History Of Renal Cell Carcinoma Research Articles

Gastrointestinal metastases in renal cell carcinoma: A retrospective multicenter GETUG (Groupe d′Étude des Tumeurs Uro-Génitales) study

BackgroundAmong patients with renal cell carcinoma (RCC), bone and visceral metastases have a poor prognosis, while endocrine gland metastases have a more favorable prognosis. Gastrointestinal metastases (GIMs) are rare, and their prognosis is still poorly understood. ObjectivesTo report clinical presentations, patient characteristics, therapeutic strategies, and prognosis of GIMs from RCC. MethodsWe retrospectively collected data from RCC patients presenting GIMs, in 10 French GETUG centers, between 2000 and 2021. ResultsWe identified 74 patients with 87 GIMs, mostly gastric or duodenal. The median age at GIM diagnosis was 69 years and 76% of patients already had other metastases. GIMs occurred after a median duration of 5.4 years (IC95%=[4.2–7.1]) and 1.9 years (IC95%=[1.2–3.8]) from RCC diagnosis and first metastasis, respectively. GIMs were symptomatic in 52 patients (70%), with anemia in 41 patients (55%) and/or gastrointestinal bleeding in 31 patients (42%). Only 22 asymptomatic patients (30%) were fortuitously diagnosed. GIM management consisted of systemic treatment only in 29 GIMs (33%), local treatment only in 23 GIMs (26%), and both local and systemic treatment in 18 GIMs (21%). For 17 GIMs (20%), there was no therapeutic modification. After diagnosis of GIM, median overall survival was 19 months. ConclusionWe report the largest retrospective cohort of GIMs in RCC patients. They should be suspected in case of anemia or gastrointestinal bleeding in any patient with a history of RCC. Their management varies widely depending on their location in the digestive tract and whether or not they are symptomatic.

Tumor-to-tumor spread: a case report and literature review of renal cell carcinoma metastasis into thyroid cancer

Tumor-to-tumor metastasis is a rare, yet important entity. Patients with a history of renal cell carcinoma (RCC) may have tumor deposits to the thyroid gland preceding or following their initial cancer diagnosis for many years. The diagnosis can be challenging, and clinicians must remain suspicious of a newly found thyroid nodule in a patient with a history of RCC. In this review, we report a case of a patient with RCC who was incidentally found to have a thyroid nodule on surveillance imaging found to be consistent with tumor-to-tumor metastasis from RCC into papillary thyroid carcinoma. It is imperative to consider this diagnosis as the thyroid is the most common site of spread, and treatment with partial or total thyroidectomy has led to improved survival.

The use of the flow-void sign on MRI: highly sensitive sign in detecting bone metastases from renal cell carcinoma.

To evaluate a range of pathologically proven malignant bone tumours, including primary bone sarcoma and metastatic bone lesions, referred to a tertiary referral centre for the presence of the flow-void sign on MR imaging. A retrospective search was performed using the radiology information system and oncology database in our institution to identify patients over the age of 40years referred with a solitary bone lesion. Patients with a range of pathologically proven malignant bone tumours, including primary bone tumours and metastatic bone lesions, were included in the study. MRI images were reviewed for the presence of the flow-void sign. The presence and type of the flow-void sign were correlated with lesion size. Two hundred and sixty-six cases were included in the study. Overall, the flow-void sign was identified in 40.9% of cases. The flow-void sign was most frequently seen in renal cell carcinoma metastasis (90.0%). The sign is highly sensitive (90%) for renal cell carcinoma metastases with a high negative predictive value (98.09%). When the flow-void sign is identified, the lesion is almost three times more likely to represent a renal cell carcinoma metastasis than any other malignant tumour in patients over the age of 40years with a solitary bone lesion. The flow-void sign is highly sensitive for renal cell carcinoma bone metastases and could negate the need for biopsy in patients with a known history of renal cell carcinoma or in whom an occult renal cell carcinoma is subsequently identified.

Vitreous Seeding of Renal Cell Carcinoma in a Patient Receiving Checkpoint Inhibitors.

