Non-Wilms' Renal Tumors In Children:A 139 Cases Series

Background:Pediatric non-Wilms renal tumors (NWRTs) which comprise a small proportion of renal tumors,are a heterogeneous group of neoplasms with variable malignant potential, mortality, and response to treatment.This study aimed to determine the clinical characteristics, management and prognosis of children with non-Wilms' renal tumors(NWRTs). Methods:Medical records of all patients (n = 139) treated for NWRTs over a 12-year period (2008.01–2019.10) at a single center were reviewed retrospectively.Results:The histopathological groups of NWRTs included malignant rhabdoid tumor of the kidney(MRTK)(n: 30, 21.6%), renal cell cancer(RCC)(n: 26,18.7%), clear cell sarcoma of the kidney(CCSK)(n: 24,17.3%), congenital mesoblastic nephroma(CMN)(n: 21,15.1%), cystic nephroma(CN)(n: 16,11.5%),metanephric tumours(n: 12, 8.6%), renal angiomyoliporma(RAML)(n: 3, 2.2%), renal primitive neuroectodermal tumor(rPNET)(n: 2, 1.4%), renal hemangioma(n: 2, 1.4%), inflammatory myofibroblastic tumor(IMT)(n: 2, 1.4%), ossifying renal tumor of infancy(ORTI)(n: 1, 0.7%). 123 children were followed up with an average of 42 months. 16 children were lost to follow-up. Tumor-free survival was observed in 94 children. 28 children(22.8%) were died.Conclusions:Pediatric NWRTs comprises 19.1% of all renal tumors in our single center. Accurate diagnoses along with appropriate management are important factors in improving patients outcome. The mainstay treatment of malignant NWRTs including MRTK,CCSK,RCC and PNET is comprehensive treatment. The mainstay treatment of benign NWRTs including RAML,CN, ORTI, CMN,metanephric tumours, and renal hemangioma is surgical resection alone.

A Case Report on Malignant Rhabdoid Round Cell Tumor in Pelvis

The malignant neoplasm is called as malignant rhabdoid tumor or renal tumor. The Malignant tumor had the highest rate of proliferation. Tiny, round, and generally undifferentiated cells make up malignant small round cell tumours. A round cell tumor is a group of malignant tumors composed of relatively small and undifferentiated cells with an increased nuclear - cytoplasmic ratio. Soft tissue malignant tumours of the abdomen and pelvis are a rare but serious kind of cancer. Examples of these tumours include Ewing's sarcoma, peripheral neuroectodermal tumour, rhabdomyosarcoma, synovial sarcoma, non-lymphoma, Hodgkin's retinoblastoma, neuroblastoma, and hepatoblastoma. Mast cell tumour, histiocytoma, lymphoma, plasmacytoma, and transmissible venereal tumours are some of the different types of round cell tumours. Melanomas are the cytologic "great impostor," as they might look on cytology as round cell tumours despite being classed as mesenchymal cancers. Rhabdoid tumours have long been thought to be extremely malignant and have a bad prognosis. Children with this form of tumour have a six to eleven-month median survival duration. They're also less common. In 5% of small round cell tumor patients, can be curable, and it is best achieved by combining systemic chemotherapy with thorough cytoreductive surgery. Here we report a 9-year-old female child who was diagnosed with a malignant rhabdoid round cell tumor in the pelvis. She has undergone excision of pelvic floor tumor andfurther managed with Chemotherapy.

Pediatric Metastatic Hepatoblastoma With an ARID1A Mutation and Rhabdoid Cells

The small cell undifferentiated component of hepatoblastoma is an uncommon histologic component and is distinguished from small cell undifferentiated like pattern (originally called hepatoblastoma and now recognized to be malignant rhabdoid tumor) by the bi-allelic SMARCB1 mutations or copy number alterations in the latter. AT-rich interactive domain-containing protein 1A ( ARID1A) is a part of the ATP-dependent switch/sucrose non-fermentable complex assembly, but mutations have not been reported as drivers of malignant rhabdoid tumor. ARID1A mutations in hepatocellular carcinoma are associated with poor prognosis but its significance in hepatoblastoma is unknown. We report a unique case of hepatoblastoma in a 19-month-old female with an unusual/atypical small cell undifferentiated component with ARID1A and beta-catenin mutations. It had an aggressive clinical course despite treatment, with metastases to the left psoas muscle, perihepatic and paratracheal lymph nodes, spinal cord, and leptomeninges. Leptomeningeal metastases resulted in diffuse cerebral edema and death. The initial diagnostic biopsy did not reveal rhabdoid cells while all metastatic foci showed cells with rhabdoid morphology in the autopsy specimens. Although this rhabdoid component resembled malignant rhabdoid tumor morphologically, molecular analyses failed to show mutations or deletions of SMARCB1.

