Turkish Journal of Pathology - 2010; 26(3)

Editorial

��kr� O�uz �ZDAMAR — 2010-09-01

Editorial

��kr� O�uz �ZDAMAR — 2010-09-01

A Survey on Pathology Laboratories of the Ministry of Health Gynecology Hospitals in Turkey

Hatice Dilek B�LB�L, Alp USUB�T�N — 2010-09-01

Objective: The aim of this study was to determine the current situation of gynecopathology in Turkey, to lead standardization processes, to find out and to discuss the problems of pathologists dealing with gynecopathology by the aid of a questionnaire that had been sent to gynecology hospitals working under the Ministry of Health. Material and Method: A survey consisting of 60 questions was submitted to 31 gynecology, and gynecology and children hospitals' pathology laboratories. The results were reviewed and analyzed. Results: It was determined that there was no specific ratio between the number of beds, pathologists and the materials in the 24 hospitals which had answered the survey. It was also identified that the pathologists had a high workload in some laboratories. Furthermore it was realised that there were some challenges in administrative support, physical conditions, personnel safety and waste product management. There was no standard for analyzing and reporting the gynecopathology materials. Conclusion: All Turkish Pathology Societies and the Federation of Turkish Pathology Societies plays a big role in setting the appropriate standarts, quality control and quality assurance for pathology, which is a considered a laboratory discipline but has important differences regarding working essentials and conditions.

The Role of D2–40, and Podoplanin in Differentiating Mesotheliomas from Primary Adenocarcinomas of the Lung and Metastatic Carcinomas of the Pleura

2010-09-01

Objective: The aim of this study was to assess the diagnostic and differential significance of two recently introduced positive mesothelial markers, namely podoplanin and D2-40. Material and Method: The study group included a total of 55 cases: 11 cases of malignant mesothelioma and equal number of cases (n:11) of primary lung adenocarcinoma, bronchioloalveolar carcinoma, metastatic carcinoma of the pleura and mesothelial proliferation. D2- 40, podoplanin, calretinin, cytokeratin 5/6, carcinoembryonic antigen, epithelial specific antigen (MOC-31) were immunohistochemically studied in all cases. The extent of staining was graded between 1+ and 4+. Results: While the 7 (63.6%) of the mesotheliomas and 10 of the mesothelial proliferations (90.9%) stained positive with D2-40, no positive staining was noted in primary lung adenocarcinoma, bronchioloalveolar carcinoma, metastatic carcinoma of the pleura. 9 of the mesotheliomas (81.8%) and 10 of the mesothelial proliferations (90.9%) were positive with podoplanin whereas no positive staining was observed in the other groups. Eight of the primary lung adenocarcinomas (72.7%), seven of the bronchioloalveolar carcinomas (63.6%), and eight of the metastatic carcinomas of the pleura (72.7%) were positive for MOC-31 while only one of the mesotheliomas (9%) was positive and no mesothelial proliferation cases were positive. The specificity of podoplanin, D2-40, calretinin and cytokeratin 5/6 for mesothelioma was 100% and their sensitivity was 81.8%, 63.6%, 81.8% and 54.5%, respectively. The highest sensitivity, (i.e. 100% sensitivity) for mesothelioma was observed with the D2-40, podoplanin, and calretinin combination. Conclusion: D2-40 and Podoplanin were effective in differentiating malignant mesothelioma from primary lung adenocarcinomas, bronchioloalveolar carcinoma and metastatic carcinomas of the pleura. However, since they may not yield precise results it was therefore concluded that a panel combined with positive and negative mesothelial markers including these two markers will lead to more accurate results.

