Metastatic Origin Research Articles

Dissection of primary prostate cancer to determine the clonal origin of synchronous lymph node metastasis.

e17614 Background: Primary prostate cancer often consists of multiple, genomically-distinct clones. The clonal source of lymph node metastasis in multifocal disease is unknown. We sought to analyze and determine the histopathologic and molecular characteristics of the tumor sub-clones capable of metastasis in primary prostate cancers with synchronous lymph node metastasis. Methods: We identified patients with primary prostate cancer found to have lymph node (LN) metastasis at the time of radical prostatectomy, including those with multifocal disease. Punch biopsies were obtained from multiple regions of primary tumors and LN metastases. Targeted next generation sequencing to assess somatic DNA mutations, copy number alterations (CNA), and TMPRSS2:ERG fusion status. Bioinformatic analyses were performed using in-house developed pipelines. Phylogenetic evolutionary analyses were performed to delineate the primary cancer clone responsible for LN metastasis. Results: We identified 2 patients with LN cancer regions. In one patient, while all four Grade Group (GG) 5 primary tumor (PT) regions showed concordant TP53 and TPR non-synonymous mutations and broad copy number alterations (CNAs) with two LN foci, only two regions shared high level CNAs with both lymph node foci. In this case, a GG1 tumor focus showed no TP53 somatic mutation or CNA overlap with the high-grade tumor or lymph node samples. Critically, phylogenetic analysis revealed that the GG5 PT with extra-prostatic extension (EPE) showed higher concordance with the LN metastases than regions confined to the prostate. In another patient with four PT, phylogenetic analysis revealed that the PT with EPE closely resembled the LN metastasis; both were TMPRSS2:ERG fusion positive share PTEN copy number loss. Two PT (GG1 and 2) appeared to be independent clones and were TMPRSS2:ERG fusion negative. One of the six circulating tumor cells (isolated pre-prostatectomy) from this patient demonstrated a significant PTEN copy loss consistent with the findings in the region of EPE and the LN metastasis. Conclusions: Our findings confirm molecular heterogeneity of primary prostate cancers and homogeneity of LN metastases supporting the use of shared molecular alterations to infer clonal lineage. Our results highlight the critical role of adverse pathologic features, such as grade and EPE, in prostate cancer with synchronous lymph node metastasis.

Metastasis to the scalp as the first finding of Clear Cell Carcinoma of the Kidney: Case Report and Review of the Literature

The case of a 70-year-old man, with no previous pathological history, who consulted for post-traumatic injury to the scalp; it was managed as a benign lesion and it was taken to surgical resection with a histopathology and immunohistochemistry study compatible with clear cell neoplasia of metastatic renal origin. Extension studies were performed with findings of pulmonary nodules that suggested metastatic disease and with a finding of right renal mass. Radical nephrectomy is performed confirming the diagnosis of renal cell carcinoma subtype clear cells. A review of the literature was carried out, which shows that a skin lesion may be the first symptom of an internal neoplasm, with breast cancer being the most frequent one reported in the literature in cutaneous metastases. The finding of a posttraumatic injury to the scalp as the first sign of a clear cell carcinoma of renal origin is very rare. The diagnosis of skin metastases requires a histopathology and immunohistochemistry study, which must be timely because it may be the first link in the research chain to detect an occult neoplasm. In conclusion, the surgeon who faces a soft tissue tumor on the scalp must consider the characteristics of the lesion, the patient’s risk factors in an articulated way that allows him to suspect malignancy in a skin lesion and that allows him diagnose a previously unknown and asymptomatic neoplasm.