U cơ vân ngoài thận ác tính biểu hiện tại vùng mặt ở trẻ sơ sinh

TÓM TẮT U cơ vân ác tính ngoài thận rất hiếm gặp ở trẻ sơ sinh. Chúng tôi báo cáo trường hợp u cơ vân ác tính biểu hiện vùng môi dưới - cằm xuất hiện từ sau sinh ở một trẻ gái. Khối u tăng nhanh về kích thước cho đến thời điểm nhập viện trẻ 2 tháng tuổi. Với kết quả chẩn đoán hình ảnh gợi ý khối u ác tính, sinh thiết được chỉ định với kết quả hóa mô miễn dịch mất biểu hiện gen INI1, hình ảnh u cơ vân ác tính ngoài thận. Sau khi thảo luận đa chuyên khoa, trẻ được chỉ định hóa trị và kết quả bước đầu cho thấy khối u có xu hướng nhỏ lại. Qua trường hợp này, chúng tôi thảo luận về đặc điểm dịch tễ học, lâm sàng, tiếp cận chẩn đoán và lựa chọn phương pháp điều trị cho u cơ vân ác tính ngoài thận biểu hiện tại vùng mặt. Từ khóa: U cơ vân, ác tính, ngoài thận, vùng mặt. ABSTRACT EXTRARENAL MALIGNANT RHABDOID TUMORS PRESENTING WITH A FACIAL TUMOR IN A NEONATE Malignant rhabdoid tumor (MRT) are very rare in neonates. We report a case of MRT presenting in the lower lip - chin region after birth in a girl. The tumor’s size increased rapidly until the time of hospitalization, when the child was 2 - month - old. With imaging findings suggestive of malignancy, biopsy was indicated with immunohistochemistry with loss of INI1 expression, imaging of MRT. After multidisciplinary consultations, the child was prescribed chemotherapy and the initial results showed that the tumor tended to minimize. Through this case, we discuss the epidemiological, clinical features, diagnostic approaches and treatment options for MRT in the facial region.

Primary Adrenal Malignant Rhabdoid Tumor in a 14-Year-Old Female: A Case Report and Literature Review

Malignant rhabdoid tumor (MRT) is a rare, SWItch/sucrose nonfermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 ( SMARCB1)-deficient, aggressive tumor, occurring predominantly in children below 3 years of age. Primary adrenal MRT is extremely rare, with only 3 cases reported in the literature. A previously healthy 14-year-old female presented with left upper quadrant/epigastric abdominal pain. Imaging studies revealed an 8.0 × 8.0 × 6.5 cm, heterogeneous, partially enhancing mass along the superior margin of the left kidney encasing the adrenal gland. Surgical resection of the tumor revealed a hypercellular heterogeneous neoplasm arising from the adrenal gland. It was composed predominantly of primitive small round blue cells with focal true rosettes and areas of vague glandular epithelial differentiation and chondroid differentiation. Classic rhabdoid-type cytoplasmic inclusions were focally present. Mitoses, tumor necrosis, and hemorrhage were readily seen. Tumor cells showed complete loss of SMARCB1 (INI1) nuclear staining, demonstrated strong, and diffuse positivity for glypican 3, patchy positivity for CD99, cytokeratin, Sal-like protein 4, Lin-28 homolog A, epithelial membrane antigen, and S100. Molecular studies revealed biallelic frameshift mutations in the SMARCB1 gene (c.673delG and c.683dupT) without pathogenic copy number aberrations. The histologic, immunohistochemical, and molecular findings support a diagnosis of MRT. The unusual age, location, and mutations of this case expand the clinicopathologic and molecular spectrum of MRT.

