Insights into Renal Cell Carcinoma with Novel Imaging Approaches.

This article presents a comprehensive overview of new imaging approaches and techniques for improving the assessment of renal masses and renal cell carcinoma. The Bosniak classification, version 2019, as well as the clear cell likelihood score, version 2.0, will be discussed as new imaging algorithms using established techniques. Additionally, newer modalities, such as contrast-enhanced ultrasound, dual energy computed tomography, and molecular imaging, will be discussed in conjunction with emerging radiomics and artificial intelligence techniques. Current diagnostic algorithms combined with newer approaches may be an effective way to overcome existing limitations in renal mass and RCC characterization.

Learning From Experience- Confronting Challenges and Adapting to Change in a Large Academic Abdominal Radiology Practice: Insights From a Faculty Retreat.

RATIONALE: Substantial organizational changes, increasing clinical volumes, and the COVID-19 pandemic presented compound stressors to faculty radiologists in our large academic abdominal radiology division and necessitated multiple changes in our practice. METHODS: To address the challenges and establish group consensus, we conducted a virtual divisional faculty retreat centered on themes of team building, clinical work, trainee education, and faculty mentorship. A pre-retreat survey evaluated satisfaction with aspects of professional life and clinical work practices and invited personal reflections. Survey data were presented in the retreat segments focused on each theme, and subsequent discussion was facilitated in small group breakouts. RESULTS: Responses to the team-building survey revealed common values and sources of gratitude, including health, family and meaningful work and relationships. Faculty reported a strong sense of personal accomplishment, but with varied emotional exhaustion scores. Faculty were satisfied with remote work assignments but identified opportunities to improve the clinical work schedule including reversion of some remote assignments to in-person and increased interventional radiology shift staggering. Compared to pre-COVID practice, faculty respondents perceived giving lower quality and less frequent feedback to trainees; evolving educational resource needs were identified. A more formal approach to faculty mentoring was sought. A post-retreat survey revealed high participant satisfaction. OUTCOMES: In the future, we plan to continue divisional retreat activities to respond to evolving challenges and further improve team building, clinical workflow, trainee education, and faculty mentorship.

Computed Tomography Texture Analysis for Predicting Clinical Outcomes in Patients With Metastatic Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors.

BACKGROUND: The treatment responses of immune checkpoint inhibitors in metastatic renal cell carcinoma (mRCC) vary, requiring reliable prognostic biomarkers. We assessed the prognostic ability of computed tomography (CT) texture analysis in patients with mRCC treated with programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors. MATERIALS AND METHODS: Sixty-eight patients with mRCC treated with PD-1/PD-L1 inhibitors between 2012 and 2019 were revaluated. Using baseline and first follow-up CT, baseline and follow-up texture models were developed to predict overall survival (OS) and progression-free survival (PFS) using least absolute shrinkage and selection operator Cox-proportional hazards analysis. Patients were divided into high-risk or low-risk group, and the survival difference was assessed using Kaplan-Meier and log-rank test. Multivariable Cox models were constructed by including only the clinical variables (clinical models) and by combining the clinical variables and the texture models (combined clinical-texture models), and their predictive performance was evaluated using Harrell's C-index. RESULTS: The baseline texture models distinguished longer- and shorter-term survivors for both OS (median, 60.1 vs. 17.0 months; P = .048) and PFS (5.2 vs. 2.8 months; P = .003). The follow-up texture models distinguished longer- and shorter-term overall survivors (40.3 vs. 15.2 months; P = .008) but not for PFS (5.0 vs. 3.6 months; P = .25). The combined clinical-texture model outperformed the clinical model in both predicting the OS (C-index, 0.70 vs. 0.63; P = .03) and PFS (C-index, 0.63 vs. 0.55; P = .04). CONCLUSION: CT texture analysis performed at baseline and early after starting PD-1/PD-L1 inhibitors is associated with clinical outcomes of patients with mRCC.

Clinical Activity and Safety of Cabozantinib for Brain Metastases in Patients With Renal Cell Carcinoma.

