Congenital Mesoblastic Nephroma (CMN)

CLINICAL FEATURES

• Congenital mesoblastic nephroma (CMN) is a stromal neoplasm confined to infancy.

• Median age at diagnosis 2 months, >90% within the first year of life.

• Hypercalcemia and hyperreninism commonly seen.

GROSS FINDINGS

• Most tumors are centered near the hilus of the kidney and nearly all involve the renal sinus.
• 0.8 to 14 cm in greatest dimension, mean, 6.2 cm.
• Solitary, unilateral masses with soft or firm, bulging cut surfaces often indistinguishable from a nephroblastoma.
• Cysts, hemorrhage, and necrosis are common features.

MICROSCOPIC FINDINGS

• Predominantly monomorphic neoplasms composed of spindled mesenchymal cells of fibroblastic or myofibroblastic lineage.
• Classic type CMN
  • <1/3 of CMN.
  • Closely resembles infantile fibromatosis, characterized by intersecting fascicles of spindle cells, resembling fibroblasts or myofibroblasts, interspersed with scant collagen fibers.
  • Dilated, thin-walled vascular spaces are often prominent.
  • Mitotic activity is variable but generally less conspicuous than in the cellular pattern.
  • The tumor margins are highly irregular, with radiating bands of cells extending into the renal parenchyma and often into the perirenal soft tissue.
  • Abnormal metaplastic changes in tubules or glomeruli adjacent to or entrapped by the lesion are present in many specimens, including papillary hyperplasia and small nodules of hyaline cartilage. Extramedullary hematopoiesis is common. Skeletal muscle differentiation is not a feature of CMN.
• Cellular type CMN
  • Most common.
  • Characterized by increased cellular density and a high proliferative rate, imparting a sarcomatous appearance to the tumor.
  • Most commonly consist of plump cells with vesicular nuclei and a small to moderate amount of cytoplasm.
  • Lesions are sharply circumscribed grossly, without the interdigitating margins of classic lesions.

  • Slight to moderate nuclear pleomorphism may be present and the cells often grow in sheets of somewhat elongated cells.

  • Rare tumors contain cells with prominent nucleoli as well as areas of necrosis, closely resembling the features of a rhabdoid tumor.

  • In some cellular CMNs, a prominent capillary vasculature that mimics the vasculature of a clear cell sarcoma of the kidney (CCSK).

     

    	Cellular	Classic
    Interface with kidney	Circumscribed, unencapsulated	Highly irregular, interdigitating
    Genetic features	t(12;15)(p13;q25), trisomy chromosome 11	None known
    Cytology	Plump, slightly spindled cells	Markedly elongated
    Extrarenal equivalent	Infantile fibrosarcoma	Infantile fibromatosis

     

• Mixed mesoblastic nephroma: cellular and classic patterns coexist in ~20% of CMNs.

IMMUNOHISTOCHEMICAL STAINING

• Positive for antibodies to myofibroblast.
• Positive for vimentin, desmin, and actin.
• Negative for laminin, cytokeratins, S-100 protein, and WT1.

DIFFERENTIAL DIAGNOSES

• CCSK
• Rhabdoid tumor

CYTOGENETIC STUDIES

• t(12;15) (p13;q25). ETV6 on 12p13, ETS transcription factor family, neurotrophin-3 receptor (NTRK3) gene on 15q25, a membrane-bound protein with tyrosine kinase activity. Also seen in infantile fibrosarcoma.
• Trisomy for chromosome 11. Also seen in infantile fibrosarcoma.

TREATMENT AND PROGNOSIS

• CMNs are treated by complete surgical excision without adjuvant chemotherapy unless gross residual tumor remains.
• Recurrences and metastases occur in 5-10% of patients overall and are confined to tumors containing cellular histology.
• The most significant factors associated with local recurrence and metastases are: 1) the presence of cellular histology; 2) tumors of stage III or greater; and 3) involvement of intrarenal or sinus vessels.

REFERENCES

• AFIP, tumor of the kidney, bladder and related urinary structures, series 4