Cytological diagnosis of mesoblastic nephroma: A report of three cases with summary of prior published cases

Congenital mesoblastic nephroma (CMN) is a rare pediatric renal neoplasm, occurring most commonly in the first few months of life, with a favourable clinical outcome. Accurate pre‐operative cytological diagnosis of this entity is important as pre‐operative chemotherapy is not recommended and surgery is the treatment of choice. Cytodiagnosis of this rare tumor is discussed in only a few case reports. Here two cases of CMN and one case of cellular congenital mesoblastic nephroma (CCMN) diagnosed on FNAC along with their morphological differential diagnoses has been reported. They also take this opportunity to compare the cytological features of CMN with cellular CMN. Diagn. Cytopathol. 2016;44:823–827. © 2016 Wiley Periodicals, Inc.     

Cytodiagnosis of congenital mesoblastic nephroma: A case report

Mesoblastic nephroma (MN) is the most common renal tumor diagnosed in infancy. A case of congenital MN was diagnosed in a 6‐month old child by fine‐needle aspiration cytology. The smears were cellular and consisted of plump spindle cells arranged in clusters along with scattered naked nuclei in the background. Blastemal, epithelial, or glomeruloid structures were not seen. Considering the age and the cytomorphology, a diagnosis of cellular variant of MN was offered which was confirmed on histopathology. Unlike Wilms tumor, preoperative chemotherapy is not required for MN. Hence cytologic diagnosis is important. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Cellular mesoblastic nephroma in an infant: Report of the cytologic diagnosis of a rare paediatric renal tumor

Congenital mesoblastic nephroma is a rare pediatric tumor with a favorable clinical outcome. Cytological features of this uncommon tumor and diagnostic difficulties with other commoner pediatric renal neoplasms have been inadequately discussed in the available literature. We describe the case of a 1‐year‐old girl who presented with a right renal mass. Fine‐needle aspiration smears consisted of a few cellular clusters of spindle cells with mitotic activity and mild nuclear pleomorphism. No blastema was identified. A cytologic impression of mesoblastic nephroma was rendered, which was confirmed on histopathological examination of the right nephrectomy specimen as a cellular mesoblastic nephroma. Cytologic diagnosis of mesoblastic nephroma has important prognostic and therapeutic implications. The cytopathologist should carefully evaluate smears from such patients and attempt to differentiate mesoblastic nephroma from Wilms' tumor and clear cell sarcoma. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Prenatal sonographic diagnosis of a fetal renal mesoblastic nephroma occurring after transfer of a cryopreserved embryo.

Here we report the first case of prenatally diagnosed fetal renal mesoblastic nephroma occurring after transfer of a cryopreserved embryo. A 37 year old woman, having immunological infertility, was treated by in-vitro fertilization (IVF) and embryo transfer. Following unsuccessful IVF using fresh embryos, the patient conceived after transfer of cryopreserved-thawed embryos. The chromosomal analysis identified a normal karyotype at 16 weeks' gestation when amniocentesis was performed. The pregnancy course was uneventful until 28 weeks' gestation when polyhydramnios associated with fetal renal tumour was detected using ultrasonography. A male infant weighing 2564 g was born via Caesarean section at 34 weeks' gestation. A left nephrectomy was performed 5 days after delivery and the tumour was identified histologically as a mesoblastic nephroma. The postoperative course was uncomplicated to this point.     