To describe a case of vitreous seeding with tractional retinal detachment due to metastatic renal cell carcinoma (RCC) in a patient on systemic checkpoint inhibitors. Case Report. A 44-year-old Hispanic woman with a history of RCC with metastases to the lungs, adrenal glands, hilar lymph nodes, and peritoneum presented with a complaint of severe floaters and blurry vision of the right eye for two months. She was found to have dense, web-like vitreous opacities and a peripheral tractional retinal detachment of the right eye. We performed a pars plana vitrectomy, membrane peeling, endolaser, air-fluid exchange, gas injection, and vitreous biopsy. The vitreous and membranes were sent for cytology with stains including AE1/AE3, PAX-8, CK-7, CA-IX, AMACR, and S-100. Cytology revealed crowded groups of glandular cells, some in papillary like formations. Positive stains included AE1/AE3, PAX-8, CK-7, CA-IX, and AMACR. Cytology and pathology demonstrated that vitreous seeding of metastatic RCC without an ocular mass lesion. We hypothesize that the use of checkpoint inhibitors played a role in allowing for the atypical and previously unreported seeding of RCC to the vitreous.

The role of [68Ga]Ga-FAPI-04 PET/CT in renal cell carcinoma: a preliminary study.

We aimed to investigate the role of [68Ga]Ga-FAPI-04 PET/CT and uptake patterns of primary and metastatic lesions in patients with renal cell carcinoma (RCC). Twenty patients with a suspicious lesion considered primary renal malignancy or a history of RCC were included in our study. Two patients were excluded from further analyses due to other confirmed malignancies. Six patients were newly diagnosed, while the indication of 12 patients was restaging. All patients underwent [68Ga]Ga-FAPI-04 and [18F]F-FDG PET/CT. SUVmax and tumor-to-background ratio (TBR) of primary (n = 7) and local recurrent lesions (n = 6) and lymph node (n = 26), lung (n = 32), bone (n = 5), and other metastases (n = 14) were compared between the two tracers. We detected 90 lesions in 18 patients with varying FAPI and FDG uptake values on both PET/CT. The median TBR of FAPI-PET/CT of all lesions was higher than TBR of FDG-PET/CT with statistically significance (5.6 vs. 2.1, p < 0.001). In primary and recurrent lesions, the median SUVmax, TBR, and tumor volume on FAPI-PET/CT were higher than FDG-PET/CT. The median SUVmax of lung lesions on FAPI-PET/CT was statistical significantly higher than FDG-SUVmax (3.8 vs. 1.8, p = 0.02). The median of FAPI-SUVmax on primary lesions was lower in the early stage based on TNM compared to the advanced stage. FAPI-SUVmax in 49% of all lesions were SUVmax ≥ 6, and 13% were SUVmax ≥ 10. In patient-based analyses, seven patients (39%) had at least one lesion with FAPI-SUVmax ≥ 10; 12 patients (67%) had at least one lesion with FAPI-SUVmax ≥ 6. This study showed the potential utility of [68Ga]Ga-FAPI-04 PET/CT showing promising results in RCC. We have presumed that FAPI-PET/CT may be performed for complementary imaging modality providing prognosis and possibility of theranostic application in selected patients.

Clinical, cytological, and pathological characteristics of metastatic renal cell carcinoma to the thyroid: A study of 14 cases at a Japanese single institution.

A preoperative diagnosis of metastatic renal cell carcinoma to the thyroid (MRCCT) is important for determining clinical management but is challenging even in cases with a clinical history of renal cell carcinoma (RCC). This study aimed to elucidate the clinical, cytological, and pathological characteristics of MRCCT. Fourteen MRCCT cases extracted from 18 320 malignant thyroid tumors were included in this study. Twelve MRCCT (85.7%) occurred as solitary lesions and the most frequently suspected lesions on ultrasonography were follicular tumors. On cytology, 46.2% of cases were reported as RCC or suspected RCC; a medical history of RCC and immunocytochemistry were helpful in interpretation. RCC metastasized to a follicular adenoma in 50.0% of the solitary lesions. MRCCTs with a long interval from the initial presentation, solitary lesion, and Ki-67 labeling index <10% showed significantly longer disease-free survival. MRCCT is characterized by a long interval from the initial presentation of RCC, appearance as a solitary nodule, ultrasonographic similarity to follicular tumors, sharing cytological findings with primary thyroid tumors, and high frequency of metastasis within follicular adenoma. A long interval from the initial presentation, occurrence as a solitary lesion, and low Ki-67 labeling index may be favorable prognostic factors.

Genetic testing outcomes and pathogenic germline mutation prevalence in renal cell carcinoma.

