4.3Mesoblastic Nephroma

4.3.1Introduction

•Mesoblastic nephroma is also called congenital mesoblastic nephroma (CMN) or fetal renal hamartoma.

•This tumor was first described as a separate entity by Bolande et al. in 1967.

•Prior to this, it was erroneously confused with congenital Wilms tumor.

•Congenital mesoblastic nephroma (or simply mesoblastic nephroma) represents 3–10 % of all pediatric renal tumors.

•It is called congenital because it can be diagnosed in utero by ultrasound or within the first 3 months of life.

•Approximately 50 % occur during the neonatal period and 80 % of cases are reported within the first month of life.

•Congenital mesoblastic nephroma represents 3–10 % of all pediatric renal tumors. It was initially confused with congenital Wilms’ tumor.

•Mesoblastic nephroma is the most common renal tumor identified in the neonatal period and the most frequent benign renal tumor in childhood.

•Mesoblastic nephroma is most commonly diagnosed in the first 3 months of life.

•About 90 % present in the first year of life, 50–75 % of cases occur in young infants, and almost none occur after the age of 3 years.

•It is more common in males than females.

•The tumor is considered a hamartoma.

•It is presumed to originate from proliferating nephrogenic mesenchyme.

•Congenital mesoblastic nephroma is almost always unilateral and is rarely malignant.

•It may extend beyond the renal capsule, but rarely metastasizes to distant organs.

•Metastases to distant organs such as the brain, bone, and lungs have been reported.

•Commonly, mesoblastic nephroma appear as a large, solitary, predominantly solid, coarse, and echogenic renal mass that may contain cystic areas.

•Congenital renal tumors comprise 2.5–7 % of all perinatal tumors.

•Congenital renal neoplasms include, in decreasing order of frequency:

–Congenital mesoblastic nephroma

–Wilms tumor

–Rhabdoid tumor of the kidney

–Clear cell sarcoma

–Hamartomas

–Ossifying tumor of infancy

•The Diagnosis is usually made in the antenatal period or immediately after birth.

•Mesoblastic nephroma is considered generally a benign renal tumor.

•Among the renal tumors:

–Wilms tumor is the most common renal tumor, accounting for 80–85 % of all pediatric renal tumors.

–Congenital mesoblastic nephroma accounts for about 10–15 % of all pediatric renal tumors

–Rhabdoid tumor of the kidney accounts for 5–10 % of all pediatric renal tumors.

–Clear cell sarcoma (CCSK) accounts for 5–10 % of all pediatric renal tumors.

•The differential diagnosis based on age at presentation and includes the following tumors:

– Mesoblastic nephroma: from birth to

1year.

–Rhabdoid tumor: from 1 to 2 years of age.

–Clear cell sarcoma of the kidney: from 2 to

3years of age.

–Wilm’s tumor: over 3 years of age (Mean 3.5 years).

•There is an association between CMN and:

–Polyhyramnios with or without hydrops fetalis

–Hypertension

–Prematurity

–Some mesoblastic nephromas are associated with paraneoplastic syndromes such as:

• Hypertension: This is secondary to increased secretion of renin (hyperreninemia).

• Hypercalcemia: This is due to prostaglandin secretion from the tumor cells.

•Congenital mesoblastic nephroma arises from renal mesenchyma and is usually benign.

•Although CMN is considered a benign tumor, it could behave aggressively.

•The tumor lacks renal blastema and neoplastic metanephric elements, thereby differentiating it from Wilms tumor.

•In addition, it tends to infiltrate the kidney, rather than form the pseudocapsule of classic Wilms tumor.

•Congenital mesoblastic nephroma is almost always unilateral.

•It may extend beyond the renal capsule, but rarely metastasizes to distant organs.

4.3.2Classification

•Mesoblastic nephroma is a mesenchymal tumor.

•Macroscopically the tumor is a solid unencapsulated mass which often occurs near the renal hilum.

•It tends to invade the surrounding structures and renal parenchyma.

•Haemorrhage and necrosis are infrequent.

•Histologically, it is typically composed of connective tissue growing between nephrons, usually replacing most of the renal parenchyma.

•The classic cytological description of the lesion is that of cellular clusters of spindle cells, mild nuclear pleomorphism, mitotic activity and no blastema.

•Pathologically, mesoblastic nephroma are divided into two types:

–The classic variant

–The cellular variants

•The two types differ in the age at presentation, histologic characteristics, imaging characteristics and the biologic behavior of the tumors.

•The classic variant:

–This presents earlier, usually before age 3 months.

–It usually presents as a solid mass with small foci of necrosis or hemorrhage.

–It does not invade the perinephric tissues or the vascular pedicle.

–It is associated with an excellent outcome after complete surgical resection of the tumor.

–On gross examination, the tumor:

•Is noncapsulated

•Has a whorled trabeculated appearance

similar to leiomyomas, hence the name leiomyomatous hamartoma of the kidney.

–Histologically:

•It consists of uniform spindle cells arranged in bundles with scattered foci of entrapped normal glomeruli and tubules.

•The cellular variant:

–This type presents later, usually after age 3 months.

–More heterogeneous in appearance on imaging

–Tends to be larger and presents later in infancy

–May exhibit aggressive behavior including vascular encasement and metastasis

–It demonstrates more aggressive imaging characteristics, with larger areas of necrosis and hemorrhage.

–It may invade the perinephric fat and connective tissues.

–It is associated with a higher rate of local recurrence and metastatic disease.

–On gross examination:

•The tumor is fleshy with multiple foci of necrosis, cystic change, and hemorrhage.