MP08-01 SETD2/MIR-378/OCT-4 PATHWAY REGULATES THE SELF-RENEWAL AND MOTILITY IN CD105(+) KIDNEY CANCER STEM CELLS

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (MP08)1 Apr 2020MP08-01 SETD2/MIR-378/OCT-4 PATHWAY REGULATES THE SELF-RENEWAL AND MOTILITY IN CD105(+) KIDNEY CANCER STEM CELLS Guoliang Sun, Libin Yan, and Yue Ge* Guoliang SunGuoliang Sun More articles by this author , Libin YanLibin Yan More articles by this author , and Yue Ge*Yue Ge* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000828.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Renal cell carcinoma (RCC) is one of the few cancer types that are resistant to both radiotherapy and conventional platinum-based chemotherapy. Clear cell RCC (ccRCC) is the most common type and its 5-year survival rate can be as poor as 8% in high risk patients. What’s worse, cancer cells tend to be more and more drug resistant after many rounds of treatments. To this end, cancer stem cell model was brought to explain that a subpopulation within thousands of cancer cells represents as the origin of tumor relapse, progression and metastasis. Previously, we proved that CD105(+) cells possess the property of cancer initiating cells in ccRCC and might serve as a potential therapeutic target. Here, we aimed to uncover the mechanism of self-renewal and motility of CD105(+) renal cell stem cells (RCSCs). METHODS: Overexpression and interference plasmid were construct and transfected into cell lines. Scratch assay, modified 3D transwell assay, sphere formation assay and in vivo kidney cancer orthotopic model, etc. were conducted to explore the function of genes. RESULTS: A non-coding microRNA miR-378 was found to be downregulated in the CD105(+) RCSCs in a panel of 30 microRNAs we screened. Furthermore, artificial overexpression of miR-378 can not only significantly decrease the motility in scratch assay and a modified 3D transwell assay, but also decrease the self-renewal of RCSCs via sphere formation assay. In addition, the in vivo kidney cancer orthotopic model further validated that miR-378 can inhibit RCSCs’ tumorigenesis. Mechanistically, Oct-4 was verified to be a putative target of miR-378 while Oct-4, act as a transcriptional factor can also negatively regulates miR-378. The decrease in motility and sphere formation ability of RCSCs brought by miR-378 can be abrogated by Oct-4 overexpression. In the upstream of miR-378, SETD2 was validated to be one of its regulatory proteins mediating the histone methylation of miR-378, which was verified by ChIP. Also, miR-378 was found to be increased upon SETD2 downregulation. CONCLUSIONS: Collectively, SETD2/miR-378/Oct-4 regulatory pathway plays a critical role in RCSCs’ self-renewal and motility, which signifies its potential therapeutic application in targeting the stem cells in clear cell carcinoma. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e105-e105 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Guoliang Sun More articles by this author Libin Yan More articles by this author Yue Ge* More articles by this author Expand All Advertisement PDF downloadLoading ...

Clinical Significance of Circulating Tumor Cells in Gastrointestinal Carcinomas.

The idea of a liquid biopsy to screen, surveil and treat cancer patients is an intensively discussed and highly awaited tool in the field of oncology. Despite intensive research in this field, the clinical application has not been implemented yet and further research has to be conducted. However, one component of the liquid biopsy is circulating tumor cells (CTCs) whose potential for clinical application is evaluated in the following. CTCs can shed from primary tumors to the peripheral blood at any time point during the progress of a malignant disease. Following, one single CTC can be the origin for distant metastasis at later cancer stage. Thus, CTCs have great potential to either be used in cancer diagnostics and patient stratification or to function as a target for new therapeutic approaches to stop tumor dissemination and metastasis at the very early beginning. Due to the biological fundamental role of CTCs in tumor progression, here, we provide an overview of CTCs in gastrointestinal cancers and their potential use in the clinical setting. In particular, we discuss the usage of CTC for screening and stratifying patients’ risk. Moreover, we will discuss the potential role of CTCs for treatment specification and treatment monitoring.

