Juxtacortical tumors or surface tumors of bone are neoplasms [abnormal and excessive growth] arising from or just outside the cortex, and are composed of different histologic types.

Some of the important juxtacortical tumors are

• Periosteal or juxtacortical chondroma
• Periosteal or juxtacortical chondrosarcomas
• Periosteal or juxtacortical  osteosarcomas

Juxtacortical tumors are divided into 5 major categories

• Cartilaginous [most common]
• Fibrous
• Lipomatous
• Osseous
• Metastatic

Juxtacortical chondroma and chondrosarcoma are cartilaginous, osteosarcoma is an example of the bony lesion.

Chondromyxoid fibroma is a fibrous lesions. Metastases and lipomatous juxtacortical tumors are less common.

Juxtacortical Chondroma or Periosteal Chondroma

Periosteal chondroma is a benign cartilage juxtacortical tumor that develops on the surface of bone under the periosteum and consists of mature hyaline cartilage.

Periosteal chondromas account for less than 1% of all chondromas.

A slight male predominance exists. 

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are known to be associated.

Periosteal chondroma is known to grow into adulthood as well. Osteochondroma stops growing after skeletal growth stops.

The proximal humerus is most commonly affected [50%]. It may also involve the bones of the hands and feet.

Microscopic features are typical of a chondroma with a hyaline cartilage matrix. On average, juxtacortical chondromas can show mild nuclear atypia or binucleated chondrocytes. Scalloping and erosion of the outer cortex are seen microscopically.

Some periosteal chondromas may bulge for a short distance into intervening lamellar bone.

A fibrous capsule typically overlies the tumor. Occasional foci of necrosis and myxoid degeneration may be present.

This surface lesion most often presents as slowly progressive painful mass. The pain is due to enlargement of the lesion or from impingement on adjacent soft-tissue structures.

Physical examination reveals a firm and immobile mass which is painful to touch.

Deep-seated juxtacortical chondromas near tendon insertion sites may cause pain and local discomfort on activity.

Periosteal chondromas are always not symptomatic though. These are sometimes discovered incidentally on radiographs.

X-rays reveal a well-circumscribed surface lesion of bone, usually of size 1-5 cms, with variable punctate calcifications on radiographs. The cartilaginous nature of juxtacortical chondroma is easy to recognize on plain radiographs.

The cortex beneath the lesion is usually eroded but not completely disrupted. There would a varying degree of subcortical sclerosis beneath the lesion.

The elevated periosteum is seen as solid buttresses of mature subperiosteal bone. It can sometimes slightly overhang the edges of the central excavation especially in cases of the smaller periosteal chondromas

Computed tomography, magnetic resonance imaging, or both modalities also may be needed to evaluate the extent of involvement

Asymptomatic stable lesions can be monitored. Though the risk of malignant transformation is very small, asymptomatic periosteal chondromas should be followed regularly with clinical examination and x-rays.

A lesion that enlarges over a period or is symptomatic should be treated.

Complete local excision of juxtacortical chondroma is a curative procedure. Because periosteal chondromas may demonstrate radiologic overlap with juxtacortical chondrosarcoma, excision of the lesion is the preferred mode of the treatment.

Periosteal Chondrosarcoma

Periosteal chondrosarcoma or juxtacortical chondrosarcoma is a malignant cartilage tumor that is seen in the second to fourth decades of life. 

The patient presents with a slowly growing mass. Pain is less common. The distal femur is the most common site followed by proximal humerus.

Perioseal chondrosarcoma is difficult to differentiate from periosteal chondroma.The larger size and cortical breach [compare with juxtacortical chondroma] suggest chondrosarcoma.

MRI shows multilobulated lesions, confined to the juxtacortical area without medullary involvement.

Microscopically, the lesions are low-to-intermediate grade. An occasional high-grade area may be seen.

Increased of expression of matrix metalloproteinases 1, 2, and 9 is noted but less consistently than central or dedifferentiated chondrosarcoma.

Osseous metaplasia or enchondral ossification may lead to pockets of bone formation in the tumor.

Like juxtacortical chondrosarcomas, mutations in IDH1 and IDH2 have been noted.

Treatment consists of surgical removal with tumor-negative margins. With adequately resected margins, local recurrence is unusual. Metastases also are unusual, and if they occur, they occur late in the disease process. ^]

Juxtacortical Osteosarcoma

Parosteal Osteosarcoma, periosteal osteosarcoma and high-grade surface osteosarcoma are three types of osteosarcomas that form juxtacortical osteosarcomas.

Parosteal Osteosarcoma

Parosteal osteosarcoma is the most common representing 65% of juxtacortical osteosarcomas. It forms  3-6% of all osteosarcomas

Posterior surface of the distal femur is most commonly involved.  Occasionally proximal humerus is involved. Most of the cases are seen in persons aged 15-40 years.

