Turkish Journal of Pathology - 2011; 27(3)

EDITORIAL

Kutsal Y�R�KO�LU, �lhan TUNCER — 2011-09-01

EDITORIAL

Kutsal Y�R�KO�LU, �lhan TUNCER — 2011-09-01

Hamdi Suat-Hulusi Beh�et: An Affective Trainee - Tutor Relationship from Turkish Medical History

G�lay SATAR, Selim KADIO�LU — 2011-09-01

This article is about the trainee - tutor relationship between two eminent figures of Turkish medical history, namely Hamdi Suat Aknar (1873-1936) and Hulusi Beh�et (1889-1948). Hamdi Suat Aknar was the pioneer of modern pathology in Turkey. Alongside his scientific achievements, he took educational activities seriously and exerted a great effort to train his students as proficient clinicians and physicians with good command of histology and histopathology. Hulusi Beh�et met Hamdi Suat Aknar when he was a medical student and did not lose his contact with him ever since, even after becoming an internationally well-known scientist. Hulusi Beh�et mentioned his tutor with gratitude at every opportunity and wrote a necrology full of sincerity after his death.

β-Catenin Expression in In Situ and Infiltrative Ductal Carcinomas of the Breast

Tuba KARABACAK, Reyhan E��LMEZ, Rabia BOZDO�AN ARPACI, Ebru SER�NS�Z PFEIFFER — 2011-09-01

Objective: Cascades that include β-catenin that has a function in adhesion and interaction with tumor suppressor genes such as APC have important roles in many neoplasms. The aim of the current study was to confirm the effect of the β-catenin pathway in breast tumor carcinogenesis and invasion. Material and Method: Polyclonal rabbit β-catenin antibody was applied to 52 cases of infiltrative ductal carcinoma and 28 cases of ductal carcinoma in situ using the Avidin Biotin complex immune peroxidase method. The intensity and cellular localization of immunostaining were evaluated and compared. Results: β-catenin immunoreactivity similar to that of normal epithelium was observed in 7 (8.75%) cases and weak or absent β-catenin expression was noted in 45 (56.25%) infiltrative ductal carcinoma cases. β-catenin expression was strong in 5 (6.25%) cases of ductal carcinoma in situ but weak or absent immunostaining was observed in 23 (28.75%) cases. Membranous β-catenin immunoreactivity was observed in 18 (22.5%) cases of infiltrative and 14 (%17.5) cases of ductal carcinoma in situ. Cytoplasmic immunostaining or complete absence of staining was noted in 34 (42.5%) cases of infiltrative and 14 (17.5%) cases of ductal carcinoma in situ. Conclusion: Similar quantitative and qualitative changes in β-catenin expression were detected in a considerable proportion of in situ and infiltrative ductal carcinomas in the current study. These findings suggest that β-catenin plays a role in the carcinogenesis of infiltrative ductal carcinoma but similar expression patterns of β-catenin in infiltrative and in situ ductal carcinomas indicates that changes in β-catenin expression occur early in carcinogenesis.

Factors Predicting Non-Sentinel Lymph Node Involvement in Sentinel Node Positive Breast Carcinoma

2011-09-01

Objective: In routine practice, axillary lymph node dissection is performed in early invasive breast cancer patients with positive sentinel node biopsy. However, sentinel node is the only involved axillary node in 40-70% of patients, and determining factors that predict axillary non-sentinel node involvement will therefore prevent unnecessary axillary lymph node dissection and decrease morbidity. Material and Method: In this study, 119 invasive breast cancer patients with sentinel node metastasis who underwent axillary lymph node dissection between 1998-2009 at our institution were studied. Primary tumor characteristics and features of the metastatic tumors in sentinel nodes, such as microanatomic location, size of metastasis, and the ratio of metastatic tumor area to the total sentinel node area were evaluated. Student's t-test and multivariate logistic regression were used for statistical analysis. Results: The mean age of the patients was 50.7 years (28-80). Forty-three patients (36%) had invasive ductal and 25 patients (21%) had invasive lobular carcinoma. Most of the patients had either pT1 (44%) or pT2 (54%) tumors. Fifty-four patients (45%) had no further positive nodes in the axilla. The metastatic deposits in the sentinel node were subcapsular in 16 patients (13%). The percent area of sentinel node occupied by tumor (p<0.001), number of sentinel nodes (p=0.041), and microanatomic location of metastatic tumor (p=0.002) were significantly associated with non-sentinel node metastasis in univariate analysis. The percent area of sentinel node occupied by tumor (p<0.001) and number of sentinel nodes (p=0.033) remained significantly associated with non-sentinel node involvement in multivariate analysis. Conclusion: In patients with invasive breast cancer and positive sentinel node, area percent of sentinel node occupied by tumor, and the number of sentinel nodes removed are independently predictive of non-sentinel node involvement.

