Primary malignant tumours of the bone

Primary bone tumours of bone are rare, with approximately 400 new cases per year in the UK. The diagnosis of bone tumours are hampered by delays in presentation and diagnosis. There are x-ray changes which are often characteristic for each type of bone tumour and x-rays should alert the physician to investigate further. Investigations should include blood tests, local staging and systemic staging. MRI, CT of the chest and isotope bone scans are important in evaluating the tumour. The most common types of bone tumour are Osteosarcoma, Chondrosarcoma, Ewing’s sarcoma, Spindle Cell Sarcoma of bone and Chordoma. The important features and treatment of each type of tumour are described in the article. Early contact to a tertiary referral bone tumour unit is mandatory when a bone tumour is suspected, where a multidisciplinary team approach is employed. Biopsy and surgical treatment should only be undertaken in such a unit and all patients should be enrolled in international clinical trials in an attempt to improve outcomes. The survival rates from most bone tumours are of the order of 60-80% with appropriate treatment.     

Primary malignant tumours of the bone

Primary bone tumours are rare, with a prevalence of approximately 550 cases per year in the UK. Late presentation and identification of tumours delays diagnosis and negatively impacts on the survival of these patients. Characteristic clinical and radiological features of bone tumours should alert the physician to investigate further. Investigations should include blood tests and local and systemic imaging. MRI, CT and isotope bone scans are important in evaluating the tumour. The most common types of bone tumour are osteosarcoma, chondrosarcoma, Ewing sarcoma, spindle cell sarcoma of bone and chordoma. The important pathological features and treatment of each type of tumour are described in this article. Early contact with a supra-regional bone tumour unit is mandatory when a bone tumour is suspected, where a multidisciplinary approach to management is employed. Biopsy and surgical treatment should be carried out in these units wherever possible. Patients should be enrolled in international clinical trials, where feasible, to gather data that will ultimately improve outcomes. The survival rates from most bone tumours are 60–80% with appropriate treatment.     

Pathology of paediatric bone tumours

Primary bone tumours account for less than 0.2% of all neoplasms but malignant bone tumours represent the third most common cause of cancer deaths in children and adolescents. The rarity of bone tumours in itself is a diagnostic challenge but is compounded by the number of tumour subtypes on top of which the imaging and histological features of degenerative and reactive processes, and benign bone tumours can simulate bone sarcomas. Furthermore, even in children bone lesions may represent metastatic disease. Hence the assessment of a bone tumour in a child or adolescent should be performed in a specialist referral bone tumour centre which has access to a multidisciplinary team and molecular diagnostic tests: the latter provides greater diagnostic accuracy. It is now appreciated that germline alterations occur more commonly than previously recognised in children and young adults presenting with osteosarcoma and Ewing sarcoma. Awareness of this is important as genetic counselling and screening may be appropriate. In this article epidemiology, radiology, pathology, genetics, treatment and prognosis of most commonly encountered bone tumours among the paediatric population are reviewed.     

Diagnosis and staging of malignant bone tumours in children: what is due and what is new?

PurposeAlthough malignant bone tumours in children are infrequent, it is important to know how to properly diagnose and stage them, in order to establish an adequate treatment.MethodsWe present a review of the diagnostic workflow of malignant bone tumours in children, including history and clinical examination, imaging, laboratory tests and biopsy techniques. Moreover, the two most commonly used staging systems are reviewed.ResultsHistory, clinical examination and laboratory tests are nonspecific for diagnosing malignant bone tumours in children. Radiographs remain the mainstay for initial diagnosis, with MRI the modality of choice for local assessment and staging. Fluorine-18 labelled fluoro-deoxy-glucose-positron emission tomography scans provide a noninvasive method to assess the aggressiveness of the tumour and to rule out metastasis and is replacing the use of the bone scintigraphy. Biopsy must be always performed under the direction of the surgeon who is to perform the surgical treatment and after all diagnostic evaluation has been done. Staging systems are useful to study the extent of the tumour and its prognosis. They are expected to evolve as we better understand new molecular and genetic findings.ConclusionWhen a malignant bone tumour is suspected in a child, it is essential to make a correct diagnosis and referral to an experienced centre. Following an appropriate workflow for diagnosis and staging facilitates, prompt access to treatment improves outcomes.Level of EvidenceLevel V Expert opinion     

Extraskeletal osteosarcoma

A 50 years old male presented with ulcer and swelling in left leg for 2 years. X-ray showed soft tissue sarcoma and excision was done. A diagnosis of extraskeletal osteosarcoma was made. Extraskeletal osteosarcomas are rare malignant mesenchymal neoplasms. By definition, these are located in soft tissue without primary involvement of bone or periosteum. Since these tumours mimic other soft tissue tumours and tumour like conditions, radiology and histopathology along with tumour markers studies are important in diagnosis of this tumour.     