Identification of primordial germ cell-like cells as liver metastasis initiating cells in mouse tumour models

Liver metastasis, characterized by the spread of tumors to the liver from other areas, represents a deadly disease with poor prognosis. Currently, there is no effective therapeutic strategies and/or agents to combat liver metastasis primarily due to the insufficient understanding of liver metastasis. To develop a promising strategy for targeting liver metastasis, understanding of a cell origin responsible for liver metastasis and how this cell can be pharmacologically eliminated are therefore crucial. Using diverse tumor models including p53−/− genetic mouse model and syngeneic tumor models, we identified primordial germ cell (PGC)-like tumor cells, which are enriched in earliest liver micro-metastasis (up to 99%), as a cell origin of liver metastasis. PGC-like tumor cells formed earliest micro-metastasis in liver and gradually differentiated into non-PGC-like tumor cells to constitute late macro-metastasis in the course of tumor metastasis. The liver metastasis-initiating cells (PGC-like tumor cells) display cell renewal and differentiation capabilities, resemble primordial germ cells (PGCs) in morphology and PGC marker gene expression, and express higher level of the genes linked to metastasis and immune escape compared with non-PGC-like tumor cells. Of note, Stellarhigh PGC-like tumor cells, but not Stellarlow non-PGC-like cells, sorted from primary tumors of p53−/− mice readily form liver metastasis. Depletion of PGC-like tumor cells through genetic depletion of any of key germ cell genes impairs liver metastasis, while increased PGC-like tumor cells by SMAD2 knockout is correlated with markedly enhanced liver metastasis. Finally, we present the proof of principle evidence that pharmacologically targeting BMP pathways serves as a promising strategy to eliminate PGC-like tumor cells leading to abrogating liver metastasis. Collectively, our study identifies PGC-like tumor cells as a cell origin of liver metastasis, whose depletion by genetically targeting core PGC developmental genes or pharmacologically inhibiting BMP pathways serves a promising strategy for targeting liver metastasis.

Predicting primary site of secondary liver cancer with a neural estimator of metastatic origin.

Purpose: Pathologists rely on relevant clinical information, visual inspection of stained tissue slide morphology, and sophisticated molecular diagnostics to accurately infer the biological origin of secondary metastatic cancer. While highly effective, this process is expensive in terms of time and clinical resources. We seek to develop and evaluate a computer vision system designed to reasonably infer metastatic origin of secondary liver cancer directly from digitized histopathological whole slide images of liver biopsy. Approach: We illustrate a two-stage deep learning approach to accomplish this task. We first train a model to identify spatially localized regions of cancerous tumor within digitized hematoxylin and eosin (H&E)-stained tissue sections of secondary liver cancer based on a pathologist's annotation of several whole slide images. Then, a second model is trained to generate predictions of the cancers' metastatic origin belonging to one of three distinct clinically relevant classes as confirmed by immunohistochemistry. Results: Our approach achieves a classification accuracy of 90.2% in determining metastatic origin of whole slide images from a held-out test set, which compares favorably to an established clinical benchmark by three board-certified pathologists whose accuracies ranged from 90.2% to 94.1% on the same prediction task. Conclusions: We illustrate the potential impact of deep learning systems to leverage morphological and structural features of H&E-stained tissue sections to guide pathological and clinical determination of the metastatic origin of secondary liver cancers.

Quantification of multicellular colonization in tumor metastasis using exome-sequencing data.

Metastasis is a major cause of cancer‐related mortality, and it is essential to understand how metastasis occurs in order to overcome it. One relevant question is the origin of a metastatic tumor cell population. Although the hypothesis of a single‐cell origin for metastasis from a primary tumor has long been prevalent, several recent studies using mouse models have supported a multicellular origin of metastasis. Human bulk whole‐exome sequencing (WES) studies also have demonstrated a multiple “clonal” origin of metastasis, with different mutational compositions. Specifically, there has not yet been strong research to determine how many founder cells colonize a metastatic tumor. To address this question, under the metastatic model of “single bottleneck followed by rapid growth,” we developed a method to quantify the “founder cell population size” in a metastasis using paired WES data from primary and metachronous metastatic tumors. Simulation studies demonstrated the proposed method gives unbiased results with sufficient accuracy in the range of realistic settings. Applying the proposed method to real WES data from four colorectal cancer patients, all samples supported a multicellular origin of metastasis and the founder size was quantified, ranging from 3 to 17 cells. Such a wide‐range of founder sizes estimated by the proposed method suggests that there are large variations in genetic similarity between primary and metastatic tumors in the same subjects, which may explain the observed (dis)similarity of drug responses between tumors.

