Cellular Congenital Mesoblastic Nephroma Research Articles

Pediatric Fibromatosis Lacks the Internal Tandem Duplication of EGFR Seen in Congenital Mesoblastic Nephroma.

Classical and mixed congenital mesoblastic nephroma (CMN) are characterized by an internal tandem duplication (ITD) of the EGFR gene, in contrast to cellular CMN that usually harbors an ETV6::NTRK3 gene fusion. This same fusion occurs in infantile fibrosarcoma, and this tumor can be considered as the soft tissue equivalent of cellular CMN. A soft tissue equivalent of classic/mixed CMN remains undefined at the genetic level. Since classical CMN resembles fibromatosis of soft tissue histologically, we asked whether fibromatosis in children might show EGFR ITD. ITD was investigated using the polymerase chain reaction and primers for exons 18 and 25 of the EGFR gene. Seven of the eight cases of classical or mixed CMN were positive by this approach, but none of the five cellular CMNs. Of 11 cases of fibromatosis (six plantar, two digital, and three desmoid), none were positive for EGFR ITD. Within the limits of this small study, we conclude that pediatric fibromatosis is likely not characterized by EGFR ITD. There are isolated reports of pediatric soft tissue tumors that harbor EGFR ITD, but these have the appearance of infantile fibrosarcoma or mixed CMN rather than fibromatosis. We did not find any such cases, since all 14 cases of infantile fibrosarcoma in our study had an ETV6::NTRK3 fusion. The soft tissue tumors with EGFR ITD are not a morphologic match for the low-grade histology of classical CMN. Whether they have a similar favorable biology or behave more like fibrosarcoma with an ETV6::NTRK3 fusion or an alternative fusion involving other kinases remains to be determined.

Imaging characterization of paediatric tumours with the neurotrophic tyrosine receptor kinase fusion transcript.

The neurotrophic tyrosine receptor kinase (NTRK) fusion transcript (FT) is a major genetic landmark of infantile fibrosarcoma (IFS) and cellular congenital mesoblastic nephroma (cCMN) but is also described in other tumours. The recent availability of NTRK-targeted drugs enhances the need for better identification. We aimed to describe the anatomic locations and imaging features of tumours with NTRK-FT in children. Imaging characteristics of NTRK-FT tumours of 41 children (median age: 4 months; 63% <1 year old; range: 0-188) managed between 2001 and 2019 were retrospectively analysed. The tumours were located in the soft tissues (n = 24, including 19 IFS), kidneys (n = 9, including 8 cCMN), central nervous system (CNS) (n = 5), lung (n = 2), and bone (n = 1). The tumours were frequently deep-located (93%) and heterogeneous (71%) with necrotic (53%) or haemorrhagic components (29%). Although inconstant, enlarged intratumoural vessels were a recurrent finding (70%) with an irregular distribution (63%) in the most frequent anatomical locations. Paediatric NTRK-FT tumours mainly occur in infants with very variable histotypes and locations. Rich and irregular intra-tumoural vascularization are recurrent findings. Apart from IFS of soft tissues and cCMN of the kidneys, others NTRK-FT tumours locations have to be known, as CNS tumours. Better knowledge of the imaging characteristics may help guide the pathological and biological identification.

