Hepatocellular Carcinoma Incidence Threshold for Surveillance in Virologically Cured Hepatitis C Individuals.

BACKGROUND & AIMS: Guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in hepatitis C individuals with cirrhosis if the HCC incidence rate is above 1.5 per 100 person-years (PY). However, the incidence threshold for surveillance in individuals who achieve a virologic cure is unknown. We estimated the HCC incidence rate above which routine HCC surveillance is cost-effective in this growing population of virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis. METHODS: We developed a Markov-based microsimulation model of the natural history of HCC in individuals with hepatitis C who achieved virologic cure with oral direct-acting antivirals. We used published data on the natural history of hepatitis C, competing risk post virologic cure, HCC tumor progression, real-world HCC surveillance adherence, contemporary HCC treatment options and associated costs, and utilities of different health states. We estimated the HCC incidence above which biannual HCC surveillance using ultrasound and alpha-fetoprotein would be cost-effective. RESULTS: In virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis, HCC surveillance is cost-effective if HCC incidence exceeds 0.7 per 100 PY using $100,000 per quality-adjusted life year willingness-to-pay. At this HCC incidence, routine HCC surveillance would result in 2650 and 5700 additional life years per 100,000 cirrhosis and advanced fibrosis persons, respectively, compared with no surveillance. At $150,000 willingness-to-pay, surveillance is cost-effective if HCC incidence exceeds 0.4 per 100 PY. Sensitivity analysis showed that the threshold mostly remained below 1.5 per 100 PY. CONCLUSIONS: The contemporary HCC incidence threshold is much lower than the previous 1.5% incidence value used to guide HCC surveillance decisions. Updating clinical guidelines could improve the early diagnosis of HCC.

Effectiveness of a Multi-component Delirium Prevention Program Implemented on General Medicine Hospital Units: an Interrupted Time Series Analysis.

BACKGROUND: Delirium is among the most prevalent harmful events in hospitals that is associated with an elevated risk for severe outcomes such as functional decline, falls, longer length of stay, and increased mortality. OBJECTIVE: To evaluate the impact of the implementation of a multi-component delirium program on the prevalence of delirium and the incidence of falls among patients staying on general medicine inpatient hospital units. DESIGN: A pre-post intervention study using retrospective chart abstraction and interrupted time series analysis. COHORT: Patients were selected from adult patients that stayed at least 1 day on one of the five general medicine units in a large community hospital in Ontario, Canada. A total of 16 random samples of 50 patients per month for 8 consecutive months pre-intervention (October 2017 to May 2018) and 8 months post intervention (January 2019 to August 2019) were selected for a total of 800 patients. There were no exclusion criteria. INTERVENTION: The delirium program included multiple components: education of staff and hospital leadership, twice per day bed-side screen for delirium, non-pharmacological and pharmacological prevention, and intervention strategies and a delirium consultation team. MEASUREMENT: Delirium prevalence was assessed using the evidence-based delirium chart abstraction method, CHART-del. Demographic data as well as fall incidence were also collected. RESULT: Our evaluation showed that the implementation of a multicomponent delirium program led to a reduction in delirium prevalence and fall incidences. The reduction in both delirium and falls was the largest for patients in the ages between 72 and 83 years old and varied across inpatient units. CONCLUSION: A multi-component delirium program to improve the prevention, recognition, and management of delirium reduces the prevalence of delirium and fall incidence among patients in general medicine units.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication.

BACKGROUND & AIMS: Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. METHODS: We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. RESULTS: In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in 'very early'/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in 'very early'/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. CONCLUSION: Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. LAY SUMMARY: Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

Genetic testing to guide screening for pancreatic ductal adenocarcinoma: Results of a microsimulation model.

