Turkish Journal of Pathology - 2012; 28(3)

Who Owns These Tissues? General Principles on the Use of Material Submitted to Pathology Departments for Healthcare, Education and Research Purposes

S�meyye EKMEK��, Osman Ar�kan NACAR, Tar�k T�HAN — 2012-09-01

The study of human tissues procured through invasive procedures for diagnostic and treatment purposes constitutes one of the most important functions of pathology departments worldwide. The final diagnosis, determination of appropriate therapy and detailed insight on many diseases are possible only through the analysis of these tissues with the use of modern analytical techniques. While these statements present no controversy, the laws and regulations on how to use these tissues for diagnostic, educational and research purposes are woefully insufficient and cause significant debate. In addition to the lack of principles that define the possession and use of these tissues, there are a number of prejudices in our country that are not consistent with the scientific and medical facts. This study aims to frame the problems arising in this matter and provides a review of the rules, experience and legislation in various countries with a discussion of some examples. We aim to provide ideas on the general fundamental principles that should be incorporated in future legislation in our country. We also hope that our study initiates a healthy discussion of this critical topic.

The Situation of Consultation Practice in Pathology in Turkey

Alp USUB�T�N, Serdar BALCI, Kutsal Y�R�KO�LU — 2012-09-01

Objective: There are some suggestions regarding the methods of consultation practice in the literature including which case will be consulted, to whom, by which transport means, the payment methods as well as the ethical issues. There are no standards for consultations in Turkey. The standardization committee of the Federation of Turkish Pathology Societies has conducted a survey to detect the current situation, determine the problematic aspects, compare the situation with international methods and offer methods specific to Turkey. Material and Method: A survey has been prepared to cover all the aspects of consultation practice using the literature and referring to the current methods used in Turkey. The survey has been announced on the internet and 83 replies were collected. Results: Multiple choice questions were evaluated in terms of percentages and open ended questions were grouped according to the answer contents. It was seen that problems could be grouped as follows: absence of written procedures covering each step, means of transport, reaching the consultant, payment, reporting and ethical issues. The absence of procedures and issues regarding the payment methods were the interfering factors for each step of consultation. Conclusion: There are many problematic issues in consultation practice in pathology in Turkey. The basis of these problems is the absence of written regulations for procedural and payment methods. Regulations addressing these issues should be developed.

Digitally Reinforced Polarization of Hematoxylin-Eosin in the Diagnosis of Renal Amyloidosis

Sait �EN, Banu SARSIK KUMBARACI — 2012-09-01

Objective: Systemic amyloidosis is a rare disorder, characterized by extracellular accumulation of Congo red positive fibrillar amyloid protein deposits that have an amorphous, eosinophilic appearance on hematoxylin-eosin stained preparations. The kidney is the most commonly affected organ by systemic amyloidosis. Congo red staining increases the positive birefringence of the weakly birefringent unstained amyloid. In this study, we investigated the potential diagnostic power of digitally reinforced birefringence of routine hematoxylin-eosin stained slides from renal biopsies. Material and Method: We reviewed 130 hematoxylin-eosin stained slides for polarization. Sixty-five new amyloidosis cases were diagnosed by renal biopsy. All renal biopsies were evaluated by light microscopy and immunofluorescence. Slides were reevaluated blindly using a microscope (Olympus BX51) that was attached polarization filters and connected to a digital camera (Olympus DP21, SAL). Deposits that showed green birefringence on hematoxylin-eosin preparations with digitalized microscopy were considered positive and the results were confirmed using Congo red. Results: Of the 65 Congo red confirmed amyloid positive biopsies, 61 showed green birefringence with hematoxylin-eosin. Of the 65 Congo-red confirmed amyloid negative biopsies, two were considered to be false positive. The sensitivity, specificity, and positive and negative predictive values were estimated as 94%, 97%, 97% and 94% respectively. Conclusion: We concluded that polarized hematoxylin-eosin sections can be used digitally as a fast and first step diagnostic method for renal amyloidosis

The Selective Expression of Ret Finger Protein in Endometrial Cancer: Can RFP be a Marker of Serous Carcinomas?

