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Journal of Bone and Soft Tissue Tumors (JBST) is the official Journal of The Indian Musculo Skeletal Oncology Society
Evaluation of Osteogenic Sarcoma
Volume 2 | Issue 1 | Jan-Apr 2016 | Page 8-12 | Mandip Shah, Chetan Anchan.
Authors: Mandip Shah[1], Chetan Anchan[2]
[1] SPARSH orthopedic Oncology Clinic, 9th floor, Medicare building, Ellisbridge, Ahmedabad. India
[2]Bombay Hospital & Medical Research Centre, Mumbai, India
Address of Correspondence
Dr. Mandip C Shah (M.S Ortho)
SPARSH orthopedic Oncology Clinic
9th floor, Medicare building, Ellisbridge, Ahmedabad, 380006
Email: drmandip@gmail.com
Abstract
Primary malignant bone tumors are very rare diseases and the initial symptoms and signs can be vague and nonspecific resulting in such patients receiving, at best, some symptomatic care, with the expectation that the problem would resolve naturally. Often the patient may wait out a period of weeks or months hoping that the problem would settle on its own with some home remedy. The foundation of optimal outcome in the treatment of any malignant disease is early detection and correct diagnosis. Osteosarcoma (also called as osteogenic sarcoma) is a high grade malignant disease which is fatal unless treated in time. Early detection and correct diagnosis can make a big difference in the outcome of treatment of these diseases. Awareness of these conditions and the knowledge of vulnerable age groups is the perfect start for achieving this goal. A detailed history of the presenting complaints and a thorough clinical evaluation of the patient will provide vital clues that should alert the clinician to a possible bone tumor. Radiographs and MRI form the mainstay of radiological investigation of bone tumors. Besides aiding in detection of the bone tumor, radiographs are of vital diagnostic value; whereas MRI provides very detailed anatomical information of the extent of the disease. No diagnosis of a malignant bone tumor is complete without histological confirmation of the disease and therefore biopsy is the final step in the diagnostic evaluation of a suspected malignant bone tumor. As for all malignant tumors, staging investigations must be done before starting treatment for osteosarcoma.
Keywords: Osteogenic Sarcoma, diagnosis, evaluation.
Introduction
Osteosarcoma is a malignant tumor of mesodermal origin where the tumor cells produce bone or osteoid [1]. It is the most common primary malignant bone tumor, excluding hematopoietic bone tumors [1, 2]. Despite the simple and clear definition of this disease, the term osteosarcoma represents a family of tumors with significant diversity in its histological features, grade and clinical behavior [1]. However, it is a very rare disease and represents less than 1% of all cancers diagnosed in the United States [4]. It is seen most frequently in children and adolescents peaking in the second decade, which coincides with the growth spurt [3]. In these young patients, it chiefly affects the metaphysis of long bones. The most commonly involved region is the knee with the distal femur being the most affected, followed by the proximal tibia [3]. Besides the appendicular skeleton, osteosarcoma can affect other bones too; including the skull, axial, and very rarely, the acral bones. Although the majority of osteosarcomas occur in children and adolescents, there is a second spike in its incidence which is seen in the elderly – above the age of 60 years [5]. Unlike in the younger patients where most of the osteosarcomas arise de novo, a large number of osteosarcomas in the elderly arise in preexisting bone pathologies like Paget’s disease, fibrous dysplasia and in areas previously treated with radiation for some other cause [6, 7]. Males are more frequently affected than females. The overall world male to female ratio of osteosarcoma, in the age group of 0-24 years is 1.43:1 [8]. This difference steadily decreases with increasing age [8]. Osteosarcoma is a high grade malignant tumor which is fatal unless detected and diagnosed in time, and treated appropriately. Due to the rarity of this disease and lack of very obvious early clinical diagnostic features, there is often a delay in its detection and diagnosis; adversely affecting the outcome of treatment. Early detection and correct diagnosis gives the patient the best start to a long and difficult fight. In this article we describe a simple, logical and practical approach to evaluating a patient for a suspected bone tumor.
Evaluation of Osteosarcoma
A systematic approach is involved in the evaluation of any suspected bone neoplasm so as to reach a correct diagnosis, following which optimal treatment can be planned. As for most bone tumors, in cases of suspected osteosarcoma, this involves detailed clinical, radiological and histological evaluation.
Clinical evaluation
The three chief presenting symptoms of any bone tumor are pain, swelling and disability (Fig 1). Of these, pain is the most common presenting complaint in osteosarcoma, which, to begin with, may be experienced during activity that loads the affected bone. The pain may be in the form of a dull ache or such non-specific nature which could be attributed to more common causes like bone/muscle/ligament injury, articular pathologies etc. The duration of this pain may range from days to months. Special attention must be paid to patients in the vulnerable age group, especially when the complaint is unilateral, localized, persistent or progressive. Some individuals may associate the onset of the disease with some past injury. However, there is no evidence to substantiate that injury can lead to genesis of osteosarcoma.
Unexplained musculoskeletal pain should be taken very seriously, especially in children and adolescents, and should not be dismissed without proper investigation. In general, one must rule out a neoplastic cause for the musculoskeletal pain if one or more of the points mentioned below are noted.
1) Unilateral and localized extremity pain without a known cause
2) Pain intensity/duration/evolution in conflict with assumed routine cause
3) Pain with swelling
4) Pain since weeks/months
5) Persistent or progressively increasing pain
6) Pain, only temporarily / not relieved – with conservative care (rest and analgesics)
7) Pain causing disability, or affecting activity which is considered normal for the patient
8) Pain aggravated/triggered with activity
9) Rest/night pain
The next common presenting complaint is swelling in the affected region. This swelling may be visible or/and palpable – depending on the size and location of the tumor. It is unusual for a patient of osteosarcoma to present with a painless swelling, with the possible exception of parosteal osteosarcoma. Unlike pain, which is far more likely to be due to some injury or many such routine causes, a swelling is clearly an indication of a pathology, the significance of which should be investigated without further delay. Again, one must be aware that there are many causes of bony swelling ranging from infection to various types of benign and malignant tumors, and tumor like conditions. It is useful to get answers to the following questions when a patient presents with a bony swelling.
1) Location and size of swelling?
2) Is the swelling painful or painless?
3) Did the pain lead to discovery of the swelling or an existing swelling became painful?
4) Duration – Days/weeks/months/years?
5) Rate of growth?
6) Solitary or multiple?
Pain or/and swelling may result in some form of disability. Pain in the lower limb may affect ambulation or cause limitation of range or function across the adjacent joint. Rarely, patients with osteosarcoma may present with a pathological fracture. Pathological fracture is uncommon in osteosarcoma as majority of these patients would have sought medical attention before such an event occurred [9]. The risk of pathological fracture is higher in telangiectatic variant of osteosarcoma as it is a lytic expansile disease. Pathological fracture in children and adolescents is far more likely to be due to benign conditions like simple bone cyst, fibrous dysplasia, aneurysmal bone cyst, etc. Nevertheless, an occasional telangiectatic osteosarcoma can present in a similar way. Therefore, it becomes essential that a clear diagnosis of the cause of the fracture is established before deciding on the treatment. To identify a pathological fracture, one must rely a lot on the circumstances of the fracture rather than the X-ray alone. One must seek answers to the following questions:
1) How did the fracture occur? Was the cause significant or trivial?
2) Did the patient have complaints of pain/swelling/disability in the affected region prior to the fracture?
3) Has the patient suffered similar fractures in the past in the same location or in other bones?
There are generally no systemic or constitutional symptoms due to osteosarcoma, unless the disease is very advanced with extensive metastases. Lungs are the most common site for metastasis and these patients mainly present with breathlessness [10]. Some patients may present with bone metastases, which is the most common site for extra-pulmonary metastasis [10]. Regional nodal metastases and systemic metastasis to other organs/tissue is rare [10].
Clinical Evaluation
A detailed clinical examination is the next step in the evaluation of a patient with suspected bone tumor. A detailed local examination assessing the exact location, size and extent of the lesion should be done. The findings could range from subtle signs like raised local temperature/deep tenderness/vague swelling, to a very obvious painful, tender and large bony swelling with stretched hypervascular overlying skin and restriction of associated joint function. One must also make a note of the function of the adjacent joint and any distal neuro-vascular deficit. Although nodal metastasis is very rare in osteosarcoma, as a routine practice, regional draining nodes should be examined.
Blood investigations
There are no specific serum markers for osteosarcoma. Patients with high pre-treatment Lactate Dehydrogenase (LDH) levels have been reported to have 20% lower disease free survival as compared to those with normal LDH levels [12]. Similarly, a high pretreatment level of serum Alkaline Phosphatase has been reported to be an independent adverse prognostic marker in the outcome of treatment of non-metastatic osteosarcoma of extremities [13].
Radiological Evaluation
The next logical step in the work-up of a suspected bone tumor is imaging. MRI and CT scan have revolutionized medical imaging of human body and have contributed hugely to the success in the treatment of musculoskeletal tumors. However, when it comes to diagnosing bone tumors, the imaging modality that matters the most is the plain radiograph. With few exceptions, all other imaging modalities help mainly in understanding the anatomical extent of the disease and are of limited/selective diagnostic value.
