PURE vs. mixed clear cell ovarian carcinomas: Is there any impact on survival?

OBJECTIVE: Our primary aim in this study is to define the clinical characteristics of patients with clear-cell ovarian carcinoma and evaluate the prognostic factors affecting survival. STUDY DESIGN: Records of 85 patients, operated between 2000 and 2018, for an adnexal mass and whose final pathology reported clear cell ovarian carcinoma were reviewed. The study considered demographic data, clinical characteristics of the patients, as well as pure and mixed-type clear cell histology. The patients' follow-up time, disease-free and overall survival recorded. The primary outcomes were disease-free survival (DFS) and overall survival (OS). RESULTS: The median age of the patients at diagnosis was 52. In 64.7 % of the cases, clear cell histology was pure, while the others (35.3 %) were mixed. Patients with ovarian endometriosis constituted 27.1 % of the whole population. The median OS for the entire population was 92 months (95 %CI:72-124). On univariate and multivariate analyses, advanced age was found to have a significant independent impact on OS and DFS (p < 0.05) and, was associated with a worse prognosis. Also, the multivariate analyses showed that the presence of endometriosis has a significant independent impact on OS (p < 0.05). When examining the relationship between the histological origin (mixed vs. pure) and 5-year survival, the mixed type showed longer OS and DFS rates (76.8 % vs. 69.8 %, 61.5 % vs. 53.8 %), the difference was not statistically significant (p > 0.05). CONCLUSION: This retrospective study showed that although mixed type histological origin was associated with higher OS and DFS rates compared to pure type in patients with CCOC, the difference was not statistically significant. Advanced age and the presence of endometriosis was found to have a significant independent effect on OS and DFS and was associated with a worse prognosis. Overall, this study provides useful insights into the clinical characteristics of patients with CCOC and identifies important prognostic factors affecting survival.

Prognosis-related novel immunostaining pattern for programmed cell death ligand 1 and prognostic value of tumour-infiltrating lymphocytes in triple-negative breast cancer.

This study aims to determine the prognostic significance of programmed cell death ligand 1 (PD-L1) expression and tumour-infiltrating lymphocytes (TILs) in triple- negative breast cancer (TNBC). PD-L1 expression and TIL percentage were determined in TNBCs that did not receive neoadjuvant therapy. The relationship between PD-L1 expression and the percentage of TILs with survival was investigated. The presence of intratumoural PD-L1-positive tumour-infiltrating immune cells (TIICs) in tumours with ≥ 1% PD-L1 expression was identified as a new PD-L1 evaluation parameter. The presence of intratumoural PD-L1-positive TIICs as a new parameter in PD-L1-positive cases increased overall survival. The percentage of TILs increased in both overall and distant metastasis-free survival (p = 0.040 and p = 0.006, respectively). As a result, it was found that the risk of death was increased 5.18-fold (p = 0.013) in patients without intratumoural PD-L1-positive TIICs. This risk of death was calculated to be 5.40-fold higher in patients with TIL percentage ≤ 10% than in those with > 40% (p = 0.024), and the risk of distant metastasis was calculated to be 11.95 times higher. In our study, we discovered that the percentage of TILs made a statistically significant difference in TNBC survival. The presence of intratumoural PD-L1-positive TIICs in PD-L1-positive cases significantly increased survival.

[A rare carcinoma metastasizing to the lung: Sertoli-leydig cell tumor]. / Akcigere metastaz yapan nadir bir karsinom: Sertoli-leydig hücreli tümör.