Report and follow-up on two new patients with congenital mesoblastic nephroma

BackgroundTumors are rare in neonatal age. Congenital mesoblastic nephroma (CMN) is a usually benign renal tumor observed at birth, or in the first months of life. It may also be identified prenatally and associated with polyhydramnios leading to preterm delivery. Effective treatment is surgical in most cases, consisting in total nephrectomy. In literature, very few studies report on the neonatal management of such a rare disease, and even less are those describing its uncommon complications.Cases presentationWe report on two single-center newborns affected with CMN. The first patient is a preterm female baby, born at 30+ 1 weeks of gestation (WG) due to premature labor, with prenatal (25 WG) identification of an intra-abdominal fetal mass associated with polyhydramnios. Once obtained the clinical stability, weight gain, instrumental (computed tomography, CT, showing a 4.8 × 3.3 cm left renal neoformation) and histological/molecular characterization of the lesion (renal needle biopsy picture of classic CMN with ETV6-NTRK3 translocation), a left nephrectomy was performed at 5 weeks of chronological age. The following clinical course was complicated by intestinal obstruction due to bowel adherences formation, then by an enterocutaneous fistula, requiring multiple surgical approaches including transitory ileo- and colostomy, before the conclusive anastomoses intervention. The second patient is a 17-day-old male term baby, coming to our observation due to postnatal evidence of palpable left abdominal mass (soon defined through CT, showing a 7.5 × 6.5 cm neoformation in the left renal lodge), feeding difficulties and poor weight gain. An intravenous diuretic treatment was needed due to the developed hypertension and hypercalcemia, which regressed after the nephrectomy (histological diagnosis of cellular CMN with ETV6-NTRK3 fusion) performed at day 26. In neither case was chemotherapy added. Both patients have been included in multidisciplinary follow-up, they presently show regular growth and neuromotor development, normal renal function and no local/systemic recurrences or other gastrointestinal/urinary disorders.ConclusionsThe finding of a fetal abdominal mass should prompt suspicion of CMN, especially if it is associated with polyhydramnios; it should also alert obstetricians and neonatologists to the risk of preterm delivery. Although being a usually benign condition, CMN may be associated with neonatal systemic-metabolic or postoperative complications. High-level surgical expertise, careful neonatological intensive care and histopathological/cytogenetic-molecular definition are the cornerstones for the optimal management of patients. This should also include an individualized follow-up, oriented to the early detection of any possible recurrences or associated anomalies and to a better quality of life of children and their families.

EGFR internal tandem duplications in fusion-negative congenital and neonatal spindle cell tumors.

Next-generation sequencing (NGS) assays can sensitively detect somatic variation, and increasingly can enable the identification of complex structural rearrangements. A subset of infantile spindle cell sarcomas, particularly congenital mesoblastic nephromas with classic or mixed histology, have structural rearrangement in the form of internal tandem duplications (ITD) involving EGFR. We performed prospective analysis to identify EGFR ITD through clinical or research studies, as well as retrospective analysis to quantify the frequency of EGFR ITD in pediatric sarcomas. Within our institution, three tumors with EGFR ITD were prospectively identified, all occurring in patients less than 1year of age at diagnosis, including two renal tumors and one mediastinal soft tissue tumor. These three cases exhibited both cellular and mixed cellular and classic histology. All patients had no evidence of disease progression off therapy, despite incomplete resection. To extend our analysis and quantify the frequency of EGFR ITD in pediatric sarcomas, we retrospectively analyzed a cohort of tumors (n=90) that were previously negative for clinical RT-PCR-based fusion testing. We identified EGFR ITD in three analyzed cases, all in patients less than 1year of age (n=18; 3/18, 17%). Here we expand the spectrum of tumors with EGFR ITD to congenital soft tissue tumors and report an unusual example of an EGFR ITD in a tumor with cellular congenital mesoblastic nephroma histology. We also highlight the importance of appropriate test selection and bioinformatic analysis for identification of this genomic alteration that is unexpectedly common in congenital and infantile spindle cell tumors.

ALK rearrangements in infantile fibrosarcoma-like spindle cell tumours of soft tissue and kidney.

Recurrent alterations in receptor tyrosine kinase (RTK) and downstream effectors are described in infantile fibrosarcoma (IFS)/cellular congenital mesoblastic nephroma (cCMN) and a subset of spindle cell sarcomas, provisionally designated 'NTRK-rearranged' spindle cell neoplasms. These two groups of tumours demonstrate overlapping morphologies and harbour alterations in NTRK1/2/3, RET, MET, ABL1, ROS1, RAF1 and BRAF, although their relationship is not fully elucidated. We describe herein a cohort of paediatric tumours with clinicopathological features not typical for inflammatory myofibroblastic tumour, but rather with similarities to cCMN/IFS harbouring ALK fusions. Clinicopathological features were assessed and partner agnostic targeted RNA sequencing on clinically validated platforms were performed. Tumours occurred in patients aged from 2 to 10 years (median age 2 years) with a 2:2 male to female ratio and an average size of 8.4 cm. Two tumours arose in soft tissues and two in the kidney. Morphological features included spindle to ovoid cells arranged in long fascicles or haphazardly within a myxoid to collagenised stroma; a subset of cases had either dilated, ectatic vessels or focal perivascular hyalinosis. By immunohistochemistry, all cases tested showed cytoplasmic expression of anaplastic lymphoma kinase (ALK) and one case demonstrated co-expression of CD34 and S100. This series of ALK-rearranged IFS-like tumours expands the spectrum of targetable kinases altered in these tumours and reinforces the potential overlap between IFS/cCMN-like tumours and the provisional entity of 'NTRK-rearranged' spindle cell neoplasms.

