Applied Basic Sciences
Chapter 24 Musculoskeletal oncology
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Definitions#
As in all other areas of the viva examinations, knowing basic definitions gives you an easy starting point when answering questions and gives the impression to the examiners that you have both a logical and clear thought process, and are in command of the subject matter.
Neoplasm/tumour:
A growth or swelling, which enlarges by cellular proliferation more rapidly than surrounding normal tissue and continues to enlarge after the initiating stimuli cease. Usually lacks structural organization and functional coordination with normal tissues and serves no useful purpose to the host.
Malignant tumour:
Malignant tumours have a predisposition to invasive and destructive local growth, and to distant metastasis usually via the vascular or lymphatic systems.
Benign tumour:
Benign tumours do not metastasize but can still exhibit locally aggressive behaviour.
Sarcoma:
A diverse and rare group of malignant tumours of mesenchymal/connectiv e tissue origin.
Tumours of peripheral nerves are often included in this group.
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Generic structured oral examination question 1#
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Biopsy
EXAMINER
So how would you obtain a tissue diagnosis?
So how would you obtain a tissue diagnosis?
CANDIDATE
A tissue sample can be obtained by biopsy. In general terms this can be performed by excisional, incisional or percutaneous means, but I would not perform a biopsy without first having discussed the case with a bone and soft tissue tumour MD T.
A tissue sample can be obtained by biopsy. In general terms this can be performed by excisional, incisional or percutaneous means, but I would not perform a biopsy without first having discussed the case with a bone and soft tissue tumour MD T.
EXAMINER
Good. Let’s suppose you are the bone tumour surgeon now. When might you perform an excision biopsy?
Good. Let’s suppose you are the bone tumour surgeon now. When might you perform an excision biopsy?
CANDIDATE
The indications for an excision biopsy are narrow. The entire lesion is removed, and the margins are often marginal. Hence, this type of biopsy is really only applicable to benign lesions where the imaging has been diagnostic, for example lipomas, or where the lesion is small and superficial such that excision biopsy would not compromise later re-excision. However, if there is any doubt about the diagnosis I would perform a percutaneous or incisional biopsy first.
The indications for an excision biopsy are narrow. The entire lesion is removed, and the margins are often marginal. Hence, this type of biopsy is really only applicable to benign lesions where the imaging has been diagnostic, for example lipomas, or where the lesion is small and superficial such that excision biopsy would not compromise later re-excision. However, if there is any doubt about the diagnosis I would perform a percutaneous or incisional biopsy first.
EXAMINER
OK, tell me how you would perform an incisional biopsy.
OK, tell me how you would perform an incisional biopsy.
CANDIDATE
First, I would ensure I had appropriate imaging, ideally an MRI scan. I would perform the procedure through a short longitudinal incision. I would plan the incision using the imaging and position it such that the entire biopsy tract could be excised enbloc during the definitive resection, and such that it does not contaminate more than one compartment or key neurovascular structures. I would pay close attention to haemostasis and use minimal tissue dissection in or der to minimize local tissue seeding.
First, I would ensure I had appropriate imaging, ideally an MRI scan. I would perform the procedure through a short longitudinal incision. I would plan the incision using the imaging and position it such that the entire biopsy tract could be excised enbloc during the definitive resection, and such that it does not contaminate more than one compartment or key neurovascular structures. I would pay close attention to haemostasis and use minimal tissue dissection in or der to minimize local tissue seeding.
EXAMINER
We perform most of our biopsies percutaneously now. Do you know any advantages or disadvantages to doing it this way?
We perform most of our biopsies percutaneously now. Do you know any advantages or disadvantages to doing it this way?
CANDIDATE
I’ve seen biopsy performed by Tru-Cut needle. The procedure can be performed easily in clinic under local anaesthetic, which removes delay and the requirement for theatre time. W elker et al. have shown that it is safe, has a low complication rate and reliably provides enough tissue for diagnosis and treatment planning [1]. Other advantages are that it can be combined with imaging modalities, for example ultrasound for soft -tissue lesions and C T for bony lesions. The disadvantage is that necrosis and mitotic rate are less reliable on core needle, but this rarely affects management, and an incisional biopsy can always be performed subsequently if more information is required.
I’ve seen biopsy performed by Tru-Cut needle. The procedure can be performed easily in clinic under local anaesthetic, which removes delay and the requirement for theatre time. W elker et al. have shown that it is safe, has a low complication rate and reliably provides enough tissue for diagnosis and treatment planning [1]. Other advantages are that it can be combined with imaging modalities, for example ultrasound for soft -tissue lesions and C T for bony lesions. The disadvantage is that necrosis and mitotic rate are less reliable on core needle, but this rarely affects management, and an incisional biopsy can always be performed subsequently if more information is required.
EXAMINER
What do you understand by a marginal margin?
What do you understand by a marginal margin?
CANDIDATE
A marginal margin, as described by Enneking, is when the resection line passes through the reactive zone of the tumour being excised [2].
A marginal margin, as described by Enneking, is when the resection line passes through the reactive zone of the tumour being excised [2].
EXAMINER
Explain to me what you mean by the reactive zone.
Explain to me what you mean by the reactive zone.
CANDIDATE
Tumours grow in a centi fugal fashion and this leads to compression and subsequent atrophy of the surrounding tissue forming a pseudocapsule. Outside the pseudocapsule is an area of oedema where inflammatory cells and micronodules of tumour are present. This is the reactive zone. Hence, if a resection line passes through this reactive zone, as in a marginal margin, then micronodules of tumour are likely to be left behind, increasing the risk of a local recurrence.
Tumours grow in a centi fugal fashion and this leads to compression and subsequent atrophy of the surrounding tissue forming a pseudocapsule. Outside the pseudocapsule is an area of oedema where inflammatory cells and micronodules of tumour are present. This is the reactive zone. Hence, if a resection line passes through this reactive zone, as in a marginal margin, then micronodules of tumour are likely to be left behind, increasing the risk of a local recurrence.
EXAMINER
So, what other margins did Enneking describe and what do you understand by them?
So, what other margins did Enneking describe and what do you understand by them?
CANDIDATE
Enneking described three other possible margins. He described intralesional margins, where the resection line passes through the tumour leaving macroscopic deposits of tumour in the surgical wound. He described wide margins, where the resection line passes outside the reactive zone and the tumour is excised with a surrounding cuff of normal tissue. In wide margins it is still possible that tumour will remain in the form of skip lesions. Finally, he described the radical margin, where the entire compartment in which the tumour resides is excised enbloc, in theory removing the entire tumour [2].