The lung is the most common site of metastasis for many malignancies. Especially the gastrointestinal system, gynecological malignancies and osteosarcomas frequently metastasize to the lung. It accounts for less than 0.5% of all ovarian neoplasms. The frequency of recurrence and metastasis is less than 5%. In most cases, they are stage I tumors, limited to the ovary and carry a good prognosis. Here, while investigating the nodules in the lung that were detected incidentally at the age of 64, the rare Sertoli-Leydig cell tumor of the lung is discussed clinically, radiologically and pathologically in the presence of a 64-year-old patient who was found to have undergone ovarian surgery 9 years ago. Since imaging methods and tumor markers did not yield significant results in terms of primary malignancy, wedge resection was performed from the left lung nodules. The histology of the lung nodule was the same as the poorly differentiated foci of the ovarian tumor. The immunohistochemical profiles of the two tumors were also similar. As a result of the evaluation of the patient's old materials belonging to the ovary and the samples taken from the lung together; The diagnosis was reached by obtaining similar results with the primary tumor in the immunohistochemical examination performed for the metastatic focus. Sex cord stromal tumors of the ovary, which rarely cause lung metastasis and have a tendency to recur and metastasis in a very long time after the first diagnosis, should also be kept in mind in the elderly woman and the patient with a gynecological history.

Immunohistochemical HER2 Status Evaluation in Breast Cancer Pathology Samples: A Multicenter, Parallel-Design Concordance Study.

OBJECTIVE: As patients with increased human epidermal growth factor receptor (HER2) overexpression are more likely to benefit from trastuzumab treatment, the accuracy of HER2 receptor status in breast cancer patients is significant for appropriate disease management. However, this assessment is not harmonized and results may be highly variable between centers. The aim of this study was to investigate the degree of interlaboratory variability in the results of HER2 expression reported by 5 participating centers and to assess the concordance between these centers and a reference laboratory.Materials and Methods: A total of 30 breast cancer samples were tested and scored for HER2 expression using immunohistochemical method in 5 centers from Turkey and in a reference laboratory from Netherlands (Academic Medical Center, Amsterdam). All the participating centers had an experience of more than 10 years regarding the HER2 testing. The results were compared both among the centers and with the reference laboratory. RESULTS: When the concordance of participating centers and the reference laboratory was evaluated regarding negative (0-1+), equivocal 2(+) and positive 3(+) classification of HER2 immunostaining, the highest concordance was found in Center-A, and the lowest in Center-C (Kendall's tau-b concordance coefficient 0.911 and 0.724, respectively). The concordance of the centers with reference laboratory was 80.0% both in equivocal and positive samples, while it increased up to 91.8% in negative samples. CONCLUSIONS: This study showed that in general there is sufficiently good agreement between the reference laboratory and the participating centers for immunohistochemical HER2 assessment.

Reflectance confocal microscopy of mammary Paget disease.

Mammary Paget disease is the intraepidermal adenocarcinoma of the nipple area which is characterized usually by a well-demarcated eczematous plaque. Reflectance confocal microscopy (RCM), is an in vivo noninvasive diagnostic tool with a high-resolution imaging of the skin, almost comparable to conventional histology. RCM findings of Paget disease are limited in the literature. Most of the reported cases are the extramammary type. In this report, we aimed to evaluate the RCM findings of a non-pigmented mammary Paget disease in a 65 year-old woman.

Comparison of HER2 status determination methods in HER2 (2+) patients: Manual fluorescent in situ hybridization (FISH) vs. dual silver enhanced in situ hybridization (SISH).

HER2 amplification has been demonstrated in 15-25% of invasive breast carcinomas and can be assessed using immunohistochemical and in situ hybridization methods. Here, we compared the accuracy of dual SISH to manual FISH in HER2 (2+) breast carcinoma and evaluated the feasibility of dual SISH method in routine practice. Sixty HER2 (2+) consecutive tumor samples diagnosed between January 2009 and February 2013 were selected. Demographic, histological and immunohistochemical features and FISH results were recruited from patient records and compared to dual SISH results. Nine (15%) of the 60 tumor samples were excluded from statistical analysis due to lack of interpretable SISH signals. HER2 staining percentages by immunohistochemistry differed between 20 and 80%. HER2 amplification was shown in 7 (13.7%) and 8 (15.7%) patients by FISH and SISH, respectively. Very good agreement was observed between FISH and SISH methods (kappa value: 0.92). Significant correlation was found between HER2 staining percentage and FISH positivity, in contrast to SISH positivity (p=0.012 vs. p=0.069). Our results are consistent with previously reported literature, indicating SISH can be used to determine HER2 status. However, preanalytical and analytical problems may cause inadequate or uncountable signals, making interpretation impossible for the pathologist and highlighting the importance of standardization and quality control programs.