10601 Background: Germline mutations have been observed in renal cell carcinoma (RCC) with varying frequencies reported from 5% to 18% of patients. Due to the prevalence of germline mutations, current guidelines by the National Comprehensive Cancer Network (NCCN) recommend genetic testing for patients with RCC and high-risk factors such as young age, bilateral or multifocal tumors, family history of RCC, as well as certain RCC histologies. However, the germline mutational landscape in RCC has not been fully characterized. Here, we report the genetic testing results and clinicopathologic factors of patients with RCC who were referred for germline testing. Methods: All patients with a diagnosis code of kidney cancer and referred to the Cancer Genetics clinic at the University of Michigan between 2004 and 2022 were identified. Patients were excluded if they had erroneous RCC diagnosis codes, no history of RCC diagnosis, known familial/hereditary mutation or syndrome, or did not undergo germline testing. Genetic testing outcomes, germline mutation frequency, and clinical factors were obtained through chart review and analyzed using descriptive statistics. Results: A total of 322 patients with a history of RCC and referred for genetic testing were identified. The median age at diagnosis in all patients was 47 (interquartile range: 38-58). Males accounted for 56.8% of the cohort. Most patients (62.4%) had clear cell histology at initial diagnosis, whereas 30.7% had non-clear cell histology. The majority of patients (61.5%) were diagnosed at stage 1. Bilateral and multifocal tumors at diagnosis accounted for 18.9% and 12.7%, respectively. Pathogenic or likely pathogenic variants (P/LP) were identified in 43 patients (13.4%); 225 patients had negative germline testing (69.9%); 54 patients (16.8%) had a variant of unknown significance (VUS). The most frequently mutated RCC-associated genes were FLCN (n=10, 3.1%), SDHA/B/D (n=7, 2.2%), VHL (n=4, 1.2%), MLH1 (n=3, 0.9%), and FH (n=2, 0.6%). Common mutations in other cancer-related genes were CHEK2 (n=4, 1.2%), ATM (n=2, 0.6%), and RAD50 (n=2, 0.6%). Most patients (81.4%) with a P/LP test result had at least 1 of the following: diagnosis age ≤ 46 years, bilateral or multifocal tumors, or at least 1 first-degree relative with RCC. Out of the patients with a P/LP result, 18 patients (39.1%) had a potentially actionable mutation. Conclusions: Among patients with RCC who were unselected for a known familial/hereditary predisposition, P/LP variants were present in 13.4% which is consistent with previous studies. The prevalence of FLCN mutations was higher in our cohort (3.1%) compared to prior observations. Most patients with a P/LP variant met the NCCN criteria for genetic testing. Future studies should optimize the current genetic testing criteria to identify a broader group of patients who may have germline mutations given potential cascade testing and therapeutic implications.

Extramammary paget disease of the penoscrotal region.

Extramammary Paget disease is an uncommon slow growing intraepithelial malignant neoplasm. It can be classified into primary and secondary subtypes, with secondary subtype associated with underlying malignancy. Extramammary Paget disease of the penoscrotal region is extremely rare with very limited literature available describing its clinicopathologic characteristics. We present 6 cases of penoscrotal EMPD diagnosed at our academic medical center over a 20 year period. These included 5 cases of scrotal EMPD and 1 case of penile EMPD. The mean age at diagnosis was 68.6 yrs. (Range 61-78 years), One case of scrotal EMPD had history of renal cell carcinoma and prostatic adenocarcinoma, while one other case presented as recurrent EMPD with initial disease in the left groin. EMPD in the glans penis was associated with a history of urothelial carcinoma in the ureter with pagetoid spread. 3 cases had no progression of the disease till recent follow up, 2 were lost to follow up while 1 case rapidly deteriorated resulting in death. This case had bone metastatic and associated peritoneal carcinomatosis. Thus, Extramammary Paget disease of the penoscrotal area is extremely rare, can be primary or associated with visceral malignancies and usually tends to present at an older age. Peritoneal spread and distant metastasis are associated with rapid progression of the disease.

Identifying metastatic renal cell carcinoma in thyroid fine-needle aspirates by molecular testing.