–Histologically:

•It consists of spindle cells arranged in a haphazard sheets with a limited tendency to form bundles as seen in the classic form.

–The cellular variant may also demonstrate the t(12;15) translocation, which is diagnostic.

–On reverse-transcription polymerase chain reaction (RT-PCR), it may demonstrate the ETV6-NTRK3 gene fusion, a feature also seen in congenital infantile fibrosarcoma, hence the name infantile fibrosarcoma of the kidney.

•Factors that increase the risk of recurrence and metastasis include:

–Cellular variant

–Older age at presentation

–Positive surgical resection margins

•Metastases to distant organs such as the brain,

bone, and lungs have been reported. These are seen in cellular variant.

•The cellular variant has been shown to bear the t(12;15)(p13;q25) and ETV6 (chromosome 12)-NTRK3 (chromosome 15) gene fusion. These combined genes are thought to activate tyrosine kinase growth signaling. This gene fusion transcript is also reported in congenital or infantile fibrosarcoma

4.3.3Epidemiology

•Mesoblastic nephroma is the most common renal tumor in neonates and infants and represents 3–10 % of the pediatric renal tumors.

•Mesoblastic nephroma is the most common renal tumor presenting in the neonatal period and accounts for approximately 54 % of tumors in this age group.

•It was initially described as a benign tumor, but currently a spectrum of mesoblastic nephroma exists:

–The classic type representing the benign disease

–The cellular variant representing the aggressive disease (40–60 %)

–The mixed tumors falling somewhere in the middle.

–Mesoblastic nephroma has a slight male predominance, with a male-to-female ratio of 1.5:1.

–Histologically, the classic form is characterized by rare mitoses and absence of necrosis. Entrapped tubules and/or glomeruli are usually seen at the periphery of the tumor.

–Atypical or cellular variant is characterized by a high mitotic index, hypercellularity, and an atypical growth pattern with necrosis, hemorrhage, and invasion of adjacent structures.

4.3.4Histopathology (Figs. 4.69 and 4.70)

•Mesoblastic nephroma is a solid tumor and mostly these tumors are located near the hilum of the kidney and may extensively involve the renal sinus.

•Cysts are rarely seen but there may be hemorrhage and necrosis.

•The tumor is usually well circumscribed, but it may be seen infiltrating the renal parenchyma and even the perirenal fat.

•The cut surface of the tumor specimen shows a yellow-tan tumor with a “whorled” appearance that is similar to a uterine leiomyoma with spindled cell bundles.

•It is composed of immature renal stromal cells.

•The tumor lacks renal blastema and neoplastic metanephric elements, thereby differentiating it from Wilms tumor.

Figs. 4.69 and 4.70 Clinical photograph of a resected mesoblastic nephroma. Note the whorled appearance of the tumor. Note also the normal kidney tissue. Note that

the normal kidney is infiltrated by the tumor and not compressed like Wilms’ tumor. Note also the absence of a capsule

•The tumor tends to infiltrate the kidney, rather than form the pseudocapsule of classic Wilms tumor.

•There are two pathologic variants of mesoblastic nephroma:

–Classic

–Atypical or cellular.

•The classic type is characterized by rare mitoses and absence of necrosis. Entrapped tubules and/or glomeruli are usually seen at the periphery of the tumor.

•Classic mesoplastic nephroma:

–Fascicles and whorls of spindly cells.

–These cells have the features of secondary mesenchyme, which, in contrast with those of primary mesenchyme (mesoblast), lack the capacity to form epithelial structures.

–Instead, the proliferating cells acquire the features of fibroblasts, myofibroblasts, or smooth muscle cells.

–These cells contain vimentin, fibronectin, and sometimes actin, but not keratin or laminin.

–The tumor has irregular borders, with bands of tumor extending into surrounding soft tissue.

–It also permeates the adjacent renal parenchyma to encircle groups of tubules and glomeruli.

–Metaplastic tissues are usually found at the tumor-kidney interface or near entrapped renal tubules and glomeruli, most commonly cartilage.

–Extramedullary hematopoiesis and cuboidal metaplasia may also be present.

–Mitotic figures may be encountered, but frequent mitoses are more characteristically seen in cellular mesoblastic nephroma.

•Atypical or cellular variant is characterized by:

–A high mitotic index.

–Hypercellularity.

–An atypical growth pattern with necrosis, hemorrhage, and invasion of adjacent structures.

–The cellular type accounts for 40–60 % of mesoblastic nephroma cases.

•Cellular mesoblastic nephroma:

–This is more cellular than the classical type and has a sarcomatous appearance consisting of tightly packed cells with frequent mitoses (25–30/10 HPF).

–Data from the National Wilms Tumor Study show that cellular mesoblastic nephroma is commoner than classic mesoblastic nephroma with a ratio of 3:1.

–Cellular mesoblastic nephroma presents a few months later in life than the classic mesoblastic nephroma.

–Unlike the classic type, cellular mesoblastic nephroma may reach a huge size and can weigh more than 1 kg (Fig. 4.71).

–Histologically, two types of cells are seen. The more common cell type is a plump cell with ample cytoplasm and a vesicular nucleus. The less common type is a blue cell, which shows less cytoplasm and resembles cells of infantile fibrosarcoma.

•The cellular variant has been shown to bear the t (12; 15) (p13; q25) and ETV6 (chromosome 12)-NTRK3 (chromosome 15) gene fusion. These combined genes are thought to activate tyrosine kinase growth signaling. This gene fusion transcript is also reported in congenital or infantile fibrosarcoma.

Fig. 4.71 A clinical photograph showing an excised large mesoblastic nephroma that weighed more than one kilogram