Turkish Journal of Pathology - 2011; 27(1)

Editorial

��kr� O�uz �ZDAMAR — 2011-01-01

Editorial

��kr� O�uz �ZDAMAR — 2011-01-01

Neural Stem Cells and their Role in the Pathology and Classification of Central Nervous System Tumors

Tar�k T�HAN, Melike PEKMEZC�, Anthony KARNEZIS — 2011-01-01

Today, one of the most popular and controversial topics in medicine is undoubtedly the rapidly developing field of stem cell research. Some of the controversy in this field arises from lack of uniform terminology and different interpretation of concepts such as brain tumor stem cells. In addition, lack of reliable and universal markers that can identify stem cells and define precursor cells in a particular differentiation pathway further confounds the interpretation of results in many studies. Stem cells are undoubtedly critical in normal cellular development as well as tumor biology and better characterization of these cells is likely to have profound influence on the classification schemes of tumors. In this manuscript, we present the generally accepted definitions of key concepts in stem cell biology and review some of the related molecular pathways. In addition, we put forth our position on how progress in this field should be affecting the future classification schemes of central nervous system neoplasia. We strongly believe that the ever increasing knowledge in the field of neural and brain tumor stem cells should be influential in the subsequent attempts to classify brain tumors.

Cytopathologic Diagnosis in Pleural Effusion and Cyto-Histopathologic Correlation

Adile Ferda DA�LI, �irin K��K, M�ge SEZER, �zlem ��ER — 2011-01-01

Objective: Cytological examination of pleural fluids is a fast, efficient and non-invasive diagnostic method. Identification of malignant effusions bears critical importance in treatment and prognosis. The aim of this study was to investigate the distribution of cytopathologic diagnoses in pleural effusions and the cyto-histopathologic correlation rates. Material and Method: A total of 298 pleural fluid cases diagnosed from 2008 to 2009 in our laboratory were retrospectively identified as the study group. Evaluation results were classified in 5 groups as inconclusive, benign, atypical, suspicious and malignant, and compared with the biopsy results. Results: Of the total 298 pleural fluid cases, 114 (38.3%) were females and 184 (61.7%) were males. The age range was between 15 and 89 with a mean value of 58.4�17.8. Of the cases, 3 (1%) were diagnosed as inadequate, 246 (82.6%) benign, 8 atypical, 10 suspicious, and 31 malignant by cytology. Among the cases who were diagnosed as malignant, 24 (8.1%) were reported as metastatic carcinoma and 7 (2.3%) as malignant mesothelioma. Of the 8 cases reported as atypical, biopsy results of 2 showed malignant mesothelioma, and of the 10 cases reported as suspicious, 1 case whose biopsy result was obtained was diagnosed as epidermoid carcinoma metastasis. Conclusion: Cytological examination is the most valuable diagnostic method for pleural effusions which may have various etiological causes. The most common cause of pleural effusions in our region is metastatic carcinomas including those from the lung, breast and ovarian tumors, followed by malignant mesothelioma.

Expression of p16 Protein and Cyclin D1 in Periampullary Carcinomas

2011-01-01

Objective: The majority of the tumors in periampullary region are pancreatic and ampulla of Vater carcinomas. The aim of this study was to compare histopathological features of ampulla of Vater carcinomas with pancreatic ductal adenocarcinomas and to determine diagnostic and predictive values of p16 protein and cyclin D1 expression. Material and Method: Tissue samples from pancreatic ductal adenocarcinomas and ampulla of Vater carcinomas were obtained from 31 patients who underwent pancreticoduodenectomy for periampullary carcinoma. The study group was composed of 12 women and 19 men. Their median age was found to be 62.32 years (range 26-85 years). The parameters analyzed in the study included lymph node metastases, perineural invasion, differentiation, duodenal invasion, grade of intraepithelial neoplasia and p16 and cyclinD1 expression in tumoral and peritumoral pancreatic tissues. Results: In both tumor groups, the loss of p16 protein expression was significantly correlated with perineural invasion (p=0.0001). Perineural invasion was more frequent in the pancreatic ductal adenocarcinoma group than the ampulla of Vater carcinoma group (p=0,01). When desmoplasia and lymphoplasmacytic stromal infiltration were examined, desmoplastic reaction was significantly higher in pancreatic ductal adenocarcinomas than ampulla of Vater carcinomas (p=0.01). No significant difference was observed between tumor groups for Cyclin D1 (p>0.05). Conclusion: The results suggest that loss of p16 protein expression may be a sign for poor prognosis in periampullary cancers that is correlated mainly with perineural invasion. Desmoplastic stromal reaction may be a distinctive feature for pancreatic ductal adenocarcinoma compared with ampulla of Vater carcinoma.

