Lytic Bone Lesions

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Continuing Education Activity

Bone tumors are mostly benign. The most important determinants in imaging of bone tumors are morphology on plain radiograph (well-defined lytic, ill-defined lytic, and sclerotic lesions) and the age of the patient at presentation. Well-defined osteolytic bone tumors and tumor-like lesions have a plethora of differentials in different age groups. This activity reviews the etiology, presentation, evaluation, and management of lytic bone lesions and reviews the role of the interprofessional team in evaluating, diagnosing, and managing the condition.

Objectives:

  • Summarize the etiology of various types of lytic bone lesions.
  • Describe the radiographic exam findings that accompany lytic bone lesions according to type.
  • Review the treatment and management of lytic bone lesions according to specific etiology.
  • Explain the importance of improving coordination among the interprofessional team to enhance care for patients affected by lytic bone lesions.

Introduction

Bone tumors are mostly benign. The most important determinants in imaging of bone tumors are morphology on plain radiograph (well-defined lytic, ill-defined lytic, and sclerotic lesions) and age of the patient at presentation.

Well-defined osteolytic bone tumors and tumor-like lesions have a plethora of differentials in different age groups. For simplicity, a widely used mnemonic for lytic bone lesions is extremely helpful: FEGNOMASHIC. We have attempted to describe the most characteristic features of each of these tumors.

The different bone tumors and lesions discussed are as follows: fibrous dysplasia (FD),[1] eosinophilic granuloma (EG), enchondroma, giant cell tumor (GCT), non-ossifying fibroma, osteoblastoma,[2] aneurysmal bone cyst (ABC), solitary bone cyst (SBC), hyperparathyroidism (Brown tumor), infection (always kept in differential diagnosis while dealing with bone lesions), chondroblastoma, CMF, metastasis, myeloma (any bone lesion detected in age above 40 years, must be ruled out for metastasis and myeloma).

The normal variant that can mimic lytic bone lesion is pseudocyst. It is an area of focal trabecular rarefaction at a low-stress region.[3] Pseudocysts most commonly occur in the greater tuberosity of the humerus, calcaneus, and radial tuberosity.

An osteolytic lesion with an ill-defined zone of transition is generally typical of malignant bone tumors (Ewing sarcoma, osteosarcoma, metastasis, leukemia) and aggressive benign lesions (giant cell tumor, infection, eosinophilic granuloma).

Etiology

The etiology of bone tumors varies greatly. They can be congenital, developmental, secondary to metabolic disorders and other primary bone tumors, or metastasis of primary elsewhere.  For example, fibrous dysplasia arises from sporadic mutation of alpha-subunit Gs stimulatory protein leading to inappropriate overproduction of cyclic-adenosine monophosphate (c-AMP)[4]. It causes the replacement of normal bone formation with fibrous stroma and islands of immature woven bone.

Epidemiology

Benign tumors and tumor-like lesions constitute about 79.3% of cases of all musculoskeletal lesions and show a slight female predominance. However malignant tumors constitute only 20.7% of lesions and show a male predominance.[5] The most common benign bone lesions are osteochondroma, enchondroma, and simple bone cysts. Benign bone tumors are more prevalent than malignant bone tumors in the younger age group.[6] Malignant bone tumors mainly metastasis and myeloma are more common in the older age group especially after 40 years of age.

Pathophysiology

Imaging characteristics to narrow the differential diagnosis of lesions:

Periosteal reaction: Periosteal reaction or periostitis is a non-specific radiographic finding which occurs due to irritation caused by underlying bone tumor either benign or malignant. The periosteal reaction is classifiable into continuous versus interrupted, single versus multiple layers, and benign versus aggressive forms.

Benign periosteal reaction: Chronic low-grade irritation allows periosteum to lay down thick, wavy and uniform callus resulting in a solid periosteal reaction. Fracture healing, osteoid osteoma, and chronic osteomyelitis can all lead to a solid periosteal reaction.

Aggressive periosteal reaction: This results when there is not enough time for the periosteum to lay down and consolidate the bone formation. The cortex appears multilayered, lamellated, amorphous or spiculated (sunburst), sometimes there is Codman's periosteal reaction. A malignant lesion like osteosarcoma causes interrupted periosteal reaction and Codman's triangle. Ewing's sarcoma causes lamellated and interrupted periosteal reaction. The aggressive periosteal reaction can be present in benign lesions like infection, eosinophilic granuloma, ABC, osteoid osteoma, trauma, and hemophilia.

