Clear Cell Adenocarcinoma Research Articles

Histopathological Subtypes and PD-L1 Expression in Primary Urethral Adenocarcinoma: A Series of 5 Cases

Urethral adenocarcinoma is a rare disease with poor prognosis that can display multiple histologic patterns and has an unclear histogenesis. Radical surgery with extensive periurethral resection is the preferred therapeutic approach. Both chemotherapy and radiotherapy have been used as complementary treatment options. Due to the tendency of these tumors to recur, treatment-associated complications, and the limited choice of therapeutic options, patient management can be difficult. Given the lack of literature regarding immunotherapy in urethral adenocarcinoma, our objective was to explore the expression of programmed death receptor-ligand 1 (PD-L1) throughout the different histological subtypes of primary urethral adenocarcinoma. We reviewed all primary urethral adenocarcinomas diagnosed at our hospital between 1965 and 2019, performed immunohistochemical assays on the tissue blocks, classified them according to their histology and origin, and performed PD-L1 (22C3) immunohistochemistry assays in all cases. We found a total of 5 cases of primary urethral adenocarcinoma. All of the patients were women. One of the cases was a cribriform adenocarcinoma, 2 were columnar-mucinous adenocarcinomas, and 2 were clear cell adenocarcinomas. One of the clear cell adenocarcinomas strongly expressed PD-L1. In addition, a profuse inflammatory infiltration constituted by CD3-positive and CD8-positive T lymphocytes within tumor cells was observed in this case. None of the other cases showed PD-L1 expression. In conclusion, some urethral adenocarcinomas may strongly express PD-L1 and thus could potentially allow the use of immunotherapy in selected cases of advanced or recurrent adenocarcinoma.

Clear cell carcinoma of the urinary bladder: a systematic review.

We conducted a systematic review of the literature on primary clear cell carcinoma (CCC) of the urinary bladder. A literature search using keywords and MeSH terms related to "clear cell carcinoma", "clear cell adenocarcinoma", "mesonephroma" and "urinary bladder" in EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials was performed. A manual search was performed with web-based search engine Google Scholar. Reference lists of the included studies were screened for additional articles. Articles up till 16th July 2020 were retrieved. Observational human studies on primary CCC in urinary bladder with English full-text were included for further analysis. 904 articles were identified and 44 articles were included for further analysis. Data including clinical features, tumour characteristics, treatment and oncological outcomes were reviewed. There were 70 patients (44 females and 26 males) reported in literatures and included in this review. Gross haematuria was the most common presentation (79.7%), followed by irritative urinary symptoms (47.5%). Regarding the histology, tubulocystic pattern is the most common histologic pattern (49.1%), and 52.6% had muscle invasion. Most cases were CK7 (96.6%) and CK20 (88.9%) positive. CA125 (96%) was commonly positive, indicating its potential origin from mullerian duct. Most patients received surgery (95.5%) as primary treatment. However, the oncological outcomes were unsatisfactory with a 2-year survival rate of 60.0%. Clear cell carcinoma is an uncommon subtype of bladder cancer which can be diagnosed by histology and immunohistochemical staining result. The majority of patients presented with muscle invasion and had a poor survival despite aggressive treatment.

A Case of Mixed Neuroendocrine-non-neuroendocrine Neoplasm of the Extrahepatic Bile Duct Coexisting with a Mixed G1 Clear Cell Neuroendocrine Tumor and Adenocarcinoma

A Case of Mixed Neuroendocrine-non-neuroendocrine Neoplasm of the Extrahepatic Bile Duct Coexisting with a Mixed G1 Clear Cell Neuroendocrine Tumor and Adenocarcinoma