Profile of Gallbladder Diseases Diagnosed at Afyon Kocatepe University: A Retrospective Study

2011-01-01

Objective: Gallbladder is one of the most commonly encountered specimen in a pathology laboratory. A diverse spectrum of diseases affect the biliary system, often presenting with similar clinical signs and symptoms. We aimed to define the profile of gallbladder diseases in our region, and to determine potential correlations between histopathologic features we observed. Material and Method: We reviewed all cholecystectomies processed in Department of Pathology of Afyon Kocatepe University Hospital between January 2000 and March 2008. Gross and histopathologic features of the specimens were reevaluated. Results: Among 1500 patients; 69.9% were women and 30.1% were men. We found out fourteen primary gallbladder carcinomas (0.93%) with adenocarcinomas being the most frequent type (78.57%). The rate of cholelithiasis was found as 89.9%. The most common type of gallstones was mixed cholesterol type gallstones with 67.5% followed by black pigment and brown pigment types as 23.83% and 5.89%, respectively. The association of metaplasia with dysplasia and also gallstones were statistically significant (p<0.001, p<0.005). The rate of the gallbladder polyps was 2.6% with the cholesterol polyps being the most common type (56.4%). Conclusion: Gallbladder diseases often present with similar clinical signs and symptoms and a surgical pathologist should be alert especially of precancerous lesions. With our results, we also conclude that elderly women with longstanding gallstone disease should undergo elective surgery even when no symptoms are present.

Imp3 Expression in Urothelial Carcinomas of the Urinary Bladder

Nihal �ZKALAY �ZDEM�R, Nilay �EN T�RK, Ender D�ZCAN — 2011-01-01

Objective: Superficial tumors including Ta, Tis, and T1 make up 75% of urothelial carcinomas of the bladder. While the behavior of these superficial urothelial cancers is relatively benign, invasive tumors have a significant mortality rate. However, Ta and T1 tumors might display different biological behavior. There is therefore a great need for biomarkers that can accurately distinguish the behavior of urothelial carcinomas in addition to tumor grade and stage. Our aim was to determine the immunohistochemical expression profile of insulin like growth factor II mRNA binding Protein 3 (IMP3) and its correlation with tumor stage and grade in benign urothelium and bladder urothelial carcinomas. Material and Method: The expression of IMP3 in 91 patients with benign urothelium (20 cases), low grade invasive (17 cases) / noninvasive (20 cases) urothelial carcinoma and high grade invasive (20 cases) / non-invasive (14 cases) urothelial carcinoma was evaluated by immunohistochemistry in this study. Results: IMP3 was not expressed in benign urothelium, low-grade non-invasive urothelial carcinoma and high grade non-invasive urothelial carcinoma. Expression of IMP3 was found in 11.76% of low-grade invasive urothelial carcinomas and 55% of high grade invasive urothelial carcinomas. Statistical analysis including χ2 tests showed that IMP3 expression of invasive urothelial carcinomas was statistically significant (p<0.000). Conclusion: The detection of IMP3 only in invasive carcinomas although some of them were low grade showed that the expression of IMP3 may be related to aggressive behavior of urothelial carcinomas.

p53, bcl-2, and nm23 Expressions in Serous Ovarian Tumors: Correlation with the Clinical and Histopathological Parameters