There is a slight female predilection for this variant of osteosarcoma. Slowly growing painless mass is the usual presenting feature.  Pain and swelling occur late.

There could be a decreased range of motion of the joint as the lesion is in the vicinity of the joint.

On x-rays, the lesions are seen as radiodense mass present on the bone surface. The lesion is broad-based and may encircle the bone.

Periosteal reaction is not seen [as compared to intramedullary osteosarcoma]. Lucent areas on x-ray films suggest either aggression or dedifferentiation [presence of immature cells] of the tumor.

A clear space, on CT,  between the tumor and the bone cortex, is called clear plane or string sign. It reflects unmineralized, thickened periosteum. CT can delineate areas of cortical erosion. 

MRI  can identify soft tissue and intramedullary extent of the tumor. MRI is useful for preoperative planning and can reveal more aggressive areas within apparent parosteal osteosarcoma.

On gross examination, the dense mineralization of the tumor is noticed along with medullary involvement.

Being low grade, this variant does not express the higher MIB-1 indices [ percentage of immunoreactive tumor cells] or multiple chromosomal aberrations typically seen with higher-grade lesions.

But every tumor should be looked for pockets of high-grade changes.

Treatment of these juxtcortical tumors consists of wide resection and limb salvage when possible. Although low-grade, these tumors may recur locally with less than a wide resection margin, and dedifferentiation has been noted in cases with multiple local recurrences. 

Among osteosarcomas, this variant carries the best prognosis.

However, wide margins may be difficult to achieve due to the vicinity of neurovascular structures.

Metastases in classic parosteal osteosarcoma are rare

Parosteal osteosarcoma that contains higher-grade dedifferentiated areas has a worse prognosis.

Periosteal Osteosarcoma

Periosteal osteosarcoma represents the second most common type of surface osteosarcoma. Its occurrence is similar to conventional osteosarcoma.

It is a purely cortical lesion, the thickened intact cortex is visible. It is high grade and does not go to medulla.

There is a male predilection has been noted. 

Periosteal osteosarcoma most frequently is seen on the surface of the proximal tibia [compare with parosteal]. The patients present with a painful enlarged mass which has rapid clinical course.

X-rays show heterogeneous ossification. Radiolucent lesions are present in greater frequency than in parosteal osteosarcoma. Erosion or thickening of the underlying cortical bone may be noted.

Microscopically, the tumor is composed of moderately differentiated chondroblastic osteosarcoma. The spindle-cell component usually is of intermediate grade. Cartilage present within the tumor contributes to the lobulated appearance. However, the chondrocytes may show atypia [structural abnormalities of cells]

Treatment consists of wide surgical resection. This variant is reported to metastasize.

High-Grade Surface Osteosarcoma

It is the least common of the surface osteosarcomas. Most commonly, it affects people in the second or third decade

This variant is found more in the males.

Patients typically present with an enlarging painful mass and swelling. The natural course fo this tumor is shorter. Most of the patients present within 1-6 months. Just to compare, parosteal osteosarcoma takes about one year to present.

Midfemur or distal femur is the most common location. The tibial diaphysis is next in the list.

X-rays show a broad attachment to the cortex but there is no encircling of the cortex as seen in parosteal osteosarcoma. Involvement of the underlying cortex is seen as cortical erosion or thickening.

The lesion may be dense showing sunburst appearance or could be radiolucent.

Medullary involvement may be difficult to rule out. However, if there is substantial medullary involvement, the lesion is more likely to be conventional intramedullary osteosarcoma with extrabony extent.

The tumor is otherwise histologically identical to the conventional intramedullary form.

This tumor has the worst prognosis among the surface osteosarcomas and demands aggressive treatment.

Initial grade of the tumor, response to neoadjuvant chemotherapy, and the presence of local recurrence are prognostic factors.

References

• Seeger LL, Yao L, Eckardt JJ. Surface lesions of bone. Radiology. 1998 Jan. 206(1):17-33.
• Baker AC, Rezeanu L, O’Laughlin S, Unni K, Klein MJ, Siegal GP. Juxtacortical chondromyxoid fibroma of bone: a unique variant: a case study of 20 patients. Am J Surg Pathol. 2007 Nov. 31(11):1662-8.
• Putti TC, Kahn LB, Aprin H. Periosteal chondrosarcoma: a case report and review of the literature. Arch Pathol Lab Med. 1997 Jan. 121(1):70-4.
• Jelinek JS, Murphey MD, Kransdorf MJ, et al. Parosteal osteosarcoma: value of MR imaging and CT in the prediction of histologic grade. Radiology. 1996 Dec. 201(3):837-42.
• Miller SF. Imaging features of juxtacortical chondroma in children. Pediatr Radiol. 2014 Jan. 44 (1):56-63.
• Chaabane S, Bouaziz MC, Drissi C, Abid L, Ladeb MF. Periosteal chondrosarcoma. AJR Am J Roentgenol. 2009 Jan. 192(1):W1-6.
• Sheth DS, Yasko AW, Raymond AK, et al. Conventional and dedifferentiated parosteal osteosarcoma. Diagnosis, treatment, and outcome. Cancer. 1996 Nov 15. 78(10):2136-45.
• Bielack SS, Hecker-Nolting S, Blattmann C, Kager L. Advances in the management of osteosarcoma. F1000Res. 2016. 5:2767.