Atypical mesoblastic nephroma. Pathologic characterization of a potentially aggressive variant of conventional congenital mesoblastic nephroma

A case of an aggressive variant of conventional congenital mesoblastic nephroma (CMN) occurred in a 10-month-old male infant. The tumor proved to be fatal, with two abdominal recurrences, but no metastases were found. Of the various terms used to designate the tumor, atypical mesoblastic nephroma (AMN) is preferred. We reviewed 17 previously reported cases to attempt pathologic characterization of AMN. The features that distinguish AMN from CMN are as follows: (1) atypical gross features consisting of one or more of the following: fleshy areas, foci of hemorrhage, necrosis, involvement of adjacent structures other than connective tissue; and (2) high cellularity and mitotic index. Aggressive behavior was noted at surgery or on follow-up in seven of the 18 cases. It was characterized by one or more of the following: (1) invasion of adjacent structures, such as adrenal gland, spleen, colon, and diaphragm (three cases); (2) one or more recurrences (four cases); and (3) metastasis (two cases). Atypical mesoblastic nephroma should be recognized as a potentially aggressive lesion separate from CMN.     

A case of fetal congenital mesoblastic nephroma with oligohydramnios

Although congenital renal tumors are rare, congenital mesoblastic nephroma (CMN) is the most common renal tumor in early infancy. It is non-metastatic, well differentiated, amenable to surgical removal, and carries a good prognosis. Polyhydramnios has been detected in most of the published cases of CMN. However, we experienced a rare case of fetal CMN associated with oligohydramnios. A 28-yr old woman at 34 weeks of gestation was referred to our hospital for oligohydramnios and a fetal abdominal mass. An ultrasonography revealed a huge, well-encapsulated mass arising from the right kidney. An emergency cesarean section was performed due to fetal distress. After birth, despite intensive neonatal care, the baby died because of renal failure, disseminated intravascular coagulopathy, pulmonary edema, together with other problems.     

Two chromosomally different cell populations in a partly cellular congenital mesoblastic nephroma

The conventional fibromatous and cellular areas of a congenital mesoblastic nephroma were studied using electron microscopy, and in vitro and cytogenetic methods. In light- and electron-microscopic studies, as well as in cell cultures, mature and immature mesenchymal cell types that corresponded to the fibromatous and cellular areas of the tumor were found. The conventional fibromatous portion of the tumor showed a normal chromosomal pattern, while the cellular, pleomorphic tumor area was characterized by an aneuploid clone with 54 chromosomes. The value of cytogenetic analysis of congenital mesenchymal renal tumors as a possible diagnostic tool in histologically questionable cases is discussed.     

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 1 year 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 1 year 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.     

Cytologic characteristics of congenital mesoblastic nephroma in fine-needle aspiration cytology: a case report.

The cytologic features of congenital mesoblastic nephroma (CMN) as recognized in smears of fine-needle aspirated cytology (FNAC) are reported. These included spindle- and tadpole-shaped cells with round to oval nuclei having small nucleoli and a smooth contour. The cytoplasm of these cells was dense and homogeneously stained. The background was composed of mucoid fibrillar material. The findings appear to be different from other types of renal tumors in infancy and specific enough for this tumor to allow diagnosis by FNAC.     

Congenital mesoblastic nephroma - a semimalignant fibroleiomyomatous kidney tumor of the newborn (author's transl)]

The congenital mesoblastic nephroma is a distinct tumor entity, which should be clearly distinguished from Wilmus-tumor. The pure mesenchymal tumor is usually present at birth and palpated as a mass in the kidney. Macroscopically the tumor reveals a striking resemblance with an uterine fibroid. Histologically the tumor tissue ist characterized by 1. interlacing bundels of spindle cells with uniform cell nuclei and regular mitotic figures, 2. collagen fibres between the tumor cells, 3. an angiomatous marginal zone, no tumor capsule, 4. hematopoetic foci and dysplastic glomeruli and tubuli in areas where normal kidney parenchyma mixes with tumor tissue, 5. small myxomatous areas within in the tumor, 6. no invasion of blood vessels or pelvis.Prognosis of the congenital mesoblastic nephroma is much better than in Wilms-tumor. Metastases have not been described so far. If, however, the tumor tissue is incompletly removed during operation, the neoplasm may recur and prove fatal. Ultrastructural and DNA cytophotometric studies suggests a low grade malignancy rather than a truely benign behaviour of this tumor.     