Adenocarcinoma de células claras da uretra masculina: relato de caso clínico

Adenocarcinoma de células claras da uretra masculina: relato de caso clínico

Primary Clear Cell of Abdominal Wall, A Case Report

Background: Endometriosis occurring in a surgical scar is well recognized and occurs mainly in patients with a history of hysterectomy or caesarean section. Scar endometriosis as well as endometriosis at other sites, can undergo malignant change. Clear cell carcinoma of the endometrium is a very rare and highly malignant neoplasm that accounts for less than 5% of endometrial carcinoma. Case presentation: We report a very rare case of clear cell adenocarcinoma arising from endometriosis of the abdominal scar. We must pay more attention on the following points in the surgical treatment of clear cell carcinoma: (1) Extensively resect tumors as far as possible: (2) Surgical treatment of clear cell carcinoma would easily result in poor wound healing especially in the patients receiving chemotherapy or radiotherapy because of extensive soft tissue stripping. Conclusion: The patient died only 25 months after she was first diagnosed with the cancer. Lessons: This case highlights the difficulties in preoperative diagnosis as well as the poor prognosis of these tumors. Accurate diagnosis of a lump within a scar is important to define the prognosis and treatment. These therapeutic principles are increasingly being applied to patients presenting with tumors greater than 5 cm and negative lymph nodes or even smaller tumors who are considered to have operable disease and a better outcome. Early recognition and prompt treatment can be essential to these patients' survival.

Screening for cancers of the cervix and vagina for women exposed to diethylstilbestrol (DES) in utero

ObjectivesIn total, 80,000 women were exposed to diethylstilbestrol (DES) in utero in France (DES daughters) between 1950 and 1977. After having been dominated by the management of infertility and pregnancy accidents, monitoring must adapt to the increased risk of cancer of the cervix and vagina: doubling of the frequency of severe dysplasia and a risk of late clear-cell adenocarcinoma (CCA). Two recent changes in cervical cancer screening in France, the introduction of HPV tests in first-line screening and organized screening, should consider the particular situation of DES daughters. We aimed to assess the compliance of DES daughters with previous recommendations and propose specific screening practices in the new context. MethodA non-profit organization carried out a questionnaire survey of its members who were exposed to DES in utero. ResultsAmong the 570 participants, 64 % had annual PAP tests, 25 % within the last three years, and 11 % more than three years before or never. The reasons for "dropout" were: 1) ignorance of the recommendations by practitioners (38 %) or patients (30 %), 2) fatigue (32 %) or apprehension of the exams (14 %), and 3) difficult access to care: time to get an appointment (26 %), difficulty in finding a doctor (28 %), or cost (6 %). ConclusionThese results concern women who were sufficiently aware of the issue to be a member of an association. They are encouraging but show a need to improve the dissemination of information to all “DES daughters” and health professionals. Patient associations can play a growing role in this “rare disease” by addressing patients and healthcare professionals. We propose that screening for these women include an annual screen of not only the cervix, but also the vagina, and that it continues beyond 65 years of age and after hysterectomy, with cytological examination, because ACC is unrelated to HPV.

Mesonephric (Wolffian-derived) Adenocarcinoma of the Female Urethra

The current World Health Organization (WHO) classification of adenocarcinoma of the urinary tract including the urethra includes uncommon Müllerian-derived carcinomas such as clear cell and endometrioid adenocarcinomas. The concept of primary mesonephric (Wolffian-derived) adenocarcinoma (MA) in the urethra (and urinary tract in general) is currently regarded as controversial as the term "mesonephric" had been also inaccurately applied in the past to label Müllerian-derived carcinomas, particularly clear cell adenocarcinoma. Further, pathologically well-documented or bona fide urethral MAs have not yet to be reported. Herein, we describe 2 examples of MA in elderly females that primarily presented in the urethra and manifested clinically with obstructive lower urinary tract symptoms. Both tumors exhibited histology similar to those in MAs of the female genital tract including the distinctive tubular proliferations with luminal eosinophilic materials. The first case, in addition, showed a variety of patterns including ductal (glandular), solid, fused/sieve-like tubules, dilated tubules, and spindled cells. The second case also showed a transition to the more irregular and poorly formed tubular proliferation of cells with greater nuclear atypia and with a desmoplastic response. Both tumors showed positivity for PAX8, GATA3, and luminal CD10, and 1 tumor analyzed harbored KRAS and ARID1A mutations. One patient received neoadjuvant chemotherapy and underwent resection but had local tumor recurrence and metastasis to the lungs and lumbar spine 12 months after presentation. In conclusion, MA, similar to those occurring in the female genital tract and distinct from the recognized Müllerian-derived carcinomas, may present primarily as urethral tumors. MA in the urethra probably shares a common pathogenesis with vaginal MA as both may originate from the same caudal loci of mesonephric remnants along the closely apposed anterior vaginal and posterior urethral walls. MA should be considered in future classifications for urethral tumors and we recommend that the confusing term "mesonephroid adenocarcinoma" should no longer be used.