Enneking described three other possible margins. He described intralesional margins, where the resection line passes through the tumour leaving macroscopic deposits of tumour in the surgical wound. He described wide margins, where the resection line passes outside the reactive zone and the tumour is excised with a surrounding cuff of normal tissue. In wide margins it is still possible that tumour will remain in the form of skip lesions. Finally, he described the radical margin, where the entire compartment in which the tumour resides is excised enbloc, in theory removing the entire tumour [2].
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Generic structured oral examination question 2#
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Staging
EXAMINER
So what stage is this tumour?
So what stage is this tumour?
CANDIDATE
I would stage this tumour using the Musculoskeletal Tumour Society staging system as described by Enneking [3]. We’ve discussed that it’s a high-grade osteosarcoma, which makes it at least Stage II. It’s an intramedullary tumour that’s invaded the surrounding soft tissues making it extracompartmental and upstaging it to IIB. We’ve not discussed whether there is any evidence of metastasis yet, but, if there is, that would immediately make it a Stage III, regardless of the other features we’ve talked about. This question will usually follow a discussion about a malignant tumour, for example osteosarcoma as in this example. The Enneking system is the easiest to remember and can be applied equally to bony and soft -tissue sarcomas. The other commonly used system is the American Joint Commift ee on Cancer (AJCC) system, which is more complicated. The AJCC also has separate systems for bony and soft -tissue tumours. Table 24.1 Enneking/MSTS staging system [4].
I would stage this tumour using the Musculoskeletal Tumour Society staging system as described by Enneking [3]. We’ve discussed that it’s a high-grade osteosarcoma, which makes it at least Stage II. It’s an intramedullary tumour that’s invaded the surrounding soft tissues making it extracompartmental and upstaging it to IIB. We’ve not discussed whether there is any evidence of metastasis yet, but, if there is, that would immediately make it a Stage III, regardless of the other features we’ve talked about. This question will usually follow a discussion about a malignant tumour, for example osteosarcoma as in this example. The Enneking system is the easiest to remember and can be applied equally to bony and soft -tissue sarcomas. The other commonly used system is the American Joint Commift ee on Cancer (AJCC) system, which is more complicated. The AJCC also has separate systems for bony and soft -tissue tumours. Table 24.1 Enneking/MSTS staging system [4].
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Structured oral examination question 1#
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Osteochondroma
EXAMINER
This young lad has been referred to you urgently by his GP after his mum brought him in with a firm lump on the front of his left thighT ell me about his X-ray (Figure 24.1).
This young lad has been referred to you urgently by his GP after his mum brought him in with a firm lump on the front of his left thighT ell me about his X-ray (Figure 24.1).
Figure 24.1 Osteochondroma.
CANDIDATE
This is a lateral radiograph of his left femur including the knee joint but not the hip joint. There is a bony growth on the anterior aspect of the femur, which looks like a large osteochondroma.
This is a lateral radiograph of his left femur including the knee joint but not the hip joint. There is a bony growth on the anterior aspect of the femur, which looks like a large osteochondroma.
EXAMINER
What makes you think it’s an osteochondroma?
What makes you think it’s an osteochondroma?
CANDIDATE
Well, the cortices are incontinuity with the bone as is the medullary cavity, and the lesion is extending out from the metaphyseal region of the distal femur, which is the most common site for these (25%). This is a sessile lesion rather than the pedunculated variety and appears to be a solitary lesion, although I’d want to examine the child to look for other lumps. It is quite a large lesion and there is some slightly atypical sclerosis within it, so I would definitely get an MRI scan.
Well, the cortices are incontinuity with the bone as is the medullary cavity, and the lesion is extending out from the metaphyseal region of the distal femur, which is the most common site for these (25%). This is a sessile lesion rather than the pedunculated variety and appears to be a solitary lesion, although I’d want to examine the child to look for other lumps. It is quite a large lesion and there is some slightly atypical sclerosis within it, so I would definitely get an MRI scan.
EXAMINER
OK, so you get an MRI, which shows a nice thin cartilage cap and no worrying features. How are you going to treat it?
OK, so you get an MRI, which shows a nice thin cartilage cap and no worrying features. How are you going to treat it?
CANDIDATE
First I’d take a history and examine the child. I’d want to know if it is tender or symptomatic before I decide what to do.
First I’d take a history and examine the child. I’d want to know if it is tender or symptomatic before I decide what to do.
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EXAMINER
It’s not tender and it only bothers him occasionally if he knocks it, but his mother is adamant she wants it removed.
It’s not tender and it only bothers him occasionally if he knocks it, but his mother is adamant she wants it removed.
CANDIDATE
I would suggesta period of watchful waiting to see if it continues to grow or becomes more symptomatic Removing it would carry risks of recurrence and neurovascular damage. There is also a chance of fracture during the operation and afterwards as it’s a large sessile lesion and removing it will weaken the anterior cortex of the femur considerably.
I would suggesta period of watchful waiting to see if it continues to grow or becomes more symptomatic Removing it would carry risks of recurrence and neurovascular damage. There is also a chance of fracture during the operation and afterwards as it’s a large sessile lesion and removing it will weaken the anterior cortex of the femur considerably.
EXAMINER
His mum still w ants it removed and she’s worried that it’s going to become cancer.
His mum still w ants it removed and she’s worried that it’s going to become cancer.
CANDIDATE
If this is a solitary lesion then malignant change is very rare indeed (< 1%). If the child has multiple hereditary exostoses the risk is a bit higher. The textbooks often quote figures of 10% but it is probably more like 1–5%. Examiners may show an example of a solitary osteochondroma in an area that is General advice: difficult to access for the purposes of excision, but then insist that the patient wants it removed, e.g. posterior, proximal tibia. The resultant discussionis then used to assess knowledge of anatomy and approaches, e.g. posterior approach to the knee. If the MRI has shown no sinister features, and the lesion is asymptomatic, then you can have a reasoned discussion with the examiner about watchful waiting versus removal, i.e. both answers are perfectly acceptable. Other points Continued growth after physeal closure raises the suspicion of malignant transformation. A major consideration in determining the malignant potential of an osteochondroma is the thickness of its cartilage cap with thicknesses greater than 1 cm considered worrisome. EXT gene mutation is the genetic abnormality in multiple hereditary exostoses. It is an autosomal dominant condition.
