VOLUME

29

NUMBER

23

AUGUST

10

2011

JOURNAL OF CLINICAL ONCOLOGY

D I A G N O S I S

I N

O N C O L O G Y

Multiple Osteolytic Bone Lesions 3 Years After Ovarian Cancer: Benign or Malignant?
Case Report In September 2009, a 48-year-old Chinese woman of Han ethnicity was examined in our outpatient clinic at The First Afliated Hospital of Soochow University, Suzhou, China, for pain that had developed in her left hip. On review of her medical records, we found that she had developed epithelial ovarian cancer 3 years before and was treated with total abdominal hysterectomy without adjuvant therapy. The patient had an uneventful recovery, although she had a bowel movement only once every 2 to 3 days postoperatively. Two weeks before our examination, she complained of left hip pain and went to see her family doctor. She was managed conservatively with Celebrex (Pzer, New York, NY), but the condition did not improve. She visited her family doctor again 3 days later, and radiographs of the pelvis revealed multiple osteolytic bone lesions in both ilia (Fig 1). The patient was then referred to our orthopedic clinic. A whole-body bone scan and a computed tomography (CT) scan showed the presence of masses in her left ribs and pelvic girdle. These lesions arose from the bone marrow and resulted in thinning of the bone cortex (Figs 2 and 3). Ovarian cancer recurrence with skeletal metastases was suspected, given the presence of multiple skeletal lesions as well as the patients history of epithelial ovarian cancer. However, skeletal involvement alone with no hepatic or lung metastasis is unusual for ovarian cancers. To establish the diagnosis and select an effective and safe regimen, a CT-guided needle aspiration biopsy of the left ilium was performed, but it yielded no denitive diagnosis. An open biopsy was subsequently performed. Clinically, the sample was tannish-gray tissue. Histopathologic examination demonstrated the presence of

Fig 2.

hemorrhage, proliferating broblastic tissue, and scattered, multinucleated, osteoclastic giant cells. It was observed that bone had been replaced by an inltrate of spindle-shaped stromal cells and osteoclastic giant cells. Reactive woven bone was also seen in the brous tissue. Hemosiderin was present in the brous tissue and seemed to make the tissue reddish-brown in color (Figs 4 and 5; hematoxylin and eosin staining). These ndings were characteristics of brown tumors, which are focal skeletal lesions caused by hyperparathyroidism. The levels of tumor markers (CA-125, -fetoprotein, carcinoembryonic antigen) and renal function were normal except for an elevated ferritin level of 310.3 ng/mL. Serum calcium and alkaline phosphate levels were observed to be moderately increased (Table 1). Additional evaluation revealed a signicantly increased parathyroid hormone level of 1,367 pg/mL. These ndings were consistent with the

Fig 1. e672

Fig 3.
Journal of Clinical Oncology, Vol 29, No 23 (August 10), 2011: pp e672-e674

2011 by American Society of Clinical Oncology

Information downloaded from jco.ascopubs.org and provided by at ASCO on August 16, 2011 from 158.232.240.107 Copyright 2011 American Society of Clinical Oncology. All rights reserved.

Diagnosis in Oncology

Table 1. Abnormal Laboratory Test Results of the Patient Presented Variable Hemoglobin, g/L Red cells, millions/ L Calcium, mmol/L Potassium, mmol/L Creatinine, mol/L Alkaline phosphatase, U/L Ferritin, ng/mL Parathyroid hormone, pg/mL For adult patients. On Presentation 90 2.99 3.1 3.2 122.1 192.5 310.3 1367 Reference Range 110-150 3.50-5.00 2.02-2.67 3.50-5.50 44.2-104.0 42-140 13-150 12-72

Fig 4.

diagnosis of hyperparathyroidism. Sonographic examination was performed and a hypoechoic oval lesion was detected, 3 cm in diameter, in the right parathyroid gland. Surgical parathyroidectomy was performed. The specimen was conrmed to be a parathyroid adenoma. The nal diagnosis was brown tumors associated with a primary parathyroid adenoma. Discussion Brown tumors, caused by a reparative cellular process rather than a neoplastic process, manifest as osteitis brosa cystica. This condition is classically seen in patients with primary hyperparathyroidism,1 but is now encountered rarely because of the current use of routine serum chemical tests that allow for early diagnosis of primary hyperparathyroidism. Parathyroid hormone increases bone resorption through increased osteoclast activity.2 The normal marrow contents are replaced by broblastic tissues that simulate a neoplastic lesion. Vitamin D deciency may have a role in the development of skeletal lesions in primary hyperparathyroidism.3 Brown tumors are also common in