Zone of transition: A zone of transition can help differentiate benign versus malignant lesions. A narrow zone of transition results in a sharp well-circumscribed border and is a sign of poor biological activity. However, in patients more than 40 years of age, despite benign radiographic appearances metastasis and myeloma should be considered in differentials. A wide zone of transition results in an ill-defined or imperceptible border is a sign of high biological activity or aggressive growth and is a feature of malignant bone tumor. However, two benign bone lesions which may show similar aggressive features are infection and eosinophilic granuloma. Permeative or moth-eaten appearance of bone appears as multiple endosteal lucent lesions with a poor zone of transition. It is due to bone marrow involvement. They can present in multiple myeloma, lymphoma, infections and, eosinophilic granuloma.

Cortical destruction: Cortical destruction is a frequent finding in bone lesions. However, it is not very useful in differentiating benign versus malignant lesions. Complete cortical destruction may be present in high-grade malignant lesions like osteosarcoma, Ewing sarcoma, and also in locally aggressive benign lesions. Ballooning is a particular type of cortical destruction, involves the destruction of the inner cortex and new bone formation outside cortex at the same time. Seen in giant cell tumor (locally aggressive expansile lesion with cortical destruction, a wide zone of transition, interrupted new bone formation peripherally) and in case of chondromyxoid fibroma (well defined, expansile lesion with regular destruction of the cortex and uninterrupted new bone formation). A group of small cell tumors involving marrow like Ewing, lymphoma, small cell osteosarcoma can spread along entire Haversian canals without cortical destruction.

Matrix: Calcification or matrix mineralization are essential features to differentiate bone tumors. There are two types of matrix mineralization. The chondroid matrix presents in cases of cartilaginous tumors like enchondroma, chondroblastoma, chondrosarcoma and presents as a ring and arc, floccular, stippled, or popcorn-like. Osteoid tumors demonstrate the osteoid matrix. Trabecular ossification pattern in case of an osteoid matrix and cloud-like bone formation in case of osteosarcoma.

Location: Bone tumors are described according to their location in the skeleton (axial, appendicular, and flat bones), part of the bone (epiphysis, metaphysis, and diaphysis), and site of bone (centric, eccentric, or juxtacortical).

Age: Age is among the most vital criteria for possible differentials. At age over 40 years, multiple myeloma and metastasis must always be kept in differentials.

History and Physical

Relevant clinical history and physical examination are the initial and most important steps in bone tumor evaluation. The patient may present with pain, mass or incidental radiographic finding in radiograph taken for some other purpose. Benign bone lesions are mostly asymptomatic. They are often incidentally diagnosed on imaging. They may present with pain. Pain may be initially activity-related or due to periostitis. Periostitis is the reaction of bone adjacent to the lesion; they are present in most of the bone tumors. Benign lytic bone lesions showing no periostitis or pain need separate mention: fibrous dysplasia, enchondroma, non-ossifying fibroma, and solitary bone cyst. In the case of malignant bone tumors like primary or metastasis pain may be persistent, unrelated to activity due to the involvement of neurovascular structures. Soft tissue tumors often present as a mass except for nerve sheath tumors which present as pain.

Although some bone tumors show a sex predilection like ABC and GCT are more common in females, this rarely makes any difference in the diagnosis and management of tumors.[7] Family history can occasionally be helpful, as with multiple enchondromas (autosomal dominant) and bone dysplasia in neurofibromatosis (autosomal dominant).[8] Most benign and malignant bone tumors are known to occur in specific age groups, making age one of the most important information in guiding the differentials. Some bone lesions can be multiple like fibrous dysplasia, eosinophilic granuloma, enchondroma, metastasis, and myeloma, hyperparathyroidism, hemangiomas, and infection. Specific syndromes can cause bone lesions like fibrous dysplasia in McCune-Albright syndrome and Mazabraud syndrome.

Physical examination should include a general examination which includes the overall health of the patient, any other abnormality or findings other than the region of interest like cafe-au-lait spots in the skin must be noted. Specific examination of the region interest which includes inspection, palpation, change with mobility, inspection of adjacent structures, and other relevant examinations.