Radiograph
A good quality plain radiograph in two perpendicular planes screening the entire bone should be taken. Conventional osteosarcoma can have varying appearance on the plain X-ray. It appears like an ill-defined cloudy/fluffy radiodensity in the bone which may show a mixture of lytic and sclerotic areas. The borders of this lesion are ill-defined and it appears to permeate through the normal bone around. It does not have a precisely identifiable border on the X-ray and there is a wide zone where the disease merges with the normal bone. This is described as a “wide zone of transition” and is a sign of an aggressive disease. Once the disease breaches the cortex, it lifts up the periosteum which elicits a periosteal reaction which may have varying appearances described as a sunburst /spiculated/lamellated reaction or as a Codman triangle. All such patterns of periosteal reaction, which is described as an interrupted periosteal reaction, are a very important sign of a potentially malignant disease. Large osteosarcomas can have soft tissue extension of the disease which appears as a soft tissue shadow on the X-ray and which may show cloudy/fluffy radiodensities within it. Besides these classic X-ray findings of a conventional osteosarcoma, many of the rare variants of osteosarcoma have X-ray characteristics which are unique to that particular sub-type and could help in suspecting/identifying them [11] (Fig 2).
MRI
MRI is the investigation of choice in suspected case of osteosarcoma for local staging [14, 15]. One must insist on a contrast study screening of whole involved bone to rule out any skip lesion [16]. MRI must ideally be done before the biopsy as it helps in planning the biopsy approach and also in targeting representative areas within the lesion, avoiding areas of tumor necrosis. Also, doing an invasive procedure before the MRI may alter the MRI findings by causing procedure related artifacts and edema. MRI gives useful information on intra medullary and extramedullary extent of disease, presence of any skip lesion, proximity of the tumor to the neurovascular structures and involvement of joint / physeal plate etc (Fig. 3,4,5). An additional MRI study is usually advised after the completion of neoadjuvant chemotherapy, just prior to the surgery for local management of the osteosarcoma, Post chemotherapy response prediction can be assisted with MRI as well. Reduction in the size of the soft tissue mass/vascularity/reactive zone and intramedullary edema, thickening of the peritumoral capsule and presence of necrosis are some of the signs of good response to chemotherapy. Assessment of chemotherapy response is best done by contrast enhanced, diffusion weighted study [17,18].
Histopathological Evaluation
Although, the diagnosis of osteosarcoma can be assumed with a fair degree of certainty based on the clinical and radiological findings, under no circumstances the treatment can be started without histological confirmation. Osteomyelitis, osteoblastoma, bone metastasis, lymphoma, GCT, ABC, are the radiological differentials to osteosarcoma. On the other hand, one cannot rely only on biopsy alone for diagnosis of osteosarcoma – the classic example is of callus which can be indistinguishable from osteosarcoma on histology. Hence it is very important to correlate clinical, radiological and histological information to reach a diagnosis of any bone tumor. Biopsy is a procedure where a representative sample of the disease tissue is procured for histological studies. There are many ways this sample can be obtained. The routine procedures are open biopsy, needle biopsy and fine needle aspiration cytology (FNAC). Before doing a biopsy, it is advisable to complete all the radiological imaging studies. The most important step in planning a biopsy of any bone tumor is to decide on the approach. This is very important because, during the definitive surgery of a malignant bone tumor, the entire biopsy tract including the skin scar is excised en masse with the tumor. Therefore, it is very essential that the biopsy incision is placed in the line of the incision of the future surgery [19]. Open biopsy is a surgical procedure where tissue samples are obtained through a minor surgical procedure. The incision should be just adequate to obtain the deeper tissue and should be parallel to the long axis of the limb, in a location that would allow its easy excision along with the tumor at the time of definitive surgery. Needle biopsy is a procedure where tissue samples are obtained using a bone biopsy needle through a small stab incision. There are several advantages of needle biopsy over open biopsy. It causes limited contamination of the biopsy tract as it has a small footprint, which makes excision of the biopsy tract much easier during definitive surgery and also results in much less loss of skin as a result of the same. Besides this, it has several advantages like faster recovery, less hospital stay, lower cost etc. Also, the longer reach of the needle makes it easier to sample different regions of the tumor. As with open biopsy, the placement of the biopsy incision is important. Also, sampling of different regions of the lesion should be done through the same incision by just changing the angle of the needle and not through another skin incision. The only relative disadvantage of this procedure as compared to open biopsy is perhaps the smaller quantity of tissue sample that may be obtained, which could prove challenging to the pathologist to work on. However, in experienced hands this is generally not a problem. Frozen section may be used to confirm that the tissue sample obtained is representative. However, it should not be relied on to make a definitive diagnosis of bone tumors. FNAC as a procedure has many advantages, being minimally invasive and practically without morbidity, and with the least risk of tumor seeding along the biopsy tract. There are many reports of bone tumor diagnosis using FNAC. However, it has some limitations especially related to adequate representative tissue sampling and hence is not ideal for a definitive diagnosis of bone tumors like osteosarcoma [20].
Staging in Osteosarcoma
Cancer staging is a process to know the magnitude of the primary tumor and possible spread of the disease in a particular patient. It helps to understand the severity of the disease and hence the prognosis and thus aids in optimal treatment planning. Staging any cancer is therefore mandatory before starting its treatment. The most common site for metastasis in osteosarcoma is lung, followed by the skeletal system. At presentation, the reported incidence of lung metastasis is 15-20% whereas for skeletal metastasis it is 4%. Staging investigations includes High Resolution CT scan of thorax (plain) + Tc-99m methylene diphosphonate (Tc-99m MDP) Bone scan. Nowadays, 18 Fluoro Deoxy Glucose PET-CT scan is showing great promise as an alternative staging investigation. Plain chest radiograph can only detect large lung metastasis. For detection of early smaller lung lesions, a high resolution CT scan of thorax without contrast is recommended [21]. Typically metastases appear of soft tissue attenuation, dull, well circumscribed rounded lesions, more often in the periphery of the lung. Patients who present with metastatic pulmonary disease have a poorer prognosis. However, cure can be achieved in a small number of patients who respond well to chemotherapy and undergo pulmonary metastatectomy [22, 23]. (Tc-99m MDP) Triple-phase, whole-body bone scintigraphy still remains standard of care for determining the sites of metastatic disease in the skeletal system [24]. It may also detect skip lesions, although MRI is more accurate for this purpose. Whole-body turbo STIR MRI is also a reliable method for screening patients with suspected skeletal metastases. It is more specific than bone scan. This technique is also advantageous in that it reveals extraskeletal organ and soft tissue metastases [25]. Longer study time and cost are the limiting factors. Functional or metabolic imaging in form of 18 Fluoro Deoxy Glucose PET-CT scan is much more sensitive and specific than Tc-99m MDP bone scan in picking up the skeletal metastasis in osteosarcoma [26]. Moreover it gives valuable information on viable disease representation in proposed site for biopsy and some idea of the grade of the sarcoma. As it remains unaffected by presence of metallic prosthesis and radiation beam hardening artifacts, it is extremely valuable in detecting and defining a suspected recurrence [27]. However its scarce availability and prohibitive cost at present, makes it a difficult investigation to recommend in every case. Most popular staging system for bone and soft tissue sarcomas has been the Enneking’s staging system (Table 1). It is based on histological grade of sarcoma, local extent of disease i.e. intra or extra- compartmental involvement and presence or absence of metastasis [28]. American Joint committee on Cancer (AJCC) has also developed a staging system for sarcomas. (Table 2) It takes into the consideration the size of sarcoma, tumor grade, presence, and location of metastases [29].
Conclusion
Osteosarcoma is a high grade malignant disease which is fatal unless treated appropriately, in time. Effective treatment is available for this disease with a high cure rate. However, despite the availability of such treatment in developing countries, the cure rates for osteosarcoma are much lower as compared to the western population. One of the most significant points of failure is timely detection and diagnosis of this condition. Awareness of this disease and the knowledge of the vulnerable age group can go a long way in improving the prospects for osteosarcoma patients in developing countries. Time tested clinical skills along with readily available radiological imaging modalities and histopathology will help us reach accurate diagnosis and staging in most cases of osteosarcoma.
References
1. Klein MJ, Siegal GP. Osteosarcoma: anatomic and histologic variants. Am J Clin Pathol. 2006 Apr; 125(4):555-81.
2. Dorfman HA, Czerniak B. Bone Cancers. Cancer supplement. 1995;75(1):203–10.
3. Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009;152:3-13.
4. Lisa Mirabello, Rebecca J. Troisi, and Sharon A. Savage. Osteosarcoma incidence and survival rates from 1973 to 2004: Data from the Survei llance, Epidemiology, and En d R esults Program. Cancer. 2009 Apr 1; 115(7): 1531–1543.
5. Unni KK. Dahlin’s bone tumors: general aspects and data on 11,087 cases. 5. Philadelphia: Lippincott-Raven; 1996. pp. 143–83.
6. Huvos AG. Osteogenic sarcoma of bones and soft tissues in older persons. A clinicopathologic analysis of 117 patients older tha n 60 years. Cancer . 1986 Apr 1;57(7):14 -42 9
7. Jhala DN, Eltoum I, Carroll AJ, et al. Osteosarcoma in a patient with McCune-Albright syndrome and Mazabraud’s syndro me: a case rep ort emp hasizin g the cytological and cy togenetic findings. Hum Pathol. 2003;34:1354-1357
8. Lisa Mirabello, Rebecca J. Troisi, and Sharon A. Savage. International osteosarcoma incidence patterns in children an d adolesce nts, middle ages, and elderly persons. Int J Cancer. 2009 Jul 1; 125(1): 229–234.
9. Lee RK1, Chu WC, Leung JH, Cheng FW, Li CK. Pathological fracture as the presenting feature in pediatric osteosarcoma . Pediatr Bloo d Cance r. 2013 Jul;60(7):1118-21.
10. Jeffree GM, Price CH, Sissons HA. The metastatic patterns of osteosarcoma. Br J Cancer. 1975 Jul; 32(1): 87–107
11. Yarmish G1, Klein MJ, Landa J, Lefkowitz RA, Hwang S. Imaging characteristics of primary osteosarcoma: nonconventional subtypes. Radiographics. 2010 Oct;30(6):1653-72.