Noncanonical IL6 Signaling-Mediated Activation of YAP Regulates Cell Migration and Invasion in Ovarian Clear Cell Cancer.

Ovarian clear cell adenocarcinoma (OCCA) is characterized by a particularly poor response to conventional chemotherapy and a short overall survival time in women with established disease. The development of targeted treatments for OCCA relies on a better understanding of its molecular characteristics. IL6 is strongly expressed in OCCA and may therefore provide a novel therapeutic target. Here we use CRISPR/Cas9 and conditional short hairpin interfering RNA to perform loss-of-function studies in human OCCA cell lines to explore the requirement for IL6 in vitro and in vivo. While reduction of IL6 expression exerted limited effects in vitro, its attenuation significantly impaired tumor growth and neovascularization in vivo. In contrast to typical signaling via STAT3, IL6 in OCCA signaled via a noncanonical pathway involving gp130, Src, and the Hippo pathway protein YAP. A high-throughput combination drug screen identified agents that enhanced cell killing following reduction of IL6 signaling. Intersection of screen hits obtained from two cell lines and orthogonal approaches to attenuation of IL6 yielded AKT and EGFR inhibitors as enhancers of the inhibitory monoclonal IL6 receptor antibody tocilizumab. This study defines for the first time the requirements for, and mechanisms of, signaling by IL6 in human OCCA cell lines and identifies potential combinatory therapeutic approaches. Given the molecular diversity of OCCA, further in vitro and in vivo studies are warranted to determine whether such approaches will overcome the limited efficacy of tocilizumab observed in ovarian cancer to date. SIGNIFICANCE: This study defines the requirements for and mechanisms of noncanonical signaling by IL6 in human ovarian clear cell adenocarcinoma cell lines and identifies combinatory therapeutic approaches to be explored clinically.

Clear Cell Adenocarcinoma of Uterine Cervix: A Single Institution Retrospective Experience.

PurposeThe purpose of the study is to summarize the clinical characteristics and identify the prognosis of clear cell adenocarcinoma of the uterine cervix (CCAUC) in patients without a history of diethylstilbestrol (DES) exposure.MethodsForty-two patients with CCAUC, treated initially at Sun Yat-sen University Cancer Center between 1985 and 2017, were studied.ResultsOf all the CCAUC patients, the median age was 47 years old, and the median tumor size was 3 cm. Thirty-four early stage patients (IB = 28, IIA = 6) underwent radical surgery. Eight advanced stage patients (IIB = 8) received concurrent chemoradiotherapy (n = 4) or radical surgery (n = 4). Survival analysis showed that patients with early stage (IB-IIA) had a significantly better 5–year progression-free survival (PFS) and overall survival (OS) than those with advanced stage (IIB) (p < 0.05). The patients with negative pelvic lymph node (PLN) had a significantly better 5-year PFS and OS than those with positive PLN (p < 0.05). Radiotherapy (RT) did not affect PFS or OS in early stage patients with intermediate risk factors (p > 0.05). Adjuvant chemotherapy (CT) did not affect PFS or OS in early stage patients without risk factors (p > 0.05).ConclusionThe FIGO stage and pelvic node status were important prognostic factors for both PFS and OS. For treatment modality, we recommended that radical surgery alone was used in early stage patients without high risk factors. Ovarian preservation in early stage patients involved some risk.

Primary adenocarcinomas of the vulva and related structures: An enigmatic and diverse group of tumors✰.