Deniz ARIK, Sezer KULA�O�LU — 2011-01-01

Objective: We studied p53, bcl-2, and nm23 expressions in serous benign, borderline and malignant tumors of the ovary. Our aim was to determine the association between these expressions and some clinical (patient age, tumor dimension, omenthal involvement, the presence of malignant cells in peritoneal fluid) and histopathological (grade, number of mitosis, nuclear pleomorphism, structural pattern) parameters in malignant serous tumors. Material and Method: A total of 71 tumors including 29 benign, 14 borderline, and 28 malignant ovarian serous tumors were included in the study. p53, bcl-2, and nm23 immunohistochemical staining was performed on the paraffin blocks. The results were scored as (+), (++) and (+++) according to the extent of staining. Results: There was no staining for p53 in benign or borderline tumors. p53 was positive in 42.9% of malignant tumors. nm23 expression was revealed as 44.8%, 64.3% and 67.9% in benign, borderline and malignant tumors, respectively. Bcl-2 was positive in only 17.2% of benign, 35.7% of borderline and 25% of malignant tumors. Conclusion: The p53 positivity detected only in serous carcinomas shows its role in carcinogenesis. p53 was expressed at a significantly higher rate in advanced stage carcinomas (p=0.031). nm23 expression in benign, borderline and malignant tumors was not significantly different. nm23 positivity was higher in advanced stage carcinomas (p=0.032). This suggest that nm23 acts like an oncogene in ovarian carcinomas. There was no significant difference between the groups in terms of bcl-2 expression.

LSIL/ASC-H (LSIL-H) in Cervicovaginal Smear: Histopathological Outcomes and Clinical Significance

Ecmel I�IK KAYGUSUZ, Handan �ET�NER, Davut �AH�N — 2011-01-01

Objective: Conventional Pap smears exhibiting unequivocal features of ‘low grade squamous intraepithelial lesion' (LSIL) are occasionally mixed with some cells suspicious for, but not diagnostic of ‘high grade squamous intraepithelial lesion' (HSIL) on daily routine. The 2001 Bethesda System does not address the significance of such cytological entities. We have referred to these changes in our laboratory as ‘LSIL, atypical squamous cells cannot exclude HSIL' (LSIL/ASC-H). In this study, we aimed to compare the cytology and biopsy results of LSIL/ ASC-H to LSIL, ASC-H and HSIL. Material and Method: Out of 37884 cases which were evaluated between 2005-2009 in our laboratory, cases interpreted as LSIL, LSIL/ ASC-H, HSIL and ASC-H were reevaluated and 153 cases for which biopsy materials were available were selected. Results: The rate of histological CIN2 or worse associated with LSIL/ ASC-H (45%) was between the rates of LSIL (10%) and HSIL (65%), but not significantly different from ASC-H (50%). However, LSIL/ ASC-H was more frequently associated with a definitive histological diagnosis of any CIN2 than ASC-H (30% vs. 8%). Conclusion: Based on our results, we recommend LSIL/ASC-H to be added to Bethesda System, and Pap test cases of LSIL/ASC-H may need to be clinically followed-up in a manner similar to ASC-H, i.e., with colposcopy for all patients.

The Importance of Consumption of the Epidermis in Malignant Melanoma and Correlation with Clinicopathological Prognostic Parameters

Selda SE�K�N, Elmas �ZG�N — 2011-01-01

Objective: The aim of the study was to investigate the importance of consumption of the epidermis as an additional diagnostic criteria for malignant melanoma and to evaluate its relationship to clinicopathological findings. Material and Method: The age, gender, localization of the lesion and the histopathological parameters such as tumor type, Breslow thickness, ulceration, Clark's level, mitosis/mm² , lymphocytic infiltration were noted in 40 malignant melanoma cases. Consumption of the epidermis was evaluated in tumor sections. Consumption of the epidermis (COE) due to thinning of the epidermis and loss of rete ridges was noted as (+) or (-). Furthermore, COE was compared with clinical and histopathological parameters. The Shapiro Wilk and Logistic Regression tests were used for statistical analysis. The results were accepted as significant if the p value was <0.05. Results: COE was detected in 60% (24/40) of malignant melanoma cases. A positive correlation was present between COE and head and neck localization (p=0,698), superficial spreading melanoma (p=0,341), ulceration (p=0,097) and brisk lymphocytic infiltration (p=0,200) but the results were not statistically significant. COE was frequently detected in males but the difference was not statistically significant (p=0.796). There was no correlation or significant statistical association between COE and age, Breslow thickness, Clark's level or the mitotic index. Conclusion: The detection of COE in most of the patients suggests that COE could be a histopathological criterion in the diagnosis of malignant melanoma. The frequent association between COE and the presence of ulceration could also direct attention to COE as regards prognostic importance.

