Primary Clear Cell Carcinoma Research Articles

Integrative analysis of protein-coding and non-coding RNAs identifies clinically relevant subtypes of clear cell renal cell carcinoma

Protein-coding genes and non-coding RNAs cooperate mutually in cells. Integrative analysis of protein-coding and non-coding RNAs may facilitate characterizing tumor heterogeneity. We introduced integrated consensus clustering (ICC) method to integrate mRNA, miRNA and lncRNA expression profiles of 431 primary clear cell renal cell carcinomas (ccRCCs). We identified one RCC subgroup easily misdiagnosed as ccRCC in clinic and four robust ccRCC subtypes associated with distinct clinicopathologic and molecular features. In subtype R1, AMPK signaling pathway is significantly upregulated, which may improve the oncologic-metabolic shift and partially account for its best prognosis. Subtype R2 has more chromosomal abnormities, higher expression of cell cycle genes and less expression of genes in various metabolism pathways, which may explain its more aggressive characteristic and the worst prognosis. Moreover, much more miRNAs and lncRNAs are significantly upregulated in R2 and R4 respectively, suggesting more important roles of miRNAs in R2 and lncRNAs in R4. Triple-color co-expression network analysis identified 28 differentially expressed modules, indicating the importance of cooperative regulation of mRNAs, miRNAs and lncRNAs in ccRCC. This study establishes an integrated transcriptomic classification which may contribute to understanding the heterogeneity and implicating the treatment of ccRCC.

On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models.

Clear cell renal cell carcinoma, the most common form of kidney cancer, is usually linked to inactivation of the pVHL tumour suppressor protein and consequent accumulation of the HIF-2α transcription factor (also known as EPAS1). Here we show that a small molecule (PT2399) that directly inhibits HIF-2α causes tumour regression in preclinical mouse models of primary and metastatic pVHL-defective clear cell renal cell carcinoma in an on-target fashion. pVHL-defective clear cell renal cell carcinoma cell lines display unexpectedly variable sensitivity to PT2399, however, suggesting the need for predictive biomarkers to be developed to use this approach optimally in the clinic.

Hepatitis and Solitary Left Renal Mass: Renal Hepatocellular Carcinoma

Solitary renal tumours are often primary clear cell carcinoma. A 48-year-old man with chronic hepatitis, hepatocellular carcinoma (HCC), and orthotropic liver transplant 6years ago presented with a solitary left renal mass. Histology revealed metastatic HCC of the left kidney with extensive reactive changes in lymph nodes. Interestingly, biopsy of the transplanted liver showed no evidence of HCC recurrence. Metastatic disease to the kidney often disseminate locally through transcelomic spread, or hematogenous affecting both kidneys. It is important to recognize extrahepatic HCC metastases to the contralateral kidney, especially in patients with active hepatitis, and radical lymph node clearance is needed.

Abstract 207: Regulation of mitochondrial biogenesis in primary human clear cell renal cell carcinoma cells

Abstract Clear cell renal cell carcinoma, ccRCC, is the most prevalent type of kidney cancer. In over 90% of ccRCCs the tumor suppressor protein von Hippel Lindau is inactivated, leading to a pseudohypoxic phenotype with vast effects on angiogenesis as well as energy metabolism. In accordance with the Warburg effect, aerobic glycolysis increases, while mitochondrial oxidative phosphorylation is decreased. We have previously published data showing that also the number and activity of mitochondria is strikingly reduced in primary human ccRCC cells compared to normal kidney epithelial cells. This was not seen in any of the established RCC cell lines included in the study. We are now continuing these studies by investigating the regulation of mitochondrial biogenesis in primary human ccRCC cells, and how the number and activity of mitochondria influences the tumorigenic properties of these cells. RNA has been isolated from ccRCC tissue areas identified as mitochondria high or low. The expression profile in these samples will be analyzed by RNA sequencing. Human primary ccRCC cells obtained from patient nephrectomies are kept in culture and the regulation of mitochondrial biogenesis in these cells is investigated. How the mitochondrial content affects tumorigenic properties such as proliferation, migration and resistance to apoptosis is also investigated. Preliminary data indicate that primary ccRCC cells have an absent or severly limited capability to increase the number of mitochondria on metabolic demand, and that the regulation of mitogenesis is defective. These results point towards a malfunctioning energy sensing and mitochondrial biogenesis in ccRCC cells that might be part of the explanation to the very low mitochondrial content in these cells. Citation Format: Helén Å. Nilsson, Martin E. Johansson. Regulation of mitochondrial biogenesis in primary human clear cell renal cell carcinoma cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 207.

