History Of Renal Cell Carcinoma Research Articles

Pheochromocytoma Presenting in a Elderly Female With a History of Uterine Leiomyoma and Renal Cell Carcinoma

Background: Adrenal incidentaloma are masses that are found coincidentally on radiologic imaging usually performed for indications other than evaluation for adrenal disease. Pheochromocytomas are rare, usually sporadic catecholamine-producing adrenal tumors and represent 5% of adrenal incidentalomas. While pheochromocytomas can present on their own, they can also present as part of a spectrum of disease found in certain familial syndromes. We present a case of pheochromocytoma found in a patient with a history of renal cell carcinoma and fallopian tube leiomyoma.Case Presentation: A 67 year old female with a past medical history of diabetes mellitus type II, end stage renal disease on hemodialysis, hypertension, skin cancer, right fallopian tube leiomyoma, and right renal mass suspected for renal cell carcinoma presented to the clinic for evaluation of a left adrenal mass. Left adrenal mass was incidentally found 3 years ago on CT abdomen for evaluation for renal transplant and noted to be 2.2 cm in diameter. There were also incidental findings of a 1.3cm right renal mass and a 5.6x4.8cm right adnexal mass. Patient underwent robot assisted total laparoscopic hysterectomy with bilateral salpingo-oophrectomy and surgical pathology results showed leiomyoma of the myometrium. Surveillance CT imaging done 3 years after showed the left adrenal mass and right renal mass increased in size with the adrenal mass increasing to 4.3 cm in diameter with central necrosis and right renal mass increasing to 3.2 x 1.3 cm. Screening biochemical test were done, and initial test and confirmatory test confirmed pheochromocytoma. Dexamethasone suppression test and aldosterone/renin ratio results were normal. Surgical pathology confirmed pheochromocytoma and biopsy of the right renal mass 8 months later confirmed renal cell carcinoma.Conclusion: Majority of pheochromocytomas are sporadic but up to 40% have been identified as inherited in origin due germline mutations. They have been known to present as a part of a spectrum of disease pathologies specific for certain familial syndromes such as Neurofibromatosis Type 1, Von Hippel Lindau Syndrome, Multiple Endocrine Neoplasia Type 2, and Familial Paragangliomas. One relatively uncommon syndrome, Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome due to a mutation in the fumarate hydratase gene, has been known to present with pheochromocytoma in rare cases. Our patient presented with pheochromocytoma, renal cell carcinoma, and uterine leiomyoma which is suspicious for Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome. The diagnosis was not confirmed as genetic testing was not done. Due to a high rate of inherited patterns of pheochromocytoma, routine genetic testing should be done as identification of gene mutations may lead to diagnosis, treatment, and surveillance for patients and their relatives.

Metastatic Non-Functional Pancreatic Neuroendocrine Tumor in a Patient With a Pathogenic TSC1 Mutation

Abstract Introduction: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder caused by mutations in two tumor suppressor genes (TSC1 and TSC2) encoding proteins critical in cell growth and proliferation and is associated with an increased risk for benign and malignant tumors. Pancreatic neuroendocrine tumors (PNET) occur in 1.5-1.8% of patients with TSC. They have been primarily reported in TSC2, with only a few cases in the context of TSC1. We describe a non-functional metastatic PNET in a patient with a known pathogenic TSC1 mutation. Case Description: A 49-year old female with a past medical history of bipolar disease, a family history of TSC1 in a daughter, a known pathologic TSC1 mutation (c.2356C>T), and previous history of renal cell carcinoma (RCC) was evaluated for a pancreatic lesion with likely liver metastases. Two years prior to the presentation, a 10 mm pancreatic lesion was initially noted on the CT scan during a renal mass evaluation. Nephrectomy confirmed the RCC. Two years later, surveillance imaging revealed two new lesions in the liver, and the pancreatic lesion had enlarged to 1.3 cm. She denied symptoms suggestive of a functional PNET, and her physical exam was unremarkable. Gallium-68 dotatate (GA-68) PET/CT scan demonstrated avid lesions of both the pancreatic tail and left hepatic lobe. Biopsy of the 3 cm liver mass revealed a metastatic high-grade neuroendocrine carcinoma (mib-1 proliferation index of 15%) favoring a primary PNET. Immunohistochemical stains were positive for chromogranin A, synaptophysin, EMA, PAX 8, CK 20, and villin. Stains for CA 19-9 and CK 7 were negative. Biochemical testing suggested that the PNET was non-functional. Specifically, serum concentrations of gastrin, somatostatin, glucagon, glucose, C-peptide, proinsulin, pancreatic polypeptide, chromogranin A, and vascular endothelial growth factor were within normal limits. The patient underwent distal pancreatectomy and resection of the liver mass. Pathological specimens confirmed the diagnosis of a PNET. The patient remained asymptomatic and was monitored regularly with MRI and GA-68 PET/CT scans without further evidence of the disease for 1.5 years. Conclusions: We conclude that this patient harboring a c.2356C>T TSC1 mutation developed a non-functional metastatic PNET. PNET is a likely component of TSC1.