Atypical congenital mesoblastic nephroma. Report of a case with karyotypic and flow cytometric analysis

Atypical congenital mesoblastic nephroma is a rare infantile renal tumor that may behave aggressively in older infants. A case of atypical congenital mesoblastic nephroma occurring in an 8-month-old hispanic male was analyzed by routine histopathologic, cytogenetic, and retrospective flow cytometric analysis for DNA ploidy. Light microscopy revealed marked hypercellularity. The karyotype was abnormal, with the following configuration: 45,XY,-1,-3,-9,-9,-15,-17,-21,+del(1)(q21q25),+der(3), t(3;9;15)(q23;p22;q11),+der(9),t(3;9;15) (q23;p22;q11),+der(9),t(9;?) (p?22;?),+r21, + mar. Retrospective DNA ploidy analysis revealed a DNA index of 1.0. The significance of karyotypic changes occurring in mesenchymal renal tumors of this type is currently unknown. Cytogenetic analysis might be of prognostic value in these potentially aggressive tumors.     

KIT expression in normal and neoplastic renal tissues: immunohistochemical and molecular genetic analysis

Renal chromophobe cell carcinomas (ChCC) and oncocytomas express KIT. This character seems to reflect their common histogenesis from distal nephrons. In the normal kidney, however, the expression and localization of KIT are unclear. KIT expression in angiomyolipoma and congenital mesoblastic nephroma (CMN), is still controversial. c-kit mutations are reportedly rare in ChCC, but there is little information in other renal neoplasms, and no reported data on mutations of platelet-derived growth factor receptor (PDGFR). In order to address these issues the authors examined five ChCC, five oncocytomas, seven papillary cell carcinomas, two collecting duct carcinomas, 12 angiomyolipomas, and three CMN, as well as 10 normal renal tissues. In the normal kidney KIT was specifically expressed in the distal nephrons. Nine of 12 (75%) angiomyolipomas contained scattered KIT-positive cells, whereas all three CMN were completely negative for KIT. The presence of KIT-positive cells in angiomyolipomas was likely to correspond to that of melanocytic marker-positive cells, which mainly showed epithelioid morphology. Polymerase chain reaction-single-strand conformation polymorphism showed no evidence of mutations of c-kit or PDGFR in any of the tumors examined.     

Multicystic nephroma: Report of a case with fine-needle aspiration findings

This report presents the fine-needle aspiration biopsy (FNAB) findings of a multicystic renal tumor in a 52-yr-old woman. The aspirate smears contained clusters of cells with large, irregular nuclei and cytoplasmic vacuoles. Subsequent nephrectomy revealed a multicystic nephroma (MCN). Although most common in childhood, MCN should always be considered in the FNAB differential diagnosis of a multicystic renal mass in adult patients. Even in cases where the diagnosis of MCN is considered, it may be difficult to distinguish from cystic renal cell carcinoma on the basis of radiographic and FNAB findings. Diagn Cytopathol 1996;14:60–63. © 1996 Wiley-Liss, Inc.     

Identification of an acidic fibroblast growth factor-like activity in a mesoblastic nephroma

An acidic fibroblast growth factor-like activity was detected in a primary mesoblastic nephroma. Identification was based upon Northern blot analysis of renal tumor RNA and by a biochemical characterization of the growth factor activity. The activity extracted from the tumor stimulated DNA synthesis in both mouse fibroblasts and bovine endothelial cells. This activity was heat-sensitive and enhanced in the presence of heparin. The extract activity bound to immobilized immobilized heparin, eluting at 1.2 M NaCl, and cross-reacted with antiserum to recombinant acidic fibroblast growth factor. We also present evidence for acidic fibroblast growth factor-like molecules in normal immature human kidney, although the amount of the activity detected is less than that in the mesoblastic nephroma. These data suggest that acidic fibroblast growth factor-like activity is present in the developing normal human kidney, and that some renal tumors can continue to express a similar activity.