Older Male with Renal Mass

Specimen Type:

Kidney

History:

A 70-year-old man with a renal mass underwent nephrectomy. Grossly, almost the entire renal parenchyma was replaced by numerous cystic and solid lesions. Cysts were multiloculated or uniloculated bridged by thin septa of less than 0.1 cm thick. Complex papillae measuring 1.0 – 1.5 cm in diameter were protruding from the septum to some cysts. Firm fibrous nodules were also noted. Representative cross-sections were submitted.

Pathologic Features:

Sections revealed a multi-cystic and partially solid tumor consisting of a mixture of spindle cells and epithelial elements. There were complex, branching papillae (fig5.1) with paucicellular, hyalinized stromal cores (fig 5.2). The epithelial cells were flat, cuboidal, columnar and hobnail in shape (fig 5.3). There was no evidence of blastema, or clear cells (fig 5.4). A small fibroma and multiple cortical cysts were also present.

Differential Diagnosis:

  • Wilms’ tumor and Cystic partially differentiated Nephroblastoma (fig 5.5 and 5.5 bis HE 200X)
  • Cystic nephroma (fig 5.6 HE 200X)
  • Cystic multilocular clear cell renal cell carcinoma
  • Mixed epithelial and stromal tumor
  • Metanephric adenofibroma
  • Congenital mesoblastic nephroma (fig 5.7 HE 200X)

Wilms’ tumor and Cystic partially differentiated nephroblastoma: Wilms’ tumor (Nephroblastoma) is a malignant neoplasm that comprises more than 80% of renal tumor in childhood. It occurs most frequently in children 2 to 4 years old. The tumor is typically composed of a variable mixture of blastema, epithelium, and stroma, although in some tumors only one or two components are present. Rarely Wilms’ tumor may be composed entirely of cysts with delicate septa and are designated cystic partially differentiated nephroblastoma: within the septa are small foci of blastema, immature-appearing stromal cells, and primitive or immature epithelium.

Cystic nephroma: Cystic nephroma is a benign cystic neoplasm composed of epithelial and stromal elements. Typically, this lesion occurs in young adult and has an 8:1 female to male ratio. Cystic nephroma is well-circumscribed, encapsulated, composed entirely of cysts and cyst septa. The cysts are lined by a single layer of flattened, cuboidal, or hobnail epithelium. The fibrous septa are paucicellular or cellular resembling ovarian stroma and may contain clusters of mature tubules.

Cystic multilocular clear cell renal cell carcinoma: Cystic renal cell carcinoma counts for 15% of all renal cell carcinoma. A few clear cell renal cell carcinomas are grossly multilocular and consist mainly of fibrous septa containing small groups of clear cells indistinguishable from grade I clear cell carcinoma. Although this tumor is a variant of clear cell renal cell carcinoma, it has a very low potential for recurrence or metastasis.

Mixed epithelial and stromal tumor: Mixed epithelial and stromal tumor is a complex renal neoplasm composed of a mixture of stromal and epithelial elements. There is a 6:1 predominance of women over men, all have been adults (mean age is perimenopausal). The tumor is typically composed of multiple cysts and solid areas, growing as expansile masses frequently herniating into the renal pelvic cavity. There are structures with complex, branching architecture with formation of papillae. Densely collagenous stroma is common and mitotic figures and atypical nuclei are absent. Surgery has been curative in all cases.

Metanephric adenofibroma: Metanephric adenofibroma is a biphasic neoplasm that occurs in children and young adults. The nodules of epithelium, identical to metanephric adenoma, are embedded in sheets of moderately cellular spindle cells consisting of fibroblast-like cells, usually negative for actin and desmin. Cysts are uncommon and, if present, are only focal findings.

Congenital mesoblastic nephroma: Congenital mesoblastic nephroma is a low-grade fibroblastic sarcoma. It is the predominant renal neoplasm in the first 3 months of life and is uncommon after 6 months. Grossly, the tumor is large, unencapsulated and typically interdigitates with the surrounding kidney. The classic type (24% of cases) is composed of thick interlacing bundles of spindle cells with a low mitotic activity. Entrapment of glomeruli and renal tubules is common. The cellular type (66% of cases) is morphologically identical to infantile fibrosarcoma with a high mitotic rate and a pushing border.

