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Importance of Biopsy of New Bone Lesions in Patients with Previous Carcinoma

Clayer, Mark, MD, MBBS; Duncan, William, MBBS

Clinical Orthopaedics and Related Research®: October 2006 - Volume 451 - Issue - p 208-211
doi: 10.1097/01.blo.0000229296.52216.77

Development of destructive bone lesions in a patient with a history of visceral carcinoma may be assumed to be meta-static disease. However, this assumption may lead to inappropriate treatment. We prospectively enrolled 50 patients (54 previous malignancies) from the South Australian Musculoskeletal Tumour Service with new metastases to bone after a previous diagnosis of localized visceral carcinoma. We performed biopsies on the new lesions and reviewed the patients' histories. The most common diagnosis was breast carcinoma (24 patients), followed by prostate (11 patients) carcinoma. The mean time between the first primary malignancy and the development of a bony lesion was 84 months (range, 30-83 years). The longest latency was with breast carcinoma and the shortest was with lung carcinoma. The bone abnormality was a new tumor in nine patients (15%), necrotic tissue in two patients, and normal tissue in one patient. A new tumor was most likely in patients with breast carcinoma (five patients) or prostate carcinoma (three patients). The bone lesion was always the same malignancy in patients with a history of renal or lung carcinoma. Failure to do a biopsy would have resulted in serious treatment errors in two of the three patients who had new tumors develop. We recommend performing biopsies for new bone lesions, especially if breast carcinoma was the previous primary malignancy.

Level of Evidence: Therapeutic study, Level II (prospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.

From the Department of Orthopaedics and Trauma, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Received: December 27, 2004

Revised: May 24, 2005; October 20, 2005; November 13, 2005; May 18, 2006

Accepted: June 5, 2006

Each author certifies that he has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that the institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research but the institution waived approval for informed consent.

Correspondence to: Mark Clayer, MD, MBBS, Department of Orthopaedic Surgery and Trauma, Royal Adelaide Hospital, Frome Road, Adelaide 5000, South Australia, Australia. Phone: 61-8-8222-5584; Fax: 61-8-8271-2490; E-mail:

The advent of systemic treatment for carcinoma has resulted in longer survival rates.1 As a result, metastatic disease is becoming more common as patients are living longer with disease.1 Bone is a common site for the development of metastasis, especially after breast carcinoma. Assuming the development of a new lesion in bone indicates metastatic disease has little basis in fact. Although metastasis to bone has been reported in as much as 85% of patients with breast carcinoma,1,14 not all bone lesions after carcinoma are metastatic carcinoma. The ramifications of this assumption may result in under-treatment or over-treatment. However, it is not known how often a new lesion reflects a new diagnosis rather than metastasis from the earlier malignancy, or how often it alters the treatment plan.

We hypothesized that the development of a bone lesion after a previous visceral carcinoma always represents the development of metastatic disease from the original carcinoma and no new tumors occur. We also hypothesized that there would be no difference in the risk of a new tumor developing on the basis of the original malignancy, and treatment would not be affected adversely by not performing a biopsy.

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We prospectively enrolled 50 patients (54 malignancies) from the South Australian Musculoskeletal Tumour Service. This service provides treatment for patients from Central Australia with musculoskeletal tumors-a population of approximately 1.5 million people. All patients were tertiary referrals to our subspecialty unit. All patients had at least one plain radiograph that showed a bone lesion and had a history of localized carcinoma before referral. The bone lesion was the first indication that metastatic disease may have developed. The lesions occurred in some patients who were having routine surveillance after treatment of a localized carcinoma, but most were identified after investigating some symptom. All patients with a questionable finding on routine radiographs and a history of carcinoma were included in the study. The 50 patients had 54 previous carcinomas (Tables 1 and 2), the most common carcinoma being breast carcinoma (24 patients), prostate carcinoma (11 patients), renal carcinoma (six patients), and lung carcinoma (five patients). One patient had a history of three different carcinomas (breast, ovarian, and cervical), and another patient had two different carcinomas (prostate and lung). We performed technetium-labeled methylene diphosphonate bone scanning on all patients ideally before biopsy to determine if a more easily accessible lesion existed, however, owing to institutional constraints, the scan often was obtained after the biopsy despite an attempt to perform it before the biopsy. There were no exclusions or withdrawals.