Approximately half of adenocarcinomas that involve the vulva are secondary, either through direct extension or metastases from elsewhere. Primary vulvar adenocarcinomas are rare and encompass a diverse array of neoplasms that are nominally classified based on the presumed tissue or organ of origin, the tumoral phenotype, or both. In this review, we summarize the clinicopathologic features of adenocarcinomas that originate from the vulva and related structures, including the terminal urethra. Adenocarcinomas of this region encompass lesions that are defined by their primary site (such as adenocarcinomas of the Bartholin gland, which by definition must be in the region of the Bartholin gland), histomorphology and immunophenotype (such as clear cell carcinoma and adenocarcinoma of intestinal [cloacogenic] type), or both (such as adenocarcinoma of skene gland origin, which is associated with that specific organ but which also displays a distinctive phenotype that is similar to the phenotype of high grade prostatic adenocarcinoma). Other types, such as mammary-type adenocarcinomas, are presumed to originate from the putative mammary-like glands of the vulva and display a spectrum of pathologic features that are similar to their mammary counterparts. Similarly, vulvar carcinomas of sweat gland origin are pathologically similar to their counterparts in the non-vulvar skin and include a variety of cutaneous adnexal-type malignancies such as apocrine adenocarcinoma and eccrine adenocarcinoma. Some tumors, such as adenoid cystic carcinoma, may represent a Bartholin gland adenocarcinoma, a carcinoma of sweat gland origin, or a carcinoma arising from extramammary Paget disease (EMPD), depending on the context. Invasive carcinomas of various types have been reported in 7-12.7% of EMPD, and these are likely the most common primary glandular malignancy of the vulva. Occasional vulvar adenocarcinomas have been reported to be HPV-associated, although this association has not been established for the broader group of vulvar adenocarcinomas. Rare adenocarcinomas are not classifiable by the aforementioned nosologic scheme, and are designated as vulvar adenocarcinoma NOS.

Clear Cell Adenocarcinoma in Men: A Series of 15 Cases.

Clear cell adenocarcinoma (CCA) is a rare tumor in the genitourinary tract with female predominance and few reports in men. We identified 15 cases of CCA in men evaluated at our institution. Five arose in the bladder, 7 in the prostate or prostatic urethra, 2 in the membranous urethra (1 multifocal in the prostatic and membranous urethra), 1 periprostatic (likely from an embryologic remnant), and 1 between rectum and bladder (likely in a prostatic utricle cyst). No cases showed associated Müllerian structures. One case showed separate foci of nephrogenic adenoma at diagnosis, and 1 case showed urothelial carcinoma in situ on a later follow-up biopsy. Four tumors extended into other organs (prostate to seminal vesicle and periprostatic soft tissue, periprostatic soft tissue to prostate, prostatic urethra to bladder and rectum, and prostate to bladder neck). One tumor showed extraprostatic extension alone. Four tumors metastasized to lymph nodes, with 3 also metastasizing to other sites (bladder, lung and adrenal, and right flank). Eleven patients underwent resection, including 3 transurethral resections. Seven underwent other treatments, including radiation (5 [1 for recurrence]), chemotherapy (3), hormonal therapy (3), immunotherapy with nivolumab (1), and targeted therapy with gefitinib (1). The mean follow-up was 35 months (range: 1 to 138 mo). At the last follow-up, 7 patients showed no evident disease and 3 were alive with disease. Four died with the cause of death unknown, with 2 cases having confirmed disease at the time of death and the remaining 2 dying less than a year after diagnosis. The mean time to death was 16 months (range: 6 to 39 mo). No follow-up was available on 1 patient. All patients who died in this series had CCA of the prostate or prostatic urethra. Pathologists need to be attuned to CCA occurring in males, given that the literature emphasizes its occurrence in females. In addition to established sites such as bladder and urethra, our series demonstrates that tumor may present in unusual adjacent sites, such as in periprostatic embryologic remnants or prostatic utricle.

Pten and Dicer1 loss in the mouse uterus causes poorly differentiated endometrial adenocarcinoma.