Colonic Lipomas Mimicking Colon Cancer

Berna AYTA�, �mer YERC�, Selim G�REL, Zarema FER�K — 2010-09-01

Objective: Colonic lipomas are uncommon tumors of the gastrointestinal tract. Most of these tumors are asymptomatic and usually detected incidentally during colonoscopy or laparotomy and do not require treatment. Large lipomas are usually symptomatic and may mimic clinic manifestations of colonic carcinoma. Here we studied seven cases of submucosal and intramuscular colonic lipomas to evaluate the clinical features, diagnosis and treatment of this disease. Material and Method: Seven patients who were diagnosed with colonic lipoma between 1999 and 2006 were evaluated as regards age, gender, size of tumor, anatomic site, symptoms, location and treatment modality. Result: The mean age was 57.8� 14.7 years. Five patients were male and two were female. The size of the lipomas ranged from 1 to 5.5 cm and all were symptomatic except one patient. Five of the gastrointestinal lipomas were located submucosally and 2 intramurally. Five lipomas arose from the ascending colon, 1 from the hepatic flexure and 1 from the splenic flexure. Four large GI lipomas were removed by subtotal resection and one case underwent hemicolectomy while two pedunculated lipomas were resected by polypectomy. No recurrence was found after at least one year follow-up with endoscopic examination. Conclusion: Colonic lipomas may mimic malignancy with their clinical manifestations. Appropriate radiological and colonoscopic evaluation is essential to avoid unnecessary wide resections.

Differences in the Cytological Features of Atypical Adenomatous Hyperplasia and Low-Grade Prostatic Adenocarcinoma

Ahmet M�D�, T�lay TEC�MER, S�heyla BOZKURT, Naziye �ZKAN — 2010-09-01

Objective: The aim of this study was to review the histological features and to define parameters distinguishing atypical adenomatous hyperplasia from prostatic adenocarcinoma grade 1 and 2. We evaluated 14 parameters related with cytological properties. Material and Method: We found 11 atypical adenomatous hyperplasia (22 foci) and 15 prostatic adenocarcinoma grade 1 and 2 (22 foci) lesions in 105 radical prostatectomy specimens. Basal cell-specific keratin (34βE12) was applied and based on the fact that prostatic adenocarcinoma grade 1 and 2 lesions do not have basal cells we grouped the lesions as atypical adenomatous hyperplasia and prostatic adenocarcinoma grade 1 and 2. Results: Statistically significant differences were found between atypical adenomatous hyperplasia and prostatic adenocarcinoma grade 1 and 2 lesions for some parameters including the largest nuclear diameter, nuclear location, 1-2 μm nucleolus, > 2 μm nucleolus, and nuclei containing multiple nucleoli. We found similar properties between the two lesions for the following parameters: irregularity of nuclear membrane, median diameter of the nucleolus, chromatin pattern, pynotic nucleus, nuclear pleomorphism, < 1 μm nucleolus nucleolar margination, and the ratio of nucleus to cytoplasm and the appearance of cytoplasm in the secretory cells. Conclusion: Evaluation of the overall histomorphological criteria is important in the differentiation of atypical adenomatous hyperplasia and prostatic adenocarcinoma grade 1 and 2 lesions.

Correlation of Hormone Receptors with Her 2/neu Protein Expression and the Histological Grade in Invasive Breast Cancers in a Cohort of Saudi Arabia

Maha ARAFAH — 2010-09-01

Objective: Data on hormone receptor and Her2/neu expression in breast cancers from Saudi Arabia and Gulf Region is sparse. We undertook this study to describe the patterns of hormone receptor and Her2/neu protein expression in breast carcinoma and compared them with the histological grade at a university hospital in Riyadh. Material and Method: We conducted a retrospective hormone receptor and Her2/neu study on 164 histologically confirmed invasive ductal carcinoma of the breast between the year 2002 and 2008. Immunohistochemical analysis for estrogen receptor, progestrone receptor and Her2/neu was done in all the cases. Fluorescent in situ hybridization (FISH) for Her2/neu gene amplification was performed in all 2+ cases and a few equivocal 1+ and 3+cases by immunohistochemistry. The results were then compared in a blinded fashion. Correlation between Estrogen Receptor, Progesterone Receptor and Her2/neu amplification and grade of tumour were calculated. Result: The prevalence of estrogen receptor, progestrone receptor and Her2/neu overexpression were 64.6%, 57.3% and 35.3% respectively. The expression of estrogen receptor and progestrone receptor were significantly correlated (p<0.001). There was also a significant negative correlation between expression of hormone receptor and Her2/neu amplification. The histological grade of the tumour was also significantly correlated to the expression of both estrogen receptor and progestrone receptor. However, the relationship between Her2/neu amplification and grade of tumour was not significant and many of the grade III tumours were Her2/neu negative. In addition Her2/neu gene amplification by FISH was observed in 84.6% of breast cancers that were 3+ and in 18.75% of the cases that were 2+ by immunohistochemistry. Conclusion: The revalence of estrogen receptor, progestrone receptor expression and Her2/neu amplification in breast cancers in Saudi Arabian population is similar to that reported internationally. There is a negative correlation between hormone receptors expression and Her2/neu amplification. However, not all high-grade breast cancers showed Her2/neu positive status.