Correlation of HER 2/neu Gene Amplification with Immunohistochemistry and Other Prognostic Factors in Breast Carcinoma

2011-09-01

The purpose of this study was to determine relationship between HER-2/neu status and estrogen receptor, progesterone receptor, grade and age by comparing fluorescence in situ hybridization and immunohistochemistry. One hundred invasive breast carcinomas were reviewed and fluorescence in situ hybridization analysis was performed in all cases. Immunohistochemical scores showed a perfect concordance with fluorescence in situ hybridization amplification ratios (p<0.0001). The results indicated a significant correlation between HER-2/neu and grade, but an inverse relationship between HER-2/neu and hormone receptors. In women aged ≤45 years, an inverse relationship between HER-2/neu and progesterone receptor was found and no association was noted between HER-2/neu and other factors. In women aged >45 years, the results indicated a significant correlation between HER-2/neu and grade, and there was an inverse relationship between HER-2/neu and hormone receptors.

Vascular Endothelial Growth Factor Expression in Low and High Grade B-cell Non-Hodgkin's Lymphomas

�rem Hicran �ZBUDAK, Bahar AKKAYA, G�lten KARPUZO�LU — 2011-09-01

Objective: Angiogenesis is critical for the development of tumors. Although vascular endothelial growth factor is a well-known proangiogenic factor, its impact on B-cell non-Hodgkin's lymphoma is not clear. The aim of this study is to evaluate vascular endothelial growth factor expression in subtypes of B-cell non-Hodgkin's lymphoma. Material and Method: Fifty-one patients with diagnoses of low and high grade B-cell non-Hodgkin's lymphoma were randomly selected and proper slides were immunostained with vascular endothelial growth factor antibody. The percentage of positive cells was recorded as the vascular endothelial growth factor score. A cut-off point was determined by using the median vascular endothelial growth factor score of all cases. The patients were subclassified as negative, weak or strong positive according to this cut-off point. Results: The study cohort included 26 women and 25 men, aged 5 to 82 years. The number of low-grade patients diagnosed as grade I follicular lymphoma and small lymphocytic lymphoma were 7 and 6; while the number of high grade patients diagnosed as diffuse large B-cell lymphoma and Burkitt's lymphoma were 29 and 9, respectively. Twenty-five patients (49.0%) showed strong and 10 patients (19.6%) showed weak vascular endothelial growth factor immunoreactivity, while 16 patients (31.4%) showed no staining. No statistically significant difference was found for vascular endothelial growth factor expression between subtypes of B-cell non-Hodgkin's lymphoma; as well as between low and high grade groups. Conclusion: Further studies in large and specific series are needed to determine the role of vascular endothelial growth factor receptor related pathways in the development and progression of B-cell non-Hodgkin's lymphomas.

Multicystic Dysplastic Kidney: Four-Year Evaluation

Berna AYTA�, �brahim �EH�TO�LU, Hakan VURUSKAN — 2011-09-01

Objective: Multicystic dysplastic kidney is a relatively common developmental abnormality in infants and children. Additional abnormalities like vesicoureteral reflux, ureteropelvic junction obstruction, and ureterovesical junction obstruction may accompany multicystic dysplastic kidney. In this article, we reviewed the pathogenesis, diagnosis, associated urinary tract anomalies and results of management of multicystic dysplastic kidney in the light of the literature. Material and Method: We retrospectively assessed 20 children with unilateral multicystic dysplastic kidney between January 2005 and December 2009. Mean duration of follow-up was 35 � 8.7 months. All children with multicystic dysplastic kidney underwent nephrectomy. Patient characteristics, the pathology findings, associated urinary tract anomalies and results of management were reviewed. Results: Abdominal ultrasound, voiding cystourethrography and renal scintigraphy revealed vesicoureteral reflux in 3 (15%) children, ureteropelvic junction obstruction in 3 (15%) children, and a duplex system in the contralateral kidney in 1 (5%) child. Blood pressure values, serum urea, creatinine and urinalysis were within normal range in all children during follow-up. Conclusion: A conservative approach to children with multicystic dysplastic kidney has been advocated, but surgical removal is also another management modality on the basis of risk of hypertension, mass effect, potential for malignant change, and cost of repeated ultrasound examination.