Endometrial cancer remains the most common gynecological malignancy in the United States. While the loss of the tumor suppressor, PTEN (phosphatase and tensin homolog), is well studied in endometrial cancer, recent studies suggest that DICER1, the endoribonuclease responsible for miRNA genesis, also plays a significant role in endometrial adenocarcinoma. Conditional uterine deletion of Dicer1 and Pten in mice resulted in poorly differentiated endometrial adenocarcinomas, which expressed Napsin A and HNF1B (hepatocyte nuclear factor 1 homeobox B), markers of clear-cell adenocarcinoma. Adenocarcinomas were hormone-independent. Treatment with progesterone did not mitigate poorly differentiated adenocarcinoma, nor did it affect adnexal metastasis. Transcriptomic analyses of DICER1 deleted uteri or Ishikawa cells revealed unique transcriptomic profiles and global miRNA downregulation. Computational integration of miRNA with mRNA targets revealed deregulated let-7 and miR-16 target genes, similar to published human DICER1-mutant endometrial cancers from TCGA (The Cancer Genome Atlas). Similar to human endometrial cancers, tumors exhibited dysregulation of ephrin-receptor signaling and transforming growth factor-beta signaling pathways. LIM kinase 2 (LIMK2), an essential molecule in p21 signal transduction, was significantly upregulated and represents a novel mechanism for hormone-independent pathogenesis of endometrial adenocarcinoma. This preclinical mouse model represents the first genetically engineered mouse model of poorly differentiated endometrial adenocarcinoma.

Aggressive course of a rare type of urethral cancer in women

The article provides a clinical case of urethral cancer in women. Primary urethral carcinomas are rare, less than 1% of all malignant tumors. According to the Rarecare Cancer Surveillance Agency for Europe (RARECARE), urethral cancer in women is 0.6 and 1.6 in men per 1 million people per year. A 56-year-old patient with histologically verified clear cell adenocarcinoma of the proximal urethra was monitored for 18 months. An aggressive course of the tumor process has been shown, which led to the need to perform anterior exenteration of the pelvic organs. The histogenesis of primary clear cell urethral adenocarcinoma has not been definitively determined. The atypical external localization in the described case suggests the periurethral origin of this cancerous tumor from the Skenes glands. The demonstration of a rare form of urethral cancer, clear cell adenocarcinoma, contributes to the accumulation of knowledge about its histopathology and clinical course, as well as increasing cancer alertness in the treatment of urethral diseases in doctors of any specialty.

Outcomes of surgical resection for pulmonary metastasis from ovarian cancer

BackgroundDue to its rarity, information on pulmonary metastasectomy for pulmonary metastasis from ovarian cancer is limited.MethodsCases of pulmonary metastasectomy for ovarian cancer were collected in a multi-institutional setting and the outcomes were analyzed.ResultsAmong 1508 cases in which pulmonary resection was performed to treat pulmonary metastasis from tumors of various organs, 6 cases (0.4%) involved pulmonary metastasis from ovarian cancer. The mean age was 61 years (range, 39–75 years). The histological types were undifferentiated carcinoma in 2 patients, and clear cell adenocarcinoma, serous papillary cystadenocarcinoma, serous adenocarcinoma, and endometroid adenocarcinoma in 1 patient each. One patient (17%) had a history of liver metastasis at the time of pulmonary resection. The median disease-free interval was 22 months (range, 0 [synchronous]-188 months). The tumor was solitary in 5 patients (83%). The mean tumor size was 15 mm (range, 5–23 mm). All 6 patients underwent complete resection. The type of resection was wide wedge resection in 3 patients, segmentectomy in 2 patients, and lobectomy in 1 patient. Four patients (67%) received postoperative chemotherapy. Thus far, 4 patients (67%) have experienced recurrence after pulmonary resection. In terms of outcomes, 1 patient who had synchronous pulmonary metastasis with the primary tumor died in the early period after pulmonary resection, 1 patient is alive without recurrence after a short follow-up period (5 months), 3 patients have achieved mid- to long-term survival and are alive with disease (38–61 months), and 1 patient achieved long-term (61 months) disease-free survival.ConclusionsPatients with pulmonary metastasis from ovarian cancer who fulfill the eligibility criteria for pulmonary metastasectomy are rare. Pulmonary metastasectomy for ovarian cancer can provide favorable outcomes in highly selected patients. Patients with synchronous pulmonary metastasis from ovarian cancer are not good candidates for pulmonary metastasectomy.