If this is a solitary lesion then malignant change is very rare indeed (< 1%). If the child has multiple hereditary exostoses the risk is a bit higher. The textbooks often quote figures of 10% but it is probably more like 1–5%. Examiners may show an example of a solitary osteochondroma in an area that is General advice: difficult to access for the purposes of excision, but then insist that the patient wants it removed, e.g. posterior, proximal tibia. The resultant discussionis then used to assess knowledge of anatomy and approaches, e.g. posterior approach to the knee. If the MRI has shown no sinister features, and the lesion is asymptomatic, then you can have a reasoned discussion with the examiner about watchful waiting versus removal, i.e. both answers are perfectly acceptable. Other points Continued growth after physeal closure raises the suspicion of malignant transformation. A major consideration in determining the malignant potential of an osteochondroma is the thickness of its cartilage cap with thicknesses greater than 1 cm considered worrisome. EXT gene mutation is the genetic abnormality in multiple hereditary exostoses. It is an autosomal dominant condition.
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Structured oral examination question 2#
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Enchondroma
EXAMINER
Tell me about these radiographs of this chap’s right foot (Figure 24.2).
Tell me about these radiographs of this chap’s right foot (Figure 24.2).
Figure 24.2 Enchondroma.
CANDIDATE
Well they’re AP and oblique views and they show an expansile, lytic lesion in the proximal phalanx of his second toe.
Well they’re AP and oblique views and they show an expansile, lytic lesion in the proximal phalanx of his second toe.
EXAMINER
What do you think it is?
What do you think it is?
CANDIDATE
The radiographs show features consistent with an enchondroma. It has a short zone of transition and appears quite well defined. There’s also some stippled calcification within the substance of the lesion, which suggests a chondroid matrix.
The radiographs show features consistent with an enchondroma. It has a short zone of transition and appears quite well defined. There’s also some stippled calcification within the substance of the lesion, which suggests a chondroid matrix.
EXAMINER
How would you treat this lesion?
How would you treat this lesion?
CANDIDATE
Well I would want to get more information, so I would take a full history and examination. I would also want to get more imaging of the lesion with an MRI or CT and discuss the pictures with a bone tumour MDT. If there’s any doubt about the diagnosis they may want to do a biopsy, but in general the surgical treatment of an enchondroma is with curettage, with or without gratiing. Even if the diagnosis appears obvious and is of a benign lesion, don’t be rushed into offering surgical treatment. Always work through history, examination and imaging You will never be criticized for discussing the diagnosis with a bone tumour MDT, but you will end up in a very tricky discussion with the examiners and fail if you have made the wrong diagnosis, it turns out to be malignant, and you’ve not discussed it with an MDT first.
Well I would want to get more information, so I would take a full history and examination. I would also want to get more imaging of the lesion with an MRI or CT and discuss the pictures with a bone tumour MDT. If there’s any doubt about the diagnosis they may want to do a biopsy, but in general the surgical treatment of an enchondroma is with curettage, with or without gratiing. Even if the diagnosis appears obvious and is of a benign lesion, don’t be rushed into offering surgical treatment. Always work through history, examination and imaging You will never be criticized for discussing the diagnosis with a bone tumour MDT, but you will end up in a very tricky discussion with the examiners and fail if you have made the wrong diagnosis, it turns out to be malignant, and you’ve not discussed it with an MDT first.
Other points
50% of solitary enchondromas arise in the hands.
Malignant transformation is very rare, but when it does occur it is usually in large lesions of long bones.
Enchondromatosis = Ollier’s disease (risk of bone malignancy is 10%, but if visceral and brain malignancies are included then the overall risk is 25%).
Enchondromatosis + haemangiomas = Maffucci’s syndrome (risk of malignancy reported anywhere from 25% to 100%).
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Structured oral examination question 3#
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Non-ossifying fibroma
EXAMINER
Tell me about this radiograph (Figure 24.3).
Tell me about this radiograph (Figure 24.3).
Figure 24.3 Non-ossifying fibroma.
CANDIDATE
This is an AP radiograph of a left lo wer leg of a child, which includes both the ankle joint and the knee joint. There is a lucent lesion, eccentrically placed in the metaphyseal region of the tibia. The lesion is well-demarcated, and its margin is slightly sclerotic. These features are typical of a non- ossifying fibroma.
This is an AP radiograph of a left lo wer leg of a child, which includes both the ankle joint and the knee joint. There is a lucent lesion, eccentrically placed in the metaphyseal region of the tibia. The lesion is well-demarcated, and its margin is slightly sclerotic. These features are typical of a non- ossifying fibroma.
EXAMINER
Good. What else can you tell me about this lesion?
Good. What else can you tell me about this lesion?
CANDIDATE
Non-ossifying fibromas are developmental or hamartomatous lesions. They are actually very common, and some have suggested an incidence of up to 35% in normal children. They are usually asymptomatic and are often discovered as an incidental finding. Occasionally they can present after a pathological fracture, after which they tend to heal up.
Non-ossifying fibromas are developmental or hamartomatous lesions. They are actually very common, and some have suggested an incidence of up to 35% in normal children. They are usually asymptomatic and are often discovered as an incidental finding. Occasionally they can present after a pathological fracture, after which they tend to heal up.
EXAMINER
How would you treat this lesion?
How would you treat this lesion?
CANDIDATE
I can’t see any evidence of fracture. I would take a history and examine the patient to ascertain whether the lesion is painful or symptomatic and I would discuss the images with our local tumour MDT to make sure that they were in agreement with the diagnosis. That being the case, this can be treated with observation only as these lesions normally resolve by adulthood. I would plan to keep the patient under review with surveillance radiography.
I can’t see any evidence of fracture. I would take a history and examine the patient to ascertain whether the lesion is painful or symptomatic and I would discuss the images with our local tumour MDT to make sure that they were in agreement with the diagnosis. That being the case, this can be treated with observation only as these lesions normally resolve by adulthood. I would plan to keep the patient under review with surveillance radiography.
COMMENT
Again, you will not be criticize dif you say that would take advice from the bone tumour MDT. You will, however, be in a very difficult situation if you have not stated that you would take their advice and your diagnosis is wrong.
Again, you will not be criticize dif you say that would take advice from the bone tumour MDT. You will, however, be in a very difficult situation if you have not stated that you would take their advice and your diagnosis is wrong.
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Structured oral examination question 4#
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Chondrosarcoma
EXAMINER
This 60-year-old lady presented with pain and swelling around her lower back. What can you see on this CT scan (Figure 24.4)?