Evaluation

Different imaging techniques are pivotal in diagnosing bone tumors. Radiograph comprises the initial and one of the most important diagnostic modalities. Often radiographic findings and the patient's age are sufficient to arrive at a diagnosis. The radiographic examination begins with locating the site of the lesion (epiphyseal, metaphyseal, or diaphyseal). An epiphyseal lesion in an unfused physis is likely chondroblastoma whereas that in a fused physis is likely a giant cell tumor.[9] The differential diagnosis of diaphyseal lesions includes fibrous dysplasia, osteoblastoma, histiocytosis, osteomyelitis, and others. In younger patients with vertebral body lesions most likely diagnosis is histiocytosis, whereas the lesions involving posterior elements of the spine may have ABC, Osteoblastoma, and Tuberculosis as differentials. However in patients older than 40 years, while dealing with posterior element lesions, metastasis must always be kept in mind. Similarly, the aggressiveness of the lesion and whether it is benign or malignant can be a radiographic determination. Less aggressive lesions often are well marginated with a surrounding sclerotic rim. More aggressive lesions usually have an ill-defined margin with no clear sclerotic rim because the host bone response is slower than the growth of the tumor. Cortical expansion may be visible in aggressive benign lesions like ABC, but the cortical break is a feature in malignant lesions like osteosarcoma. Often bone lesion replaces normal trabecular pattern of bone matrix with chondroid or osteoid matrix. Typical cartilaginous matrix shows stippled calcification as in enchondroma or chondrosarcoma. Osteoid matrix with bone destruction is present in osteosarcoma, while disorganized osteoid formation in collagenous stroma gives the ground glass appearance seen in fibrous dysplasia. Periostitis or reactive new bone formation occurs when the tumor irritates the cortex. The periosteal reaction can be benign or aggressive like Codman's triangle or onion skinning in malignant tumors. A plain radiograph is less helpful in soft tissue tumors; however, it may give some useful information like phleboliths in hemangioma.

Computed tomography is less useful in the diagnosis of benign bone tumors as compared to that of malignant bone tumors[10]. However, CT helps assess calcification, ossification, and integrity of the cortex. It helps to localize nidus in osteoid osteoma, thin rim of reactive sclerosis in ABC and for malignant tumors, it helps assess cortical breach, soft tissue involvement, and extent of tumor involvement for surgical planning. Saggital and coronal reconstruction images help in delineating the extent of the tumor in three planes and assists in surgical planning. CT of the lungs helps in ruling out lung metastasis in case of malignancy.

MRI helps in better soft tissue imaging, differentiating certain benign bone cysts like unicameral and aneurysmal bone cysts. In malignant bone tumors, they assist in evaluating the extent of marrow involvement and skip lesions, for surgical planning.

Technetium bone scans are used to determine active bone lesions and to rule out bone metastasis. However, a bone scan may be positive in specific active benign lesions, and it may be falsely negative in multiple myeloma[11]. However, most of the time a normal bone scan is reassuring.

Positron emission tomography (PET) records the whole-body distribution of positron-emitting radioisotopes. In musculoskeletal tumors, PET is useful in staging, biopsy planning, response to chemotherapy, detecting recurrence, and follow-up imaging.

Ultrasonography is useful for differentiating solid from cystic bone lesions and better imaging of soft tissue lesions.

Blood and urine tests may be helpful in selected clinical situations. The complete blood count may help predict wound healing following surgery and to rule out any infection or leukemia. Erythrocyte sedimentation rate (ESR) may show as elevated in infection, metastatic carcinoma, leukemia, etc. Elevated prostate-specific antigen (PSA) is often present in prostate cancer metastasis. Hypercalcemia is a presenting feature in certain malignancies and hyperparathyroidism.

Biopsy should be the last step after the complete evaluation of musculoskeletal tumors for the site of lesion, the behavior of the tumor, and the extent of resectability. Type of biopsy, placement of biopsy incision, and histopathological workup of biopsy tissue require planning. MRI and bone scans can be adversely affected by biopsy and postoperative changes in the tissue; hence they are generally obtained preoperatively. 