Renal cell carcinoma (RCC) is the most common type of cancer found to metastasize to the thyroid gland. These tumors may represent a diagnostic challenge in cytology. However, most RCC tumors carry VHL alterations, which are rare in primary thyroid tumors. The aim of this study was to evaluate the utility of molecular testing in detecting metastatic RCC in thyroid fine-needle aspiration (FNA) samples. From November 2017 until March 2022, thyroid FNA samples with ThyroSeq v3 results showing both VHL alterations and low/absent expression of thyroid cell markers were analyzed. Eighteen samples from 15 patients met the inclusion criteria. On molecular analysis, deleterious VHL mutations were found in nine (50%) nodules, VHL copy number alteration (CNA) in two (11%), and both mutations and CNA in seven (39%). None of the cases showed mutations commonly found in thyroid tumors. The mean age of these patients was 68 (range, 49-89) years with a male to female ratio of 2:1. Eight (53%) patients had multiple thyroid nodules on ultrasound. On cytology, 14 (78%) nodules were diagnosed as Bethesda III, 2 (11%) as Bethesda IV, and 2 (11%) as Bethesda V. At the time of cytology review, the history of RCC, sometimes remote, was available for ten patients. Of the 14 patients with medical history or surgical follow-up available, all had history of RCC or renal mass or revealed metastatic RCC on thyroidectomy. This study demonstrates that molecular testing can reliably identify metastatic RCC in thyroid nodules with indeterminate cytology, which could improve patient management.