Evaluation of Immunohistochemistry and Silver-Enhanced In Situ Hybridization Results for HER2/neu Manually and with Image Analysis System in Human Breast Cancer

Do�u� �ZDEM�R, I��n PAK — 2010-09-01

Objective: HER2/neu (ErbB2) gene status is one of the important information while planing terapy in breast carcinoma. For HER2/ neu testing there is not standart assay that has been agreed on. Silver enhanced in situ hybridization is a cantitative and highly reproducible assay. Immunohistochemistry is a cheap and easy assay that has disadvantage of being less reproducible. Recently developed pathologist assisted computerized image analysis systems decrease the ratio of subjectivity due to manual evaluation, enable tele-consultation and make it easy to evaluate tumor morphology and markers. Our aim is to investigate the consistency of manual and computerized interpretation of the results of immunohistochemistry and silver enhanced in situ hybridization. Material and Method: Immunohistochemisty and silver enhanced in situ hybridization of 73 invasive breast carcinoma results were evaluated manually to determine HER2/neu status. Later, silver enhanced in situ hybridization and immunohistochemistry results were reevaluated with Ventana Image Analysis System. Afterwards correlation of both methods with image analysis system and manuel interpretation were calculated. Result: All cases were score 2 with immunohistochemistry. With image analysis system, 5 cases were score 1, 56 cases were score 2 and 12 cases were score 3. When in situ hybridization results were reevaluated with image analysis system, 6 cases were discordant compared with manual interpretation. Conclusion: The correlation rate of immunohistochemistry interpretation results between manuel method and image analysis system was %76; but silver enhanced in situ hybridization interpretation results between manuel method and image analysis system were %91 concordant and it was statistically significant (k= 0.832 and p<0.001).

Comparison of Immunohistochemistry and Fluorescence In Situ Hybridization for the Analysis of HER2/neu and Topoisomerase II-alpha Status in Human Breast Cancer

Emel Ebru PALA, Osman ZEK�O�LU, Necmettin �ZDEM�R, Rasih YILMAZ, Murat KAPKA� — 2010-09-01

Objective: HER2/neu is overexpressed/amplified in 20% of breast cancers. HER2/neu status plays a role in determining the patients who might benefit from hormonal therapy and targeted therapy with Trastuzumab. The main cause of HER2/neu overexpression is gene amplification. 10-25% of patients show Topoisomerase II-alpha gene alterations with HER2/neu amplification. The objective of this study was to compare and standardize immunohistochemical and fluorescence in situ hybridization methods for the analysis of HER2/ neu and Topoisomerase II-alpha. Material and Method: 78 cases with invasive breast cancer were selected from the archives. Anti-human HER2/neu, and Topoisomerase II-alpha antibodies were used to determine protein expression levels by immunohistochemistry; TOP2A/HER2/CEP17 probe set was used to examine genomic alterations by fluorescence in situ hybridization. Result: HER2/neu overexpression was observed in 59% and HER2/ neu amplification in 44.9% of the cases. The mean percentage of tumor cells that expressed Topoisomerase II-alpha was 25.9%. 12 cases with Topoisomerase II-alpha amplification (15.4%) also amplified with HER2/neu. The association between HER2/neu and Topoisomerase II-alpha amplification and their expression levels was statistically significant (p<0.01, p=0.005). The concordance between immunohistochemistry and fluorescence in situ hybridization was 71.7% in 3+ and 11.7% in 2+ cases. Two patients showed chromosome 17 polysomy. Conclusion: The concordance between immunohistochemistry and fluorescence in situ hybridization was low in 3+ and 2+ cases. Immunohistochemistry and fluorescence in situ hybridization should be performed together until the standardization of the whole process that affects immunohistochemistry and fluorescence in situ hybridization results. If Topoisomerase II-alpha gene alterations are proven by clinical studies to affect the tumor response to the anthracyclines, it will be appropriate to detect these alterations by fluorescence in situ hybridization.

