ASSOCIATION BETWEEN HASHIMOTO'S THYROIDITIS AND PAPILLARY THYROID CANCER: A SINGLE CENTER EXPERIENCE.

Purpose: To investigate the association between papillary thyroid cancer (PTC) and Hashimoto's thyroiditis (HT). Design: This study is a retrospective study that conducted during 7 consecutive years with a median 119.5 months follow-up. Subjects and Method: Patients who underwent thyroidectomy in Dokuz Eylül University Hospital during 7 consecutive years were included. Patients' demographics, biochemical, radiological, and pathological results were retrospectively assessed. Results: Four hundred sixty nine patients were evaluated. Among 469 patients who underwent thyroidectomy, 132 (28.1%) were malignant, while 182 patients were diagnosed with HT (38.8%). PTC was ranked first at 92.4% (n: 122). The prevalence of HT was 54.9% in patients with PTC and 33.1% in patients without PTC diagnosis (p<0.001). Younger age and the presence of HT were independently associated with PTC. The presence of HT was associated with increased risk of development of PTC (OR: 2.2, %95 CI: 1.4-3.5, p<0.001) but not with TNM stage or recurrence. Lymph node metastasis at presentation was the strongest predictor of recurrence (OR: 13.9, CI: 3.5-54.6, p<0.001). Conclusions: HT was an independent risk factor for development of PTC. According to our findings, HT patients (particularly with nodular HT) should be observed carefully and thyroid fine needle aspiration biopsy (TFNAB) should be encouraged if necessary.

Immunohistochemical analysis of thyroid follicular neoplasms and BRAF mutation correlation.

BACKGROUND: The accurate diagnosis of benign and malign thyroid tumors is very important for the clinical management of patients. The distinction of thyroid papillary carcinoma follicular variant and follicular adenoma can be difficult. AIM: To investigate the alternative methods like immunohistochemistry and exon 15 in the BRAF gene 1799 T/A mutation analyses for distinguishing thyroid tumors. MATERIALS AND METHODS: We applied immunohistochemical markers; CK19, HMWCK, Galectin-3, HBME-1 and Fibronectin and mutant allele-specific PCR amplification technique was used to determine 1799 T/A mutation within the BRAF gene. Formalin-fixed parafin embedded tissues from 45 surgically total resected thyroids, included 26 thyroid papillary carcinoma follicular variant (FV-TPC), 8 Follicular Adenoma (FA), 6 Minimal invasive follicular carcinoma (MIFC) and 5 Follicular Carcinoma (FC). Statistical Analyses Used: Pearson Chi-Square and Kruskal Wallis tests were performed. RESULTS: There was a positive correlation between FV-TPC and HMWCK, CK 19, HBME1, Galectin 3, fibronectin (P < 0.05), but there was no correlation with FV-TPC and BRAF gene mutation (P > 0.05). HBME-1 and CK 19 stained strong and diffuse positive in FV-TPCs but weak and focal in FAs. CONCLUSION: Our study suggests that morphologic features combined with immunohistochemical panel of HMWCK, CK19, HBME-1, Galectin-3 and fibronectin can help to distinguish benign and malign thyroid neoplasms and FV-TPC from follicular adenomas. BRAF gene 1799 T/A mutation has been non-specific but its detection can be a useful tool combined with immunohistochemistry for diagnosing FV-TPC.

Diffusion-weighted MR imaging: role in the differential diagnosis of breast lesions.