NTRK-Rearranged soft tissue neoplasms: A review of evolving diagnostic entities and algorithmic detection methods

The spectrum of tumors with NTRK1/2/3 rearrangements has expanded with widespread use of next generation sequencing (NGS) technology. For many years it was known that a majority of infantile fibrosarcomas (IFS), and their counterpart in the kidney, cellular congenital mesoblastic nephroma, contain the recurrent ETV6-NTRK3 fusion. Sequencing RNA transcripts from IFS and their morphologically similar counterparts in older children and adults has shown rearrangements with other 5′ partners combined with NTRK1, NTRK2, and NTRK3 can also occur. For those tumors occurring outside of the infant age group, this has resulted in a proposed new diagnostic entity of “NTRK-rearranged spindle cell neoplasm.” The clinical behavior of NTRK rearranged soft tissue tumors varies, though most show localized disease with rare metastases. The pathology of NTRK rearranged tumors exists on a spectrum, with overlapping features of classic infantile fibrosarcoma, lipofibromatosis, and malignant peripheral nerve sheath tumor. In this tumor spectrum, clinical and pathologic predictive factors are largely still to be determined, with no clear association between histologic grade and severity of disease. Of critical importance is detection of the NTRK rearrangement in order to guide treatment in patients with unresectable and metastatic disease. While resection is the definitive treatment, these tumors do show response to targeted TRK kinase inhibitors. Multiple detection methods are available, including immunohistochemistry, FISH, and next generation sequencing, which each have their merits and potential pitfalls. We aim to review the clinical characteristics and histomorphology of mesenchymal tumors with NTRK rearrangements as well as discuss molecular detection methods and diagnostic algorithms specific for soft tissue tumors.

Surgical management of cellular congenital mesoblastic nephroma in a neonate: a case report and review of literature

BackgroundCongenital mesoblastic nephroma (CMN) is the most common type of renal stromal tumor in neonates. It is classified into cellular, classical, and mixed types. The multidisciplinary management approach is the mainstay of management. We are reporting a case of neonatal congenital mesoblastic nephroma in a full-term boy with intrauterine growth restriction and hypertension managed effectively in our institution.Case presentationA full-term boy with intrauterine growth restriction (IUGR) with a birth weight of 2.3 kg, referred at birth with an abdominal mass. His antenatal scan at 35 weeks showed a cystic abdominal mass. On delivery, a huge visible abdominal mass of cystic consistency and smooth surface was noticed at the right side of the abdomen. blood pressure was 98/75 mmHg. It was responsive to hydralazine. Aldosterone and renin were significantly elevated at more than 100 and 500 ng/dl, respectively. Serum neurone-specific enolase (NSE) was 35 ng/ml while alfa feto protein was (AFP) 50,000 kIU/L. An abdominal ultrasound scan revealed an ill-defined large heterogeneous mass of 6.09 × 6.5 × 5.77 cm that arises from the right kidney. A computed tomography scan confirmed a right kidney mass with peripheral claw sign of the normal right renal tissue. It was crossing the midline and causing a mass effect on the adjacent structures. The right renal artery and vein were compressed and shifted posteriorly and inferomedially. Right radical nephrectomy was performed via a right lower transverse incision. The tumor was completely excised with a tumor weight of 270 g and a size of 10.5 × 8 × 5.5 cm. Histopathological diagnosis was mesoblastic nephroma of a cellular type which was confirmed by immunohistochemistry. Post-operatively, the blood pressure has significantly reduced and antihypertensive medications were eventually weaned off. The multidisciplinary team decided to preserve chemotherapy only in case of recurrence. At 3 months follow-up, no features of recurrence were noticed based on surveillance ultrasonography.ConclusionMesoblastic nephroma should be considered in any newborn with renal mass. The multidisciplinary team approach with aggressive management of hypertension, detailed radiological investigation, and complete tumor resection is fundamental for obtaining an excellent outcome for such entities.