patients with secondary hyperparathyroidism caused by chronic renal insufciency.4 Although rare, brown tumors are reported in patients with secondary hyperparathyroidism caused by celiac disease, malabsorption, and hypocalcaemia.5 Epithelial ovarian cancers derive from malignant transformation of the ovarian surface epithelium, which is contiguous with the peritoneal epithelium. Epidemiology suggests that the incidence of epithelial ovarian cancer is lowest in Japan and developing countries.6 Although ovarian cancers usually have a poor prognosis, patients with an early stage of the disease who are treated with surgery alone have a 5-year survival rate of 90% to 95%.7 The common presentation of relapse is an elevated serum CA-125 level with an absence of clinical symptoms and CT scan ndings.8 BRCA1 and BRCA2 genes are important ovarian cancer susceptibility genes. Patients who carry either gene may have an increased risk of breast cancers, melanomas, and prostate, pancreatic, gallbladder, bile duct, or stomach cancers. Serum ferritin is elevated in many malignancies. In some patients, this overall increase in circulating ferritin is also associated with a shift in the composition of ferritin to a more hydrogren-rich species.9 Mechanisms underlying these changes are unclear. Thus far, little is known about whether there is any association between ovarian cancers and parathyroid adenomas. We herein describe a patient with a history of ovarian cancer and subsequent brown tumors of the bone as a result of primary hyperparathyroidism; this patient presented with persistent bone pain and was initially misdiagnosed as having metastatic bone tumors. Although uncommon, brown tumors may mimic metastatic bone disease, especially in patients with a history of cancer. When a monist approach is used in the diagnosis of a tumor, it may be mistaken for metastatic disease on radiographs and bone scans. This is an interesting clinical scenario, illustrating the presence of brown tumors caused by a parathyroid adenoma in a patient with a history of ovarian cancer. Because the treatment and prognosis of metastatic disease and a brown tumor differ greatly, this case highlights the importance of employing multiple clinical tools to evaluate such skeletal lesions.

Jiong Jiong Guo, Wei Liu, Huilin Yang, Haixin Qian, and Tiansi Tang
The First Afliated Hospital of Soochow University, Suzhou, China

Ling Qin
Fig 5. www.jco.org Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China e673

2011 by American Society of Clinical Oncology

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Guo et al

ACKNOWLEDGMENT

We thank Dr Soon Hock Chye, consulting spine and orthopedic surgeon, LohGuanLye Specialists Centre, Penang, Malaysia, for his contributions in the preparation of the manuscript. J. J.G. and W.L. contributed equally to this article.
AUTHORS DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conicts of interest.

REFERENCES
1. Buchanan WW, Kraag GR, Palmer DG, et al: The rst recorded case of osteitis brosa cystica. Can Med Assoc J 124:812-815, 1981 2. Yasuda H, Shima N, Nakagawa N, et al: Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 95:3597-3602, 1998 3. Rao DS, Agarwal G, Talpos GB, et al: Role of vitamin D and calcium nutrition in disease expression and parathyroid tumor growth in primary

hyperparathyroidism: A global perspective. J Bone Miner Res 17:N75-N80, 2002 (suppl 2) 4. Nassar GM, Ayus JC: Images in clinical medicine: Brown tumor in end-stage renal disease. N Engl J Med 341:1652, 1999 5. Demay MB, Rosenthal DI, Deshpande V: Case records of the Massachusetts General Hospital: Case 16-2008 A 46-year-old woman with bone pain. N Engl J Med 358:2266-2274, 2008 6. Hennessy BT, Coleman RL, Markman M: Ovarian cancer. Lancet 374:13711382, 2009 7. Cannistra SA: Cancer of the ovary. N Engl J Med 351:2519-2529, 2004 8. Ozols RF: Recurrent ovarian cancer: Evidence-based treatment. J Clin Oncol 20:1161-1163, 2002 9. Wang W, Knovich MA, Coffman LG, et al: Serum ferritin: Past, present and future. Biochim Biophys Acta 1800:760-769, 2010

DOI: 10.1200/JCO.2011.35.1098; published online ahead of print at www.jco.org on June 13, 2011

e674

2011 by American Society of Clinical Oncology

JOURNAL OF CLINICAL ONCOLOGY

Information downloaded from jco.ascopubs.org and provided by at ASCO on August 16, 2011 from 158.232.240.107 Copyright 2011 American Society of Clinical Oncology. All rights reserved.