Giant Cell Tumor of the Rib: A Report of Two Patients

Introduction

Giant cell tumor of bone is a locally aggressive and rarely metastasizing tumor that accounts for 4% to 5% of all primary bone tumors. ¹ Its etiology is not well known. ¹ It typically affects the epiphysis of long bones during the third and fourth decades of life. ¹ Less than 10% of all giant cell tumor of bone are malignant. ¹ Rib location represents less than 1% of all giant cell tumor of bone. ² Only one previous giant cell tumor of the rib detected after local traumatism has been reported. ³ The objective of this article is to present the clinical, radiological, and histopathological features, as well as describe the management of 2 patients with this very rare giant cell tumor of bone location.

Materials and Methods

La Paz University Hospital and Ramón y Cajal Hospital in Madrid are tertiary hospitals and 2 of the expert hospitals for bone and soft tissue tumors management in Spain. All diagnosed giant cell tumor of bone tumors in the Pathology Departments of both hospitals between 1966 and 2022 were included in the present study. Clinical information and radiological images were obtained from the medical records. All available materials from the pathology files were reviewed, including hematoxylin and eosin-stained slides, as well as immunohistochemical stains.

Results

A total of 186 patients with giant cell tumor of bone were registered in both hospitals. Bone location was reviewed, with only 2 of them presenting rib location (1.1%). Both patients have a history of a local trauma. Consent for publication was obtained from the patients.

Patient 1

A 32-year-old woman with no relevant medical antecedents presented a slow-growing mass for 10 months in her left anterior thorax. She had a traffic accident 6 months before, and radiological images revealed no fracture, bony destruction, or mass at that time. A current physical examination revealed a barely movable, painless mass in the medial left anterior thorax. The plain radiography showed an ill-defined mass on the inferior left hemithorax (Figure 1A). Computerized tomography (CT) images demonstrated a markedly expansile lytic mass with an osseous epicenter measuring 15.5 cm (Figure 1B). It was arising from the seventh left rib, with expansion to adjacent soft tissues. The results of magnetic resonance imaging (MRI) scan showed a heterogeneous mass presenting enhancement after gadolinium administration (Figure 1C). Bone scintigraphy was performed, revealing an intense increase in osteogenic reaction. No other bone alterations were detected. Fibrous dysplasia and chondrosarcoma were considered, being the most frequent expansile lesions in ribs, but without calcified matrix inside. Other differential diagnoses included in this young patient were chronic expansive hematoma, brown tumor, solid subtype of an aneurysmal bone cyst, chondroblastoma, eosinophilic granuloma, round cell sarcoma, or diffuse large B cell lymphoma.

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Figure 1.

(A) Plain radiography: ill-defined radiolucent mass on the inferior left hemithorax. (B) Chest computerized tomography (CT): large expansile mass centered on seventh anterior left rib with peripheral calcified shell. (C) Axial T1-WI: large well-defined and homogeneously hypointense mass extending both sides of the left chest wall. (D) Mononucleated monomorphic cells and numerous multinucleated osteoclast-like giant cells (H&E ×100). (E) Well defined and encapsulated mass. (F) Heterogeneous mass arising from the rib with soft tissue and skin coverage. (G) Peripheral reactive bone formation (H&E ×40). (H) Reactive bone formation related to mononucleated non-atypical cells and small vascular spaces (H&E ×100). (I) Positive mononucleated cells (antihistone H3.3 G34W ×200).

An ultrasound-guided core biopsy was performed. The histological analysis showed a densely cellular tumor with a diffuse growth pattern. It consisted mainly of multinucleated osteoclast-like giant cells with over 30 nuclei, on a background of monotonous mononucleated stromal cells (Figure 1D) and frequent hemorrhagic areas. Neither mitotic figures nor necrotic foci were found. Based on these findings, a conventional giant cell tumor of bone diagnosis was made. After evaluation by the Bone and Soft Tissue Tumors Committee (BSTTC) and given that denosumab treatment was unavailable at that time, surgical treatment was planned. Thoracic wall resection with osteosynthesis plate and Gore-Tex® dual mesh reconstruction was performed. No postoperative complications arose. A partial costal resection including 6 ribs and skin coverage was analyzed in the Pathology Department (Figure 1E). A heterogeneous mass with hemorrhagic areas and whitish solid areas was observed on sectioning (Figure 1F). Surgical margins were macroscopically free.