12. Bacci G, Longhi A, Ferrari S, Briccoli A, Donati D, De Paolis M, Versari M. Prognostic significance of serum lactate dehydrogenase in osteosarcoma of the extremity: experience at Rizzoli on 1421 patients treated over the last 30 years. Tumori. 2004 Sep-Oct;90(5):4 78-8 4
13. 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 Mar 1;106(5): 1154-61.
14. Rubin DA. Magnetic resonance imaging: Practical considerations. In: Resnick D, Kransdorf MJ, editors. Bone and joint imaging. 3rd ed. Philadelphia Pennsylvania: Elsevier Saunders; 2005. pp. 118–32.
15. Bohndorf K, Reiser M, Lochner B, Feaux DL, Steinbrich W. Magnetic resonance imaging of primary tumors and tumor-like lesions of bone. Skeletal Radiol. 1986;15:511–7.
16. Skip Metastases in Osteosarcoma: Experience of the Cooperative Osteosarcoma Study Group JCO April 1, 2006 vol. 24 no. 10 1535-1541 Leo Kager, Andreas Zoubek, Ulrike Kastner et al.
17. Holscher HC, Bloem JL, Vanel D, Hermans J, Nooy MA, Taminiau AH, et al. Osteosarcoma: Chemotherapy induced changes at MR imaging. Radiology. 1992;182:839–44.
18. Uhl M, Saueressig U, van Buiren M, Kontny U, Niemeyer C, Köhler G, et al. Osteosarcoma: Preliminary results of in vivo assessment of tumor necrosis after chemotherapy with diffusion- and perfusion-weighted magnetic resonance imaging. Invest Radiol. 2006;41:618–23.
19. Liu PT, Valadez SD, Chivers FS, Roberts CC, Beauchamp CP. Anatomically Based Guidelines for Core Needle Biopsy of Bone Tumors: Implications for Limb-sparing Surgery Radiographics. 2007 Jan-Feb;27(1):189-205; discussion 206.
20. Jorda M1, Rey L, Hanly A, Ganjei-Azar P. Fine-needle aspiration cytology of bone: accuracy and pitfalls of cytodiagnosis. Cancer. 2000 Feb 25;90(1):47-54.
21. Picci P, Vanel D, Briccoli A et al. Computed tomography of pulmonary metastases from osteosarcoma: the less poor technique. A study of 51 patients with histological correlation. Ann Oncol 2001; 12: 1601–1604.
22. Rasalkar DD1, Chu WC, Lee V, Paunipagar BK, Cheng FW, Li CK. Pulmonary metastases in children with osteosarcoma: characteristics and impact on patient survival. Pediatr Radiol. 2011 Feb;41(2):227-36.
23. Bacci G, Picci P, Briccoli A, Avella M, Ferrari S, Femino FP, et al. Osteosarcoma of the extremity metastatic at presentation: results achieved in 26 patients treated with combined therapy (primary chemotherapy followed by simultaneous resection of the primary and met astatic lesions). Tumori. 1992;78:200–6.
24. Schneider R. Radionuclide technique. In: Resnick D, Kransdorf MJ, editors. Bone and joint imaging. 3rd ed. Philadelphia Pennsylvania: Elsevier Saunders; 2005. pp. 86–117.
25. Frat, Ali, Ağldere, Muhtesem , Gençoğlu, Arzu et al. Value of Whole-Body Turbo Short Tau Inversion Recovery Magnetic Resonance Imaging With Panoramic Table For Detecting Bone Metastases: Comparison With 99MTc-Methylene Diphosphonate Scintigraphy; Journal of Comp uter Assisted Tomography: January/February 2006 – Volume 30 – Issue 1 – pp 151-156
26. Byun BH, Kong CB, Lim SM et al. Comparison of (18) F-FDG PET/CT and (99 m)Tc-MDP bone scintigraphy for detection of bone metastasis in osteosarcoma. Skeletal Radiol. 2013 Dec; 42(12):1673-81.
27. Benz MR, Tchekmedyian N, Eilber FC et al. Utilization of positron emission tomography in the management of patients with sarcoma. Curr Opin Oncol 2009; 21: 345 –351.
28. Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop. 1980;153:106–20.
29. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual (7th ed). New York, NY: Springer; 2010.
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Osteosarcoma – A Clandestine Enigma
Vol 2 | Issue 1 | Jan – Apr 2016 | page:6-7 | Ashish Gulia.
Author: Ashish Gulia[1]
[1] Orthopaedic Oncology, Tata Memorial Hospital, Mumbai, India.
Address of Correspondence
Dr. Ashish Gulia MS (Ortho), Mch – Surgical Oncology
Fellowship – Musculoskeletal Oncology (TMH – HBNI)
Asst. Professor – Orthopaedic Oncology, Tata Memorial Hospital, Mumbai, India
Osteosarcoma – A Clandestine Enigma
Bone tumors form a small part of all human cancers. As per the SEER data about 2570 new cases of bone sarcomas were diagnosed in the United States in the year 2005. Osteosarcoma, earlier called as “Osteogenic Sarcoma” is the most common primary bone tumor in humans, which has a predilection for metaphysis of long bones in children, adolescents, and young adults and most commonly involves the bones around the knee joint in about 65% of cases. The earliest published literature takes us to 1879, where in his publication, Gross advocated early amputation as the only treatment modality for extremity osteosarcoma with dismal survival outcomes. Since then the overall outcome of osteosarcoma has seen a sea change. This journey of evolution of treatment of osteosarcoma has been a roller coaster ride with its ups and downs. The world has seen remarkable survival improvements with some rapid strides in 1970s and 1980s. Introduction of multi-agent chemotherapy improved the 5 year survival from a dismal 20% to almost 70%. This fast paced growth reached a stagnant phase with no further improvements in the survival in almost last three decades. Though multiple agents have been tested in both phase II and phase III randomized controlled trials, none has been significant enough to be incorporated in clinical practice. Similar to the oncological outcomes, functional outcomes have also seen a dramatic improvement over last half a century. Limb salvage has become a norm in today’s orthopedic oncology practice, which wasn’t so in 1970s. Advent of neo-adjuvant chemotherapy, refinements in surgical skills, availability of durable metallic endo-prosthesis have led to a “limb salvage revolution” where about 85% to 90% of extremity osteosarcoma patients use their own extremity at the end of the treatment. The exponential growth in function preservation still continues with more technology driven innovations and solutions making the commonly encountered implant related complications like aseptic loosening and frequent breakage, a thing of the past. The current standards of care warrant a multi-disciplinary approach in the management of osteosarcoma. The approach is not only required in treatment phase involving a multi-agent neo adjuvant chemotherapy followed by optimal surgical resection & reconstruction and adjuvant chemotherapy, but also in evaluation, diagnosis and staging process. A seamless integration between musculoskeletal surgeon, musculoskeletal radiologist and sarcoma pathologist can achieve higher levels of accuracy in diagnosis in order to initiate the optimum line of treatment within an ideal time frame. The presence of metastatic disease at presentation is one of the most significant negative prognostic factors. Western data have shown that about 15% to 20% of patients will have clinically detectable metastases at presentation with lung being the most common site of metastasis in about 85% of cases followed by bone as the second most common site. These figures may be higher in developing countries as patients typically present with large volume disease. Lack of awareness, belief in alternative medicine and poor socio economic status are some of the factors contributing to higher percentages in these countries. Delay in diagnosis due to lack of suspicion and inappropriate initial evaluation as well as management has also led to dismal outcomes. The present symposium on Osteosarcoma tries to address the above issues and provide evidence based robust data, which will help the clinicians to understand the principles for evaluation and management of extremity osteosarcoma. The importance of understanding the presenting symptomatology and clinical evaluation is well scripted in the first article [1]. This article also stresses the importance of multi disciplinary strategy to diagnose a suspected bone lesion correctly. It discusses in depth the role of sequential radiological and histopathological evaluation of a suspected case of osteosarcoma. Staging of osteosarcoma is also discussed, which eventually helps clinicians to plan the treatment and estimate the prognosis. Radiological evaluation, whether it is with radiographs or with high end cross sectional imaging, has been the cornerstone for diagnosis and the local staging of the disease. Osteosarcoma exhibits various radiological and histological forms, which have deep implications on their treatment. These varied radiological presentations are discussed in the second article, which gives a tabulated comparison of various characteristics and their differentials [2]. The modern era is dominated by technology driven tools and this surge is quite evident in evaluation of bone tumors too. Emergence of PET scan as a “one stop shop” for the evaluation of bone tumors has created some whirlpools, leading to unending debates in recent era. Though more data is being collected to prove its worth in osteosarcoma, it is now being used to replace invasive investigations in other tumors like Ewing sarcoma and chondrosarcoma. The third article discusses the use of PET scan as a single modality to stage as well as to assess the chemo response evaluation in osteosarcoma [3]. The recent advances of this bio-imaging tools and the probable futuristic avenues are addressed in the third article. Complete surgical resection has been the single most important criteria to achieve adequate local control. Local relapses are associated with very poor overall survivals. The surgeons need to work to achieve a fine balance between complete tumor resection and retaining function. Over the years this has been addressed by “concept of margins” which was first popularized by the godfather of musculoskeletal oncology, Dr. W.F. Enneking. The concept was further revisited and modified by Kawaguchi, who gave the concept of “barrier effects” and challenged the traditionally propagated concept of “quantitative margins” and replaced it with a new concept of “qualitative margins”. The fourth article in the symposium address the similar issues regarding the adequacy of margins in the resection of osteosarcoma [4]. The article also explains the relationship of local failures with respect to resection margins and tumor necrosis. As discussed earlier multi-agent chemotherapy forms an integral part of management of osteosarcoma. The next article details the evolution of various chemotherapy protocols and current standards of chemotherapy for osteosarcoma [5]. Osteosarcoma is considered as a radio-resistant tumor, thus radiotherapy had a limited role in the management of osteosarcoma. Similar to the other specialties of medicine, radiation oncology has seen major changes in understanding the mechanism of radio tumor kill and also in the development of the delivery system. The advent of high-end technique like carbon ion and proton beam radiotherapy with their high accuracy, ability to give very high focused dosage and reduced side effects have made radiotherapy a new tool in the armamentarium for local control in osteosarcoma. Though these techniques are more useful in non-resectable lesions of axial skeleton, these are becoming increasingly popular in margin positive cases to avoid amputations. The latest updates regarding the use of this modality are explained in the last article of the symposium [6]. This symposium on osteosarcoma has been divided in to two sets, this first set encompasses articles related to evaluation and overall management of extremity osteosarcoma. Next issue will contain the second half of the symposium which will have articles on surgical management and advances in the management of osteosarcoma.