Reasons for False-Negative and False-Positive Diagnosis in Fine Needle Aspiration Cytology of the Breast: 286 Cases with Cyto-Histopathologic Correlation

2010-09-01

Objective: Fine needle aspiration cytology is the first step in the diagnosing breast lesions. This study evaluated factors causing falsenegative and false-positive diagnoses when evaluating breast lesions using this technique. Material and Method: In this study, we retrospectively examined 511 breast diagnoses, based on Fine needle aspiration cytology specimens, made in the Medical School of Zonguldak Karaelmas University, Department of Pathology, between 2002 and 2009. Factors affecting the reliability of fine needle aspiration cytology were evaluated by comparing the cytological and biopsy diagnoses and using the clinical parameters in the diagnosis of breast lesions. Result: In our series, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of fine needle aspiration cytology were 77%, 99%, 95%, 93%, and 95%, respectively. The falsenegative diagnosis rate was 4% and the false-positive diagnosis rate was 1%. Conclusion: Sampling errors and erroneous interpretation of cellular monomorphism are the most important reasons for false-negative diagnosis results in the evaluation of breast lesions with fine needle aspiration cytology. Increased cellularity and reactive cell atypia in benign proliferative breast lesions are the most frequent reasons for false-positive diagnosis.

The Role of CD56, HBME-1, and p63 in Follicular Neoplasms of the Thyroid

H�lya ETEM, Selver �ZEK�NC�, B�lent MIZRAK, Senem �ENT�RK — 2010-09-01

Objective: Carcinomas originating from thyroid follicular cells are the commonest of all endocrine system malignancies. In this study we evaluated the importance of the expressions of CD 56, HBME-1 and p63 in the differential diagnosis of the follicular variant of papillary carcinoma from other follicular neoplasms. Material and Method: We re-evaluated 80 cases of thyroid neoplasms, comprising 40 cases of follicular variant of papillary thyroid carcinoma and 40 cases of follicular neoplasm, diagnosed at Dicle University Medical School, Department of Pathology between 2005 and 2008. All neoplasms were stained with CD 56, HBME-1 and p 63 compared to each other. Statistical analysis was with Student's t test and the Yates corrected chi-square test. Result: There was no statistically significant difference in the expression of CD 56 between follicular neoplasms and papillary carcinomas, but HBME-1 and p63 expressions were statistically significantly different between these neoplasms (p=0.005, p=0.0001). Conclusion: The use of HBME-1 and p63 may be helpful in differentiating papillary carcinoma, particularly follicular variant, from follicular neoplasms.

Fine Needle Aspiration Cytology of Fibromatosis Colli

Indranil CHAKRABARTI , Arghya BANDYOPAHYAY, Bidyut Krishna GOSWAMI — 2010-09-01

Fibromatosis colli, also known as sternomastoid tumor, is considered a rare benign lesion of infancy of uncertain etiology and pathogenesis. Usually a self-limiting condition, diagnosis of this lesion by less invasive techniques is important to avoid an unnecessary surgical procedure. We report a case of a one-month-old male infant who presented with a firm 3 cm swelling on the left side of the neck. Fine needle aspiration was performed and the cytological features were suggestive of fibromatosis colli. Fibromatosis colli has to be differentiated from various congenital, inflammatory and neoplastic conditions that can occur in a similar location. Fine needle aspiration cytology appears to be a cheap, rapid, less invasive and fairly accurate diagnostic aid for excluding other causes and detection of this type of lesion. Identification of these lesions is important as they are usually self-eliminating with some cases requiring conservative management and rarely surgical intervention.