EMPYEMA NECESSITANS DUE TO MULTIDRUG-RESISTANT (MDR) PSEUDOMONAS AERUGINOSA: A CASE REPORT

SESSION TITLE: Critical Care in Chest Infections Case Report Posters 1SESSION TYPE: Case Report PostersPRESENTED ON: 10/17/2022 12:15 pm - 01:15 pmINTRODUCTION: Empyema Necessitans (EN) is a rare complication of pleural empyema that spreads outside of the pleural space and involves the chest wall. We present a case of EN due to Pseudomonas aeruginosa (PA) in a 66-year-old male with a prolonged hospitalization course.CASE PRESENTATION: A 66-year-old male with history of renal cell carcinoma with metastases to the lung and systolic congestive heart failure presented with confusion, expressive aphasia, and right-sided facial droop. Computed Tomography (CT) of the head showed an intra-axial mass for which he was started on empiric antibiotics and steroids but the biopsy was postponed due to refractory thrombocytopenia and concerns for ITP. The hospitalization course was complicated by vancomycin-resistant Enterococcus bacteremia and transferred to the intensive care unit (ICU) for respiratory failure. While in the ICU, the patient was found to have a right-sided loculated empyema for which he underwent thoracentesis. Microbiological analysis of the fluid revealed multidrug-resistant (MDR) PA for which he was started on ceftolozane-tazobactam. A repeat CT scan of the chest 1 week later showed an increase in loculated right-sided pleural effusion with the extension of the effusion into the surrounding soft tissue concerning EN. A right chest tube was placed for management of EN and repeat imaging showed improving EN.DISCUSSION: The most common microbial etiologies of EN include Mycobacterium tuberculosis, Actinomyces Spp, Staphylococcus aureus, Fusobacterium Spp, and Streptococcus milleri (1). In the case of our patient, EN was associated with MDR PA which has been reported previously mostly in children. In most cases, early detection and treatment of infections involving the pleural cavity will prevent complications such as EN. However, the emergence of MDR organisms and patients with prolonged hospitalizations who would have received antibiotics for other reasons has made this complicated as was the case with our patient. When EN develops, the treatment goal involves antimicrobial therapy as well as interventions to drain the fluid including aspiration under radiological guidance or open drainage with the placement of a chest tube for drainage of empyema (2). In our case, we were limited to the placement of a chest tube as the patient was unstable and had refractory thrombocytopenia. Among MDR gram-negative bacteria, MDR PA has limited treatment options and causes serious outcomes. Current evidence suggests that ceftazidime-avibactam and ceftolozane-tazobactam may have a role in the treatment of MDR PA (3).CONCLUSIONS: Here, we describe the rare case of a 66-year-old male with MDR PA EN and review the management. We would like to highlight that early detection and management of infections involving the pleural space would prevent complications such as EN. Management of EN usually involves antibiotic therapy and drainage of the fluid.Reference #1: Alfageme I, Muñoz F, Peña N, Umbría S. Empyema of the thorax in adults. Etiology, microbiologic findings, and management. Chest. 1993 Mar;103(3):839–43.Reference #2: Akgül AG, Örki A, Örki T, Yüksel M, Arman B. Approach to empyema necessitatis. World J Surg. 2011 May;35(5):981–4.Reference #3: Nguyen L, Garcia J, Gruenberg K, MacDougall C. Multidrug-Resistant Pseudomonas Infections: Hard to Treat, But Hope on the Horizon? Curr Infect Dis Rep. 2018 Jun;20(8):23.DISCLOSURES: No relevant relationships by Hemanth Krishna BoppanaNo relevant relationships by Ming-Yan ChowNo relevant relationships by Chengu Niu SESSION TITLE: Critical Care in Chest Infections Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Empyema Necessitans (EN) is a rare complication of pleural empyema that spreads outside of the pleural space and involves the chest wall. We present a case of EN due to Pseudomonas aeruginosa (PA) in a 66-year-old male with a prolonged hospitalization course. CASE PRESENTATION: A 66-year-old male with history of renal cell carcinoma with metastases to the lung and systolic congestive heart failure presented with confusion, expressive aphasia, and right-sided facial droop. Computed Tomography (CT) of the head showed an intra-axial mass for which he was started on empiric antibiotics and steroids but the biopsy was postponed due to refractory thrombocytopenia and concerns for ITP. The hospitalization course was complicated by vancomycin-resistant Enterococcus bacteremia and transferred to the intensive care unit (ICU) for respiratory failure. While in the ICU, the patient was found to have a right-sided loculated empyema for which he underwent thoracentesis. Microbiological analysis of the fluid revealed multidrug-resistant (MDR) PA for which he was started on ceftolozane-tazobactam. A repeat CT scan of the chest 1 week later showed an increase in loculated right-sided pleural effusion with the extension of the effusion into the surrounding soft tissue concerning EN. A right chest tube was placed for management of EN and repeat imaging showed improving EN. DISCUSSION: The most common microbial etiologies of EN include Mycobacterium tuberculosis, Actinomyces Spp, Staphylococcus aureus, Fusobacterium Spp, and Streptococcus milleri (1). In the case of our patient, EN was associated with MDR PA which has been reported previously mostly in children. In most cases, early detection and treatment of infections involving the pleural cavity will prevent complications such as EN. However, the emergence of MDR organisms and patients with prolonged hospitalizations who would have received antibiotics for other reasons has made this complicated as was the case with our patient. When EN develops, the treatment goal involves antimicrobial therapy as well as interventions to drain the fluid including aspiration under radiological guidance or open drainage with the placement of a chest tube for drainage of empyema (2). In our case, we were limited to the placement of a chest tube as the patient was unstable and had refractory thrombocytopenia. Among MDR gram-negative bacteria, MDR PA has limited treatment options and causes serious outcomes. Current evidence suggests that ceftazidime-avibactam and ceftolozane-tazobactam may have a role in the treatment of MDR PA (3). CONCLUSIONS: Here, we describe the rare case of a 66-year-old male with MDR PA EN and review the management. We would like to highlight that early detection and management of infections involving the pleural space would prevent complications such as EN. Management of EN usually involves antibiotic therapy and drainage of the fluid. Reference #1: Alfageme I, Muñoz F, Peña N, Umbría S. Empyema of the thorax in adults. Etiology, microbiologic findings, and management. Chest. 1993 Mar;103(3):839–43. Reference #2: Akgül AG, Örki A, Örki T, Yüksel M, Arman B. Approach to empyema necessitatis. World J Surg. 2011 May;35(5):981–4. Reference #3: Nguyen L, Garcia J, Gruenberg K, MacDougall C. Multidrug-Resistant Pseudomonas Infections: Hard to Treat, But Hope on the Horizon? Curr Infect Dis Rep. 2018 Jun;20(8):23. DISCLOSURES: No relevant relationships by Hemanth Krishna Boppana No relevant relationships by Ming-Yan Chow No relevant relationships by Chengu Niu

S3528 A Rare Presentation of Small Bowel Metastasis From Renal Cell Carcinoma: A Case Report and Review

