Origin Of Clear Cell Carcinoma Research Articles

SUN-480 An Unusual Clear Cell Carcinoma in the Thyroid. Where Is the Primary?

Background: Clear cell carcinoma in the thyroid gland is rare. It is important to distinguish primary thyroid clear cell carcinoma from metastases, since its clinical behaviors and treatment options were different. Clinical Case: A 47-year-old woman without past medical history presented to our outpatient surgery department with right neck mass for 8 months. Thyroid ultrasonography revealed a 3.9 cm nodule in the right thyroid. Thyroid function test was within the normal range. Fine needle aspiration cytology of the nodule showed suspicious for neoplasm. She underwent radical total thyroidectomy and lymph node dissection. Pathology revealed an unusual carcinoma comprising cuboidal cells with irregular nuclear contours, some eosinophilic or clear cytoplasm, arranged in infiltrating nests or cords with marked stromal hyalinization, highly suggestive of a clear cell carcinoma. Ectopic thymic tissue was present adjacent to the tumor. By immunohistochemical (IHC) staining, tumor cells were p63 (+), TTF-1 (-), thyroglobulin (-), PAX8 (-), synaptophysin (-), CD5 (-), and CD117 (-). Tumor genetic sequencing detected EWSR1-CREM fusion genes. For disease extent evaluation, two out of seven lymph nodes obtained during operation were positive of tumor metastases. Whole body computed tomography (CT) 3 months after operation revealed no residual thyroid tissue, neck lymphadenopathies or intra-abdominal metastases. A pulmonary ground-glass opacities of 7mm in diameter was found, which was stationary at a repeated CT scan 6 months later. Clinical Lesson: Clear cell carcinoma in the thyroid gland could be primary, arising from clear cell change of follicular or papillary thyroid carcinoma. The negative IHC stain of thyroglobulin, TTF, PAX8, as well as lack of papillary or follicular architecture made primary thyroid clear cell carcinoma unlikely. Most of the metastatic clear cell carcinoma to the thyroid gland arose from renal primary. However, there was no clinical or radiographic evidence of renal tumor in our case. Although ectopic thymic tissue was identified on pathology, negative IHC staining of PAX8, CD5 and CD117 made thymic origin less likely. Positive IHC staining of p63 and a novel EWSR1-CREM fusion gene confirmed the diagnosis of salivary clear cell carcinoma. According to our literature review, there were only 3 cases of clear-cell carcinoma with EWSR1-CREM fusion gene (1), and our case is the first case who presented with clear cell carcinoma in the thyroid. In conclusion, the importance of IHC stain and molecular testing in determining the primary origin of clear cell carcinoma were addressed in our case. Reference: (1) Chapman E, et al. Am J Surg Pathol. 2018;42(9):1182-1189

Major clinical research advances in gynecologic cancer in 2010.

This review summarizes 11 major clinical research advances in gynecologic oncology in 2010. For ovarian cancer, bevacizumab as a leading molecular targeted agent, pegylated liposomal doxorubicin in recurrent disease, the role of neoadjuvant chemotherapy in an advanced setting, an effective screening method, and ARID1A mutations as a clue to the origin of clear cell carcinoma are mentioned. For cervical cancer, confirmation of the efficacy and the introduction of a self collection method of the human papillomavirus (HPV) test, and the association between the HPV vaccine and miscarriage are examined. For endometrial cancer, the superiority of laparoscopy in staging operation, the role of vaginal brachytherapy in an adjuvant setting, and the effect of para-aortic lymph node dissection are reviewed. In addition, the trend of geriatric oncology and chemotherapy in carcinosarcomas is also assessed.

Hepatocyte nuclear factor-1beta(HNF-1beta) in human urogenital organs: its expression and role in embryogenesis and tumorigenesis.