Important imaging features of certain different lytic bone lesions bear mentioning:

Fibrous dysplasia: FD is a common benign lesion with no age predilection. Classically it presents as well-defined lytic lesion, ground glass matrix, no periosteal reaction. Common sites are ribs (monostotic disease), pelvis, and extremities.[12] Clinically four types of FD are known: Monostotic, polyostotic, craniofacial, and cherubism ( maxilla and mandible in children). It is a disorder of bone characterized by the replacement of bone with structurally disorganized fibrous tissue. Fibrous dysplasia lesions may be quiescent, nonaggressive, or aggressive types

Eosinophilic granuloma: It is a form of histiocytosis X. It can be lytic or blastic, with or without sclerotic margin, with or without periostitis. There are no clear radiological features for this entity. However, based on previous experiences EG is rare in age over 30 years. It can be monostotic or polyostotic. It is also known to show sequestrum.

Enchondroma: It is the most common benign lesion of phalanges. Calcified chondroid matrix is invariable except when in phalanges. No periostitis. The most important differential is bone infarct. The syndrome associated with multiple enchondromas is Ollier disease and if presenting with multiple hemangiomas then, Maffucci syndrome.

Giant cell tumor: They occur typically in closed epiphysis, eccentric lesion, subarticular abutting the epiphysis with possible extension into metaphysics, and sharply defined nonsclerotic border; they are considered a moderately aggressive tumor.

Nonossifying fibroma: It is one of the most common incidental bone tumors. They are benign, asymptomatic tumors with a well-defined sclerotic margin. They are usually juxtacortical in location and typically occur in the metaphysis of long bones, and are most common in the under 30 age group. When the lesion is smaller than 2 cm, it is called a fibrous cortical defect (FCD).

Aneurysmal bone cyst[13]: They are an expansile lytic lesion, typically seen in the under 30 age group. An MRI shows multiple fluid-fluid levels. They can be of two types primary and secondary with other underlying lesions like osteosarcoma and chondrosarcoma and frequently presents with pain.

Osteoblastoma: This is a rare solitary benign tumor. It is one of the differentials of tumors involving the posterior element of the spine. Typically it is more than 2cm, to differentiate from osteoid osteoma.

Solitary bone cyst: This is a well-defined lytic lesion, central in a location involving proximal humerus and femur. It occurs in an age group of under 30 years. Most commonly presents with pain due to fracture through the cyst wall.

Chondroblastoma, chondromyxoid fibroma (CMF):  These are cartilaginous tumors. They typically arise in the epiphysis and show no calcified matrix.

Metastasis: must be included in the differential in age over 40 years, whether lytic or sclerotic, and well defined or ill-defined. Bone metastasis has a predilection for hematopoietic bone marrow such as spine, pelvis, rib, cranium, and proximal long bones.

Myeloma: It must be a consideration in the differential for individuals greater than 40 years. The most common location is an axial skeleton. It demonstrates multiple punched-out lesions on CT. It does not show any uptake on bone scan.

Infection: Infection of bone or osteomyelitis is a great mimicker of the tumor. It can present anywhere in bone.

Hyperparathyroidism or browns tumor: Browns tumor can occur in any bone and presents as multiple osteolytic lesions. Important differentials are metastasis, ABC, and GCT according to the site of the lesion.

Treatment / Management

The diagnosis of most bone lesions is on the basis of their clinical, radiological, and biopsy characteristics. Enneking and others have proposed a staging system for benign and malignant musculoskeletal tumors.[14] Staging helps in planning the treatment, prognosis of tumors, and comparing different treatment options.

Benign tumors staging is as follows:

Stage 1: Latent (intracapsular, asymptomatic, and incidental) lesions. Radiograph shows a well-defined lesion with a thick sclerotic rim and no cortical destruction or expansion. These lesions do not necessitate treatment because they do not compromise the strength of the involved bone. For example, small asymptomatic non-ossifying fibroma diagnosed incidentally. 

Stage 2: Active (intracapsular, actively growing, presents with symptomatic pain or pathological fracture) lesions. They have well-defined margins but may expand and thin the cortex. They usually have a thin rim of reactive margin. Treatment involves extended curettage. 

Stage 3: Aggressive (extracapsular) lesions. They are known to breach natural anatomical barriers, usually have broken through the cortex. Extended curettage, marginal resection, or wide resection if needed.

Musculoskeletal sarcomas are also staged according to histological grade, local extent, presence or absence of metastasis by Enneking as follows:

  • Stage IA/B: low-grade lesions, intracompartmental/extracompartmental, no metastasis
  • Stage IIA/B: high grade, intracompartmental/extracompartmental, no metastasis
  • Stage IIIA/B: any tumor that has metastasis regardless of grade or size of the tumor

Alternatively, many orthopedic oncologists stage musculoskeletal tumors according to American Joint Committee on Cancer System (AJCC) which is periodically updated.