This 60-year-old lady presented with pain and swelling around her lower back. What can you see on this CT scan (Figure 24.4)?
Figure 24.4 Chondrosarcoma.
CANDIDATE
This is an axial section showing the sacrum and iliac wings. There is an expansile lesion in the left iliac wing , which has extended into the soft tissues. The lesion has both ly tic and sclerotic elements to it.
This is an axial section showing the sacrum and iliac wings. There is an expansile lesion in the left iliac wing , which has extended into the soft tissues. The lesion has both ly tic and sclerotic elements to it.
EXAMINER
What do you think the diagnosis might be?
What do you think the diagnosis might be?
CANDIDATE
The expansile nature, as well as the permeative margin and local invasion suggesta malignant process. Malignant tumours of bone can then be broken down into primary, metastatic, or immunohaematopoietic lesions Metastatic and immunohaema topoietic tumours tend to produce lytic lesions within bones whereas this lesion has areas of sclerosis and is much more expansile. Primary bone tumours can be classified according to their matrix as either bone-producing, cartilag e- producing, fibrous tissue-pr oducing, or non-matrix-producing. The patchy sclerosis within this lesion is in keeping with either a bone- or cartilag e-producing primary tumour, although I would not rule out other diagnoses without further investigations [ 5].
The expansile nature, as well as the permeative margin and local invasion suggesta malignant process. Malignant tumours of bone can then be broken down into primary, metastatic, or immunohaematopoietic lesions Metastatic and immunohaema topoietic tumours tend to produce lytic lesions within bones whereas this lesion has areas of sclerosis and is much more expansile. Primary bone tumours can be classified according to their matrix as either bone-producing, cartilag e- producing, fibrous tissue-pr oducing, or non-matrix-producing. The patchy sclerosis within this lesion is in keeping with either a bone- or cartilag e-producing primary tumour, although I would not rule out other diagnoses without further investigations [ 5].
EXAMINER
You’re right to suggesta primary lesion in this case. You’ve suggested bone- or cartilag e- producing as the likely matrix. Which do you think is more likely here?
You’re right to suggesta primary lesion in this case. You’ve suggested bone- or cartilag e- producing as the likely matrix. Which do you think is more likely here?
CANDIDATE
It is most likely to be a chondrosarcoma. The incidence of chondrosarcoma increases with age. This lady is 60 and although there is a second peak in the incidence of osteosarcoma in elderly patients the majority of cases occur in adolescents around the growth spurt. The site of the tumour also makes chondrosarcoma the more likely diagnosis. Only around 5% of osteosarcomas occur in the pelvis, whereas up to 30% of chondrosarcomas are pelvic in origin. Finally, there is the appearance on the CT. It’s not the clearest image, but I’m trying to convince myself that there’s stippled calcification, which would indicate a chondroid lesion.
It is most likely to be a chondrosarcoma. The incidence of chondrosarcoma increases with age. This lady is 60 and although there is a second peak in the incidence of osteosarcoma in elderly patients the majority of cases occur in adolescents around the growth spurt. The site of the tumour also makes chondrosarcoma the more likely diagnosis. Only around 5% of osteosarcomas occur in the pelvis, whereas up to 30% of chondrosarcomas are pelvic in origin. Finally, there is the appearance on the CT. It’s not the clearest image, but I’m trying to convince myself that there’s stippled calcification, which would indicate a chondroid lesion.
EXAMINER
Very good. What treatment options are there for an aggressive-looking chondrosarcoma like this is?
Very good. What treatment options are there for an aggressive-looking chondrosarcoma like this is?
CANDIDATE
Chondrosarcomas are poorly chemo- and radiosensitive, so the only treatment option is wide local excision plus or minus reconstruction However, despite surgical excision, longer-term survival is dependent on the presence or absence of metastases.
Chondrosarcomas are poorly chemo- and radiosensitive, so the only treatment option is wide local excision plus or minus reconstruction However, despite surgical excision, longer-term survival is dependent on the presence or absence of metastases.
EXAMINER
So, what do you think the prognosis is for this high-grade lesion?
So, what do you think the prognosis is for this high-grade lesion?
CANDIDATE
The key is the presence or absence of metastasis and the patient needs staging investigation sIn general, low-grade, or grade I, lesions are rarely metastatic and have a better than 90% 5-year survival. High grade III lesions, as you’ve intimated this one is, are metastatic ino ver 70% of cases and have only a 30% 5-year survival.
The key is the presence or absence of metastasis and the patient needs staging investigation sIn general, low-grade, or grade I, lesions are rarely metastatic and have a better than 90% 5-year survival. High grade III lesions, as you’ve intimated this one is, are metastatic ino ver 70% of cases and have only a 30% 5-year survival.
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Structured oral examination question 3#
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Chondrosarcoma
EXAMINER
This is a very fit and well 50-year-old chap, who has come into Accident & Emergency after falling down the stairs at home, sustaining this injury to his left leg. T ell me how you are going to manage this (Figure 24.5).
This is a very fit and well 50-year-old chap, who has come into Accident & Emergency after falling down the stairs at home, sustaining this injury to his left leg. T ell me how you are going to manage this (Figure 24.5).
CANDIDATE
I would manage this patient initially using the principles of A TLS.
I would manage this patient initially using the principles of A TLS.
EXAMINER
Fine. No issues with ABC and the patient is alert and orientated.
Fine. No issues with ABC and the patient is alert and orientated.
CANDIDATE
Moving on, I want to assess whether the patient has any other injuries, and regarding this injury I want to know whether it is open or closed and whether the limbis neurovascularly intact.
Moving on, I want to assess whether the patient has any other injuries, and regarding this injury I want to know whether it is open or closed and whether the limbis neurovascularly intact.
EXAMINER
OK. This is his only injury. It’s an open fracture with a 1-cm wound on the lateral thigh. The limbis neurovascularly intact. How are you going to manage this?
OK. This is his only injury. It’s an open fracture with a 1-cm wound on the lateral thigh. The limbis neurovascularly intact. How are you going to manage this?
CANDIDATE
If it’s an open injury then I would take a picture of the wound and cover it with a sterile- soaked swab. The patient needs IV antibiotics and coverage for tetanus, depending on their vaccination history. Some form of immobilization is also important for patient comfort and nursing care. In this case I can see that a Thomas splint has been applied.