Molecules responsible for embryogenesis are often involved in tumorigenesis. Recent exhaustive cDNA microarray analyses in human neoplasms expanded knowledge of such molecules. Hepatocyte nuclear factor-1beta (HNF-1beta) is a homeobox transcription factor that functions as a homodimer or heterodimer with HNF-1alpha. In contrast to HNF-1alpha, HNF-1beta is very weakly expressed in the liver and is commonly expressed in the kidneys. During human embryonic stage, HNF-1beta plays an important role in organogenesis, especially of the urogenital system. In the human fetus, HNF-1beta expression is common in mesonephric duct derivatives and metanephros (permanent kidneys). HNF-1beta germline mutations cause malformations of these structures. Recent microarray analyses have disclosed that HNF-1beta is aberrantly up-regulated in clear cell carcinoma of the ovary, which is a carcinoma of müllerian nature, but which was initially misnamed "mesonephroma". HNF-1beta is also expressed in ovarian endometriosis, which is a probable origin of clear cell carcinoma. On the other hand, HNF-1beta is down-regulated in renal neoplasms, such as chromophobe cell carcinoma. In this review, we first summarize HNF-1beta expression in the developing urogenital system of the human embryo. Then, we describe the HNF-1beta status in human urogenital neoplasms and discuss its role in tumorigenesis.

Origins and molecular pathology of ovarian cancer

Epithelial ovarian cancer comprises the majority of malignant ovarian tumors in adult women. These neoplasms are classified into distinct morphologic categories based on the appearance of the epithelium into tumors of serous, mucinous, endometrioid, clear cell, transitional, squamous, mixed and undifferentiated type. Current data indicate that each of these histologic subtypes is associated with distinct morphologic and molecular genetic alterations: high-grade serous and possibly endometrioid carcinomas most probably arise from surface epithelial inclusion glands with TP53 mutations and dysfunction of BRCA1 and/or BRCA2; low-grade serous carcinomas probably arise in a stepwise fashion in an adenoma-borderline tumor-carcinoma sequence from typical to micropapillary borderline tumors to low-grade invasive serous carcinoma via activation of the RAS-RAF signaling pathway secondary to mutations in KRAS and BRAF; mucinous carcinomas arise via an adenoma-borderline tumor-carcinoma sequence with mutations in KRAS; low-grade endometrioid carcinomas arise from endometriosis via mutations in CTNNB1 (the gene encoding beta-catenin) and PTEN. Although the morphologic data strongly support an origin of clear cell carcinoma from endometriosis, there is limited data on the genetic alterations in these uncommon tumors. Thus it is likely that most low-grade, relatively indolent ovarian carcinomas of serous, mucinous and endometrioid type arise from pre-existing cystadenomas or endometriosis whereas most high-grade serous carcinomas arise without an easily identifiable precursor lesion.

Origins and molecular pathology of ovarian cancer

Epithelial ovarian cancer comprises the majority of malignant ovarian tumors in adult women. These neoplasms are classified into distinct morphologic categories based on the appearance of the epithelium into tumors of serous, mucinous, endometrioid, clear cell, transitional, squamous, mixed and undifferentiated type. Current data indicate that each of these histologic subtypes is associated with distinct morphologic and molecular genetic alterations: high-grade serous and possibly endometrioid carcinomas most probably arise from surface epithelial inclusion glands with TP53 mutations and dysfunction of BRCA1 and/or BRCA2; low-grade serous carcinomas probably arise in a stepwise fashion in an adenoma–borderline tumor–carcinoma sequence from typical to micropapillary borderline tumors to low-grade invasive serous carcinoma via activation of the RAS–RAF signaling pathway secondary to mutations in KRAS and BRAF; mucinous carcinomas arise via an adenoma–borderline tumor–carcinoma sequence with mutations in KRAS; low-grade endometrioid carcinomas arise from endometriosis via mutations in CTNNB1 (the gene encoding β-catenin) and PTEN. Although the morphologic data strongly support an origin of clear cell carcinoma from endometriosis, there is limited data on the genetic alterations in these uncommon tumors. Thus it is likely that most low-grade, relatively indolent ovarian carcinomas of serous, mucinous and endometrioid type arise from pre-existing cystadenomas or endometriosis whereas most high-grade serous carcinomas arise without an easily identifiable precursor lesion.