Laser enucleation of a renal cell carcinoma (RCC) lung metastasis. This video demonstrates a metastasis enucleation using a laser fiber with a power of 60 W. The 64-year-old former heavy smoker male with a history of RCC 18 months prior, was admitted with undefined pulmonary nodules. The procedure started with a uniportal video-assisted thoracic surgery (VATS) wedge resection from segment

Laser enucleation of a renal cell carcinoma (RCC) lung metastasis. This video demonstrates a metastasis enucleation using a laser fiber with a power of 60 W. The 64-year-old former heavy smoker male with a history of RCC 18 months prior, was admitted with undefined pulmonary nodules. The procedure started with a uniportal video-assisted thoracic surgery (VATS) wedge resection from segment

Clinical features with anti fibroblast growth factor receptor 3 (FGFR3) antibody-related polyneuropathy: a retrospective study

BackgroundDespite its initial association with sensory neuropathies, anti-fibroblast growth factor receptor 3 (FGFR3) antibodies have been since reported with a broad range of neuropathies and clinical features. The aim of the study is to report the clinical and electro diagnostic findings in a cohort of patients with sensory or sensorimotor polyneuropathy and anti-FGFR3 antibodies.MethodsWe performed a retrospective chart review to assess the clinical characteristics of patients with sensory or sensorimotor neuropathy related to FGFR3 antibodies. Descriptive statistics were reported using frequencies and percentages for categorical variables and median and interquartile range (IQR) for continuous variables.ResultsThis study included 14 patients (9 women) with a median age of 51.9 years (IQR 48–57). The most common presenting symptoms were painful paresthesia (100%), gait instability (42.9%), constitutional symptoms (42.9%), and autonomic symptoms (28.6%). Onset of symptoms was chronic (≥12 weeks) in eight patients (57.1%). Examination showed a distal loss of sensation to pin prick (100%), as well as impaired vibration sensation (78.6%) and proprioception (35.7%), in the distal extremities. We also observed mild weakness in the distal lower-extremities (42.9%). Three patients (21.4%) had trigeminal neuralgia, three patients (21.4%) had co-existing autoimmune disease, and one patient (7.1%) had a history of renal cell carcinoma. The mean titer of FGFR3 antibody was 14,285.71 (IQR 5000–16,750). All 14 patients produced normal results in the neuropathy workup. Nerve conduction study and electromyography showed sensory axonal neuropathy in four patients (28.6%), sensorimotor axonal neuropathy in seven patients (50%), and a normal result in three patients (21.4%). For those with a normal NCS/EMG, a skin biopsy showed a non-length-dependent small fiber neuropathy.ConclusionsNeuropathy related to FGFR3 antibodies can potentially involve small and large fibers, sensory and motor fibers, and even the trigeminal nerve, which contributes to a highly variable clinical presentation.

Robotic enucleation of pancreatic head insulinoma in two cases with challenging tumor locations

Presenter: John D Karalis MD | University of Texas Southwestern Medical Center Background: Insulinomas are rare neuroendocrine tumors for which surgical resection is the cornerstone of treatment. Enucleation of insulinomas located in the head of the pancreas can be challenging but is preferable to avoid the morbidity associated with pancreaticoduodenectomy. Our video-presentation aims to describe our technique for robotic enucleation of pancreatic head insulinomas. Methods: Our video describes the clinical presentation, diagnostic imaging and technical aspects of the surgical approach in two patients with pancreatic head insulinomas that underwent robotic enucleation. Results: The first patient is a 76-year-old female who presented with a 2-month history of syncope. Biochemical work-up revealed a blood glucose level of 35 mg/dl, C-peptide of 3.3 ng/mL, and proinsulin of 90 pmol/L. CT imaging revealed a 1.5x1.3 cm medial pancreatic head mass, located posterior to the superior mesenteric artery and superior mesenteric vein, anterior to the left renal vein, and in close proximity to the pancreatic duct. Pre-operatively, to aid with intra-operative visualization of the pancreatic duct, a pancreatic duct stent was placed endoscopically. Robotic enucleation of the mass was performed. Intraoperative ultrasound was used to identify the mass and preserve the integrity of the pancreatic duct. Pathology revealed a 1.2 cm well-differentiated neuroendocrine tumor. The patient’s post-operative course was uneventful; her glucose levels normalized, she received a diet on post-operative day 1, her drain was removed on post-operative day 3, and she was discharged home on post-operative day 5. The second patient is a 61-year-old male with a previous history of renal cell carcinoma treated with a robotic-assisted right nephrectomy who presented with mild symptoms attributed to hypoglycemia, with a blood glucose level ranging from 50-70 mg/dl. Biochemical work-up revealed an elevated C-peptide and proinsulin of 8.9 ng/ml and 98 pmol/L, respectively. CT imaging revealed a 1.2 cm pancreatic head mass in close proximity to the pancreatic duct. Pre-operatively, to aid with intra-operative visualization of the pancreatic duct, a pancreatic duct stent was placed endoscopically. Robotic enucleation of the mass was performed. Intraoperative ultrasound revealed that the mass was abutting the main pancreatic duct requiring careful dissection. Pathology revealed a 1.5 cm well-differentiated neuroendocrine tumor. The patient’s post-operative course was uneventful; he received a diet on post-operative day 1, his drain was removed on post-operative day 4, and she was discharged home on post-operative day 5. Conclusion: Robotic enucleation is a safe and feasible option for treatment of pancreatic head tumors in challenging locations. Preoperative pancreatic duct stenting is useful for identification and preservation of the pancreatic duct during the operation, and the use of intraoperative ultrasound is essential for tumor localization. Surgical proficiency and profound understanding of the anatomy of the pancreas are essential for successful robotic enucleation of pancreatic head tumors.