Maffucci syndrome is a rare disorder is characterized by enchondromas, bone deformities with venous malformations with or without spindle cell hemangiomas.

The condition was first reported by Maffucci in 1881. There is no racial or sexual predilection.

It usually manifests early in life, usually around age 4-5 years. About one-fourth of the cases are congenital. But familial inheritance is not seen.

Only less than 150 cases of this syndrome have been reported.

Pathophysiology

Maffucci syndrome has been shown to be associated with heterozygous somatic mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) genes. 

The syndrome mainly affects the skin and skeletal systems. Venous malformations often protrude as soft nodules or tumors. These are usually seen on the distal extremities, unilateral or bilateral but they can appear anywhere.

The lesions are compressible, soft, red-blue papules and nodules.

Thrombi often form within vessels and develop into phleboliths.

Venous malformations have also been reported in sites other than skin. These are the leptomeninges, eyes, respiratory tract, and GI tract. The cutaneous vascular malformations may also be present on mucosal surfaces.

Less commonly venous-lymphatic malformations and hemangioendotheliomas can occur.

Enchondromas mainly occur in small tubular bones and the long bones though they may occur anywhere. These lead to bony deformities and secondary fractures. Fracture malunion may occur. malunion of fractures. 

Transformation to chondrosarcoma is seen in about 30% of patients.

Vascular neoplasms like hemangiosarcomas and lymphangiosarcomas have been reported but rarely.

Other malignancies associated are

• Pancreatic adenocarcinoma
• Hepatic adenocarcinoma
• Ovarian tumors
• Brain gliomas
• Astrocytomas

Clinical Presentation

Parents often notice soft, blue-colored growths on the distal aspects of the extremities.

The children usually are short statured. Patients with Maffucci syndrome are usually short in stature and may have unequal arm or leg lengths due to the bone abnormalities.

Enchondromas usually involve small bones of hand and feet but occur in long bones too.

Walking and use of objects may be affected.

Patients need to be watched for complications. Malignant transformation to chondrosarcoma is most dreaded and present in about 30% cases. Fracture and limb inequality are others.

Differential Diagnoses

• Ollier Syndrome
• Isolated venous malformation
• Multiple glomuvenous malformations
• Servelle-Martorell syndrome
• Skin manifestations of
  • Kaposi sarcoma
  • Proteus syndrome
• Blue Rubber Bleb Nevus Syndrome

Diagnosis

Maffucci syndrome can be diagnosed on clinical presentation and radiological imaging.

X-rays will reveal findings suggestive of enchondromas. Skeletal surveys can be undertaken for ascertaining the bones involved.

Differentiation from chondrosarcoma is important and the patient is followed regularly to recognize any changes occurring over the course of life.

Clinically the malignant changes are suspected by an increase in size and pain. On x-rays,  cortical destruction, endosteal cortical erosion, and zones of lucency within a previously mineralized area are signs suggestive of malignant change.

CT and/or MRI, while routinely not done, are able to provide better information about the lesion and its surrounding soft tissue.

A needle biopsy should provide a diagnosis which would reveal poorly differentiated pleomorphic chondrocytes. 

Treatment of Maffucci Syndrome

Patients who are without symptoms do not require any treatment. Patients are kept in follow up to to evaluate any changes in the skin and bone lesions.

Venous malformations management depend on their severity of symptoms and the severity of the lesion.

Anticoagulation therapy, compression dressings, or sclerotherapy ar various treatment options. Rapamycin injections have been tried with varied success. 

Nd: Yag laser may be efficacious for small, superficial lesions.

Surgical excison is considered when other treatments fail.

The treatment decision is made by taking into account the location, number and progression of the lesions, and potential complications.

Prognosis

Patients lead reasonable normal lives with a normal life expectancy in case here is  malignant transformation.

patients manage to perform activities of daily living rather well. Some times bone deformities may cause restraints.

References

• Prokopchuk O, Andres S, Becker K, Holzapfel K, Hartmann D, Friess H. Maffucci syndrome and neoplasms: a case report and review of the literature. BMC Res Notes. 2016 Feb 27. 9:126.
• Shepherd V, Godbolt A, Casey T. Maffucci’s syndrome with extensive gastrointestinal involvement. Australas J Dermatol. 2005 Feb. 46(1):33-7.
• Albregts AE, Rapini RP. Malignancy in Maffucci’s syndrome. Dermatol Clin. 1995 Jan. 13(1):73-8.
• Steiner F, FitzJohn T, Tan ST. Surgical treatment for venous malformation. J Plast Reconstr Aesthet Surg. 2013 Dec. 66 (12):1741-9.
• Radmanesh M, Radmanesh R. Successful treatment of isolated venous malformation with 1444-nm fiberoptic Nd-YAG laser. J Cosmet Laser Ther. 2016. 18 (2):91-4.

