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  Table of Contents    
CASE REPORT  
Year : 2021  |  Volume : 64  |  Issue : 2  |  Page : 394-397
Malignant transformation of monostotic fibrous dysplasia into angiosarcoma in the proximal tibia


1 Department of Surgical Pathology, Uludag University, Faculty of Medicine, Uludag University, Bursa, Turkey
2 Department of Orthopaedics and Traumatology, Uludag University, Faculty of Medicine, Uludag University, Bursa, Turkey
3 Department of Radiology, Faculty of Medicine, Uludag University, Bursa, Turkey

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Date of Submission29-Jul-2020
Date of Decision22-Sep-2020
Date of Acceptance29-Oct-2020
Date of Web Publication9-Apr-2021
 

   Abstract 


The majority of bone angiosarcomas are primary tumors while secondary angiosarcomas arise after radiation therapy or bone infarctus. This article presents a case of malignant transformation of monostotic fibrous dysplasia into angiosarcoma. An 80-year-old female presented with pain on right cruris. Radiological examination revealed a lesion with lytic areas and destruction of cortical bone on right tibia. Gross and histopathological examination showed two areas with an abrupt transition. The solid component was composed of curved, immature bony trabeculae in a fibroblastic stroma. The other component involved epitheloid cells forming slit-like vascular spaces. The diagnosis of angiosarcoma and fibrous dysplasia was given. Malignant transformation of fibrous dysplasia into angiosarcoma is extremely rare; as this is the sixth case in the existing literature. Prognosis of fibrous dysplasia is generally good and less than 1% of the patients develop a malignant tumor. Therefore, patients with fibrous dysplasia should be offered a life-long follow-up.

Keywords: Angiosarcoma, bone, fibrous dysplasia, histopathology, malignant transformation

How to cite this article:
Narter S, Yalcinkaya U, Bilgen MS, Yazici Z. Malignant transformation of monostotic fibrous dysplasia into angiosarcoma in the proximal tibia. Indian J Pathol Microbiol 2021;64:394-7

How to cite this URL:
Narter S, Yalcinkaya U, Bilgen MS, Yazici Z. Malignant transformation of monostotic fibrous dysplasia into angiosarcoma in the proximal tibia. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 May 8];64:394-7. Available from: https://www.ijpmonline.org/text.asp?2021/64/2/394/313306





   Introduction Top


Angiosarcoma of the bone is rarely seen, accounting for less than 1% of malignant bone tumors. It can occur in any part of the skeleton with preferential involvement of tubular bones of the extremities. These tumors have a rapid progression and it is initially investigated as metastatic tumor.[1],[2],[3] The majority of angiosarcomas are primary tumors with an unknown etiology. Secondary angiosarcomas are known to develop after radiation therapy or bone infarcts.[2] The most common presenting symptom is pain and occasionally patients present with pathological bone fracture. Histopathologically, angiosarcomas are composed of epithelioid or less frequently, spindle-shaped cells that make anastomosing vascular spaces or grow in solid sheets. Tumor cells express endothelial markers while cytokeratins and EMA are frequently positive. The treatment of bone angiosarcoma is wide excision combined with chemoradiotherapy, similar to other bone sarcomas. However, angiosarcoma of the bone has a poor prognosis. One-year survival rate is approximately 55%.[2],[3]

Fibrous dysplasia is a benign bone lesion in which the neoplastic fibro-osseous tissue replaces normal medullary bone. These tumors constitute 2.5% of all bone tumors.[4] Fibrous dysplasia can be encountered as monostotic or polyostotic disease. Craniofacial bones and femur are the most common sites of involvement in both forms.[4],[5],[6] Most lesions are asymptomatic and are found incidentally. Occasionally patients complain of pain and swelling and rarely present with pathological fracture.[6] Histopathologically, fibrous dysplasia is characterized by irregularly shaped, branching bony trabeculae surrounded by a hypocellular stroma, formed by oval to spindle-shaped fibroblasts with no cytological atypia. The prognosis usually good. Radiation therapy is not recommended as it may lead to sarcomatous change.[5],[6]

