Skeletal Radiol DOI 10.1007/s00256-013-1785-2
CASE REPORT
Giant cell tumor of bone with secondary aneurysmal bone cyst-like change producing β-human chorionic gonadotropin Valerie A. Fitzhugh & Gordana Katava & Cornelia Wenokor & Natalie Roche & Kathleen S. Beebe
Received: 20 August 2013 / Revised: 9 November 2013 / Accepted: 12 November 2013 # ISS 2013
Abstract Giant cell tumor of bone is a benign, locally aggressive neoplasm that is composed of sheets of neoplastic mononuclear cells interspersed amongst non-neoplastic, uniformly distributed, osteoclast-like giant cells. They represent approximately 4–5 % of primary bone tumors. Rarely, bone tumors have been noted to produce human chorionic gonadotropin, a finding most often reported in osteosarcoma. We present the case of a young woman who presented with a lowlevel human chorionic gonadotropin level which, after resection of her recurrent giant cell tumor of bone with secondary aneurysmal bone cyst-like change, became undetectable in her blood. Furthermore, cells within the aneurysmal bone cyst component were immunohistochemically positive for βhuman chorionic gonadotropin. This is the first report of such a finding in the literature. Keywords Giant cell tumor of bone . β-human chorionic gonadotropin . Aneurysmal bone cyst . Neoplasm
V. A. Fitzhugh (*) : G. Katava Department of Pathology and Laboratory Medicine, Rutgers, the State University of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA e-mail: [email protected] C. Wenokor Department of Radiology, Rutgers, the State University of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA N. Roche Department of Obstetrics, Gynecology, and Women’s Health, Rutgers, the State University of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA K. S. Beebe Department of Orthopaedics, Rutgers, the State University of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA
Introduction Giant cell tumor of bone is a benign neoplasm of bone that consists of neoplastic mononuclear cells that are surrounded by a large population of non-neoplastic osteoclast-like giant cells. These tumors represent approximately 4–5 % of all primary tumors of bone [1]. They can be locally aggressive, as they can recur. Aneurysmal bone cyst-like areas are identified as a secondary feature in approximately 10–14 % of giant cell tumors [1, 2]. β-Human chorionic gonadotropin (hCG) is a glycoprotein hormone secreted by the syncytiotrophoblasts of the developing placenta. β-hCG is also seen in several different germ cell tumors [3]. Increased serum levels of β-hCG as a paraneoplastic syndrome have been described most commonly in several case reports of osteosarcoma [3–6]. We present a case of a young woman whose recurrent giant cell tumor of bone with secondary aneurysmal bone cyst-like change caused an increase in serum β-hCG, which returned to undetectable levels after resection of the lesion.
Case report The patient was a 17-year-old female who first presented to the orthopedic clinic in August of 2011 with a 1-month history of left knee pain. No history of trauma was noted. Her past medical history was significant only for a seizure disorder, which was being managed by divalproex sodium. Physical examination was remarkable for mild tenderness to palpation along the lateral aspect of the left femur with pain at the end of the 1–130° range of motion exam. Radiographs and a computed tomography (CT) scan (Fig. 1) were performed, demonstrating a 6.5×4.6×4-cm expansile, eccentric, lytic lesion of the distal femur involving the metaphysis and extending into the epiphysis, which
Skeletal Radiol
Fig. 1 Radiograph (a), coronal (b), and sagittal (c) computed tomography scans prior to the first surgery demonstrating a large expansile, lytic mass of the distal femur
appeared closed. The lesion was felt to most likely represent a giant cell tumor of bone radiographically. The patient underwent biopsy of the lesion followed by resection curettage and cementation. The resected specimen was a giant cell tumor of bone with focal changes suggestive of aneurysmal bone cyst. Following the surgery, the patient underwent a 3-month course of physical therapy after which she continued to complain of pain. A radiograph to assess for evidence of local recurrence was ordered. The radiograph was remarkable for a lucent zone identified between the cement–bone interface in the distal femoral metadiaphyseal region. Furthermore, there was cortical thinning present, which was suspicious for tumor recurrence. A CT scan followed and demonstrated an area of lucency around the cement mantle measuring 9×3.5 cm Additionally, a soft tissue mass was also identified (Fig. 2). This finding was consistent with tumor recurrence. The patient underwent a routine preoperative urine pregnancy test which was positive. A follow-up quantitative βhCG level of 11 mIU/ml (normal value 0 mIU/ml) was reported. A follow-up β-hCG performed 2 days later remained at 11 mIU/ml. A final β-hCG performed 1 week later was 9 mIU/ml. The patient was referred to gynecology. The patient’s past gynecologic history was unremarkable. The gynecologic physical exam was normal. The general physical exam was within normal limits with the exception of pain about the left