Enchondromatosis: insights on the different subtypes

Enchondromatosis is the presence of multiple enchondromas.

Enchondromas are benign, and often asymptomatic lesions of hyaline cartilage in the metaphyses and diaphyses of the short and long tubular bones of the limbs. They are especially common in hands and feet.

They are often found as incidental lesions, usually solitary on the radiological examination for some other reason.

When there are multiple enchondromas, the condition is called enchondromatosis.

Classification of Enchondromatosis

Following are the main types of enchondromatosis depending on the pattern of distribution, genetic transmission, and associations.

No spinal involvement

Non-hereditary

• Ollier disease
• Mafucci syndrome

Autosomal dominant

• Metachondromatosis
  • Enchondromas with osteochondroma-like lesions
• Genochondromatosis
  • Symmetric with normal stature
  • Type 1 clavicular thickening
  • Type 2 normal clavicle

Spinal Involvement

Autosomal Recessive

• Spondyloenchondrodysplasia

Unknown mode [recessive or dominant]

• Cheirospondylochondromatosis
• Dysspondyloenchondromatosis

How Does Enchondromatosis occur?

The mechanism of development of enchondroma is largely elusive.

Enchondromas arise in the metaphysis in close proximity to the growth plate and are thought to be the result of terminal differentiation of growth plate chondrocytes.

About 10% of patients with enchondromatosis have a mutation in the receptor, PTH1R, which acts as a receptor for parathyroid hormone and for the parathyroid hormone-related peptide.

Some studies have reported that genes affecting heparan sulfate pathways are also affected.

Ollier disease

Ollier disease is the most common type of enchondromatosis. It was first detailed in 1889.

It is non-hereditary and is characterized by the presence of multiple enchondromas with asymmetric distribution.

Ollier disease is encountered early in childhood and affects both genders equally. Few cases of familial occurrence have been reported.

Often the lesions involve one side of the skeleton. It is most common in short tubular bones of hands and feet followed by long bones like humerus and femur. It is known to affect axial skeleton less commonly but the skull and vertebral bodies are very rarely involved.

Malignant transformation is estimated to occur in 5–50% of the patients. It often occurs in long tubular and flat bones while this is far less common in the small bones of hands and feet.

Intracranial tumors of glial origin are other associations with Ollier disease.

The cause is not known and a somatic mosaic mutation is thought to be responsible

Thus, PTH1R mutations may contribute to the disease in a small subset of Ollier patients but are probably not causative for the disease.

[Read more about Ollier’s disease]

Maffucci’s syndrome

Maffucci’s syndrome is enchondromatosis identical to that of Ollier’s disease coexists with extraskeletal, predominantly soft tissue angiomatosis typically involving viscera, such as the lungs and liver.

Maffucci syndrome is also called

• Dyschondrodysplasia with hemangiomas
• Enchondromatosis with multiple cavernous hemangiomas
• Kast syndrome
• Hemangiomatosis chondrodys-trophica

It was first described in 1881.

It is rarer than Ollier disease.

Vascular lesions in Maffucci’s syndrome most typically represent cavernous hemangiomas with frequent thrombosis and calcified thrombi, which are often seen on plain radiographs as phleboliths. Hemangiomas in Maffucci’s syndrome tend to be more pronounced in the areas of skeletal involvement by enchondromatosis but are not restricted to these regions.

Often the skeleton lesions manifest earlier and the disease initially may be labeled as  Ollier’s disease. Later, vascular lesions may develop.

Apart from hemangiomas, aneurysms, lymphedema, and lymphangiomas may occur. Nodular goiter and adrenal insufficiency malignancy in Maffucci’s syndrome can be associated.

The risk of malignant transformation is even higher than that in Ollier’s disease. Intracranial tumors may be associated

Metachondromatosis

In metachondromatosis, there are multiple enchondromas and multiple osteochondroma-like lesions.

Interestingly, the enchondromas mainly involve the iliac crests and metaphyses of the long bones of the lower extremities whereas the osteochondroma-like lesions are mainly located in hands and feet.

The syndrome can present in early childhood.

The usual osteochondromas point away from joint but osteochondroma-like lesions in the metachondromatosis point towards the joint.

These lesions are not associated with bony deformities.

The disease is extremely rare and transmitted in autosomal dominant fashion.