IMPORTANCE: Patients with brain metastases from renal cell carcinoma (RCC) have been underrepresented in clinical trials, and effective systemic therapy is lacking. Cabozantinib shows robust clinical activity in metastatic RCC, but its effect on brain metastases remains unclear. OBJECTIVE: To assess the clinical activity and toxic effects of cabozantinib to treat brain metastases in patients with metastatic RCC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients with metastatic RCC and brain metastases treated in 15 international institutions (US, Belgium, France, and Spain) between January 2014 and October 2020. Cohort A comprised patients with progressing brain metastases without concomitant brain-directed local therapy, and cohort B comprised patients with stable or progressing brain metastases concomitantly treated by brain-directed local therapy. EXPOSURES: Receipt of cabozantinib monotherapy at any line of treatment. MAIN OUTCOMES AND MEASURES: Intracranial radiological response rate by modified Response Evaluation Criteria in Solid Tumors, version 1.1, and toxic effects of cabozantinib. RESULTS: Of the 88 patients with brain metastases from RCC included in the study, 33 (38%) were in cohort A and 55 (62%) were in cohort B; the majority of patients were men (n = 69; 78%), and the median age at cabozantinib initiation was 61 years (range, 34-81 years). Median follow-up was 17 months (range, 2-74 months). The intracranial response rate was 55% (95% CI, 36%-73%) and 47% (95% CI, 33%-61%) in cohorts A and B, respectively. In cohort A, the extracranial response rate was 48% (95% CI, 31%-66%), median time to treatment failure was 8.9 months (95% CI, 5.9-12.3 months), and median overall survival was 15 months (95% CI, 9.0-30.0 months). In cohort B, the extracranial response rate was 38% (95% CI, 25%-52%), time to treatment failure was 9.7 months (95% CI, 6.0-13.2 months), and median overall survival was 16 months (95% CI, 12.0-21.9 months). Cabozantinib was well tolerated, with no unexpected toxic effects or neurological adverse events reported. No treatment-related deaths were observed. CONCLUSIONS AND RELEVANCE: In this cohort study, cabozantinib showed considerable intracranial activity and an acceptable safety profile in patients with RCC and brain metastases. Support of prospective studies evaluating the efficacy of cabozantinib for brain metastases in patients with RCC is critical.

Pathogenicity of VHL variants in families with non-syndromic von Hippel-Lindau phenotypes: An integrated evaluation of germline and somatic genomic results.

Von Hippel-Lindau (VHL) syndrome is a hereditary tumor syndrome associated with germline loss-of-function pathogenic variants (PVs) in the VHL gene. VHL is classically associated with a high penetrance for many different tumor types. The same tumors may be sporadic in the setting of somatic VHL PVs. With more large-scale genome sequencing, variants with low penetrance or variable expressivity are identified. This has introduced challenges in patient management and the clinical interpretation of germline VHL variants identified in non-classic families. Herein, we report individuals from 3 non-classic families with VHL variants who presented with unexpected or non-syndromic phenotypes, but often with a VHL component tumor. In family 1, two siblings, age 61, with pathogenic VHL p.Leu188Val presented with clear cell renal cell carcinoma and lobular breast cancer. In family 2, the proband, age 82, was found to have pathogenic germline VHL p.Tyr98His on testing for metastatic bladder cancer. In family 3, four members carried germline VHL p.Pro81Ser (variant of uncertain significance), after the proband, age 40, presented with cerebellar hemangioblastoma. None of the individuals in the above three families met clinical criteria of classic VHL, suggesting germline VHL p.Leu188Val, p.Y98H, and p.Tyr98His may be low penetrant variants. Large studies are needed to evaluate penetrance and possible effect of genetic and non-genetic modifiers. Somatic sequencing performed on their respective tumors could help discern the etiology of the component tumors, highlighting the role of somatic evaluation in these cases. Paired examination of somatic and germline findings provided a more complete landscape of genome alterations in cancer development.

Subcutaneous metastasis from an atypical pulmonary carcinoid tumor.

Pulmonary carcinoid tumors are uncommon neuroendocrine tumors that rarely metastasize to the skin. We report the case of a 71-year-old woman with a longstanding history of primary atypical pulmonary carcinoid tumor who presented with a new tender cutaneous nodule. Immunostaining of the nodule was consistent with metastatic atypical carcinoid tumor of the skin including positive staining for neuroendocrine markers chromogranin and synaptophysin. Dermatologists should consider cutaneous neuroendocrine metastasis when evaluating new nodules in patients with stable pulmonary carcinoid tumors or in those with concomitant concerning respiratory symptoms.

