|Year : 2017 | Volume
| Issue : 1 | Page : 139-141
Recurrent osteosarcoma with calcified liver metastases: Uncommon development of a common disease
Shikha Goyal, Pramod K Julka
Department of Radiotherapy, All India Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||16-May-2017|
Department of Radiotherapy, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Osteosarcoma is the commonest primary malignant bone tumor. Since bones lack a lymphatic system, metastatic spread in these tumors is exclusively hematogenous, the commonest sites being lungs and bone. We report a case of osteosarcoma humerus which recurred locally after primary therapy consisting of neoadjuvant chemotherapy and limb salvage surgery, who developed calcified liver metastases in addition to local and pulmonary relapse. Liver, though a common site of hematogenous spread in most solid tumors, has rarely been reported to be involved in metastatic osteosarcomas.
Keywords: Calcification, liver metastases, osteosarcoma
|How to cite this article:|
Goyal S, Julka PK. Recurrent osteosarcoma with calcified liver metastases: Uncommon development of a common disease. J Can Res Ther 2017;13:139-41
| > Introduction|| |
The outcome of osteosarcoma both in terms of survival and limb function has considerably improved with institution of neoadjuvant chemotherapy and limb salvage protocols. Nearly 11% have systemic metastases at the time of diagnosis, the commonest sites being lungs and bones. Lymphatic spread is rare. The classic pattern and time frame of metastatic dissemination of osteosarcoma has been modified by use of adjuvant chemotherapy. A study by Bacci et al., reported metastases to unusual sites such as kidneys, brain and heart. Liver metastases, despite being an extremely common finding in several solid malignancies through hematogenous route, have rarely been observed in osteosarcoma. We discuss a case with local and systemic relapse including liver involvement, along with a description of patterns of liver spread reported in English literature.
| > Case Report|| |
A 28-year-old lady presented with history of pain left upper arm for 6 months and swelling in the same region for 3 months. There was no history of trauma, or any motor or sensory deficit distal to the swelling. Biochemistry showed elevated lactate dehydrogenase and serum alkaline phosphatise. MRI showed a growth involving upper end of left humerus with a large soft tissue component extending into the left axilla (7.5 × 8 × 10 cm 3). Bone scan showed tracer uptake at primary site only. No systemic metastases were detected. She was given neoadjuvant chemotherapy and later taken up for limb salvage surgery. Postoperative histopathology revealed an 11 × 10 × 8 cm 3 growth involving upper end of humerus with focal necrosis and positive margins, infiltration of skeletal muscle and breach of articular cartilage in left shoulder. The possibility of an early recurrence was discussed with the patient in view of the residual disease but she denied further surgery in the form of forequarter amputation, and thus was given postoperative chemotherapy. Within 6 months from surgery, she presented with a large recurrent painful swelling (12 × 10 × 10 cm) involving left axilla and chest wall. [Figure 1] Imaging showed multiple bilateral ossified lung metastases [Figure 2]. In addition, NCCT of the abdomen revealed a large hypodense mass involving right lobe of liver with ossification at the rim of the lesion. [Figure 3] She was given palliative radiotherapy to the axillary mass (8 Gray in a single fraction). Given her poor performance status at recurrence, she was kept on best supportive care only.
|Figure 1: Non-contrast CT scan of left arm and chest showing a large calcified recurrent mass around the humerus prosthesis also extending to involve left axilla and chest wall|
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|Figure 2: Non-contrast CT scan of the chest showing multiple calcified metastatic lesions involving both lungs|
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|Figure 3: Non-contrast CT scan of the abdomen showing a large (7 × 5 × 5 cm3) hypodense lesion involving the right lobe of the liver with peripheral rim ossification|
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| > Discussion|| |
The commonest site of metastases in osteosarcoma is lung (80-90%) followed by bone. Involvement outside these regions has rarely been described in regional lymph nodes, mesentery or abdominal viscera. Despite the known propensity of hematogenous spread, liver involvement has been described in only a handful of cases till date. Chan et al. showed a metastatic liver osteosarcoma with amorphous calcification at the superior aspect of the lesion in non-enhanced CT scans, and a lace-like enhancement pattern at the center of the lesion similar to the primary bone lesion but no necrosis, hemorrhage or cystic component. Several presentations and diagnostic features that have been described include (a) calcification of liver lesions seen on plain radiography, CT or MRI, (b) densely ossified multiple liver metastases visible on both CT scan and bone scan, (c) diffuse abdominal involvement with peritoneal spread and deposits on liver surface, (d) delayed uptake on Strontium-85 (Sr-95) scan in the metastatic liver deposits in the absence of initial activity on Technitium-99m sulphur colloid scan and a Sr-95 scan of the skeletal system, (e) F-18 uptake within metastatic deposits on a fluoride scan, and (f) small rounded hypodense lesions without calcification mimicking a simple cyst or hemangioma.,,,,,,, With increasing use of more aggressive chemotherapeutic regimens, the incidence of such unusual sites of metastases may increase, thus, the need for anticipating and identifying such uncommon presentations.