Rarely malignant transformation can occur in both monostotic and polyostotic fibrous dysplasia. Frequency of malignant transformation is known to be higher in polyostotic form with McCune-Albright or Mazabraud's syndrome. Also, radiation therapy at lesion site is a well-known reason for sarcomatous transformation.[4],[7] For the diagnosis of malignant transformation, both fibrous dysplasia and the malignant tumor must be histopathologically recognized or radiological recognition of a malignant tumor must be given in a patient with fibrous dysplasia.[8]

Bone angiosarcoma transformed from fibrous dysplasia is extremely unusual. This article presents a case of malignant transformation of monostotic fibrous dysplasia into angiosarcoma in the proximal tibia in a patient with no previous history of radiation therapy.


   Case Report Top


An 80-year-old female who had been diagnosed with microinvasive ductal carcinoma of breast 2 years ago, presented to our clinic with a painful mass on right cruris. The patient had not received any adjuvant treatment for microinvasive carcinoma and was followed clinically. When admitted she had no evident disease or metastasis. Complete blood count and serum biochemistry panel were normal except for low hemoglobin of 9,97 g/dL. Serum calcium, phosphorus, alkaline phosphatase, lactate dehydrogenese levels and serum tumor markers were all normal. Patient's comprehensive history revealed that she had been diagnosed with a benign bone lesion in another center 50 years ago, however she did not know the histopathological diagnosis of the lesion nor did she receive any treatment.

X-ray imaging of the right cruris showed a mixed-density lesion in the proximal metaphysis and diaphysis of the tibia causing deformation of tibia. The upper part of the lesion had ground-glass density with well-defined margin and the lower part was lytic with ill-defined margin showing cortical destruction [Figure 1]a. Magnetic resonance imaging without contrast revealed that the upper part of the lesion had homogenous hyperintensity on T2-weighted images and hypointensity on T1-weighted images; the lower part of the lesion had mixed intensity with extraosseous extension [Figure 1]b and [Figure 1]c.
Figure 1: Frontal radiograph of the right cruris shows a bone lesion in the proximal tibia metaphysis and diaphysis. The upper part of the lesion is well-circumscribed and ground-glass like in density; lower part is destructive and lytic with ill-defined margins, which shows a more aggressive appearance (a). On T1-weighted coronal (b) and fat-supressed protone density sagittal (c) magnetic resonance images, the lesion has homogeneous intensity in its upper part and heterogenous intensity in its lower part with extraosseous extension (arrow)

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According to the consensus of expert meeting, the tumor site resection with tumor prosthesis implantation without performing preoperative biopsy was decided because of the aggressive appearance of the lesion with a high risk for pathologic fracture. The patient underwent radical proximal tibial resection and the resection site was reconstructed with endoprosthesis.

The gross examination of the specimen revealed an 11,5 × 4,3 cm intramedullary tumor. The distance from tumor to the distal surgical margin was measured 0,9 cm. Tumor was composed of two distinct areas with an abrupt transition; a gray-white solid component and a cystic-hemorrhagic component. The hemorrhagic cystic area of the tumor showed cortical destruction and tumor extension to surrounding soft tissue [Figure 2]a.
Figure 2: Intramedullary tumor with two distinct components on right proximal tibia resection (a). Fibrous dysplasia (b) characterized by irregularly distributed, curved bony trabeculae within a fibrous stroma (H and E ×200). Fibrous dysplasia and angiosarcoma (c) showing an abrupt transition (H and E ×40). Angiosarcoma (d) composed of epitheloid cells forming vascular spaces (H and E ×200)

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Histopathological evaluation revealed that the solid component was composed of thin, curved, immature bone trabeculae in a hypocellular fibroblastic stroma. The stroma was composed of spindle shaped cells with no cytological atypia [Figure 2]b. The two components showed an abrupt transition [Figure 2]c. In the cystic-hemorrhagic component, cells with an epitheloid appearance and prominent pleomorphism created vascular and slit-like structures. Areas of hemorrhage and necrosis were seen [Figure 2]d and [Figure 3]. Immunohistochemical studies revealed positive staining with CD31, CD34, Factor VIII, FLI-1, focal positivity with epithelial membrane antigen (EMA) and podoplanin, ki67 proliferative index of 20% and no staining with p53, CDK4, MDM2, cytokeratin [Figure 4]. No tumor cells were microscopically seen at the resection margin.
Figure 3: Higher power view of angiosarcoma showing tumor cells with cytological atypia and areas of hemorrhage (H and E ×200)

