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Primary de novo malignant giant cell tumor of kidney: a case report
© Kanthan and Torkian; licensee BioMed Central Ltd. 2004
Received: 10 December 2003
Accepted: 18 June 2004
Published: 18 June 2004
Osteoclast-like giant cell tumors are usually observed in osseous tissue or as tumors of tendon sheath, characterized by the presence of multinucleated giant cells and mononuclear stromal cells. It has been reported in various extraosseous sites including breast, skin, soft tissue, salivary glands, lung, pancreas, female genital tract, thyroid, larynx and heart. However, extraosseus occurrence of such giant cell tumors in the kidney is extremely rare and is usually found in combination with a conventional malignancy. De-novo primary malignant giant cell tumors of the kidney are unusual lesions and to our knowledge this is the second such case.
We report a rare case of extraosseous primary denovo malignant giant cell tumor of the renal parenchyma in a 39-year-old Caucasian female to determine the histogenesis of this neoplasm with a detailed literature review.
Primary denovo malignant giant cell tumor of the kidney is extremely rare. The cellular origin of this tumor is favored to be a pluripotential mesenchymal stromal cell of the mononuclear/phagocytic cellular lineage. Awareness of this neoplasm is important in the pathological interpretation of unusual findings at either fine needle aspiration or frozen section of solid renal masses.
Osteoclast-like giant cell tumors are primarily observed in osseous tissue or as tumors of tendon sheath. As the name implies, this tumor is characterized by the presence of multinucleated giant cells and mononuclear stromal cells. In spite of mitotic activity in the tumor, diagnosis of malignancy is reserved for those cases with bizarre mitoses and cellular atypia or an association with malignant stromal sarcoma . Although metastasis of the tumor is not commonly observed, tumor thrombi occur in up to 5% of the tumors . Occurrences of tumors with osteoclast-like giant cells, have been reported in various extraosseous sites including breast, skin, soft tissue, salivary glands, lung, pancreas, female genital tract, thyroid, larynx and heart [3–12].
Review of published cases of giant cell lesions of the kidney and renal pelvis
Author & Reference
Vimentin+, CD68+, Cytokeratin-ve, CAM 5.2-ve, AE1/AE3-ve
Malignant fibrous histiocytoma (MFH)
Disease free at 1 year
Chen C.H et al. 
Associated sarcomatoid spindle cells with osteoid production (osteosarcoma)
Disease free at 6 months
Lee, C.H et al. 
Keratin & EMA -ve, Focally vimentin+
Clear cell type RCC, sarcomatoid
Disease free at 14 months
Koga, F. et al 
CD68++ Scattered cytokeratin+, S100+
Died 2 months later
Heller, K.N et al. 
CD68+, CAM2.5+, AE1/3+, EMA+, Vimentin+ (Keratin positive)
No associated sarcomatoid component
Disease free at 9 months
Chetty R, Cvijan D 
S100+, CD68+, EMA+; Vimentin+
Liver and lung metastasis in 5 months
Molinie, V. 
Clear cell type RCC and sarcomatoid
el-Naggar, A.K et al. 
Borg-Grech, A. et al. 
Disease free at one month
Kenney, R.M et al. 
Disease free at 1 year
Kimura, K et al. 
SCC of the renal pelvis
Hou, L.T & Willis, R.A 
Tubular and papillary adenocarcinoma
Hou, L.T & Willis, R.A 
In March 2003, a 39-year-old Caucasian female was admitted to the Royal University hospital, Saskatoon, with a large right renal mass. Further investigations showed the presence of a tumor in the right kidney extending into the renal vein and up the vena cava. She underwent a radical right nephro-ureterectomy and partial excision of the vena cava wall was performed as a result of tumor adhesions to the vein. The immediate postoperative course was uneventful and the patient was discharged.
Pathological findings of the resected tissues are as follows:
Neoplasms associated with osteoclast-like giant cells have been reported in various extraosseous epithelial sites [3–12]. Frequently, these neoplasms have been associated with a conventional carcinomatous element. In the kidney this is a rare tumor and majority of the cases reported seem to occur in association with papillary, transitional, clear cell type of renal cell carcinoma or sarcomatoid carcinoma or osteosarcomatous transformation [13–20]. Kimura et al reported the occurrence of a multinucleated giant cell tumor of the renal pelvis that was considered to be primary, de-novo and benign . Heller et al.  were the first to report malignant osteoclast-like giant cell tumor of the kidney without an association with a carcinoma or sarcoma. This case report is the second in this series of de-novo primary malignant giant cell tumor of the kidney not associated with any other conventional renal neoplasm.
The diagnosis of primary malignancy in a giant cell tumor of bone is reserved for those lesions that display bizarre mitoses and cytological atypia or secondary malignancy of a sarcomatous growth in previously documented benign giant cell tumor of bone . Our case was diagnosed as malignant as it exhibited features such as widespread areas of necrosis and hemorrhage; perineural, vascular and angiolymphatic invasion; vena caval tumor thrombus and the presence of tumor metastasis within adjacent hilar lymph nodes.
The cell of origin of this tumor is believed to be from the mesenchymal cell of mononuclear phagocyte cell line [2, 19, 21], although others [13, 14, 17, 20] suggested an epithelial origin. Some authors also felt that these giant cells were non-neoplastic and represented a stromal response to the conventional carcinomatous element [15, 16, 18]. The multinucleated giant cells of the present case showed strongly positive immunoreactivity with CD68, confirming its monohistiocytic origin. CD68 is widely used to identify cells of monohistiocytic origin. The CD68 antigen is a 110 kilo Dalton highly glycosylated transmembrane protein which is mainly located in the lysosomes. The antibody stains macrophages in many human tissues. In addition, the antibody reacts with plasmacytoid T-cells that are present in many reactive lymph nodes, and these are also believed to be of monocyte/macrophage origin. However Chetty et al.  noted that a positive reaction to CD68, a lysosomal marker, can be positive in tumors of diverse histogenesis with a granular cytoplasm and can be misleading. The strongly positive staining of the CD68 exclusively in the giant cells of the present case indicates a monocytic/histiocytic origin of these cells. The co-expression of MAC387, lysozyme, faint expression of S-100 and a strong immunohistochemical expression of vimentin of the stromal cells favors a mesenchymal/histiocytic/monocytic origin of the tumor cells. There was no supporting evidence for an epithelial origin for this lesion despite the use of an extensive immunohistochemical epithelial marker panel.
Ultra structural analysis in the present case also supported a non-epithelial origin of the tumor by the presence of rough endoplasmic reticulum with dilated cisterna and mitochondria, absence of true desmosomes, the most important organelle in the ultrastructural definition of epithelium and also no evidence of external lamina tonofibrils or tonofilaments. These findings are also supported in Kimura's case report of giant cell tumor of the kidney .
Primary denovo malignant giant cell tumor of the kidney is extremely rare. The cellular origin of this tumor is favored to be a pluripotential mesenchymal stromal cell of the mononuclear /phagocytic cellular lineage. Awareness of this neoplasm is important in the pathological interpretation of unusual findings at either fine needle aspiration or frozen section of solid renal masses.
"Written consent was obtained from the patient or their relative for publication of study"
The authors also would like to thank Mr. Todd Reichert, Michelle Hesson and Karen Slattery for their expert technical assistance in the production of the illustrations.
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