References
1. Shah M, Anchan C. Evaluation of Osteogenic Sarcoma. Journal of Bone and Soft Tissue Tumors Jan-Apr 2016;2(1):8-12.
2. .Janu A, Jain N, Juvekar S, Gulia A. Radiological Review of Extremity Osteosarcoma. Journal of Bone and Soft Tissue Tumors Jan-Apr
2016;2(1):13-18.
3. Purandare NC, Rangarajan V. Emerging role of PET/CT in osteosarcoma. Journal of Bone and Soft Tissue Tumors Jan-Apr 2016;2(1):19-21.
4. Cloake T, Jeys L.How important are surgical margins in Osteosarcoma? . Journal of Bone and Soft Tissue Tumors Jan-Apr 2016;2(1):22-26
5. Jain S, Kapoor G. Chemotherapy in Osteosarcoma: Current Strategies. Journal of Bone and Soft Tissue Tumors Jan-Apr 2016;2(1):27-32.
6. Kakoti S, Khanna N, Laskar S. The Current Role of Radiation Therapy for Osteogenic Sarcoma. Journal of Bone and Soft Tissue Tumors Jan-Apr
2016;2(1):33-35.
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Extraskeletal Myxoid Chondrosarcoma- Rare ‘Non-chondroid’ soft tissue Sarcoma!!!
Volume 2 | Issue 1 | Jan-Apr 2016 | Page 36-38 |Shital Biradar, Sujit Joshi, Yogesh Panchwagh, Vikram Ghanekar, Pradeep Kothadiya.
Authers: Shital Biradar[1], Sujit Joshi[1], Yogesh Panchwagh[2], Vikram Ghanekar[3], Pradeep Kothadiya[4].
[1]Dept. of Pathology, Deenanath Mangeshkar hospital, Pune.
[2]Histopathologist, Deenanath Mangeshkar hospital, Pune.
[3]Orthopedic Onco-surgeon, Deenanath Mangeshkar hospital, Pune.
[4]Surgical oncologist, S.G.M. Hospital; Chiplun.
[5]Orthopedic Surgeon, Kothadiya Hospital; Solapur.
Address of Correspondence
Dr. Sujit Joshi
Flat No: 2, Lunawat Reality, Opp. Vanaz Company, Paud road, Kothrud, Pune-411038.
Email ID: sujitjoshi30@gmail.com
Abstract
Extraskeletal myxoid chondrosarcoma (ESMC) is an uncommon but distinct entity with clearly different clinicopathological, immunohistochemical and cytogenetic features from those of conventional skeletal chondrosarcoma. Because of its better prognosis as compared to conventional skeletal chondrosarcoma, an accurate diagnosis is essential. We present 2 cases of this tumor with different clinical presentations.
1. 40 year old house wife presenting with a 9x8cm size mass around lower end of femur. On imaging, it was a soft tissue mass abutting the femoral surface with minimal bone invasion.
2. 50 year old lady presenting with a huge fungating soft tissue mass over left lower leg and foot associated with similar cutaneous nodules over right arm and left thigh. The left leg mass had caused destruction of entire lower end of fibula.
Histopatholgical evaluation of both cases showed features of Extraskeletal Myxoid Chondrosarcoma (ESMC). Characteristic histopathological features include a malignant soft tissue neoplasm with lobulated growth pattern, abundant myxoid matrix and fairly bland looking tumor cells. There is no convincing evidence of cartilagenous differentiation or chondroid matrix production. Immunohistochemistry has a limited role.
ESMC is a tumor with long survival but a prolonged follow up is necessary in view of high local recurrence, high metastatic rates and high disease related mortality. The diagnosis of this tumor largely depends upon knowledge of this entity and its characteristic histopathological features.
Key words: Extra-skeletal myxoid chondrosarcoma; ESMC.
Introduction
Extraskeletal myxoid chondrosaroma (ESMC) is a rare malignant soft tissue sarcoma described as a distinct clinico-pathologic entity by Enzinger and Shiraki in 1972 [1]. WHO categorized this tumor as a tumor of uncertain differentiation since there is paucity of convincing evidence of cartilagenous differentiation. It is a rare tumor, accounting for less than 3% of soft tissue sarcomas [2,3]. The tumor usually develops in deep parts of the proximal extremities and in middle-aged adults [4]. More than two-thirds of the tumors occur in the proximal extremities and limb girdles, especially the thigh and popliteal fossa. Here, we are presenting the detailed clinico-pathological findings of two such cases, which were diagnosed in our institute.
Case Report
Case 1: 40 year old housewife presented with lower limb swelling and pain just above the knee joint which started since 5 months (Fig 1). Plain radiographs reveal a soft tissue mass abutting the femoral surface with minimum bony involvement in supracondylar region of femur suggestive of a soft tissue neoplasm (Fig. 2). MRI revealed a large extra-osseous soft tissue lesion with minimal intra-osseous extension suggestive of a juxtacortical neoplasm or soft tissue sarcoma (Fig. 3). Open biopsy was done elsewhere and reports were reviewed at authors institute. It showed microscopic features of ESMC. Considering the interosseous involvement and safe oncological margins, a wide resection was planned. The patient underwent limb salvage surgery in form of wide local excision of distal femur along with the mass and reconstruction with a megaprosthesis. Pathological Findings: On gross examination of the wide local excision specimen of distal femur, there was an extra-osseous mass at the lower end of femur on the postero-lateral aspect measuring 9×8 cm in size. It was a soft to firm, ovoid, lobulated mass which on cut section, was gelatinous, mucoid and gray-white. There was no evidence of necrosis or haemorrhage noted (Fig 4). Microscopically, it showed a characteristic multi-nodular pattern. Tumor cells were small round with hyperchromatic nuclei and a narrow rim of cytoplasm (Fig 5a). Cells were arranged in cords and strands separated by abundant myxoid material (Fig 5b,c). No cartilaginous matrix production was seen in the stroma. On Immuno-histochemestry (IHC) the cells showed strong positivity for Vimentin and focal positivity for S-100 protein. These cells were negative for Cytokeratin, EMA, Synaptophysin and Chromogranin. Based on morphological and IHC findings, a diagnosis of Extra-skeletal myxoid chondrosarcoma (ESMC) was reached.
Case 2: 50 year old lady presented with a huge fungating soft tissue mass over left foot associated with similar cutaneous nodules over right arm and left thigh. The foot lesion was progressively increasing over a year but not associated with pain. (Figure 6a, 6b)
X-ray of left foot and lower limb revealed a large soft tissue mass destroying the metatarsals , devoid of any matrix and periosteal reaction (Fig. 7a). Similar lesion was seen destroying the ipsilateral distal fibula (Fig. 7b). Biopsies from the foot mass and the arm nodule revealed histopathological and IHC findings consistent with Extraskeletal Myxoid Chondrosarcoma (ESMC). This patient defaulted for further treatment and follow up.
Discussion:
Extraskeletal myxoid chondrosarcoma (ESMC) is a rare, morphologically distinct soft tissue sarcoma with characteristic nodular architecture & abundant myxoid matrix. In 1972, Enzinger and Shiraki were the first ones who coined ESMC as a distinct entity [1]. In spite of it’s name, Extraskeletal myxoid chondrosarcoma (ESMC) is considered as a “Tumor of uncertain differentiation” because there is no definite evidence of cartilage matrix production in the tumor. Histogenesis of ESMC is still subject of controversy. Incidence of this tumor is only 2.3% of all soft tissue sarcomas as reported by Tsuneyosi et al [2]. Mainly the adult age group (35 years and above) is affected by this tumor, with equal sex predilection [3]. Most common sites are deep soft tissues of the proximal extremities and limb girdles, especially the musculature [4]. However, few uncommon sites are also been described like mediastinum, retroperitoneum, abdomen and the digits [5-7]. In both of our cases, imaging showed that it was a lobulated soft tissue mass without bony periosteal reaction or any radiologically evident matrix production. Histopathologically, both cases showed presence of uniform eosinophilic cells arranged in cords & deposited in an abundant myxoid stroma. There was no evidence of cartilage/osteoid matrix deposition.
The most important clue to the diagnosis of this rare entity is the typical arrangement of cells in cords and columns with a very prominent myxoid background [8]. ESMC appears to exhibit a high tendency of local recurrence & distant metastases, predominantly to the lungs, sometimes years after the initial diagnosis [9]. ESMC should be considered an intermediate grade tumor rather than a low-grade malignant neoplasm as the estimated 5, 10 and 15-year survival rates described by Meis-Kindblom et al were 90%, 70% & 60% respectively [4]. Wide local excision of the tumor is the treatment of choice. If a wide margin can not be obtained, a high rate of local recurrence is observed with poor response to chemotherapy & radiotherapy. Therefore, surgery with appropriate adequate margins continues to be the treatment of choice, for primary as well as recurrent or metastatic tumors.
