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CASE REPORT
Year : 2010  |  Volume : 6  |  Issue : 3  |  Page : 394-396

Radiation-induced chondrosarcomas: A case report with review of literature


Department of Histopathology, Rajiv Gandhi Cancer Institute & Research Centre, Rohini, Delhi, India

Date of Web Publication29-Nov-2010

Correspondence Address:
J S Gandhi
C-2-C/12/58, Janak Puri, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.73340

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 > Abstract 

Radiation therapy has become an important component of various cancer treatments. The development of second malignancy as a result of radiation therapy is a well-known sinister complication. However, radiation-induced sarcomas (RIS) are rare complications of radiation therapy. The timescale between completion of the radiotherapy and the development of a second malignancy, known as the latent period, can vary widely from as little as 5 years to 50 years later. Radiation-induced sarcomas per se are very rare and those with histomorphology of chondrosarcomas are even rarer. We report a rare case of RIS of left iliac bone in a 62-year-old lady after combined chemotherapy and external beam radiation therapy for cervical carcinoma (stage IIb). This case is being reported for its extreme rarity, vivid histology and clinical presentation.

Keywords: Radiation-induced sarcoma, chondrosarcoma, cervical carcinoma, radiation therapy


How to cite this article:
Gupta G, Hafiz A, Gandhi J S. Radiation-induced chondrosarcomas: A case report with review of literature. J Can Res Ther 2010;6:394-6

How to cite this URL:
Gupta G, Hafiz A, Gandhi J S. Radiation-induced chondrosarcomas: A case report with review of literature. J Can Res Ther [serial online] 2010 [cited 2019 May 25];6:394-6. Available from: http://www.cancerjournal.net/text.asp?2010/6/3/394/73340


 > Introduction Top


Radiation-induced sarcomas (RIS) are rare malignancies with an incidence of 0.03 - 0.8%. Radiation therapy forms an important part of treatment regimens in different cancers. Modern treatment regimens are aimed to improve better survival and quality of life in cancer patients but are not without long-term complications. The timescale between completion of the radiotherapy and the development of a second malignancy, known as the latent period, can vary widely from as little as 5 years up to 50 years later. [1] RIS are rare which commonly includes osteogenic sarcomas and fibrosarcomas. [2],[3] Chondrosarcomas are even rarer with histology different from primary chondrosarcomas, spindle cell component being a prominent feature with varied histology. [3] This report adds to the list of a very rare complication of RIS.


 > Case Report Top


A 62-year-old lady, seven years back at the age of 55 years, presented with bleeding per vaginum and friable cervix. A punch biopsy from cervix was done which showed a moderately differentiated adenocarcinoma. A total hysterectomy was done followed by radiation dose of 50 Gy of Co60 to the whole pelvis along with three cycles of weekly concurrent chemotherapy with cisplatin. After two years, patient presented with lymph node recurrence. She was given six cycles of chemotherapy with injection cisplatin, paclitaxel and ifosfamide together with external beam radiation therapy. After these therapies, the patient enjoyed good health for five years, with regular follow up with computed tomography (CT) scans of pelvis. Five years later, she presented with pain in left hip radiating to the left leg.

Physical examination revealed firm, non-ballotable mass with fullness in left iliac lumbar region. Magnetic resonance imaging (MRI) showed a soft tissue mass measuring 12.6 × 10.1 cm in the left iliac fossa which seemed to originate from left iliac bone [Figure 1]a. Positron emission tomography - computed tomography (PET-CT) showed a metabolically active lesion in left iliac wall with involvement of left ilio-psoas and gluteal muscles. An ultrasound guided core biopsy was taken which revealed a chondrosarcoma grade 2. Subsequently, the patient underwent a left internal hemi-pelvectomy for the same.
Figure 1: (a) MRI showing a soft tissue mass in the left iliac fossa appearing to be arising from left iliac bone. (b) Cut surface of tumor showing a glistening white lobulated tumor

