Clinico-pathological Conference
Date 31/1/2001 @ ISC Conference Room
H2599/2000 Renal Cell Carcinoma

Pathologic findings:

Consists of a partially cut open right kidney with the perirenal fat weighing 350 gm and measuring 10.0x6.0x4.0 cm in dimension. A segment of grossly normal ureter measuring 7.0 cm and the adrenal gland are also included. Complete cut surface shows a yellowish tumour measuring 3.5x3.5 cm at the middle part of the kidney. This had partly bulged onto the renal surface but the capsule appears intact grossly. The renal hilum shows no enlarged nodes or involvement of the renal pelvis.
 

Gross appearance of cut surface. Closer view of tumour.

Sections show a tumour with a rather uniform appearance throughout. It consists of diffuse sheets and nests of malignant epithelial cells with a 'hypernephroid' appearance. These cells form small solid clusters. They have small round nuclei and abundan clear cytoplasm. The tumour stroma is congested and focally haemorrhagic. Several microgranulomata are seen within the tumour, accompanied by foreign body and Langhan's type giant cells. The edge of the tumour also show focal dense chronic inflammatory infiltrate. No vascular invasion is found. Although the renal capsule is stretched very thin by the tumour, the capsule appears intact and there is no perirenal fat infiltration. However a small granuloma is seen in the perirenal fat apparently not associated with tumour tissues. The ureter shows no tumour involvement. The adrenal glands is normal. The perihilar fat shows no lymph node. The residual renal parenchyma shows no further pathology.
 

Figure 1: Capsule area, low power view Figure 2: Capsule area, higher power view. Figure 3: Tumour low power view.
Figure 4: Tumour low power view. Figure 5: Tumour high power view. Figure 6: Granuloma

Pathologic Diagnosis:

Right kidney - Renal cell carcinoma. Renal capsule appears intact. No vascular invasion seen.

Pathologist Comments:

Renal cell carcinoma is a tumour differentiating towards the renal tubular epithelium and is thus a form of adenocarcinoma. It generally arises in the adult or elderly with a slight predilection for male (M:F ratio varing from 2:1 to 3:1). It rarely arises in childhood and in this age group, the tumour need to be carefully distinguished from clear cell sarcoma of the kidney which is a very aggressive tumour. Rare familial cases are associated with the von Hippel-Lindau disease.

Renal cell carcinoma is known for some interesting peculiarities:

  1. occasional regression in the abscence of all treatment
  2. most common 'recipient' of a metastatic tumour e.g. from the lung
  3. para-neoplastic endocrine syndromes (hypercalcemia, hypertension, polycythemia etc)
  4. high tendency for invasion/extension into renal vein, inferior vena cava and even right atrium
  5. Although it commonly metastasize to the lungs and bones, it is also known to metastasize to unusual sites e.g. nasal cavity, oral cavity, larynx, parotid, thyroid, heart and pituitary gland
  6. appearance of metastasis years or decades after removal of the primary tumour
The classical triad of hematuria, flank pain and abdominal mass occurs in only about 9% of patients. Many cases are not discovered until the tumour is large.

Grossly, most tumours are well circumscribed, often protruding as an apparently extrarenal mass. Cut surfaces are typically solid bright yellowish, with haemorrhages, necrosis and myxoid changes resulting in a typical variegated appearance. Some cases are predominantly or entirely cystic and diagnosis can only be confirmed by extensive microscopic examination of the cyst wall.

Tumour cells generally have two appearances: clear cell and granular. The former appearance is due to cytoplasmic accumulation of glycogen and fat and is not due to mucin production. They look like 'vegetable cells'. The tumour is graded based on nuclear features but this is subjective. Other histological types include papillary tumours, chromophobe cell type carcinoma, collecting duct carcinoma and sarcomatoid renal cell carcinoma. The significance of the granulomas in this patient is unknown. It is possibly related to some products or proteins produced by the tumour cells.

The tumour cells expresses various epithelial markers, and in addition, vimentin. A host of other enzymes, proteins and hormones had also been detected, possibly related to the fact that they differentiate in the direction of proximal renal tubular cells. Non-papillary types of tumours often have terminal deletion of the short arm of chromosome 3.

Prognostic factors:

  1. Distant metastasis occurs in 1/3 cases at diagnosis. Single most important parameter.
  2. Tumour size: Not useful except for tumours less than 3 cm or more than 12 cm
  3. Invasion of renal vein now thought to have little adverse effect on prognosis except in high grade cases.
  4. DNA ploidy correlate with nuclear grading
  5. Flow cytometry: S-phase fraction correlate with prognosis.
  6. p53 overexpression associated with metastatic disease.
Staging and survical rates:
 
Stage Description 5-year survival
Stage I Confined to the kidney. 60-80%
Stage II Extension to perirenal fat but within Gerota's fascia 40-70%
Stage III Renal vein or vena caval involvement, or regional lymph node metastases 10-40%
Stage IV Extension to adjacent organs other than adrenal, or distant metastases <5%

Reference:

  1. Ackerman's Surgical Pathology, Eight Edition 1996, 01145-1153.