Introduction: At the time of diagnosis, around 25–30% of patients with renal cell carcinoma (RCC) had metastatic disease. The most common locations for metastasis of renal cancer in order of frequency include lung, bone, liver, lymph nodes and brain. RCC metastases to the small intestine are extremely rare, with limited reports in the literature (Table). Case Description/Methods: A 20-year-old male presented with a 3-week history of dull epigastric pain, nausea, and vomiting. Past medical history was significant for iron deficiency anemia, and metastatic RCC was diagnosed in 2021 status post right open radical nephrectomy. The biopsy showed Xp11.2 translocation associated renal cell carcinoma WHO grade 4. The patient had lost follow-up previously. His laboratory workup this admission showed persistent iron deficiency anemia with mild leukocytosis and thrombocytosis and elevated liver enzymes. CT chest/abdomen/pelvis showed concern for intussusception in the distal jejunum causing an obstruction. Surgery team was consulted who took patient for diagnostic laparoscopy. Intraoperatively intussusception was partially reduced laparoscopically but could not be completely reduced since there was a big mass acting as a lead point. The decision was then made to convert to a mini-laparotomy. Small bowel resection with primary anastomosis was performed. Pathology from the specimen confirmed metastatic RCC. Oncology was consulted who plan to start pembrolizumab plus axitinib for systemic therapy. (Figure) Discussion: RCC intraluminal metastases in the small intestine are unusual reported as 2-4% incidence. Bowel metastases from RCC can manifest in several different forms including intussusception, bowel perforation, gastrointestinal bleeding and symptoms of intestinal obstruction due to the presence of a mass within the intestinal wall. This case presented a young male with metastatic RCC to small bowel which has not been reported so far. Clinicians should be aware that, in patients presenting with anemia, clinical symptoms of bowel obstruction and a history of RCC, intestinal tumor involvement should be considered. Metastasectomy may extend patient survival and surgical resection of the involved intestinal segment has been recommended as the treatment of choice.Figure 1.: A: Axial-enhanced CT scan of the abdomen showing Intussusception in the distal jejunum causing the obstruction. B: Intraoperative pictures of intussusception. C: A resected segment of the small intestine with a mass found at the lead point. Table 1. - Published reports of intussusception from renal cell carcinoma No. Author, Year No. of pts Stage of RCC (TNM) Gender Age (years) Histological subtype Outcome 1 Vani et al., 2017 2 NA M, F 65, 68 NA Pt. 1: Death 3 months after surgery. Pt. 2: Death 6 months after surgery. 2 Mishra et al., 2015 1 NA M 57 Clear cell NA 3 Wan Kyu Eo et al., 2008 1 pT1aN0M1 M 47 Clear cell NA 4 Venugopal et al.,2017 1 NA NA NA NA NA 5 Ekbote et al., 2015 1 NA M 52 Clear cell Alive after ten months 6 Bellio et al., 2016 1 pT1bN0 M 75 Clear cell NA 7 Deguchi et al., 2000 1 NA M 58 NA NA 8 Ogiso et al., 2005 1 pT1aN0M1 F 57 NA NA 9 Hegde R J et al., 2014 1 NA M 52 Clear cell NA 10 Budmiger et al., 2015 1 NA M 61 NA NA 11 Kerkeni B et al., 2013 1 pT2bNxM1 F 32 Clear cell Not interpretable 12 Khan AB et al., 1991 1 NA NA NA NA NA 13 Trojaneillo et al., 2017 1 NA M 75 NA Pt. died 9 months after surgery. 14 Tutar et al., 2008 1 NA M 59 Clear cell NA 15 Aissa et al., 2012 1 NA M 64 Tubulo- Papillary NA 16 Longo et al., 2013 1 NA F 52 Clear cell NA 17 Budmiger et al., 2015 1 NA M 61 Clear cell NA 18 Sasaki et al., 2006 1 NA M 64 Clear cell Pt died after few months after jejunal resection 19 Roviello et al., 2006 1 NA M 48 Clear cell Alive at follow up. 20 Rampersad et al., 2006 1 NA F 69 NA NA 21 Collet et al., 2001 1 NA F 77 NA NA Abbreviations: NA, not applicable; F, Female; M, Male.

A Von Hippel-Lindau Disease-Associated Microcystic Adenoma of the Ethmoid Sinus Mimicking Metastatic Clear Cell Renal Cell Carcinoma.