PURPOSE: To evaluate the diagnostic value of magnetic resonance diffusion-weighted imaging (DWI) using apparent diffusion coefficient (ADC) values to the characterization of breast lesions and differentiation of benign and malignant lesions. MATERIALS AND METHODS: Thirty-seven women (mean age, 38 years) with 37 enrolled in the study. DWI and ADC maps in the axial plane were obtained using a 1.5 Tesla MRI device. Mean ADC measurements were calculated among cysts, normal fibroglandular tissue, benign lesions and malignant lesions were evaluated. RESULTS: Out of 37 women, 4 had normally breast MRI findings. The diagnosis of remaining 33 patients with 37 breast lesions were as follows; malign lesions (n = 23), benign lesions (n = 10) and simple breast cyst (n = 4). The ADC values were as follows (in units of 10(-3) mm2/s): Normal fibroglandular tissue (range: 1.39-2.06; mean: 1.61 ± 0.23), benign breast lesions (range: 1.09-1.76; mean: 1.47 ± 0.25), cyts (range: 2.27-2.46, mean: 2.37 ± 0.07) and malignant breast lesions (range: 0.78-1.26, mean: 0.96 ± 0.25). The mean ADC obtained from malignant breast lesions was statistically different from that observed in benign solid lesions (p < < 0.01) and normal fibroglandular breast tissue (p < 0.01). Furthermore, the mean ADC values of benign breast lesions was not statistically different from cyst (p ≥ 0.01) and normal fibroglandular breast tissue (p ≥ 0.01). A ADC value of 1.1 x 10(-3) mm'/s as a treshold value provided differantiation for malign and benign lesions, with a sensitivity of 91.3% and a specificity of 85.7% compared with conventional breast MRI values. CONCLUSION: DWI with quantitative ADC measurements is a reliable tool for differentiation of benign and malignant breast lesions.

Characterization of immunohistochemical markers in triple negative breast carcinomas.

PURPOSE: Triple negative (TN) breast carcinomas (estrogen receptor/ER, progesterone receptor/PR and HER-2/neu negative) constitute 15-25% of all breast carcinomas and have been correlated with aggressive behavior and poor prognosis. Our aim was to describe and characterize the immunophenotype of these tumors in a group of patients from Turkey. METHODS: We used the immunohistochemical markers CK5/6, CK14, EGFR, E-cadherin, p53 and androgen receptor. Formalin-fixed, paraffin-embedded tissues from 51 breast carcinoma patients (36 TN and 15 non TN) were included into this study. RESULTS: The mean values of the distribution of immunohistochemical markers in TN vs non-TN groups were as follows: CK5/6 78.4 vs 5.3%, CK14 84.8 vs 8%, EGFR 87.2 vs 8%, E-cadherin 96.9 vs 53.2%, p53 87.3 vs 7.3% and androgen receptor 89.5 vs 33.3% (all p-values<0.001). CK5/6 stained significantly different in the grade 2 and 3 cases (p=0.035) in the TN group.The other markers demonstrated no significant differences between grades. CONCLUSION: TN breast carcinomas in Turkish patients express basal cytokeratins, and have high levels of p53 compared to non-TN breast carcinomas.

Vitamin D receptor gene polymorphisms and male breast cancer risk in Turkish population.

PURPOSE: Male breast cancer (MBC) is a rare disease. However, as global populace ages, there is a trend for MBC increase. Although its etiology is still unclear, constitutional, environmental, hormonal (abnormalities in estrogen/androgen balance) and genetic (positive family history, Klinefelter syndrome, mutations in BRCA1 and BRCA2) risk factors are already known. One potential target is the vitamin D receptor (VDR). We have investigated whether polymorphisms in the VDR gene are associated with altered MBC risk in a Turkish population. METHODS: We recruited 25 men with known breast cancer and 96 men selected from blood donations. Polymorphic sites in VDR gene ApaI (rs7975232), TaqI (rs731236) and FokI (rs10735810) were determined by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) analysis. RESULTS: The unconditional logistic regression analysis demonstrated no significant association for the VDR ApaI (p=0.70), TaqI polymorphism (p=0.88) and FokI polymorphism (p=0.075). CONCLUSION: Our results do not support potential effects of VDR polymorphisms on MBC risk and possible differential effects of receptor status of the tumor. However, further studies focusing on the influence of polymorphisms and haplotypes on VDR functionality, activity and concentration are needed.

Success of minimally invasive single-gland exploration using the quick intraoperative parathyroid assay.

