Primary de novo malignant giant cell tumor of kidney: a case report

The gross specimen consisted of a right nephro-ureterectomy, adrenalectomy and fragments of the vena caval tumor thrombus. There was a pale tan tumor mass that measured 7.5 × 7 × 6 cm within the upper pole of the kidney. There was mild dilatation of the pelvicalyceal system towards the upper pole with extension of the tumor onto the mucosal surface of the pelvis. Full-faced slices of the tumor showed the tumor to extend close to the inked margins of the perinephric fat. (Figure 1)

Light microscopic examination with routine hematoxylin and eosin stained slides showed the presence of ovoid plump shaped mononuclear cells interspersed with multinucleated giant cells in a vascularized stroma. Both the stromal and the multinucleated giant cells appeared morphologically to be highly reminiscent of giant cell tumor lesions of bone (Figure 2). The stromal cells consisted of mononuclear round to spindle shaped cells with evidence of mitotic activity and mild cellular atypia. The giant cells had multiple nuclei, often numbering 25 to 40, many of which were ovoid with occasional nucleoli. Mitosis and pleomorphism in the giant cells was not easily observed though apoptotic giant cells were easily observed (Figure 2-inset). Detailed examination with multiple sections revealed no evidence of any associated papillary or sarcomatoid or typical renal cell carcinoma. The tumor infiltrated widely through the hilar region into the pelvis of the kidney and extended as nodules into the adjacent cortex abutting onto the renal capsule and was also present in the adjacent perirenal fat (Figure 3) However, the tumor was limited externally by the Gerota's fascia. Multiple sections of the hilar region showed the presence of tumor metastasis within the hilar lymph nodes (Figure 4) Invasion of the tumor was also observed in the renal vein, vena cava, perirenal fat, lymphatic and perineural space. Invasion to the vena cava presented as a tumor thrombus. Large areas of necrosis and hemorrhage were also seen within the neoplastic lesion. Neither osteoid nor cartilaginous differentiation were demonstrated. Sections of the non-neoplastic areas of the kidney showed mild interstitial lymphocytic infiltrate as a peritumoral response.

Various immuno-histochemical markers were performed with appropriate positive and negative controls. Negative controls were achieved by omission of the primary antibody. The lesional cells showed no expression with low and high molecular weight keratin, pan-cytokeratin there was no expression of CK7, CK20, CK17, P53, BCL2, CD45 and HMB45 either. Anti body staining for S-100 was faintly expressed in some of the lesional cells. However, staining with CD68 antibodies was strongly positive in the multinucleated giant cells (Figure 5). Majority of the stromal mononuclear cell component was highlighted with antibodies to MAC387 (Figure 6). Vimentin also highlighted the same and occasional giant cells. Staining with Ki67 antibodies was over expressed in the lesional cells in keeping with the high proliferative and apoptotic nature of the lesion.

The electron microscopic study was performed on tissue samples obtained from the formalin fixed specimen. Both multinucleated giant cells and the stromal cells were examined in detail. Examination of the giant cells showed the cytoplasm to be filled with numerous vesicles and vacuoles many of which were consistent with primary or secondary lysosomes (Figure 7). Many of the secondary lysosomes typically exhibited a heterogeneous content with some prominent lipid accumulation. Scattered mitochondria and rough endoplasmic reticulum were also identified within these cells. They also contained multiple nuclei of various contours and irregular shapes with occasional one or two prominent nucleoli. Small foot-like projections and cell processes were observed on the surface of these multinucleated giant cells. These projections/processes did not qualify as true microvilli as they lacked the filamentous core rootlet and did not possess any evidence of secretory granules at the base of these pseudorootlets (Figure 8). Examination of the stromal cells showed abundant rough endoplasmic reticulum with dilated cisternae and mitochondria. Simple cell matrix junctions were observed but no true desmosomes were identified (Figure 9). There was no evidence of an external lamina, focal densities, microfilaments, tonofibrils or tonofilaments. Some cells showed the presence of intracytoplasmic accumulation of unusual filaments many of which were in a well-defined curving and somewhat rolled appearance in keeping with vimentin type of intermediate filaments (Figure 10). The extracellular matrix and stroma consisted mainly of filamentous collagen fibres with its distinctive cross-striated pattern.