Morphological and Immunohistochemical Features of Malignant Vascular Tumors with Special Emphasis on GLUT1, and FKBP12 Expressions

Kemal K�SEMEHMETO�LU G�khan GED�KO�LU, �evket RUACAN — 2011-01-01

Objective: Angiosarcomas and hemangioendotheliomas are rare malignant vascular neoplasms (MVTs). Here, we reviewed the clinicomorphological characteristics of 27 MVTs with the implementation of two novel immunohistochemical markers: GLUT1, and FKBP12. Material and Method: MVTs, except for Kaposi's sarcoma, were retrieved from the archive and reviewed. Tumor size, the presence of hemorrhage and necrosis, growth pattern, cellularity, cellular characteristics and mitotic activity were recorded as morphological variables. Immunohistochemically, CD34, CD31, GLUT1, FKBP12, mdm2, p53, c-kit, and CD99 were applied. Clinical information was gathered from hospital records and computer-based patient data systems. Results: The median age was 53 years (range 16-77). Extremities (37%) were the most common primary site followed by the head and neck. Five of 16 (31%) low grade and 7 of 11 (64%) high grade tumors were metastasized to varying organs, mainly the liver and lungs. The median survival was 49 months. Ninety percent of high grade tumors were larger than 3 cm. Hemorrhage and necrosis were seen in 85% and 41% of cases, respectively. Nuclear pleomorphism, cellularity and mitotic activity were higher in high grade tumors than in low grade ones (p<0.0001). While 68% of the cases expressed CD34, 81% of them were positive with CD31. All cases except one low grade tumor were strongly and diffusely stained with FKBP12. Significant GLUT1 expression was observed in 23% of cases, especially in areas showing epithelioid morphology. Either mdm2 or p53 was positive in over one third of the tumors. Conclusion: The studied markers were not able to distinguish between low and high grade MVTs. FKBP12 may take a role in the diagnostic panel of MVTs. GLUT1 expression, previously proposed for the diagnosis of infantile hemangioma, should be assessed carefully since almost one quarter of MVTs were also GLUT1 positive.

Pulmonary Carcinosarcoma: A Case Report

2011-01-01

Pulmonary carcinosarcoma, belonging to sarcomatoid carcinomas, is a quite rare tumor that contains both malignant epithelial and mesenchymal elements. This tumor has different phenotypic characteristics and clinical course compared to non-small cell lung tumors. A case diagnosed as carcinosarcoma is presented and its clinical and pathological features and the differential diagnosis are discussed. The case was a 74-year-old male admitted with shortness of breath and cough. The chest x-ray showed a left lung mass and a bronchoscopic examination was performed. Histopathological examination of the bronchoscopic biopsy showed necrosis and a malignant tumor consisting of diffuse infiltrative anaplastic cells. Surgery was performed and the case was diagnosed as carcinosarcoma in the resection material. Pulmonary carcinosarcoma is a rare lung tumor. Determination of tumoral cells and performing advanced investigations in resection material seem to be relatively easier than in small biopsies. However, this type of tumor can be encountered in small biopsy materials as in the presented case and should be kept in mind in relation to the differential diagnosis as small tissues can have only one, particularly mesenchymal, tumoral component.

Pleomorphic Adenoma of the Upper Lip

�lk� K��K, Serdar TAN — 2011-01-01

Pleomorphic adenoma is the most common neoplasm of the salivary glands and is most commonly located in the parotis followed by the submandibular glands. Its localization in the minor salivary glands is mostly reported in the palate. Few publications report pleomorphic adenoma cases located in the lip. We present a 35-year-old male patient with a pleomorphic adenoma located in the upper lip.

