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A 3-month-old boy was found to have a right-sided abdominal mass. CT scan revealed a large, right kidney mass. A right nephrectomy was performed demonstrating a 14 x 11 x 8 cm kidney with an upper pole mass and an intact renal capsule. Cut section revealed a tan-white, focally necrotic, hemorrhagic, cystic tumor arising from the cortex, invading the renal sinus, but not extending to the resection margin.
Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2007, Case 6 and is a congenital mesoblastic nephroma, cellular type.
Criteria for Diagnosis and Comments:
This tumor is a congenital mesoblastic nephroma (CMN), cellular type. CMN is the second most common renal tumor of childhood and is the most common renal tumor in infants under 3 months of age. The median age at diagnosis is 2 months. It is termed "congenital" because of reports of antenatal detection by ultrasound and associations with the perinatal complications polyhydramnios, prematurity, and hydrops fetalis.
CMN is usually a solitary, unilateral mass lacking a capsule. Hemorrhage and necrosis, commonly present, do not signify malignancy. Most CMNs extend into the renal sinus and attention to the medial aspect of the kidney is necessary to ensure the tumor is removed in its entirety.
Two histologic variants of CMN exist: a classic type and a cellular type. The classic type infiltrates adjacent non-neoplastic tissue with long interdigitating fingers and is composed of tight bundles of interlacing elongated and spindled cells with cigar shaped nuclei and scant eosinophilic cytoplasm. This variant resembles infantile fibromatosis. The cellular type, in contrast, is a sharply circumscribed lesion composed of sheets of closely packed immature cells creating the appearance of a “small blue cell tumor”. Increased cell density and a high mitotic rate impart a sarcomatous appearance to cellular CMN. Cytoplasm is scant and variably pleomorphic nuclei exhibit vesicular chromatin.
Subtle infiltration of renal parenchyma characterizes cellular CMN in contrast to the long finger like projections at the margins of classic CMN. The cellular variant is more common than the classic, but cellular and classic mixed patterns may coexist in approximately 20% of CMNs, as illustrated in some slides distributed for this case.
Some slides distributed for this case exhibit embryonal metaplasia and papillary hyperplasia of entrapped or adjacent renal epithelial elements. Rarely, islands of cartilage may be present. These should not be interpreted as evidence establishing this lesion as a stromal predominant Wilms tumor. Rather they are interpreted as focal renal dysplasia caused by disturbances of renal development in the face of a coexisting CMN.
Fields of adipose tissue with tumor in some slides distributed in this case are interpreted as entrapped native adipose tissue created when tumor invaded the renal sinus, or adipose tissue accompanying renal vessels entrapped by tumor. The adipose tissue should not be interpreted as “heterotopic”, suggesting the diagnosis of another entity (see below).
Tumor cells of both histologic types bind antibodies directed against myofibroblasts. Epithelial antibodies are bound only by entrapped tubules. CMN is therefore typically positive for vimentin, actin, desmin and fibronectin. WT1 expression in CMN has been reported by some observers. S-100 is typically negative. Ultrastructural exam reveals mesenchymal cells with dilated, anastomosing rough endoplasmic reticulum and cytoplasmic thin filaments.
CMN chromosomal and genetic abnormalities have been identified only in the cellular variant, characterized by trisomy 11 and the t(12;15)(p13;q25) translocation which results in juxtaposition of the ETV6 and NTRK3 genes. This chromosomal translocation and gene fusion are identical to that seen in infantile fibrosarcoma and suggest that cellular CMN is in fact an infantile fibrosarcoma arising in the kidney.
The prognosis of CMN is excellent if completely resected and, unless tumor is left behind, adjuvant therapy is not indicated. Recurrence and metastasis occur in 5-10% of CMNs and are limited to those containing cellular histology. Recurrence is almost always associated with demonstrable tumor at resection margins.
CMN must be distinguished from other benign and malignant pediatric renal tumors. Its prognosis is excellent if completely resected and unless tumor is left behind, adjuvant therapy is not indicated.
Metanephric stromal tumor is an uncommon benign pediatric renal tumor of infants that may resemble CMN of both histologic types. It is about one-tenth as common as CMN. The archive of the National Wilms Tumor Study Pathology Center contains only 31 examples. It has a mean age at diagnosis of 24 months. Features distinguishing metanephric stromal tumor from CMN result from its interaction with entrapped native renal elements, e.g., concentric onionskin ring collars around tubules, angiodysplastic change in entrapped arterioles, and juxtaglomerular cell hyperplasia. Adipose tissue and neuroglial heterotopic tissues encountered in metanephric stromal tumor have not been observed in CMN.
Classic CMN may be mistaken for clear cell sarcoma of the kidney (CCSK) since the latter may also have a predominant bland cellular spindle appearance. However, the prominent arborizing vascular network characterizing CCSK is usually absent from CMN. In those CMNs with a vascular network, CMN cells bind antibodies to desmin and actin, while CCSK binds antibodies to vimentin only.
The most common pediatric renal tumor, Wilms tumor, may exhibit extensive stroma resembling CMN following pre-resection chemotherapy. However, striate muscle differentiation present in that setting does not occur in CMN and a residual epithelial component will almost always distinguish the treated Wilms tumor from CMN.
Rhabdoid tumor of the kidney, the most lethal tumor of childhood, may have fascicles of spindled cells resembling classic CMN. Rhabdoid tumor is easily distinguished from both types of CMN by the presence of large eccentric nuclei with prominent nucleoli, cytoplasmic inclusions and simultaneous expression of both mesenchymal and epithelial epitopes by individual cells. Eighty percent of renal rhabdoid tumor patients die within a year of presentation.