OBJECTIVE: Using accurate localization techniques and the quick intra-operative parathyroid assay (QPTH), surgery for primary hyperparathyroidism due to a solitary adenoma has moved from the traditional wide bilateral neck exploration to more limited approaches such as minimally invasive single-gland exploration (MISGE) and minimally invasive radio-guided parathyroidectomy (MIRP). This study investigated whether the MISGE could take the place of MIRP with the help of the QPTH. DESIGN: From 2007 to 2009, 56 patients with primary hyperparathyroidism were studied. All patients were pre-operatively investigated by imaging techniques to improve the pre-operative determination of adenomas. Twenty-five patients were in the MIRP group and 31 in the MISGE group. QPTH was routinely measured; a 50% reduction in the QPTH level indicated complete excision. RESULTS: There were no differences in the complication rates, surgical time, anaesthesia time or mean length of hospital stay between the groups. However, total hospital charges were more favourable in the MISGE group with a mean saving of $400 per case. CONCLUSION: This study demonstrates that with the additon of the QPTH, MISGE can be performed as a quick and reliable procedure in correct adenoma removal instead of MIRP. Moreover MISGE achieves the optimal time interval between injection and exploration, reduces the radiation exposure of both patient and surgeon, decreases the cost, and decreases usage of pre-operative imaging and intra-operative equipment.

Promoter methylation and expression changes of CDH1 and P16 genes in invasive breast cancer and adjacent normal breast tissue.

We studied the promoter methylation status and expression levels of P16 and CDH1 genes in breast cancer and their adjacent normal tissues with normal control breast tissues, to correlate with their histopathological parameters. Hundred twenty four samples (tumor and adjacent nonmalignant tissues) from 62 breast cancer patients and 4 normal control breast tissues were included in the study. We used methylation specific PCR to evaluate methylation status and quantitative RT-PCR to measure the gene expression levels. Methylation incidence of P16 gene and CDH1 gene in tumor tissues were 24.2 % and 33.9 %, respectively. CDH1 and P16 gene were not methylated in normal control tissues. CDH1 underexpression is found to be significant in correlation with advanced stage, histologic type, high tumor grade and lymph node involvement. P16 expression is found not to be significantly related with any histopathological parameters. But 60% of cases which overexpresses P16 were estrogen negative, and 40% of them were histologic grade 3. Both P16 and CDH1 had different expression levels in tumor tissues compared to the adjacent normal tissues and in adjacent normal tissues compared to the normal non-tumor tissues.

Synchronous appearance of male breast cancer and pancreatic cancer 15 years after the diagnosis of testicular cancer--report of a case.

The frequency of new neoplastic diseases among patients cured of testicular cancer is higher than in normal population. For these patients, synchronous occurrence of multiple neoplasms is not common. Also, less than 1% of all cases of breast cancer occur in males. We present herein a case having both breast and concurrent pancreatic cancer after being effectively treated for testicular cancer. To the best of our knowledge, this is the first case of synchronous breast and pancreatic cancer in a male patient following testicular cancer. Second cancer is the most severe long-term complication of chemotherapy or radiotherapy for patients with testicular cancer and the possibility of multiple cancers has to be taken into consideration when multiple lesions are present.

A pilot study for human tumor/DNA banking: returned more questions than answers.

A pilot study was performed for setting up the Dokuz Eylül University Breast Tumor DNA Bank (DEUBTB) to facilitate the sharing of tumor DNA/RNA samples and related data from cases collected by collaborators specializing in the breast cancer diseases between 2004 and 2006. The pilot study aimed to provide answers for certain questions on: (1) ethical concerns (informing the volunteer for donating specimen, anonymizing the sample information, procedure on sample request), (2) obtaining and processing samples (technical issues, flowchart), (3) storing samples and their products (storing forms and conditions), (4) clinical database (which clinical data to store), (5) management organization (quality and quantity of personnel, flowchart for management relations), (6) financial issues (establishment and maintenance costs). When the bank had 64 samples, even though it is quite ready to supply samples for a research project, it revealed many questions on details that may be answered in more than one way, pointing that all biobanks need to be controlled by a higher degree of management party which develops and offers quality standards for these establishments.