Nephrotic syndrome associated with carcinoma of unknown primary ‎treated with chemotherapy: A rare case report

Different glomerular diseases are associated with various neoplasms. It seems obvious that ‎Carcinoma of Unknown Primary (CUP) induced nephrotic syndrome is rare; in this regard, the ‎present article introduces a patient suffering from nephrotic syndrome associated with CUP. ‎Patient is a 65-year-old non-smoker male who referred to the clinic for one-month generalized ‎edema. The patient was also complaining from coughing and bulky yellowish sputum with no ‎signs of blood. Patient''s chest radiography revealed pulmonary pleural effusion of the left lung, ‎but no other pathological findings were revealed. Patient''s cytology report of pleural fluid ‎indicated metastatic carcinoma, and therefore; the patient needed additional examinations so that ‎the origin of metastases (lung, gastrointestinal tract, pancreas, etc.) could be detected. Finally, ‎chemotherapy treatments began when the patient was diagnosed with Carcinoma of Unknown ‎Primary (CUP). With the continuation of chemotherapy treatment and follow-up after more than ‎a year of diagnosis, the patient is now generally well-off; his nephrotic syndrome has also been in ‎remission parallel to chemotherapy. Significant point in the treatment of this patient is ‎proteinuria, hypercholesterolemia and ‎ yponatremia remission in two stages of chemotherapy. ‎These findings suggest that nephrotic syndrome is para-neoplastic.‎

Examination of the dielectrophoretic spectra of MCF7 breast cancer cells and leukocytes.

The detection of circulating tumor cells (CTCs) in blood is crucial to assess metastatic progression and to guide therapy. Dielectrophoresis (DEP) is a powerful cell surface marker-free method that allows intrinsic dielectric properties of suspended cells to be exploited for CTC enrichment/isolation from blood. Design of a successful DEP-based CTC enrichment/isolation system requires that the DEP response of the targeted particles should accurately be known. This paper presents a DEP spectrum method to investigate the DEP spectra of cells without directly analyzing their membrane and cytoplasmic properties in contrast to the methods in literature, which employ theoretical assumptions and complex modeling. Integrating electric field simulations based on DEP theory with the experimental data enables determination of the DEP spectra of leukocyte subpopulations, polymorphonuclear and mononuclear leukocytes, and MCF7 breast cancer cells as a model of CTC due to their metastatic origin over the frequency range 100kHz-50MHz at 10 Vpp . In agreement with earlier findings, differential DEP responses were detected for mononuclear and polymorphonuclear leukocytes due to the richness of the cell surface features and morphologies of the different leukocyte types. The data reveal that the strength of the DEP force exerted on MCF7 cells was particularly high between 850kHz and 20MHz. These results illustrate that the proposed technique has the potential to provide a generic platform to identify DEP responses of different biological particles.

Pulmonary metastasectomy for colorectal cancer: Prognosis analysis disaggregated by the origin of the primary tumor