EVEROLIMUS-INDUCED PULMONARY ALVEOLAR PROTEINOSIS

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a rare respiratory disease characterized by an excessive accumulation of lipoproteinaceous surfactant material in the distal air spaces. This is mostly the result of inadequate clearance of surfactant by alveolar macrophages. Autoimmune etiologies make up ∼90% of adult cases, however there are congenital and secondary etiologies as well (1). We present a unique case of drug induced PAP caused by everolimus use. CASE PRESENTATION: A 44 year old female, history of renal cell carcinoma (RCC) with lung metastasis, presents with 1 week of worsening shortness of breath following a round of chemotherapy and immunotherapy (nivolumab, ipilimumab, everolimus). Associated fever, vomiting and productive cough were also reported. On the scene, EMS reported an oxygen saturation of 81% on room air. In the ED, the patient was placed on BiPAP and started on scheduled breathing treatments, IV fluids and broad spectrum antibiotics. Chest exam revealed diffuse rales. Initial labs showed lactic acidosis without an elevated WBC. ABG showed PaO2 of 103 mmHg on 60% BiPAP. CT chest showed new onset loculated right-sided pleural effusion and extensive left-sided ground glassing, concerning for a crazy pavement appearance. Right-sided thoracentesis was attempted and failed as the fluid could not be aspirated. On Day 2, she was intubated due to worsening respiratory status. Bronchoalveolar lavage (BAL) sample was obtained. BAL cytology was negative for malignant cells or active inflammation, but showed an abundance of amorphous, eosinophilic, periodic acid-Schiff (PAS)-positive material. Bacterial, fungal and viral cultures and respiratory viral PCR were negative. She continued to decline and on day 8, in light of her terminal illness, her family decided to transition to hospice care. Compassionate extubation was done on day 9 and the patient expired shortly after. DISCUSSION: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor, often used in breast, pancreatic and renal carcinoma. Though there have been reports of PAP complicating sirolimus use, no such reports exist for everolimus (2). PAS stains of BAL or lung biopsy samples confirm the diagnosis of PAP. But without a sample, high index of clinical suspicion is needed to differentiate PAP from other pulmonary processes and intervene early. If diagnosed early, stopping the offending agent may be all that is needed. In those with moderate to severe symptoms, whole lung lavage (WLL) is the most accepted intervention. 30-50% of cases only require one lavage, others will require repeat at 6-12-month intervals. Cases refractory to WLL may require trials of GM-CSF inhaled therapy and rituximab but their efficacy has only been shown in autoimmune PAP (3). CONCLUSIONS: We present a case of everolimus induced pulmonary alveolar proteinosis in a patient with metastatic RCC. Diagnosis was confirmed with a PAS-positive BAL sample. Reference #1: Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med 2003; 349:2527. Reference #2: Kadikoy H, Paolini M, Achkar K, et al. Pulmonary alveolar proteinosis in a kidney transplant: a rare complication of sirolimus. Nephrol Dial Transplant 2010; 25: 2795–2798 Reference #3: Kumar A, Abdelmalak B, Inoue Y, Culver DA. Pulmonary alveolar proteinosis in adults: pathophysiology and clinical approach. Lancet Respir Med 2018; 6:554. DISCLOSURES: No relevant relationships by Gnananandh Jayaraman, source=Web Response No relevant relationships by Ramesh Babu Kesavan, source=Web Response No relevant relationships by Robert Liu, source=Web Response No relevant relationships by Sivatej Sarva, source=Web Response

