This case report describes a 14-year-old female patient with a history of osteosarcoma in the left femur who later developed a metachronous osteosarcoma in the right femur. She initially received chemotherapy for the first osteosarcoma but later experienced pain in the right knee and imaging showed a tumor in the right distal femur. She ultimately developed metastases in the lung and died. While it is difficult to distinguish primary from metastatic osteosarcoma histologically, the features in this case were consistent with a second primary tumor in the right femur rather than a metastasis, as it appeared more than 10 months after the initial diagnosis. Metachronous osteosarcomas developing more than

1. Metachronous Osteosarcoma
:A Case Report
Clinical Meet, March 2017
Presenter:
Dr. Sarthak Moharir
PGY1,Dept. Of
Radiotherapy
Moderator:
Dr. KL Gupta
Professor & Head
Dept Of Radiotherapy
Moderator:
Dr. Amit Varma
Professor & Head,
Dept. Of Pathology

2.  A 14 year old female child, known case of osteosarcoma left lower end
femur, diagnosed on HPE on Jan. 2015 came to us with complaints of
pain, swelling and foul smelling discharge over the left knee.
 Patient had received 3 cycles of chemotherapy with Ifosfamide +
Adriamycin 6 months prior to presentation in our department. (August
2015)

3. General Examination
 Pallor present
 Pitting Edema over left foot
 left inguinal node 2.5x2.5cm tender, hard, fixed.
Local Exam: 30x40cm mass over left knee and thigh, with foul
smelling discharge and bleeding. Tenderness present.

4. MRI left Knee (06/8/15) A large irregular lobulated solid
cystic mass lesion circumferentially arising from distal
metaphysic and epiphysis of left femur with altered marrow
signal and trabecullar cortical erosions. It measures
approximately 19x 17 x 18 cm, for which, amputation was
planned.
Above knee Amputation of left leg was done (7/8/15)
Post Op HPE(12/8/15) Tumor infiltrating periosteum and
involving surrounding soft tissue with large area of necrosis
and hemorrhage (viable area approximately 20-25%) –
Osteogenic sarcoma with involvement of soft tissue

5.  CT Scan Chest and Abdomen(6/9/15) Negative for any metastatic
disease.
 Amputated site healed and healthy.
 Patient was then started on adjuvant chemotherapy with
Cisplatin 100 mg/m2+ Adriamycin 25 mg/m2. (7/9/15)
 After first cycle, patient developed pain in right knee.
 O/E: Slight swelling around the right knee joint, for which MRI was
done.

6.  X-ray showed periosteal reaction, and sunray appearance suggestive
of osteogenic sarcoma.
 MRI right knee and hip joint(15/9/15): Diffuse heterogenous signal
alteration in distal femoral shaft and distal metaphyses and femoral
condyles with patchy cortical erosions and periosteal elevation and
normal sub-periosteal soft tissue on both medial and lateral aspect-
possibility of metachronous osteogenic sarcoma of right distal femur.
 Patient was advised for bone scan.

7.  Bone Scan: Intense hot spot on the distal end of right
femur, probably neoplastic with rest of skeleton
unremarkable, for which biopsy was advised but patient
declined.
 X-ray Chest NAD, no evidence of metastatic deposits.
 Since patient declined for biopsy, we advised right knee
amputation, on clinico-radiologic grounds, but attendants
refused and patient was lost to further treatment.

8.  Patient reported after 10 months with diffuse
swelling with bleeding over right knee, along
with breathlessness.
 O/E: 30x22 cm swelling present over Rt. Knee
joint.
 X-ray Chest: S/o 3x3 cm deposit in right
upper lobe with cardiomegaly
 2D Echo: S/o pericardial effusion.
 In view of locally advanced metastatic
disease, patient was advised amputation to
improve the quality of life, which was done on
4/8/2016, and HPE reported as osteogenic
sarcoma.

9.  Patient was assessed for fitness for administration of
definitive chemotherapy, but was found to be unfit.
 Subsequently started on metronomic chemotherapy with
Cyclophosphamide 50mg OD in last week of August
2016.
 Patient reported to us in last week of December, with
painful swelling in the right operated site and
breathlessness. Clinically, patient was severely anemic,
with diffuse tender swelling in the right hemipelvis
suggestive of metastatic disease.
 X-ray Chest revealed extensive pulmonary metastasis
and massive pericardial effusion with destruction of right
iliac bone.
 Patient was kept on palliative management, but soon
succumbed to her disease.