A 38-year-old man with von Hippel-Lindau (VHL) disease and a history of renal cell carcinoma presented with a 2-month history of recurrent epistaxis. MRI revealed a microcystic tumor in the left ethmoid sinus with strong contrast enhancement. 18 F-FDG PET/CT showed FDG uptake (SUV max , 4.2) in the lesion. Under the suspicion of renal cell carcinoma metastasis, the patient underwent 2 surgical resections. However, based on the morphological and immunohistochemical findings, the patient was finally diagnosed with a VHL-associated microcystic adenoma of the ethmoid sinus, which is an extremely rare tumor that occurs in VHL disease.

Characterization of tumor thrombus in renal cell carcinoma with prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT).

Venous tumor thrombus (TT) occurs as part of the natural history of renal cell carcinoma (RCC) local progression in a small minority of cases. MRI is currently the most accurate imaging modality for determining TT extent. PSMA PET/CT may improve RCC staging and IVC TT characterization. The objective of this study was to investigate the role of PSMA PET/CT in defining superior extent of TT in RCC and TT IVC tributary vessel spread, with comparative accuracy vs. MRI, to assess suitability for resection and inform preoperative surgical planning. Patients who underwent PSMA PET/CT for assessment of renal malignancy with TT from 2015 to 2020 at 3 tertiary hospitals in Brisbane, Australia, were retrospectively identified. TT extent was classified using Mayo Clinic levels and compared according to imaging modality. Fourteen patients were included, all of which were clear cell RCC. Ten patients also underwent MRI, 6 of which were concordant in extent according to MRI and PSMA PET. Discordant extent occurred in 4 patients, of which 2 patients had non-PSMA avid thrombus (Mayo level 0 and level 3 on MRI). Further discordance was seen in a patient with adrenal vein and lumbar vein TT only seen on MRI and PSMA PET/CT, respectively. Finally, discordant extent was seen in another patient with Mayo level 4 TT without lumbar vein involvement on MRI vs. level 3 on PSMA PET/CT with lumbar vein involvement. PSMA PET/CT can provide additional information about TT extent in RCC which may not be seen on MRI. Additional information from PSMA PET/CT in this setting may assist surgical planning, in addition to detection of metastatic disease.

The Limiting Reagent for Peristalsis

Question: A 62-year-old woman with a history of renal cell carcinoma surgically managed via left nephrectomy and small bowel obstructions treated surgically presented with 4 days of oral intolerance and abdominal distention. Her last bowel movement and flatus were 3 days prior. She was afebrile, vital signs stable, with a white blood cell count of 12.9 × 103/μL. Computed tomography findings were significant for marked distension of the stomach and proximal duodenum, with a transition point in the left midabdomen and distal collapsed loops of small bowel and colon.

How a woman’s myomectomy saved her father’s life: evidence of fumarate hydratase–deficient uterine leiomyoma and early detection of germline variants in fumarate hydratase

ObjectiveTo describe a case of a personal and family history of early uterine leiomyomatosis that revealed a pathogenic variant in the FH gene encoding fumarate hydratase. After the patient’s diagnosis, a first-degree relative was detected with early-stage renal cell carcinoma. The patient decided to undergo preimplantation genetic testing to reduce the risk to her future children.DesignA case report of autosomal dominant hereditary leiomyomatosis and renal cell cancer syndrome where the patient underwent 2 cycles of in vitro fertilization with preimplantation genetic testing for monogenic disease/aneuploidy (PGT-MA) that resulted in 3 unaffected, euploid embryos.SettingLarge academic single-center hospital.Patient(s)A 35-year-old nulligravida woman with a personal history of an early-onset uterine leiomyomatosis and a family history of renal cell carcinoma and uterine leiomyomas, who is heterozygous for a pathogenic variant in FH and diagnosed with hereditary leiomyomatosis and renal cell cancer syndrome. Informed consent was obtained.Intervention(s)Two laparoscopic myomectomies were performed, and tissue was sent for histopathology and immunostaining. Hereditary leiomyomatosis and renal cell cancer syndrome was confirmed by germline testing, and 2 cycles of PGT-MA were performed.Main Outcome Measure(s)Through PGT-MA, the patient was able to mitigate the risk of passing a known familial variant to her future children.Result(s)After 2 cycles of in vitro fertilization with PGT-MA, 3 unaffected embryos were available for transfer. An unaffected, euploid embryo was transferred for pregnancy, and the patient is currently pregnant in her second trimester.Conclusion(s)Pathogenic variants in FH should be suspected in patients with early-onset uterine leiomyomas and a family history of cutaneous and/or uterine leiomyomas. Familial variant testing is crucial in identifying relatives at risk to start early screening.