Diagnostic and Treatment Reproducibility of Cervical Intraepithelial Neoplasia / Squamous Intraepithelial Lesion and Factors Affecting the Diagnosis.

OBJECTIVE: Inter-observer differences in the diagnosis of HPV related cervical lesions are problematic and response of gynecologists to these diagnostic entities is non-standardized. This study evaluated the diagnostic reproducibility of "cervical intraepithelial neoplasia" (CIN) and "squamous intraepithelial lesion" (SIL) diagnoses. MATERIAL AND METHOD: 19 pathologists evaluated 66 cases once using H&E slides and once with immunohistochemical studies (p16, Ki-67 and Pro-ExC). Management response to diagnoses was evaluated amongst 12 gynecologists. Pathologists and gynecologists were also given a questionnaire about how additional information like smear results and age modify diagnosis and management. RESULTS: We show moderate interobserver diagnostic reproducibility amongst pathologists. The overall kappa value was 0.50 and 0.59 using the CIN and SIL classifications respectively. Impact of immunohistochemical evaluation on interpretation of cases differed and there was lack of statistically significant improvement of interobserver diagnostic reproducibility with the addition of immunohistochemistry. We saw that choice of treatment methods amongst gynecologists varied and overall concordance was only fair to moderate. The CIN2 diagnostic category was seen to have the lowest percentage agreement amongst both pathologists and gynecologists. We showed that pathologists had diagnostic "styles" and gynecologists had management "styles". CONCLUSION: In summary each pathologist had different diagnostic tendencies which were affected not only by histopathology and marker studies, but also by the patient management tendencies of the gynecologist that the pathologist worked with. The two-tiered modified Bethesda system improved diagnostic agreement. We concluded that immunohistochemistry should be used only to resolve problems in select cases and not for every case.

Do tumor-infiltrating lymphocytes really indicate favorable prognosis in epithelial ovarian cancer?

OBJECTIVE: The aim of this study is to evaluate the impact of lymphocyte infiltration on prognostic parameters, recurrence and survival in ovarian cancer. STUDY DESIGN: Sixty-two patients who were primarily operated for epithelial ovarian carcinoma between 1997 and 2008 were included. CD3, CD4, CD8, CD20 and FoxP3 expressions were evaluated immunohistochemically on sections obtained from paraffin-embedded tissues. RESULTS: Median follow up was 87 months. In whole cohort, CD3+ and CD8+ T lymphocyte infiltrations were significantly higher in patients with high-grade tumors, advanced stage tumors and the patients with omental metastasis (for CD3 p=0.0001, p=0.029, p=0.016; for CD8 p=0.044, p=0.002, p=0.046, respectively). DFS was significantly lower among patients with CD8+ T lymphocytes with regard to patients who did not have CD8+ T lymphocyte infiltration (p=0.028). In univariate analysis, presence of CD8 cytotoxic T lymphocyte infiltration (p=0.03), stage (0.0001), tumor grade (p=0.007), omental metastasis (p=0.0001) and lymph node metastasis (p=0.0001) were significant risk factors for recurrence. But in multivariate analysis, only stage [HR: 116.6 (95% CI: 13.09-1039.45) (p=0.0001)] was found as an independent risk factor for recurrence. CONCLUSION: CD3+ and CD8+ T lymphocyte infiltrations were related with advanced stage, high-grade tumor and the omental metastasis in ovarian cancer. DFS was significantly shorter in patients with CD8+ T lymphocyte infiltration. CD3+ and CD8+ T lymphocyte infiltrations were related with poor prognosis in ovarian cancer.

Primary ovarian leiomyoma: A case report.