The tumor was histologically similar to the cellularity observed in the previous biopsy. Bone trabeculae reactive formation was found in the periphery (Figure 1G) and in the center of the tumor (Figure 1H). It was covered by non-atypical small cells. Small vascular structures were observed. No lymphovascular invasion images were seen. No chondroid matrix, “blue bone,” or foamy histiocytes were found. Antihistone H3.3 G34W (Clone RM263, Ready to Use [RTU], Agilent-Dako) immunostaining was performed and revealed a diffuse positivity in mononucleated cells (Figure 1I). Surgical margins were histologically unaffected. No local radiotherapy or systemic treatment were established by the BSTTC. A chest control plain radiography was performed every 6 months. After 14 years of follow-up, the patient remains disease-free.

Patient 2

A 45-year-old man with no relevant medical antecedents presented a back irradiated right costal pain that worsened with movements and depth breath. A fast-growing mass appeared in the area. He referred a one-month previous local chest trauma during sport activity. Radiological images exhibited no fracture, bony destruction, or mass at that time. The current physical examination showed a painful mass in the seventh rib region. The current plain radiography revealed a probable bone fracture callus of the fifth rib. A CT scan (Figure 2A) demonstrated destruction of the right anterior fifth costal arch, with an associated solid heterogeneous mass of 7.4 cm extending into soft tissues and the subcostal region. Calcified foci were detected. After contrast administration enhancement was found. Bone scintigraphy was also performed, revealing an intense increase in heterogeneous osteogenic reaction and significant associated hyperemia in the right rib cage (Figure 2B). Given the patient's age, the initial suspicion included aggressive lesions, such as metastases, myeloma, or round-cell sarcoma. Chondrosarcoma and fibrous dysplasia were considered in this location despite the lack of certain typical features.

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Figure 2.

(A) Axial computerized tomography (CT): solid and heterogeneous mass centered in the anterior fifth right rib with small foci of calcification. (B) Bone scintigraphy: intense increase in osteogenic reaction of a heterogeneous nature in the right rib cage. (C) Mononucleated monomorphic cells and numerous multinucleated osteoclast-like giant cells (H&E ×100). (D) Positive mononucleated cells (antihistone H3.3 G34W ×200). (E) Well defined and encapsulated whitish mass. (F) Heterogeneous tumor with whitish and brownish areas. (G) Extensive hyalinization (H&E ×40). (H) Interconnected bone trabeculae formation and spindle cell stroma (H&E ×100). (I) Bland spindle cell proliferation (H&E ×400).

An ultrasound-guided core biopsy was performed, and similar histological findings as in the patient 1 biopsy were observed (Figure 2C and D). The diagnosis of a conventional giant cell tumor of bone was made. Upon evaluation by the BSTTC, denosumab was administered. In the CT study, intralesional calcifications were observed. No other bone findings were detected. Surgery was performed 2 months after the first administrated doses of denosumab. Partial right thoracic wall resection with osteosynthesis plate and Gore-Tex® dual reconstruction were performed. No postoperative complications arose.

A partial costal resection of 3 ribs was received in the Pathology Department (Figure 2E). A rounded and capsulated 8 cm measuring mass was observed erasing the architecture of the seventh rib (Figure 2F). Upon sectioning, the mass presented a firm consistency and heterogeneous aspect, with whitish and brownish areas. Surgical margins were grossly free. Posttreatment effects consisted of extensive hyalinization (Figure 2G), longitudinally or interconnected bone trabeculae formation (95%) (Figure 2H) and a CD68 (Clone, PG-M1, RTU, Agilent-Dako) and smooth muscle actin (Clone 1A4, RTU, Agilent-Dako)-positive bland spindle cell proliferation (5%) (Figure 2I). No significant atypia, high mitotic activity, extensive necrotic areas, or preexisting bone infiltration were seen. Surgical margins were not histologically affected. No local radiotherapy or systemic treatment administration was referred by the BSTTC. A chest control CT was performed every 3 to 4 months. After 3 years of follow-up, the patient remains disease-free.

Discussion

Giant cell tumor of bone is a locally aggressive and rarely metastasizing bone tumor that normally arises in the ends of long bones. ¹ Ribs are an extraordinarily rare tumor location for giant cell tumor of bone, accounting for less than 1% of all reported patients.^2,4 Most tumors involve the posterior rib arc. ⁵ Up to 10% of all rib giant cell tumor of bone undergo a malignant transformation. ⁶ Another huge giant cell tumor of bone rib tumors have been documented. The patient described by Cordeiro et al ⁷ occupied the entire hemithorax. The tumor reported by Blanco et al ⁸ showed spine extension and a patient described by Yang et al ⁹ measured 16 cm, causing compressive effects. None of these tumors were detected after local traumas.

