Anaplastic sarcoma of the kidney (DICER1-sarcoma of the kidney): A report from the International Pleuropulmonary Blastoma/DICER1 Registry.

BACKGROUND: Anaplastic sarcoma of the kidney (ASK) is a DICER1-related neoplasm first identified as a distinctive tumor type through the evaluation of unusual cases of putative anaplastic Wilms tumors. Subsequent case reports identified the presence of biallelic DICER1 variants as well as progression from cystic nephroma, a benign DICER1-related neoplasm. Despite increasing recognition of ASK as a distinct entity, the optimal treatment remains unclear. METHODS: Individuals with known or suspected DICER1-related tumors including ASK were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry. Additionally, a comprehensive review of reported cases of ASK was undertaken, and data were aggregated for analysis with the aim to identify prognostic factors and clinical characteristics to guide decisions regarding genetic testing, treatment, and surveillance. RESULTS: Ten cases of ASK were identified in the Registry along with 37 previously published cases. Staging data, per Children's Oncology Group guidelines, was available for 40 patients: 13 were stage I, 12 were stage II, 10 were stage III, and five were stage IV. Outcome data were available for 37 patients. Most (38 of 46) patients received upfront chemotherapy and 14 patients received upfront radiation. Two-year event-free survival (EFS) for stage I-II ASK was 81.8% (95% confidence interval [CI]: 67.2%-99.6%), compared with 46.6% EFS (95% CI: 24.7%-87.8%) for stage III-IV (p = .07). Two-year overall survival (OS) for stage I-II ASK was 88.9% (95% CI: 75.5%-100.0%), compared with 70.0% (95% CI: 46.7%-100.0%) for stage III-IV (p = .20). Chemotherapy was associated with improved EFS and OS with hazard ratios of 0.09 (95% CI: 0.02-0.31) and 0.08 (95% CI: 0.02-0.42), respectively. CONCLUSION: ASK is a rare DICER1-related renal neoplasm. In the current report, we identify clinical and treatment-related factors associated with outcome including the importance of chemotherapy in treating ASK. Ongoing data collection and genomic analysis are indicated to optimize outcomes for children and adults with these rare tumors.

Multilocular cystic nephroma in an adult: a diagnostic quandary.

Multilocular cystic nephroma (MLCN) is an unusual, benign slow-growing renal cystic neoplasm which mimics other cystic renal lesions and has such clinical, radiological, and morphological features that causes diagnostic dilemma. MLCN lies in the spectrum of mixed epithelial and stromal tumor (MEST) family of kidney. According to World Health Organization (WHO 2016 classification), MEST encompasses spectrum of tumors ranging from predominantly cystic tumors, adult cystic nephroma (ACN) to tumors that are variably solid (MEST), thus creating diagnostic dilemma. Moreover, it has several benign and malignant differentials due to its several overlapping histomorphological features which when not cautiously dealt with may result in misdiagnosing it as malignant lesion. We hereby present a case of a woman in late twenties who presented with left flank swelling and pain since 6 months which was misdiagnosed as renal cell carcinoma on radiology which turned out to be ACN on histology and further verified on immunohistochemistry.

Three Dimensional (3D) Laparoscopic Nephron-sparing Treatment of a Huge Cystic Nephroma: A Case Report and Literature Review.

Background/Aim: Cystic nephroma (CN) is a very rare, benign, renal cystic lesion, which is characterized by a usually unilateral, multicystic kidney mass. In adults it is seen more frequently in females (1:8 male-to-female ratio). The peak incidence of CN is between 50 and 60 years of age. Median age at diagnosis is 55 years for females and 44 years for men and it is a rare entity in adults under 30 years of age. Case Report: We report the case of a 52-year-old female patient with chronic right-flank pain, who was treated at our hospital. A multiloculated 10×8.6 cm Bosniak IV renal cyst tumor was depicted on retroperitoneal computed tomography. After a three-dimensional laparoscopic partial nephrectomy, the histopathological specimen examination revealed: a multilocular cystic nephroma. Conclusion: CNs are rare benign tumors that should be included in the differential diagnosis when treating large multiloculated complex renal cysts.

Cystic partially differentiated nephroblastoma in an 18-month-old girl: a case report.

Introduction and importance: Cystic partially differentiated nephroblastoma (CPDN) is a rare cystic tumor that affects the kidney. It has a low potential for malignancy. It usually presents as an abdominal mass. It may be difficult to confirm the diagnosis of CPDN without a histopathological study. Case presentation: The authors report a case of an 18-month-old girl with abdominal distention, which was noticed by her parents. An abdominal computed tomography scan showed a large multilocular cystic mass arising from the lower pole of the left kidney. A left total nephrectomy was performed. Immature blastemal elements without evidence of malignant cells were observed on histological analysis. Conclusion: The authors report a case of an 18-month-old girl with CPDN managed by total nephrectomy. CPDN should be considered in the differential diagnosis of patients with cystic renal lesions. The authors would also like to affirm that partial or total nephrectomy should be done in all cases of CPDN and other cystic renal tumors.