Morphological Evaluation of Parathyroid Adenomas and Immunohistochemical Analysis of PCNA and Ki-67 Proliferation Markers

Ebru DEM�RALAY, G�l�m ALTACA, Beyhan DEM�RHAN — 2011-09-01

Objective: Parathyroid adenomas are the most common cause of primary hyperparathyroidism. Biological studies have shown that parathyroid adenomas are monoclonal proliferations. Up to date, five cell types have been identified in normal parathyroid tissues; chief cells, vacuolated chief cells, dark chief cells, oxyphil cells and transitional oxyphil cells. Most parathyroid adenomas are predominantly composed of chief cells. In this study, we aimed to indicate the relationship between the predominant cell type in parathyroid adenomas and proliferating cell nuclear antigen, Ki-67 antigen, and serum parathormone levels and the gland weight. Material and Method: 15 cases who had a diagnosis of parathyroid adenomas were included in the study. Histopathologically, the predominant cell type was determined in all the cases. Paraffin blocks were immunohistochemically stained with proliferating cell nuclear antigen and Ki-67. Results: The average parathormone level of the cases was 239.52 � 36.61 pg/ml before surgery. Mean gland weight was 1.69 � 0.49 g. Two of the cases showed atypical adenoma characteristics. The predominant cell type was vacuolated chief cell. Immunohistochemical investigation showed that the mean average Ki-67 index value was 4.26 � 0.86%. The mean proliferating cell nuclear antigen index was 93.20� 45.72/10�. There was a meaningful relationship between gland weights and serum parathormone levels. There was no meaningful relationship between predominant cell types and serum parathormone levels, proliferating cell nuclear antigen index, and Ki-67 index. The chief cell was identified as the predominant cell type. Conclusion: It can be concluded that parathyroid adenomas come into existence as a result of neoplastic proliferation of chief cells, especially vacuolated chief cells.

General Evaluation of Hepatectomy and Hepatocellular Carcinoma Cases

2011-09-01

Objective: Although the clinical and histopathological findings of hepatocellular carcinoma are well described, there are few national studies. In this study, we aimed to investigate the relationship between these findings in total or partial hepatectomy specimens in our series. Material and Method: We first collected 190 cases of total or partial hepatectomies performed because of hepatocellular carcinoma, cirrhosis or other disorders from the archives of Pathology. After re-examining the histopathological and clinical features such as age, gender and etiology, the relationship between them and serology results were statistically analyzed using the chi square and Multiple Comparison Tests. Results: Among 190 cases, there were 168 (88.5%) total and 18 (9.5%) partial hepatectomies and 4 (2%) tumorectomy or metastasectomy cases. After gross and microscopic examination, 170 (89.5%) cases had a diagnosis of cirrhosis, 85 (44.7%) hepatocellular carcinoma, 3 parasitic cyst, 7 metastasis, 1 hepatoblastoma, 1 hepatocellular adenoma, 2 cholangiocarcinoma, 2 Budd Chiari Syndrome, 1 focal nodular hyperplasia, 1 cavernous hemangioma, and 2 acute fulminant hepatitis. Among the hepatocellular carcinoma cases, 53 had Hepatitis B virus, 15 Hepatitis C virus , 3 Hepatitis B virus and Hepatitis C virus, and 3 Hepatitis B virus and Hepatitis delta virus etiology, while 6 were alcoholic and 4 were due to other causes. Among cirrhosis patients, 84 (49.4%) had hepatocellular carcinoma. The male to female ratio of hepatocellular carcinoma cases was 74/11. The mean age was 55 and the median age 56.7. Conclusion: The results of this study demonstrated that the most common hepatic disorder was cirrhosis due to Hepatitis B virus in the hepatectomy specimens of our series that mostly consisted of total hepatectomies performed for transplantation where 50% had hepatocellular carcinoma.

Cancer Statistics of ��rnak City

Korkut BOZKURT, Sevda SERT BEKTA�, Nurg�l DO�RU — 2011-09-01

Objective: The aim of this study is to investigate the cancer incidence and distribution in the province of ��rnak by examining the two years data of two pathology laboratories in ��rnak and Cizre State Hospital. Material and Method: One hundred fifty two cases of cancer diagnosed between January 2009 and December 2010 were reviewed retrospectively from the archive. Types of cancer, age and gender profile of the patients with the pathology reports were obtained. Results: Sixty-two patients (40.78%) were male and 90 (59.22%) were female. The male to female ratio was 0.68. The youngest patient was 14, the oldest patient was 96 years old, and the mean age was 54.81. Fifty-nine patients (38.81%) were under the age of 50 and 93 (61.19%) were aged 50 and over. In order of frequency, the most common cancer was skin cancer (43.42%), followed by thyroid cancer (14.47%), colorectal cancers (9.86%), breast cancer (21.9%), gastric cancer (5.26%), esophageal cancer (3.28%), soft tissue, bladder and appendix cancers (1.97%), lung and cervical cancers (31.1%) and nasal cavity, gall bladder, testicular, liver, ovary, endometrium, prostate, kidney and lymph node cancer (0.65%). The five most common cancers were skin, colorectal, stomach, thyroid, esophagus cancer in men and skin, thyroid, breast, colorectal, esophagus cancer in women. Basal cell carcinoma was the most common skin cancer. Conclusion: Skin cancers and thyroid and colorectal cancers are common in our region. Skin cancers are the most common cancers in both genders.