BackgroundThe metastatic pattern differs between colon cancer and rectal cancer because of the distinct venous drainage systems. It is unclear whether colon cancer and rectal cancer are associated with different prognostic factors based on the anatomic difference. MethodsWe assessed the prognostic factors and survival outcomes of patients with colorectal cancer who underwent pulmonary metastasectomy (PM), disaggregated by the location of primary colorectal cancer. The Cox proportional hazards model was used to identify variables that influenced the outcomes of pulmonary metastasectomy. ResultsBetween 2008 and 2017, 179 patients underwent PM classified into colon cancer and rectal cancer groups based on the site of origin of metastasis. The median postoperative follow-up was 2.3 years (range, 0.1–10.6). The post-PM 5-year survival rate in the colon cancer and rectal cancer groups was 42.5% and 39.9%, respectively (p = 0.310). On multivariable Cox proportional hazards analysis, presence of previous liver metastasis [hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.19–4.51; p = 0.013], numbers of tumors (≥2; HR, 6.56; 95% CI, 2.07–20.79; p = 0.001), and abnormal preoperative carcinoembryonic antigen (CEA) level (HR, 2.50; 95% CI, 1.34–4.64; p = 0.001) were independent prognostic factors in patients with metastatic rectal cancer. ConclusionsPrognostic correlates of post-PM survival differ between colon and rectal cancer. Rectal cancer patients have worse prognosis if they have a history of liver metastasis, multiple pulmonary metastases, or abnormal preoperative CEA. These results may help assess the survival benefit of PM and facilitate treatment decision-making.

The Diagnostic Value of the Apparent Diffusion Coefficient Values Derived from Magnetic Resonance Imaging and Diffusion-Weighted Imaging in Differentiating the Types of Metastatic Brain Tumors

BackgroundIn brain metastatic lesions, peritumoral edema assessed by advanced imaging modalities is reported to have infiltration by neoplastic cells; however, determining the tumor border is still inaccurately depicted even by applying such modalities. More importantly, the apparent diffusion coefficient (ADC) values of this area for predicting tumor-related characteristics such as diametric and morphologic characteristics of lesions, as well as their primary source, remain uncertain.ObjectivesIn the current study, we aimed at assessing the value of ADCs in both intratumoral and peritumoral areas to determine the metastatic brain tumor source and to predict the morphological characteristics of the tumor.MethodsThis study was conducted on 80 biopsy-proven patients with brain metastasis and underwent magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) examination. All tumor characteristics including the number and size of lesions, the origin of metastasis, the zone of metastasis, and the presence of necrosis or edema in the lesions were collected based on imaging. The origins of the metastasis were also determined.ResultsThe ADCmin and ADCmean values of the peritumoral area were strongly associated with the grade of edema in this area; however, none of the values could accurately predict the origin of metastasis. Determining the ADCmin and ADCmean in the intratumoral area could not be indicators for lesion characteristics such as size and location of the lesion, the presence of necrosis or edema, as well as the source of the metastatic tumor such as breast or lung. Similarly, the ADCmin and ADCmean in the peritumoral area could not be an effective predictor for determining the source of metastasis and also diameter, location, or necrotic nature of the tumor and only can predict the edematous pattern of the lesion.ConclusionsThe ADC values in both intratumoral and peritumoral areas of the brain tumor metastatic lesion may not be predictive for the assessment of tumor morphology or its origin.

Malignancies in Pleural, Peritoneal, and Pericardial Effusions

The incidence and types of malignancies in effusion cytology are largely limited to studies performed in the 1970s through the 1990s. To examine how the incidence of different types of malignancies in effusions has changed with time. A computerized search for fluid cytology from 2000 through 2016 (database included age, gender, cytologic diagnosis, and type of malignancy) was performed, and all cases were reviewed. Of 30 085 effusion specimens, 3285 (11%) were positive for malignancy (2175 pleural, 955 peritoneal, and 155 pericardial). Of those, 1023 (31%) had known primary sites (648 pleural, 267 peritoneal, and 108 pericardial). Malignancy was more common in females than males in both pleural (15% versus 9%) and peritoneal (14% versus 5%) effusions (P < .001). The most common metastatic tumors in pleural fluid were lung for males and breast for females; in peritoneal fluid, hematolymphoid for males and Müllerian tumors for females; in pericardial fluid, lung for both genders. Among invasive mammary carcinomas, lobular carcinoma tended to metastasize to peritoneal fluid, whereas ductal carcinoma tended to metastasize to pleural fluid (P < .001). Plasma cell neoplasms metastasized to pleural and pericardial but not peritoneal fluid (P = .002). Although pulmonary and Müllerian tumors continue to be the most common origin of metastasis in pleural and peritoneal fluid for males and females, respectively, the frequencies for other malignancies have changed. Familiarity with the more common sites of metastasis in effusion cytology is important, especially in patients with unknown primary, as this will be valuable in judicious triaging of specimens for ancillary studies.