INTRODUCTION: Primary ovarian leiomyoma is a rare benign tumour of the ovary seen in women between 20 and 65 years old. It is usually diagnosed incidentally during pelvic examination or pathologic examination after surgery. PRESENTATION OF CASE: We describe a case of unilateral, ovarian leiomyoma. Transvaginal ultrasonography and magnetic resonance imaging (MRI) revealed a right adnexial mass. Unilateral salpingo-oophorectomy was performed, and histological examination revealed a leiomyoma arising primarily in the ovary. The diagnosis was confirmed immunohistochemically. DISCUSSION: The tumour may be asymptomatic or may manifest with lower abdominal pain like in our case. The definitive diagnosis of these lesions is difficult prior to surgical removal. Because there is no pathognomonic symptoms or characteristic imaging findings. The correct diagnosis of an ovarian leiomyoma requires identification of the smooth muscle nature of the tumour. CONCLUSION: This rare tumour of the ovary should be considered in the differential diagnosis of solid ovarian masses. An immunohistochemical analysis is recommended for definitive diagnosis.

The effect of freezing on the immunoprofile of breast carcinoma cells.

BACKGROUND: Intraoperative frozen section procedure may be required in some operations performed for breast masses. AIMS: We investigated the effect of frozen section procedure on the immunoprofile of breast carcinoma cells. STUDY DESIGN: Cross-sectional study. METHODS: A total of 53 breast carcinoma cases evaluated with intraoperative frozen sections were included in this study. Immunohistochemically, oestrogen (ER), progesterone (PR) and HER2 primary antibodies were evaluated in both frozen and non-frozen sections of each tumour sample. RESULTS: No difference was found between the frozen and non-frozen sections in 33 cases in terms of staining rate and intensity of ER, PR and HER2. A decrease was found in the ER, PR and HER2 staining rate (in 10 cases, 9 cases and 6 cases, respectively). Likewise, a decrease was detected in ER, PR and HER2 staining intensity in 6 patients for each. Although there was no staining in frozen sections, immunopositivity was observed in 3 non-frozen sections for ER, in 2 for PR and in 5 for HER2. Statistically, a significant difference was found between the frozen and non-frozen sections in terms of staining rate and intensity for each of the three markers. CONCLUSION: In this study, the frozen section procedure in breast carcinoma had a negative effect on the immunoprofile. However, considering the importance of hormone receptor status in the treatment, these results should be supported with larger series.

Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists.

Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists' diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted κ values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.

Cervical adenoid Basal carcinoma: a case report.

Adenoid basal carcinoma (ABC) is a rare epithelial tumor of the cervix. It makes up approximately 1% of all cervical adenocarcinomas. Rare cases have been associated with common cervical epithelial tumors. We present a case of ABC associated with typical squamous cell carcinoma. A 54-year-old post-menopausal woman underwent D&C for vaginal bleeding. Histologically, the tumor was characterized by small cells with a narrow cytoplasm, making up islands and cords. Peripheral palissading in the cells surrounding the cystic areas that contained central cellular debris and keratin was noted. The patient underwent total hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy and omentectomy. Large cell keratinized type squamous cell carcinoma areas in the cervix were noted besides the limited ABC areas. After surgery, the patient was treated with radiation therapy. A retroperitoneal metastasis was found on the first year and chemotherapy was administered. The patient has no evidence of disease 27 months after the first diagnosis. ABC makes up quite a rare group of cervical cancers and should be kept in mind during the evaluation so that a differentiation can be made with tumors with similar morphology as it can show various histological patterns, and can be seen together with more aggressive cancers.

Investigation of galectin-3 and heparanase in endometrioid and serous carcinomas of the endometrium and correlation with known predictors of survival.