Gaye G�ler TEZEL, Zehra ORDULU, �i�dem H�MMETO�LU, Alp USUB�T�N — 2012-09-01

Objective: Endometrial cancer is a common malignancy of the gynecological system and has been classified into two major groups, Types I and II. Type I tumors are estrogen-related, low-grade endometrioid tumors, whereas type II tumors are aggressive, high-grade non-endometrioid tumors. Ret finger protein is a nuclear transcription factor with a tripartite motif that is highly expressed in different tumor cells. Material and Method: To analyze the expression of ret finger protein in endometrial tissues and cancer, 18 cases of secretory and proliferative endometrium, endometrial polyp, endometrial hyperplasia and endometrial intraepithelial neoplasia and 21 cases of types I and II endometrial carcinoma were evaluated immunohistochemically. Results: Although rare cases of secretory endometrium showed a weak focal nuclear positivity, remaining proliferative endometrium, endometrial hyperplasia and type I endometrioid cancer cases were negative. In contrast, all cases of serous cancers showed strong nuclear positivity. After these strong positive results for serous endometrial cancer, 12 more cases of ovarian and endometrial serous carcinoma cases were added to the study. All of the additional cases were also strongly positive for ret finger protein. Conclusion: We suggest that ret finger protein might play a role in the carcinogenesis of the serous tumors of gynecological system and can be used to differentiate serous carcinomas from other epithelial tumors.

Expression of p16, p53, CD24, EpCAM and Calretinin in Serous Borderline Tumors of the Ovary

I��l Yildiz AKTA�, Meral BU�DAYCI, Alp USUB�T�N — 2012-09-01

Objective: According to the widely accepted pathway, a serous borderline tumor becomes invasive either by progressing into a noninvasive micropapillary tumor or directly through microinvasion. Our objective was to investigate the role of serous borderline tumors and their accompanying extraovarian lesions in pathogenesis of serous ovarian cancer using immunohistochemistry as a tool. Material and Method: An immunohistochemical panel of p16, p53, CD24, EpCAM and calretinin was applied to cutting edge matrix assembly-like tissue arrays of 46 cases consisting of typical, focal micropapillary, micropapillary, microinvasive, cystadenoma, and low-grade carcinoma cases. These tissue arrays are better choices than conventional tissue arrays to examine thin walled and heterogenous neoplasia like serous borderline tumors as they facilitate the analysis with linear sections rather than a core. Results: For two tumor supressor gene markers; no diffuse and strong expression of p53, and strong and patchy/heterogenous expression of p16 were detected in all cases. Focal and strong calretinin expression was detected in micropapillary tumors while expression of EpCAM was lost in the same areas. Strong cytoplasmic CD24 expression was detected in cases with peritoneal implants, favoring the theory that change of expression localization of cell adhesion molecules is in accordance with phenotypical changes and tumor progresssion. Furthermore, circumfrential membranous and cytoplasmic expression of CD24 and EpCAM was detected in neoplastic cells in lymph nodes and microinvasion areas. Conclusion: Our results show that different levels of serous ovarian tumor progression are accompanied by changes in the immunohistochemical expression pattern of EpCAM, CD24, and calretinin.

The Influence of Cervicovaginitis Agents on Epithelial Cell Changes: Comparison of Mardin City's Data with the Literature

I��k �kbal BARI�, Ay�e Nur KELE�, Yeliz ARMAN KARAKAYA — 2012-09-01

Objective: The aim of this paper was to observe the reactive changes of epithelial cells exposed to the influence of cervicovaginitis agents that play an important role in the cytology practice and may cause an exaggerated appearance. Material and Method: 378 cases with cervicovaginitis caused by a specific agent were compared with 100 control cases. It was recorded if the inflammation had concomitant cellular changes and atypia or not. After treatment, control smears were examined. The reactive and atypical situations of the cells were considered after the treatment. With the aid of the previous data, the answer to the following question was searched: Is epithelial atypia a real event or a reactive atypia that accompanies an existing cervicitis agent? Results: In the first interpretation, Candida group had the most frequent reactive and ASC-US (Atypic Squamous cells of Undetermined Significance) changes (56,4% and 59,5% respectively). The bacterial vaginosis and Trichomonas vaginalis groups showed ASC-US rates of 25% and 9,5% respectively while in control group the rate was 6,0%. After treatment, the number of cases of ASC-US decreased from 50 to 11. Similarly, the number decreased from 21 to 10 in the bacterial vaginosis group. Conclusion: Cervicovaginitis agents need more attention because of their outcomes. Being aware of the cervicovaginitis agents during interpretation is essential for preventing a false positive diagnosis and unnecessary anxiety especially where cellular atypia is concerned.