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 > Pathology Top


Left iliac bone resection was received that appeared as a large grey white, polypoidal mass measuring 18 × 17 × 10 cm [Figure 1]b. Cut surface revealed a grey white, firm lesion with cystic areas. The patient's pathological staging was pT2b N0. Sections showed a tumor made up of chondrocytes in lacunae (hyaline) with areas of increased cellularity and pleomorphism. A similar, lobular pattern with hyocellular (chondroid) and hypercellular areas of spindle cells are seen in chondromyoid fibroma. Few areas showed lack of cartilage formation with clear cell and spindle cell areas showing nuclear crowding and focal necrosis, thus raising suspicion of dedifferentiation. However, the spindle cell element could be seen merging with cartilaginous areas and was present throughout the tumor [Figure 2]A. Mitotic activity was rare. Some areas presented a hemangiopericytomatous pattern resembling mesenchymal chondrosarcoma [Figure 2]B. Immunostains for S-100 protein were positive in both spindle and chondroid areas [Figure 3]. Immunostains for CD34, CD 99, P53 and SMA were negative in the spindle cell element. Thus, a diagnosis of chondrosarcoma grade 2 was confirmed.
Figure 2: (A) Showing spindle cell element, which could be seen merging with cartilaginous areas and was present throughout the tumor. (H and E, x 100). (B) Showing hemangiopericytomatous pattern with tumor giant cells. (H and E, × 200)

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Figure 3: (A and B) Spindle cell and differentiated chondrosarcomatous areas showing immunopositivity for S-100 protein. 3A (DAB x 100), 3B (DAB x 400)


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We had a three-months follow up of the patient where the patient presented with operative site abscess formation for which she underwent wound debridement and antibiotic treatment. The patient was subsequently lost to follow up.


 > Discussion Top


Malignant change in tissues exposed to ionizing radiation has been reported for more than hundred years. [4] Benign and malignant bone tumors have occurred even when the bone was not involved in the process being treated, but was only incidentally included in the field.

Literatures reveal an estimated incidence of 0.09-0.11% of sarcomas after all cases of radiation therapy. [5] An estimated incidence of 0.03%-0.8% of gynecologic malignancies as an absolute risk of post radiation sarcoma has also been reported [6]

According to Cahan's criteria for post radiation bone sarcoma which includes: (a) histological or radiologic proof that there was no previous tumor in the involved bone, (b) development of sarcoma in an irradiated area, (c) a sufficiently long interval between irradiation and development of sarcoma, and (d) histological proof of sarcoma. [7] These authors suggested an interval of five years, although three-4fouryears were thought to be sufficient by Arlen et al. [8] With the technological advance in radiation therapy, this relation changed and thus, Cahan's criteria were revised by Murray in 1999 which stated that radiation must have been given previously and the subsequent development of sarcoma must have arisen in the area included within 5% isodose line. [7],[9] Our case fulfilled all the above mentioned criteria.

The rarity of these tumors is reflected in the very few series reported in the English language medical literature. In a series of 130 patients diagnosed with RIS at the Mayo Clinic between 1933 and 1992, only 3.7% had chondrosarcoma. [10]

Our case had a unique histological pattern showing lobular pattern with hypo and hypercellular areas and spindle cell component that resembled chondroid myxoma along with hemangiopericytoma like areas with tumor giant cells. These features at times can be confused with mesenchymal chondrosarcomas. The presence of S-100 immunostaining in our case confirmed the cartilaginous nature of the tumor.