BACKGROUND: First-degree relatives (FDRs) of patients with pancreatic ductal adenocarcinoma (PDAC) have elevated PDAC risk, partially due to germline genetic variants. We evaluated the potential effectiveness of genetic testing to target MRI-based screening among FDRs. METHODS: We used a microsimulation model of PDAC, calibrated to Surveillance, Epidemiology, and End Results (SEER) data, to estimate the potential life expectancy (LE) gain of screening for each of the following groups of FDRs: individuals who test positive for each of eight variants associated with elevated PDAC risk (e.g., BRCA2, CDKN2A); individuals who test negative; and individuals who do not test. Screening was assumed to take place if LE gains were achievable. We simulated multiple screening approaches, defined by starting age and frequency. Sensitivity analysis evaluated changes in results given varying model assumptions. RESULTS: For women, 92% of mutation carriers had projected LE gains from screening for PDAC, if screening strategies (start age, frequency) were optimized. Among carriers, LE gains ranged from 0.1 days (ATM+ women screened once at age 70) to 510 days (STK11+ women screened annually from age 40). For men, LE gains were projected for all mutation carriers, ranging from 0.2 days (BRCA1+ men screened once at age 70) to 620 days (STK11+ men screened annually from age 40). For men and women who did not undergo genetic testing, or for whom testing showed no variant, screening yielded small LE benefit (0-2.1 days). CONCLUSIONS: Genetic testing of FDRs can inform targeted PDAC screening by identifying which FDRs may benefit.

Fluoropyrimidine-Associated Cardiotoxicity: A Retrospective Case-Control Study.

BACKGROUND: The fluoropyrimidines, 5-fluorouracil (5-FU) and capecitabine, are commonly used chemotherapeutic agents that have been associated with coronary vasospasm. METHODS: In this retrospective case-control study, we identified patients at our institution who received 5-FU or capecitabine in 2018. We compared characteristics of patients who experienced cardiotoxicity with controls. We described phenotypes and outcomes of cardiotoxic cases. RESULTS: We identified 177 patients who received fluoropyrimidines. After adjudication, 4.5% of the cohort met the criteria for cardiovascular toxicity. Coronary artery disease was more common among cases than controls (38% vs. 7%, p < .05). There was also a trend toward increased prevalence of cardiovascular risk factors in cases compared with controls. Most cardiotoxic cases had chest pain, although a minority of cases presented with nonischemic cardiomyopathy. CONCLUSION: Cardiotoxicity phenotypes associated with fluoropyrimidine use are not limited to coronary vasospasm. Cardiac risk factors and ischemic heart disease were highly prevalent among patients with cardiotoxicity.

Family communication and patient distress after germline genetic testing in individuals with pancreatic ductal adenocarcinoma.

BACKGROUND: Germline genetic testing currently is recommended for patients with pancreatic ductal adenocarcinoma (PDAC). In the current study, the authors assessed how often results are communicated to first-degree relatives within 3 months and the emotional impact of testing on patients. METHODS: A total of 148 patients who were newly diagnosed with PDAC and who had undergone testing of 32 cancer susceptibility genes at 3 academic centers were selected; 71% participated. Subjects completed the Multidimensional Impact of Cancer Risk Assessment (MICRA) and a family communication survey. The results of both surveys were assessed at 3 months according to the genetic test result (positive, negative, or variant of unknown significance [VUS]) and whether a patient met criteria for genetic testing. RESULTS: A total of 99 patients completed the MICRA survey and 104 completed the family communication survey. The average age of the patients was 67 years, 47% were female, 29% had stage III/IV (AJCC 8th edition) disease, and 42% met genetic testing criteria. Approximately 80% of patients told at least 1 first-degree relative about their result. There was a trend toward greater disclosure among patients who tested positive (93% vs 77% for those with a VUS result [P = .149] and 74% for those who tested negative [P = .069]). Patients not meeting genetic testing criteria were less likely to disclose results (69% vs 93%; P = .003). MICRA scores did not differ by test result, age, stage of disease, or sex. CONCLUSIONS: The rate of result communication was high, although it was lower among patients who did not meet genetic testing criteria, those who tested negative, or those who had a VUS result. Testing-associated distress was similar across patient groups, and was comparable to that reported by other patients with cancer. Improved communication for all patients is crucial given the prognosis of PDAC, which limits time for disclosure.