Treatment of bone lesions must be undertaken by experienced surgeons who are well aware of the basic principles of management of different bone tumors. The choice of treatment depends on a variety of factors. Surgical intervention versus conservative treatment, single-drug therapy or a combination of curettage, bone grafting, and cyst injections, management of difficult areas like tumor involving spine and effect of therapy on continued skeletal growth, must be considered while deciding on treatment. As an example, ABC is managed by curettage and bone grafting or injection and embolization while infection needs appropriate antibiotic treatment and surgical debridement if necessary.[15] The primary goal of treatment in case of primary bone malignancy is to make patients disease-free. While in the case of metastatic disease of bone, the primary purpose of treatment is pain management. Combination therapy with radiotherapy, chemotherapy, and surgery is a common choice

There are specific benign bone lesions that do not need any intervention; they are better left alone. These are benign lesions and normal variants. A good example of obviously benign lesions like nonossifying fibroma. It is a lytic lesion located in the cortex of metaphysis of a long bone with a well-defined sclerotic border. Their involuting nature may show increased activity in a bone scan. When diagnosed by a radiologist, it does not need a biopsy. Another similar frankly benign lesion is a unicameral bone cyst of the calcaneus. They are asymptomatic and rarely undergo fracture as other limb lesions. Bone infarct also never causes a diagnostic dilemma to a reporting radiologist, hence don't need a biopsy.[16]

Differential Diagnosis

Epiphyseal Lesions

  • Chondroblastoma (10 to 25 years)
  • Giant cell tumor ( 20 to 40 years)
  • Chondrosarcoma (rare) 

Diaphyseal Lesions

  • Ewing sarcoma (5 to 25 years)
  • Lymphoma
  • Fibrous dysplasia (5 to 30 years)
  • Adamantinoma (in tibia)
  • Histiocytosis ( 5 to 30 years)

Multiple Lesions

  • Histiocytosis
  • Enchondroma
  • Osteochondroma
  • Fibrous dysplasia
  • Metastasis
  • Multiple myelomas
  • Infection
  • Hyperparathyroidism
  • Hemangioma

Complications

Complications related to benign bone tumors can be due to the tumor itself like, pain, pathological fracture, the formation of an aneurysmal bone cyst, or malignant transformation. Treatment-related complications include recurrence, mobility disorder, and other side effects. Malignant bone lesions are known to cause pain, pathological fracture, loss of function, and poor quality of life associated with treatment side effects and in extreme cases leading to death. Management of musculoskeletal lesions includes dealing with all these issues. 

Deterrence and Patient Education

The patients should receive education about their disease and available treatment options. Musculoskeletal lesions include a vast variety of pathologies, each of which would require an individualistic treatment approach. For example, benign bone lesions which are asymptomatic and inactive are usually left alone; while those tumors which are active and present with pain/pathological fractures need active intervention. More aggressive bone tumors may require extended curettage or wide resection. The primary goal in metastatic bone lesions is usually pain management and palliative care; while primary malignant bone tumors receive aggressive treatment whenever possible. The understanding is that case management of musculoskeletal lesions depends on a variety of factors and patients must be educated about their condition for better treatment results.  

Enhancing Healthcare Team Outcomes

An interprofessional/interprofessional approach is necessary for the appropriate management of these lesions.[17] Patients must be provided with all the essential information about their disease, different modalities of treatment, and early introduction of palliative care if needed. Physicians, nurse practitioners, orthopedic surgeons, and radiologists play a very important role in the appropriate diagnosis and management of musculoskeletal lesions. Malignant bone lesions must be managed by experienced oncologists to reduce the chances of treatment misadventures. Nursing professionals with specialized training in oncology treatment administration, monitoring, and patient education also play a vital role in the overall improvement of survival and quality of life.[18] An interprofessional team approach will produce the best results. [Level 5] Most of the available literature on lytic bone lesions is based on level 4/5 evidence.


Article Details

Article Author

Surabhi Subramanian

Article Editor:

Vibhu Krishnan Viswanathan

Updated:

8/25/2021 4:53:05 PM

PubMed Link:

Lytic Bone Lesions

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