S1656 Not Your Standard Adenocarcinoma, a Case of Medullary Carcinoma of the Colon

INTRODUCTION: Adenocarcinoma of the colon is the most common type of colon cancer. Medullary carcinoma (MC) of the colon is a rare histological subtype of adenocarcinoma. MC has been described to have specific histopathological features but can still be difficult to distinguish from poorly differentiated adenocarcinoma. We aim in this case report to shed light on this rare subtype of colon cancer and describe its histopathological features. CASE DESCRIPTION/METHODS: 76-year-old male presented to our hospital reporting 3 months of back pain, fatigue, and 10lb weight loss. Past medical history significant for atrial fibrillation and history of renal cell carcinoma. CT abdomen/pelvis showed a necrotic mass within the ascending colon suggestive of colon cancer. Metastatic lymph nodes were also suspected on the scan. Subsequent colonoscopy showed a large mass at the hepatic flexure. Multiple biopsies were taken from mass. Histopathologic sections showed sheets of malignant epithelial cells extending from the submucosa into the lamina propria. Immunohistochemical staining demonstrated that the malignant cells were positive for pan-cytokeratin, but negative for CK20, CDX2, S-100, CD45, synaptophysin, chromogranin, and PSA. These initial findings were consistent with invasive poorly differentiated carcinoma. Further immunohistochemical testing was done and showed mismatch repair deficiency with loss of MLH1 and PMS2 consistent with medullary carcinoma of the colon, which typically shows aberrant loss of CK20 and CDX2 (typical markers of colorectal adenocarcinoma). Due to patients advanced disease (stage IV), decision made to start palliative chemotherapy with Xeloda + Oxaliplatin + Avastin. Patient passed away approximately three months after initial diagnosis. DISCUSSION: MC of the colon is extremely rare with limited clinical and epidemiologic data. Based on population-based analysis, medullary carcinoma makes up 5-8 cases for every 10,000 colon cancers diagnosed. Most patients are diagnosed earlier in the disease course and metastatic disease is seen in 10% of patients at time of diagnosis. Immunohistochemical analysis is essential to differentiate from poorly-differentiated and undifferentiated colon adenocarcinomas. Classic findings include loss of staining for MLH-1 and CDX-2. In the current published data, overall prognosis of MC is favorable when compared to poorly differentiated or undifferentiated adenocarcinomas. However, data is limited regarding available treatment strategies and response.Figure 1

Abstract 4719: Novel germline variants in hereditary renal cell carcinoma genes elucidated by whole genome sequencing

Abstract Whole genome sequencing (WGS) may be utilized to reveal novel germline variants in renal cell carcinoma (RCC) syndrome genes that cannot be characterized by conventional methods. Patients who present with clinical manifestations of von Hippel-Lindau (VHL), Hereditary Leiomyomatosis Renal Cell Carcinoma (HLRCC), or Hereditary Papillary Renal Carcinoma (HPRC) are routinely evaluated for germline mutations in the VHL, FH (fumarate hydratase), or MET gene, respectively, by genetic testing. Rarely, either a negative result or an unusual finding is reported. For one patient who exhibited multiple clinical manifestations of VHL in the kidneys, pancreas, cerebellum and epididymis but no germline mutation, karyotype analysis revealed that the patient possessed a germline translocation between chromosomes 1 and 3. Two patients with family history of papillary type 1 RCC but no point mutation in MET were determined to have novel germline duplications in all or part of the MET gene. Finally, seven patients with clinical manifestations of HLRCC including cutaneous and uterine leiomyomas and/or family history of RCC, had negative genetic testing. Paired-end WGS was performed on the DNA derived from peripheral blood leucocytes from these patients. WGS for the patient with VHL manifestations revealed that the breakpoint between chromosomes 1 and 3 falls directly within intron 2 of the VHL gene, leading to a novel disruption of VHL in the germline. Sanger sequencing was performed to determine the exact breakpoints on both chromosomes. We believe this to be the first report of a germline chromosomal translocation resulting in VHL syndrome Likewise, both MET duplications were sequenced across the exact breakpoints, revealing a tandem duplication of 601,339 bp including the entire MET gene in one patient, and a tandem duplication of 101,464 bp including exons 5 through 21 in the other patient. As MET is an oncogene, we theorize that these duplications result in increased expression levels. Finally, 4 of 7 patients with clinical manifestations of HLRCC, including a family of three affected members, were found to possess a novel intronic A to G variant in intron 9 of FH that has not been reported in any human genome databases. This variant introduces a cryptic splice acceptor site and thus adds an extra exon of 57 bp to the transcript, resulting in a premature stop codon and thus a truncated protein of 474 amino acids. A cutaneous leiomyoma from one patient demonstrates loss of heterozygosity, substantiating loss of FH function. In conclusion, germline whole genome sequencing should be considered for patients who exhibit clinical manifestations of a hereditary RCC disease syndrome but for whom no sequence variants are detected by standard genetic testing, in order to improve the detection rate of novel germline variants. Citation Format: Cathy D. Vocke, Christopher J. Ricketts, Daniel R. Crooks, Martin Lang, Laura S. Schmidt, Mayank Tandon, Bao Tran, Christina Fitzsimmons, Pedro J. Batista, Mark W. Ball, W. Marston Linehan. Novel germline variants in hereditary renal cell carcinoma genes elucidated by whole genome sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4719.