Testing for Verification Bias in Reported Malignancy Risks for Side-Branch Intraductal Papillary Mucinous Neoplasms: A Simulation Modeling Approach.

OBJECTIVE: The objective of our study was to test for the possibility that published malignancy risks for side-branch intraductal papillary mucinous neoplasms (IPMNs) are overestimates, likely due to verification bias. MATERIALS AND METHODS: We tested for possible verification bias using simulation modeling techniques. First, in age-defined hypothetical cohorts of 10 million persons, we projected the frequency of pancreatic ductal adenocarcinoma (PDAC) arising from side-branch IPMNs over 5 years using published estimates of their prevalence (4.4%) and rate of malignant transformation (1.9%). Second, we projected the total number of PDAC cases in corresponding cohorts over the same time horizon using national cancer registry data. For each cohort, we determined whether the percentage of all PDAC cases that arose from side-branch IPMNs (i.e., side-branch IPMN-associated PDAC cases) was clinically plausible using an upper limit of 10% to define plausibility, as estimated from the literature. Model assumptions and parameter uncertainty were evaluated in sensitivity analysis. RESULTS: Across all cohorts, percentages of side-branch IPMN-associated PDACs greatly exceeded 10%. In the base case (mean age = 55.7 years), 80% of PDAC cases arose from side-branch IPMNs (7877/9786). In the oldest cohort evaluated (mean age = 75 years), this estimate was 76% (14,227/18,714). In a secondary analysis, we found that if an upper limit threshold of 10% for side-branch IPMN-associated PDAC was imposed, the model-predicted rate of malignancy for side-branch IPMNs would be less than 0.24% over a 5-year time horizon, substantially lower than most literature-based estimates. CONCLUSION: Our results suggest that reported malignancy risks associated with side-branch IPMNs are likely to be overestimates and imply the presence of verification bias.

Prospective study of germline genetic testing in incident cases of pancreatic adenocarcinoma.

BACKGROUND: The objective of this study was to investigate the prevalence of pathogenic germline variants (PGVs) in 32 cancer susceptibility genes in individuals with newly diagnosed pancreatic ductal adenocarcinoma (PDAC). A key secondary objective was to evaluate how often PGVs would have been undetected with existing genetic testing criteria. METHODS: From May 2016 through May 2017, this multicenter cohort study enrolled consecutive patients aged 18 to 89 years with histologically confirmed PDAC diagnosed within the previous 12 weeks. Demographics, medical histories, and 3-generation pedigrees were collected from participants who provided samples for germline DNA analysis. RESULTS: Four hundred nineteen patients were deemed eligible, 302 were enrolled, and 298 were included in the final cohort. Clinically actionable variants were reported in 29 PDAC patients (9.7%), with 23 (7.7%) having a PGV associated with an increased risk for PDAC. Six of 23 individuals (26%) with PDAC-associated gene mutations did not meet currently established genetic testing criteria. According to guideline-based genetic testing, only 11 of the 23 PGVs (48%) in known PDAC genes would have been detected. Six additional patients (2%) had PGVs associated with an increased risk for other cancers. CONCLUSIONS: These findings support the significant prevalence of PGVs associated with PDAC and the limitations of current paradigms for selecting patients for genetic testing, and they thereby lend support for universal germline multigene genetic testing in this population.

Progression to pancreatic ductal adenocarcinoma from pancreatic intraepithelial neoplasia: Results of a simulation model.