knee. The gynecologist recommended that orthopedics proceed with the tumor resection. Biopsy confirming giant cell tumor recurrence followed by extensive resection and distal femoral replacement was performed. Histologically, the tumor consisted of numerous giant cells with 10s to 100s of nuclei with interspersed mononuclear cells similar in appearance to those within the giant cells (Fig. 3). Additionally, there was a second component that demonstrated cavernous spaces. The walls of the spaces lacked an endothelial lining and contained fibroblastic spindle cells, multinucleate giant cells, and thin strands of remodeling bone (Fig. 4). Each of the submitted sections was carefully screened for anaplasia, increased mitotic activity, and heterologous tissue foci. Anaplasia was not identified. Mitotic activity was limited to one mitosis per ten high-power fields; this was confirmed by immunohistochemical staining with Ki-67, which demonstrated a proliferative index of 10 %. No heterologous elements were identified in either the giant cell tumor foci or the aneurysmal bone cyst foci. Additionally, immunohistochemistry for β-hCG was performed, and showed positive staining, predominately in the areas of aneurysmal bone cyst (Fig. 5). The case was diagnosed as a recurrent giant cell tumor of bone with secondary aneurysmal bone cyst and focal β-hCG positivity. β-hCG immunohistochemistry was subsequently performed on the patient’s original tumor and it also demonstrated positive staining predominately in the
Fig. 2 Radiograph (a), coronal (b), and sagittal (c) computed tomography scans prior to the second surgery demonstrating an area of lucency around the cement mantle and extension into the soft tissue, consistent with tumor recurrence
Skeletal Radiol
Fig. 3 Histology of the resected lesion demonstrating mononuclear cells (thin arrows) interspersed between giant cells (thick arrows), diagnostic of giant cell tumor of bone (hematoxylin and eosin stain, 200×)
Fig. 5 β-hCG immunohistochemistry demonstrating focal positivity (arrows) (β-hCG, 200×)
aneurysmal bone cyst component. After surgery, the patient’s β-hCG level returned to
CASE REPORT
Giant cell tumor of bone with secondary aneurysmal bone cyst-like change producing β-human chorionic gonadotropin Valerie A. Fitzhugh & Gordana Katava & Cornelia Wenokor & Natalie Roche & Kathleen S. Beebe
Received: 20 August 2013 / Revised: 9 November 2013 / Accepted: 12 November 2013 # ISS 2013
Abstract Giant cell tumor of bone is a benign, locally aggressive neoplasm that is composed of sheets of neoplastic mononuclear cells interspersed amongst non-neoplastic, uniformly distributed, osteoclast-like giant cells. They represent approximately 4–5 % of primary bone tumors. Rarely, bone tumors have been noted to produce human chorionic gonadotropin, a finding most often reported in osteosarcoma. We present the case of a young woman who presented with a lowlevel human chorionic gonadotropin level which, after resection of her recurrent giant cell tumor of bone with secondary aneurysmal bone cyst-like change, became undetectable in her blood. Furthermore, cells within the aneurysmal bone cyst component were immunohistochemically positive for βhuman chorionic gonadotropin. This is the first report of such a finding in the literature. Keywords Giant cell tumor of bone . β-human chorionic gonadotropin . Aneurysmal bone cyst . Neoplasm
V. A. Fitzhugh (*) : G. Katava Department of Pathology and Laboratory Medicine, Rutgers, the State University of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA e-mail: [email protected] C. Wenokor Department of Radiology, Rutgers, the State University of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA N. Roche Department of Obstetrics, Gynecology, and Women’s Health, Rutgers, the State University of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA K. S. Beebe Department of Orthopaedics, Rutgers, the State University of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA
Introduction Giant cell tumor of bone is a benign neoplasm of bone that consists of neoplastic mononuclear cells that are surrounded by a large population of non-neoplastic osteoclast-like giant cells. These tumors represent approximately 4–5 % of all primary tumors of bone [1]. They can be locally aggressive, as they can recur. Aneurysmal bone cyst-like areas are identified as a secondary feature in approximately 10–14 % of giant cell tumors [1, 2]. β-Human chorionic gonadotropin (hCG) is a glycoprotein hormone secreted by the syncytiotrophoblasts of the developing placenta. β-hCG is also seen in several different germ cell tumors [3]. Increased serum levels of β-hCG as a paraneoplastic syndrome have been described most commonly in several case reports of osteosarcoma [3–6]. We present a case of a young woman whose recurrent giant cell tumor of bone with secondary aneurysmal bone cyst-like change caused an increase in serum β-hCG, which returned to undetectable levels after resection of the lesion.