Metatarsal metastasis from clear cell renal cell carcinoma: a case report and literature review

BackgroundBone metastasis is known to occur in some patients with cancer, usually in the spine, pelvis or ribs, and less than 0.01% of patients have metastases in the foot bone, so metatarsal metastasis is quite rare. The initial symptoms of osseous metastases are swelling, pain, or both.Case presentationWe report a 68-year-old man with solitary metatarsal metastasis 26 months after a diagnosis of renal clear cell carcinoma. The patient suffered intermittent swelling of his right foot and pain for one year due to trauma and was not treated. The doctor attributed the symptoms to trauma, administering massage therapy and a plaster cast to the patient at the local clinic. After reviewing the medical records, we found that this patient had a history of clear cell renal cell carcinoma. The patient underwent radiological examination and open biopsy of the first metatarsal bone of the right foot. These findings confirmed that the patient had a metatarsal metastasis from clear cell renal cell carcinoma. The patient subsequently underwent right foot amputation. No local recurrence or distant metastasis was found after a 6-month follow-up.ConclusionClinicians should be aware of a history of renal cell carcinoma (RCC) and fully understand the patient’s past medical history. When treating patients with clear cell renal cell carcinoma who have unresolving bony pain or swelling, clinicians should always keep in mind the possibility of bone metastasis of RCC.

Multinodular goiter in a patient with a history of renal cell carcinoma

Multinodular goiter in a patient with a history of renal cell carcinoma

The natural history of renal cell carcinoma with isolated lymph node metastases following surgical resection from 2006 to 2013

IntroductionRenal cell carcinoma (RCC) with isolated lymph node (LN) involvement (pN1 M0 RCC) is a rare clinical entity associated with a poor prognosis. Prior studies comprised cohorts treated predominantly prior to the introduction of targeted systemic therapy. We therefore examined the natural history of pN1M0 RCC following surgical resection in a contemporary cohort, and evaluated clinicopathologic features associated with survival. Patients and methodsWe identified patients aged 18 to 89 years who underwent radical or partial nephrectomy with LN dissection for pN1 M0 RCC from 2006 to 2013 in the National Cancer Database. The associations of clinicopathologic features with overall survival (OS) were evaluated using Cox regression models, and a simplified risk score was developed. ResultsA total of 2,679 patients were found to have pN1 M0 RCC after nephrectomy. Median follow-up was 19.2 (interquartile range 8.2, 39.8) months, during which time 1,782 patients died. One-, 5-, and 8-year OS rates were 68%, 28%, and 19%, respectively. On multivariable analysis, older age (HR 1.50; P< 0.001 for ≥70 vs, 18–<50 years old), rural location (HR 1.49; P= 0.01), larger tumor size (HR 1.29; P= 0.01 for 5–<10 cm; HR 1.34; P= 0.01 for 10–<15 cm; HR 1.43; P= 0.01 for ≥15 cm vs. <5 cm); higher pT stage (HR 1.25; P= 0.04 for pT3; HR 2.41; P< 0.001 for pT4 vs. pT1), positive surgical margins (HR 1.55; P< 0.001), number of positive LNs (HR 1.18; P= 0.01 for 2–3; HR 1.37; P< 0.001 for >3 vs. 1), and nonclear cell histologic subtype (HR 1.32; P< 0.001) were independently associated with decreased OS. A simplified risk score was developed based on the multivariable results. Five-year OS was 49%, 28%, 22%, and 10% for patients with scores of <4, 4 to 6, 7 to 9, and >9, respectively. ConclusionsIn this large, contemporary cohort, pN1 M0 RCC was associated with a poor prognosis, with 5-year survival less than 30%. A simplified risk score was developed to facilitate postoperative risk-stratification and selection of patients for consideration of adjuvant therapy and clinical trial enrollment.