A Pathogenic Germline BRCA1 Variant in a Patient With Cellular Congenital Mesoblastic Nephroma: A Case Report.

Benign cystic tumors of the kidney are well-described in infants and young children. Here we report an infant diagnosed with a cellular congenital mesoblastic nephroma (CMN) with a germline pathogenic variant in BRCA1. This finding is novel because BRCA1 is an adult-onset cancer predisposition gene causing breast, ovarian, pancreatic, and prostate cancers. However, increasing studies are indicating the presence of germline BRCA1 in both malignant and benign childhood cancers.

Frozen Section Biopsy and Nephron-Sparing Surgery for a Multiloculated Cyst of the Kidney; Is this the Ideal Approach?

Multiloculated cystic renal masses are uncommon in the pediatric population. The presentation may be as an asymptomatic incidental finding on imaging, abdominal mass, abdominal pain, or urinary tract infection. The differentiation between benign and malignant causes of a cystic lesion by clinical and radiological examination is difficult. Tru-cut biopsy is not recommended due to fear of upgrading a malignant tumor. A definitive diagnosis is confirmed histopathologically only after surgery. Based on certain imaging characteristics, benign nature can be suspected and a conservative approach to surgery can be contemplated to save the kidney. Frozen section biopsy is useful in ruling out malignancy while doing nephron-sparing surgery (NSS) in these patients. NSS may be done by an open or minimally invasive approach. After histological confirmation of cystic nephroma, no other adjuvant treatment is necessary, but long-term surveillance is strongly recommended.

Differentiating pediatric cystic nephroma from common renal multicystic lesions: A case report.

Pediatric cystic nephroma is a rare, clinically benign, renal tumor. Pediatric renal cystic lesions are complex. Imaging findings and tumor appearance are often nonspecific, and careful pathological examination is necessary. We discuss diagnosis of pediatric cystic nephroma and how to differentiate it from multicystic dysplastic kidney and cystic partially differentiated nephroblastoma.

Mixed epithelial and stromal tumor-adult cystic nephroma of the kidney: a case report with immunohistochemical analysis.

The mixed epithelial and stromal tumor family of kidney contain neoplasms with biphasic epithelial and stromal component. According to the 2016 World Health Organization Classification, they encompasses a spectrum of tumors ranging from predominantly cystic tumors (adult cystic nephroma) to tumors that are variably solid (Mixed epithelial and stromal tumor-MESTs). We present the case of a 20-year-old woman with an adult cystic nephroma which was verified by immunohistochemical examination.

PRAME protein expression in DICER1-related tumours.

DICER1 syndrome is an autosomal dominant tumour predisposition syndrome usually affecting persons under 30 years of age. Many of the associated benign and malignant lesions occur almost exclusively in DICER1 syndrome. One such tumour, pituitary blastoma (pitB), overexpresses PRAME 500x above control levels. PRAME (PReferentially expressed Antigen in MElanoma) is expressed in malignancies that are not DICER1-related (e.g. melanoma). To address whether PRAME expression is part of the DICER1 phenotype, or simply a feature of pitB, a series of 75 DICER1-mutated specimens and 33 non-mutated specimens was surveyed using immunohistochemistry for PRAME, together with EZH2, which complexes with PRAME. In DICER1-mutated specimens, positive staining for PRAME was only seen in malignant tumours; 7 of 11 histological types and 34/62 individual tumours were positive, while non-tumourous lesions were always negative. Pleuropulmonary blastoma (PPB) showed a continuum in staining, with type I lesions being PRAME negative (n = 7) but all type II and type III lesions PRAME positive (n = 7). Similarly, cystic nephroma (CN) was negative (n = 8), with anaplastic sarcoma of the kidney being positive (n = 2). However, one atypical CN with mesenchymal cell proliferation was PRAME-positive. Embryonal rhabdomyosarcoma (RMS) with DICER1 pathogenic variants (PVs) was positive for PRAME (5/6), but the same tumour type without DICER1 PVs was also positive (9/15). Staining for EZH2 corresponded to that seen with PRAME, validating the latter. This study leads us to conclude that (1) PRAME expression occurs in two-thirds of DICER1-related malignancies; (2) PRAME may be a marker for the progression that certain DICER1-related lesions are thought to undergo, such as PPB and CN; and (3) PRAME expression in some tumours, such as RMS, appears to be an intrinsic feature of the tumour, rather than specifically related to DICER1 PVs. Therapy directed against PRAME may offer novel treatment options in patients with the DICER1 syndrome.