On follow up part, our first patient is disease free at 6 years from date of surgery with excellent function in the operated limb (MSTS score 97%). The second patient defaulted for further treatment and was lost to follow up. Some adverse pathological prognostic factors reported in literature include Tumor size ≥ 10 cm, high cellularity, anaplasia or rhabdoid features, mitotic activity more than two per 10 high-power fields, and Ki-67 proliferative index of ≥ 10%. These indicate more aggressive behavior, requiring a closer follow-up of the patient [10]. In summary, ESMC is an uncommon but distinct soft tissue sarcoma, clearly different from conventional skeletal chondrosarcoma. Knowledge of this entity and accurate diagnosis is essential because of the difference in its behaviour and prognosis.
References
1. Enzinger FM, Shiraki M. Extraskeletal myxoid chondrosarcoma. An analysis of 34 cases.Hum Pathol 3: 421-35,1972.
2. Tsuneyoshi M, Enjoji M, Iwasaki H and Shirahama N: Extraskeletal myxoid chondrosarcoma: a clinicopathologic and electron microscopic study. Acta Pathol Jpn 31: 201-208, 1981.
3. Antonescu CR, Argani P, Erlandson RA, et al: Skeketal and extraskeletal myxoid chondrosarcoma: a comparative clinicopathologic, ultrastructural, and molecular study. Cancer 83:1504-1521, 1998.
4. Meis-Kindblom JM, Bergh P, Gunterberg B, et al: Extraskeletal myxoid chondrosarcoma: a reappraisal of its morphologic spectrum and prognostic factors based on 117 cases. Am J Surg Pathol 23: 636-650, 1999.
5. Oliveira AM, Sebo TJ, McGrory JE, et al: Extraskeletal myxoid chondrosarcoma; A clinocopathologic, immunohistochemical, and ploidy analysis of 23 cases. Mod Pathol 13: 900-908, 2000.
6. Patel SR, Burgess MA, Papadopculos NE, Linke KA and Benjamin RS: Extraskeletal myxoid chondrosarcoma: long-term experience with chemotherapy. Am J Clin Oncol 18: 161-163,
1995.
7. Okamoto S, Hara K, Sumita S, et al: Extraskeletal myxoid chondrosarcoma arising in the finger. Skeletal Radiol 31: 296-300, 2002.
8. Jakowski JD, Wakely PE Jr. Cytopathology of extra-skeletal myxoid chondrosarcoma: Report of 8 cases. Cancer 2001; 111:298-305
9. Weiss SW and Goldblum JR: Extraskeletal myxoid chondrosarcoma. In: Soft Tissue Tumors 4th Edition. Mosby, St. Louis,pp1368-1379, 2001.
10. Oliveria Am, Sebo TJ, McGrory JE, Gaffey TA, Rock MG, Nascimento AG. Extraskeletal myxoid chondrosarcoma: A clinicaqopthologic, immunohistochemical & ploidy analysis of 23 cases. Mod Pathol 2000; 13:900-8.
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Fibrous Dysplasia – an Update
Volume 2 | Issue 1 | Jan-Apr 2016 | Page 39-43 | Ashish Gulia, Pankaj Kumar Panda.
Author: Ashish Gulia [1] , Pankaj Kumar Panda [2]
[1]Orthopaedic Oncologist, Tata Memorial Hospital, Mumbai.
[2]Post-graduate Student, Clinical Research, Tata Memorial Hospital, Mumbai
Address of Correspondence
Dr Ashish Gulia
Associate Professor, Orthopedic Oncology, Dept. of Surgical Oncology, Tata Memorial Hospital,
Mumbai – 400012, India.
Email: aashishgulia@gmail.com
website: animaljam2.net
Abstract
Background: Fibrous dysplasia (FD) belongs to a group of non-hereditary benign pathologies in which immature bone and fibrous stroma replaces normal medullary bone. The gene for FD is located on band 20q13, an area that codes for the α subunit on G-protein receptors. It is most commonly diagnosed in the first three decades of life. Amongst the 4 major clinical forms of FD (namely monostotic, polyostotic, McCune-Albright syndrome, Mazabraud’s syndrome) the monostotic form predominates (70-80%) in comparison to the polyostotic form. “Ground Glass appearance is a characteristic appearance on plain radiograph. Histopathologically fibrous component is relatively avascular, composed of cytologically bland spindle cells with few trabecular structures. The management ranges from watchful observation to surgical intervention.
Key-words: Fibrous dysplasia, polyostotic, monostotic, bone grafting, bisphosphonates.
Introduction
Fibrous dysplasias (FD) are a group of non-hereditary benign pathologies in which immature bone and fibrous stroma replace normal medullary bone as a result of abnormal differentiation of osteoblasts characterized by solitary (monostotic) or multi focal medullary (polyostotic) fibro osseous lesions. They contain mutated fibroblast cells and osteoblasts of varying functionality, which produce abnormally immature woven bone [1]. They are accounted for 2.5% of all the bone tumors and 5–7% of all benign bone tumors [2]. The detailed description as a benign developmental disorder of the bone was given by Lichtenstein and Jaffe in 1942 and thus it is referred as Lichtenstein-Jaffe disease [3]. The dormancy of FD increases from childhood to adulthood, however there is a life time risk of malignant transformation that of around 1–4% [4].
Etiopathogenesis
Cessation of bone maturation process at the stage of woven bone formation leading to inability to produce mature lamellar bone accounts for development of fibrous dysplasia. There have been many theories which have tried to explain the genesis of fibrous dysplasia. Excessive production of interleukin-6 production at local site has been related to increased resorption of bone by increasing the numbers of osteoclasts in these lesions. Genetic theory postulates that somatic mutation early in embryonic life causes a gene mosaicism. The earlier the mutation occurs, the more widespread the effects will be. The gene is located on band 20q13, an area that codes for the α subunit on G-protein receptors Mutations in the gene (GNAS I) result in a cascade which may lead to alteration in cellular differentiation and osteoblastic proliferation [5, 6]. According to hormonal theory, osteoblasts in fibrous dysplastic lesions have an elevated number of hormone receptors and thus have altered responses of bone formation. Hormonal alteration occurring during life, like in pregnancy usually sees exuberated growth of these lesions, thus explaining its hormonal genesis. Another theory explains that cAMP also activates Fos, which inhibits osteoblastic specific genes as well as stimulating cytokines that promote bone resorption by osteoclasts. Hypophosphatemia/phosphaturia, sometimes found in FD, is caused by excess secretion of a phosphatonin fibroblast growth factor [7].
Clinical Presentation and evaluation
FD is most commonly observed between 3 to 15 years age group, and majority of the cases are diagnosed in the first three decades of life. Polyostotic lesions usually present earlier as they are associated with a more severe form of the disease. Males and females are equally affected [9, 10]. Majority of patients with the polyostotic form of FD are symptomatic before the age of 10 years [7]. The monostotic form predominates (70-80%) in comparison to the polyostotic form [8]. Site affection may vary with the form of the disease. According to the sites of involvement for the polyostotic form femur, tibia are most commonly involved followed by skull and facial bones, pelvis, rib, humerus, radius and ulna, lumbar spine, clavicle, and cervical spine. The lesions may be unilateral or, less commonly, bilateral. Symptoms are related to the severity of the disease. Monostotic lesions may be asymptomatic and found incidentally. Polyostotic lesions present early with more symptoms in 60% of the patients. Pain along with swelling and deformity are the most common presenting complaints which is due to structural weakness and micro fractures in the affected bone. Deformity occurs due to abnormal bone growth or micro fractures and subsequent remodeling. Deformities of the lower limb especially the proximal femur can cause an antalgic gait and have a high risk of developing leg length discrepancies and pathological fractures. Common deformities are varus deformity of the proximal femur also known as the “shepherd’s crook deformity”, tibial bowing, bossing of the skull, prominent jaw, rib and chest wall masses. Symptoms may get exacerbated during pregnancy [7, 11].
Four types of fibrous dysplasias have been reported so far based on clinical conditions [11].
Monostotic FD: This represents around 70-80% of all FDs. This is the only form where craniofacial bones are affected. It occurs mostly in the age group of 20-30 years. Non-osteogenetic fibroma, aneurysmal bone cyst, giant cell tumor of bone, adamantinoma, eosionophilic granuloma and plasma cell myeloma should be considered in the differential diagnosis of monostotic FD [8, 12]
Polysototic FD: It accounts for 20-25% of all FDs. More than one of the bones in the skeletal and craniofacial system is affected and it occurs in the first decade of life. Hyperparathyroidism, polyostotic Paget’s disease, neurofibromatosis and cherubism should be considered in the differential diagnosis of polyostotic FD [8, 12].
McCune-Albright syndrome: It is a triad of polyostotic fibrous dysplasia, cutaneous café-au-lait spots and endocrine dysfunction. The syndrome was named after 2 physicians, Donovan McCune and Fuller Albright, who separately described the triad in 1937. It accounts for about 3% of all fibrous dyplasias and 35% to 50% of cases of polyostotic fibrous dysplasias. Females are affected more than males. Patient suffering from this syndrome will have hyperpigmented skin lesions with irregular “coast of Maine” borders with ipsilateral bony ground glass lesions. Endocrinopathies include hyperprolactinemia, gonadotropin-independent precocious puberty, growth hormone excess, hyperthyroidism, FGF23-mediated renal phosphate wasting and Cushing’s syndrome [13].
