Primary Renal Osteosarcoma

AJCP / Case Report

Primary Renal Osteosarcoma Antonio Lopez-Beltran, MD, PhD,1 Rodolfo Montironi, MD, FRCPath, IFCAP,2 Jose L. Carazo, MD,3 Alfredo Vidal, MD, PhD,1 and Liang Cheng, MD4 From the 1Department of Pathology and Surgery, Cordoba University Medical School, Cordoba, Spain, and Fundação Champalimaud, Lisbon, Portugal; 2Institute of Pathological Anatomy and Histopathology, Polytechnic University of the Marche Region, Ancona, Italy; 3Urology Service, Reina Sofia University Hospital, Cordoba, Spain; and 4 Departments of Pathology and Laboratory Medicine and Urology, Indiana University School of Medicine, Indianapolis. Key Words: Kidney; Osteosarcoma; Primary renal sarcoma; Osteogenic sarcoma; Soft tissue tumor Am J Clin Pathol May 2014;141:747-752 DOI: 10.1309/AJCPM86FVHAMWJSR

Objectives: To investigate primary osteosarcoma (osteogenic sarcoma) of the kidney, a rare and aggressive neoplasm. Methods: We present clinical and pathologic features of three female patients, aged 50, 66, and 78 years, affected by primary osteosarcoma of the kidney. The diagnosis was made by H&E-stained samples from totally (cases 1 and 2) or partially (case 3) embedded tumors. Results: Reported cases showed histologic features of low-grade (n = 1), chondroblastic (n = 1), and osteoblastic (n = 1) osteosarcoma. Tumor size ranged from 3 to 7 cm, and pT category was pT1a (n = 1), pT1b (n = 1), and pT3a (n = 1). Immunohistochemistry gave focal positive results with PAX2 and CD10 in case 1 and S100 in case 2. On follow-up, two patients were disease free at 25 and 68 months and one died of metastases. Conclusions: Surgically treated primary renal osteosarcoma might not be as aggressive as previously thought if diagnosed early with low pT status.

Extraosseous osteogenic sarcoma can occur anywhere in the body, but its location in renal tissue is exceedingly rare.1-20 Twenty-four cases of primary osteosarcoma of the kidney have been reported in the literature.1-20 Most frequently, these tumors are stage III or IV at diagnosis.18-20 Surgery, chemotherapy, and radiotherapy are often palliative treatments for this tumor, and the prognosis is poor.21-24 The exact histogenesis remains unclear, and the diagnosis is based on radiologic and histologic findings.18-20,25 We report on the clinical and pathologic features of three additional cases of primary renal osteosarcoma: two patients with stage I carcinoma with no evidence of disease at 25 and 68 months and one patient with stage IV carcinoma who died of disease 14 months after surgery. We hypothesized that if early diagnosis is performed, resulting in a low-stage tumor, primary osteosarcoma of the kidney might not be as aggressive as reported in the current literature.

Materials and Methods The study was approved by the Institutional Review Board of the University of Cordoba. Clinical Findings Case 1 A 50-year-old woman was admitted with pelvic and back pain in April 2007. X-ray showed a calcified mass in the left kidney. A computed tomography (CT) scan displayed a calcified 5.5 × 4.9-cm mass thought to be a calcified renal cell carcinoma or tuberculosis. Gammagraphy showed no bone lesion or metastasis. The patient did not receive treatment for osteoporosis. A laparoscopic radical nephrectomy was performed subsequently. Histologic assessment included 57

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ABSTRACT

Lopez-Beltran et al / Osteosarcoma of the Kidney

sections with total embedding of tumor specimen. Randomly selected nonneoplastic areas, including the renal pelvis, were sampled and submitted for pathologic evaluation. Pathologic review of the specimen rendered the diagnosis of low-grade primary renal osteosarcoma. The patient has followed up every year since treatment at urology and medical oncology clinics and remained free of disease as of June 2013 at the most recent review.