Genochondromatosis

• Extremely rare
• Autosomal dominant
• Manifests in childhood
• Stature is normal
• Symmetrically distributed enchondromas
  • Metaphysis is a characteristic location
  • No spinal involvement
• Two subtypes
  • Type I involves clavicle
  • Type II involves short tubular bones of the hand, wrist, and feet but clavicle spared
• No bony deformities
• Tend to regress in adulthood
• No malignant transformation reported

Spondyloenchondrodysplasia

• An autosomal recessive inherited disorder
• Higher prevalence in Israel
• Usually manifests from birth to infancy
• Vertebral dysplasia combined with enchondromas like lesions in the pelvis or long tubular bones.
• Features
  • Platyspondyly – Flat, often rectangular vertebral bodies on X-ray
  • Irregular areas of increased and decreased mineralization
  • Short broad ilia.
  • Short stature (short limbs)
  • Increased lumbar lordosis
  • Kyphoscoliosis
  • Genu valga or vara
  • Facial anomalies
  • Barrel chest
  • Clumsy movements.
• Two types
  • Type I – classic
  • Type II – Also affects the central nervous system
    • Spasticity
    • Developmental delay
    • Late-onset cerebral calcifications

The spine is less severely affected as compared with dysspondyloenchondromatosis and cheirospondyloenchondromatosis.

There is also an autosomal dominant inheritance pattern that has been reported for this disease.

Dysspondyloenchondromatosis

It is a non-hereditary disorder characterized by spondyloenchondromatosis and spinal malformation.

Presence of irregular vertebral anomalies differentiates dysspondyloenchondromatosis from other enchondromatosis with spinal involvement. The disorder manifests itself at birth.

Features are

• Vertebral abnormalities
  • Severe segmentation abnormalities
  • Secondary deformities of the vertebral column can be seen
• Neonatal dwarfism
• Unequal limb length
• Asymmetric limb shortening
• Flat midface with a frontal prominence
• Progressive kyphoscoliosis can be found
• Multiple enchondromas
  • Long tubular and flat bones
  • Bones of hands and feet not affected or mildly affected.

Malignant transformation has not been reported.

Cheirospondyloenchondromatosis

It has symmetrically distributed multiple enchondromas with marked involvement of metacarpals and phalanges.

Short hands and feet are seen with mild platyspondyly. It occurs at a very early age.

Mild to moderate dwarfism is seen. Joints of fingers become enlarged.

Mental retardation is frequently found.

Mode of transmission is not known.

and joints, especially of the fingers, become enlarged. Mental retardation is frequently seen. Genetic transmission is unknown.

References

• Unni KK. Cartilaginous lesions of bone. J Orthop Sci. 2001;6:457–72
• D’Angelo L, Massimi L, Narducci A, Di RC. Ollier disease. Childs Nerv Syst. 2009;25:647–53
• Spranger J, Kemperdieck H, Bakowski H, Opitz JM. Two peculiar types of enchondromatosis. Pediatr Radiol. 1978;7:215–9. 
• Ikegawa S, Nagano A, Matsushita T, Nakamura K. Metachondromatosis: a report of two cases in a family. Nippon Seikeigeka Gakkai Zasshi. 1992;66:460–6. 
• Le Merrer M, Fressinger P, Maroteaux P. Genochondromatosis. J Med Genet. 1991;28:485–9.
• Menger H, Kruse K, Spranger J. Spondyloenchondrodysplasia. J Med Genet. 1989;26:93–9
• Freisinger P, Finidori G, Maroteaux P. Dysspondylochondromatosis. Am J Med Genet. 1993;45:460–4
• . Mellon CD, Carter JE, Owen DB. Ollier’s disease and Maffucci’s syndrome: distinct entities or a continuum. Case report: enchondromatosis complicated by an intracranial glioma. J Neurol. 1988;235:376–8.

Enchondroma is a common intramedullary benign neoplasm composed of mature cartilage. It has limited growth potential, and a majority of enchondromas are small, asymptomatic lesions less than 3 cm in diameter. It is a type of chondroma that occurs within the medullary cavity.

Enchondroma accounts for 12% to 24% of the benign bone tumor and 3% to 10% of all bone tumors.

Though these lesions are distributed throughout all decades of life, the third and fourth decades are considered the peak age.

There is no sex predilection.

Most common sites of involvement are small bones of the hands and feet [60%]. The hands are more frequently involved than the feet.

Next, in frequency are long tubular bones [17%]. Most of the lesions are metaphyseal [near bone ends] and involvement of diaphysis [midshaft] is very rare.

In long bones, proximal humerus is the most common site involved. Other bones are involved less commonly.

Enchondromas are rare in axial skeleton [pelvis, ribs, scapulae, and vertebrae].

Enchondroma is highly unlikely in craniofacial bones.

Multiple enchondromas are known as Ollier disease, and Maffucci syndrome is characterized by multiple enchondromas with hemangiomas. 

Pathophysiology

Enchondromas are the growth plate remnants that are not resorbed and persist or grow in the medullary canal. They are typically found on the metaphyseal side of the growth plate.

The cartilage in cortex could become cortical and juxtacortical chondromas. These isolated fragments of cartilage grow very slowly in a lobular configuration and demonstrate ossification at their periphery.

