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Histology of kidney cancer

The diagnostic material from renal tumors, are needle biopsies or operation specimens (nephrectomy or resections). When pathologists report on an operation specimen detailed information must be included, such as tumor size, whether the os cystic, solid, necrotic or with bleeding, and relation to normal renal tissue as well as resection borders.

When the kidney with surrounding fat and adrenal gland are removed, the pathologist must also describe the tumor relation to the capsule (Gerota's fascia), adrenal gland, renal tissue, and lymph nodes if present. It is important for the pathologist to study many microscopic sections in order to correctly classify the tumor and determine whether it is benign or malignant. A correct classification of the tumor is necessary to determine treatment and follow-up.

Standard histological investigation is usually sufficient to determine the tumor type, although it may sometimes be necessary to confirm the diagnosis using immunohistochemistry and/or cytogenetic studies. At present, molecular studies are not considered mandatory in diagnostic workup.

Most renal tumors are derived from renal tubules and most of them are malignant.

Benign tumors

Benign renal cyst

Some renal cysts can be malignant. Based on CT images, the cysts are categorized into the Bosniak categories from 1-4. For category 4, the cyst is most likely malignant. For categories 3 and 4, surgery is recommended. 

Papillary adenomas

Papillary adenomas are the most frequent benign tumors and are found in 10-40% of all adults in autopsy material. When these tumors exceed 5 or more in diameter, they should be classified as malignant. Cytogenetic studies have shown loss of chromosome Y or three copies of chromosome 7 and 17.

Oncocytomas

Oncocytomas constitute 3–5% of kidney tumors in adults. They are most often discovered during X-ray for other conditions. Oncocytomas are well-defined with solid, light brown surfaces. There may be scar tissue and bleeding. They can be multiple centimeters in size, and in 5-6%, multiple tumors occur in one or both kidneys. Cytogenetic examinations have shown that these are often a blend of normal and abnormal karyotype. Translocation of t(5;11)(q35;q13) and loss of chromosome Y,1 and 11 are known.

Kidney specimen with oncocytoma. Click to enlarge. Photomicrograph of oncocytoma. Click to enlarge. Kidney specimen with cystic nephroma. Click to enlarge.

Other types

Metanephric adenoma and mesenchymal tumors that derive from renal support tissue such as leiomyoma and angiomyolipoma are less common. There are also benign mixed tumors having both epithelial and mesenchymal components.

Malignant tumors

Renal cell carcinomas

Renal cell carcinomas are classified into subgroups based on photomicroscopic and cytogenetic findings (chromosomal deviations). 

Clear cell renal cell carcinoma

Renal cell carcinoma of the clear cell type is the most common and makes up 75% of malignant renal tumors. Cytogenetic investigations have shown multiple chromosomal deviations, but the most common is a deletion of the short arm of chromosome 3 causing mutation in the VHL gene. The prognosis depends on the stage. Tumors less than 7 cm confined to the renal capsule have a good prognosis if found in stage I. Five year survival is 90%. Tumors involving Gerota's fascia or lymph nodes have a very poor prognosis (stage IV, 5 year survival is 10-20%).

Kidney specimen with clear cell carcinoma. Click to enlarge. Photomicrograph of clear cell renal cell carcinoma. Click to enlarge.

Papillary renal cell carcinoma

This subgroup makes up around 15% and is separted into type I or type II based on photomicroscopic findings. They have a better prognosis than clear cell renal cell carcinoma, but poorer than chromophobe type I tumors. Cytogenetic examinations have shown specific chromosomal deviations (trisomo/tertrasomo 7, trisomo 17 and loss of chromosome Y) with associated mutation in c-Met and FH genes.

Photomicrograph of papillary renal cell carcinoma. Click to enlarge. Kidney specimen with chromophobe renal cell carcinoma. Click to enlarge. Photomicrograph of chromophobe renal cell carcinoma. Click to enlarge.

Chromophobe renal cell carcinoma

Chromophobe renal cell carcinoma makes up 5% and also has a good prognosis with 5 year survival greater than 90%. Cytogenetic examinations have shown loss of a series of chromosomes (Y, 1, 6, 10, 13, 17 and 21) leading to hypodiploid tumors and mutation in the BHD gene. 

Other types

  • About 7% of renal cell carcinomas cannnot be further classified.
  • About 1% of renal cell carcinomas are derived from rare variants which are either very agressive (collecting duct renal cell carcinoma and medullary renal cell carcinoma) or have a very good prognosis (mucinous, tubular, and spool cell renal cell carcinoma).
  • Malignant tumors originating from support tissue are known as sarcomas (for example leiomyosarcoma originating from muscle tissue and angiosarcoma from vascular tissue). 
  • In children, malignant tumors such as Wilms tumor (nephroblastoma) can occur, or tumors associated with hereditary syndromes.

Grading

A special grading system is used for renal cell carcinoma known as Fuhrman, named after an American pathologist who developed the criteria in 1982. She and others have shown that this grading system has prognostic value, even if reproducibility among pathologists and individual pathologists is low. Only clear cell and papillary renal cell carcinomas are graded according to Fuhrman. The rest are not graded. Fuhrman's grading system is from I–IV based on nuclear morphology (size of nucleus, pleomorphology, and size of nucleolus). The low-grade renal cell carcinomas (Fuhrman grade I–II) have good prognoses compared to the more high-grade renal cell carcinomas (Fuhrman grad III–IV). If sarcomatoid differentiation is observed in renal cell carcinomas, they should be classified ast Fuhrman grade IV. All variations of renal cell carcinomas can have sarcomatoid differentiation, which have very poor prognoses. 

Clear cell renal cell carcinoma, Fuhrman grade I. Click to enlarge. Clear cell renal cell carcinoma, Fuhrman grade II. Click to enlarge. Clear cell renal cell carcinoma, Fuhrman grade III. Click to enlarge.

  

Clear cell renal cell carcinoma,
Fuhrman grade IV. Click to enlarge.
Renal cell carcinoma with sarcomatoid differentiation, Fuhrman grade IV. Click to enlarge.

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