and pleural metastasis from intracranial meningioma: a case report and review of the literature

SummaryA case of recurrent meningioma with atypical features and extracranial metastases is reported. A 34-year-old female was operated in 1996, 2000, and 2002, and frontal parasagital meningioma was extirpated. Histological diagnoses of all the resected tumors were meningotheliomatous meningioma, WHO Grade I. However, 2 years later, the tumor recurred in the frontal scalp and was removed again totally. Histological diagnosis was reported as an atypical meningioma; meningotheliomatous type; WHO Grade II. She received radiation therapy. But the tumor had metastasized to the lung and pleura. Transthoracic tru-cut biopsy was performed from large mass of the left lung. Cytopathology was consistent with malignant meningioma, metastasis from the patient’s known intracranial meningioma. Ki-67 staining index at the primary and metastatic sites of the present cases were 7 and 5%, respectively. We reviewed and discussed the histopathological features and mechanisms of metastasizing meningioma.

Non‐puerperal inversion of the uterus caused by leiomyosarcoma: A case report and clinical management

Uterine inversion is a rare complication of the postpartum period, but it is an even rarer complication of the non‐puerperal period. A 49‐year‐old nulliparous woman was admitted to the hospital with the following complaints: abnormal vaginal bleeding, pain, anuria and a mass protruding from the vulva. The mass was removed by twisting and a laparotomy was required for massive bleeding due to the inversion. The diagnosis of complete inversion was made during the laparotomy. Total abdominal hysterectomy and bilateral salpingo‐oophorectomy was performed and the pathological examination revealed a leiomyosarcoma. Uterine inversion in the non‐puerperal period is an extremely rare event and it should be kept in mind that the cause of the inversion may be a malignant disease, like leiomyosarcoma.

Extramedullary relapse in the pleura in acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloblastic leukemia with specific clinical, morphologic and genetic features and a good response to all trans retinoic acid (ATRA). However, extramedullary (EM) relapse is an interesting feature of these cases, especially those treated with ATRA. Recently, we have encountered an EM relapse in the pleura in a case with APL receiving an ATRA containing regimen. This case is reported and the relevant literature is reviewed.

Granulomatous reaction after chemotherapy for Hodgkin's disease

There are some reports that relate the coexistence of sar-coidosis and lymphoma. This coexistence has been calledthe sarcoidosis–lymphoma syndrome. Generally, sarcoido-sis precedes the lymphoma in these cases. On the other handthere are some other reports about sarcoidosis or sarcoid likereaction following the therapy of lymphoma. We report herea case with sarcoid like reaction developing after systemicchemotherapy for Hodgkin’s disease (HD) and discuss thepossible definitions.1. Case reportA 55-year-old man was admitted to our hospital withrelapsed HD. He had a history of lymphocyte rich-HD dia-gnosed in November 1999. He had cervical and abdomi-nal lymph nodes, right pleural effusion, splenomegaly andconstitutional symptoms. He had the history of six coursesof ABVD chemotherapy at another hospital. Cervical, tho-racic and abdominal CT scans were found to be normaland 2-microglobulin ( 2M) was within normal limits(2772ng/ml) after chemotherapy. Two months later he com-plained of constitutional symptoms and at that time, CTscans showed cervical, intraabdominal and retroperitoneallymph nodes, splenomegaly and mediastinal lymph nodes.Physical examination disclosed cervical and inguinallymph nodes. Laboratory results: Hb was 11.7g/dl, Hctwas 35.4%, WBC was 10 × 10

Coincidental visualization of an atypical bronchial carcinoid on Tc-99m-sestamibi scan in Kallmann's syndrome

We report a case of an atypical bronchial carcinoid showing sestamibi uptake. A 27-year-old man with Kallmann’s syndrome and hyperparathyroidism had parathyroid scintigraphy with99mTc-sestamibi. A focal uptake was observed on the right perihilar region, and this right perihilar mass was demonstrated on computed tomography and proved histologically to be an atypical bronchial carcinoid tumor. Factors which may explain the tumoral avidity for sestamibi are increased blood flow, transmembrane potentials of plasma and mitochondrial membranes and the relative number of mitochondria present in the cells of this carcinoid tumor. The importance of this case is the coincidence of an atypical carcinoid in a patient with significant failure of secondary sexual characteristics, right renal agenesis and bilateral anosmia associated with Kallmann’s syndrome.