Pathology Laboratories Productivity Evaluation in Turkey

Kutsal Y�R�KO�LU, Sarp �NER, Fevzi HARORLU, Alp USUB�T�N — 2011-09-01

Objective: Efficiency criteria and automation in pathology laboratories have been set in a limited number of studies usually originated from the United States. A questionnaire has been prepared to determine the situation and define the criteria for adaptation in our country. Material and Method: The survey was sent to all pathology laboratories and, 302 responded. The survey questionned of pathology laboratories efficiencies, staff workloads, methods applied, devices used, and physical conditions. Work flow productivity was obtained by dividing the annual number of blocks to working hours multiplied by the number of technicians. The hospitals were categorized to 3 groups according to providing training or not and privacy, and to 4 groups according to the annual biopsy numbers. The data entered through the SPSS 16.0 statistical package program, analysis of distribution criteria, significance of the difference between means tests were used. Results: The annual biopsy numbers were significantly higher in education units, but below the limit of productivity levels for all laboratories. The device hardware and automation correlated with annual biopsy numbers. However, the laboratories of limited capacity have redundant automation. Histochemical and immunohistochemical staining numbers were high. Liquid-based cytology techniques were used more significantly in private hospitals. Archiving times were not standard. A serious shortage of working space in service hospitals was noted. Work flow productivity in education units was at the border, and low in other units. Conclusion: All pathology laboratories in our country should define and improve their productivities. Formalizing of archiving times is very important for future malpractice lawsuits.

Chediak-Higashi Syndrome – A Report of Two Cases with Unusual Hyperpigmentation of the Face

2011-09-01

Chediak-Higashi syndrome is a rare autosomal recessive disorder due to a qualitative defect in leucocyte function characterized clinically by partial oculocutaneous albinism, recurrent bacterial infections, photophobia etc. The diagnostic feature is the presence of abnormal giant intracytoplasmic granules in neutrophils and their precursors. Here we report this syndrome in two siblings who presented with an unusual hyperpigmentation of the face and extremities.

Rapidly-Growing Nodular Pseudoangiomatous Stromal Hyperplasia of the Breast: Case Report

Nuket EL�YATKIN, Ba�ak KARASU, Elif SELEK, Yavuz KE�EC�, Hakan POSTACI — 2011-09-01

Pseudoangiomatous stromal hyperplasia is a benign proliferative lesion of the mammary stroma that rarely presents as a localized mass. Pseudoangiomatous stromal hyperplasia is characterized by a dense, collagenous proliferation of the mammary stroma, associated with capillary-like spaces. Pseudoangiomatous stromal hyperplasia can be mistaken with fibroadenoma on radiological examination or with low-grade angiosarcoma on histological examination. Its main importance is its distinction from angiosarcoma. The presented case was a 40-year-old woman who was admitted with a rapidly growing breast tumor. Physical examination revealed an elastic-firm, well-defined, mobile and painless mass in her right breast. Mammograms revealed a 6.7x3.7 cm, lobulated, well-circumscribed mass in her right breast but no calcification. Sonographic examination showed a well-defined and homogenous mass, not including any cyst. Based on these findings, a provisional diagnosis of fibroadenoma was made. Considering the rapid growth history of the mass, tumor excision was performed. The excised tumor was well demarcated and had a smooth external surface. Histological examination revealed the tumor to be composed of markedly increased fibrous stroma and scattered epithelial components (cystic dilatation of the ducts, blunt duct adenosis). The fibrous stroma contained numerous anastomosing slit-like spaces. Isolated spindle cells appeared intermittently at the margins of the spaces resembled endothelial cells. Immunohistochemical staining showed that the spindle cells were positive for CD34 and negative for Factor VIII-related antigen. The lesion was diagnosed as nodular pseudoangiomatous stromal hyperplasia.