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Figure 4: CD34 (a) and FLI-1 (b) positivity in angiosarcoma (DAB ×100)

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The histological and immunohistochemical findings were consistent with the diagnosis of angiosarcomatous malignant transformation of monostotic fibrous dysplasia. The patient received no adjuvant treatment due to osteomyelitis of the tibia developed postoperatively and concomitant severe cardiac dysfunction. The patient was followed clinically in another center and was dead of other cause in postoperative 5 months.


   Discussion Top


Rarely, malignant transformation occurs in fibrous dysplasia in less than 1% of the cases.[9] It can occur during childhood or in adulthood; however, time interval between initial presentation of fibrous dysplasia and malignant tumor varies in the literature. In some case reports, simultaneous diagnoses of both tumors are made, similar to our case.[10] Malignant change is more common in polyostotic form and rarely reported in monostotic form of the fibrous dysplasia.[4],[7] Liposclerosing myxofibrous tumor, believed to be a variant, carries a higher risk of malignant transformation compared to fibrous dysplasia.[11]

The most common sites involved in sarcomatous transformation are craniofacial bones, femur and humerus.[10],[12] Exposure to radiation in the lesion site is believed to be the main reason of malignant transformation. However, cases with no previous history of radiation has developed malignancies, similar to our case, suggesting an unknown mechanism in malignant transformation.[9],[10],[12],[13] Sudden increase in symptoms like pain, swelling or a rapid change in radiological appearance of fibrous dysplasia should alert the clinician about a possible malignant transformation. Radiologically, lesion with cystic areas, moth-eaten pattern, cortical destruction or the formation of a soft tissue mass instead of the usual radiolucent “ground-glass” appearance of fibrous dysplasia should raise the concern of a sarcomatous growth.[10],[12]

Osteosarcoma is the most common secondary tumor arising in fibrous dysplasia, followed by fibrosarcoma and chondrosarcoma. Also, few cases of angiosarcoma, spindle cell sarcoma and malignant fibrous histiocytoma have been reported to develop.[7],[9],[13] Qu et al. reported 10 cases of monostotic form with malignant transformation and osteosarcoma was the most common tumor detected.[4]

Angiosarcoma arising in fibrous dysplasia is extremely uncommon and no more than a few cases have been described. It was first reported in 1999 by Fukuroku et al. in two patients; one with polyostotic disease and tumor involving right humerus and the other with monostotic fibrous dysplasia involving right tibia.[14] Since then, three other cases have been reported.[13],[15],[16] Cases of angiosarcoma with fibrous dysplasia found in the English literature are summarized in [Table 1]. Eguchi et al. published a case of co-existing fibrous dysplasia and angiosarcoma on chest wall in a patient with no previous history of fibrous dysplasia, similar to our case.[15]
Table 1: Cases of angiosarcoma with fibrous dysplasia

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Although the prognosis is generally good, there is no cure for fibrous dysplasia. Therefore, patients with known disease should be offered life-long follow-up to detect malignant transformation as early as possible.[10]


   Conclusion Top


In our case, the patient had not been diagnosed with fibrous dysplasia as far as we know and had no previous history of radiotherapy. Both tumors were detected at the same time yet we believe that this case is a sarcomatous transformation. We report this unusual case of malignant transformation of fibrous dysplasia into angiosarcoma to contribute to the existing literature. Further investigation is required to clarify the pathogenesis of sarcomatous transformation of fibrous dysplasia and patients with fibrous dysplasia should be monitored for malignant changes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Oc Y, Kilinc BE, Ertugrul R, Sezer HB, Eren OT. Epithelioid angiosarcoma in femur: A case presentation. World J Oncol 2017;8:196-8.  Back to cited text no. 1
    