Case 3 A 78-year-old woman was admitted with flank pain and intermittent macroscopic hematuria. A CT scan displayed a calcified neoplasm measuring 7 × 6 × 5.1 cm. The patient did not receive treatment for osteoporosis. Radical left nephrectomy was performed. Histologic assessment included 31 sections with partial embedding of tumor specimen. Randomly selected nonneoplastic areas, including the renal pelvis, were sampled and submitted for pathologic evaluation. Pathologic review of the specimen rendered the diagnosis of high-grade primary renal osteosarcoma, osteoblastic type. On follow-up, lung and brain metastases were detected a year later. The patient died of disease 2 months after the appearance of the metastases. Immunohistochemistry Immunohistochemical studies were conducted on decalcified, 5-µm-thick, formalin-fixed, paraffin-embedded tissue sections using prediluted antibodies (Dako, Carpinteria, CA). Appropriate negative and positive controls were used for each immunostain.

Results Histopathologic and Immunohistochemical Findings Case 1 Macroscopic examination showed an organ-confined calcified mass measuring 5 × 4 cm. The tumor was gray-white with a firm and gritty texture ❚Image 1❚. 748 748

Am J Clin Pathol 2014;141:747-752 DOI: 10.1309/AJCPM86FVHAMWJSR

Case 2 Macroscopic examination showed an organ-confined calcified mass measuring 3.5 × 3.2 × 3.2 cm. The tumor was gray-white with a firm texture ❚Image 2❚. Microscopic examination showed a moderately cellular tumor producing mineralized neoplastic bone intimately associated with the tumor cells. Neoplastic high-grade hyaline cartilage was present. The neoplastic cells displaying a chondrocytic phenotype demonstrated severe cytologic atypia and resided in lacunar spaces in a hyaline matrix. No necrosis was present. Despite extensive sampling of the tumor, definite epithelial malignancy could not be identified. Immunostains for cytokeratin AE1/AE3 (–), p63 (–), high-molecular-weight cytokeratin (–), S100 protein (+), and PAX2 (–) gave appropriate results. On the basis of the histologic findings, the neoplasm was diagnosed as pT1aN0M0 high-grade chondroblastic primary osteosarcoma of the kidney. Case 3 Macroscopic examination showed a partly calcified tumor mass measuring 7 × 6 × 5.1 cm. The cut surface presented a firm whitish tumor with necrotic and hemorrhagic areas. The tumor was mainly cortical with extension to the perinephric fat tissue and hilar adipose tissue. Microscopic examination showed a highly cellular tumor producing eosinophilic unmineralized neoplastic osteoid and bone intimately associated with variably pleomorphic tumor cells, intermingled with lacelike to compact trabeculae. Despite extensive sampling of the tumor, definite epithelial malignancy could not be identified. Immunohistochemistry was not performed in this case. On the basis of the histologic findings, the neoplasm was diagnosed as pT3aN0M1 highgrade osteoblastic primary osteosarcoma of the kidney. © American Society for Clinical Pathology

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Case 2 A 66-year-old woman was admitted with back pain in December 2011. X-ray showed a 3.5 × 3.2 × 3.2-cm calcified tumor that was followed by left radical nephrectomy. The patient did not receive treatment for osteoporosis. Histologic assessment included 23 sections with total embedding of tumor specimen. Randomly selected nonneoplastic areas, including the renal pelvis, were sampled and submitted for pathologic evaluation. Pathologic review of the specimen rendered the diagnosis of primary high-grade renal osteosarcoma, chondroblastic type. CT–positron emission tomography showed no evidence of disease. Last follow-up was in March 2013. The patient has remained well and disease free.

Microscopic examination showed a hypocellular to moderately cellular fibroblastic proliferation with variable amounts of osteoid production. Moderate to heavy amounts of bone along longitudinal mineralized trabeculae, suggesting lamellar-like bone, were present. The spindle-shaped tumor cells were arranged in fascicles or interlacing bundles that permeated surrounding cortical and/or cancellous-like bone. The cells had a somewhat epithelioid appearance, with minimal cytologic atypia and few mitotic figures (