Mutations and Response to Rapalogs in Patients with Metastatic Renal Cell Carcinoma.

We previously showed that alterations in mTOR pathway genes were correlated with response to rapalog therapy in metastatic renal cell carcinoma (mRCC), when the analysis focused on extremes of response. Herein, we expand on the prior cohort and examine genetic correlations with rapalog response in a dataset not selected for extremes of response. Tumors from 58 patients from the phase III trial of temsirolimus and 51 local patients with mRCC treated with rapalogs were studied. Somatic mutations were investigated using a targeted sequencing platform covering 27 genes. Clinical benefit (CB) was defined as patients with complete remission, partial response, or stable disease lasting at least 22 weeks. Mutational analyses focused on 5 mTOR pathway genes (TSC1, TSC2, MTOR, PTEN, PIK3CA) and 6 genes commonly mutated in RCC (BAP1, KDM5C, PBRM1 SETD2, TP53, and VHL). Among the 109 patients, 93 (85%) patients had clear cell histology, and 31 (28%) showed CB. Nine of 30 (30%) patients harboring mTOR pathway mutations in their tumor achieved CB versus 22 of 79 (28%) in the wild-type group. There was no distinct association between any individual or combination of mTOR pathway gene mutations and CB. Three of 7 patients with TSC1 mutations showed CB. In addition, none of the 6 genes commonly mutated in RCC showed a mutation pattern that correlated with CB. Overall, in this large and diverse population of patients with mRCC, there is no suggestion of a correlation between response to rapalog therapy and mutation status for mTOR pathway genes.

Multimodality imaging of indolent B cell lymphoma from diagnosis to transformation: what every radiologist should know.

Indolent B cell lymphomas are a group of lymphoid malignancies characterized by their potential to undergo histologic transformation to aggressive lymphomas. While different subtypes of indolent B cell lymphomas demonstrate specific clinical and imaging features, histologic transformation can be suspected on cross-sectional imaging when disproportionate lymph node enlargement or new focal lesions in extranodal organs are seen. On PET/CT, transformed indolent lymphoma may show new or increased nodal FDG avidity or new FDG-avid lesions in different organs. In this article, we will (1) review the imaging features of different subtypes of indolent B cell lymphomas, (2) discuss the imaging features of histologic transformation, and (3) propose a diagnostic algorithm for transformed indolent lymphoma. The purpose of this review is to familiarize radiologists with the spectrum of clinical and imaging features of indolent B cell lymphomas and to define the role of imaging in raising concern for transformation and in guiding biopsy for confirmation.

What Is New in the 2017 World Health Organization Classification and 8th American Joint Committee on Cancer Staging System for Pancreatic Neuroendocrine Neoplasms?

The diagnosis and management of pancreatic neuroendocrine neoplasms (NENs) have evolved significantly in recent years. There are several diagnostic and therapeutic challenges and controversies regarding the management of these lesions. In this review, we focus on the recent significant changes and controversial issues regarding the diagnosis and management of NENs and discuss the role of imaging in the multidisciplinary team approach.

Radiogenomics in renal cell carcinoma.

Radiogenomics, a field of radiology investigating the association between the imaging features of a disease and its gene expression pattern, has expanded considerably in the last few years. Recent advances in whole-genome sequencing of clear cell renal cell carcinoma (ccRCC) and the identification of mutations with prognostic significance have led to increased interest in the relationship between imaging and genomic data. ccRCC is particularly suitable for radiogenomic analysis as the relative paucity of mutated genes allows for more straightforward genomic-imaging associations. The ultimate aim of radiogenomics of ccRCC is to retrieve additional data for accurate diagnosis, prognostic stratification, and optimization of therapy. In this review article, we will present the state-of-the-art of radiogenomics of ccRCC, and after briefly reviewing updates in genomics, we will discuss imaging-genomic associations for diagnosis and staging, prognosis, and for assessment of optimal therapy in ccRCC.