Effects of locally applied 5-fluorouracil on the prevention of postmastectomy seromas in a rat model.

BACKGROUND: Seroma formation is the most common complication following mastectomy and axillary dissection (AD). Currently available interventions have aimed at obliterating dead space by inducing fibrosis and through various mechanical methods. Here, 5-fluorouracil (5-FU), used as a sclerosing agent for the prevention of seroma formation, was investigated in a rat mastectomy model. METHODS: 20 rats were divided into two groups (5-FU and control). All rats underwent mastectomy and AD. Immediately following the operation, equal volumes of saline and 5-FU were administered under the surgical flaps. One week after the operation, seroma formation and wound-healing processes were evaluated using histopathological and biochemical investigations. RESULTS: 5-FU did not act as a sclerosing agent, yet it was highly effective in preventing seroma formation. The intensity of acute inflammation, vascularity, as well as leukocyte and fibroblast infiltration, were significantly lower in the 5-FU group than the control; the tissue collagen fractions and total seroma collagen contents were found to be similar between the two groups. CONCLUSIONS: The mechanisms underlying seroma prevention by 5-FU are probably related to a decrease in the inflammation and angiogenesis rather than a local fibrotic process. Seroma formation may be due to a prolonged inflammatory phase of wound healing.

Prevention of cyclophosphamide-induced ovarian damage by concomitant administration of GnRHa in mice: a dose-dependent relationship?

OBJECTIVE(S): This experimental study investigates the dose-related effects of cyclophosphamide (Cy) on primordial follicular reserve in young mice, and examines whether the concomitant administration of a gonadotropin-releasing hormone agonist (GnRHa) may protect gonadal reserve, even at different doses of Cy. METHODS: Forty sexually mature virginal Balb/c mice aged five to six weeks were administered different doses (0, 50, 75,100 mg/kg) of Cy. Another 40 animals were treated with increasing doses (0, 50, 75, 100 mg/kg) of Cy in combination with GnRHa. GnRHa treatment was initiated one week prior to chemotherapy and also continued after chemotherapy for one week. The ovaries were removed seven days after Cy administration and the total number of primordial follicles in both ovaries was counted. RESULTS: Primordial follicular destruction occurred at all levels of Cy exposure. There was a positive correlation between increasing doses of Cy and higher proportion of follicular loss (p < 0.0001). GnRHa was not able to protect against the chemotherapy-induced negative effect on primordial follicular count at low doses (50 mg/kg and 75 mg/kg). Mean +/- SD primordial follicle count in the 100 mg/kg Cy-treated group was significantly lower than in the 100 mg/kg Cy + GnRHa treatment group (73.9 +/- 33.1 vs 89 +/- 17.9, p = 0.047). CONCLUSION: Our data suggest a possible ovarian protective effect of GnRHa cotreatment only at high doses of Cy treatment. However, in spite of co-administration of GnRHa, loss of primordial follicular reserve occurred at all doses of Cy in mice.

99mTc sestamibi scintimammography. Screening mammographic non-palpable suspicious breast lesions: preliminary results.

AIM: Investigation of the diagnostic role of technetium-99m methoxyisobutylisonitrile ((99m)Tc sestamibi) scintimammography in non-palpable, suspicious breast lesions described as microcalcification, mass and increased density using mammography. PATIENTS AND METHOD: 35 women with non-palpable breast lesions were enrolled in the study. Anterior, left and right lateral, ipsilateral posterior oblique images were obtained 15 min after the injection of 740 MBq of (99m)Tc sestamibi. All scintigraphic images were evaluated visually and focal increased (99m)Tc sestamibi uptake was accepted as malignant lesion. Breast lesions were classified as microcalcification (13 women), mammographic mass (16 women) and increased density (6 women). Excisional biopsy was performed in all of them irrespective of the scintigraphic results. RESULTS: The focally increased (99m)Tc sestamibi uptake was seen in 11 breast lesions with malignant lesions and in 4 breast lesions with benign lesions. The diffuse uptake of (99m)Tc sestamibi was seen in 18 breast lesions with benign lesions and 2 breast lesions with malignant lesions. There was no false positive result of (99m)Tc sestamibi in microcalcification group and there was no false negative result of the mammographic mass and increased density groups. CONCLUSION: Scintimammography might be a complementary method in decision making for the non-palpable, suspicious breast lesions that were evaluated as microcalcification, mass and increased density mammograpically.