SURGICAL MANAGEMENT OF THE ADRENAL GLAND TUMORS - SINGLE CENTER EXPERIENCE.

Incidentally discovered solid adrenal tumors must be evaluated from two points of view: the risk of malignancy and the secretory feature. Our aim was to evaluate the surgical technique option in relation with clinical and histopathologic features. We performed a retrospective study that included patients with adrenal gland tumors. All patients were operated between 2012 and 2019 by the same surgical team in a single center. The batch included 102 patients with adrenal tumors operated through open surgery (OS, n=41) and laparoscopic surgery (LS, n=61). Tumor localization was especially on the right adrenal gland (n=52, 50.98%). Primary origin of the adrenal gland tumors was in 82 cases (80.39%) and a metastatic origin in 16 cases. Average dimension for surgical resected tumors was 4.02 cm (0.9-12 cm) for the LS group as compared to 7.22 cm (1.3-19 cm) for OS group with a predominant type of surgery represented by adrenalectomy and a conversion rate of 2.94%. The hospital stay was 7.22 days (5-12 days) in the LS group versus 12.72 days (6-57 days) in OS group with significant differences (p<0.01). Also, the postoperative recovery was significantly different (6.5 days versus 2.62 days, p<0.01). Laparoscopic approach represents the gold standard in adrenal gland tumors less than five centimeters in size. Adrenalectomy is mostly performed by LS and adenoma is the most frequent histopathologic type, while pheochromocytoma is operated through OS. LS has a significantly reduced hospitalization and postoperative stay compared to OS.

Cutaneous metastasis as a presenting feature of adenocarcinoma of lung

Metastasis is a neoplastic lesion which arises from another neoplasm with which it is no longer in continuity. Cutaneous metastasis is the spread of malignant cells from a primary malignancy to the skin. Skin metastases occur in about 5.3% of patients with internal malignancies and represent 2% of all skin tumors. Breast cancer, in women, and lung cancer, in men, are the most common origins of cutaneous metastasis. It mostly occurs late in the course of disease. Herein, we report the case of a 97-year-old male who presented with asymptomatic, hyperpigmented, indurated plaques with crusting and few overlying tense bullae over the right side of the chest extending to the right axilla for 4 months. On evaluation, he was diagnosed as a case of metastatic adenocarcinoma, the primary being from the lung. He succumbed to his illness within 2 months of diagnosis.

P231 Cardiac metastasis mimicking a myocardial infarction

Abstract We present the case of a 79 years old male patient affected by a lung squamous cell carcinoma (T4 N0 M1a) diagnosed in december 2018 with a 5x5 cm mass in the inferior lobe of the left lung close to the pericardium and a second 5 cm mass in the apical lobe of the right lung. TT echocardiography at that time was normal. Treatment with gemcitabine was scheduled with slight progression of the disease at the CT scan control in april 2019 when initial invasion of the left inferior pulmonary vein was detected. An ECG performed during routine control revealed the presence of q waves and ST segment elevation in the inferior leads. The patient was asymptomatic about the heart but the blood tests revealed a slight increase of HS Troponin I. We decided to repeat the TT echo, which showed the presence of a rounded mobile mass of about 3x2.5 cm in the left atrium close to the upper left pulmonary vein and another formation of about 5x2 cm infiltrating the inferior wall of the left ventricle that appeared akynetic. Both metastatic and thrombotic origins were debated and anticoagulant therapy with LMWH was started. We chose to perform a TE echocardiography, which confirmed the presence of the rounded mass in the left atrium, enlarged as compared to the TT evaluation. At the 3D reconstruction, it appeared to come from the left inferior pulmonary vein, completely occluding it, and expanding to the left superior vein, narrowing but not closing its orifice. The mass was well delimitated, disomogenous and vacuolated, thus confirming its likely neoplastic origin. From the trans-gastric view, we confirmed the large infiltration of the inferior wall of the left ventricle. General conditions of the patients quickly deteriorated and he experienced an ischemic stroke. At the TT echo re-evaluation the mass in the left atrium was greatly reduced as compared to the previous control. Cardiac metastases are a rare and frequently clinically silent occurrence; However, in a minority of cases they may present with ECG alterations such as ST-T segment modifications. In neoplastic patients an ischaemic ECG pattern not following its typical progression, without typical symptoms of ischaemia should rise the suspicion of a cardiac metastasis. In our case the abnormalities could be caused by a loss of viable myocardium secondary to the infiltrating mass or by a compression of the right coronary artery. In this context the echocardiography, both TT and especially TE, is a valuable tool that allow to recognize the real cause of these abnormalities and provides useful informations that enable to distinguish neoplastic mass from a thrombus. The ischaemic stroke was probably due to an embolization of the mass from the left atrium, as confirmed by its important reduction at the last echo control. Abstract P231 Figure. ECG abnormalities and TE echo alteration