Malignant Melanoma of Unknown Primary Site Simulating A Salivary Gland Neoplasm

Kiran AGARWAL, Sonal JAIN, Jasmita DASS, Manoj ANDLEY — 2011-01-01

Malignant melanoma with its varied clinical presentations and histomorphological patterns is a perplexing problem both for the diagnosticians and clinicians. A small proportion of melanomas present with metastatic tumors with unknown primary sites and at these sites they mimic the more common primary neoplasms. We hereby report a case of malignant melanoma presenting as a submandibular lump in a 40 year old female. This lump was present for six months and was rapidly increasing in size. On cytology it was diagnosed as salivary gland neoplasm.

A Rare Neoplasm of the Testis: Capillary Hemangioma

Sevdeg�l MUNGAN, Havvanur TURGUTALP, �afak ERS�Z, Ferda KESK�N, �mer KUTLU — 2011-01-01

Intratesticular vascular neoplasms are extremely rare tumors and mostly seen in children or young adults. We reported a case of capillary hemangioma of the testis to attract attention to testicular hemangioma and also to prevent invasive surgery of the testis. The patient was an 18-year-old boy with a testicular mass. Scrotal sonography revealed a varicocele in the left testis and a simple cyst in the left epididymis. There was a solid hypoechoic neoplastic area 75 mm in diameter in the right testis. The laboratory findings including tumor markers and serum levels of α-fetoprotein and �-human chorionic gonadotrophin were normal. The patient underwent right orchiectomy and the pathology diagnosis was capillary hemangioma. Testicular neoplasms derived from connective tissue, blood vessels and musculature are uncommon and intratesticular tumors of vascular origin are extremely rare. There are only 21 cases reported in the literature. The pathologists and the surgeon have to be aware of this entity as the prognosis of the neoplasm determines the method of surgery. Capillary hemangioma of the testis can be similar to malignant testicular tumors on clinical presentation, as well as on ultrasonography and magnetic resonance imaging. Although it is impossible to differentiate a hemangioma from a seminoma before the operation, intraoperative frozen study may be helpful in the differential diagnosis. Frozen section must be performed if the neoplasm has significant vascular proliferation identified by Doppler sonography. Because of the benign nature of this lesion, conservative surgical treatment by means of tumor enucleation with preservation of the testis is possible if intraoperative frozen section examination can be performed.

Primary “Botryoid” Embryonal Rhabdomyosarcoma in Mesentery

Kiran AGARWAL, Ruchika KUMAR GOEL, Vandana PURI — 2011-01-01

Rhabdomyosarcoma is a soft tissue neoplasm arising from primitive embryonal mesenchyma. Embryonal rhabdomyosarcoma mostly affects children younger than 10 years of age, but it also occurs in adolescents and young adults. Pleomorphic rhabdomyosarcoma is a rare variant that almost always arises in adults older than 45 years of age. Mesentery is a rare site for botyroid embryonal rhabdomyosarcoma and on extensive search we found only one case of a botryoid rhabdomyosarcoma in a child of 2 years. We report a rare case of botyroid embryonal rhabdomyosarcoma occurring in the mesentery of a 30 year old female.

Childhood Intracranial Germinoma with Granulomatous Reaction

G�len G�LN�FL�O�LU, Mehtat �NL�, Nurullah Y�CEER, Erdener �ZER — 2011-01-01

Central nervous system tumors are the second most common type of childhood cancer in Turkey. Germinomas constitute two thirds of intracranial germ cell tumors. The granulomatous inflammation occurring around germinomas can cause histological diagnostic difficulty. We present a 12-year-old girl with a diagnosis of germinoma in the corpus callosum associated with granulomatous reaction to emphasize the diagnostic challenge which may occur during stereotactic biopsy interpretation or intraoperative consultation.

Dermatofibrosarcoma Protuberans of the Scalp: A Relatively Unusual Site of Occurrence

Indranil CHAKRABARTI, Kaushik MAJUMDAR, Amita GIRI — 2011-01-01

Dermatofibrosarcoma protruberans is an uncommon low grade soft tissue tumor comprising of only 5% of adult soft tissue sarcomas. Scalp is a relatively uncommon site of occurrence for this tumor. Its identification at this site and differentiation from benign fibrous histiocytoma is important due to the propensity of recurrence and metastasis in the former unless a wide, optimal surgical margin is ensured during excision.