Malignant tumours of bone: clinical aspects and natural course.

An accurate pathological diagnosis must be made prior to treatment of a primary malignant bone tumour. Consideration must be given to the clinical and radiologic aspects as well as the histology. Both benign and malignant tumours occur more frequently in certain decades. A search should be made for precursor lesions such as Paget's disease. The presenting manifestations of pain, a mass and dysfunction are not specific for tumours. Laboratory tests may be helpful, especially in distinguishing tumours from infections and metabolic diseases. Metastasis is usually via the blood stream to the lungs and bones. The low survival rate following amputation for osteosarcoma and radiation therapy for Ewing's sarcoma has been improved by chemotherapy. The lower-grade tumours such as aggressive giant cell tumour and low-grade chondrosarcoma can often by treated successfully by resection and insertion of an autograft, an allograft or a metallic implant.     

Genitourinary lymphomas

Lymphomas of the genitourinary tract represent rare tumours for which the diagnosis is crucial regarding the specificity of the treatment. The most frequent localisations are the kidney (solitary tumour or multiple nodules) and the testis; other sites of the genitourinary tract are uncommon. One of the main challenges is to obtain an appropriate immunohistochemical diagnosis with a good staging which is necessary to adapt the therapeutic options. These are mostly based on chemotherapy (with immunotherapy in B-cell lymphomas), of which the intensity and number of cycles depend on initial prognosis factors.     

Positron emission tomography for urological tumours

For urological tumours, positron emission tomography (PET) is currently most useful in testicular cancer. In patients with residual masses or raised marker levels after treatment, PET is both sensitive and specific for detecting recurrent disease, at suspected and unsuspected sites. Although fewer studies are available it also appears to be useful for staging at diagnosis, although this requires further investigation. Prostate cancer imaging has been more variable, with studies showing that PET cannot reliably differentiate between tumour and hypertrophy. It is not as good as a bone scan for defining bone metastases. In renal cancer, PET can be used to define the primary tumour, providing better staging of local recurrence than computed tomography (CT), and to define metastatic disease. There are few studies in bladder cancer, and despite excretion of the tracer via the bladder in early studies, it has better results than CT or magnetic resonance imaging for local staging; again it can detect metastases. Overall, the place of PET in urological tumours is developing, with the strongest areas undoubtedly being testicular and renal cancer. Tracers other than fluorodeoxyglucose are being examined and are providing further information.     

Primary Tumours in the Spine and Pelvis in Adolescents: Clinical and Radiological Features

In 34 patients in their two first decades of life with primary bone tumours in the spine and pelvis, the most common benign tumour was histiocytosis X and the most common malignant tumour, Ewing's sarcoma. X-rays were positive in 32 out of 34 cases but of little diagnostic value and primary complaints were without significance. The final diagnosis can only be made after a biopsy.     

Primary tumours in the spine and pelvis in adolescents: clinical and radiological features.

In 34 patients in their two first decades of life with primary bone tumours in the spine and pelvis, the most common benign tumour was histiocytosis X and the most common malignant tumour, Ewing's sarcoma. X-rays were positive in 32 out of 34 cases but of little diagnostic value and primary complaints were without significance. The final diagnosis can only be made after a biopsy.     

De novo malignant peripheral nerve sheath tumor of the breast: case report number one

Summary BACKGROUND: Sarcomas of the breast are rare, representing less than 1% of malignant breast tumours. Malignant peripheral nerve sheath tumour (MPNSTs) is the malignant counterpart to benign soft tissue tumours such as neurofibromas and schwannomas. It is the most common sarcoma arising in the setting of von Recklinghausen's disease. METHODS: We report a de novo malignant peripheral nerve sheath tumour of the breast in 18-year-old patient. To the best of our knowledge, this is the first reported case of sporadic MPNST occurring in the breast in the absence of neurofibromatosis. RESULTS: Immunohistochemical examination is essential to establish the diagnosis and helpful in excluding other lesions in the differential diagnosis. CONCLUSIONS: The surgeon should approach these tumours according to the established guidelines for soft tissue sarcoma surgery.      

MRI surveillance after resection for primary musculoskeletal sarcoma

This study reports the experience of one treatment centre with routine surveillance MRI following excision of musculoskeletal sarcoma. The case notes, MRI and histology reports for 57 patients were reviewed. The primary outcome was local tumour recurrence detected on either surveillance MRI in asymptomatic patients, or interval MRI in patients with clinical concern. A total of 47 patients had a diagnosis of soft-tissue sarcoma and ten of a primary bone tumour. A total of 13 patients (22%) had local recurrence. Nine were identified on a surveillance scan, and four by interval scans. The cost of surveillance is estimated to be pound4414 per recurrence detected if low-grade tumours with clear resection margins are excluded. Surveillance scanning has a role in the early detection of local recurrence of bone and soft-tissue sarcoma.     