If it’s an open injury then I would take a picture of the wound and cover it with a sterile- soaked swab. The patient needs IV antibiotics and coverage for tetanus, depending on their vaccination history. Some form of immobilization is also important for patient comfort and nursing care. In this case I can see that a Thomas splint has been applied.
EXAMINER
OK. So, shall I book this patient for theatre with a plan to perform a debridement of the wound and nailing of the fracture?
OK. So, shall I book this patient for theatre with a plan to perform a debridement of the wound and nailing of the fracture?
CANDIDATE
Well I know it’s an open fracture, but I have some concerns about the X-ray. There’s some odd calcification within the medullary cavity, so I’m worried that this is a pathological fracture through a bony lesion.
Well I know it’s an open fracture, but I have some concerns about the X-ray. There’s some odd calcification within the medullary cavity, so I’m worried that this is a pathological fracture through a bony lesion.
EXAMINER
Why does that make a difference?
Why does that make a difference?
CANDIDATE
It’s a rare situation, but if this is a pathological fracture through a bone tumour, and we open up the fracture site and nail it, we would spread tumour the length of the femur and might convert a resectable tumour into one that is unresectable.
It’s a rare situation, but if this is a pathological fracture through a bone tumour, and we open up the fracture site and nail it, we would spread tumour the length of the femur and might convert a resectable tumour into one that is unresectable.
EXAMINER
But doesn’t the open fracture need washing out?
But doesn’t the open fracture need washing out?
CANDIDATE
It’s a small puncture wound, and I’ve put the patient on IV antibiotics, so I think the infection risk is low. In this case I would arrange some urgent investigations, get more information and discuss the case immediately with the bone tumour MDT before rushing the patient to theatre. Always look at the available evidence carefully and look out for any atypical features. If in doubt, say so! You will never be criticized for taking advice, but you will fail if you have blazed on with treatment and taken this patient to theatre for washout and nailing. If there is no threat to life or limb, then there is always time for further investigations, and to seek further opinions. Always take timet o look carefully before answering, especially if a question on a fracture comes up in the adult and pathology viva station!
It’s a small puncture wound, and I’ve put the patient on IV antibiotics, so I think the infection risk is low. In this case I would arrange some urgent investigations, get more information and discuss the case immediately with the bone tumour MDT before rushing the patient to theatre. Always look at the available evidence carefully and look out for any atypical features. If in doubt, say so! You will never be criticized for taking advice, but you will fail if you have blazed on with treatment and taken this patient to theatre for washout and nailing. If there is no threat to life or limb, then there is always time for further investigations, and to seek further opinions. Always take timet o look carefully before answering, especially if a question on a fracture comes up in the adult and pathology viva station!
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Figure 24.5 Chondrosarcoma 2.
Other points
Chondrosarcomas are the second most frequent primary malignant tumour of bone.
Chondrosarcomas are chemo- and radioresistant because of the presence of hyaline dense extracellular matrix, low mitotic activity and poor vascularity. As such, surgery remains the mainstay of treatment.
Low-grade (Gd1) tumours can be managed with extensive intralesional curettage with adjuvant therapy such as cryotherapy phenolization or ar gon beam laser followed by a void-filling procedure.
High-grade lesions invariably require en-bloc resection.
Currently a plethora of targeted therapies are under clinical evaluation in patients with chondrosarcoma (e.g. Phase II study using Imatinib).
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Structured oral examination question 6#
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Osteosarcoma [6]
EXAMINER
This young lad presented with a painful knee and a lump after a football injury. What do you think of the X-ray (Figure 24.6)?
This young lad presented with a painful knee and a lump after a football injury. What do you think of the X-ray (Figure 24.6)?
CANDIDATE
When I was shown the X-ray I immediately thought that the diagnosis was an osteosarcoma and described the X-ray changes that supported my initial reaction. The reis an intramedullary sclerotic lesion with a wide z one of transition and the reis extension through the cortices and in to the soft tissu esTher e is sunray spiculation, butat this resolution I c an’t see an obvious Codman’s triangle.
When I was shown the X-ray I immediately thought that the diagnosis was an osteosarcoma and described the X-ray changes that supported my initial reaction. The reis an intramedullary sclerotic lesion with a wide z one of transition and the reis extension through the cortices and in to the soft tissu esTher e is sunray spiculation, butat this resolution I c an’t see an obvious Codman’s triangle.
EXAMINER
What’s a Codman’s triangle?
What’s a Codman’s triangle?
CANDIDATE
I knew what a Codman’s triangle was, but I did not have a clear definition a t my fingertips (a triangle of reactive bone at the edge of the tumour where the periosteum is elevated). I struggled for a few seconds but managed to explain that it is indicative of a periosteal reaction.
I knew what a Codman’s triangle was, but I did not have a clear definition a t my fingertips (a triangle of reactive bone at the edge of the tumour where the periosteum is elevated). I struggled for a few seconds but managed to explain that it is indicative of a periosteal reaction.
EXAMINER
So, what do you think the diagnosis is?
So, what do you think the diagnosis is?
CANDIDATE
I think the diagnosis is an osteosarcoma. The imaging shows an osteogenic tumour in an adolescent male. It is also in a classical position in the metaphyseal region of the distal femur, where about 35% of these tumours occur.
I think the diagnosis is an osteosarcoma. The imaging shows an osteogenic tumour in an adolescent male. It is also in a classical position in the metaphyseal region of the distal femur, where about 35% of these tumours occur.
EXAMINER
So how would you investigate it further?
So how would you investigate it further?
CANDIDATE
I would take a history and examine the patient. I would refer the child on to a bone tumour MDT immediately rather than delay the process by organizing more investigations locally.
I would take a history and examine the patient. I would refer the child on to a bone tumour MDT immediately rather than delay the process by organizing more investigations locally.
EXAMINER
OK, so you’re working for the bone tumour MDT, what further investigations would you request?
OK, so you’re working for the bone tumour MDT, what further investigations would you request?
CANDIDATE
I would request investigations to further delineate the tumour itself and I would arrange tests to assess for metastatic disease. An MRI scan is the best modality for investigating the tumour itself and will delineate the local extent of the tumour, its relationship to key neurovascular structures, and the presence or absence of skip lesions. A CT scan can also be helpful as these lesions are osteogenic and therefore showup well on CT. These investigations can also be used to plan a biopsy. To stage the tumour one might initially get a chest X-ray, but CT scan of the chest is mandatory to look for metastases and these are sadly found in about 30% at diagnosis. Other investigations you might use are bloodtests, for example alkaline phosphatase and lactate dehydrogenase, which, if elevated, are associated with a poorer prognosis.