Ancient (Sklerozan) Timoma: Olgu Sunumu

Duygu G�REL, Aydanur KARGI, Erkan YILMAZ, Ayd�n �ANLI — 2010-09-01

A 43-year-old female who had dyspnea and had been diagnosed as myasthenia gravis was found to have a mass lesion of the anterior mediastinum that protruded to the left and contained calcified areas on radiological investigation. The patient was operated on with a preliminary diagnosis of thymoma. Macroscopically the tumoral lesion was 5x4.5 cm in size and was light tan, firm and solid without necrosis or hemorrhage. Histological investigation showed epithelial islands without atypical features scattered within large areas of hyalinized collagenous tissue and the presence of immature T lymphocytes some of which were TdT positive, which led to a preliminary diagnosis of sclerosing thymoma. Sclerosing thymoma is a rare type of thymoma and has first been reported in 1994. Since there are only a few reports in the literature detailed information on clinical features and pathogenesis is needed. The possibility of sclerosing thymoma should always be kept in mind in the differential diagnosis of mediastinal lesions with marked sclerosis that can lead diagnostic difficulties especially when evaluating small mediastinoscopic biopsies.

Coexistence of Atypical Adenomatous Hyperplasia and Hamartoma of the Lung

Ahmet M�D�, Rahmi �UBUK, A. Ne�e YENER, Alpay �RK�, B�lent ARMAN — 2010-09-01

Atypical adenomatous hyperplasia is considered to be a preliminary lesion for pulmonary adenocarcinoma while lung hamartomas (mesenchymomas) are non-neoplastic, tumor-like malformations. A patient underwent transthoracic fine-needle aspiration biopsy for a pulmonary mass and then lingulectomy following a diagnosis of adenocarcinoma. The surgical specimen was solid and 25 mm in diameter. Microscopic investigation revealed that the mass was a hamartoma with an atypical adenomatous hyperplasia focus at the periphery. We believe that the cells leading the cancer diagnosis had come from the atypical adenomatous hyperplasia focus around the hamartoma. We presented this case as atypical adenomatous hyperplasia contains atypical epithelium and can be diagnosed as a malignancy on fine needle aspiration biopsy and the coexistence of atypical adenomatous hyperplasia and hamartoma has not been reported previously.

Giant Hyperplastic Polyp in the Stomach

Fazilet U�ur DUMAN, Semin AYHAN, Ayd�n ��SA�, �smail YAMAN — 2010-09-01

Hyperplastic polyps, which account for nearly 75% of all gastric polyps, are generally small (<1 cm), single, sessile, polyps and located in antrum. They are usually asymptomatic. A 77-year-old man was admitted to hospital due to severe fatigue as a consequence of irondeficiency anemia. The upper gastrointestinal endoscopy which was done to discover an etiological factor revealed a papillomatous mass 6 cm in diameter that had a malignant endoscopic appearance. Numerous macroscopic sections were taken since larger gastric polyps (especially those greater than 2 cm in diameter) have a greater risk of malignancy development. No dysplasia was detected on histological and immunohistochemical evaluation and it was therefore diagnosed as a giant hyperplastic polyp in the stomach. The large size of the polyp in the presented case led us to emphasize the importance of searching for dysplasia in such cases.

