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Osseous metaplasia in renal cell carcinoma: Report of a rare case Murugan P, Basu D, Manikandan R, Dorairajan L N, Kumar S - Indian J Pathol Microbiol
Indian Journal of Pathology and Microbiology
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CASE REPORT Table of Contents   
Year : 2008  |  Volume : 51  |  Issue : 3  |  Page : 399-401
Osseous metaplasia in renal cell carcinoma: Report of a rare case


1 Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India
2 Department of Urology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India

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   Abstract  

Focal calcifications are frequently seen in renal masses including renal cell carcinoma (RCC). Osseous metaplasia, on the other hand, is a rare finding in RCC. We report a case of RCC with radiological evidence of speckled calcification that showed osseous metaplasia on histopathological examination. The clinical and pathologic differential diagnosis for this tumor is discussed along with a review of the literature on this unusual phenomenon.

Keywords: Calcification, metaplasia, osseous, renal cell carcinoma

How to cite this article:
Murugan P, Basu D, Manikandan R, Dorairajan L N, Kumar S. Osseous metaplasia in renal cell carcinoma: Report of a rare case. Indian J Pathol Microbiol 2008;51:399-401

How to cite this URL:
Murugan P, Basu D, Manikandan R, Dorairajan L N, Kumar S. Osseous metaplasia in renal cell carcinoma: Report of a rare case. Indian J Pathol Microbiol [serial online] 2008 [cited 2014 Mar 5];51:399-401. Available from: http://www.ijpmonline.org/text.asp?2008/51/3/399/42532



   Introduction   Top


The updated WHO histological classification offers a subdivision of renal cell carcinoma (RCC) by both the morphological and cytogenetic features into clear cell, granular cell, chromophobe cell, papillary, spindle cell and collecting duct carcinoma. [1] Computerized tomography (CT) demonstrates calcification in up to 31% of RCCs, with an increasing incidence of calcification noted with increasing size. [2] In the vast majority, the calcifications are either mottled or punctate. [3] However, reports of osseous metaplasia occurring in RCC are few. [4],[5],[6] We report an interesting case of RCC, which radiologically demonstrated speckled calcification and on histological examination, showed osseous metaplasia within the tumor.


   Case history   Top


A 35-year-old female patient was admitted with complaints of pain in the right loin of 5-month duration. The pain was dull and present throughout the day and was not relieved by analgesics. There was no history of hematuria. She did not have a history of renal calculus disease, tuberculosis, or diabetes. On examination, she was thin built and pale. Abdominal examination revealed tenderness in the right renal angle, but no mass was palpable. Her hemoglobin was 5.4 g/dL with microcytic hypochromic red blood cells; ESR was 10 mm at the end of first hour. Renal function and liver function tests were normal. Urine microscopy did not reveal any red blood cells. Urine culture was sterile.

X-ray of kidney, ureter and bladder showed stippled calcification in the right renal region. Ultrasonography revealed a heterogeneous mass lesion measuring 12 cm × 8.5 cm, involving the upper pole of the right kidney with specks of calcification and cystic areas. The left kidney was normal. CT scan showed a 12 × 9-cm heterogeneously dense enhancing mass lesion, with stippled calcification involving the upper pole of the right kidney with cystic areas suggestive of tumor necrosis [Figure 1]. The tumor was confined to Gerota's fascia. No lymph nodal enlargement was seen in the hilar region.

The patient underwent right radical nephrectomy. On gross examination, the radical right nephrectomy specimen measured 12.5 × 8.7 cm with a nodular bulge in the upper pole. Fascia and capsule could be stripped off completely. Cut section through the kidney showed a well-circumscribed, grey-white, lobulated tumor 8 × 6 cm in diameter, occupying the upper pole. It was soft in consistency with intervening whitish fibrous areas. Multiple tiny cystic spaces could be made out and some areas were gritty to feel and cut through. The tumor did not appear to infiltrate the surrounding normal kidney and was free from the renal sinus and the pelvis. The renal vein and ureter were unremarkable. Adrenal gland, measuring 4 × 1.5 cm, was also identified.

A diagnosis of RCC of the conventional type of Fuhrman grade 2 with a microscopic focus of capsular invasion was made after microscopic examination of multiple sections taken from the tumor. The tumor cells were positive for vimentin, epithelial membrane antigen and cytokeratin. The unique histological feature of this tumor was the presence of extensive areas of osseous metaplasia that were seen closely admixed and in between tumor islands [Figure 2] and [Figure 3].


   Discussion   Top


Calcification has been reported in various renal diseases such as RCC, Wilms' tumor, cystic renal disease, abscess, echinococcal disease, schistosomiasis, tuberculosis, xanthogranulomatous pyelonephritis, arteriovenous malformations and hematoma. [3],[4],[7]

Renal cell carcinoma is associated with calcification in a significant percentage of patients. [7] Through a radiological review of 2709 renal masses, Daniel et al. reported 10.3% cases of RCC with calcified foci. [3] In their study, 2.3% of renal cysts also demonstrated calcification. In the vast majority, the calcifications were either mottled or punctate. CT now demonstrates calcification in up to 31% of RCCs. The incidence of calcification increases with the increase in size of the tumor. [2]

Perez-Ordonez et al. , in their study of 70 cases of renal oncocytoma, reported that calcification in hypocellular and hyalinized areas were relatively common, being present in 31% of cases. [8] This phenomenon appears to be non-specific and most likely represents dystrophic calcification, so often seen in areas of fibrosis in other neoplastic and non-neoplastic processes. Such calcospherites have been reported in renal oncocytoma with prominent papillary architecture, a finding parallel to other papillary neoplasms like that of papillary carcinoma of thyroid. [9]