Renal cell carcinoma with unusual metachronous metastasis up to 22 years after nephrectomy: two case reports

IntroductionRenal cell carcinoma is the third most common malignant tumor in the urogenital tract. An estimated 25% of renal cell carcinomas are in stage IV when diagnosed. The 5-year-survival with stage IV is about 20%. Late metastases are found after an extended disease-free interval up to 20 years after primary nephrectomy.Case presentationHere, we present two cases with late-onset metastasis of renal cell carcinoma with different clinical presentations. The first patient, an 88-year-old Caucasian man, presented with bleeding of the upper gastrointestinal tract. Biopsies taken from the duodenal bulb showed a tumor compatible with a solitary metastasis from renal cell carcinoma 22 years ago. The second patient, a 79-year-old Caucasian man, consulted our gastroenterological department with results of an outpatient computed tomography scan with multiple suspected tumor areas in the liver, omentum, thyroid, and mediastinum. A computed tomography-guided liver biopsy was performed that showed a clear-cell tumor consistent with a metastasis of the renal cell carcinoma 17 years ago.ConclusionBoth cases show that patients with a history of renal cell carcinoma should be followed up for a longer time than patients with other malignant tumors.

Using Contrast-Enhanced Ultrasound in Addition to Cross-Sectional Imaging for Indeterminate Renal Cysts May Lead to Overclassification in Bosniak III Category: A Case-Control Study

Introduction: Indeterminate renal cysts may require several imaging modalities before clinical decision. The aim of this study was to investigate the effect of the imaging modality used to characterize indeterminate renal cysts on the pathological findings after surgical resection. Methods: From our institutional database, we identified all patients surgically treated for Bosniak III renal masses between January 2008 and January 2018. All complex renal cysts were characterized with a combination of computed tomography (CT) and/or magnetic resonance imaging (MRI), and/or contrast-enhanced ultrasound (CEUS) and discussed during a multidisciplinary tumor board. Potential association between clinical/radiological characteristics and the pathological findings were investigated, using univariate and multivariate analyses. Results: Of the 52 renal cystic lesions surgically removed, with a preoperative diagnosis of Bosniak III renal cyst, 19 (37%) were malignant and 33 (63%) were benign. The proportion of malignant lesions decreased from 47% when the renal cyst was characterized with cross-sectional imaging (CT and/or MRI) to 17% when the diagnosis required CEUS in addition to cross-sectional imaging. In multivariate analysis, prior history of renal cell carcinoma was associated with a higher risk of malignancy (p = 0.016) and diagnosis made with CEUS was associated with a lower risk of malignancy (p = 0.040). Conclusion: We found that using CEUS in addition to cross-sectional imaging to characterize indeterminate renal cysts tends to redefine Bosniak III as lesions with a lower risk of malignancy and can lead to overclassification.

Fat Necrosis Mimicking Renal Cell Carcinoma Recurrence Following Cryotherapy, Partial Nephrectomy, and Nephrectomy

ObjectiveTo present our experience with three patients surgically treated for suspected recurrent renal cell carcinoma whose final pathology was consistent with tumefactive fat necrosis. MethodsThree patients underwent definitive therapy for biopsy proven renal cell carcinoma (cryoablation, partial nephrectomy, and nephrectomy) and later demonstrated evidence of recurrent renal cell carcinoma on follow up imaging. All three patients underwent surgical resection of the suspected recurrences with final pathology consistent with tumefactive fat necrosis. ResultsThe three patients were 60, 74, and 39-years old, respectively. The previous definitive therapies for renal cell carcinoma were percutaneous ablation, RAPN, and nephrectomy. Each patient had previous surgical pathology that confirmed prior renal cell carcinoma. Signs of recurrence on diagnostic imaging occurred 2 years, 23 months, and 8 months post-definitive therapy. ConclusionIn patients with a history of renal cell carcinoma, consideration of fat necrosis should be taken into account upon seeing imaging concerning for tumor recurrence. Continued analysis of cases with such a diagnosis will be beneficial in recognizing this possibility to avoid unnecessary surgery or therapy when possible.

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&amp;gt;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&amp;gt;T TSC1 mutation developed a non-functional metastatic PNET. PNET is a likely component of TSC1.