INTRODUCTION: Inhibitors of tumor angiogenesis and metastasis are emerging as important new drug candidates for cancer therapy. Galectin-3 and heparanase have been shown to function in tumor progression and metastatic spread. Both of them exert pleiotropic effects; proliferation, cell migration, differentiation and tissue remodeling. The aim of this study was to investigate heparanase and galectin-3 expression in endometrioid and serous carcinomas of the endometrium and their relation with well-known prognostic factors, in addition to estrogen, progesterone, C-erbB-2, Ki-67 and p53. MATERIALS AND METHODS: Sixty-four endometrial cancers, which include 24 serous types, were obtained from previously untreated patients. Immunohistochemical analysis of 64 carcinomas, 20 endometrial hyperplasia (ten of simple hyperplasia and ten of complex atypic hyperplasia) and 20 normal endometrium (ten of proliferative and ten of secretory) was performed. CONCLUSION: This investigation suggests that the decreased expression of galectin-3 may be involved in the pathogenesis of endometrial carcinomas from normal endometrium to carcinoma. Also down-regulated stromal expression of galectin-3 in endometrial carcinoma may be involved in lymph node metastasis. Further studies on a larger advanced stage (FIGO stage 3-4) endometrial carcinoma group may determine the value of heparanase in the endometrial carcinoma.

Fine needle aspiration cytologic features of medullary carcinoma of the breast: a study of 20 cases with histologic correlation.

OBJECTIVE: To analyze fine needle aspiration cytology (FNAC) material from 20 cases of histologically verified medullary carcinoma (MC) of the breast and correlate the cytomorphologic features with histologic appearance to improve the diagnostic sensitivity and specificity of FNAC. STUDY DESIGN: We reviewed the cytologic features of 20 cases of MC of the breast in the archives of Ege University Hospital between 1994 and 2006. RESULTS: Twenty patients with an aspirate and confirmed diagnosis of MC were identified. Patient age was 30-74 years (mean, 48). The initial cytologic diagnoses were positive for cancer in 17 cases, atypical/suspicious for cancer in 2 cases and negative for cancer in 1 case. The cytologic picture was characterized by cellular smears composed of highly atypical epithelial tumor cells in loosely cohesive sheets and lying singly, admixed with polymorphous lymphocytes, plasma cells and neutrophils. Tumor cells had predominantly abundant finely granular, eosinophilic cytoplasm and moderate to marked nuclear pleomorphism with prominent nudcleoli. Histologic examination confirmed that 11 cases were atypical MC and 9 were pure MC. CONCLUSION: Breast MC is a rare, distinct category that appears to have rather characteristic cellular features. Familiarity with the cell components is a prerequisite in cytologic accuracy.

Florid vascular proliferation in mature cystic teratoma of the ovary: case report and review of the literature.

A case of mature cystic teratoma that contained florid vascular proliferation is reported. The ovarian tumor occurred in a 9-year-old girl; symptoms consisted of vomiting, abdominal pain and a palpable mass. The microscopic findings were mostly typical of a mature cystic teratoma, but also abundant vascular proliferation mimicking hemangioma in association with mature neural tissue was observed. There was a disorganized arrangement of medium- and large-sized spaces lined by cuboidal endothelial cells. Immunohistochemical staining for vascular proliferation showed immunoreactivity for CD31 and smooth muscle actin. Florid vascular proliferation may be seen in association with neural tissue of ovarian teratomas and should not be misdiagnosed as immature teratoma or a vascular neoplasm.

Chondromatous differentiation in clear cell carcinoma of the ovary: a rare finding challenging the differential diagnosis.

OBJECTIVE: Ovarian surface epithelial tumors rarely have heterologous elements including bone or cartilage that may appear histologically benign or malignant. There are a few case reports in the literature of ovarian tumors containing chondromatous areas. CASE: We report a clear cell carcinoma of the bilateral ovary showing chondromatous differentiation in a 56-year-old woman. Histopathologic study of the specimen showed clear cell carcinoma with many small foci of chondromatous differentiation. Immunohistochemical studies demonstrated positivity for S-100 confirming the diagnosis. The patient was alive with disease on chemotherapy for 16 months. CONCLUSION: A rare case of benign appearing chondromatous differentiation in an ovarian clear cell carcinoma of the ovary is described, and the significance of this finding is discussed.