Cystic Fibroadenoma of the Breast: A Case Report

Merih G�RAY DURAK, Ilg�n KARAMAN, T�lay CANDA, P�nar BALCI, �mer HARMANCIO�LU — 2011-09-01

Fibroadenoma is the most common breast tumor in adolescent and young women. Fibroadenomas that consist of sclerosing adenosis, papillary apocrine metaplasia, epithelial calcifications, and/or cysts greater than 3 mm are considered as complex fibroadenoma. The relative risk of developing breast cancer in patients with complex fibroadenoma is increased, compared to women with noncomplex fibroadenoma. Extensive cystic degeneration in a fibroadenoma, so called “cystic fibroadenoma” is very rare. Herein, we present a case of such a lesion in a 43-year-old female who has been on follow-up for fibrocystic changes of the breast, and discuss both radiological and histopathologic differential diagnosis of this lesion with other cystic lesions of the breast, including cystic papilloma. The patient is free of disease after 17 months of clinical follow-up.

Cotyledonoid Leiomyoma of Uterus: A Case Report

2011-09-01

The diagnosis of uterine smooth muscle tumors is usually not difficult. Occasionally, benign tumors with an unusual growth pattern may cause some diagnostic confusion for pathologists who had not experienced such a tumor before. A fifty-one year old female patient had admitted to our gynecology outpatient clinics with abnormal uterine bleeding (menorrhagia) and undergone a surgery with a diagnosis of pelvic mass. A neoplasm consisting of spindle cell nodules with prominent hydropic degeneration was observed at pathological examination. Tumor cells were positive for vimentin, desmin and smooth muscle actin at immunohistochemical evaluation. Cotyledonoid leiomyomas are rare benign smooth muscle tumors of uterus which are recently defined in the literature. In this article we report a case of cotyledonoid leiomyoma of uterus with an exophytic growth pattern in the serosa and did not contain an intramural dissecting component.

Hashimoto's Disease in a Bilateral Benign Cystic Ovarian Teratoma: A Case Report

Rupinderjeet KAUR, Jasbir SINGH, Anureet KAUR, Rimpi BANSAL, Satish SHARMA — 2011-09-01

A wide array of tissues derived from all the three germinal layers is seen in ovarian teratomas. Among these, thyroid tissue is present in 10% cases of all mature cystic teratomas. We report this case of Hashimoto's thyroiditis in a clinically euthyroid patient who tested positive for antithyroid peroxidase antibodies in spite of normal thyroid hormone profile. While the histological features of several disorders of thyroid tissue may be discovered, Hashimoto's thyroiditis is extremely rare finding in ovarian teratomas.

Aspergillus Colonization of an Echinococcal Cyst Cavity: Case Report

Duygu G�REL, Aydanur KARGI, Mehtat �NL�, Ayd�n �ANLI, Erkan YILMAZ — 2011-09-01

Although lungs are common sites for the occurrence of saprophytic or invasive mycosis as well as hydatid cyst, aspergilloma within a hydatid cyst is a rare occurrence. A 36-year-old immunocompetent male presented with hemoptysis episodes of about 1 year duration. Chest X-ray revealed a smooth countered mass lesion located in the upper part of lower lobe of left lung. Surgical enucleation of the cyst wall was performed. Microscopic examination showed that the laminated membranes of hydatid cyst were invaded by septated fungal hyphea oriented with acute angles consistent with aspergillus. Herein, we report such a unique coexistence of hydatid cyst and aspergilloma, and emphasize possible complications depending on the immunostatus of the patient, if the aspergillus colonization is unnoticed in resected cystectomy material.

Germ Cell Tumor Located in the Midline of the Anterior Neck

Tatyana PIRDOPSKA, Ivan TERZIEV, Sv. HRISTOVA, W. MLADENOVSKY, R. PETKOV — 2011-09-01

Primary germ cell tumors involving midline of the anterior neck are extremely rare. Here we report a 68-year-old male who was operated due to a mass lesion in the anterior neck with infiltration of the isthmus of the thyroid gland. Histopathological examination revealed a germ cell tumor with extragonadal localization in the anterior neck infiltrating the isthmus of the thyroid gland.

Auricular Angioleiomyoma: A Case Report

Rana ��T�L, Harun �IRALIK, Asiye G�L, Hamide SAYAR — 2011-09-01

Angioleiomyoma (vascular leiomyoma or angiomyoma) is a rare, benign smooth muscle tumor that originates in the tunica media of blood vessels. These tumors may be found anywhere in the body. They usually occur in the lower extremity. Auricular angioleiomyoma is very rare, and only a few cases have been reported. We describe here a 38-year-old male patient with angioleiomyoma on the left auricular helix.