The unique histological feature of our case was the presence of osseous metaplasia within the tumor. Osseous metaplasia in RCC is a distinctly rare finding. Extensive calcification with osseous metaplasia was described in a 25-year-old female patient with multilocular cystic RCC. [4] Bielsa et al. reported a case of synchronous, bilateral RCC with osseous metaplasia. [6] It has also been reported in cases of chromophobe RCC. [10],[11] Macke et al. described bone formation in sarcomatoid variant of RCC. [12]

In RCC or any tumor for that matter, bone can originate through two different processes: osseous differentiation of the tumor or osseous metaplasia. In the case reported by Macke et al. , [12] the focus of bone formation was morphologically like that of an osteogenic sarcoma in a sarcomatoid RCC, as distinct from the present case and other reports where the ossification was metaplastic and hence benign.

Several hypotheses have been proposed including a metaplastic or reparative response in these tumors or surrounding tissues, the production of bone by tumor cells or the ossification of preexisting mucin or calcified focus. [5] Osseous metaplasia may occur secondary to ischemia, necrosis, or inflammation in the tumor or surrounding tissues.

It has been suggested that RCC with calcification or bony metaplasia tend to be hypovascular and that this may predispose the tumor to ischemia and subsequent metaplasia. [13] Recently, Yamasaki et al. reported involvement of bone morphogenic protein 2, an inducer of osteoblastic differentiation of pluripotential cells, in ossification of RCC. [14]

Osseous metaplasia has been suggested to be a marker for favorable prognosis because there is typically no tumor invasion beyond the gross margin of ossified RCC. [5] However, some reports suggest that it may also be associated with high-grade tumors and poor prognosis. [6]

 
   References   Top

1. Mostofi FK, Davis CJ. Histological typing of kidney tumors. World Health organization International Histological Classification of tumours. 2 nd ed, Berlin: Springer; 1997.  Back to cited text no. 1    
2. Zagoria RJ, Wolfman NT, Karstaedt N, Hinn GC, Dyer RB, Chen YM. CT features of renal cell carcinoma with emphasis on relation to tumor size. Invest Radiol 1990;25:261-6.  Back to cited text no. 2  [PUBMED]  
3. Daniel WW Jr, Hartman GW, Witten DM, Farrow GM, Kelalis PP. Calcified renal masses: A review of ten years experience at the Mayo Clinic. Radiology 1972;103:503-8.  Back to cited text no. 3  [PUBMED]  
4. Bloom TL, Gray Sears CL, Williams TR, Linfesty RL, Amling CL. Multilocular cystic renal cell carcinoma with osseous metaplasia in a 25-year-old woman Urology. 2003;61:462.  Back to cited text no. 4    
5. Cribbs RK, Ishaq M, Arnold M, O'Brien J, Lamb J, Frankel WL. Renal cell carcinoma with massive osseous metaplasia and bone marrow elements. Ann Diagn Pathol 1999;3:294-9.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6. Bielsa O, Loreta J, Arango O, Serrano S, Gilbert-Mas A. Bone metaplasia in a case of bilateral renal cell carcinoma. Urol Int 2001;66:55-6.  Back to cited text no. 6    
7. Patterson J, Briscoe G, Lohr D, Briscoe C, Flanigan RC. Calcified renal masses Urology 1987;29:353-6.  Back to cited text no. 7    
8. Perez-Ordonez B, Hamed G, Campbell S, Erlandson RA, Russo P, Gaudin PB, et al . Renal oncocytoma: A clinicopathologic study of 70 cases. Am J Surg Pathol 1997;21:871-83.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9. Ejeckam G, Tolnai G, Sarkar K, McCaughey WT. Renal oncocytoma: Study of eight cases. Urology 1979;14:186-9.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10. Kuroda N, Liyama T, Moriki T, Shuin T, Enzan H. Chromophobe renal cell carcinoma with focal papillary configuration, nuclear basaloid arrangement and stromal osseous metaplasia containing fatty bone marrow element. Histopathology 2005;46:712-3.  Back to cited text no. 10    
11. Yokozaki H, Ukai R, Kawashita E, Ikeda H, Kuniyasu H, Tahara E. Chromophobe renal cell carcinoma with osseous metaplasia: A case report. Jpn J Clin Oncol 2000;30:101-4.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12. Macke RA, Hussain MB, Imray TJ, Wilson RB, Cohen SM. Osteogenic and sarcomatoid differentiation of a renal cell carcinoma. Cancer1985;56:2452-7.  Back to cited text no. 12  [PUBMED]  
13. Fukuoka T, Honda M, Namiki M, Tada Y, Matsuda M, Sonoda T. Renal cell carcinoma with heterotopic bone formation. Urol Int 1987;42:458-60.  Back to cited text no. 13  [PUBMED]  
14. Yamasaki M, Nomura T, Mimata H, Nomura Y. Involvement of bone morphogenetic protein 2 in ossification of renal cell carcinoma. J Urol 2004;172:475-6.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]

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Correspondence Address:
Debdatta Basu
Department of Pathology, DII/18, JIPMER Campus, Pondicherry - 605 006
India
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PMC citations 1

DOI: 10.4103/0377-4929.42532

PMID: 18723970

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    Figures

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