Extrapulmonary metastases are associated with a more aggressive behavior. Several researchers have tried to determine the prognostic factors and molecular contributors to metastatic potential. Prognostic indices combining clinical factors such as age, tumor location, size, symptom duration and histologic type have helped classify patients into good, intermediate and poor risk groups, and such classification may help devise tailored treatment protocols., Novel prognostic markers that show promise for osteosarcoma biology include:,,,
- Ezrin, a cytoskeleton linker protein involved in cell-cell interaction, cell-matrix adhesion and signal transduction, is dysregulated in osteosarcomas and its expression on immunohistochemistry is higher in metastatic tumors versus primary tumors
- P53 protein upregulated expression is associated with reduced overall (OS) and disease-free survival (DFS)
- Anti-Vascular endothelial growth factor (VEGF) agents such as endostatin reduce recurrence and metastases rates
- Chemokine receptors CXCR4 and CCR7 are under investigation to determine the metastatic destination of tumor cells, and their expression correlates inversely with OS and metastases-free survival
- Upregulated proteins such as matrix metalloproteinase 2, cycloxygenase 2, insulin-like growth factor receptor type 1 and RANK-L are all associated with inferior outcomes
- Endothelin-1 polymorphism and peroxiredoxin2 expression have been linked to increased chemoresistance
- Enhanced expression of glycoprotein periostin results in higher metastatic potential and poor outcomes. It has a significant association with pathologic subtype, tumor size and stage
- Special AT-rich-binding protein 2 (SATB2) has increased expression in osteosarcomas. Short hairpin RNA-mediated knockdown of SATB2 decreases cell migration and invasion without affecting proliferation or viability, via effects on EPLIN (actin-binding protein Epithelial Protein Lost In Neoplasm) and cytoskeleton
- Altered microRNA profiles may serve either as tumor suupressors or as oncogenes in osteosarcomas. Expression of microRNA 34 cluster is known to downregulate Notch 1 and Notch 2 pathways and correlates inversely with tumor invasiveness.
Further research elucidating a clearer role of above molecular markers and pathways may help discern several therapeutic targets which would potentially help reduce metastatic potential and thus improve longevity and quality of life in osteosarcomas.
| > References|| |
Kager L, Zoubek A, Pötschger U, Kastner U, Flege S, Kempf-Bielack B, et al
. Primary metastatic osteosarcoma: Presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol 2003;21:2011-8.
Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A, Picci P. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer 2006;106:1154-61.
Chan HH, Chan JK, Ng WM, Shek TW, Chan FL. Lace-like enhancement pattern of osteosarcoma of rib and liver metastasis in CT scans. Australas Radiol 2001;45:305-8.
Shapiro RS, Mendelson DS, Norton KI, Janus C, Gendal ES, Hermann G. Case report: Calcified liver metastases from osteosarcoma. J Comput Tomogr 1988;12:196-8.
Kim SJ, Choi JA, Lee SH, Choi JY, Hong SH, Chung HW, et al
. Imaging findings of extrapulmonary metastases of osteosarcoma. Clin Imaging 2004;28:291-300.
Daw NC, Kaste SC, Hill DA, Kun LE, Pratt CB. Metastatic osteosarcoma to the liver after treatment for synovial sarcoma: A case report. Pediatr Hematol Oncol 2001;18:123-8.
Costa CM, de Camargo B, Bagietto R, Alcantra PS, Chojniak R, Sredni ST. Abdominal recurrence of osteogenic sarcoma: A case report. J Pediatr Hematol Oncol 1998;20:271-3.
Dalinka MK, Fiveash AE, Aston JK. Metastatic extraosseous osteosarcoma to the liver: A case demonstrated by 85 Sr and 99m Tc-colloid scanning. J Nucl Med 1971;12:754-5.
O'Mara RE, Brettner A, Danigelis JA, Gould LV. 18 F
uptake within metastatic osteosarcoma of the liver. A case report. Radiology 1971;100:113-4.
Yu WX, Yao Y. Metastatic osteosarcoma to the liver and the kidney: A case report and review of the literature. BMJ Case Rep 2009;2009.
Ali RH, Lee CH, Hayes MM. Metastatic small cell osteosarcoma to the liver: A diagnostic pitfall for fine-needle aspiration cytology. Diagn Cytopathol 2014;42:161-4.
Bentzen SM, Poulsen HS, Kaae S, Jensen OM, Johansen H, Mouridsen HT, et al
. Prognostic factors in osteosarcomas. A regression analysis. Cancer 1988;62:194-202.
Petrilli AS, Gentil FC, Epelman S, Lopes LF, Bianchi A, Lopes A, et al
. Increased survival, limb preservation, and prognostic factors for osteosarcoma. Cancer 1991;68:733-7.
Wadhwa N. Osteosarcoma: Diagnostic dilemmas in histopathology and prognostic factors. Indian J Orthop 2014;48:247-54.
] [Full text]
Hu F, Wang W, Zhou HC, Shang XF. High expression of periostin is dramatically associated with metastatic potential and poor prognosis of patients with osteosarcoma. World J Surg Oncol 2014;12:287.
Seong BK, Lau J, Adderley T, Kee L, Chaukos D, Pienkowska M, et al
. SATB2 enhances migration and invasion in osteosarcoma by regulating genes involved in cytoskeletal organization. Oncogene. 2014 Sep 15. doi: 10.1038/onc.2014.289.
Hughes DP. How the NOTCH pathway contributes to the ability of osteosarcoma cells to metastasize. Cancer Treat Res 2009;152:479-96.
[Figure 1], [Figure 2], [Figure 3]
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