I would request investigations to further delineate the tumour itself and I would arrange tests to assess for metastatic disease. An MRI scan is the best modality for investigating the tumour itself and will delineate the local extent of the tumour, its relationship to key neurovascular structures, and the presence or absence of skip lesions. A CT scan can also be helpful as these lesions are osteogenic and therefore showup well on CT. These investigations can also be used to plan a biopsy. To stage the tumour one might initially get a chest X-ray, but CT scan of the chest is mandatory to look for metastases and these are sadly found in about 30% at diagnosis. Other investigations you might use are bloodtests, for example alkaline phosphatase and lactate dehydrogenase, which, if elevated, are associated with a poorer prognosis.
EXAMINER
Tell me about the general principles of treatment in cases like this.
Tell me about the general principles of treatment in cases like this.
CANDIDATE
Before commencing treatment, a confirmatory tissue diagnosis is made by biopsy and staging investigations are completed. Treatment for osteosarcoma then follows four distinct phases:
Before commencing treatment, a confirmatory tissue diagnosis is made by biopsy and staging investigations are completed. Treatment for osteosarcoma then follows four distinct phases:
source p. 1433
neoadjuvant chemotherapy, surgical excision and reconstruction, adjuvant chemotherapy, and follow-up with clinical examination and imaging to look for recurrent disease or distant metastases.
EXAMINER
Why does the treatment start with neoadjuvant chemotherapy? Why don’t we start by excising the tumour and then start chemotherapy?
Why does the treatment start with neoadjuvant chemotherapy? Why don’t we start by excising the tumour and then start chemotherapy?
CANDIDATE
There are three main reasons for beginning treatment with neoadjuvant chemotherapy rather than primary surgery. First, to treat occult micrometastases, which are likely to be present in a much greater proportion of patients than the 30% who present with radiologically detectable metastases at diagnosis; second, to reduce the inflammation around the primary tumour, aiding later surgical resection; and finally , to allow assessment of response to the neoadjuvant chemotherapy, determine prognosis, and direct adjuvant chemotherapy.
There are three main reasons for beginning treatment with neoadjuvant chemotherapy rather than primary surgery. First, to treat occult micrometastases, which are likely to be present in a much greater proportion of patients than the 30% who present with radiologically detectable metastases at diagnosis; second, to reduce the inflammation around the primary tumour, aiding later surgical resection; and finally , to allow assessment of response to the neoadjuvant chemotherapy, determine prognosis, and direct adjuvant chemotherapy.
EXAMINER
You mentioned assessment of response to neoadjuvant chemotherapy. Why is this important?
You mentioned assessment of response to neoadjuvant chemotherapy. Why is this important?
CANDIDATE
Response of the tumour to chemotherapy treatment is measured as a percentage necrosis on histology of the resected specimen. A greater than 90% necrosis is considered a good response, and this carries a better prognosis than poor or non-responders. The reason for this is that if the tumour has a good response to chemotherapy then occult, but clinically undetectable, micrometastases are more likely to be eliminated by treatment, reducing the risk of then enduring and developing into detectable metastases, and ultimately fatal disease.
Response of the tumour to chemotherapy treatment is measured as a percentage necrosis on histology of the resected specimen. A greater than 90% necrosis is considered a good response, and this carries a better prognosis than poor or non-responders. The reason for this is that if the tumour has a good response to chemotherapy then occult, but clinically undetectable, micrometastases are more likely to be eliminated by treatment, reducing the risk of then enduring and developing into detectable metastases, and ultimately fatal disease.
EXAMINER
Do you know of any novel treatments?
Do you know of any novel treatments?
CANDIDATE
I have read about muramyl tripeptide (MT PIt is not directly tumoricidal but works by stimulating the immune system, causing macrophages to exhibit cytotoxic antitumour activity . In a randomized trial, Meyers et al. showed that, when MTP was added to the standard chemotherapy regime of cisplatin, do xorubicin, and methotrexate, 6-year overall survival improved from 70% to 78% [7]. At the current time, NICE have not permift ed its use for osteosarcoma, but this decision is under further discussion and appraisal.
I have read about muramyl tripeptide (MT PIt is not directly tumoricidal but works by stimulating the immune system, causing macrophages to exhibit cytotoxic antitumour activity . In a randomized trial, Meyers et al. showed that, when MTP was added to the standard chemotherapy regime of cisplatin, do xorubicin, and methotrexate, 6-year overall survival improved from 70% to 78% [7]. At the current time, NICE have not permift ed its use for osteosarcoma, but this decision is under further discussion and appraisal.
source p. 1434
Figure 24.6 Osteosarcoma.
Other points
Recently, it has been suggested that a more reliable way of predicting the likelihood of local recurrence in high-grade osteosarcoma would be to combine both the measured surgical margin (in millimetres) as well as the tumour necrosis rate [9].
source p. 1435
Structured oral examination question 7#
source p. 1436
Aneurysmal bone cyst
EXAMINER
This is a 20-year-old lad who presents with pain in his proximal left tibia. What do you make of his MRI scan (Figure 24.7)?
This is a 20-year-old lad who presents with pain in his proximal left tibia. What do you make of his MRI scan (Figure 24.7)?
CANDIDATE
This is an axial T2 image, which shows a lesion in the posterolateral tibia. It appears well circumscribed with a sclerotic margin, is eccentrically placed, and there are multiple septations and loculations with fluid levels. These appearances would be in keeping with an aneurysmal bone cyst.
This is an axial T2 image, which shows a lesion in the posterolateral tibia. It appears well circumscribed with a sclerotic margin, is eccentrically placed, and there are multiple septations and loculations with fluid levels. These appearances would be in keeping with an aneurysmal bone cyst.
EXAMINER
That’s right. What’s the normal management for these?
That’s right. What’s the normal management for these?
CANDIDATE
First, it’s important to confirm the diagnosis and I would always discuss bony lesions of this type with a bone tumour MDT. Aneurysmal bone cysts, or ABCs, can often formas a reactive change to another benign lesion, for example an osteoblastoma or giant cell tumour, which needs to be ruled out. The differential diagnosis of an aneurysmal bone cyst also includes a telangiectatic osteosarcoma, which would require very different management. In general, treatment of ABCs is with curettage and gratiing , but the recurrence rate can be as high as 50%. I am aware of newer therapies with promising results reported with the use of Denosumab, a RANKL inhibitor; however, its use in ABCs is currently off-label.