Mazabraud’s syndrome: Patients suffering from this syndrome present with soft tissue myxomas with polyostotic fibrous dysplasia. The myxomas generally develop later than FD adjacent to the affected bones. These are more commonly seen in extremities alongside long bones. [14].
Cherubism: It is an autosomal dominant disorder which is characterized by symmetric involvement of both the mandible and maxilla and manifests during the second decade of life. These lesions generally become static at skeletal maturity [15].
Radiological evaluation
Plain radiograph: Plain radiograph is the gold standard to evaluate a fibrous dysplasia lesion. It typically shows a well defined medullary lesion, which is usually mildly expansile and is centered in either metaphysis or diaphysis with or without endosteal scalloping with a varying degree of translucency. The medullary canal is replaced with fibrous tissue formed of delicate woven bone spicules that give the tissue its “ground glass” appearance. There may be endosteal scalloping of the inner cortex, but the periosteal surface is smooth and nonreactive. [16]. The deformities (shephard’s crook curvature of femur and coxa vara deformity of the knee) may vary in severity (Figure 1: Radiograph (AP view) of the pelvis showing polyostotic fibrous dysplasia with classic “Shephard’s Crook Deformity”). Radiological characteristics of the lesions differ with respect to the bone and fibrous matrix ratio and are usually seen as three different patterns. Firstly the pagetoid pattern where the rate of the bone–fibrous matrix is equal, secondly sclerotic pattern in which the bone structure is in the foreground and thirdly the radiolucent pattern where the fibrous matrix is in the foreground [17].
Computed tomography: A CT scan demonstrates the extent of the lesion. The appearance may vary according to the amount of calcification and ossification in the lesion. CT Imaging may be more useful in evaluation of craniofacial FDs. [11].
Bone scintigraphy: It is helpful in detecting the extent of disease and distribution particularly of active lesions in adolescent period [18]. It may also be helpful in detecting stress fractures.
Magnetic resonance Imaging (MRI): MRI is helpful in assessing the exact location, extent, shape and content of FD lesion. It characteristically demonstrates a low-intensity signal on T1-weighted images due to its fibrous content. T2-weighted images demonstrate moderately intense signals which are darker than signal of malignant tissue, fat or fluid. MRI is also helpful in detecting malignant transformation of a FD lesion, which may be evident with features like cortical bone erosion, destruction and soft tissue masses [19].
Histopathological evaluation
The lesions show an expanded bone with well-circumscribed, tan grey mass that is dense and variably fibrous with a gritty consistency due to the presence of bone trabeculae. It may show cystic areas in older lesions with some yellow-tinged fluid. A glassier, blue-tinged appearance may be found in cases with chondroid metaplasia [7].
Microscopic appearance: Microscopic evaluation shows varying proportions of fibrous and osseous tissue. The fibrous component is avascular and composed of cytologically bland spindle cells demonstrating low mitotic rate without atypia. Trabecular structures show an abnormal arrangement resembling Chinese letters which is composed of woven bone. Secondary myxoid and aneurysmal bone cyst like changes can be seen. Occasional nodules of benign hyaline cartilage may also be seen. Osteoblastic cells create fibrous tissue instead of a normal bone tissue in the bone medulla [20, 21]
Differential Diagnosis
The differential diagnosis of FD varies based on location, extent of lesion and age of the patient. These mainly include simple bone cyst, enchondroma, eosinophilic granuloma, brown tumor of hyperparathyroidism, giant cell tumor, neurofibromatosis, osteoblastoma, hemangioma of bone. osteofibrous dysplasia, fracture callus, non-ossifying fibroma, and low-grade Osteosarcoma can be included in the differential diagnosis based on histopathological findings. Low-grade chondrosarcoma may be part of the differential diagnosis if there is a prominent chondroid component. Osteofibrous dysplasia and fracture callus can be differentiated by the history and location of the lesion, and they typically have prominent osteoblastic rimming around the bone trabeculae[7].
Treatment
Management of FD should focus on reducing pain, optimizing function, and managing endocrinopathies, if they exist. The choice of treatment is usually guided by, site & extent of lesion, growth of lesion, related symptoms and age of the patient; it can vary from a watchful observation to surgical intervention. Monostotic asymptomatic lesions can be observed and followed up with serial radiographs to look for progression of the lesion. Large symptomatic lesions especially in the lower limb require active management, which may include non surgical (medical) or surgical management. Surgical interventions should be dealt with caution as complete resections are not possible mostly and incomplete resections have high chances of recurrence [22]. Medical management with bisphosphonates is helpful in most sympotomatic monostotic lesions without fractures or deformity. Third generation bisphosphonates (zolendronic acid) have shown remarkable success rate in relieving bone pain and healing of lesions. This is radiologically evident by improved cortical thickness, ossification of the lesion and improved function. These have also shown to reduce the rate of complications like pathological fracture. Intravenous 4 mg zolendronic acid along with vitamin D and oral calcium supplements is the choice of treatment [23]. Denosumab also appears to be effective in reducing bone turnover in adult patients with active FD. However, caution should be exercised, and patients should be monitored carefully as significant fluctuations in biochemical and hormonal indices can occur [24] and hence Denosumab is not recommended for regular use. Surgical intervention is indicated in cases of failure of nonsurgical therapy, large painful lesions, progressive deformity, non-union or malignant transformation. Curettage and bone grafting is the main cornerstone of surgical management. Cortical strut allograft should be used whenever possible as cancellous grafts may get resorbed due to natural disease process. Appropriate internal fixation should be used judiciously. Deformities especially in lower limb require surgical correction. Valgus osteotomy and medial displacement osteotomy are used to correct these deformities. (Figure 2: (a) Radiograph showing Fibrous dysplasia (mixed lytic sclerotic expansile lesion) in the proximal metadiaphyseal region of the right tibia. (b) Post treatment radiograph showing curettage and bone grafting and interfixation) [24].
Prognosis: Generally the prognosis of FD patient is excellent in the absence of malignant transformation. Monostotic FDs have better prognosis than polyostotic or syndromal FDs. Medical management is also more successful in monostotic lesions. Femoral lesions, younger age group patients, polyostotic disease and surgical interventions without internal fixation are the negative prognostic factors for surgical management. Malignant transformation is rare (Figure 3: Radiograph of right femur showing malignant transformation in a pre existing fibrous dysplasia lesion) [25].
Complications: Main complications related to FD are uncontrolled pain, deformities, pathological fractures, limb length discrepancy and malignant transformation. Malignant transformation commonly occurs to osteosarcoma or fibrosarcoma. It generally presents with increase intensity of pain with associated progressively increasing mass with or without pathological fracture. It is more common in polyostotic disease with Endocrinopathies. The rates of malignant transformation have been estimated to be about 0.5% with monostotic FD and about 4% with McCune-Albright syndrome [26]. Prognosis is usually poor. These are managed with multimodality treatment including surgery and chemotherapy [27]
Conclusion
Fibrous Dysplasia even though has good prognosis, there is a wide range of severity in patients all over. While some are minimally affected, some present with numerous fractures and significant deformities. With the advent of advanced imaging modalities and molecular pathology, a better understanding of the pathogenesis of FD has been possible. Non-surgical treatment regimens are increasingly being followed owing to their better compliance and overall improvement in patients’ quality of life by minimizing pain.
References
1. Araghi HM, Haery C. Fibro-osseous lesions of craniofacial bones. The role of imaging. Radiol Clin North Am 1993 Jan;31(1):121–34.
2. Gupta A, Mehta VS, Sarkar C. Large cystic fibrous dysplasia of the temporal bone: case report and review of literature. J Clin Neurosci 2003;10(3):364–7.
3. Lichtenstein L. Polyostic fibrous dysplasia. Arch Surg 1938;36:874.
4. StantonRP. Surgery for fibrous dysplasia. J Bone Miner Res 2006; 21(Suppl 2): P105–P109.
5. Diaz A, Danon M, Crawford J. McCune-Albright syndrome and disorders due to activating mutations of GNAS1. J Pediatr Endocrinol Metab. 2007; 20(8): 853–880.
6. Lietman SA, Schwindinger WF, Levine MA. Genetic and molecular aspects of McCune-Albright syndrome. Pediatr Endocrinol Rev. 2007; 4(suppl 4):380–385.
7. Riddle ND , Bui MM. Fibrous Dysplasia. Arch Pathol Lab Med. 2013;137:134–138
8. Grabias SL, Campbell CJ. Fibrous dysplasia. Orthop Clin North Am 1997; 8:771–83.
9. Sharma RS, Mahapatra AK, Pawar SJ, et al. Symptomatic cranial fibrous dysplasia: clinico-radiological analysis in a series of 8 operative cases with follow-up results. J Clin Neurosci 2002; 9(4):381–90.
10. Rajendran R, Sivapathasundharam R. Shafer’s textbook of oral pathology 5th edition. New Delhi, India: Elsevier, a division of Reed Elsevier India Private Limited; 2006. p. 971–9.
11. DiCaprio MR, Enneking WF. Fibrous dysplasia: pathophysiology, evaluation, and treatment. J Bone Joint Surg Am. 2005; 87(8):1848–1864.
12. Resnick D. Diagnosis of bone and joint disorders. 4th ed. Philadelphia, PA: Saunders; 2002. 4285–4840.
13. Campanacci M. Bone and soft tissue tumors: clinical features, imaging, pathology and treatment. 2nd ed. Wien, Austria: Springer; 1999. p. 435–60.
14. Iwasko N, Steinbach LS, Disler D, et al. Imaging findings in Mazabraud’s syndrome: seven new cases. Skeletal Radiol 2002; 31:81–7.