Abstract A56: Novel L-sugar linked glycosylated antitumor ether lipids for killing platinum-resistant human epithelial ovarian cancer cells

Abstract Glycosylated antitumor ether lipids (GAELs) are a promising class of investigational anticancer agents with potent antitumor activity against a range of cancers, including platinum-resistant high-grade serous ovarian cancer (HGSOC). We previously demonstrated that epithelial ovarian cancer (EOC) cell lines (HGSOC and endometrioid) and primary cells derived from patient ascites (HGSOC and clear cell) were sensitive to the cell-killing effects of D-glucosamine-derived GAELs via an apoptosis-independent mechanism. However, D-linked carbohydrates are metabolized by endogenous glucosidases in vivo, rendering the GAEL inactive. Thus, the aim of the current study was to synthesize a novel class of GAELs with L-linked carbohydrates and to evaluate their efficacy in EOC cell lines and patient samples. Out of seven novel compounds tested, L-rhamnose-GAEL was identified as the compound with the greatest efficacy for killing EOC cell lines and patient cells that were grown under adherent or nonadherent (3D) conditions. The drug-sensitive and drug-resistant syngeneic endometrioid EOC cell lines, A2780s and A2780cp, respectively, as well as the NIH:OVCAR-3 and COV362 HGSOC lines, were incubated with L-rhamnose-GAEL for 48 hours and the CC50 determined as 15 μM for A2780s, 22.5 μM for A2780cp, and 5 μM for NIH:OVCAR-3 and COV362 cells. Similar experiments were conducted with primary EOC cells, chemo-naïve EOC126 (clear-cell adenocarcinoma), and platinum-resistant EOC 183I (HGSOC). Cell viability decreased in a dose-dependent manner with CC50 of 12 μM for EOC126 and 22.5 μM for EOC183l. For comparison, when EOC126 and EOC183I were grown as 3D cultures the CC50for cisplatin was 20 μM and 40 μM, respectively. To evaluate the effect of using low-dose treatment of L-rhamnose-GAEL on primary EOC cells (chemo-naive and chemoresistant), cells were exposed to L-rhamnose-GAEL for 96 hours. These studies revealed that prolonged incubation led to low CC50 of 1-5 μM. These results showed that primary EOC cells derived from chemo-naïve and platinum-resistant patients were sensitive to the L-rhamnose-GAEL and offer a novel drug class capable of killing chemotherapy-resistant EOC cells. Citation Format: Mark W. Nachtigal, Frank Schweizer, Gilbert Arthur. Novel L-sugar linked glycosylated antitumor ether lipids for killing platinum-resistant human epithelial ovarian cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A56.

Appendageal tumors and tumor-like lesions of the testis and paratestis: a 32-year experience at a single institution

The testicular hilum and paratestis contain several embryologically diverse anatomic structures, including the spermatic cord, tunica vaginalis, epididymis, rete testis, and several other embryonic remnants. Several benign and malignant lesions arise from these morphologically distinct structures, andowing to their proximity, it is challenging to classify and subsequently stage these tumors. Herein, we conducted a retrospective review of the paratesticular appendageal and rete testis tumors and tumor-like lesions diagnosed at our department from 1985 to 2016. Soft-tissue lesions/tumors were excluded. A total of 146 paratesticular appendageal and rete testis tumors and tumor-like lesions were identified. Most were benign (n=107; 73%). Adenomatoid tumor (26%) was the most common benign tumor, followed by different types of cysts (19%), mesothelial hyperplasia (18%), serous cystadenoma (5.5%), and rete testis adenoma (4%). Malignant lesions comprised 23% of the cases, with mesothelioma the most common (15%), followed by adenocarcinoma of the rete testis (4%), serous cystadenocarcinoma (2%), and papillary and clear cell adenocarcinoma of the epididymis (2%). Finally, serous borderline tumors and melanotic neuroectodermal tumor (retinal anlage tumors) comprised the remaining 4% of cases. In conclusion, a wide range of benign and malignant lesions can arise from the paratesticular region. Awareness of these lesions and their histologic spectrum is crucial to avoid diagnostic pitfalls and to allow pathologists to establish a correct diagnosis and subsequent treatment plan.

A clinical study of tremelimumab alone or in combination with olaparib in patients with advanced epithelial ovarian cancer.