All lesions were within bone, soft tissue extension was rare, and needle biopsies were deemed unsuitable. After obtaining appropriate consent, the patients had a biopsy under general anesthesia. The preferred approach of the senior surgeon (MC) was an open biopsy through a small incision, with attention to planned definitive surgical treatment, using a 4-mm trephine under image-intensifier guidance. After a unicortical drill hole was made using a 4.5-mm drill bit, the trephine was passed three times in different directions through the single cortical drill hole to produce three cores for histologic review. This was advantageous by providing an adequate amount of tumor tissue to allow various immunohistochemical techniques. It also allowed direct control of hemostasis and packing of the defect with Gelfoam® (Pharmacia & Upjohn, Kalamazoo) to reduce the risk of a hematoma after the biopsy. The specimens were reviewed by an assigned pathologist who compared the previous carcinoma with the original histologic section when possible.

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The mean length of time between the original carcinoma and the development of a bone lesion was 84 months (range, 1-361 months). The latency between the original carcinoma and the development of a bone lesion was longest for breast carcinoma at 113 months (range, 5-276 months) and the shortest was for lung carcinoma at 10 months (range, 1-31 months).

The data refuted our first hypothesis: among the 50 patients, a new tumor was identified in the bone in 9, and no tumor was identified in the remaining patient (Table 2). The new tumors included nonHodgkin's lymphoma (two patients), lung carcinoma (two patients), and myeloma (two patients), and (one each) chondrosarcoma, renal carcinoma, and Langerhan's cell histiocytosis. Normal bone was found in one patient, and the specimens were too necrotic for definitive diagnosis to be made in two patients. In this situation, we assumed the lesion was the same as the original condition.

The data also refuted our second hypothesis as a history of prostate carcinoma was most likely to produce a new diagnosis; treatment was changed in nine patients based on the new diagnosis. Four of the 11 patients with previous prostate carcinoma did not have metastatic prostate carcinoma. In these four patients, lung carcinoma (two patients) and renal carcinoma (one patient) were the new diagnoses of malignancy. In one patient, the radiographic abnormality was normal bone. The planned treatment was hormonal therapy for presumed metastatic prostate carcinoma. The treatment was revised in four patients after the biopsy results. Twenty-four patients had a history of breast carcinoma (Tables 1 and 2). Four patients had a new tumor presenting as a bone metastasis (Table 2). Four were new malignancies: nonHodgkin's lymphoma (two patients), myeloma (two patients), chondrosarcoma (one patient), and a benign lesion (Langerhan's cell histiocytosis) (one patient). The planned treatments were radiation and cytotoxic chemotherapy. Three patients had radiation therapy but the chemotherapeutic regimen was changed substantially to treat the myeloproliferative malignancy. The patient with Langerhan's cell histiocytosis received no treatment and the lesion resolved spontaneously. One patient with a history of melanoma had a new lesion develop, and one patient with a history of ovarian carcinoma and cervical carcinoma had a new lesion of nonHodgkin's lymphoma develop.

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Bone is the third most common site for distant metastasis by adenocarcinomas.1 Carcinomas known to metastasize to bone include breast, lung, and prostate carcinoma.2 Breast, lung, prostate, renal, and thyroid carcinomas comprise more than 85% of the bone metastases found by radionuclide scans in patients with primary adenocarcinomas.14 However, current therapy has improved the mean survival and quality of life of patients with metastatic disease.2-7,9,13

We reviewed a consecutive series of patients with bony lesions and histories of localized carcinomas. The main limitation is the risk that this group is not truly representative. Although this institution is the main tertiary referral center, there are other institutions that may have treated patients with bone lesions. Therefore, a 100% referral rate is not guaranteed. It is reasonable to assume numerous patients were diagnosed elsewhere but have not presented to our center. However, the number of patients most likely is low.

The risk of a patient presenting with an apparent solitary bone metastasis from a known primary carcinoma but actually presenting with a second primary has been suggested,8,10 however, the actual incidence has not been reported. Bone scans are an unreliable indicator of meta-static disease. McNeil11 reported 45% of abnormal bone scans in patients with a history of carcinoma did not reflect bone metastasis, but rather trauma (25%), infection (10%), and other causes (10%) as the etiology of the abnormality. The assumption that a new bone lesion represents the development of metastatic disease may result in unnecessary or inadequate treatment. Twenty percent of our patients presenting with a bone lesion had a different diagnosis from the original carcinoma. This was more likely after prostate or breast carcinoma. Our data also suggest failing to confirm the tissue diagnosis via biopsy may result in inadequate treatment.

Our findings suggest restaging is important after the development of a new lesion, and we recommend biopsies be done in all patients who present with a new lesion in bone. Our findings did not support the assumption that the new lesions were metastases.

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