OBJECTIVES: To gain insight into the natural history and carcinogenesis pathway of Pancreatic Intraepithelial Neoplasia (PanIN) lesions by building a calibrated simulation model of PanIN progression to pancreatic ductal adenocarcinoma (PDAC) METHODS: We revised a previously validated simulation model of solid PDAC, calibrating the model to fit data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program and published literature on PanIN prevalence by age. We estimated the likelihood of progression from PanIN states (1, 2, and 3) to PDAC and the time between PanIN onset and PDAC (dwell time). We evaluated a hypothetical intervention to test for and treat PanIN 3 lesions to estimate the potential benefits from PanIN detection. RESULTS: We estimated the lifetime probability of progressing from PanIN 1 to PDAC to be 1.5% (men), 1.3% (women). Progression from PanIN 1 to PDAC took 33.6 years and 35.3 years, respectively, and from PanIN 3 to PDAC took 11.3 years and 12.3 years. A hypothetical test for PanIN 3 detection and treatment could provide a maximum, average life expectancy gain of 40 days. CONCLUSIONS: Our modeling analysis estimates PanINs have a relatively indolent course to PDAC, supporting the feasibility of potential future early detection strategies.

Managing hereditary breast cancer risk in women with and without ovarian cancer.

Current guidelines recommend that all women with ovarian cancer undergo germline genetic testing for BRCA1/2. Increasingly, genetic testing is being performed via panels that include other genes that confer a high or moderate risk of breast cancer. In addition, many women with a family history of breast or ovarian cancer are not found to have a mutation, but may have increased risk of breast cancer for which surveillance and risk reduction strategies are indicated. This review discusses how to assess and manage an increased risk of breast cancer through surveillance, preventive medications, and risk-reducing surgery. Assessing and managing the increased risk of breast cancer in BRCA1/2 mutation carriers after a diagnosis of ovarian cancer can be challenging. For the first few years after an ovarian cancer diagnosis, BRCA1/2 mutation carriers have a relatively low risk of breast cancer, and their prognosis is largely determined by the ovarian cancer. However, if these women remain in remission after two years, the risk of breast cancer becomes comparable with, and in some cases exceeds, their risk of ovarian cancer recurrence. For these women, breast cancer surveillance and risk reduction becomes important to their overall health. Specifically, for BRCA1/2 carriers who are diagnosed with early-stage ovarian cancer, we recommend regular breast cancer surveillance and consideration of risk reduction with medication and/or prophylactic mastectomy. For women with advanced ovarian cancer who do not achieve remission, breast cancer surveillance or prophylaxis is not of value. However, among carriers with more favorable advanced disease, it is reasonable to initiate breast cancer surveillance. Patients with less favorable advanced stage disease who achieve sustained remission (>2-5years) should also consider more aggressive strategies for breast cancer screening and prevention. For mutation carriers who remain in remission after five years, prophylactic mastectomy can be considered.

Cabozantinib in the treatment of hepatocellular carcinoma.

Despite clinical studies with different mechanisms of action, no new systemic therapies were approved for hepatocellular carcinoma (HCC) between sorafenib in 2007 and regorafenib in 2017. This is an area of interest to improve outcomes and quality of life. Cabozantinib is oral, small-molecule tyrosine kinase inhibitor that primarily targets MET, VEGFR2, AXL and RET, with additional effect on KIT and FLT3. Cabozantinib is approved for progressive metastatic medullary thyroid cancer and previously treated renal cell carcinoma, and is in development for multiple solid tumors. Given positive results from a Phase II study, cabozantinib is under evaluation in a Phase III randomized controlled trial for patients with advanced HCC previously treated with sorafenib. It has been granted orphan drug status in the USA for this indication. This review summarizes the development of cabozantinib in HCC.

Does concomitant thyroidectomy increase risks of parathyroidectomy?

BACKGROUND: Concomitant thyroid pathology in patients with primary hyperparathyroidism is common. This study compares complications of patients who underwent parathyroidectomy to those who underwent parathyroidectomy with a concomitant thyroidectomy. METHODS: A retrospective review of prospectively collected data on 709 patients who underwent parathyroidectomy was performed. Patients who had prior thyroid or parathyroid procedures were excluded. Chi-square, Fisher's exact, Student's t-test, and Wilcoxon rank-sum tests were used to compare cohorts. RESULTS: Of the 641 patients included, 90% underwent parathyroidectomy alone and 10% underwent parathyroidectomy with a concomitant thyroidectomy. Overall, 49% had preoperative thyroid disease and 22% of patients with thyroid disease had a thyroid procedure. When compared with parathyroidectomy alone, parathyroidectomy with a concomitant thyroidectomy was associated with longer operative times (91 min versus 57 min, P < 0.001), increased rate of overnight stay (69% versus 17%, P < 0.001), and increased rate of transient hypocalcemia (15% versus 3%, P < 0.001). CONCLUSIONS: Parathyroidectomy with a concomitant thyroidectomy is associated with longer operative times, increased rate of overnight stay, and increased transient hypocalcemia.