SUN-420 Pituitary Apoplexy Associated With Apixaban

Background: Pituitary apoplexy (PA) is a relatively rare condition associated with sudden hemorrhagic pituitary infarction, and usually occurs in the setting of a pituitary adenoma. Patients typically present with the acute onset of headache, visual changes and pituitary hormonal deficiencies. Oral anticoagulation therapy is a known risk factor for PA and has recently been described in association with the newer anticoagulants, including both thrombin and Factor Xa inhibitors. Clinical Case: An 82 year-old woman with a history of renal cell carcinoma and recent post-operative pulmonary embolism treated with apixiban, presented with acute-onset headache, diplopia, and vomiting. Mental status remained intact. Vital signs were normal. Her physical exam was significant for a left superior temporal quandrantanopsia and was otherwise normal. Brain imaging revealed an 8 x 11 x 12 mm hyperdense mass within the sella representing hemorrhage. She had no known history of pituitary disease. The patient was admitted to the neurosurgical service for close monitoring of her neurologic and hemodynamic status. She was treated with conservative management and empiric glucocorticoids. Pituitary hormone assessment on admission was significant for inappropriately low LH of 0.5 mIU/mL (reference range 10-60) and FSH of 8.6 mIU/mL (reference range 17-114) in a postmenopausal woman. TSH was <0.03 mIU/L (reference range 0.4-5), and free T4 was elevated at 3.31 ng/dL (reference range 0.6-1.2). IGF-1 was within normal limits at 85ng/mL (reference range 31-208). Serum prolactin level was 13.7 ng/mL (normal <20). Cortisol and ACTH were measured after the patient had received empiric stress dose steroids and were thus unreliable. Of note, the patient did not exhibit signs or symptoms of adrenal insufficiency, such as hypotension or electrolyte derangements. Her headache and visual field deficit resolved with conservative treatment and she was discharged on physiologic glucocorticoid replacement therapy. Approximately two months after her initial presentation, the patient generally felt well except mild tremor and insomnia. Repeat endocrine evaluation confirmed central hypogonadism and primary hyperthyroidism. She was diagnosed with Graves’ disease and treated with methimazole. An ACTH stimulation test was normal and hydrocortisone replacement was discontinued. A repeat pituitary MRI demonstrated resolution of the hemorrhage and no evidence of a pituitary adenoma. Conclusion: Anticoagulation therapy, including the newer anticoagulants, is a risk factor for PA and is typically associated with an underlying pituitary tumor. To our knowledge, this is the first case of pituitary hemorrhage in a patient treated with apixaban without evidence of a pituitary tumor.

Simultaneous resection of gastric and gallbladder metastasis from renal cell carcinoma treated by laparoscopic and endoscopic cooperative surgery: a case report

BackgroundMetastases to the stomach or gallbladder from any malignancy is rarely noted, and simultaneous metastases to both organs are atypical. We present a unique case of simultaneous multifocal metastases of the stomach and gallbladder from renal cell carcinoma (RCC).Case presentationThe case involved a 60-year-old man, with a past history of RCC (clear cell type, G2, T1b N0 M0 Stage I) treated by a right nephrectomy. Three years after the nephrectomy, a routine gastrointestinal endoscopy found an ulcerative lesion in the greater curvature of the gastric body. The gastric tumor was pathologically proven to be a metastasis from RCC. Furthermore, computed tomography incidentally revealed a mass lesion in the fundus of the gallbladder, which was also diagnosed as a potential metastasis from RCC. As endoscopic ultrasonography of the gastric tumor suggested the tumor potentially invaded to the submucosal layer, gastric wedge resection via a laparoscopic and endoscopic cooperative surgery (LECS) technique was applied to the gastric tumor, and laparoscopic cholecystectomy to the gallbladder tumor was simultaneously performed. Histological examination confirmed that the tumors of the stomach and gallbladder were both metastatic RCC. The hospitalization period after surgery was not eventful, and the patient was discharged on postoperative day 7. Thereafter, the patient required examination every 3 months, did not use anticancer agents, and has survived without relapse to 9 months after the surgery.ConclusionsFor patients with locally resectable RCC metastases, complete metastasectomy may bring long-term tumor control. Moreover, LECS for gastric metastasis is a reasonable approach for minimal invasiveness and an oncologically feasible outcome.

The natural history of renal cell carcinoma with pulmonary metastases illuminated through mathematical modeling

The goal of this study is to uncover some unobservable aspects of the individual-patient natural history of metastatic renal cell carcinoma (RCC) through mathematical modeling. We analyzed four clear cell RCC patients who at the time of primary tumor resection already had pulmonary metastases. Our description of the natural history of cancer in these patients was based on a parameterized version of a previously proposed very general mathematical model adjusted to these clinical cases. For each patient, identifiable model parameters were estimated by the method of maximum likelihood from the volumes of lung metastases computed from CT scans taken at or around the time of surgery. The model-based distribution of the volumes of lung metastases with likelihood maximizing parameters provided an excellent fit to the data for all patients analyzed. We found that, according to the model, the most likely scenario in all four patients had the following clinically important features: (1) duration of metastatic latency was very small compared to the growth period; (2) seeding of the first lung metastasis occurred before primary tumor reached detectable size, which implies that early cancer detection would not have prevented metastasis; (3) primary tumor contained a relatively fast growing subpopulation of metastasis-producing cells, which is consistent with the observed aggressive course of the disease; and (4) the volume of the primary tumor at the time of metastasis survey does not seem to be correlated with such characteristics of the metastatic burden as the number of detected lung metastases, their total volume, and the volume of the largest detected lung metastasis.