Long-term survival and prognosis for primary clear cell carcinoma of the liver after hepatectomy

BackgroundThe aim of this study was to investigate the long-term survival and prognosis for primary clear cell carcinoma of the liver (PCCCL) of the liver after hepatectomy.MethodsOur study retrospectively analyzed the clinicopathological data of 64 patients with PCCCL (PCCCL group) and 247 with nonclear cell hepatocellular carcinoma (NHCC group) after hepatectomy between January 1996 and December 2006. The overall survival (OS) and disease-free survival of the two groups was compared using the Kaplan–Meier method. Prognostic factors of survival were identified by multivariate analysis.ResultsThe 1-, 3-, and 5-year OS (P=0.016) and disease-free survival (P<0.001) of the PCCCL group were significantly higher than that of the NHCC group. In mutivariate analysis, tumor size >5 cm, presence of portal vein tumor thrombosis and proportion of clear cells ≤70% were risk factors for OS of the PCCCL group. The prognosis of a subgroup with higher proportion of clear cells was markedly better than that of the subgroup with a lower proportion of clear cells.ConclusionOur results suggested that the prognosis of patients with PCCCL was better than that of the patients with NHCC. The higher the proportion of clear cells, the better the prognosis.

Molecular status of PI3KCA, KRAS and BRAF in ovarian clear cell carcinoma: an analysis of 63 patients

AimsTo evaluate the incidence of PI3KCA, KRAS and BRAF mutations in primary ovarian clear cell carcinoma (OCCC).Methods63 consecutive patients, with a proven diagnosis of OCCC, according to WHO criteria, were...

Edmondson grade predicts survival of patients with primary clear cell carcinoma of liver after curative resection: A retrospective study with long-term follow-up.

Primary clear cell carcinoma of liver (PCCCL) is a specific and rare subtype of primary hepatocellular carcinoma (HCC). We performed a retrospective study with long-term follow-up to investigate predictive factors and prognosis of intrahepatic recurrences of PCCCL after radical resection. We retrospectively analyzed records of 38 patients with PCCCL who were diagnosed at Peking Union Medical College Hospital between January 1989 and September 2010, with a long-term follow up to January 2015, to determine their clinical characteristics and postoperative survival. The data were compared with 400 patients received radical hepatectomy for common type hepatocellular carcinoma (CHCC) during the study period. PCCCL tumors were smaller than those of CHCC (P < 0.001) and the incidence of vascular invasion of tumors in PCCCL group was significantly lower than that in CHCC (P = 0.029). The 1-, 3-, and 5-year overall survival (OS) for PCCCL patients were 94.6%, 67.3%, and 58.5%, respectively; 1-, 3-, and 5-year disease-free survival (DFS) were 89.2%, 54.1%, and 48.6%, respectively. Both OS and DFS were significantly better for PCCCL patients than for CHCC (P = 0.039 and 0.044). Cox modeling showed high Edmondson grade to be the only independent predictive factor for survival of PCCCL patients, which were different from those of CHCC. PCCCL is a less malignant subtype of HCC than CHCC, patients with PCCCL likely have later intrahepatic recurrences and a better prognosis. Edmondson grade predicts survival of patients with PCCCL after curative resection; those with higher Edmondson grades may require more careful follow-up and aggressive post-hepatectomy therapy.