Benign Renal Tumors in Pediatric Age Group: Retrospective Analysis.

BACKGROUND: Benign renal tumors are extremely rare and were studied here. This series also includes a renal teratoma in a horseshoe kidney, probably only the second in the pediatric literature. MATERIALS AND METHODS: Retrospective review of children with benign renal tumors operated between 2006 and 2018 at one center. RESULTS: Twelve patients (M:F ratio 10:2), age range 3 weeks (31-week gestation) to 13 years presented with large palpable renal swelling (n = 12) and hematuria (n = 3). Computed tomography (CT) scan showed features typical of the tumor. Final histopathology (age group [mean]) showed: multilocular cystic nephroma (MLCN) - n = 5 (41.7%), (11-16 months [13.6]); congenital mesoblastic nephroma (CMN) - n = 4 (33.3%) (classic 1, cellular 3) (0.75-5 months [2.125]); mature cystic teratoma - n = 1 (8.3%): (48 months, in a horseshoe kidney), and angiomyolipoma (AML) - n = 2 (16.7%) (144 months [sporadic] and 156 months [tuberous sclerosis]) One patient with cystic teratoma with no calcification on CT scan received pre-operative chemotherapy as fine-needle aspiration cytology (FNAC) reported malignant small blue cell tumor. Nephroureterectomy with Gerota's fascia could be done easily in all without intraoperative complications. Delay in presentation in MLCN and CMN led to increased symptoms and CT scan changes. All patients did well in 1.5-12 years (median 3 years) follow-up including cellular mesoblastic nephroma. CONCLUSIONS: Benign renal tumors often occur in specific age groups but may overlap that of Wilms tumor. Proper interpretation of clinical presentation, CT scan, and FNAC findings help in avoiding preoperative chemotherapy. Upfront nephroureterectomy is curative. Histopathological findings decide further treatment. Children with AML and tuberous sclerosis need lifelong follow-up.

Ovarian Sertoli-Leydig Cell Tumor, Multinodular Goiter, Cystic Nephromas and DICER1 Mutations: Case Report and Literature Review.

INTRODUCTION: DICER1 syndrome is a rare tumor predisposition syndrome caused by germline DICER1 mutation, which is related to a variety of benign and malignant diseases. Our report is the first described case of these three disease phenotypes of DICER1 syndrome. The female patient with a novel germline DICER1 nonsense mutation (c.1088_1089delCTinsAA p.F363X) in exon 8 that was inherited from her mother. In addition to germline DICER1 mutation, two different hotspot somatic DICER1 mutations were detected in her ovarian tissue and goiter tissue. Our report will expand the report of DICER1 mutations in DICER1-syndrome-related diseases and provide case references for further research in the future. CONCLUSION: When the related disease phenotype appears in childhood, it should be considered whether it is DICER1 syndrome. Genetic testing can help diagnose DICER1 syndrome and develop related surveillance strategies. Awareness of the DICER1 syndrome may result in early recognition of these rare pediatric tumors and appropriate therapeutic management.

Cystic Nephroma and its Varied Management Scenarios: A Report of two Cases.

Cystic nephroma is a rare benign cystic neoplasm of the kidney. The preoperative diagnosis with its malignant counterparts cystic partially differentiated nephroblastoma or cystic Wilms' tumor is not easy but is important when one is considering for nephron-sparing surgery.

Cystic nephroma treated with nephron-sparing technique: A case report.

Multilocular cystic nephroma is a rare benign kidney tumor, which is typically characterized by a unilateral, multicystic renal mass without solid elements. Cystic nephroma has a bimodal distribution and two-thirds of tumors involve children aged between 3 months and 2 years, with male predominance; a second peak affects the age group >30 years old, in which females are predominantly affected. The incidence rate for this rare tumor in patients aged 5-30 years is only 5%. The present study reports a case of a 31-year-old woman affected by a multilocular cystic nephroma in the upper pole of the right kidney, with direct tumor extension into the renal pelvis through a calyx. After a partial nephrectomy on the patient, the pathological examination confirmed a multilocular cystic nephroma in the right renal specimens.

Clinical and Molecular Characteristics and Outcome of Cystic Partially Differentiated Nephroblastoma and Cystic Nephroma: A Narrative Review of the Literature.