Prognosis for patients diagnosed with a post radiation sarcoma is generally poor. Lagrange had reported a median survival of 23 months in a series consisting of eighty patients. [3]

According to literature, the mechanism behind the RIS is due to loss of material from chromosome arm 3p, in particular 3p21-3pter, in 8 cases analyzed by comparative genomic hybridization (CGH). [11] The most frequent imbalance detected by CGH in their series was gain of 15cen-q15 (3 cases), followed by loss of chromosome 13 and gain of 5p, and 7cen-q22, each detected in two cases. Extensive expression of the KIT protein, but no mutations in exon 11 of the c-kit gene, has also been described. [12] Some authors suggested the role of TP53 gene mutations, which are commonly accompanied by immunohistochemical p53 over expression, in the pathogenesis of post radiation sarcoma. [13]

Surgery remains the cornerstone of treatment in RIS. When primary surgery fails, survival is usually short due to lack of available effective adjuvant or palliative treatment modalities. The role of chemotherapy and re-radiation is not well established. Recently, treatment with imatinib mesylate has been described for patients with post-radiation sarcomas having KIT expression. [12]

Radiation-induced chondrosarcomas are rare second malignancies with vivid histomorphology and should not influence treatment decisions.

 
 > References Top

1.Walton A, Broadbent AL. Radiation-induced second malignancies. J Pall Med 2008;11:1345-52.  Back to cited text no. 1
    
2.Patel SG, See AC, Williamson PA, Archer DJ, Evans PH. Radiation-induced sarcoma of the head and neck. Head Neck 1999;21:346-54.  Back to cited text no. 2
    
3.Lagrange JL, Ramaioli A, Chateau MC, Marchal C, Resbeut M, Richaud P, et al. Sarcoma after radiation therapy: retrospective multiinstitutional study of 80 histologically confirmed cases. Radiation Therapist and Pathologist Groups of the Fιdιration Nationale des Centres de Lutte Contre le Cancer. Radiology 2000;216:197-205.  Back to cited text no. 3
    
4.Peimer CA, Yuan HA, Sagerman RH. Postradiation chondrosarcoma. A case report. J bone Joint Surgery 1976;58:1033-6.  Back to cited text no. 4
    
5.Amendola BE, Amendola MA, McClatchey KD, Miller CH. Radiation-associated sarcoma: a review of 23 patients with post radiation sarcoma over a 50-year period. Am J Clin Oncol 1989;12:411-5.  Back to cited text no. 5
    
6.Mark RJ, Poen J, Tran LM, Fu YS, Heaps J, Parker RG. Postradiation sarcoma of the gynaecologic tract: a report of 13 cases and a discussion of radiation-induced gynaecologic malignancies. Am J Clin Oncol 1996;19:59-64.  Back to cited text no. 6
    
7.Cahan WG, Woodhard HQ. Sarcoma arising in irradiated bone; report of 11 cases. Cancer 1948;1:3-29.  Back to cited text no. 7
    
8.Arlen M, Higinbotham NL, Huvos AG, Marcove RC, Miller T, Shah IC. Radiation induced sarcoma of bone. Cancer 1971;28:1087-99.   Back to cited text no. 8
    
9.Murray EM, Werner D, Greeff E A, Taylor DA. Postradiation sarcomas: 20 cases and literature review. Int J Rad Oncol Biol Phys 1999;45:951-61.   Back to cited text no. 9
    
10.Wiklund TA, Blomqvist CP, Raty J, Elomaa I, Rissanen P, Miettinen M. Post irradiation sarcoma. Analysis of a nationwide cancer registry material. Cancer 1991;68:524-31.  Back to cited text no. 10
    
11.Mertens F, Larramendy M, Gustavsson A, Gisselsson D, Rydholm A, Brosjo O, et al. Radiation-associated sarcomas are characterized by complex karyotypes with frequent rearrangements of chromosome arm 3p. Cancer Genet Cytogenet 2000;116:89-96.  Back to cited text no. 11
    
12.Komdeur R, Hoekstra HJ, Molenaar WM, Van Den Berg E, Zwart N, Pras E, et al. Clinicopathologic assessment of postradiation sarcomas: KIT as a potential treatment target. Clin Cancer Res 2003;9:2926-32.  Back to cited text no. 12
    
13.Nakanishi H, Tomita Y, Myoui A, Yoshikawa H, Sakai K, KatoY, et al. Mutation sof the p53 gene in post radiation sarcoma. Lab Invest 1998;78:727-33.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]


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