Comparison of mammographic and sonographic findings in typical and atypical medullary carcinomas of the breast.

AIM: The aim of this study was to describe the contribution of mammographic and sonographic findings to the discrimination of typical and atypical histopathologic groups of medullary carcinomas of the breast. MATERIALS AND METHODS: Imaging findings were retrospectively assessed in 33 women with medullary carcinomas (15 typical medullary carcinomas and 18 atypical medullary carcinomas) identified during pre-operative mammography. Twenty-nine of these women also had ultrasound and these findings were reviewed. RESULTS: Mammography showed a well circumscribed mass in 10 of the 15 (67%) typical medullary carcinomas and in four of the 17 (24%) atypical medullary carcinomas (P < 0.02). One small tumour in a woman with atypical medullary carcinoma was missed on mammography and was shown only on sonography. Sonographically, an irregular margin surrounding the whole mass or part of it was seen in three out of 14 (21%) patients with typical medullary carcinoma and in nine out of 15 (60%) patients with atypical medullary carcinomas (P < 0.05). Posterior acoustic shadowing was more often observed in the typical medullary carcinoma group than in atypical medullary carcinoma and the difference was found to be statistically significant (P < 0.05). None of the other mammographic and sonographic findings were sufficiently characteristic to allow for a differentiation between two groups. CONCLUSION: When typical medullary carcinomas were compared with atypical medullary carcinomas according to imaging features, they tended to be well circumscribed masses on both mammography and sonography, and a posterior acoustic shadow was not found on sonography. However, the imaging findings in these two subgroups often resembled each other and histopathology will always be required to confirm the diagnosis.

Bilateral breast involvement in Sézary syndrome.

Cutaneous T-cell lymphoma is a term used for mycosis fungoides and Sézary syndrome, the distinct clinical entities where the skin is the primary organ of involvement. Sézary syndrome is the leukemic variant of mycosis fungoides, presenting with generalized erythroderma, lymphadenopathy, and atypical cells (the Sézary cells) in the peripheral blood and bone marrow. The dissemination of cutaneous T-cell lymphoma may occur with no exception of the organs; however, no prior report exists about the Sézary syndrome secondarily involving the breasts. We report the clinical and radiological findings of bilateral breast involvement in a case of Sézary syndrome.

Ossified thoracic spinal meningioma in childhood: a case report and review of the literature.

Spinal ossified meningiomas are extremely rare. This is a report of a study on a 15-year-old boy with thoracic spinal ossified meningioma. The meningioma was resected totally. Histopathological examination revealed a transitional meningioma (psammomatous+meningothelial). Immunohistochemically, Ki 67 antibody was applied but no positive staining was present. The surgical and pathological aspects of spinal ossified meningiomas were reviewed.

Curschmann's spirals in cyst fluid associated with a teratoma of the ovary. A case report.

BACKGROUND: Curschmann's spirals, first described more than 100 years ago, are common in cytologic specimens from the respiratory tract and have also been observed in cervical smears, urine, and peritoneal and pleural effusions. No simple theory can explain the exact mode of spiral formation, which is presumed to be a complex physical and biochemical phenomenon. CASE: A 29-year-old woman, gravida 2, para 2, underwent right ovarian cyst excision after an abdominal ultrasound examination revealed a cystic mass of the right ovary. Histologically, the cyst was an immature cystic teratoma containing respiratory epithelium with mucous glands in the submucosa. Cytologic examination of the cyst fluid showed the presence of Curschmann's spirals. CONCLUSION: To the best of our knowledge, the formation of Curschmann's spirals associated with an immature cystic teratoma has not been previously reported. In this situation, the presence of spirals could be explained by formation from mucus normally found in that environment.