Predictors of hemodynamic instability during surgery for pheochromocytoma.

BACKGROUND: Resection of pheochromocytoma is often associated with hemodynamic instability (HDI). We examined patient and tumor factors that may influence HDI. The effect of pretreatment with nonselective α blockade phenoxybenzamine (PXB) versus selective α blockade on HDI and outcomes was also evaluated. METHODS: The records of 91 patients who underwent adrenalectomy between 2002 and 2013 were retrospectively reviewed. HDI was determined by number of intraoperative episodes of systolic blood pressure (SBP) > 200 mmHg, those greater than or less than 30 % of baseline, heart rate > 110 bpm, and the need for postoperative vasopressors. Fishers exact, t test and regressions were performed. RESULTS: Among 91 patients, 78 % received PXB, 18 % selective α blockade and 4 % no adrenergic blockade. Patient demographics, tumor factors and surgical approach were similar among the blockade groups. On multivariate analysis, increasing tumor size was associated with a significant rise in the number of episodes of SBP > 30 % [rate ratio (RR) 1.40] and an increased postoperative vasopressor requirement [odds ratio (OR) 1.23]. Open adrenalectomy and use of selective blockade were associated with an increased number of episodes of SBP > 200 mmHg (RR 27.8 and RR 20.9, respectively). Open adrenalectomy was also associated with increased readmissions (OR 12.3), complications (OR 5.6), use of postoperative vasopressors (OR 4.4) and hospital stay (4.6 days longer). There were no differences in other HDI measurements or postoperative outcomes among the blockade groups. CONCLUSIONS: Tumor size, open adrenalectomy, and type of α blockade were associated with intraoperative HDI during pheochromocytoma resection. Selective blockade was associated with significantly more episodes of intraoperative hypertension but no perioperative adverse outcomes.

Efficacy of dual checkpoint inhibitors in a patient with a mixed hepatocellular cholangiocarcinoma.

A woman in her 60s was diagnosed with a metastatic, unresectable rare histological type of liver cancer; combined hepatocellular cholangiocarcinoma. She had palliative chemotherapy, initially with gemcitabine and cisplatin, and then with oxaliplatin, L-folinic acid and fluorouracil. Both treatment strategies demonstrated disease progression, and somatic mutation profiling revealed no actionable mutations. The patient was started on immuno-oncology (IO) with nivolumab and ipilimumab, followed by maintenance nivolumab. She has achieved a sustained ongoing partial response since the start of this therapy for at least 12 months. The outcome in this patient is in keeping with the growing evidence of the role that IO agents have in metastatic biliary tract cancer and also serves to highlight their importance in mixed histology liver tumours.

Cancer of Unknown Primary: When Imaging, Pathology, and Molecular Biology Do Not Match.

Introduction: Cancers of unknown primary are aggressive and rare malignancies with a complex diagnosis and management. Here we present a case in which imaging, pathology, and molecular biology did not match for a specific tumor site and the importance of a multidisciplinary team for these complicated cases. Case Presentation: A man in his 70s with strong smoking history under workup for suspicion of metastatic lung cancer underwent lung mass biopsy. Immunohistochemical stains corresponded to hepatocellular/cholangiocarcinoma or germ cell tumor; however, dedicated liver and testicular studies including imaging and iscochrome 12p FISH were negative. Additionally, somatic variant profiling was not specific for any malignancy nor targetable variants. Given the pattern of disease, risk factors, and patient history, the patient received treatment for lung adenocarcinoma (carboplatin, pemetrexed, and pembrolizumab). The patient had a drastic improvement in dyspnea, weight gain, and was able to return to work. Conclusion: This report describes a case in which immunohistochemistry and molecular profiling did not identify the tissue of origin and highlights the importance of a multidisciplinary team to reach a diagnosis and guide treatment without delaying patient care in patients with these diagnoses.