Approximately 60% of all enchondromas are located in small bones of hands and feet. These enchondromas are typically diaphyseal lesions that sometimes involve the bone ends. They regularly produce endosteal scalloping and expand the bone contour.

Enchondromas of the long tubular bones account for approximately 45% of cases and are ofen metaphyseal. The proximal humeral metaphysis and distal femoral metaphysis are most frequently involved.

Enchondromas of the pelvis, spine, ribs, and sternum are very rare.

Pathologic fracture and malignant transformation, which may be associated with pathologic fracture are main complications of enchondroma

When multiple enchondromas coexist, the diagnosis of enchondromatosis should be considered of which main are Ollier disease and Maffucci syndrome.

Enchondroma and Chondrosarcoma Differentiation

Enchondromas carry a risk of malignant transformation to chondrosarcoma. Added to that, a benign enchondroma may look and behave like low grade chondrosarcoma.

Therefore the differentiation is important. Different locations behave differently in this context.

Pain at the site, soft tissue mass, cortical breach, and endosteal scalloping are features suggestive of chondrosarcoma.

• Enchondromas of short tubular bones like hands and feet
  • Expansion and scalloping can occur in benign cases too
  • Same features in long tubular and flat bones are highly suggestive of a low-grade malignant tumor.
• Enchondromas of the long tubular bones
  • May be microscopically indistinguishable from low-grade chondrosarcomas
  • Benign lesions – typically asymptomatic, are incidentally discovered and usually measure less than 3cm.
  • The adjacent bone and the overlying cortex are normal.
  • Microscopically, the cellularity is low, the matrix is hyaline, and the lesion is well demarcated. Any deviation from this pattern should be considered suspicious for malignancy.
• Enchondroma of trunk bones
  • Considered potentially clinically aggressive especially when they are bigger than 3cm in size.
  • A benign lesion is less common here and is represented by low cellularity, no nuclear atypia, and has mature hyaline matrix.
  • Any deviation, even minimal from this pattern suggests an aggressive lesion.

Gross and Microscopic Pathology of Enchondroma

Often the enchondroma is received as curetted material. An intact enchondroma after removal is seen as made of confluent lobules of cartilage varying in size from several millimeters to 1 cm. The color is ivory-white due to calcification or ossification or both.

Microscopically, enchondromas are composed of mature cartilage. The individual lobules can be separated by normal bone marrow spaces with hematopoietic elements or more frequently by fibrovascular septa.

Overall cellularity is low and occasional binucleated cells may be seen.

The chondroid matrix is typically of hyaline type and foci of fine or coarse calcifications and even of enchondral ossification can be present.

Immunohistochemically, the cells of enchondroma are positive for S-100 protein and vimentin.

Clinical Presentation

Most of the enchondromas are not symptomatic and are discovered incidentally on x-rays or radioisotope scans performed for other reasons.

In short tubular bones of hand and feet, enchondroma can cause bone expansion and may be felt as  a palpable mass.

Pathologic fractures can also be a presenting feature in short tubular bones [phalanges, metacarpals, metatarsals].

Pain is not a feature. Pain signifies activity and should raise the suspicion of malignancy [if the pathological fracture is absent.

Lab Studies

Lab studies are not diagnostic as there are no specific tests.

Imaging

X-rays

In the small tubular bones, the lesion is usually diaphyseal, but epiphyseal extension is also frequently present. In the long tubular bones, enchondromas are most frequently located in the metaphysis. A midshaft or epiphyseal localization is extremely uncommon.

Enchondroma produces a localized, radiolucent defect with punctate or stippled calcifications. The lesion can vary from being sharply defined to the one with indefinite is sharply defined or has indefinite outlines.

The degree of radiographic calcification can vary considerably.

A classic pattern of calcifications is described as rings and arcs in the short bones, such as hand and is considered pathognomonic.

In the major long bones, the cortex and the bone contour are usually not altered, and there is no periosteal new bone formation.

Enchondromas that fill the medullary cavity of short tubular bones may show some cortical thinning. The contour of the small bones is typically expanded along with cortical thinning.

It is hard to differentiate between enchondroma and low-grade chondrosarcoma on x-ray.

[Therefore, in presence of pain, appearance notwithstanding, further investigation is warranted]

A  predominantly lucent lesion or the one that is not uniform in calcification should be further evaluated.

Presence of cortical break, a soft-tissue mass, and deep endosteal scalloping of the cortex are associated more with chondrosarcoma but may not be so in hands and feet because of expansile nature of lesions in these locations.

Computed Tomography

Findings are similar to x-ray findings. CT may be able to show pathological fracture not visible on x-ray.

A uniformly mineralized lesion showing a lucent region indicates degeneration of the enchondroma to chondrosarcoma and biopsy is desired.