2.
Bovee JVMG, Rosenberg AE. Vascular tumors: Angiosarcoma. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO Classification of Tumors of Soft Tissue and Bone. Lyon: IARC; 2013. p. 337-8.  Back to cited text no. 2
    
3.
Baliaka A, Balis G, Michalopoulou-Manoloutsiou E, Papanikolaou A, Nikolaidou A. Primary angiosarcoma of bone. A case report. Hippokratia 2013;17:180-2.  Back to cited text no. 3
    
4.
Qu N, Yao W, Cui X, Zhang H. Malignant transformation in monostotic fibrous dysplasia: Clinical features, imaging features, outcomes in 10 patients, and review. Medicine 2015;94:e369.  Back to cited text no. 4
    
5.
Siegal GP, Bianco P, Dal Cin P. Tumors of undefined neoplastic nature: Fibrous dysplasia. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO Classification of Tumors of Soft Tissue and Bone. Lyon: IARC; 2013. p. 352-3.  Back to cited text no. 5
    
6.
Unni KK, Inwards CY. Conditions that commonly simulate primary neoplasm of bone: Fibrous dysplasia. In: Unni KK, Inwards CY, editors. Dahlin's Bone Tumors. Philadelphia, PA: Lippincott Williams & Wilkins; 2010. p. 317-26.  Back to cited text no. 6
    
7.
Doganavsargil B, Argin M, Kececi B, Sezak M, Sanli UA, Oztop F. Secondary osteosarcoma arising in fibrous dysplasia, case report. Arch Orthop Trauma Surg 2009;129:439-44.  Back to cited text no. 7
    
8.
Dabska M, Buraczewski J. On malignant transformation in fibrous dysplasia of bone. Oncology 1972;26:369-83.  Back to cited text no. 8
    
9.
Altay M, Bayrakci K, Yildiz Y, Sağlik Y. The development of osteosarcoma following radiotherapy for fibrous dysplasia. Acta Orthop Traumatol Turc 2004;38:353-6.  Back to cited text no. 9
    
10.
Mardekian SK, Tuluc M. Malignant sarcomatous transformation of fibrous dysplasia. Head Neck Pathol 2015;9:100-3.  Back to cited text no. 10
    
11.
Regado ER, Garcia PB, Caruso AC, de Almeida AL, Aymoré IL, Meohas W, et al. Liposclerosing myxofibrous tumor: A series of 9 cases and review of the literature. J Orthop 2016;13:136-9.  Back to cited text no. 11
    
12.
Kim GT, Lee JK, Choi BJ, Kim J, Han SH, Kwon YD. Malignant transformation of monostotic fibrous dysplasia in the mandible. J Craniofac Surg 2010;21:601-3.  Back to cited text no. 12
    
13.
Oh SH, Kang JH, Seo YK, Kim JH, Choi YS, Hwang EH. Malignant transformation of fibrous dysplasia into angiosarcoma. Oral Radiology 2020;36:116-20.  Back to cited text no. 13
    
14.
Fukuroku J, Kusuzaki K, Murata H, Nakamura S, Takeshita H, Hirata M, et al. Two cases of secondary angiosarcoma arising from fibrous dysplasia. Anticancer Res 1999;19:4451-7.  Back to cited text no. 14
    
15.
Eguchi K, Ishi S, Sugiura H, Noga K. Angiosarcoma of the chest wall in a patient with fibrous dysplasia. Eur J Cardiothorac Surg 2002;22:654-5.  Back to cited text no. 15
    
16.
Hakozaki M, Yamada H, Hasegawa O, Watanabe K, Konno S. 18F-FDG PET/CT of secondary epithelioid angiosarcoma of the proximal femur in a patient with polyostotic fibrous dysplasia. Clin Nucl Med 2017;42:e454-6.  Back to cited text no. 16
    

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Correspondence Address:
Selin Narter
Department of Surgical Pathology, Uludag University, Faculty of Medicine, 16059, Gorukle, Bursa
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_897_20

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