15. Ruggieri P, Sim FH, Bond JR, et al. Malignancies in fibrous dysplasia. Cancer 1994;73:1411–24.
16. Nager GT, Kennedy DW, Kopstein E. Fibrous dysplasia: a review of the disease and its manifestations in the temporal bone. Ann Otol Rhinol Laryngol 1982(Suppl 92):1–52.
17. Fitzpatrick KA, Taljanovic MS, Speer DP, Graham AR, Jacobson JA, Barnes GR, Hunter TB. Imaging findings of fibrous dysplasia with histopathologic and intraoperative correlation. AJR Am J Roentgenol 2004; 182:1389–98.
18. Zhibin Y, Quanyong L, Libo C, Jun Z, Hankui L, Jifang Z, Ruisen Z. The role of radionuclide bone scintigraphy in fibrous dysplasia of bone. Clin Nucl Med 2004; 29:177–80.
19. Yavuzer R, Khilnani R, Jackson IT, Audet B. A case of atypical McCune-Albright syndrome requiring optic nerve decompression. Ann Plast Surg 1999; 43(4): 430-5.
20. Parekh SG, Donthineni-Rao R, Ricchetti E, Lackman RD. Fibrous dysplasia. J Am Acad Orthop Surg 2004; 12(5):305–13.
21. Sargin H, Gozu H, Bircan R, Sargin M, et al. A case of McCune-Albright syndrome associated with Gs alpha mutation in the bone tissue. Endocr J 2006; 53(1):35–44.
22. Amit M, Collins MT, FitzGibbon EJ, Butman JA, Fliss DM, Gil Z 2011 Surgery versus watchful waiting in patients with craniofacial fibrous dysplasia–a meta-analysis. PLoS One. 2011;6(9):e25179
23. Wu Di, Ma Jie , Bao Suqing , Guan Haixia. Continuous effect with long-term safety in zoledronic acid therapy for polyostotic fibrous dysplasia with severe bone destruction. Rheumatol Int. 2015 Apr;35(4):767-72
24. Ganda K, Seibel MJ. Rapid biochemical response to denosumab in fibrous dysplasia of bone: report of two cases. Osteoporos Int. 2014 Feb;25(2):777-82
25. Yabut SM Jr, Kenan S, Sissons HA, Lewis MM. Malignant transformation of fibrous dysplasia. A case report and review of the literature. Clin Orthop Relat Res. 1988; 228:281-9.
26. Jhala DN, Eltoum I, Carroll AJ, et al. Osteosarcoma in a patient with McCune-Albright syndrome and Mazabraud’s syndrome: a case report emphasizing the cytological and cytogenetic findings. Hum Pathol. 2003; 34(12):1354–1357.
27. Bielack SS, Kempf-Bielack B, Heise U, Schwenzer D, Winkler K; Cooperative German-Austrian-Swiss Osteosarcoma Study Group. Combined modality treatment for osteosarcoma occurring as a second malignant disease. J Clin Oncol 1999; 17(4):1164.
28. Eversole R, Su L, ElMofty S. Benign fibro-osseous lesions of the craniofacial complex. A review. Head Neck Pathol. 2008 Sep;2(3):177-202
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Guest Editorial: Osteosarcoma – Has it really been a Success Story?
Volume 2 | Issue 1 | Jan-Apr 2016 | Page 3-5 | Shekhar M Kumta.
Author: Dr. Shekhar M Kumta [1].
[1] Department of Orthopaedic Surgery, The Prince of Wales Hospital, Chinese University of Hong Kong.
Address of Correspondence
Prof. Shekhar Madhukar Kumta
Department of Orthopaedic Surgery, The Prince of Wales Hospital,
Chinese University of Hong Kong. Shatin NT, Hong Kong.
Email: Kumta@cuhk.edu.hk.
Guest Editorial: Osteosarcoma – Has it really been a Success Story?
Osteosarcoma was once considered a fatal disease, but following the successful development of chemotherapy in the early 1970’s, spectacular improvements in survival have been reported. Neo-adjuvant chemotherapy is now a mandatory necessity not only for survival but also for the successful local control of disease as it facilitates surgical excision and has extended the limits of functional limb salvage in the extremity as well as in the pelvis. The current data suggests that 56- 79% of Osteosarcoma patients should expect to survive at least 5 years, while 52-70% may remain alive, 10 years after primary eradication of disease [1,2, 3].
The remarkable reduction of fatality in Osteosarcoma was often touted as a major medical success story, particularly in comparison with other more prevalent and dismally fatal visceral cancers such as that of the Lung, Liver and breast. But in recent years, advances in Genomic studies and newer understandings of molecular-genetic pathways that control neoplasia and response to drugs, have facilitated the development of targeted therapies for a variety of visceral and haemopoetic malignancies, resulting in equally impressive reversal of fatalities and optimization of treatments, particularly in breast, colon, lung and liver carcinomas [4]. Very little of these developments have translated to better outcomes for Osteosarcoma patients.
Indeed the so-called success of Osteosarcoma therapy has eluded significant population groups, particularly in developing countries. Seldom do survival rates exceed 40-50 % in many developing countries and long term survival outcomes data from high-volume centres, even from large countries such as India, is not freely available. Treatment costs remain a significant burden and even if generic drugs are made available, the nutritional, physical and psychosomatic support required for successful long term survival and coping with burden of disease, are either poorly developed or out of reach of most patients in many such countries.
Another important and often overlooked aspect is the burden of disease. The difficulties with access to health care services in many populations, amongst many other reasons, often results in delayed presentations. Such patients may present with huge tumors, sometimes with metastases at presentation. While tumor burden is known to be negatively associated with response to drugs and therefore survival, no effective adjustments, either to drugs, the dose-intensity of treatment, or surgical alternatives, have been recommended through proper controlled studies, conducted specifically in the context of such patients. Instead this has been left to the decisions of individuals. Balancing the decision between risking life and abandoning limb salvage is not an easy task, particularly if it is based only upon empirical data and personal experiences.
A closer look at global Osteosarcoma data suggests that disease relapses in 30-40% of cases, despite optimal treatments in patient’s presenting with early disease; only 20% of these patients may survive 5 years or longer [5]. Relapse may also occur in patients who have shown excellent response to chemotherapy and in some patients, late relapse 8-15 years after clinical remission, has been noted. The small repertoire of drugs available for Osteosarcoma significantly reduces the chances of salvage with secondary and tertiary agents; indeed without surgical induction of remission there is no possibility of survival [5,6].
The surgical treatment for disease eradication in Osteosarcoma is fairly well established and based on validated principles. Impressive rates of limb salvage (81-91%) are now possible in most patients presenting with early extremity disease.
It is the failure of disease despite optimum treatments that remains frustrating, and demands a strategic look at integration of emerging technologies and the development of novel approaches to treat this disease.
1. Genomic Studies and Molecular Genetic Pathways
Following the success of the Human Genome project, new technologies have enabled the rapid sequencing and identification of Genes involved in neoplasia and other diseases. NEXT-Gen [7]sequencing technologies have now made it possible to identify groups of cancer-specific genes expressed in individual patients and even in single cells, opening up the possibility of classifying tumors and identifying patients not only on the histological identification of the tumor but on the genetic signature expressed in their neoplastic cells.
While some disease have a well-defined genetic abnormality, either in terms of a known gene or group of mutant genes and translocations, conventional Osteosarcoma does not have a typical genetic profile. Nonetheless, given that neoplasms are driven by genetic perturbations, a bio-informatics approach may, in the near future, help us identify prognostic features, expression of drug resistance, molecular signaling and metabolic pathways as potential actionable targets for therapeutic considerations. Collecting and storing tumor tissues in bio-banks and tagging tissues with clinical outcomes data is therefore crucial. Given that Osteosarcoma is a relatively rare disease, the greater the sample base the more relevant and applicable the results of genomic and bioinformatics analysis are likely to be.
2.Targeted Therapies and Less-Toxic Drugs
Conventional drugs for Osteosarcoma are highly toxic. This imposes significant limitations to dose-intensification even in the context of primary chemo-naive disease. In the case of large tumors, systemic toxicity limits dose-escalation in proportion to tumor burden, leading to the development of drug resistance. Addition of drugs that act synergistically or target metabolic processes and pathways specific to neoplastic cells are attractive possibilities. Drugs targeting the mTOR [8] and CREB pathways have shown great promise in Pediatric Neuroblastoma. Rapidly growing neoplastic cells rely on extracellular arginine to support necessary biological processes. Arginine auxotrophy is a characteristic of neoplastic cells and arginine deiminase (ADI) and arginase I, target arginine metabolism and are a promising novel therapy for Osteosarcoma [9].
3. Improvements in Drug Delivery and Reversal of Drug Resistance
Given that the neoplastic cells in Osteosarcoma are embedded within a dense matrix of osteoid, the optimal penetration of drugs has always been a concern. The conjugation of cytotoxic drugs with bone-seeking compounds, polymer-based nano-particles to expedite and improve intracellular delivery of drugs are attractive possibilities, but as yet, remain under investigation [10, 11].
Drug resistance is rarely present at diagnosis. This may be associated with expression of MDM2, P-glycoprotein and several other known factors. Importantly drug resistance is often developed during the course of the disease and is an acquired feature of the disease. A number of small molecules targeting key intra-cellular kinases [12] involved in modulating drug resistance have shown promising in-vitro results.