Case report The patient was a 17-year-old female who first presented to the orthopedic clinic in August of 2011 with a 1-month history of left knee pain. No history of trauma was noted. Her past medical history was significant only for a seizure disorder, which was being managed by divalproex sodium. Physical examination was remarkable for mild tenderness to palpation along the lateral aspect of the left femur with pain at the end of the 1–130° range of motion exam. Radiographs and a computed tomography (CT) scan (Fig. 1) were performed, demonstrating a 6.5×4.6×4-cm expansile, eccentric, lytic lesion of the distal femur involving the metaphysis and extending into the epiphysis, which
Skeletal Radiol
Fig. 1 Radiograph (a), coronal (b), and sagittal (c) computed tomography scans prior to the first surgery demonstrating a large expansile, lytic mass of the distal femur
appeared closed. The lesion was felt to most likely represent a giant cell tumor of bone radiographically. The patient underwent biopsy of the lesion followed by resection curettage and cementation. The resected specimen was a giant cell tumor of bone with focal changes suggestive of aneurysmal bone cyst. Following the surgery, the patient underwent a 3-month course of physical therapy after which she continued to complain of pain. A radiograph to assess for evidence of local recurrence was ordered. The radiograph was remarkable for a lucent zone identified between the cement–bone interface in the distal femoral metadiaphyseal region. Furthermore, there was cortical thinning present, which was suspicious for tumor recurrence. A CT scan followed and demonstrated an area of lucency around the cement mantle measuring 9×3.5 cm Additionally, a soft tissue mass was also identified (Fig. 2). This finding was consistent with tumor recurrence. The patient underwent a routine preoperative urine pregnancy test which was positive. A follow-up quantitative βhCG level of 11 mIU/ml (normal value 0 mIU/ml) was reported. A follow-up β-hCG performed 2 days later remained at 11 mIU/ml. A final β-hCG performed 1 week later was 9 mIU/ml. The patient was referred to gynecology. The patient’s past gynecologic history was unremarkable. The gynecologic physical exam was normal. The general physical exam was within normal limits with the exception of pain about the left
knee. The gynecologist recommended that orthopedics proceed with the tumor resection. Biopsy confirming giant cell tumor recurrence followed by extensive resection and distal femoral replacement was performed. Histologically, the tumor consisted of numerous giant cells with 10s to 100s of nuclei with interspersed mononuclear cells similar in appearance to those within the giant cells (Fig. 3). Additionally, there was a second component that demonstrated cavernous spaces. The walls of the spaces lacked an endothelial lining and contained fibroblastic spindle cells, multinucleate giant cells, and thin strands of remodeling bone (Fig. 4). Each of the submitted sections was carefully screened for anaplasia, increased mitotic activity, and heterologous tissue foci. Anaplasia was not identified. Mitotic activity was limited to one mitosis per ten high-power fields; this was confirmed by immunohistochemical staining with Ki-67, which demonstrated a proliferative index of 10 %. No heterologous elements were identified in either the giant cell tumor foci or the aneurysmal bone cyst foci. Additionally, immunohistochemistry for β-hCG was performed, and showed positive staining, predominately in the areas of aneurysmal bone cyst (Fig. 5). The case was diagnosed as a recurrent giant cell tumor of bone with secondary aneurysmal bone cyst and focal β-hCG positivity. β-hCG immunohistochemistry was subsequently performed on the patient’s original tumor and it also demonstrated positive staining predominately in the
Fig. 2 Radiograph (a), coronal (b), and sagittal (c) computed tomography scans prior to the second surgery demonstrating an area of lucency around the cement mantle and extension into the soft tissue, consistent with tumor recurrence
Skeletal Radiol
Fig. 3 Histology of the resected lesion demonstrating mononuclear cells (thin arrows) interspersed between giant cells (thick arrows), diagnostic of giant cell tumor of bone (hematoxylin and eosin stain, 200×)
Fig. 5 β-hCG immunohistochemistry demonstrating focal positivity (arrows) (β-hCG, 200×)
aneurysmal bone cyst component. After surgery, the patient’s β-hCG level returned to