Fine needle aspiration cytology of glycogen-rich clear cell carcinoma of the breast: review of 37 cases with histologic correlation.

OBJECTIVE: To analyze fine-needle aspiration cytology (FNAC) material from 37 cases of breast glycogen-rich clear cell cancer (GRCC) and correlate cytomorphologic features with histologic appearance to determine characteristics of GRCC on FNAC. STUDY DESIGN: We reviewed cytologic features of 37 cases of breast GRCC from the archives of Ege University Hospital diagnosed between 1994 and 2006. RESULTS: Thirty-seven patients with available aspirate and confirmed GRCC were identified. The female patients ranged from 32 to 81 years (mean 52 years). The initial cytologic diagnoses were adenocarcinoma for 27 and atypical or suspicious for cancer for 10. The cytologic picture was characterized by hypercellular tumor cells in loosely cohesive syncytial groups and some single cells. Most tumor cells had abundant, finely granular eosinophilic cytoplasm or foamy to clear cytoplasm with well-defined cytoplasmic membranes and moderate to marked nuclear pleomorphism with prominent nucleoli. Histologic examination confirmed all cases to be pure GRCC. CONCLUSION: Breast GRCC is a rare, distinct category with cytologic features that overlap considerably with those of other carcinomas. Awareness of variability in cytomorphologic appearance of GRCC and routine assessment for glycogen facilitate accurate diagnosis of these lesions by FNAC and enable prompt treatment of these poor-prognosis breast cancers.

Fine needle aspiration cytology of mammary carcinoma with choriocarcinomatous features: a report of 2 cases.

BACKGROUND: Neoplasms of the breast containing multinucleated giant cells (MGCs) include both benign and malignant entities, such as benign soft tissue giant cell tumors, atypical fibrous histiocytoma, sarcomas, metaplastic carcinomas and the uncommon carcinomas containing osteoclast-like giant cells (OGC). Breast carcinoma with choriocarcinomatous features (BCCF) is a distinct variant of breast cancer. CASES: We report the cytologic features, pathologic findings and immunohistochemical profile in 2 cases of this unusual variant of breast carcinoma. Two women aged 53 and 50 years women presented with a history of left and right breast lump but no local lymphadenopathy, respectively. Fine needle aspiration cytology (FNAC) of both cases revealed abundant MGC with highly pleomorphic tumor cells in the hemorrhagic necrotic background. Both of the cases were histopathologically diagnosed as BCCF. CONCLUSION: Choriocarcinomatous differentiation with multinucleated syncytiotrophoblast-like giant cells is extremely rare in breast tumors. Although rare, FNAC of breast cancer with pleomorphic MGC requires careful search for differential diagnosis; breast carcinoma with giant cell features (choriocarcinomatous features, OGC features) must be differentiated from metastatic tumors and other breast lesions containing giant cells.

Lipoadenofibroma of the endometrium: a rare variant of benign mullerian mixed tumor.

OBJECTIVE: Adenofibroma is a form of mixed mesodermal tumor in which epithelial and stromal components are benign, and usually arises in the endometrium of postmenopausal women. We report a case of lipoadenofibroma of the endometrium that appeared as an intracavitary mass, which is very unusual because endometrioid adenofibroma rarely contains mature adipose tissue, only the second such case described in detail. CASE: An endometrial polypoid mass measuring 1,5 cm with maximum diameter was found incidentally during total abdominal hysterectomy for keratinizing large cell carcinoma of the cervix in a 60-year-old woman. The endometrial polypoid mass was found to be a lipoadenofibroma composed predominantly of collagenated fibrous stroma populated by cystically dilated and occasionally crowded glands lined with proliferative endometrium, intermingled with abundant mature adipose tissue. CONCLUSION: We suggest that uterine adenofibromas with lipomatous areas belong to the family of mixed tumor of Mullerian origin. We discuss the pathogenesis of this entity and review the previously documented similar cases.