6045 Background: Single agent immunotherapy (IO) has shown only modest clinical activity for the treatment of ovarian cancer. The combination of anti-programmed death-1 and PARP inhibitors showed promising activity in early trials. Here, we report the results of an open-label, parallel arm, dose escalation study of tremelimumab (T) alone or in combination with olaparib (O) in patients (pts) with advanced epithelial ovarian cancer (EOC). Methods: Pts with recurrent/persistent EOC who had progression &lt; 12 months from last platinum exposure were enrolled. Prior therapy with IO (except anti-CTLA-4) or PARP inhibitor was allowed. Pts were randomized to either T 10mg/kg every 4 weeks (wks) x 7 then every 12 wks (Arm A) or T with O twice daily at three planned dose levels (Arm B). The primary objectives were safety, pharmacodynamic (PD) change in CD4+ICOShi peripheral T cells by flow cytometry, and identification of the optimal dose combination of T with O. Secondary objectives included 6-month progression-free survival (PFS6) and objective response rate (ORR). Results: A total of 24 pts were treated, 12 on Arm A, and 12 on two Arm B dose levels. Pts had a median age of 60 years (range 44-81). Histologic subtypes included high-grade serous EOC (20 pts, 83%), clear cell (3 pts, 13%), and moderately-differentiated adenocarcinoma (1 pt, 4%). BRCA1 mutation (mt) was present in 2 cases, BRCA2 mt in 1. Median number of prior regimens was 3.5 (range 1-9). Most adverse events (AEs) were attributable to T, the most common grade 3 toxicities were rash (13%), immune-mediated hepatitis (8%), and colitis (8%). No grade ≥4 toxicities were identified. Immune-mediated AEs also included acute kidney injury, hypophysitis, and hypothyroidism. No dose limiting toxicities were identified on Arm B. Two pts in Arm B had &gt;PFS6. Of 20 pts evaluable for response, there was 1 partial response (Arm B), and 9 pts had stable disease (6 on Arm A, 3 on Arm B). Mean percentage of CD4+ICOShi T cells was significantly increased on Days 15 and 22 compared to Day 1 at both T dose levels (Table).T at 3 mg/kg with O at 150mg is the optimal dose of those tested. Conclusions: T and T with O was tolerable, with modest clinical activity in this pt population. AEs were as expected, and peripheral CD4+ICOShi T cells increased on therapy. Clinical trial information: 02485990. [Table: see text]

Primary clear cell adenocarcinoma of the vagina in a young female with uterus didelphys

Adenocarcinomas of clear cell type are uncommon tumors accounting for 5-10% of all vaginal tumours which in turn account for approximately 2% of all gynaecologic malignancies. Though Clear cell Adenocarcinomas arising in the setting of previous Di-Ethyl–Stilbesterol [DES] exposure have been reported quite often, only few cases of these not associated with DES have been documented. Amongst non-DES exposed patients, CCAs are said to be sporadic or in association with endometriosis in women of peri/postmenopausal age or in association with some congenital genitourinary anomalies mostly affecting young females. A 16 year old female presented with heavy bleeding per vaginum since 2 months. On per vaginal examination a polypoidal mass was felt on posterior wall of vagina. Ultrasonography revealed the presence of a uterus didelphys in addition to this mass. Polypectomy was done. On microscopy, a diagnosis of clear cell adenocarcinoma was made which was confirmed on immunohistochemistry. There was no history of any DES exposure in the mother. We present here a case of an adolescent female with uterus didelphys and no DES exposure who was diagnosed as a case of Vaginal Clear cell Adenocarcinoma. The rarity of this tumour among DES-exposed cases and its presence in non-exposed patients warrants a more thorough search for the underlying pathology.

Ovarian Endometriosis with Borderline Serous Tumor- Association or Coincidence – A Case Report and Review of Literature

AbstractEndometriosis is the presence of endometrial glands outside the endometrium, and ovary is the common site for endometriosis. Endometriosis can also transform into malignant tumors. When endometriosis is present within the tumors, the term endometriosis-derived tumor applies, whereas when endometriosis is recognized adjacent to the tumor, it is called as endometriosis-associated tumor. Borderline serous tumor is surface epithelial ovarian tumor. The endometriosis-associated ovarian malignancies are clear cell adenocarcinoma and endometrioid adenocarcinoma, whereas serous and mucinous are rare malignancies with endometriosis. Here, we are presenting a case report in which endometriosis was associated with borderline serous tumor.

Personalized chemotherapy in clear cell adenocarcinoma of the urethra: A case report

Personalized chemotherapy in clear cell adenocarcinoma of the urethra: A case report