An unusual fusion gene EML4-ALK in a patient with congenital mesoblastic nephroma.

Congenital mesoblastic nephroma (CMN), the most common renal tumor of infancy, is a mesenchymal neoplasm histologically classified into classic, cellular, or mixed types. Most cellular CMNs harbor a characteristic ETV6-NTRK3 fusion. Here, we report an unusual congenital mesoblastic nephroma presenting in a newborn boy with a novel EML4-ALK gene fusion revealed by Anchored Multiplex RNA Sequencing Assay. The EML4-ALK gene fusion expands the genetic spectrum implicated in the pathogenesis of congenital mesoblastic nephroma, with yet another example of kinase oncogenic activation through chromosomal rearrangement. The methylation profile of the tumor corresponds with infantile fibrosarcoma showing the biological similarity of these two entities.

Congenital mesoblastic nephroma is characterised by kinase mutations including EGFR internal tandem duplications, the ETV6-NTRK3 fusion, and the rare KLHL7-BRAF fusion.

Congenital mesoblastic nephroma (CMN) is histologically classified into classic, cellular and mixed subtypes. The aims of this study were to characterise the clinical, pathological and molecular features of a series of CMNs, and to determine the utility of pan-Trk and epidermal growth factor receptor (EGFR) immunohistochemistry as surrogate markers for NTRK gene fusions and EGFR internal tandem duplications (ITDs). Twenty-two archival CMN cases (12 classic, five cellular, and five mixed) were tested for the ETV6-NTRK3 fusion and EGFR ITD transcripts by the use of reverse transcriptase polymerase chain reaction (PCR), and next-generation sequencing-based anchored multiplex PCR. All 12 classic CMNs had EGFR ITD. Of the five cellular CMNs, four had the ETV6-NTRK3 fusion and one had the KLHL7-BRAF fusion. Of the five mixed CMNs, four had EGFR ITD, and one had the ETV6-NTRK3 fusion. Pan-Trk immunoreactivity was 100% sensitive and 94.1% specific for the presence of NTRK rearrangement. However, EGFR staining was only 62.5% sensitive and 33.3% specific for EGFR ITD. EGFR ITD is a consistent genetic event in classic CMN. A majority of cellular CMNs have the ETV6-NTRK3 fusion. Rare cellular CMNs may harbour non-canonical mutations such as the KLHL7-BRAF fusion, which was found in one case. Mixed CMNs may have either EGFR ITD or the ETV6-NTRK3 fusion. Pan-Trk immunohistochemistry is a sensitive, albeit not perfectly specific, marker for NTRK rearrangement. EGFR immunohistochemistry is not helpful as a marker of EGFR ITD.

Abstract IA15: Tissue-agnostic development of TRK inhibitors for pediatric cancer