A review of the principles of texture analysis and its role in imaging of genitourinary neoplasms.

Advances in the management of genitourinary neoplasms have resulted in a trend towards providing patients with personalized care. Texture analysis of medical images, is one of the tools that is being explored to provide information such as detection and characterization of tumors, determining their aggressiveness including grade and metastatic potential and for prediction of survival rates and risk of recurrence. In this article we review the basic principles of texture analysis and then detail its current role in imaging of individual neoplasms of the genitourinary system.

Imaging Advances in the Management of Kidney Cancer.

New developments in cross-sectional imaging, including contrast-enhanced ultrasound, dual-energy computed tomography, multiparametric magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography, together with novel application of existing and novel radiotracers, have changed the landscape of renal mass characterization (ie, virtual biopsy) as well as the detection of metastatic disease, prognostication, and response assessment in patients with advanced kidney cancer. A host of imaging response criteria have been developed to characterize the response to targeted and immune therapies and correlate with patient outcomes, each with strengths and limitations. Recent efforts to advance the field are aimed at increasing objectivity with quantitative techniques and the use of banks of imaging data to match the vast genomic data that are becoming available. The emerging field of radiogenomics has the potential to transform further the role of imaging in kidney cancer management through eventual noninvasive characterization of the tumor histology and genetic microenvironment in single renal masses and/or metastatic disease. We review of the effect of currently available imaging techniques in the management of patients with kidney cancer, including localized, locally advanced, and metastatic disease.

Radium-223 Dichloride in Combination with Vascular Endothelial Growth Factor-Targeting Therapy in Advanced Renal Cell Carcinoma with Bone Metastases.

Purpose: This study investigates the biologic activity of radium-223 with VEGF-targeted therapy in patients with advanced renal cell carcinoma (aRCC) and bone metastases.Patients and Methods: Fifteen treatment-naïve patients (n = 15) received pazopanib 800 mg orally once daily, and 15 previously treated patients received sorafenib 400 mg orally twice daily. Radium-223 55 kilobecquerel/kg was administered concurrently every 4 weeks for up to six infusions in both cohorts. The primary endpoint was decline in bone turnover markers (Procollagen I Intact N-Terminal, N-telopeptide, C-telopeptide, osteocalcin, and bone-specific alkaline phosphatase) compared with baseline. Secondary endpoints included safety, rate of symptomatic skeletal event (SSE) and time to first SSE, objective response rate, change in analgesic use, and quality of life. Exploratory analysis of tumor genomic alterations was performed.Results: Of the 30 patients enrolled, 83% had IMDC intermediate- or poor-risk disease, 33% had liver metastases, and 83% had a history of SSE prior to enrollment. No dose-limiting toxicity was observed. All bone turnover markers significantly declined from baseline at week 8 and 16. Forty percent of patients experienced treatment-related grade ≥3 adverse events. Response rates were 15% and 18% per RECIST v1.1 and bone response was 50% and 30% per MD Anderson criteria, in the pazopanib and sorafenib cohort, respectively. Median SSE-free interval was 5.8 months and not reached, respectively. Analgesic use remained stable over the study time.Conclusions: Radium-223 combined with VEGF-targeted therapy is biologically active and safe. Randomized-controlled trials are needed to define the role of radium-223 in aRCC with skeletal metastases. Clin Cancer Res; 24(17); 4081-8. ©2018 AACR.

Mass Compression from Recurrent Lymphoma Mimicking Lower Extremity Cellulitis.

Cellulitis is a common skin and soft tissue infection with substantial misdiagnosis rates due to its nonspecific clinical characteristics. In this report, we present a patient with recurrent metastatic diffuse large B-cell lymphoma (DLBCL) masquerading as a unilateral lower extremity cellulitis. A 62-year-old man with a history of DLBCL, in remission for two years, presented with a two-week history of swelling and erythema of the right thigh and leg. Despite treatment with clindamycin and cephalexin, the redness and swelling continued to progress. On presentation to the emergency department, vitals were within normal limits, laboratory workup was significant only for borderline anemia and thrombocytopenia, and bilateral lower extremity ultrasound was negative for a clot. The patient was evaluated by a dermatologist who recommended further imaging workup for proximal vascular compression given the uniformity of inflammation and edema in the absence of fever or systemic symptoms. Imaging revealed retroperitoneal lymphadenopathy, right pelvic side wall and right inguinal lymphadenopathy, an intramuscular lymphomatous involvement of the right iliopsoas muscle, and mass compression of the right external iliac vein. Bone marrow and soft-tissue biopsies confirmed recurrent and metastatic DLBCL. In this patient, the atypical cellulitis-like features are likely due to venous and lymphatic obstruction secondary to mass effect from metastasis. Going forward, clinicians should consider compression-induced edema as a sign of primary or recurrent malignancy in patients with refractory or atypical cellulitis.