The management of soft tissue sarcomas

BackgroundSoft tissue sarcomas are a rare and heterogeneous group of malignancies that are derived from the mesenchymal cell lines. In the last few decades, the management of these lesions has been improved by the introduction of dedicated Multi Disciplinary Teams (MDTs) where most bone and soft tissue tumours are now treated.¹Following the recent changes to management outlined by the NICE/IOGs, we believe it is pertinent to review the current thinking on soft tissue tumour management.² We also discuss the principles of diagnosis and treatment and the role of adjuvant therapy.MethodsThis is a retrospective review. In the preparation of this paper, we have referred to recent NICE guidelines in this field and have performed a Medline search of the existing literature.ResultsThe key to success is early and appropriate patient referral. Whilst the responsibility for performing surgery has shifted away from the generalist and towards the super-specialist, improvements in survivability can be achieved by promoting basic knowledge within the medical profession as a whole.ConclusionsBoth excision and biopsy of a soft tissue sarcoma by a non-specialist surgeon have been shown to increase the risk of tumour recurrence and all invasive procedures should now be performed within the MDT setting.     

A guide to oncological management of soft tissue tumours of the abdominal wall

Introduction

An abdominal mass is a common clinical presentation, and a small percentage of such patients will have an abdominal wall tumour with the two most common pathologies being fibromatosis and soft tissue sarcoma.

Methods

Here we present the available literature on the diagnosis and management of both fibromatosis and soft tissue sarcoma, in the context of our experience in a tertiary referral centre for sarcoma.

Results and discussion

Appropriate cross-sectional imaging and a pre-operative tissue diagnosis by percutaneous core biopsy are necessary to define management. Desmoid fibromatosis can be managed initially by observation with serial imaging, with surgery being reserved for those patients who demonstrate progression.  Soft tissue sarcoma can display a range of pathologies from relatively indolent tumours to locally aggressive sarcomas that can readily metastasise. An accurate pre-operative histological diagnosis and staging enables a multidisciplinary approach to management. This may include chemotherapy and radiotherapy, but the mainstay of treatment remains wide surgical resection and abdominal wall reconstruction. Patient outcomes are worse if referral is delayed or if the sarcoma is incompletely resected without an initial tissue diagnosis.     

Transurethral Resection of Non–muscle-invasive Bladder Cancer

Transurethral resection of the bladder (TURB) is the initial and critical step in the management of bladder tumours. The aim of the procedure is to establish the histologic diagnosis, determine the tumour stage and grade, and achieve complete removal of papillary non–muscle-invasive tumours. Although TURB is a frequently performed procedure, its results are limited by the high recurrence rate and by the risk of tumour understaging. The major prerequisite for optimal outcomes is a systematically and meticulously performed procedure by a well-trained urologist. Smaller tumours can be resected en bloc; tumours >1 cm should be resected separately in fractions. Deep resection, including the detrusor muscle, is essential for correct staging. The biopsy should be taken from all areas suggestive of carcinoma in situ (CIS), and biopsies from normal-looking mucosa are recommended only in patients with positive cytology or non-papillary tumours. TURB should be performed with modern equipment, including new telescopes and video systems. Moreover, urologists should be aware of promising innovations, including new imaging techniques, and their possible benefits.Re-TUR can improve recurrence-free survival (RFS) and tumour staging. It is recommended in any patient with a T1 or high-grade tumour at initial resection and when the pathologist has reported that the specimen contained no muscle. It should also be considered in cases where the urologist is not sure that the initial resection was complete, especially in extensive and multiple tumours.     

Excisional biopsy for bone tumours

Summary Compartmental muscular resections without open biopsy is a common procedure for soft tissue tumours suspected of malignancy. In bone tumours, where the diagnosis is supposed to be sarcoma, an excisional biopsy is seldom possible without severe reconstructive problems and it may be unnecessarily mutilating should the tumour be benign. For the fibula, the clavicula, metatarsal and metacarpal bones, the distal third of ulna and the proximal third of radius, however, excisional biopsy as the primary procedure should be taken into account. The resulting loss of function is minor and can well be accepted even if the tumour turns out to be benign. On the other hand, if it is malignant as supposed, the radical excisional biopsy saves the patient from amputation. When incisional biopsy is used instead of excisional biopsy the definite surgery has to be made much wider and will often be mutilating. A case of chondrosarcoma illustrates the advantage and the disadvantage of this principle as well as an unusual reconstruction.     