10. Past History
 History Of trauma in October 2014, followed by gradually progressive swelling
associated with pain over left knee.
 X-RAY left knee joint(1/11/2014): Irregularity of margins in lower end of left femur
with periosteal reaction suggestive of chronic inflammation / neoplastic lesion.
 MRI left Lower Limb (1/11/2014): A large lobulated exophytic lesion in
metadiaphyseal region of left femur extending inferiorly in medial condyle upto
articular surface of knee joint with marked periosteal reaction collection and soft
tissue reactions suggestive of osteosarcoma.
 CECT Chest & Abdomen: No evidence of metastatic deposits.
 Histopathology (28/01/15) suggestive of Osteogenic Sarcoma, and was
administered 3 cycles of chemotherapy, and then reported to us August 2015.

11. Discussion &
Review Of Literature
 Osteosarcoma is a highly malignant and most frequently occurring
bone tumor with an incidence of 0.2-0.3/lakh population, and highest
in adolescents(15-19 years), three times more commonly occurring in
males.
 It mainly involves a single location in the metaphysis of a long bone,
Most commonly seen around the knee joint.
 Multifocal Osteosarcoma (MFOS) is rarer, and comprises 1-10% of all
osteoarcomas.
 Metachronous MFOS comprises 0.2-1.5% of all osteosarcoma, and
about 16% of all MFOS.
 Common presenting symptoms include local pain, associated swelling
of the afflicted area and limitation of joint movement.

12.  Two major theories exist in literature, over the multi-focality of
Osteogenic sarcoma. These include:
 Multisite lesions arising simultaneously, presumably all representing
multiple, synchronous, primary lesions
 Single site origin, with one dominant site, and then development of
new lesion: Metachronous/Metastatic

13.  Amstutz classification:
Types 1 & 2 represent synchronous MFOS, so called
osteochondromatosis:
 TYPE 1: <18 years old, with multiple, synchronously occurring bone
lesions with rapid progression within 5 months of diagnosis.
 TYPE 2: >18 years old, with multiple synchronously occurring bone
lesions arising within 5 months of presentation with a dominant mass.
Type 3 represents the categories of metachronous MFOS:
 TYPE 3a: Patients of any age, with metachronous metastatic bone
disease appearing 5-24 months of diagnosis.
 Type 3b: Patients of any age with metachronous metastatic bone
disease, appearing after 24 months of diagnosis.

14.  It is still an ongoing debate whether MFOS represents true multiple
primaries, or metastatic disease.
 Many authors have proposed that MFOS is caused by multiple primary
tumors because osteosarcoma manifests as a single primary bone
lesion that most frequently metastatizes to the lungs and less
frequently has bony metastasis.

15.  Parham et al.: No significant differences between patients presenting with or
without pulmonary metastasis. Absence of pulmonary metastasis is not sufficient to
prove the hypothesis of multiple primary origins.
 Mohoney et al. : Metachronous osteosarcoma probably represents metastatic
osteosarcoma to bone because pulmonary metastasis is frequently combined.
HOWEVER, some cases of Metachronous MFOS might represent new primary
lesions occurring in damaged/dystrophic mesenchymal tissue which have a
propensity to undergo malignant change, because the tumor-free period between
the primary and secondary skeletal lesions and long-term survival are unusual
features in metastatic osteosarcoma.
 Jeffree et al. : Median time for lung metastasis: 5-6 months after starting
treatment, and for Extra-Pulmonary metastasis: 9-10 months.

16. Discussion
MANAGEMENT:
 Neoadjuvant chemotherapy, followed by Surgery followed by adjuvant
chemotherapy is the mainstay of treatment.
 Radiation reserved for positive resection margins, unresectable
disease, local control and palliation.
 Stereotactic Ablative Body Radiotherapy (SABR) reserved for
oligometastasis (eg. Lung)
 1st line chemotherapy:
 Cisplatin+doxorubicin
 MAP(High dose Mtx.+Cisplatin+Doxorubicin)
 Doxorubicin+Cisplatin+Ifosfmide+High dose Mtx.
 Ifosfamide+Cisplatin+Epirubicin

17.  Second Line Therapy:
 Docetaxel+Gemcitabine
 Cyclophosphamide+Topotecan
 Gemcitabine single agent
 High dose Ifosfamide+Etoposide
 Ifosfamide+Carboplatin+Etoposide
 High dose Mtx+Etoposide+Ifosfamide
 Sorafenib
Discussion
MANAGEMENT:

18.  In our case, the metchronous lesion in the right femur appeared at the lower
end of right femur after 10 months, and pulmonary metastasis appeared
after 21 months of initial diagnosis.
 It is known that it is impossible to differentiate between primary and
metastatic osteosarcoma on histopathological grounds.
 The secondary lesion in this case had radiologic features of a typical primary
periosteal osteosarcoma. Therefore, we consider this case to be an example
of osteosarcoma from multiple primary origins.
 The diagnosis of metachronous (Amstutz Type 3) was made for our patient,
which itself presents as a rare entity developing >6 months of the initial
diagnosis.
Discussion

19. Thank You