Lytic Bone Lesions


Article Author:
Surabhi Subramanian


Article Editor:
Vibhu Krishnan Viswanathan


Editors In Chief:
Shivajee Nallamothu
Matthew Varacallo
Joshua Tuck


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
4/4/2019 7:14:38 PM

Introduction

Bone tumors are mostly benign. 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 tumour), 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 greater tuberosity of humerus, calcaneus and radial tuberosity.

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 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 the 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 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 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 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 imperceptable 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 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 step 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 needs 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 overall health of the patient, any other abnormality or findings other than the region of interest like cafe-au-lait spots in 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 modality. Often radiographic findings and patient's age are sufficient to arrive at a diagnosis. The radiographic examination begins with locating the site of 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, 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 host bone response is slower than the growth of the tumor. Cortical expansion may be visible in aggressive benign lesion 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 tumor irritates 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, they 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 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 tumor in three planes and assists in surgical planning. CT of 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 test 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 tumor and extent of resectability. Type of biopsy, placement of biopsy incision and histopathological workup of biopsy tissue requires planning. MRI and bone scan 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 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 with 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 metaphysis and sharply defined nonsclerotic border; they are considered 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 2cm, it is called fibrous cortical defect (FCD).

Aneurysmal bone cyst[13]: They are an expansile lytic lesion, typically seen in the under 30 age group. On 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: 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 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 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 trough 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 patient 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 which 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 nNonossifying 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 undergoes 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

The differential diagnosis for Epiphyseal lesion

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

Differential Diagnosis for Diaphyseal lesions:

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

Differential Diagnosis for 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

A multidisciplinary/interprofessional approach is necessary for 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 V] Most of the available literature on lytic bone lesions are based on level 4/5 evidence.


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Lytic Bone Lesions - Questions

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A 14-year-old boy is brought in by his father for left leg pain. He had injured his left leg several weeks earlier playing football. The pain has moderate despite minimal activity since that time, and the pain has not been relieved with the use of ibuprofen. The family history is also negative for any significant medical problems. He has been doing well in school and had been active in sports prior to this injury, with no history of prior leg injuries. On physical exam, he is well-appearing with normal vital signs. His left leg appears grossly normal, but is tender above the left knee. Radiographs reveal a lytic bone lesion in the distal left femur, with no fracture. Which of the following is NOT included in the differential diagnosis of painful bony lesions in children?



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A 60-year-old male patient presents with back pain for the last 3 weeks. Over the past 3 days, he has noticed progressive numbness involving both lower limbs. He has an unsteady gait and has fallen 3 to 4 times while walking over the last 2 weeks. On clinical examination, tenderness over thoracolumbar spine is elicited, and lower limb power is 4/5 extending from L2-S1 myotomes, and there is decreased pain and temperature sensation below the L2 dermatome. The bilateral lower limb reflexes are reduced, and he shows hypotonia. Radiographic exam reveals lytic lesion involving two-thirds of the T12 vertebral body, with less than 10% collapse. There were few small ill-defined lytic areas over T2, T6, and L3 vertebrae. His skeletal survey revealed multiple lytic lesions in the skull and an ill-defined lytic lesion in the proximal humerus. On detailed laboratory and radiological evaluation, diagnosis of multiple myeloma was made. What would be the next line for management of this spinal lesion presenting with neurological deficits?



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A 65-year-old woman presents with upper back pain and progressive weakness over the past 15 days. History reveals she had undergone multilevel spine surgery for vertebral compression fractures six months ago. She never heard about multiple myeloma during that period. Laboratory and radiological evaluation revealed the diagnosis of Multiple myeloma (IgG, kappa chain). CT and MRI showed lytic lesions and multiple pathological fractures involving the T5, 6, and 9 and an epidural mass compressing spinal cord at the T5 level. On lower extremity neurological examination, her lower extremity power was grade IV, was able to walk with support. High dose corticosteroid and radiotherapy were performed. Three months follow-up radiological examination revealed complete resolution of cord compression and epidural mass. One year later she presented with worsening back pain and right facial numbness. MRI revealed leptomeningeal enhancement involving right cavernous sinus, trigeminal nerve extending to involve the thoracolumbar spine. Cerebrospinal fluid obtained from lumbar puncture showed a large number of atypical mononuclear cells. Flow cytometry confirmed plasma cells with kappa light chain restriction. The patient was treated with whole brain irradiation, chemotherapy, and high dose steroids but died after three weeks due to intraparenchymal hemorrhage related to thrombocytopenia. What is the cause of the current symptoms?



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Lytic Bone Lesions - References

References

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Xu H,Nugent D,Monforte HL,Binitie OT,Ding Y,Letson GD,Cheong D,Niu X, Chondroblastoma of bone in the extremities: a multicenter retrospective study. The Journal of bone and joint surgery. American volume. 2015 Jun 3;     [PubMed]

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