Quantification of tumor cellularity and mitotic index in invasive ductal carcinoma of the breast.

OBJECTIVE: To evaluate the use of stereologically estimated tumor cell counts in the mitotic index as well as to investigate its correlation with the currently used method and test the reproducibility of the method. STUDY DESIGN: The stereologic method described by Simpson et al was used to estimate tumor cellularity in 50 invasive ductal carcinomas. Mitotic counts were also performed, and the mitotic index was calculated by the use of estimated tumor cell counts. Estimated cell counts and the mitotic index calculated were compared statistically with the actual cell counts and the traditional mitotic grades, respectively. Interobserver reproducibility of the method was also tested. RESULTS: Stereologically estimated tumor cell counts had a good correlation with actual cell counts (r = .891, P < .001). Besides, the mitotic indices calculated with tumor cell counts (calculated with both estimated and actual cell counts) in the denominator of the fraction of the mitotic index were in agreement with the currently used method (P < .01 for both). There was no statistically significant difference between the counts of two observers (P = .068). CONCLUSION: The suggested method, considering tumor cellularity as an influencing factor, was practical, reproducible and in agreement with the traditional method. This method should be studied in a large group of patients with follow-up data to determine the threshold values for different grades and determine its prognostic value during the disease course.

Familial arthropathy with camptodactyly: reports of two families.

Familial association of congenital camptodactyly and arthropathy without evidence of concurrent inflammation has an autosomal recessive pattern of inheritance. We describe four children born to consanguineous parents in two families with congenital camptodactyly and polyarthropathy which were misdiagnosed and treated as juvenile rheumatoid arthritis (JRA) for some time. The siblings in the second family also had fibrosing pleuritis. Histopathological examination of the synovial tissues of the children in the first family revealed synovial hypertrophy and presence of multinucleated giant cells with minimal inflammation and vasculitis. On the other hand, prominent fibrosis with no inflammation was present in the synovial tissue of the elder boy in the second family. Thus, while the children in the first family had the phenotypic characteristics of congenital familial hypertrophic synovitis, the latter siblings probably represent a form of the familial fibrosing serositis.

BRCA1, C-erbB-2, and H-ras gene expressions in young women with breast cancer. An immunohistochemical study.

Young age does not seem to be directly related to the aggressiveness of the disease among patients with breast cancer. Identification and analysis of the alterations in a susceptibility gene expression in breast cancer occurring in young women may allow identification of those patients in whom tumors will show an aggressive clinical course. The purpose of the present study was to evaluate the association of BRCA1, H-ras, and c-erbB-2 gene expression with clinicopathologic parameters of prognosis in breast cancer. Formalin-fixed, paraffin-embedded tissue from 35 patients with breast cancer younger than 35 years were immunohistochemically stained for BRCA1, H-ras, and c-erbB-2 expression with monoclonal antibodies. For each antibody, immunoreactivity was assessed by a semiquantitative scoring system. Each case was also graded according to the modified Bloom-Richardson criteria and evaluated for Ki-67 labeling index, hormonal status, tumor size, distant metastasis, and axillary lymph node involvement. Strong expression of c-erbB-2 and H-ras were observed in 9 cases (25.7%) and 13 cases (37.2%), respectively. Loss of BRCA1 expression was found in five cases (14.3%). Statistical analysis showed that loss of BRCA1 expression was significantly associated with higher Ki-67 labeling index and greater tumor size. In addition, stronger H-ras expression was significantly associated with lymph node involvement and distant metastasis. However, c-erbB-2 immunoreactivity did not show statistical significance with any prognostic parameters. We conclude that, although care must be taken not to overstate the importance of our results in view of the lack of information on clinical outcome, alterations in BRCA1 and H-ras gene expression might be of prognostic importance because of the role of H-ras protein on metastatic behavior and the role of BRCA1 protein on tumor growth. However, c-erbB-2 expression seems to be of no importance in the prognosis of breast cancer occurring in young women.