Synchronous Oligometastatic Lung Acinar Adenocarcinoma and Clear Cell Renal Cell Carcinoma: A case report

Synchronous tumours are complex cases, being challenging to distinguish between primary neoplasms and metastatic disease, as well as to accurately determine the origin of metastasis. Although synchronous tumours are relatively rare, its incidence has increased over the years. The authors report on a patient with localized clear cell renal carcinoma and synchronous adenocarcinoma of the lung with solitary brain metastasis, highlighting the uncertainties of the therapeutic approach and the implications to the final outcomes

Case Report: A Long Survivor Patient with Stage IV Gastric Adenocarcinoma

Gastric cancer (GC) is the fifth most common malignancy of the world and third leading cause of cancer death. At diagnosis, 35% of GC patients have distant metastases and in these cases the survival rate is very poor with a median overall survival (OS) inferior to 1 year. We report a case of a 67-year-old woman with gastric carcinoma initially deemed limited stage on diagnosis (cT2N0M0), treated surgically with radical subtotal gastrectomy with Billroth II reconstruction. In the staging CT scan, the patient presented a liver image that was considered benign. Three months later, due to abdominal pain, the patient performed another CT scan and the diagnostic of a large single liver metastasis was made; retrospectively it was observed that the lesion was present at diagnosis and that it had increased. A biopsy was performed which confirmed the metastatic origin. In a multidisciplinary team, the lesion was considered unresectable. She was proposed for first line (1st L) palliative chemotherapy (ChT) with FOLFIRI, with partial response as best response. After 30 cycles of FOLFIRI, bone metastases were diagnosed. The patient was submitted to a cementoplasty of D11-12 and L1-2. Afterwards, she started 2nd L ChT with mFOLFOX6 and at the same time she started zoledronic acid every 28 days. The best response to mFOLFOX6 was stable disease. Since November 2018, the patient has been treated with zoledronic acid every 28 days alone and maintains stable disease without ChT.

Capabilities of &lt;sup&gt;18&lt;/sup&gt;F-FDG PET/CT in the differential diagnosis of colorectal liver metastases