Immunohistochemical Characteristics of Triple Negative/Basal-like Breast Cancer

Emel Ebru PALA, �mit BAYOL, S�heyla CUMURCU, Elif KESK�N — 2012-09-01

Objective: Triple-negative-breast-cancer that accounts for 10-20% of all breast carcinomas is defined by the lack of estrogen receptor, progesterone receptor, HER2 expression, and agressive clinical behavior. Triple-negative-breast-cancer is categorized into basal like and other types. The basal-like subtype is characterized by the expression of myoepithelial/basal markers. Material and Method: We studied 41 immunohistochemically triplenegative- breast-cancer patients to determine EGFR, Cytokeratine 5/6, p53, Ki67, GCDFP-15 expression profiles, HER2 and Chromosome 17 centromere gene status by fluorescence-in-situ-hybridization method. Results: Histological type was invasive ductal carcinoma in 90.2% of the tumors. p53, Ki67, GCDFP-15 mean positivity rates were 55.6%, 51.7%, and 3.2%, respectively. GCDFP-15 positivity was noted in 8 cases of which 6 were Cytokeratine 5/6 negative. The cut-off value for Cytokeratine 5/6 positivity was 5%. EGFR immunoreactivity was grouped into 0, 1+ as negative; 2+, 3+ as positive categories. Cytokeratine 5/6 was positive in 56,1%, EGFR was positive in 51.2% of the patients. The relation between Cytokeratine 5/6 and EGFR expression was statistically significant (p<0.01). None of the cases showed HER2 amplification by fluorescence-in-situ-hybridization method. Conclusion: GCDFP-15 alone is not a useful marker to detect the metastasis of basaloid type breast cancers. Cytokeratine 5/6 and EGFR expressions showed correlation so these markers are reliable to diagnose basaloid type tumors with a 5% cut-off value.

The Important Morphological Parameters Used to Differentiate Benign/Malignant Phyllodes Tumors of the Breast

�lk� K��K, Emel Ebru PALA, �mit BAYOL, I��n G�K��L ERDO�AN — 2012-09-01

Objective: Phyllodes tumor is a rare fibroepithelial neoplasia of the breast. Tumors are classified according to the histological criteria as benign, borderline, malignant groups. Criteria used to discriminate benign/malignant cases are stromal cytological atypia, stromal hypercellularity, mitotic rate, stromal overgrowth, and tumor margins. We designed this study retrospectively to see the validity of these criteria for our case group and investigate whether we could add any new criteria. Material and Method: We included 22 cases diagnosed as phyllodes tumor from our archives. Pathology records were used for age, tumor site, macroscopic size. The Hematoxylin-Eosin stained slides were reviewed according to the defined criteria. Additionally leaf like growth pattern, stromal hyalinization, calcification, stromal giant cells, stromal neutrophil leukocyte, and mononuclear lymphocytic infiltrate were recorded qualitatively (present/absent) and numerically (mild, moderate, severe). We examined the differences between benign and malignant groups with the Mann-Whitney U and chi-square tests. Results: The previously defined criteria were statistically significant but stromal giant cells, stromal hyalinization, calcification, stromal neutrophil and mononuclear lymphocytic infiltrate intensity were not statistically significant in determining the benign-borderlinemalignant cases. Conclusion: Stromal hypercellularity, moderate/severe stromal cytological atypia, increased mitotic rate, stromal overgrowth and infiltrative tumor margins were observed in malignant phyllodes tumors. Malignant cases were also older and tumor size was bigger than benign ones.

CDX2, COX2 and MUC2 Expressions in Barrett's Esophagus: Can They Be Useful in Determination of the Dysplasia?