Abstract Fusions involving in the NTRK1, NTRK2, and NTRK3 genes that encode the TRKA, TRKB, and TRKC neurotrophin receptors (TRK fusions) occur across a wide range of cancers in children and adults. These fusions result in constitutive expression and ligand-independent activation of the TRK kinase. TRK fusions are pathognomonic for certain rare cancers, including infantile fibrosarcoma and cellular congenital mesoblastic nephroma, and occur at a lower frequency across a range of more common cancers in children including soft-tissue sarcomas, gliomas, and leukemias. Recently, larotrectinib was FDA approved for the treatment of TRK fusion solid tumors in children and adults, representing the first kinase inhibitor to receive FDA histology-agnostic approval for the treatment of cancer. This approval was based on a combined analysis of three clinical trials, including an ongoing pediatric phase 1/2 trial that demonstrated a 94% response rate in 34 children with TRK fusion-positive solid tumors. Remarkably, due to nearly concurrent development in pediatrics and adults, more than 30% of the patients with TRK fusion solid tumors treated with larotrectinib on clinical trials to date have been children. Other TRK inhibitors are also in pediatric development, including entrectinib and LOXO-195, and clinical trials of additional agents including repotrectinib are planned. Entrectinib, which also antagonizes ROS1 and ALK, was reported to induce responses in 11/11 children whose tumors harbored fusions of the TRK, ROS1 or ALK genes. LOXO-195 and repotrectinib have the potential to antagonize resistance mutations that can develop during treatment with first-generation TRK inhibitors, and we reported a 45% response rate to LOXO-195 among 20 patients enrolled to either single-patient treatment protocols or an ongoing pediatric and adult phase 1 study who harbored a TRK kinase resistance mutation. In this talk, I will review the data on the use of TRK inhibitors for TRK fusion cancers in children, discuss unanswered questions related to the use of TRK inhibitors in children and planned clinical trials designed to address these, and highlight the challenges and opportunities that arise when studying novel therapies for rare, molecularly defined diseases. Citation Format: Theodore W. Laetsch. Tissue-agnostic development of TRK inhibitors for pediatric cancer [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA15.

Tag-n-trak study: Preliminary analysis of an unselected biobank tumors with NTRK fusion transcript, the French SFCE society contribution.

10540 Background: NTRK ( Neurotrophic receptor tyrosine kinase) fusion transcript was initially described in infantile fibrosarcoma (IFS) and is now known to be present in many other rare types of tumor with a lower incidence. The main objective of the study is to describe the presentation and outcome of unselected tumors with NTRK fusion transcript (NTRK-FTT) to better consider the role of TRK inhibitors (TRKi) in such entities. Methods: We selected patients (pts) from the Institut Curie biobank (adults and children) with NTRK-FTT and which were assessed by RT-qPCR then RNA sequencing in a prospective or retrospective process, between 2001 and 2019. Results: We identified 62 NTRK-FTT among 2119 screened tumors (2.2 cases/year with RT-qPCR and 6.9 cases/year with RNA seq after 2016), NTRK3 (44 cases) (including 41 NTRK3-ETV6), NTRK2 (9) or NTRK1 (9). Most of pts had under 2 years (y) (74%) and only 7 pts were adults. We report preliminary analysis of clinical observation for the first 27 pts. Median age was 0.4 y [0-60.2]. Pathologic diagnosis was IFS (12 cases), various CNS tumors (4), atypical teratoid rhabdoid tumor (1), myofibroblastic inflammatory tumor (2), benign tumors (3), cellular congenital mesoblastic nephroma (2), lipofibromatosis like neural tumor, myxoïd liposarcoma, unclassifiable sarcoma (1 each). Two pts had metastatic tumors. Among all, 22 had surgery (1 mutilating), 15 chemotherapy, 4 radiotherapy, and 5 received TRKi, as second line treatment (2 pts) or ≥ third line (3 pts). After a median follow-up of 50 months [range, 1-155], 20/27 pts remained in complete remission, 3 had stable residue, and 4 had progressive disease (associated to 1 disease-related and 1 toxic deaths). Five-year OS is 88% [95%CI, 73.5-100] and 5y-EFS 59.5% [95%CI, 41.7-84.9]. Conclusions: This descriptive study showed that NTRK-FTT is rare (2.9%), encompasses a variety of different histotypes (n = 14). Systematic RNA sequencing allowed to depict 3.5 times more NTRK-FTT than targeted RT-qPCR. Overall outcome is favorable despite frequent tumor events. According to tumor type and the uncertainties regarding the long-term side effects of TRKi, the benefit/risk ratio must be carefully evaluated before using these drugs in first line.

Recurrent Congenital Mesoblastic Nephroma: A Case Report

Congenital mesoblastic nephroma (CMN) is the most common tumor of kidney in early infancy. We present here a case of antenatally detected right renal mass that was excised and reported cellular CMN. He developed recurrence while on adjuvant chemotherapy. We emphasize that the management of cellular CMN, especially adjunct chemotherapy, has not been standardized yet.