In children presenting with a predominantly cystic renal tumor, the most likely diagnoses include cystic partially differentiated nephroblastoma (CPDN) and cystic nephroma (CN). Both entities are rare and limited information on the clinical and molecular characteristics, treatment, and outcome is available since large cohort studies are lacking. We performed an extensive literature review, in which we identified 113 CPDN and 167 CN. The median age at presentation for CPDN and CN was 12 months (range: 3 weeks-4 years) and 16 months (prenatal diagnosis-16 years), respectively. No patients presented with metastatic disease. Bilateral disease occurred in both entities. Surgery was the main treatment for both. Two/113 CPDN patients and 26/167 CN patients had previous, concomitant, or subsequent other tumors. Unlike CPDN, CN was strongly associated with somatic (n = 27/29) and germline (n = 12/12) DICER1-mutations. Four CPDN patients and one CN patient relapsed. Death was reported in six/103 patients with CPDN and six/118 CN patients, none directly due to disease. In conclusion, children with CPDN and CN are young, do not present with metastases, and have an excellent outcome. Awareness of concomitant or subsequent tumors and genetic testing is important. International registration of cystic renal tumor cohorts is required to enable a better understanding of clinical and genetic characteristics.

A MEST up classification? Review of the re-classification of mixed epithelial and stromal tumor and adult cystic nephroma for the abdominal radiologist.

Mixed epithelial and stromal tumor (MEST) and the tumor formerly known as adult cystic nephroma (ACN) are uncommon renal tumors that have historically been described as separate entities in terms of histologic and imaging findings. However, these entities share many epidemiologic, radiologic, and pathologic features. While recent surgical and pathological literature has supported classifying MEST and ACN within the same tumor family, most radiologists and radiology texts continue to describe MEST and ACN as separate entities.

Renal epithelial and stromal tumor with a multiple cystic lesion localized in the upper portion of the right kidney.

A 60-year-old Japanese woman was admitted because of the polycystic mass with right flank pain localized in the upper portion of the right kidney. Right nephrectomy was performed because the mass lesion had continuously increased in size over the past 10 years. A surgical specimen showed histology consistent with a mixed epithelial and stromal tumor, which is closely related to multilocular cystic nephroma, and was diagnosed by a defined capsule between the cystic mass lesion and normal renal tissue by CT and MRI, and histology. Localized renal cystic disease that does not have a capsule was excluded from differential diagnosis.

Pediatric Renal Tumors: Updates in the Molecular Era.

Molecular characterization has led to advances in the understanding of pediatric renal tumors, including the association of pediatric cystic nephromas with DICER1 tumor syndrome, the metanephric family of tumors with somatic BRAF mutations, the characterization of ETV6-NTRK3-negative congenital mesoblastic nephromas, the expanded spectrum of gene fusions in translocation renal cell carcinoma, the relationship of clear cell sarcoma of the kidney with other BCOR-altered tumors, and the pathways affected by SMARCB1 alterations in rhabdoid tumors of the kidney. These advances have implications for diagnosis, classification, and treatment of pediatric renal tumors.

Cystic partially differentiated nephroblastoma: a rare pediatric renal tumor-case report.

Cystic partially differentiated nephroblastoma is a rare renal tumor of childhood. It is part of a spectrum of multicystic renal tumors that also includes cystic nephroma and cystic Wilms' tumor. We present a case of cystic partially differentiated nephroblastoma, highlighting the clinical and imaging diagnostic challenge. Although the histological diagnostic criteria for all these 3 entities are well established, they are clinically and radiologically indistinguishable. Cystic partially differentiated nephroblastoma is often observed in male children under 2 years old. Typical clinical presentations include abdominal masses, abdominal pain and/or hematuria. Patients should be treated according to tumor histology and stage.

DICER1 Syndrome and Cancer Predisposition: From a Rare Pediatric Tumor to Lifetime Risk.

DICER1 syndrome is a rare genetic condition predisposing to hereditary cancer and caused by variants in the DICER1 gene. The risk to present a neoplasm before the age of 10 years is 5.3 and 31.5% before the age of 60. DICER1 variants have been associated with a syndrome involving familial pleuropulmonary blastoma (PPB), a rare malignant tumor of the lung, which occurs primarily in children under the age of 6 years and represents the most common life-threatening manifestation of DICER1 syndrome. Type I, II, III, and Ir (type I regressed) PPB are reported with a 5-year overall survival ranging from 53 to 100% (for type Ir). DICER1 gene should be screened in all patients with PPB and considered in other tumors mainly in thyroid neoplasms (multinodular goiter, thyroid cancer, adenomas), ovarian tumors (Sertoli-Leydig cell tumor, sarcoma, and gynandroblastoma), and cystic nephroma. A prompt identification of this syndrome is necessary to plan a correct follow-up and screening during lifetime.