A 2-week-old boy born at term following an uncomplicated gestation is examined by a pediatrician after the mother palpated a right-upper quadrant mass while giving him a bath. The pediatrician confirms the abnormal finding and admits the patient to the hospital for further evaluation. 

An abdominal ultrasound reveals a 6.0 cm in greatest dimension solid mass involving the renal hilum and extending to the upper aspect of the right kidney. Initial laboratory tests, including electrolytes and catecholamines, are within expected limits. Subsequent contrast enhanced computed tomography (CT) imaging confirms the presence of the right renal mass and excludes evidence of lymphadenopathy and/or metastatic deposits. 

The patient undergoes a radical nephrectomy. The resected right kidney weighs 98 grams and measures 7.0 x 5.5 x 5.5 cm. The well-circumscribed light yellow and whorled firm tumor measures 6.0 cm in greatest dimension and appears to focally disrupt the renal capsule.

Master List of Diagnoses

  • Clear cell sarcoma, cellular variant
  • Mesoblastic nephroma/congenital mesoblastic nephroma
  • Metanephric fibroma
  • Rhabdoid tumor
  • Wilms tumor, blastema-predominant
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This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2017, Case 13, and is Mesoblastic nephroma/congenital mesoblastic nephroma of the kidney.

Criteria for Diagnosis and Comments

Upon histologic evaluation the renal tumor is characterized by a proliferation of interlacing bundles of minimally atypical spindle-shaped cells with focal myxoid degeneration. Entrapped renal elements, including renal tubules and immature glomeruli, are noted in some areas. Mitotic figures are scarce and there is focal hemorrhage and cyst formation; necrosis is not prominent. Extramedullary hematopoiesis is focally identified. The neoplastic proliferation has an infiltrative pattern and involves the renal sinus, the renal parenchyma, and focally extends to the pericapsular adipose tissue. The microscopic findings are consistent with those of a mesoblastic nephroma - classic variant (“fibromatosis-like”).

Mesoblastic nephroma (MN, also known as congenital mesoblastic nephroma) is a neoplasm of low malignant potential that comprises 3% - 5% of all childhood renal tumors. It is the most common renal tumor in patients under 1 year of age and is usually diagnosed during the first 3 months of life. Some references indicate that MN affects boys and girls at the same rate, while others point out that it affects twice as many males as females. MN is occasionally seen in association with Beckwith-Wiedemann syndrome. Although it usually presents as an abdominal mass, it can also be associated with hypercalcemia, hypertension, and congestive heart failure. Prenatal fetal diagnosis is achieved by ultrasonography and may be associated with polyhydramnios, nonimmunologic fetal hydrops, and premature delivery. Tumors with histological features of MN arising in the kidneys of adult patients have been reported in the literature.

Grossly MN presents as a single, unilateral, and non-encapsulated renal tumor that tends to arise centrally (near the renal hilum). The firm cut surfaces are whorled or trabeculated (reminiscent of a leiomyoma) and gray-white to yellow. Although commonly well-circumscribed, infiltrating borders can be grossly appreciated. Gross evidence of cystic change, hemorrhage and/or necrosis (of no prognostic significance) may be present. According to some authors, tumors with a cellular pattern (see below) may be grossly soft and fleshy, with multicystic areas associated with blood or clear fluid accumulation and may be larger than the classic variant at the time of diagnosis. The results of ultrasonography, CT, and magnetic resonance imaging studies are usually non-specific and include solid, cystic, and mixed solid and cystic features.

Three microscopic patterns (or variants) are recognized: classic, cellular and mixed.

  • In the classic (“fibromatosis-like”) pattern (24% of cases) interlacing bundles of minimally atypical spindle-shaped cells, often associated with entrapped renal elements (that may have dysplastic features), exhibit low mitotic activity (0 - 1 mitoses per 10 HPFs) and infiltrating borders. Neoplastic cells may be arranged in a herringbone pattern. Foci of extramedullary hematopoiesis and/or hyaline cartilage can also be appreciated. This pattern lacks a consistent genetic abnormality, histologically resembles infantile fibromatosis/myofibromatosis, and is described as having a favorable prognosis. The mean age at presentation is 7 days.
  • In the cellular (“sarcomatoid” or “atypical”) pattern (66% of cases) the cells are spindle-shaped or polygonal, with high nuclear-to-cytoplasmic ratios; moderate nuclear pleomorphism may be present and the cells may be arranged in a herringbone pattern. This highly cellular pattern exhibits brisk mitotic activity (8 - 30 mitoses per 10 HPFs) and a pushing border. At the molecular level it is identical to infantile fibrosarcoma (it has the same t(12;15)(p13;q25) chromosomal translocation, resulting in ETV6-NTRK3 fusion gene rearrangement). This pattern of MN has a more aggressive behavior than the classic pattern. The mean age at presentation is 4 months.
  • In the mixed pattern (10% of cases) areas of classic MN alternate with areas of cellular MN. According to several studies tumors with this pattern can be positive for the ETV6-NTRK3 fusion gene, but this finding is not consistently reported in the literature. The mean age at presentation is 2 months.