NTRK-rearranged mesenchymal tumours: diagnostic challenges, morphological patterns and proposed testing algorithm

Oncogenic fusions involving neurotrophic receptor tyrosine kinase (NTRK) genes are being increasingly identified in a range of mesenchymal tumours unrelated to infantile fibrosarcoma or cellular congenital mesoblastic nephroma, where the canonical ETV6-NTRK3 fusion was first described more than two decades ago. Recognition of these NTRK-rearranged tumours poses a diagnostic challenge to surgical pathologists due to their non-specific clinical and pathological features. However, their recognition is of heightened importance, particularly in locally advanced and metastatic sarcomas, due to the recent availability of selective and highly effective targeted therapy. Herein, we present an Australian multi-institutional series of six of these rare NTRK-rearranged mesenchymal neoplasms to share the local experience and diagnostic challenges as well as to highlight key morphological patterns and immunoprofiles that provide the most helpful clues in routine practice. We also propose a diagnostic algorithm for the detection of these fusions, drawing attention to the limitations of ancillary studies including immunohistochemistry against tropomyosin receptor kinase (TRK) protein, fluorescence in situ hybridisation (FISH) and next generation sequencing.

Congenital Mesoblastic Nephroma in a Premature Neonate: Should We Give Adjuvant Chemotherapy?

Congenital mesoblastic nephroma (CMN) is a rare renal tumor of infancy. Complete surgical excision is often sufficient. A premature neonate underwent left radical nephrectomy for CMN without any adjuvant therapy. Pathology was consistent with cellular type CMN. Six months postoperatively, the patient developed recurrence. He subsequently underwent re-excision without any adjuvant chemotherapy. The baby is tumor free for more than a year.

TRK Fusion Cancers in Children: A Clinical Review and Recommendations for Screening.

Chromosomal translocations involving the NTRK1, NTRK2, and NTRK3 genes (TRK fusions), which encode the neurotrophin tyrosine kinase receptors TRKA, TRKB, and TRKC, can result in constitutive activation and aberrant expression of TRK kinase. Certain cancers almost universally harbor TRK fusions, including infantile fibrosarcoma, cellular congenital mesoblastic nephroma, secretory breast cancer, and mammary analog secretory carcinoma of the salivary gland. TRK fusions have also been identified at lower frequencies across a broad range of other pediatric cancers, including undifferentiated sarcomas, gliomas, papillary thyroid cancers, spitzoid neoplasms, inflammatory myofibroblastic tumors, and acute leukemias. Here we review the prevalence and diseases associated with TRK fusions and methods of detection of these fusions in light of the recent development of selective TRK inhibitors, such as larotrectinib, which demonstrated a 75% response rate across children and adults with TRK fusion cancers. We provide recommendations for screening pediatric tumors for the presence of TRK fusions, including the use of immunohistochemistry or fluorescence in situ hybridization for patients with tumors likely to harbor TRK fusions. Further, we recommend next-generation sequencing for tumors that have a relatively low prevalence of TRK fusions, both to identify patients who may benefit from TRK inhibition and to identify other targetable oncogenic drivers that exist in the same tumor types.

Recurrent and metastatic congenital mesoblastic nephroma: where does the evidence stand?

Fifty years ago, Bolande described Congenital Mesoblastic Nephroma (CMN) as a benign lesion. Unexpected aggressive clinical behaviors prompted a sub-classification based on histology. Recent molecular genetic evidence has identified the aggressive cellular variant to be the renal manifestation of congenital infantile fibrosarcoma. We submit a reappraisal and analysis of the available literature on recurrent and metastatic CMN. An electronic search of PubMed, MEDLINE, EMBASE, and Scopus yielded 38 children with local recurrence and/or metastases. Of the 38 children with local recurrence and/or metastasis, 59% were girls. Median time to recurrence was 6months (range 1-12months). The commonest sites of metastases were the lung (39%) and liver (29%). Fifty percent of these children died of disease. The outcome of additional chemotherapy (p=0.5) did not differ from that of surgery alone. The choice of chemotherapy did not influence the outcome (p=0.6). Recurrence and metastasis in cellular CMN are much more common than described earlier and carry a high mortality. Children with cellular and mixed CMN require close clinical and radiological follow-up for a minimum of 12months after primary surgery. Surgery is the mainstay of the treatment of recurrent and metastatic lesions. Neoadjuvant chemotherapy is recommended only if the lesion is inoperable. Targeted therapy may be an option in treatment of refractory cases.