Again, differentiation of the enchondroma and chondrosarcoma is difficult on CT

Signs of malignant transformation are

• Cortical erosion,
• Soft tissue mass
• Irregularity of tumor surface

Enchondromas are well circumscribed as compared to chondrosarcoma.

Extension into soft tissue with a completely disrupted cortex and the presence of reactive periosteal new bone formation should be regarded as indicators of malignancy.

Magnetic Resonance Imaging

MRI is useful to investigate the noncalcified lesions within the marrow cavity and helps in distinguishing enchondromas in the long bones from bone infarcts

MRI can diagnose enchondroma with more certainty and is able to differentiate it from chondrosarcoma when correlated with the clinical picture.

Nuclear Imaging

With technetium-99m (99mTc) radionuclide bone scanning, findings are typically negative in uncomplicated enchondromas, but the presence of pathologic fracture results in intense activity at the fracture site.

If the bone scan results are negative, the possibility of malignancy (eg, chondrosarcoma) is extremely remote. If the scan results are positive, a biopsy is typically necessary.

Differential diagnosis

• Low-grade chondrosarcomas
• Chondroid differentiation in fibrous dysplasia

Treatment

Enchondromas of long bones that are small and asymptomatic require no treatment.

The patient is advised to keep a note of onset of pain and report. It should be followed by clinical evaluation and x-rays.

Lesions that are border-line in size, symptomatic, or predominantly lytic or which appear doubtful should undergo curettage. The material should be subjected to histopathological examination.

Enchondromas of the small tubular bones are frequently treated with curettage and bone grafting, especially if they expand the bone contour or disturb the function of the affected site in any way.

Lesions involving the ribs, sternum, scapula, or pelvis are best treated by wide local excision and tissue subjected to pathological studies. This treatment approach is carried as most of these lesions are aggressive.

Recurrence of enchondroma in long bones usually suggests malignancy.

In short tubular bones, recurrence could be due to incomplete removal and second curettage can sure.

The term chondroma refers to a benign tumor of cartilage origin. The tumor contains cartilage cells which are similar to normal cartilage cells but contains vessels which differentiate it from normal cartilage.

Chondromas may arise inside or outside the bone. These tumors are called enchondromas when they occur in the medullary canal of the bone. The one that grows outward from the bone is called ecchondroma but popularly referred to as chondroma only and often prefixed by the site.

Thus they and are called periosteal or juxtacortical chondromas when they occur on the surface of the bone.

Chondromas can also arise from the synovial sheath are called synovial chondromas.

The lesions can occur in soft tissue like tendons of hand and feet where they are called extraskeletal or soft tissue chondromas. These are very rare.

Enchondromas are most common chondromas and 3-10% of all bone tumors. Periosteal chondromas are rarer and account only for 1% of all chondromas

No age preponderance is seen though incidence peaks in the third and fourth decades.

Enchondromas do not show any sex predilection but periosteal chondromas occur more commonly in male individuals

Pathophysiology

Chondromas develop from nests of growth-plate cartilage that have become entrapped in the medullary canal of the metaphysis or in the metaphyseal-diaphyseal junction. These are hamartomatous proliferations which persist as islands in the bone and then develop from enchondral ossification.

They respond to the same growth factors as normal cartilage and grow until adulthood.

Chromosomal abnormalities involving the 12q13-q15 chromosomal region may be associated with chondroma, especially soft-tissue chondroma.

Periosteal chondroma tends to develop within and beneath the connective tissue of periosteum. 

Synovial chondroma results from cartilage metaplasia of subsynovial connective tissue.

Clinical Presentation

Enchondroma

Two-thirds of the lesions occur in small bones of hand and feet. Long tubular bones are affected next femur, proximal humerus being most common.

Metaphyses are more commonly affected than diaphysis.

Flat bones like pelvis, ribs, scapulae, and vertebrae are rarely affected.

Most of the enchondromas do not lead to symptoms and are diagnosed on x-rays as an incidental finding.

When enchondroma involves short tubular bones of the hands, it can result in bulbous swelling of the fingers.

Pain is often not present. A complaint of pain should raise the suspicion of microfracture or a malignant transformation.

Enchondromatosis is a condition where there are multiple enchondromas typically metaphyseal commonly affecting appendicular skeleton. The condition is pathologically different from benign enchondromas and the cartilage has a propensity for continuous slow growth. These lesions carry a higher risk of secondary sarcomatous change.

Ollier disease is the most common type of enchondromatosis.

When enchondromatosis is associated with soft-tissue hemangiomas of skin, soft tissues, and visceral organs, it is called Maffucci syndrome.

Periosteal chondroma

Periosteal chondromas typically involve long bones, proximal humerus being most common. Short tubular bones can also be affected.

They are usually metaphyseal lesions but can occur in diaphyseal sites as well.

These chondromas occur on the surface of the bone and present as palpable swellings.

They are otherwise painless but may interfere with the function of these tendons and other structures leading to pain during motion of the joint.