2012-09-01

Objective: The description of Barrett's esophagus which is a risk factor for esophageal adenocarcinoma has differences, and the need of goblet cells for diagnosis is controversial. However, the pathophysiology in the metaplasia seen in Barrett's esophagus is not totally understood and new methods are searched for the assessment of progression to dysplasia. We aimed to search the immunohistochemical expression of CDX2, COX2 and MUC2 in Barrett's esophagus to detect any early evidence of intestinal metaplasia or dysplasia. Material and Method: The staining properties were examined in the intestinal metaplastic (goblet cell-containing columnar epithelium), columnar (non-goblet columnar epithelium), distant columnar (non-goblet columnar epithelium distant from intestinal metaplastic epithelium) and squamous epithelium in 59 pathologically diagnosed Barrett's esophagus, 22 of which having dysplasia. The results were compared statistically with Pearson and Fisher exact tests. Results: The distribution of the staining of intestinal metaplastic, non-goblet columnar distant columnar, and squamous epithelium, respectively were as follows: for CDX2 76.3%, 23.7%, 1.7%, 0%; for COX-2 93.2%, 47.5%, 8%, 62.9%; for MUC2 93.2%, 11.9%, 4% and 0%. The expression of CDX2, COX2 and MUC2 in the intestinal metaplastic epithelium was higher than the expression in distant and non-goblet columnar epithelium. The expression of CDX2, COX2 and MUC2 in the foci of dysplasia decreased significantly (18.2%, 27.3%, 31.9%, and p=0.039, 0.0001, 0.0001, respectively). COX2 expression in squamous epithelium was also lower when the adjacent mucosa has dysplasia (p=0.014). Conclusion: The CDX2, COX2 and MUC2 expressions were seen in the intestinal epithelium having goblet cells. The use of the markers in the diagnosis is controversial but the difference in the Barrett esophagus-dysplasia sequence seems to be meaningful.

A Regional Panorama of Dysferlinopathies

2012-09-01

Objective: We describe the characteristic features of 11 patients (6 men and 5 women) with dysferlinopathies confirmed by muscle biopsies. In addition, we aimed to provide a realistic comprehensive picture of the severe muscle diseases in the Aegean Region of Turkey. Material and Method: We retrospectively reviewed 90 patients who underwent muscle biopsy examinations between 2008 and 2011 in the pathology laboratory of Izmir Dr.Behcet Uz Children's Hospital. Biopsy specimens of all patients clinically diagnosed as muscular dystrophy referred from 4 different centers of neurological disorders were collected. Results: Dystrophinopathy was the most (n=45) and gammasarcoglycanopathy was the second common (n=13) muscular dystrophy in this series. The mean age of all 90 patients was 8.8 years (3 months- 64 years). Only 14 cases (15.5%) were older than 14, and 23 cases were younger than two years. Dysferlinopathy was the most common dystrophy in the older age group. There were statistical significant differences between the types of dystrophy and inflammation (0.021), creatine kinase levels (p= 0.001), age (p=0.001), and gender (p<0.001) of the patients. Conclusion: The present study revealed that dysferlinopathies is not an uncommon form of muscular dystrophies in western Turkey. We have concluded that if avoidance from unnecessary therapeutic interventions is desired, we must be aware of the relative frequencies of dysferlinopathies.

Synovial Sarcoma Involving the Median Nerve: A Case Report

2012-09-01

Synovial sarcoma may arise from different and unusual sites. Here a case of biphasic synovial sarcoma arising or invading the radial nerve in a 59-year-old female classically showing chromosomal reciprocal translocation (X; 18) is reported. The differential diagnosis from similar tumors is discussed.

A Case of Cd20 Positive Mediastinal Rhabdomyosarcoma

G�lden D�N�Z, Ferah GENEL, Nur Y�CEL, Ay�en T�RED�, Canan VERG�N — 2012-09-01

We present the case of a 16-year-old boy admitted with a large mediastinal mass. Both in the mediastinal tru-cut biopsy and the bone marrow biopsy, a malignant small round cell tumor was determined. The clinical diagnosis was leukemia or lymphoma. The cytoplasmic CD20 expression was shown on the tumor cells of the mediastinal tru-cut biopsy. Rhabdomyosarcoma was diagnosed by the flow cytometric analysis and immunohistochemical demonstration of muscle markers. Rhabdomyosarcomas are traditionally distinguished from lymphomas by their absence of lymphoid markers such as CD20. But in this case we have encountered CD20 expression in the tumor cells. This finding lead us to conclude that the presence of a lymphoid phenotype does not absolutely exclude the diagnosis of rhabdomyosarcoma.