EAU guidelines on testicular cancer

OBJECTIVES: To establish guidelines for the diagnosis, staging, treatment and follow-up of germ cell testicular cancer. METHODS: A search of published work was conducted using Medline. Highly evidence-based articles were selected and their findings analysed by the members of the Oncological Urology Working Group of the EAU. Testis cancer is rare and affects young men in their 3rd and 4th decades of life. The majority of these tumours are derived from germ cells (seminomatous and non-seminoma germ cell testicular cancer), and more than 50% of patients are diagnosed with stage I disease. Epidemiological, pathological and clinical risk factors are well established. The tumour, node, metastasis (TNM) staging system is endorsed, and for metastatic disease a recently devised prognostic-factor-based staging system has proven to be useful. Staging assessment includes pre- and post-orchiectomy marker levels, pathology of the testis, and nodal and visceral status. Following orchiectomy, treatment depends on the tumour type, pathological risk factors for stage I disease and clinical prognostic factors for advanced disease. The cure rate is excellent for disease stages I and II, irrespective of the treatment adopted. However, the pattern of relapse (rate, timing and site) is highly influenced by therapeutic policy. For metastatic disease, survival depends on clinical prognostic factors and treatment. Follow-up schedules are tailored according to stage, tumour type and post-orchiectomy treatment schedules. CONCLUSIONS: Excellent cure rates are achieved for early-stage germ cell testis tumours following accurate staging at diagnosis. Satisfactory survival rate can be achieved in advanced metastatic disease using a multidisciplinary therapeutic approach. Follow-up schedules vary, depending on the pathology and stage of the primary tumour and on the treatment policy adopted following orchiectomy.     

Radiation-induced sarcomas of bone: factors that affect outcome

We identified 42 patients who presented to our unit over a 27-year period with a secondary radiation-induced sarcoma of bone. We reviewed patient, tumour and treatment factors to identify those that affected outcome. The mean age of the patients at presentation was 45.6 years (10 to 84) and the mean latent interval between radiotherapy and diagnosis of the sarcoma was 17 years (4 to 50). The median dose of radiotherapy given was estimated at 50 Gy (mean 49; 20 to 66). There was no correlation between radiation dose and the time to development of a sarcoma. The pelvis was the most commonly affected site (14 patients (33%)). Breast cancer was the most common primary tumour (eight patients; 19%). Metastases were present at diagnosis of the sarcoma in nine patients (21.4%). Osteosarcoma was the most common diagnosis and occurred in 30 cases (71.4%). Treatment was by surgery and chemotherapy when indicated: 30 patients (71.4%) were treated with the intention to cure. The survival rate was 41% at five years for those treated with the intention to cure but in those treated palliatively the mean survival was only 8.8 months (2 to 22), and all had died by two years. The only factor found to be significant for survival was the ability to completely resect the tumour. Limb sarcomas had a better prognosis (66% survival at five years) than central ones (12% survival at five years) (p = 0.009). Radiation-induced sarcoma is a rare complication of radiotherapy. Both surgical and oncological treatment is likely to be compromised by the treatment received previously by the patient.     

Biological behaviour and clinical implications of micrometastases

BACKGROUND: The most important prognostic determinant in cancer is the identification of disseminated tumour burden (metastases). Micrometastases are microscopic (smaller than 2 mm) deposits of malignant cells that are segregated spatially from the primary tumour and depend on neovascular formation (angiogenesis) to propagate. METHODS: The electronic literature (1966 to present) on micrometastases and their implications in malignant melanoma and epithelial cancers was reviewed. RESULTS: Immunohistochemical techniques combined with serial sectioning offer the best accuracy for detection of nodal micrometastases. Molecular techniques should be reserved for blood samples or bone marrow aspirates. Detection of micrometastases in regional lymph nodes and/or bone marrow confers a poor prognosis in epithelial cancers. The concept of sentinel node biopsy combined with serial sectioning and dedicated screening for micrometastases may improve staging procedures. Strategies against angiogenesis may provide novel therapies to induce and maintain micrometastatic dormancy. CONCLUSION: The concept of micrometastases has resulted in a paradigm shift in the staging of epithelial tumours and our overall understanding of malignant processes.     

Surgical management of paediatric malignant bone tumours

The malignant bone tumours in children are rare, concerning 5% of the all paediatric tumours. Among all paediatric bone tumours, 15% of them are malignant. The main bone tumours in children are the osteosarcoma and the Ewing sarcoma. The diagnosis and treatment need a multidisciplinary medical team. It is essential in front of potential clinical or radiological signs, to perform quickly the specific medical exams and biopsy. The treatment needs a paediatric medical and surgical staff.