Identification of DNA Methylation-Independent Epigenetic Events Underlying Clear Cell Renal Cell Carcinoma.

Alterations in chromatin accessibility independent of DNA methylation can affect cancer-related gene expression, but are often overlooked in conventional epigenomic profiling approaches. In this study, we describe a cost-effective and computationally simple assay called AcceSssIble to simultaneously interrogate DNA methylation and chromatin accessibility alterations in primary human clear cell renal cell carcinomas (ccRCC). Our study revealed significant perturbations to the ccRCC epigenome and identified gene expression changes that were specifically attributed to the chromatin accessibility status whether or not DNA methylation was involved. Compared with commonly mutated genes in ccRCC, such as the von Hippel-Lindau (VHL) tumor suppressor, the genes identified by AcceSssIble comprised distinct pathways and more frequently underwent epigenetic changes, suggesting that genetic and epigenetic alterations could be independent events in ccRCC. Specifically, we found unique DNA methylation-independent promoter accessibility alterations in pathways mimicking VHL deficiency. Overall, this study provides a novel approach for identifying new epigenetic-based therapeutic targets, previously undetectable by DNA methylation studies alone, that may complement current genetic-based treatment strategies. Cancer Res; 76(7); 1954-64. ©2016 AACR.

Clear cell carcinoma arising in previous episiotomy scar: a case report and review of the literature

BackgroundMalignant transformation of endometriosis associated with episiotomy scar is a rare event, especially histological type of clear cell adenocarcinoma. There are only three clear cell carcinoma in episiotomy scar reported, no standard treatment established.Case presentationA 36-year-old woman presented with a two-month history of painless but puritic perineal lump which she noticed was gradually enlarging. She had undergone surgical excision of a mass in the episiotomy scar 9 year ago and resequently histological type of endometriosis. Physical examination revealed a 10 × 5 cm soft, purple scar which is closely related to the apex of the episiotomy.We underwent a local excision of the mass for a biopsy . The second surgery performed after one cycle of paclitaxel and cisplatin (TP) to permit clearance of tumor while preserving normal vaginal function.Pathological result was clear cell adenocarcinoma. Two cycles of TP adjuvant chemotherapy were administrated after surgery.ConclusionsWe report a case of primary clear cell carcinoma developing within a previous episiotomy scar in a patient with a history of endometriosis, along with a review of the literature. Accumulation of management data on these rare tumors and Long-term follow-up of such patients is therefore important.

Abstract 10: Concordance of BAP1, PBRM1, Ki-67, and TOPOIIa protein expression in primary clear cell renal cell carcinoma tumors and patient-matched metastatic tumors