Aim. To study the capabilities of &lt;sup&gt;18&lt;/sup&gt;F -FDG PET/CT in the differential diagnosis of colorectal liver metastases. Materials and methods . A retrospective analysis of &lt;sup&gt;18&lt;/sup&gt;F -FDG PET/CT data of 126 patients with colorectal cancer was carried out. The final diagnosis of colorectal cancer was established based on the analysis of morphological material obtained from the primary tumor. The metastatic or benign origins of the liver foci was confirmed by histological examination or by the results of radiation examination (dynamic observation). Sensitivity and specificity of this method were determined using ROC analysis using the SUV as a numerical classifier. Results . Colorectal liver metastases were detected in 51 (40.5%) patients. Advanced extrahepatic tumor process was detected in 25 (19.8%) cases. There were no progression in 50 (39.7%) patients. Benign tumors were detected in 22 patients with colorectal cancer: in 10 cases coupled with liver metastases, in 12 – without them. Totally 166 focal liver lesions were found: 125 (75.3%) metastases and 41 (24.7%) benign tumors. According to ROC analysis, sensitivity and specificity of &lt;sup&gt;18&lt;/sup&gt;F -FDG PET/CT with SUV ≥ 3.0 in the diagnosis of liver metastases were 84.8% and 97.6% respectively, the area under the ROC curve – 0.893 (95% CI 0.836–0.936 , p &lt; 0.0001), positive predictive value and negative predictive value were – 99.1% and 67.8%, respectively. Conclusion. &lt;sup&gt;18&lt;/sup&gt;F-FDG PET/CT is a highly informative imaging method in the differential diagnosis of colorectal liver metastases larger than 10 mm. The use of quantitative data processing with a threshold value SUV ≥ 3.0 allows to achieve high sensitivity and specificity of the method.

Molecular testing in metastatic basal cell carcinoma

Metastatic basal cell carcinoma (mBCC) is a very rare entity, and diagnosis can be challenging. Therapeutic options are limited, and response to targeted therapy is poor. To demonstrate a clonal relationship between BCCs and their metastases and to explore which hedgehog pathway-related mutations are involved in mBCC. Genetic analysis was conducted in 10 primary BCCs and their metastases. Genes relevant for BCC development were analyzed in tumor and metastasis material with small molecule molecular inversion probes (smMIPs) for PTCH1, PTCH2, SMO, SUFU, GLI2, and TP53 or with targeted next generation sequencing of the same genes and CDKN2A, CDKN2B, CIC, DAXX, DDX3X, FUBP1, NF1, NF2, PTEN, SETD2, TRAF7, and the TERT promoter. In 8 of 10 patients, identical gene mutations could be demonstrated in the primary tumors and their metastases. A broad spectrum of mutations was found. Four patients had SMO mutations in their tumor or metastasis, or both. All SMO mutations found were known to cause resistance to targeted therapy with vismodegib. In 2 patients there was insufficient qualitative DNA available for genetic analysis. Molecular testing can help to identify the origin of a BCC metastasis and may be of prognostic and therapeutic value.

Linfoma difuso de células B grandes metastásico a testículo y vejiga. Un reporte de caso

Resumen:&#x0D; Descripción del caso clínico: Presentamos el caso de un varón de 44 años, con diagnóstico de linfoma difuso de células B grandes, de tipo centro germinal, metastásico a testículo y vejiga. Se presentó con edema y dolor en miembros inferiores, retención urinaria e injuria renal aguda. Se encontró un conglomerado ganglionar retroperitoneal en la tomografía de ingreso, y alteración en los marcadores tumorales séricos. Se realizó una ecografía doppler testicular, a pesar de que el examen físico genital fue normal, encontrándose un tumor testicular. Se llevó a orquiectomía radical, y en el mismo tiempo quirúrgico, a derivación urinaria endoscópica con catéteres JJ, y se evidenció entonces, un compromiso neoplásico vesical. Los reportes histológicos de testículo y vejiga reportaron tumor maligno mal diferenciado de probable origen metastásico, y la inmuno-histoquímica reportó linfoma difuso de células B grandes de tipo centro germinal.&#x0D; Relevancia: Los linfomas no Hodgkin constituyen las principales causas de linfoma secundario de testículo y vejiga.&#x0D; Implicaciones clínicas: En pacientes hombres jóvenes con masas retroperitoneales, como en el caso de linfoma de células B grandes, es importante tomar en consideración el compromiso secundario de testículo y vejiga.&#x0D; Conclusión: el compromiso secundario de testículo y vejiga corresponde a una presentación inusual de este tipo de linfoma. Se reportó el caso con el objetivo de tomar en consideración el diagnóstico, en pacientes hombres jóvenes con masas retroperitoneales.