Gastric Carcinoma Demonstrating Rhabdoid Features

Tu�ba KARADEN�Z, Semin AYHAN, Aylin TURNA, Mustafa T�REL� — 2010-09-01

Rhabdoid tumor, first described as an aggressive kidney tumor in infants and children and also observed less commonly in extra-renal locations, is seen very exceptionally in the gastrointestinal system. Gastrointestinal tumors with rhabdoid features are also extremely rare. A 59-year-old man with a long history of nausea, vomiting and weakness had been diagnosed as “diffuse-type gastric carcinoma” by the evaluation of endoscopic biopsy specimen at an other hospital. The total gastrectomy specimen showed an ulcerated mass measuring 7x4x4 cm located at the lesser curvature. The tumor penetrated the entire gastric wall and invaded the perigastric fat. The histopathological and immunohistochemical evaluation revealed a gastric carcinoma with rhabdoid features. The tumor was presented to emphasize the importance of clinical, morphological and immunohistochemical differential diagnosis from diffuse type gastric carcinoma as it has a very poor prognosis and is rarely seen in the gastrointestinal system.

Metastatic Renal Cell Carcinoma Initially Presented as a Tongue Mass

2010-09-01

Renal cell carcinoma is one of the most common tumours after lung and breast cancer to metastasize to the head and neck. Initial presentation by tongue metastasis is extremely rare. A 67-year-oldmale presented with a 4.8 cm mass on his tongue. The result of the punch biopsy from the tongue was diagnosed as a clear cell variant of squamous cell carcinoma. The biopsy was reevaluated due to the renal mass found during the check-up and the rapid enlargement of the mass. The excision of the tongue mass and the radical nephrectomy material confirmed the diagnosis of a metastatic renal cell carcinoma in the tongue and renal cell carcinoma in the kidney. Since metastasis of renal cell carcinoma to the tongue is uncommon it may cause difficulties in diagnosis and proper management. The metastasis of renal cell carcinoma should always be considered in the differential diagnosis among the clear cell neoplasms.

Ovarian Hemangioma: Report of Two Cases and Review of the Literature

Filiz BOLAT, Serkan ERKANLI, Naz�m Emrah KO�ER — 2010-09-01

Ovarian hemangiomas are rare tumors. Most of them are asymptomatic and of the cavernous type. The ovaries have a rich vascular supply and the rarity of vascular tumors in the ovary is therefore surprising. Although often found incidentally during the surgery, these lesions may rarely be associated with systemic manifestations. Here, we report two cases of cavernous ovarian hemangiomas. One was accompanied by with an endometrial carcinoma in a patient who presented with postmenopausal bleeding, and the other was found incidentally during the histopathological examination of the hysterectomy and bilateral salphingo-oophorectomy specimen that was performed for leiomyoma uteri.

Pseudoangiomatous Stromal Hyperplasia of the Breast

Dilek YILMAZ, Yurdanur S�LL� — 2010-09-01

Pseudoangiomatous stromal hyperplasia of the breast is a benign stromal lesion that can be mistaken as fibroadenoma on clinical and ultrasonographic examination or as a low grade angiosarcoma on histological examination. Pseudoangiomatous stromal hyperplasia may be seen incidentally in about 23% of breast biopsies. Although exact etiology and pathogenesis of pseudoangiomatous stromal hyperplasia is still unknown, reactivity of myofibroblasts against endogeneous hormones particularly progesterone is thought to be responsible. Because mass forming lesions are rare we present a case of pseudoangiomatous stromal hyperplasia which was diagnosed as fibroadenoma on clinical and ultrasonographic examination. A 27- year-old woman presented with a right breast mass. After physical and ultrasonographic examination, it was diagnosed as fibroadenoma and excision was done. Histopathological examination revealed a lesion composed of complex anastomosing vessel-like slits in a dense collageneous stroma. These slits were outlined by endothelial-like spindle cells. These spindle cells were negative for CD31 while CD34 and SMA were positive. Reactivity with CD34 and SMA showed myofibroblastic differantiation of spindle cells. Although unclear, aberrant reactivity of myofibroblasts against progesterone is suggested in pathogenesis of pseudoangiomatous stromal hyperplasia. Unlike the previous reported cases, the negativity of myofibroblastic cells for progesterone in our case suggest other factors aside from progesterone may play role in the etiology.