Cells from MNs may exhibit mesenchymal, fibroblastic, and/or myofibroblastic features; immunopositivity for vimentin, fibronectin, nestin, muscle specific actin, and smooth muscle actin is reported in the literature. In a recent study of 19 MNs by El Demellawy et al., all microscopic patterns were immunonegative for WT-1 and caldesmon/calponin and were immunopositive for p16/PAX8. Immunopositivity for cyclin D1, Beta-catenin (cytoplasmic only), and DOG-1 was demonstrated in the classic and mixed patterns, but not in the cellular pattern. Another study by Shao et al., reported immunonegative staining with WT-1, Bcl-2 and CD34 in cases of MN exhibiting a cellular pattern. 

The differential diagnosis of MN includes blastema-predominant Wilms tumor, the cellular variant of clear cell sarcoma of kidney, rhabdoid tumor of the kidney, and metanephric fibroma. Detailed histological features (identified in properly sampled and well-preserved tumors) combined with immunohistochemical stains, genetic expression profile studies, and the patient’s age and clinical presentation assist in differentiating these neoplasms from MN. 

Adequate therapy for most MN patients consists of surgical resection (nephrectomy) and results in a good outcome. Incomplete resection increases the risk of recurrence. Therefore, if a partial nephrectomy is performed, complete tumor excision and negative margins may be curative in most cases. Patients diagnosed with a cellular variant MN that develop stage III disease (or higher – NWTS staging system) and are age 3 months or older at the time of diagnosis have an increased risk of recurrence, including metastases; adjuvant chemotherapy has been recommended for these patients. However, the five-year overall survival rate is 96% when diagnosed within the first 7 months of life.

  1. Which of the following statements is true regarding the cellular (“sarcomatoid”) pattern of mesoblastic nephroma (MN)?
    1. It always exhibits low mitotic activity and infiltrating borders.
    2. It is a very rare pattern, comprising less than 10% of all MNs.
    3. It is identical (at the molecular level) to infantile fibrosarcoma.
    4. It is only identified in metastatic deposits.
    5. It lacks a consistent genetic abnormality.
  2. MN comprises 3% - 5% of all childhood renal tumors and it is the most common renal tumor in which of the following age groups?
    1. Between 2 - 4 years of age
    2. Between 8 - 10 years of age
    3. Entering puberty
    4. Older than 4 years of age
    5. Under 1 year of age
  3. Adequate therapy for most MN patients consists of which of the following?
    1. Chemotherapy alone
    2. Chemotherapy and radiation therapy followed by surgical resection (partial nephrectomy)
    3. Radiation therapy alone
    4. Radiation therapy followed by surgical resection (partial nephrectomy)
    5. Surgical resection (nephrectomy)

References

  1. Constine L, Frantz C, Hayes-Jordan A, Siebel N, Shochat S. Wilms tumor and other childhood kidney tumors treatment. (PDQ®)–Health professional version. National Cancer Institute Web site.http://www.cancer.gov/types/kidney/hp/wilms-treatment-pdq. Updated: August 11,2016; Accessed: 9/29/2016.
  2. Delahunt B, Grignon DJ, Eble JN. Tumors of the kidney. In Amin MB, Grignon DJ, Srigley JR, Eble JN, eds. Urology Pathology. 1st ed. Philadelphia, PA: Lippincott Williams & Watkins; 2014:137-139.
  3. Durham JR, Bostwick DG, Farrow GM, Ohorodnik JM. Mesoblastic nephroma of adulthood. Report of three cases. Am J Surg Pathol. 1993;17(10):1029-1038.
  4. El Demellawy D, Cundiff CA, Nasr A, et al. Congenital mesoblastic nephroma: a study of 19 cases using immunohistochemistry and ETV6-NTRK3 fusion gene rearrangement. Pathology. 2016;48(1):47-50.
  5. Husain AN, Pysher TJ. The Kidney and Lower Urinary Tract. In: Stocker JT, Dehner LP, Husain AN, eds. Stocker & Dehner’s Pediatric Pathology. 3rd ed. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins; 2011:822-823.
  6. Malkan AD, Loh A, Bahrami A, et al. An approach to renal masses in pediatrics. Pediatrics. 2015;135(1):142-158.
  7. Odonez NG, Rosai J. Urinary Tract - Kidney, renal pelvis, and ureter; bladder. In: Rosai J, ed. Rosai and Ackerman’s Surgical Pathology, Volume I. 10th ed. Philadelphia, PA: Mosby Elsevier; 2011:1177-1178.
  8. Shao L, Hill DA, Perlman EJ. Expression of WT-1, Bcl-2, and CD34 by primary renal spindle cell tumors in children. Pediatr Dev Pathol. 2004;7(6):577-582.
  9. Sheth MM, Cai G, Goodman TR. AIRP Best cases in radiologic-pathologic correlation: congenital mesoblastic nephroma. Radiographics. 2012;32(1):99-103.
  10. van den Heuvel-Eibrink MM1, Grundy P, Graf N, et al. Characteristics and survival of 750 children diagnosed with a renal tumor in the first seven months of life: A collaborative study by the SIOP/GPOH/SFOP, NWTSG, and UKCCSG Wilms tumor study groups. Pediatr Blood Cancer. 2008;50(6):1130-1134.

Author

Nilsa C. Ramirez, MD
Surgical Pathology Committee
Nationwide Children’s Hospital
Columbus, OH

Answer Key

  1. It is identical (at the molecular level) to infantile fibrosarcoma. (c)
  2. Under 1 year of age (e)
  3. Surgical resection (nephrectomy) (e)