Global Chromatin Changes Resulting from Single-Gene Inactivation—The Role of SMARCB1 in Malignant Rhabdoid Tumor

Human cancer typically results from the stochastic accumulation of multiple oncogene-activating and tumor-suppressor gene-inactivating mutations. However, this process takes time and especially in the context of certain pediatric cancer, fewer but more ‘impactful’ mutations may in short order produce the full-blown cancer phenotype. This is well exemplified by the highly aggressive malignant rhabdoid tumor (MRT), where the only gene classically showing recurrent inactivation is SMARCB1, a subunit member of the BAF chromatin-remodeling complex. This is true of all three presentations of MRT including MRT of kidney (MRTK), MRT of the central nervous system (atypical teratoid rhabdoid tumor—ATRT) and extracranial, extrarenal rhabdoid tumor (EERT). Our reverse modeling of rhabdoid tumors with isogenic cell lines, either induced or not induced, to express SMARCB1 showed widespread differential chromatin remodeling indicative of altered BAF complex activity with ensuant histone modifications when tested by chromatin immunoprecipitation followed by sequencing (ChIP-seq). The changes due to reintroduction of SMARCB1 were preponderantly at typical enhancers with tandem BAF complex occupancy at these sites and related gene activation, as substantiated also by transcriptomic data. Indeed, for both MRTK and ATRT cells, there is evidence of an overlap between SMARCB1-dependent enhancer activation and tissue-specific lineage-determining genes. These genes are inactive in the tumor state, conceivably arresting the cells in a primitive/undifferentiated state. This epigenetic dysregulation from inactivation of a chromatin-remodeling complex subunit contributes to an improved understanding of the complex pathophysiological basis of MRT, one of the most lethal and aggressive human cancers.

High clinical activity of pembrolizumab in chordoma, alveolar soft part sarcoma (ASPS) and other rare sarcoma histotypes: The French AcSé pembrolizumab study from Unicancer.

11520 Background: AcSé Pembrolizumab is a Phase 2, non-randomized parallel arms, open-label, multicentric study from Unicancer investigating the efficacy and safety of pembrolizumab monotherapy in different cohorts of patients with rare cancers (NCT03012620). Here we report the results of pembrolizumab in the rare sarcoma cohort. Methods: Selected histotypes were all rare sarcomas patients (pts) (incidence < 0.2/100,000/year). Main inclusion criteria were age > 18, ECOG PS≤1 and advanced or metastatic disease resistant to standard treatment. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycle for a maximum of 2 years. The primary endpoint was the confirmed objective response rate according to RECIST v1.1 at 12 weeks. Secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), and safety. Five groups of pts were distinguished, namely chordoma, alveolar soft-part sarcoma (ASPS), desmoplastic small round cell tumor (DSRCT), smarca4 deficient malignant rhabdoid tumor (SMRT), and other histotypes. Results: 98 patients including 34 with chordoma, 14 ASPS, 11 SMRT, 8 DSCRT and 31 with other histotypes, were included from July 2017 to December 2020. The median number of cycles was 5 (range, 1 to 35) with 78 (79.6%) patients who discontinued the trial after a median of 4 cycles. There were 6 (7.3%) partial response (PR) at 12 weeks. The best response was CR in 1 patient (1%), PR in 14 patients (14.3%), and stable disease (SD) in 33 (33.7%). Median duration of response was 8.2 months [IQR, 4.1 to 9.0]. The occurrence of best response depended on the histotype, with 3 (8.8%) responses in chordoma, 7 (50%) in ASPS, 3 (27%) in SMRT, 1 (12.5%) in DSCRT and 1 (3.2%) in other histotypes (p = 0.0011). At the data cut off, median PFS was 2.75 months, and median OS was 19.7 months on the overall population. Outcomes differed according to the histotype group, with the 12 months PFS rates at 31.2% (chordoma), 35.7% (ASPS), 18.2% (SMRT), 0% (DSCRT) and 3.3% (other), respectively (p < 0.0001), and median PFS at 6.6 (chordoma), 7.5 (ASPS), 1.1 (SMRT), 2.1 (DSCRT) and 2.1 months (other), while 1-year OS rates were 76.6% (chordoma), 85.7% (ASPS), 36.4% (SMRT), 17.5% (DSCRT) and 42.9% (other) with median OS only reached for SMRT (2.4 months), DSRCT (10 months), and the other histotype group (7.1 months) (p = 0.004). The side effect profile of pembrolizumab was similar to other tumor type. Conclusions: Pembrolizumab is safe and well tolerate in this pop od STS pts, AcSé study reports high levels response rate and prolonged activity in selected subtypes of rare sarcomas. Clinical trial information: NCT03012620.