Tumori, 93: 213-216, 2007
PRIMARY OSTEOSARCOMA OF THE KIDNEY WITH RETROPERITONEAL HEMORRHAGE. CASE REPORT AND REVIEW OF THE LITERATURE Tommaso Cioppa1, Daniele Marrelli1, Alessandro Neri1, Valeria Malagnino2, Stefano Caruso1, Enrico Pinto1, and Franco Roviello1 Department of Human Pathology and Oncology, Sections of 1General Surgery and Surgical Oncology, and 2Human Pathology, University of Siena, Siena, Italy
Primary osteosarcoma of the kidney is a very rare neoplasm with a very poor prognosis and unclear histogenesis. Only 20 cases have been reported in the literature. It has a strong tendency to recur locally and spread to distant sites. We present the clinical case of a 79-year-old man affected by a primary osteosarcoma of the kidney presenting with substantial retroperitoneal tumor hemorrhage. Laparotomy revealed a massive retroperitoneal hematoma due to a bleeding large
stony renal mass with multiple bizarre calcifications. The diagnosis of primary renal osteosarcoma was made on the basis of hematoxylin-eosin staining and confirmed by electron microscopy. Hematoma drainage and radical nephrectomy were performed. To our knowledge this is the first case of bleeding renal osteosarcoma reported in the literature. The most important clinical findings, the pathogenesis and the treatment modalities of this rare neoplasm are discussed.
Key words: extraosseous sarcoma, osteosarcoma of the kidney, primary osteosarcoma, renal osteosarcoma.
Introduction
Extraosseous osteogenic sarcoma can occur anywhere in the body, but its location in renal tissue is exceedingly rare: about 20 cases of primary osteosarcoma of the kidney have been reported in the literature. Surgery, chemotherapy and radiotherapy are often palliative treatments for this tumor: the prognosis is very poor and the mean survival time after diagnosis is 18 months1. The exact histogenesis remains unclear and the diagnosis is based on radiological and histological findings. We report the clinical case of a patient affected by this particular neoplasm (the first reported case with acute bleeding) and outline the therapeutic approach with special reference to the current literature. Case report
A 79-year-old man was admitted to our department in October 2002 with a 2-month history of weakness, abdominal and left flank pain, and weight loss. His past medical history was unremarkable: no familiarity for malignant tumors, no hereditary illnesses and no comorbidities. Blood tests were within normal limits except for the serum level of alkaline phosphatase that was higher than normal levels. Serum values of the tumor markers CEA, CA 19-9 and CA 72-4 were under the respective cutoffs. Urinalysis showed microscopic hematuria but the urine was sterile on culture and urine cytology yielded no malignant cells. Cystoscopy did not reveal any abnormalities. Bone scan and skeletal survey were normal
and so was a chest radiograph. On abdominal ultrasonography a large solid lesion of the left kidney with bizarre calcification was found. Abdominal and thoracic CT scan revealed a large mass with irregular calcifications at the site of the left kidney with involvement of the quadratus lumborum and psoas muscles. Three days after admission, the patient was hemodynamically stable on clinical examination but showed a rapid decrease in hemoglobin. There was no hematuria and there was persistent pain in the left flank and hypochondrium. The patient rapidly developed an unexpected hemorrhagic shock: abdominal ultrasonography showed a large retroperitoneal hematoma around the tumor. An emergency laparotomy was performed which revealed a massive retroperitoneal hematoma extending from the left kidney to the pelvic space and a large renal tumor with involvement of perirenal fat and retroperitoneal muscles of the left side. At the upper pole of the kidney a bleeding focus was found. The patient underwent hematoma drainage and radical nephrectomy. Red blood cell transfusions were necessary during the operation. The postoperative course was uneventful and the patient was discharged 9 days later. Macroscopic examination showed an ossified large mass measuring 22 x 16 cm, with extensive involvement of the kidney (Figure 1). Microscopic examination showed atypical cells with the characteristic pattern of classic osteosarcoma: immature neoplastic osteoid and bone formation, and atypical osteoblasts around and within the sarcomatoid stroma (Figure 2). There were multiple large calcifications.
Correspondence to: Prof Franco Roviello, Dipartimento di Chirurgia Generale ed Oncologica, Università di Siena, Viale Bracci 25, Policlinico “Le Scotte”, Primo Lotto, 53100 Siena, Italy. Tel +39-0577-585156; fax +39-0577-233337; e-mail
[email protected] Received July 10, 2006; accepted September 27, 2006.
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Figure 1 - Resected specimen (radical nephrectomy): evidence of multiple large calcifications after opening of the mass with an amputation bone saw.
Figure 3 - Electron microscopy: neoplastic cells are characterized by a dilated and elongated endoplasmic reticulum with abundant proteinaceous material and some of the cells contain aggregates of microfilaments (original magnification X 8900).
volving the psoas muscle, and distant metastases to the left diaphragm, pleura and ribs. The patient died of the recurrence 7 months after primary surgery. Discussion
Figure 2 - Photomicrographs of the surgical specimen: the atypical cells show the characteristic pattern of osteosarcoma consisting of spindle cells with round nuclei in abundant immature sarcomatoid stroma and atypical osteoblasts (H&E X 150).