4.A Reexamination of Surgical Strategy – Ablation Verses Limb Salvage
Preservation of limb function with good limb salvage is goal that must be concomitant with long-term survival. Quite often, especially with large tumors that are likely to be refractory to neo-adjuvant chemotherapy, the dogmatic adherence to the doctrine of limb salvage may jeopardize survival. The difficulty lies with the lack of objective criteria and reliable evidence base upon which such criteria could be established, so as to facilitate decision-making. It is only in the most obvious of cases, such as those with neurovascular involvement, compartmental obliteration, or fungation, we can convince ourselves to proceed with amputations. The difficulty of accepting amputation from the patient’s perspective is completely understandable, but the reluctance of the surgeon, particularly in borderline cases, may put the patient’s life in jeopardy.
Are we bold enough to go back to the drawing board and reexamine this issue?
With what degree of certainty can we identify poor responders prior to therapy?
Will early amputation followed by adjuvant therapy improve survival in patients with large tumors unlikely to respond to therapy?
There have been enormous improvements in amputation prosthetic knee mechanisms including bone-anchored abutments and lightweight exoskeletons. This has enabled dramatic improvements in ambulation even with high trans-femoral amputations.
5. The Emergence of Precision Medicine
In recent years there has been a major push towards the integration of research and fundamental knowledge of human biology, behavior, genetics, environment through bioinformatics data science and computation, with the goal of developing more accurate and specific approaches towards common as well as rare diseases. Instead of a “one-size-fits-all” approach the precision medicine approach to oncology [13] may enable us to categorize neoplasms on their genetic signature and combined with a large computational database, also enable specific therapies towards common traits and cohorts. In the near future there is hope for the development of target therapies, for accurate diagnosis, identification of drug resistance and potential failure. Pharmaco-genetics is an emerging field and may help identify molecular genetic profiles in Osteosarcoma that are likely to respond to specific drugs.
Exciting and far-reaching developments in medicine and fundamental biology will enable us to have a better understanding of Osteosarcoma and its biology. However it remains critical for us to develop knowledge networks for information exchange and to categorize the diverse clinical behaviors of tumors. Accurate, reliable and credible information needs to be made available not only to the clinician and scientist, but also to our patients in a comprehensible way, so that they may participate in a much more informed manner, in the complex decision making that is involved in Osteosarcoma care.
Finally, it is not only Science that fails us in our goals towards eradication or control of disease. The challenges of economic disparity and the consequences of inequity in health resource availability are beyond the scope of this discussion; clinicians treating Osteosarcoma will need to acknowledge and address these critical issues through innovative means without losing sight of the guiding principles of oncologic care.
References
1. Mankin HJ, Hornicek FJ, Rosenberg AE, Harmon DC, Gebhardt MC. Survival data for 648 patients with osteosarcoma treated at one institution. Clin Orthop Relat Res. 2004 Dec;(429):286-91.
2. Hagleitner MM, de Bont ES, Te Loo DM (2012) Survival trends and long-term toxicity in pediatric patients with osteosarcoma. Sarcoma 2012: 636405.
3. Whelan JS, Jinks RC, McTiernan A, Sydes MR, Hook JM, Trani L, Uscinska B, Bramwell V, Lewis IJ, Nooij MA, van Glabbeke M, Grimer RJ, Hogendoorn PC, Taminiau AH, Gelderblom H. Survival from high-grade localised extremity osteosarcoma: combined results and prognostic factors from three European Osteosarcoma Intergroup randomised controlled trials. Ann Oncol. 2012 Jun;23(6):1607-16..
4. Abramson, R. 2015. Overview of Targeted therapies for cancer. https://www.mycancergenome.org/content/molecular-medicine/overview-of-targeted-therapies-for-cancer/
5. Kempf-Bielack B, Bielack SS, Jürgens H, Branscheid D, Berdel WE, Exner GU, Göbel U, Helmke K, Jundt G, Kabisch H, Kevric M, Klingebiel T, Kotz R, Maas R, Schwarz R, Semik M, Treuner J, Zoubek A, Winkler K. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol. 2005 Jan 20;23(3):559-68..
6.Wong KC, Lee V, Shing MMK, Kumta S. Surgical Resection of Relapse May Improve Postrelapse Survival of Patients With Localized Osteosarcoma. Clinical Orthopaedics and Related Research. 2013;471(3):814-819.
7. What is Next-Gen sequencing http://www.illumina.com/technology/next-generation-sequencing.html
8. Zhang H, Dou J, Yu Y, Zhao Y, Fan Y, Cheng J, Xu X, Liu W, Guan S, Chen Z, shi Y, Patel R, Vasudevan SA, Zage PE, Zhang H, Nuchtern JG, Kim ES, Fu S, Yang J. mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling. Apoptosis. 2015 Jan;20(1):50-62.
9. Wells JW, Evans CH, Scott MC, Rütgen BC, O’Brien TD, Modiano JF, Cvetkovic G, Tepic S. Arginase treatment prevents the recovery of canine lymphoma and osteosarcoma cells resistant to the toxic effects of prolonged arginine deprivation. PLoS One. 2013;8(1):e54464.
10. Wang B, Yu X-C, Xu S-F, Xu M. Paclitaxel and etoposide co-loaded polymeric nanoparticles for the effective combination therapy against human osteosarcoma. Journal of Nanobiotechnology. 2015;13:22.
11. Susa M, Iyer AK, Ryu K, et al. Inhibition of ABCB1 (MDR1) Expression by an siRNA Nanoparticulate Delivery System to Overcome Drug Resistance in Osteosarcoma. Rich BE, ed. PLoS ONE. 2010;5(5):e10764.
12. Chen H, Shen J, Choy E, Hornicek FJ, Duan Z. Targeting protein kinases to reverse multidrug resistance in sarcoma. Cancer Treat Rev. 2016 Feb;43:8-18.
13. Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015 Feb 26;372(9):793-5..
14. Stuart A. Scott, Personalizing medicine with clinical pharmacogenetics Genet Med. 2011 Dec; 13(12): 987–995.
Prof. Shekhar M. Kumta
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Tata Memorial Centre – Torch bearer for Care of Cancer in India
Vol 2 | Issue 1 | Jan- Apr 2016 | page:1-2 | Dr. Yogesh Panchwagh & Dr. Ashok Shyam.
Author: Dr. Yogesh Panchwagh [1], Dr. Ashok Shyam [2,3].
[1]Orthopaedic Oncology Clinic, Pune, India.
[2] Indian Orthopaedic Research Group, Thane, India
[3] Sancheti Institute for Orthopaedics &Rehabilitation, Pune, India
Address of Correspondence
Dr. Yogesh Panchwagh.
Orthopaedic Oncology Clinic, 101, Vasanth plot 29, Bharat Kunj Society -2, Erandwana, Pune – 38, India.
Email: drpanchwagh@gmail.com
Editorial: Tata Memorial Centre – Torch bearer for Care of Cancer in India
“Only a life lived in the service to others is worth living”: Albert Einstein.
Rarely does a place, a hospital in particular along with its healthcare providers, epitomise Einstein’s words as closely as India’s topmost tertiary cancer care hospital: Tata Memorial Hospital (TMH), Mumbai. As this editorial is being penned, TMH celebrates its platinum jubilee following its motto of service, education and research religiously throughout these years. This editorial is thus dedicated to this fine institution, which is also Asia’s largest cancer care hospital. Inaugurated on 28th February 1941, by the then governor of Mumbai Sir Roger Lumley, was a 80 bedded, 15000 square meters building. It was then expected to be a center where specialized treatment could be given and one which could lead the path of newer treatment modalities for others to follow. And it has not disappointed. It has now reached new heights with 700 beds and 75000 square meters campus, all in the service of cancer patients not just from all across India but also from the other Asian, African and Middle Eastern nations as well. TMH today leads the war against cancer in India, as Sir Lumley expected it to do. It is recognized amongst the top 5 cancer care institutes globally. This is evident from the current annual numbers of 45,000 new patients and 4,50,000 follow up patients that this institute takes care of. A philanthropic gesture by the Dorabjee Tata trust to start with, later on bloomed into a clinical wing (Tata Memorial Hospital) and a research wing (Cancer Research Institute) which together grew as Tata Memorial Centre (TMC). It was later on brought under the aegis of the Government of India. The research activities in clinical branches and basic sciences fields are carried on in the dedicated unit of ACTREC (Advanced Centre for Treatment, Research and Education in Cancer) at Kharghar, Navi Mumbai, India. The educational activities include training of students in specialty and super specialty courses affiliated to Homi Bhabha National Institute. In fact most of the practicing doctors in field of oncology in various corners of the country, including the editorial board of Journal of Bone and Soft Tissue Tumors, have been associated with this premier institute at some point of time in their lives and correctly take pride in their alma mater. The work done by the Disease managemen t group (DMG) of Bone and soft tissue services at TMH is worth noticing since this unit deals with the subject related to JBST. As per figures from DMG, the outpatient department (OPD) numbers have increased from 800 in the year 2000 to the present number of 2000 new patients in 2014. In 2014, this unit catered to around 300 new osteosarcoma cases, 200 new Ewing sarcomas, 57 Chondrosarcomas and 339 soft tissue sarcomas apart from 275 benign bone and soft tissue tumors. This forms a significant 5% of the entire work at TMH. Thousands of cancer patients and their relatives are the ones that are benefited in turn, bearing fruit to the very roots on which this institution stands firmly. The numerous individuals who dedicated their entire lives to the betterment of this institute, including some not amongst us today, would certainly and rightfully be very proud today. The editorial board of JBST salutes the passion, determination and dedication of Team TMC.
Dr Yogesh Pachwagh
Dr Ashok Shyam
(some facts and figures are based on the information taken from the TMC platinum jubilee website and B.S.T, D.M.G, T.M.H)
Yogesh Panchwagh & Ashok Shyam
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