Abstract Introduction: Efforts to improve clear cell renal cell carcinoma (ccRCC) mortality have focused primarily on evaluating prognostic biomarkers in primary tumors in order to identify indicators of response to treatment and targets for novel therapies. To date little attention has been paid to the status of these biomarkers in the more therapeutically-relevant metastatic tumor. Thus, we evaluated concordance of expression of four key prognostic ccRCC biomarkers (BAP1, PBRM1, Ki-67 and TOPOIIa) in a large cohort of patient-matched primary ccRCC and metastatic tumors. Methods: We identified 114 patients treated surgically for ccRCC between 1990 and 2005 who had synchronous (M1) or metachronous (M0) metastases, underwent metastasectomy for at least one metastatic lesion and had archived tissue available from the primary and at least one metastatic tumor. We performed IHC on all primary and metastatic tumors for BAP1, PBRM1, Ki-67, and TOPOIIa using previously-published protocols. BAP1 and PBRM1 expression was categorized as positive or negative and Ki-67 and TOPOIIa was quantified as the number of positive cells per mm2. For BAP1 and PBRM1, we calculated the concordance between patient-matched primary and metastatic tumors as the percentage of pairs where the primary and metastatic tumor had the same designation (i.e., positive or negative). For TOPOIIa and Ki-67, we assessed concordance using Spearman correlation coefficient. Analysis of variance was used to evaluate if concordance between primary-metastatic tumor pairs for TOPOIIa and Ki-67 was associated with metastatic site, metastatic timing (M0/M1), metastatic tumor grade, metastatic tumor necrosis, and metastatic tumor sarcomatoid differentiation. Results: There were a total of 161 patient-matched metastatic tumors available for the 114 patients: 78 patients had only a single metastasis while 36 patients had two or more metastases. While sites of metastases varied, pulmonary metastases were the most common (44% of all metastases). Loss of BAP1 expression was observed in19% of the primary ccRCC and 98.6% of the tumor pairs had concordant BAP1 status between the paired primary and metastatic tumors. Loss of PBRM1 was observed in 56% of the primary ccRCC tumors and 89.3% of tumor pairs showed concordant PBRM1 status. By comparison, median expression of Ki-67 was 65.0mm2 in the primary ccRCC tumors and the Pearson correlation with the patient-matched metastatic tumors was 0.43. The difference in Ki-67 expression between primary-metastatic tumor pairs was associated with necrosis in the metastatic tumor (p=0.014). Median expression of TOPOIIa was 2.6mm2 in the primary ccRCC tumors and the Pearson correlation with the patient-matched metastatic tumors was 0.25. The difference in TOPOIIa expression between primary-metastatic tumor pairs was associated with metastatic site (p=0.0006) and metastases to the heart were significantly different than pulmonary metastases (p&amp;lt;0.0001). Additionally, synchronous metastases had larger differences from their patient-matched primary tumors in comparison to metachronous metastases (p=0.012), as did necrotic metastases (p=0.028). Conclusion: We observed high concordance for loss of BAP1 and PBRM1 expression between primary ccRCC and metastatic tumors in the same patient. Conversely, we noted high discordance in protein expression of Ki-67 and TOPOIIa between patient-matched primary-metastatic tumor pairs. Moreover, this discordance varied by key pathological features. Our results suggest that using the status of a biomarker in primary ccRCC as a guide for the status in metastatic tumors is not always appropriate and needs to be evaluated on a marker-by-marker basis. Citation Format: Jeanette E. Eckel-Passow, Daniel J. Serie, John C. Cheville, Thai H. Ho, Sue M. Harrington, Tracy Hilton, Christine Lohse, Amanda Shreders, Payal Kapur, James Brugarolas, R Houston Thompson, Bradley C. Leibovich, Eugene D. Kwon, Richard W. Joseph, Alexander S. Parker. Concordance of BAP1, PBRM1, Ki-67, and TOPOIIa protein expression in primary clear cell renal cell carcinoma tumors and patient-matched metastatic tumors. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 10.

Abstract IA20: Cancer subtypes and their immune microenvironments

Abstract In the vast majority of cancer types, as demonstrated and exemplified in colorectal cancer (CRC) and non-small cell lung cancer (NSCLC), a high density of CD8+ T cells associated with high densities of tertiary lymphoid structures (TLS) in the tumor microenvironment correlates with a good prognosis for the patient. However, an opposite association has been reported in primary clear cell renal cell carcinoma (RCC) and several other cancers. Our team studied the immune infiltrates of pulmonary metastases from CRC and RCC. As in the primary tumors, a high density of CD8+ T cells correlated with good prognosis for CRC metastases, while it correlated with a bad prognosis for RCC metastases. These results suggested that the identity of the tumor cells, rather than the organ where they grow, is critical for shaping the immune contexture of a given tumor. Transcriptomic analyses of large cohorts of human CRC and RCC allow to define molecular subgroups associated with distinct risks of tumor progression. We therefore characterized the immune microenvironments of the molecular subgroups of CRC and RCC. In CRC, the MSI-enriched subgroup identified patients with high cytotoxic T cells infiltration and favorable prognosis. In CRC and RCC, we confirmed that patients with low tumoral T and B cell infiltrations presented with high risk of death; In addition, in both cancer types, we identified subgroups of poor-prognosis patients with high tumoral lymphocyte infiltration, in the context of high expression of genes related to inflammation, immunosuppression, and angiogenesis. Integration of molecular and immune tumor phenotypes refines prognostic cancer groups. Moreover, these classifications allow to select immunotherapies appropriate to specific, potentially responding, groups of patients. Citation Format: Etienne Becht, Nicolas A. Giraldo, Aurelien De Reynies, Pierre Laurent-Puig, Benoit Beuselinck, Jessica Zucman-Rossi, Marie Caroline Dieu-Nosjean, Catherine Sautes-Fridman, Wolf H. Fridman. Cancer subtypes and their immune microenvironments. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA20.

Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma.

Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer.

CMTM4 is frequently downregulated and functions as a tumour suppressor in clear cell renal cell carcinoma.

BackgroundChemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM) is a gene family involved in multiple malignancies. CMTM4 is a member of this family and is located at chromosome 16q22.1, a locus that harbours a number of tumour suppressor genes. It has been defined as a regulator of cell cycle and division in HeLa cells; however, its roles in tumourigenesis remain poorly studied.MethodsAn integrated bioinformatics analysis based on the array data from the GEO database was conducted to view the differential expression of CMTM4 across multiple cancers and their corresponding control tissues. Primary clear cell renal cell carcinoma (ccRCC) and the paired adjacent non-tumour tissues were then collected to examine the expression of CMTM4 by western blotting, immunohistochemistry, and quantitative RT-PCR. The ccRCC cell lines A498 and 786-O and the normal renal tubular epithelial cell line HK-2 were also tested for CMTM4 expression by western blotting. Cell Counting Kit-8 (CCK-8) and viable cell counting assays were used to delineate the growth curves of 786-O cells after CMTM4 overexpression or knockdown. Wound healing and transwell assays were performed to assess the cells’ ability to migrate. The effects of CMTM4 on cellular apoptosis and cell cycle progression were analysed by flow cytometry, and cell cycle hallmarks were detected by western blotting and RT-PCR. The xenograft model in nude mice was used to elucidate the function of CMTM4 in tumourigenesis ex vivo.ResultsBy omic data analysis, we found a substantial downregulation of CMTM4 in ccRCC. Western blotting then confirmed that CMTM4 was dramatically reduced in 86.9 % (53/61) of ccRCC tissues compared with the paired adjacent non-tumour tissues, as well as in the 786-O and A498 ccRCC cell lines. Restoration of CMTM4 significantly suppressed 786-O cell growth by inducing G2/M cell cycle arrest and p21 upregulation, and cell migration was also inhibited. However, knockdown of CMTM4 led to a completely opposite effect on these cell behaviours. Overexpression of CMTM4 also markedly inhibited the tumour xenograft growth in nude mice.ConclusionsCMTM4 is downregulated and exhibits tumour-suppressor activities in ccRCC, and could be exploited as a target for ccRCC treatment.

Clear Cell Renal Cell Carcinoma Subtypes Identified by BAP1 and PBRM1 Expression

In clear cell renal cell carcinoma BAP1 and PBRM1 are 2 of the most commonly mutated genes (10% to 15% and 40% to 50%, respectively). We sought to determine the prognostic significance of PBRM1 and BAP1 expression in clear cell renal cell carcinoma. We used immunohistochemistry to assess PBRM1 protein expression in 1,479 primary clear cell renal cell carcinoma tumors that were previously stained for BAP1. A centralized pathologist reviewed all cases and categorized tumors as positive or deficient for PBRM1 and BAP1. Kaplan-Meier and Cox regression models were used to evaluate association of PBRM1 and BAP1 expression with the risk of death from renal cell carcinoma and the risk of metastasis after adjustment for age and the Mayo Clinic SSIGN (stage, size, grade and necrosis) score. PBRM1 and BAP1 expression was PBRM1+ BAP1+ in 40.1% of tumors, PBRM1- BAP1+ in 48.6%, PBRM1+ BAP1- in 8.7% and PBRM1- BAP1- in 1.8%. The incidence of PBRM1 and BAP1 loss in the same tumor was significantly lower than expected (actual 1.8% vs expected 5.3%, p <0.0001). Compared to patients with PBRM1+ BAP1+ tumors those with PBRM1- BAP1+ lesions were more likely to die of renal cell carcinoma (HR 1.39, p = 0.035), followed by those with PBRM1+ BAP1- and PBRM1- BAP1- tumors (HR 3.25 and 5.2, respectively, each p <0.001). PBRM1 and BAP1 expression did not add independent prognostic information to the SSIGN score. PBRM1 and BAP1 expression identified 4 clinical subgroups of patients with clear cell renal cell carcinoma who had divergent clinical outcomes. The clinical value of these biomarkers will be fully realized when therapies targeting pathways downstream of PBRM1 and BAP1 are developed.