Immunohistochemical analysis demonstrated in the neoplastic cells a positive reaction for vimentin and a partial reaction for muscle-specific actin. Reactions to desmin and cytokeratin were not seen. Electron microscopy showed spindle and polygonal neoplastic cells in a mixoid stroma with abundant irregular collagen fibers. On electron microscopy the malignant osteoblasts were characterized by abundant dilated cisternae of rough endoplasmic reticulum (Figure 3). On the basis of the histological and electron microscopy findings the neoplasm was diagnosed as a primary osteosarcoma of the kidney with locoregional involvement and no distant metastasis. Thirty days after surgery the patient was submitted to radiation therapy of the tumor bed with a total dose of 50 Gy over 5 weeks. The patient did not undergo adjuvant chemotherapy because of his advanced age. CT scan and bone scan performed 3 months after the operation demonstrated extremely rapid progression of tumor growth with unresectable local recurrence in-
Renal causes of nontraumatic retroperitoneal bleeding are associated with spontaneous rupture of the kidney or rupture of an existing renal lesion. Renal cell carcinoma and angiomyolipoma are the most commonly reported tumors; vascular disease is the next most common cause, whereas infection, nephritis and blood dyscrasia are less common. Spontaneous retroperitoneal hemorrhages are a rare but severe complication of kidney tumors. We describe the first case in the literature of a bleeding renal osteosarcoma causing retroperitoneal hemorrhage. This complication should be taken into consideration in patients affected by this rare tumor when there is substantial blood loss. Like in other cases in the literature, the diagnosis in our case was made on the basis of ultrasonography findings and the patient was submitted to emergency surgery consisting of radical nephrectomy. In the WHO classification osteosarcoma has been recognized as a proliferative process in which the neoplastic cells produce osteoid in sarcomatoid stroma2. Primary osteosarcoma arising in the kidney is an extremely rare disease with about 20 reported cases in the world literature1,3-7. Sarcomas account for approximately 1% of primary renal malignancies in adults, with a prevalence of the leiomyosarcoma type8,9. Renal metastasis of osteogenic sarcoma occurs in up to 13% of primary skeletal osteosarcomas. The exact histogenesis of osteosarcoma of the kidney remains unclear. It was initially assumed that this neo-
PRIMARY OSTEOSARCOMA OF THE KIDNEY WITH RETROPERITONEAL HEMORRHAGE
plasm arose from mesenchymal cells. These cells have the ability to differentiate into fibroblastic, chondroblastic and osteoblastic cells according to Virchow’s theory (1884) about the metaplastic transformation of connective tissue to primitive mesenchyme with the ability to differentiate into osteoblasts10,11. Microscopically, this neoplasm consists of spindle cells and multinucleate tumor cells with diffusely calcified osteoid. Our case, by contrast, showed extensive irregular calcifications with diffuse bone formation and homogeneous ossification. Other cases reported in the literature showed immunohistochemical positivity for vimentin in all cells and positivity for muscle-specific actin in some of the neoplastic cells. A negative reaction to desmin and cytokeratin has also been reported12. Our case presented with an identical immunohistochemical pattern. From the data reported in the literature the male-tofemale ratio in renal osteosarcoma is nearly equal and the tumor occurs more frequently in the sixth to seventh decades of life10. Progressive weight loss, weakness and flank pain with occasionally gross hematuria are often the first symptoms; physical examination frequently reveals a palpable renal mass1,2,4-8,10. Blood tests are often normal except for the serum level of alkaline phosphatase, which may be normal or slightly altered13. Urinalysis may show microscopic hematuria; cystoscopy and urine cytology are often normal12-15. Signs of spaceoccupying lesions, such as organ displacement and hydronephrosis, may be evident at ultrasonography. A characteristic radiological finding is the so-called sunburst appearance within the renal contours on CT scan 13,16 . The differential diagnosis includes adult Wilm’s tumor, metastatic sarcoma, and sarcomatoid renal cell carcinoma12. This neoplasm shows a high propensity for distant metastasis and locoregional involvement of adjacent structures due to early infiltration of the renal capsule. Metastases may be located in the spleen, liver, peri-
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toneal surface, bone marrow, skin and lungs17-20; in our case, at the time of diagnosis, the tumor was mostly organ confined with limited involvement of muscular structures and without evident distant metastasis. Some authors reported homogeneous ossification of primary tumor and metastases; others found that ossification was not necessarily present in distant metastases13. Different forms of treatment have been used for this tumor including surgery, radiotherapy and chemotherapy. The therapeutic approach is aggressive and includes radical nephrectomy, partial resection of adjacent organs in case of tumor involvement, radiation of the tumor bed, and polychemotherapy13,15,18. In our case, considering the relatively locoregional extent of the tumor, the strategy of removing the primary tumor followed by adjuvant radiotherapy to prevent local recurrence was preferred. The role of radiation therapy in extraosseous osteosarcoma is very important despite the marginal utility of this treatment modality in skeletal osteosarcoma. Polychemotherapy can be administered according to the Cooperative Osteosarcoma Study Group (COSS) protocol originally used for neoadjuvant treatment of primary skeletal osteosarcoma in young patients19-22. The response to polychemotherapy can be determined by serial measurements of alkaline phosphatase levels. CT scan is used to detect distant metastases and to assess the possible ossification of the primary neoplastic mass and metastasis22,23. Due to the small number of treated cases reported in the literature, there are insufficient data about the optimal management of this tumor. Polychemotherapy is often employed to slow the evolution of the disease and reduce the frequency of relapses, but has also been used with curative intent. The prognosis of primary renal osteosarcoma is very poor because these tumors are often detected when already at an advanced stage: the mean survival is 8 to 22 months1,10,17. Our case report confirms the unfavorable prognosis of this rare and aggressive tumor.
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