First, it’s important to confirm the diagnosis and I would always discuss bony lesions of this type with a bone tumour MDT. Aneurysmal bone cysts, or ABCs, can often formas a reactive change to another benign lesion, for example an osteoblastoma or giant cell tumour, which needs to be ruled out. The differential diagnosis of an aneurysmal bone cyst also includes a telangiectatic osteosarcoma, which would require very different management. In general, treatment of ABCs is with curettage and gratiing , but the recurrence rate can be as high as 50%. I am aware of newer therapies with promising results reported with the use of Denosumab, a RANKL inhibitor; however, its use in ABCs is currently off-label.
Figure 24.7 Aneurysmal bone cyst.
source p. 1437
Other points
ABCs and GCTs may have similar appearances on plain X-rays and may only be reliably differentiated radiologically with MRI.
Traditionally , surgery was the mainstay of treatment.
‘Denosumab’ is a human monoclonal antibody that directly inhibits receptor activator of nuclear kappa B ligand (RANKL) signalling.
RANKL expression is seen in a variety of benign and malignant bone neoplasms and has higher than normal levels of expression in GCT and ABCs [10].
Among other things, ‘Denosumab’ is currently licensed for use in the treatment of skeletally mature adolescents and adults with GCT of bone [11].
There is growing evidence for its use in ABCs (off-label), with studies showing tumour regression, improved pain and – in the case of spinal lesions – improvement in neurological symptoms [12].
source p. 1438
Structured oral examination question 8#
source p. 1439
Ewing’s sarcoma [5]
EXAMINER
This is a histology slide taken from a biopsy of a tumour in the femoral diaphysis of a 16-year- old boy. What does this slide show (Figure 24.8)?
This is a histology slide taken from a biopsy of a tumour in the femoral diaphysis of a 16-year- old boy. What does this slide show (Figure 24.8)?
CANDIDATE
This picture shows a magnified view of a stained histology slide. I’m no expert at histology, but I would describe the cells’ appearance as small, round and blue, and given the brief history you provided I suspect this may represent a Ewing’s sarcoma.
This picture shows a magnified view of a stained histology slide. I’m no expert at histology, but I would describe the cells’ appearance as small, round and blue, and given the brief history you provided I suspect this may represent a Ewing’s sarcoma.
EXAMINER
Excellent. What other features might this patient have presented with?
Excellent. What other features might this patient have presented with?
CANDIDATE
Patients usually present with pain and swelling related to the tumour. They usually present around the knee, with 25% occurring in the distal femur. Frequently, erythema, systemic pyrexia, a leukocytosis and a raised ES Rare also presenting features, which can incorrectly lead the unwary to a diagnosis of infection. Hence, it ism anda tory to obtain radiographs when patients present with any unexplained pain or swelling. Patients can occasionally also present with pathological fracture through the lesion or with symptoms related to metastatic disease, such as bone pain in other sites or respiratory symptoms.
Patients usually present with pain and swelling related to the tumour. They usually present around the knee, with 25% occurring in the distal femur. Frequently, erythema, systemic pyrexia, a leukocytosis and a raised ES Rare also presenting features, which can incorrectly lead the unwary to a diagnosis of infection. Hence, it ism anda tory to obtain radiographs when patients present with any unexplained pain or swelling. Patients can occasionally also present with pathological fracture through the lesion or with symptoms related to metastatic disease, such as bone pain in other sites or respiratory symptoms.
EXAMINER
And what would be the characteristic features you’d look for on an X-ray?
And what would be the characteristic features you’d look for on an X-ray?
CANDIDATE
Ewing’s sarcoma leads to a lytic, moth-ea ten appearance to the bone. The classic finding, described as onionpeel, is seen as a laminated periosteal reaction and probably reflects phases of tumour growth.
Ewing’s sarcoma leads to a lytic, moth-ea ten appearance to the bone. The classic finding, described as onionpeel, is seen as a laminated periosteal reaction and probably reflects phases of tumour growth.
EXAMINER
How would you investigate this further?
How would you investigate this further?
CANDIDATE
I would start with a full history and examination. MRI sc an is essential to delineate the local extent of the tumour and any involvement of key neurovascular structures. It can also be used to plan the biopsy. Other investigations aim to root out any evidence of metastatic disease. ACT chest is required to look for lung metastases, but, in Ewing’s sarcoma, a bone scan and bone marrow biopsy are also required to look for widespread bony metastases. Distant bone marrow involvement carries a significantly poorer prognosis.
I would start with a full history and examination. MRI sc an is essential to delineate the local extent of the tumour and any involvement of key neurovascular structures. It can also be used to plan the biopsy. Other investigations aim to root out any evidence of metastatic disease. ACT chest is required to look for lung metastases, but, in Ewing’s sarcoma, a bone scan and bone marrow biopsy are also required to look for widespread bony metastases. Distant bone marrow involvement carries a significantly poorer prognosis.
EXAMINER
In general terms, what is the management forEwing’s sarcoma?
In general terms, what is the management forEwing’s sarcoma?
CANDIDATE
There is a national video conference MDT for all cases of Ewing’s sarcoma, which recommends on management. In broad terms, Ewing’s sarcomas are both chemo- and radiosensitive and hence these modalities form part of the management protocol. Neoadjuvant chemotherapy is the first-line treatment and usually precedes surgery, which involves wide excision and bony reconstruction where required. Occasionally lesions are treated solely with chemo- and radiotherapy, usually in surgically inaccessible lesions around the pelvis. The response to chemotherapy, like in osteosarcoma, is key to prognosis. Five-year survival is 75% with a good response, but only 20% with a poor prognosis.
There is a national video conference MDT for all cases of Ewing’s sarcoma, which recommends on management. In broad terms, Ewing’s sarcomas are both chemo- and radiosensitive and hence these modalities form part of the management protocol. Neoadjuvant chemotherapy is the first-line treatment and usually precedes surgery, which involves wide excision and bony reconstruction where required. Occasionally lesions are treated solely with chemo- and radiotherapy, usually in surgically inaccessible lesions around the pelvis. The response to chemotherapy, like in osteosarcoma, is key to prognosis. Five-year survival is 75% with a good response, but only 20% with a poor prognosis.
source p. 1440
Figure 24.8 Ewing’s sarcoma.
source p. 1441
Structured oral examination question 9#
source p. 1442
Lipoma
EXAMINER
This is an MR Iof apa tien t who has presented with a painless mass on the lateral aspect of his right elbow. To orientate you the round structure (labelled A) is the radial head. Tell me about the lesion adjacent to it, which is labelled B (Figure 24.9).