Cost-Effectiveness Analysis of Screening for Pancreatic Cancer Among High-Risk Populations.

PURPOSE: We evaluated the potential cost-effectiveness of combined magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) screening for pancreatic ductal adenocarcinoma (PDAC) among populations at high risk for the disease. METHODS: We used a microsimulation model of the natural history of PDAC to estimate the lifetime health benefits, costs, and cost-effectiveness of PDAC screening among populations with specific genetic risk factors for PDAC, including BRCA1 and BRCA2, PALB2, ATM, Lynch syndrome, TP53, CDKN2A, and STK11. For each high-risk population, we simulated 29 screening strategies, defined by starting age and frequency. Screening included MRI with follow-up EUS in a subset of patients. Costs of tests were based on Medicare reimbursement for MRI, EUS, fine-needle aspiration biopsy, and pancreatectomy. Cancer-related cost by stage of disease and phase of treatment was based on the literature. For each high-risk population, we performed an incremental cost-effectiveness analysis, assuming a willingness-to-pay (WTP) threshold of $100,000 US dollars (USD) per quality-adjusted life year (QALY) gained. RESULTS: For men with relative risk (RR) 12.33 (CDKN2A) and RR 28 (STK11), annual screening was cost-effective, starting at age 55 and 40 years, respectively. For women, screening was only cost-effective for those with RR 28 (STK11), with annual screening starting at age 45 years. CONCLUSION: Combined MRI/EUS screening may be a cost-effective approach for the highest-risk populations (among mutations considered, those with RR >12). However, for those with moderate risk (RR, 5-12), screening would only be cost-effective at higher WTP thresholds (eg, $200K USD/QALY) or with once-only screening.

Partial response in non-resectable adenosquamous carcinoma of the pancreas with high tumour mutation burden treated with gemcitabine, nab-paclitaxel and pembrolizumab.

A previously healthy man in his 60s was diagnosed with a rare histological subtype of pancreatic cancer, adenosquamous carcinoma. After somatic mutation profiling, it was found that the tumour had microsatellite instability status high and a high tumour mutational burden. The patient was started on combination therapy with gemcitabine, nab-paclitaxel and pembrolizumab. Tumour size and biomarkers showed a dramatic response eventually leading to the patient being transitioned to maintenance therapy with pembrolizumab. The patient has demonstrated continued response since the start of the treatment. This is the first report in the literature showing a sustained response in this type of neoplasm that was treated with a checkpoint inhibitor, and thus adds to the evidence supporting universal somatic testing in all pancreatic cancers for a tailored approach to therapy.

Primary Undifferentiated Neoplasm of the Left Arm with Characteristics of Extragonadal Germ Cell Tumor and High-Grade Sarcoma.

A previously healthy man in his late 20s was diagnosed with a primary undifferentiated non- metastatic tumor of the left arm. After a biopsy, a clear pathological diagnosis could not be established. The tumor had positive immunohistological markers for both an extragonadal germ cell tumor and a high-grade sarcoma. Given the presumed germ cell etiology, he was started on empiric chemotherapy with etoposide and cisplatin. After a few cycles, the tumor showed dramatic response. However, due to poor patient follow- up, it progressed to massive size with severe compromise of the joint and critical neurovascular structures, which led to the decision for limb amputation. Post-surgical checkups showed no recurrence of the primary tumor or metastasis. This is the first report in the literature showing a tumor with these histological characteristics that responded to platinum-based therapy. It provides evidence for the need of more specific markers for the pathological evaluation of undifferentiated neoplasms.