Focal Ablative Therapy for Renal Cell Carcinoma in Transplant Allograft Kidneys

ObjectiveTo evaluate outcomes after focal ablative therapy for renal cell carcinoma (RCC) in transplant allograft kidneys. MethodsAfter institutional review board approval, patients with a history of RCC in a transplanted allograft kidney who underwent focal ablative therapy were identified. Complete chart reviews were performed and the relevant data were extracted for cumulative analysis. ResultsSix patients were treated with focal ablative therapy for RCC in a transplanted allograft kidney at our institutional between 2010 and 2017. Masses were diagnosed at a median of 8 years (range 1 month-8 years) after transplantation. Median mass size was 3 cm. Three patients were treated with microwave ablation, 1 with percutaneous irreversible electroporation, 1 with laparoscopic cryoablation, and 1 with open cryoablation. Median follow-up was 45 months (range 8-61 months). The median creatinine level was 1.65 before ablation and 1.58 1 year after ablation. No patients required dialysis after ablation. No patients developed local recurrence during the follow-up period. However, 1 patient developed lymph node metastases 4 years after ablation. Two patients died during follow-up of other causes. At the time of death both patients had functioning grafts. ConclusionFocal ablative therapies are a feasible, renal-sparing intervention for the management of RCC in renal allografts at intermediate-term follow-up.

A challenging palliation via novel therapeutic approach for unusual presenting with gingival metastasis from renal cell carcinoma relapsed eight years after nephrectomy

Renal cell carcinoma (RCC) is the third most frequently seen primary source of metastatic lesions of the oral cavity. Still oral cavity metastasis is a rarely seen clinical manifestation during the course of RCC. In a patient with a known history of RCC, in the presence of newly emerged oral and maxillofacial lesion(s), possibility of metastasis should be always thought of and pathological investigation should be performed as soon as possible. In RCC, metastatic involvement of oral cavity is generally accompanied by involvement of other organs with resultant lower chance of cure and poor prognosis. Especially in conditions which adversely affect functions of chewing and swallowing consequently nutrition and quality of life, surgery is contraindicated and local interventional methods transarterial chemoembolization, microwave ablation and radiofrequency ablation can be good palliative treatment alternatives. In advanced stages of the diseases with systemic involvement application of local interventional methods either solely or in combination with radiotherapy and surgery increases compliance to the systemic treatment and can contribute markedly to the prolongation of survival. Herein we aimed to present a case with unusual histopathological characteristics and presentation in whom we achieved a longer period of disease-free survival using a different local treatment method.

Association Between Renal Cell Carcinoma and Myelodysplastic Syndromes: Epigenetic Underpinning?

Renal cell carcinoma (RCC) and certain myeloid malignancies are both characterized by widespread aberrant DNA hypermethylation. After clinical observations of patients with a personal history of both malignancies, we sought to explore a potential association, and to describe the clinical characteristics of these patients. Mayo Clinic's 'Advanced Cohort Explorer' database was used to identify patients with a history of both malignancies. Clinical features and long-term outcome were abstracted. Prevalence of myelodysplastic syndromes (MDSs) in patients≥ 65 years with a personal history of nephrectomy for RCC was then compared with the prevalence of MDSs in the Dusseldorf MDS registry and the general patient population at Mayo Clinic, using 1-sample test of proportions. A total of 59 patients with a diagnosis of both RCC and myeloid malignancy were identified. The myeloid malignancies included 38 MDSs, 12 acute myelogenous leukemia, and 9 myeloproliferative neoplasms. The cohort was characterized by marked male predominance (4.4:1). The median age at RCC diagnosis was 64 years (range, 37-87 years), and for myeloid malignancy was 75 years (range, 44-90 years). Prevalence of MDS in patients >65 years with a personal history of nephrectomy for RCC was ≈ 8.4 times that of the age-concordant general population based on the Dusseldorf registry (28/6490 or 395/100,000 vs. ≈ 47/100,000; P< .001), and 3.07 times that of the age-concordant patient population at Mayo Clinic (28/6490 or 395/100,000 vs. 128.4/100,000; P< .001). We observed a strong association between RCC and MDS. Patients with a history of RCC appear to have a substantially increased risk of developing MDS compared with the general population.