Cysts, hemorrhage, and necrosis may be present. When completely excised, congenital mesoblastic nephroma has an excellent prognosis.

Diagnosis:

Mixed Epithelial and Stromal Tumor of the Kidney

Key Features:

  • Distinctive benign renal neoplasm recently recognized
  • Occurs usually in perimenopausal women; its growth may be influenced by hormones
  • Well-circumscribed, measuring 3 to 12 cm
  • Dimorphic grossly and histologically, characterized by a mixture of epithelial and stromal elements forming cystic and solid areas
  • Its differential diagnosis at the pathologic level is limited (cfr differential dignosis considerations)
  • Stromal cells are positive for vimentin, desmin, actin, estrogen and progesterone receptors; negative for S-100, HMB-45 and CD34
  • Epithelial elements uniformly positive for the cytokeratins, negative for S-100, HMB-45 and CD34
  • Lack of genetic alteration, as found in the congenital mesoblastic nephroma ( ETV6- NTK3 gene fusion)
  • Surgery is curative in all cases

Mixed epithelial and stromal tumor of the kidney was proposed by Michal et al in 1998 as a renal counterpart of pancreatic and biliary cystadenomatous neoplasm. It is a unifying term for adult type cystic nephroma, mesoblastic nephroma, solid and cystic biphasic tumor of the kidney and cystic hamatoma of the pelvis. It occurs almost exclusively in perimenopausal women. Grossly and histologically, the tumor is dimorphic, with solid and cystic areas, consisting of an epithelial component and a spindle cell stroma. The lesion is well-circumscribed, measuring 3 to 12 cm.

Mixed epithelial and stromal tumor can be distinguished from Wilms’ tumor and cystic partially differentiated nephroblastoma by the lack of blastema. The epithelial component of mixed epithelial and stromal tumor rarely forms sheets or glands characteristic of renal cell carcinoma. The spindle cells lack the pleomorphism, cytologic atypia, necrosis, and mitotic figures typical of sarcomatoid renal cell carcinoma.

The smooth muscle component of angiomyolipoma is similar to that of mixed epithelial and stromal tumor, however, glandular elements are rarely seen in angiomyolipoma and possibly are entrapped tubules. Furthermore, characteristic immunoreactivity of angiomyolipoma with HMB-45 is absent in the mixed epithelial and stromal tumor. Similarly, CD34, a sensitive marker of solitary fibrous tumor and S-100, common in tumors with nerve sheath differentiation, are negative in mixed epithelial and stromal tumor.

Mixed epithelial and stromal tumor is easily distinguished from metanephric adenofibroma. The latter occurring in children and young adults; the epithelial component of metanephric adenofibroma having the typical appearance of metanephric adenoma and cysts are rare. The spindle cell component is negative for actin and desmin, while it is positive for actin, desmin, vimentin and less frequently for estrogen and progesterone receptors in mixed epithelial and stromal tumor.

In the past mixed epithelial and stromal tumor was most considered as an adult mesoblastic nephroma. This entity is a rare pediatric renal tumor with a peak incidence in the first 3 months of life. It is a purely mesenchymal tumor in which epithelial structures are not a component of the neoplasm: tubules and glomeruli are encased within the infiltrating spindle cells. Compared to mesoblastic nephroma, no genetic alteration has been found in mixed epithelial and stromal tumor.

There is a controversy about mixed epithelial and stromal tumor and its relationship with cystic nephroma. Some authors suggested that cystic nephroma and mixed epithelial and stromal tumor are two different diseases, others suggested these two tumors as a spectrum of the same entity.

References:

  1. Adsay NV , Eble JN, Srigley JR, et al. Mixed epithelial and stromal tumor of the kidney. Am J Surg Pathol 2000; 24(7): 958-70.
  2. Pierson CR, Schrober MS, Wallis T, et al. Mixed epithelial and stromal tumor of the kidney lacks the genetic alterations of cellular congenital mesoblastic nephroma. Hum Pathol 2001; 32(5): 513-20.
  3. Michal M, Hes O, Bisceglia M, et al. Mixed epithelial and stromal tumors of the kidney. A report of 22 cases. Virchows Arch 2004; 445(4):359-67.