CD147, The Ancillary protein of MCT4, as marker for prognosis and clinical outcome in primary clear cell renal cell Carcinoma and Metastasis

CD147, The Ancillary protein of MCT4, as marker for prognosis and clinical outcome in primary clear cell renal cell Carcinoma and Metastasis

Primary ovarian clear cell carcinoma of the abdominal wall – a systemic literature review: Implication for surgical management.

Primary ovarian clear cell carcinoma of the abdominal wall – a systemic literature review: Implication for surgical management.

MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors.

Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P = 0.1). MET expression weakly correlated between primary and matched metastatic sites (R = 0.5) and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P = 0.39). Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

Renal-type clear cell carcinoma of the prostate: A case report.

Renal-type clear cell carcinoma of the prostate is a rare and novel tumor that has only been identified in recent years. The present study describes a lesion in the prostate of a 64-year-old male with a two-year history of urinary frequency, urgency and difficulty, who was admitted to the San Ai Tang Hospital for benign prostatic hyperplasia, and subsequently underwent transurethral resection of the prostate. In total, 12 g of tissue was resected, which demonstrated morphological and immunohistochemical similarities to clear cell carcinoma of the kidney. Ultrasound inspection and computed tomography revealed prostate enlargement. Although no renal-enclosed mass was identified, metastatic lesions were revealed in the lungs, sternum and clavicles. In addition, right pleural thickening and a small amount of effusion in the pleural cavity were detected. Clear cell carcinoma was identified throughout the prostate, with surrounding regions of ordinary-type prostatic adenocarcinoma (Gleason score, 4+4). The urinary bladder exhibited no dysplasia or neoplasia. It was therefore concluded that the tumor represented a primary renal-type clear cell carcinoma that had arisen in the prostate. To the best of our knowledge, this type of extra-renal tumor has only been reported in three other previous studies.

A Giant Primary Clear Cell Hepatocellular Carcinoma in a Young Woman without Cirrhosis

Primary clear cell carcinoma of the liver (PCCCL) is an uncommon variant of hepatocellular carcinoma, usually occurring in older patients with longstanding cirrhosis. We report a case of a giant PCCCL rupturing in a young woman without cirrhosis. A 29 year-old female who presented with a three month history of abdominal pain, nausea, vomiting, food intolerance, and unintentional weight loss, was found to have gastric varices and a large liver mass measuring 22.8cm × 17.8 cm × 13.8 cm. The tumor was comprised of sheets of clear cells with delicate vesicular architecture, and was positive for Hepar 1, Glypican 3, and CD34 in a diffuse staining pattern and CD10 in a canalicular staining pattern, establishing the diagnosis of PCCCL. The patient died of hemorrhagic shock secondary to tumor rupture within two weeks of diagnosis. Conclusion: Although PCCCL most often occurs in older patients with cirrhosis, this uncommon variant of HCC can arise in younger patients without a history of liver disease. It is important to diagnose PCCCL early due to the potentially favorable prognosis of this specific cancer and in order to prevent catastrophic complications.

Primary clear cell carcinoma of the cystic duct -a case report-

Primary clear cell carcinoma of the cystic duct -a case report-