This is an MR Iof apa tien t who has presented with a painless mass on the lateral aspect of his right elbow. To orientate you the round structure (labelled A) is the radial head. Tell me about the lesion adjacent to it, which is labelled B (Figure 24.9).
CANDIDATE
There is an intramuscular mass in the extensor compartment adjacent, and lateral, to the radial head. The mass itself appears bland and is of the same intensity as the subcutaneous fat, suggesting a diagnosis of an intramuscular lipoma.
There is an intramuscular mass in the extensor compartment adjacent, and lateral, to the radial head. The mass itself appears bland and is of the same intensity as the subcutaneous fat, suggesting a diagnosis of an intramuscular lipoma.
EXAMINER
What is a lipoma?
What is a lipoma?
CANDIDATE
A lipoma is a benign tumour of mature adipocytes, identical to the surrounding adipose tissue, and showing liti le variation of cell size or shape.
A lipoma is a benign tumour of mature adipocytes, identical to the surrounding adipose tissue, and showing liti le variation of cell size or shape.
EXAMINER
And how would you treat this lesion?
And how would you treat this lesion?
CANDIDATE
I would want to start by taking a history and examination, in particular looking for any abnormal features like pain or distal neural compromise, which might suggesta more aggressive lesion than a simple lipoma and alter my management. Also, this is only a single image of the lesion and I would want to see the rest of the scan and discuss it with the sarcoma MDT. Bland, innocent- looking lesions are usually treated with excision biopsy with a marginal margin. If there is any doubt, then a biopsy should betaken prior to excision. Histology of lesions below the fascia, like this one, often come back labelled as atypical lipomas by the histologist, despite very bland appearance on MRI.
I would want to start by taking a history and examination, in particular looking for any abnormal features like pain or distal neural compromise, which might suggesta more aggressive lesion than a simple lipoma and alter my management. Also, this is only a single image of the lesion and I would want to see the rest of the scan and discuss it with the sarcoma MDT. Bland, innocent- looking lesions are usually treated with excision biopsy with a marginal margin. If there is any doubt, then a biopsy should betaken prior to excision. Histology of lesions below the fascia, like this one, often come back labelled as atypical lipomas by the histologist, despite very bland appearance on MRI.
EXAMINER
What do you mean by an atypical lipoma?
What do you mean by an atypical lipoma?
CANDIDATE
The term is quite controversial, and the literature often refers to them as lipoma-like liposarcoma sIn essence, an atypical lipoma is a lipoma with some slightly atypical features but no evidence of malignancy. The histology of such lesions shows variation of adipocyte size, in contrast to the bland adipocytes of a simple lipoma, and nuclear atypia, as well as the presence of lipoblasts. These lesions are benign and management is still with marginal excision, but they do have a low rate of local recurrence [8].
The term is quite controversial, and the literature often refers to them as lipoma-like liposarcoma sIn essence, an atypical lipoma is a lipoma with some slightly atypical features but no evidence of malignancy. The histology of such lesions shows variation of adipocyte size, in contrast to the bland adipocytes of a simple lipoma, and nuclear atypia, as well as the presence of lipoblasts. These lesions are benign and management is still with marginal excision, but they do have a low rate of local recurrence [8].
source p. 1443
Figure 24.9 Lipoma.
Other points
Atypical lipomas (ALT) and well-differentia ted liposarcomas (WD Lare equivalent terms, describing lesions that are identical histologically.
Site-specific variations in behaviour relate only to surgical resectability.
In tumours located in the periphery, complete resection is curative. They have no risk of metastasis – for these tumours the designation of AL T is preferred, as they do not behave like sarcomas.
In tumours that are large, deep-seated (e.g. retroperitoneum, pelvis, etc.), the chance of achieving negative margins is significantly diminished and the risk of local recurrence, dedifferentiation and death are increased.
These lesions are best regarded as true sarcomas and the terminology of WD Lis more appropriate.
MDM2 amplification using fluorescent in-situ hybridization (FISH) is now a well-recognized method of differentiating WD Land AL T histologically.
source p. 1444
Bibliography/Further reading
1. Welker JA, Henshaw RM, Jelinek J, Shmookler BM, Malawer MM. The percutaneous needle biopsy is safe and recommended in the diagnosis of musculoskeletal masses. Cancer. 2000;89(12):2677–2686.
2. Enneking WF, Spanier SS, Malawer MM. The effect of the anatomic seting on the results of surgical procedures for soft parts sarcoma of the thigh. Cancer. 1981;47(5):1005–1022.
3. Enneking WF, Spanier SS, Goodman MA. Current concepts review. The surgical staging of musculoskeletal sarcoma. J Bone Joint Surg Am. 1980;62(6):1027–1030.
4. NCCN. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: So Tissueḁ
Sarcoma. V.2.2008. National Comprehensive Cancer Network. 2008.
5. Bullough PG. Orthopaedic Pathology. Fourth Edition . Edinburgh: Mosby; 2007.
6. Beckingsale TB, Gerrand CH. Osteosarcoma. Orthop Trauma. 2010;24(5):321–331.
7. Meyers PA, Schwartz CL, Krailo MD, et al. Osteosarcoma: the addition of mur amyl tripeptide to chemotherapy improves overall survival – a report from the Children’s Oncology Group. J Clin Oncol.
2008;26:633–638.
8. Beckingsale TB, Gerrand CH. The management of soft -tissue sarcomas. Orthop Trauma.
2009;23(4):240–247.
9. Jeys LM, Thorne CJ, Parry M, Gaston CL, Sumanthi VP, Grimer JR. A novel system for the surgical staging of primary high-grade osteosarcoma: the Birmingham classification . Clin Orthop Relat Res.
2017;475(3):842–850.
10. Yamagishi T, Kawashima HOg ose A, et al. Receptor-activ ator of nuclear kappa b ligand expression as a new therapeutic target in primary bone tumors. PL oSONE. 2016;11(5):e0154680.
11. Van der Hejden L, Dijkstra PDS, Blay JY, Gelderblom H. Giant cell tumour of bone in the denosumab era. Eur J Cancer. 2017;77:75–73.
12. Dubory A, Missenard G, Domont J, Court C. Interest of denosumab for the treatment of giant cell tumours and aneurysmal bone cysts of the spine. About nine cases. Spine (Phil aPa 1976).
2016;41(11):E654–660.