Polymorphous Low-Grade Adenocarcinoma Located in the Maxillary Sinus

Demet ET�T, Deniz ALTINEL, �mit BAYOL, Ay�a TAN, �zlem T�REL�K, �brahim �UKUROVA — 2012-09-01

Polymorphous low-grade adenocarcinoma is a malignant epithelial tumour with low metastatic rate and infiltrative growth pattern. The palate is the most common site. Paranasal sinuses are uncommon venues for polymorphous low-grade adenocarcinoma. Here, we report a polymorphous low-grade adenocarcinoma case of the maxillary sinus, a very rare location. Although it is a low grade malignancy, progression may develop after a long time. Therefore, polymorphous low-grade adenocarcinoma should be kept in mind in the differential diagnosis even in rare sites in the head and neck.

Adenocarcinoma Arising in Warthin Tumor of the Parotid Gland

Hamide SAYAR, H�seyin �ZTARAK�I, �a�da� SAYAR, �ule A�IRBA� — 2012-09-01

Warthin tumor is a well-defined benign salivary gland neoplasm consisting of both epithelial and lymphoid components. The tumor is the second most common benign tumor next to pleomorphic adenoma. We present a case of adenocarcinoma, not otherwise classified, arising in unilateral Warthin tumor of the parotid gland in a 63-year-old male patient. Carcinomas arising in or from the epithelial component of a preexisting parotid Warthin tumor are rare and differential diagnosis of metastasis from an adenocarcinoma in Warthin tumor is important. The patient underwent a complete and thorough work-up, and no other primary malignant lesion was found. No other primary malignant lesion had manifested at the last one year follow-up period.

Pulmonary Alveolar Microlithiasis with Homozygous c.316G>C (p.G106R) Mutation: A Case Report

2012-09-01

Pulmonary alveolar microlithiasis is characterized by the presence of calcospherites in alveolar spaces. Sporadic cases are more common, but the disease also presents in an inherited familial form. The greatest number of reported cases is from Europe and especially Turkey. We present a 43-year-old female with complaints of dyspnea for many years. She had a suspicious familial history of pulmonary alveolar microlithiasis. The surgical lung biopsy specimen appeared gritty and firm. Histological sections showed diffuse involvement of the lung parenchyma by innumerable tiny calcospherites. Genetic studies showed a homozygous c.316G>C (p.G106R) mutation in exon 4 and confirmed the diagnosis of pulmonary alveolar microlithiasis. The present report aims to contribute to the literature with a pathologically and genetically confirmed new case to add insight into the etiology of this rare disease. This case confirms an autosomal recessive inheritance and does not support the role of non-genetic and other factors in the pathogenesis of pulmonary alveolar microlithiasis.

Primary Lymphoepithelioma-Like Carcinoma of the Lung: Report of a Rare Case and Review of the Literature

2012-09-01

Primary lymphoepithelioma-like carcinoma of the lung is a rare type of non-small cell lung carcinoma. In this study, we aimed to present a 62-year-old smoker male with a primary lymphoepithelioma-like carcinoma of the hilar region of the left lung. The patient underwent left pneumonectomy and no adjuvant therapy was given. There were no other abnormalities on whole body PET/CT scan including the nasopharyngeal region. The patient showed seropositivity for EBV IgG but immunohistochemistry and PCR amplification studied on paraffin-embedded tissue sections of the tumor failed to show any sign of EBV infection within the tumor cells. He is alive and disease-free four months after the operation. Although primary lymphoepithelioma-like carcinoma of the lung is usually reported in young females with no history of tobacco use and the tumor cells are infected with EBV, it may rarely be seen in elderly males with a history of tobacco use and the tumor cells not infected with EBV.

Intussusception of the Appendix Induced by Sessile Serrated Adenoma: A Case Report

�mran YILDIRIM, �smet �ZAYDIN, Havva ERDEM, Ali Kemal UZUNLAR — 2012-09-01

Intussusception of the appendix vermiformis is a rare condition. It occurs mainly in infants and children. Here, we report an intussusception case that occurred in a 65-year-old male presenting with repeated periumbilical pain, nausea, vomiting and febrile sensation. The appendix was seen to be intussuscepted at laparoscopy. The invaginated segment was reducted and simple appendicectomy was carried out. Histopathologic examination revealed a sessile serrated adenoma at the wall of the appendix, suggesting it as the cause of the intussusception.