Metastatic renal cell carcinoma in the head and neck region

&lt;p&gt;We describe 3 rare cases of metastatic renal cell carcinoma in the head and neck region. Our first case was a 72 years old male presented with profuse bleeding from the left ear. On examination, proliferative, pink, friable mass was present in the left external auditory canal. On eliciting the detailed history, it was found that patient had renal cell carcinoma in the left kidney four years back and underwent left radical nephrectomy. Patient underwent left lateral temporal bone resection with cul-de-sac closure. Histopathological examination of the specimen showed metastatic renal cell carcinoma. Our second case was a 64 years old male presented with complaints of growth in the oral cavity of 1 month duration. On examination, 5×3 cms proliferative growth was present in the hard palate. Biopsy from the growth in the hard palate showed metastatic renal cell carcinoma. Patient gave history of renal cell carcinoma in the past for which he did not receive treatment. Our third case was a 45 years old male who presented to us with a diffuse swelling in the left temporal region of 2 months duration. On examination, 3×2 cms swelling was present in the left temporal region. Patient had history of renal cell carcinoma of left kidney and underwent left nephrectomy one year prior to the presentation of the left temporal swelling. Ultrasonography guided biopsy of the left temporal region showed metastatic renal cell carcinoma.&lt;/p&gt;

Percutaneous Cryoablation of Solitary, Sporadic Renal Cell Carcinoma: Outcome Analysis Based on Clear-Cell versus Papillary Subtypes

PurposeTo evaluate treatment outcomes with percutaneous cryoablation (PCA) based on renal cell carcinoma (RCC) histology. Methods and MaterialsPatients treated with PCA for a solitary, sporadic stage T1a RCC from 2003 to 2016 were identified from a single institution’s renal ablation registry. Patients with multiple tumors, history of RCC, or genetic syndromes associated with RCC (n = 60); no specific RCC subtype determined from core biopsy (n = 66); RCC subtype other than clear-cell or papillary (n = 7); or less than 3 mo of follow-up imaging (n = 5) were excluded. In total, 173 patients met study inclusion criteria. Oncologic outcomes, clinical outcomes, and complications were evaluated based on tumor subtype. ResultsOf the 173 patients who underwent PCA for a stage T1a RCC, 130 (75%) had clear-cell RCC (ccRCC) and 43 (25%) had papillary RCC (pRCC). Median tumor size was 2.9 cm (range, 1.3–4.0 cm). Technically successful cryoablation was achieved in all 173 patients. Local tumor recurrence developed in 6 patients with ccRCC (4.6%), new renal tumors developed in 1 patient (0.8%), and metastatic RCC developed in 1 patient (0.8%) who also had local tumor recurrence. No patients with pRCC showed local tumor recurrence, new renal tumors, or metastatic disease. The 5-year disease-free survival rate in patients with ccRCC was 88%, compared with 100% in patients with pRCC (P = .48). Nine patients (5.2%), all with ccRCC, experienced major complications (P = .11). ConclusionsPercutaneous ablation is a viable treatment option for patients with clinical stage T1a pRCC and ccRCC. Percutaneous ablation may be a very favorable treatment strategy particularly for pRCC.

Metastasis of renal cell carcinoma to the pancreas 11 years postnephrectomy

The pancreas is an unusual site for tumor metastasis, accounting for only 2 to 5% of all malignancies affecting the pancreas. A 67-year-old woman with a past medical history of right renal nephrectomy for renal cell carcinoma, eleven years ago, presented with nausea, diarrhea and vertigo. On admission, the patient was pale. Laboratory tests showed a low hemoglobin level (6,4 grams per deciliter). Abdominal ultrasonography revealed a well-defined, hypoechoic, homogeneous, vascular, lobulated mass in the tail of the pancreas. Computed tomography scan demonstrated a hypervascularized tumor of the pancreatic tail. The patient subsequently underwent a distal pancreatectomy with splenectomy. Grossly, the pancreatic mass was well-delineated and encapsulated measuring 9,5 x 6,5 cm and showed extensive hemorrhage (A). Histological examination of the surgical specimen revealed that the pattern of the tumour growth was predominantly solid, with formation of large nests and acini of tumor cells separated by a stroma that was endowed with prominent sinusoid-like vessels (B). The tumour cells were large ranging from optically clear, with sharply outlined boundaries, to eosinophilic tumour cells. The final pathological diagnosis was metastatic clear-cell renal carcinoma to the pancreas. Four peripancreatic lymph nodes were free of the tumor but the pancreatic resection margins were invaded by the tumour. Postoperative course was uneventful. Renal cell carcinoma metastasis should be considered in patients with a pancreatic mass as it gives the past history of renal cell carcinoma. Awareness of this entity and a high index of suspicion would help in proper diagnosis and treatment.