Review of targeted therapy in chronic lymphocytic leukemia: what a radiologist needs to know about CT interpretation.

The last 5 years have been marked by profound innovation in the targeted treatment of chronic lymphocytic leukemia (CLL) and indolent lymphomas. Using CLL as a case study, we present a timeline and overview of the current treatment landscape for the radiologist, including an overview of clinical and radiological features of CLL, discussion of the targeted agents themselves, and the role of imaging in response and toxicity assessment. The goal is to familiarize the radiologist with multiple Food and Drug Administration (FDA)-approved targeted agents used in this setting and associated adverse events which are commonly observed in this patient population.

Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events.

The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here, we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAE) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary endpoint was time to progression from the date of treatment cessation (TTP). Most patients had clear cell histology and received anti-PD-1/PD-L1 therapy as second-line or later treatment. Median time on PD-1/PD-L1 therapy was 5.5 months (range, 0.7-46.5) and median TTP was 18.4 months (95% CI, 4.7-54.3) per Kaplan-Meier estimation. The irAEs included arthropathies, ophthalmopathies, myositis, pneumonitis, and diarrhea. We demonstrate that 68.4% of patients (n = 13) experienced durable clinical benefit off treatment (TTP of at least 6 months), with 36% (n = 7) of patients remaining off subsequent treatment for over a year after their last dose of anti-PD-1/PD-L1. Three patients with tumor growth found in a follow-up visit, underwent subsequent surgical intervention, and remain off systemic treatment. Nine patients (47.4%) have ongoing irAEs. Our results show that patients who benefitted clinically from anti-PD-1/PD-L1 therapy can experience sustained beneficial responses, not needing further therapies after the initial discontinuation of treatment due to irAEs. Investigation of biomarkers indicating sustained benefit to checkpoint blockers are needed. Cancer Immunol Res; 6(4); 402-8. ©2018 AACR.

The Clinical Presentation, Survival Outcomes, and Management of Patients With Renal Cell Carcinoma and Cardiac Metastasis Without Inferior Vena Cava Involvement: Results From a Pooled Clinical Trial Database and Systematic Review of Reported Cases.

BACKGROUND: Cardiac metastases from renal cell carcinoma (RCC) are uncommon and there are limited data regarding the presentation and outcomes of this population. The objective of this study was to evaluate the characteristics and outcomes of patients with RCC with cardiac metastasis without inferior vena cava (IVC) involvement. MATERIALS AND METHODS: We conducted a pooled retrospective analysis of metastatic RCC patients treated in 4 clinical trials. Additionally, we conducted a systematic review of cases reported in the literature from 1973 to 2015. Patients with cardiac metastases from RCC without IVC involvement were included. Patient and disease characteristics were described. Additionally, treatments, response to therapy, and survival outcomes were summarized. RESULTS: Of 1765 metastatic RCC patients in the clinical trials database, 10 had cardiac metastases without IVC involvement. All patients received treatment with targeted therapy. There was 1 observed partial response (10%) and 6 patients showed stable disease (60%). The median progression-free survival was 6.9 months. The systematic review of reported clinical cases included 39 patients. In these patients, the most common cardiac site of involvement was the right ventricle (51%; n = 20). Patients were treated with medical (28%; n = 11) and/or surgical treatment (49%; n = 19) depending on whether disease was isolated (n = 13) or multifocal (n = 26). CONCLUSION: To our knowledge, this is the first series to report on the presentation and outcomes of patients with cardiac metastasis without IVC involvement in RCC. We highlight that although the frequency of patients with cardiac metastases without IVC involvement is low, these patients have a unique clinical presentation and warrant special multidisciplinary management.