Chen et al ³ have recently reported a patient with an anterior rib giant cell tumor of bone appearing 3 months after a local trauma. Our report represents the second and third rib giant cell tumor of bone detected after a local trauma reported cases in medical literature. Both patients presented rapid progression, mimicking a malignant tumor. A few other giant cell tumor of bone associated to a prior local trauma have been reported in the patella, ¹⁰ ulna, ¹¹ and metacarpal bone. ¹² The histogenesis and pathogenesis of giant cell tumor remain incompletely defined.^1,13

Differential clinical and radiological diagnosis of thoracic bone masses includes a broad spectrum of pathological entities, including nontumoral lesions such as bone fracture callus and hematomas; benign tumors such as fibrous dysplasia, enchondroma, eosinophilic granuloma, aneurismal bone cyst (solid subtype) and posttraumatic fibro-osseous lesion ¹⁴ ; tumors with intermediate biological potential as the solitary fibrous tumor; and malignant lesions such as lymphomas, mesothelioma, thymomas, chondrosarcoma, myeloma, round cell sarcomas, and bone metastases.^3,9 Posttraumatic fibro-osseous lesions are rare and benign tumors that typically affect the ribs. ¹⁵ In most patients, these lesions affect the posterior and lateral portions of the ribs. ¹⁵ Their characteristic radiological appearance consists of an ovoid central radiolucency with a sclerotic peripheric rim. ¹⁵ They are histologically composed of fibrous connective tissue with fusiform fibroblastic cells and multiple bone trabeculae of metaplastic appearance surrounded by non-atypical osteoblasts. They may present xanthomatous areas but no osteoclastic-like giant cells are seen. ¹⁴ It may be misdiagnosed as fibrous dysplasia, the most common primary benign rib tumor. ¹⁴

Other mimickers such as aneurysmal bone cysts rarely arise in the ribs. ¹⁶ They may arise de novo or secondarily to giant cell tumors. Radiology reveals eccentric bone expansion with cortical erosion and the characteristic fluid–fluid levels on MRI. ¹⁶ They are histologically composed of blood-filled spaces separated by thin septa with scattered osteoclast cells and “blue bone.” Solid areas may be present. ¹⁶ Few chondroblastomas arising in the rib have been reported. ¹⁷ Radiologically, they are lucent lesion with geographical bone destruction and well-defined sclerotic borders. ¹⁷ Histologically, they are composed of sheets of polygonal cells with grooved nuclei and eosinophilic cytoplasm with osteoclast-like multinucleated giant cells intermixed. Immature eosinophilic chondroid matrix and pericellular chicken wire calcifications are seen. Mononucleated cells reveal diffuse immunostaining positivity against antihistone H3.3 K36M. ¹⁷ Nonossifying fibromas may occur in ribs exceptionally. ¹⁸ They originate in skeletally immature patients. Radiological images are usually pathognomonic, presenting well-defined lobulated masses in the cortical bone with scalloped and sclerotic rim. ¹⁸ They consist of a storiform proliferation of spindle cells with intermixed osteoclast-like giant cells and foamy histocytes. Ribs are not a common location for osteosarcoma. ¹⁹ The giant cell osteosarcoma subtype shows radiological aggressive signs with cortical bone disruption and soft tissue extension. ¹⁹ It consists of osteoblasts with marked nuclear pleomorphism and atypical mitoses that infiltrate preexisting bone. ¹⁹ None of these tumors show antihistone H3.3 G34W immunoreaction. ¹ Giant cell tumor of bone treated with denosumab reveal new bone formation associated with bland spindle cells and marked giant cell depletion. ¹ It may mimic de novo osteosarcoma or secondary malignant giant cell tumor of bone but the treated tumors do not present significant atypia, high mitotic activity, extensive necrosis, or infiltration of the preexisting bone. ¹ Clinical correlation with the radiological and histopathological findings is essential.

The optimal treatment of rib giant cell tumor of bone continues to be unclear. ²⁰ Surgical excision is the only curative treatment in patients with giant cell tumor of bone. ²⁰ Tumor and chest wall removal including the involved ribs with bloc resection and wide margins should be the elected surgery. ⁷ Preoperative denosumab therapy has been demonstrated to be beneficial in both resectable and unresectable tumors. ²⁰ Occasional giant cell tumor of bone with malignant transformation after denosumab treatment has been documented.^21,22 Radiation therapy is not recommended since it has also been associated with malignant transformation. ²³ Close patient follow-up during the 15 postsurgical years is recommended due to its potential malignant transformation. ⁶

Conclusion

Giant cell tumor of bone is not usually suspected in patients with chest wall masses given its low frequency in this location. It should be included in the differential diagnosis of giant thoracic rapid-growth masses. It may mimic a malignant bone tumor and a careful clinical, radiological, and pathological evaluation is necessary to ensure a correct diagnosis.