Congenital mesoblastic nephroma with distant metastasis in a premature twin gestation

Abstract Congenital mesoblastic nephroma (CMN) is a rare renal tumor of infancy. Here, we present a case of CMN presenting in a 29 week premature male in a twin gestation. An abdominal mass had been noted on prenatal ultrasound. He was initially treated with right radical nephrectomy. Pathology was consistent with cellular type CMN. Three months postoperatively, the patient developed pulmonary metastasis and underwent wedge resection of the right lung lesion. He subsequently underwent adjuvant chemotherapy, to which he has responded well. We discuss the presentation and management of patients with CMN and address the indications for postoperative chemotherapy.

The Value of Mitotic Count and Ki67 Proliferation Index in Congenital Mesoblastic Nephroma

ABSTRACTObjective: We aimed to define the histopathologic features and proliferative rate of congenital mesoblastic nephroma (CMN) as a risk factor for recurrence. Methods: Fourteen cases of CMN among 138 registered pediatric renal tumors were retrospectively reviewed. The prognostic impact for mitotic rate and Ki67 index was investigated. Results: There were four (28.6%) classic, six (42.9%) cellular, and four (28.6%) mixed type CMNs, with average Ki-67 counts of 16.75% in the classic CMN, and 53.2% in the tumors with cellular components (both mixed and cellular CMNs). Twelve patients (85.7%) were aged less than six months. Tumors with cellular component showed significantly larger tumor diameter and higher Ki-67 index (p = 0.015 and p = 0.016, respectively). The patient with cellular CMN, whose tumor showed the highest mitotic rate (4.9/HPF), but not the highest Ki67 index (57.4%), died of recurrent disease with distant metastasis. Conclusion: Proliferative markers-mitotic count and Ki67 index-have limited value to predict recurrence or metastasis in CMNs with a cellular component.

Congenital mesoblastic nephroma: Clinical analysis of eight cases and a review of the literature.

Congenital mesoblastic nephroma (CMN) is a mesenchymal renal tumor. The aim of the present study was to review the clinical characteristics and outcome of CMN in infants. A retrospective file review was conducted of eight cases of CMN treated at the Children’s Hospital of Fudan University between 2004 and 2012. Ultrasound and computerized tomography scans had been performed on all eight patients. Two cases presented with a solid tumor and exhibited pathological features consistent with those of classic CMN, five cases exhibited cystic, hemorrhagic and necrotic characteristics, with calcification and pathology consistent with the cellular variant of CMN and one case presented with a solid tumor, which exhibited pathological features consistent with ceullular CMN. Histology confirmed classic CMN in two patients and cellular CMN in six patients. For surgical intervention, four cases had radical nephrectomy, one case had a half nephrectomy and three cases had tumor enucleation performed. Two cases had received pre-operative chemotherapy, but exhibited no response, and three cases received post-operative chemotherapy. Two patients were lost to follow-up, but the remaining six patients survived to the end of follow-up without further complications. The mean follow-up time was 24.6 months. In conclusion, the differential diagnosis between CMN and Wilms’ tumor is critical. Imaging characteristics are partially correlated with pathological characteristics. Surgery is the main treatment for CMN, but pre-operative chemotherapy is not particularly effective. The efficacy of post-operative chemotherapy requires further investigation, but the prognosis is positive.

Cellular Mesoblastic Nephroma with Liver Metastasis in a Neonate: Prenatal and Postnatal Diffusion-Weighted MR Imaging

Congenital mesoblastic nephroma (CMN) is the most common renal tumor in the first year of life. Here, we present unique findings of cellular variant CMN seen on prenatal and postnatal MRI with diffusion-weighted imaging (DWI).The mass was well-visualized on prenatal MR DWI with diffusion restriction in the solid portions. After excision of the mass, follow-up whole body MRI with DWI helped identify local tumor recurrence with suspicious liver metastasis. This hepatic lesion also showed diffusion restriction.