Change in Neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma.

BACKGROUND: An elevated Neutrophil-to-lymphocyte ratio (NLR) is associated with worse outcomes in several malignancies. However, its role with contemporary immune checkpoint blockade (ICB) is unknown. We investigated the utility of NLR in metastatic renal cell carcinoma (mRCC) patients treated with PD-1/PD-L1 ICB. METHODS: We examined NLR at baseline and 6 (±2) weeks later in 142 patients treated between 2009 and 2017 at Dana-Farber Cancer Institute (Boston, USA). Landmark analysis at 6 weeks was conducted to explore the prognostic value of relative NLR change on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Cox and logistic regression models allowed for adjustment of line of therapy, number of IMDC risk factors, histology and baseline NLR. RESULTS: Median follow up was 16.6 months (range: 0.7-67.8). Median duration on therapy was 5.1 months (<1-61.4). IMDC risk groups were: 18% favorable, 60% intermediate, 23% poor-risk. Forty-four percent were on first-line ICB and 56% on 2nd line or more. Median NLR was 3.9 (1.3-42.4) at baseline and 4.1 (1.1-96.4) at week 6. Patients with a higher baseline NLR showed a trend toward lower ORR, shorter PFS, and shorter OS. Higher NLR at 6 weeks was a significantly stronger predictor of all three outcomes than baseline NLR. Relative NLR change by ≥25% from baseline to 6 weeks after ICB therapy was associated with reduced ORR and an independent prognostic factor for PFS (p < 0.001) and OS (p = 0.004), whereas a decrease in NLR by ≥25% was associated with improved outcomes. CONCLUSIONS: Early decline and NLR at 6 weeks are associated with significantly improved outcomes in mRCC patients treated with ICB. The prognostic value of the readily-available NLR warrants larger, prospective validation.

A cost-effectiveness analysis of the diagnostic strategies for differentiating focal nodular hyperplasia from hepatocellular adenoma.

OBJECTIVES: We evaluated the cost-effectiveness of a gadoxetic acid-enhanced MRI (EOB-MRI) strategy compared with conventional MRI strategy and biopsy to differentiate focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA). METHODS: A decision tree model was constructed to compare the cost-effectiveness of EOB-MRI, conventional MRI with extracellular contrast agents, and biopsy as the initial diagnostic modality in patients with incidentally detected focal liver lesions suspected of being FNH or HCA. We analysed the cost and effectiveness, i.e. probability of successful diagnosis of each strategy. Costs were based on utilisation rates and Medicare reimbursements in the USA and South Korea. RESULTS: In the base case analysis of our decision tree model, the effectiveness of the three strategies was similar. The cost of the EOB-MRI strategy ($1283 in USA, $813 in South Korea) was lowest compared with the biopsy strategy ($1725 in USA, $847 in South Korea) and the conventional MRI strategy ($1750 in USA, $962 in South Korea). One-way, two-way and probabilistic sensitivity analysis showed unchanged results over an acceptable range. CONCLUSIONS: EOB-MRI strategy is the most cost-effective strategy for differentiating FNH from HCA in patients with incidentally detected focal liver lesions in a non-cirrhotic liver. KEY POINTS: • The effectiveness of the three strategies was similar. • The cost of the EOB-MRI strategy was lowest. • EOB-MRI strategy is the most cost-effective for differentiating FNH from HCA.

Regression of multifocoal in transit melanoma metastases after palliative resection of dominant masses and 2 years after treatment with ipilimumab.

BACKGROUND: Spontaneous regression of metastatic melanoma and delayed responses more than one year after treatment with ipilimumab are rarely seen. CASE PRESENTATION: Here, we present the case of a patient with in transit metastases from cutaneous melanoma on his right lower extremity who achieved complete regression of all metastatic lesions 13 months after the first of two consecutive palliative resections of dominant masses and more than two years after treatment with ipilimumab. CONCLUSION: The exact cause of our patient's sudden onset of tumor regression remains speculative. We hypothesize that the operative trauma followed by the postoperative infections augmented an innate immune response.