Soft-tissue chondroma

Soft-tissue chondromas tenosynovial sheaths or soft tissues adjacent to tendons in the hands and feet of adults. from chondrosarcomas.

Synovial chondromas can be diffuse [multiple nodules all over synovium]  or localized [descrete mass].

In the rare nodular variety of synovial chondromatosis, a polypoidal pedunculated mass protruding into the joint may also be a feature. The large cartilaginous masses have multinodular granular surfaces, and individual nodules may range in size from less than 1 mm to 1-2 cm.

Extraskeletal chondromas are occurrence but have been reported in hands, feet, nasal tip, scalp, palate.

Soft tissue chondromas are known to undergo secondary changes like including dystrophic calcification, enchondral ossification, myxoid degeneration, and hemorrhage in the lesion which make them difficult to differentiate from chondrosarcoma.

Lab Studies

These do not help in diagnosis per se. Routine investigations are

X-ray

Enchondroma

• Localized radiolucent defect
  • Usually, metaphyseal in long bones
  • Diaphyseal in short tubular bones but may extend to the epiphysis
• Variable punctate or stippled calcifications
• Short tubular bones may be expanded
  • Usually cortices intact

Periosteal chondroma

• Well-defined surface lesion with stippled or punctate calcifications
• Underlying cortex may get eroded
• Subchondral sclerosis in long-standing tumors
• Elevation of the periosteum that overlies the lesion forming, this finding appears as solid buttresses subperiosteal bone.

CT

CT enables to visualize subtle changes such as change in calcification and can lead to early identification of malignant transformation.

(PET)-CT [Positron emission tomography] is better at differentiating chondroma from intraosseous chondrosarcoma in long bones.

MRI

MRI can be used for assessment of

• Noncalcified intramedullary chondroid lesions
• Any local extension [spread is seen in chondrosarcoma but not in chondroma]

Biopsy

If the lesion is clinically and radiologically benign, a biopsy is not needed.

The biopsy is done in case of doubtful diagnosis.

Grossly, enchondromas are small lobules with irregular periphery with or without satellite lesions.

Cross section appears ivory white because of calcification.

Periosteal chondromas are as lobulated, cartilaginous covered with fibrous tissue. The cortex might be scalloped and thickened.

Microscopic findings are that of lobules of mature hyaline cartilage with varying cellularity. Areas of myxoid change or focal necrosis may be seen.

Fine or coarse calcifications and areas of enchondral ossification may be visible.

Treatment of Chondroma

Enchondroma

In long bones, enchondromas are often not symptomatic. Therefore, no treatment is needed in most of the lesions.

For painful lesions and lesions where the diagnosis is not definite, curettage may be done. The tissue removed is subjected to histopathological examination. If it is enchondroma, nothing further needs to be done.

If the lesion comes out to be malignant, further workup and treatment is desired.

Patients with pathologic fractures with chondromas would require fixation. The lesion may be curetted at the time of surgery.

Short tubular bones get deformed with enchondromas and often are treated with curettage and bone grafting.

Enchondromas of axial skeleton [rare] are always treated with wide local resection. This is because enchondromas look like low-grade chondrosarcoma and can often not be differentiated. Secondly, the axial skeleton is more common site for chondrosarcoma than enchondroma.

Tissue removed should be subjected to histopathological examination.

Recurrence of the lesion should also raise the suspicion of malignancy.

Recurrence is more common in tubular bones especially in multiple enchondromas but malignant transformation is rare.

Periosteal chondroma

Wide local excision is a curative procedure for this lesion

Synovial chondroma

Synovial chondroma is a local self-limiting condition and may reach a quiescent stage. Depending on the symptoms (especially if they are only mechanical), removal of loose bodies may be all that is required. However, if the lesion produces frequent symptoms, synovectomy may be needed to control the disease. Frequent recurrences with short intervening periods should raise the suspicion of synovial chondrosarcoma.

Long-Term Monitoring and risk of Malignancy

There is a risk of malignant transformation associated with chondromas especially in patients with enchondromatosis [Ollier or Maffucci syndrome].

Patients should be educated about the warning signs of malignant transformation which are

• Deep dull ache
• Night pain
• Increase in size of the swelling

X-rays obtained at regular follow-ups should be looked for any differences in the radiologic appearance of the lesion than previous x-rays.

Look for

• Change in shape of the lesion
• Increase in size of the lesion
• Change in lucency
• Decrease of calcification
• Recurrence of a lytic lesion in a grafted area suggests malignancy
• Break in the cortex
• Esp in short tubular bones where the lesion causes bone expansion
• Increase in radiolucency of a calcified lesion [indicates active dividing cartilage]

Patients with Ollier disease or Maffucci syndrome need more rigorous follow up than simple benign chondroma.

References

• Lubahn JD, Bachoura A. Enchondroma of the Hand: Evaluation and Management. J Am Acad Orthop Surg. 2016 Sep. 24 (9):625-33. .
• Lewis MM, Kenan S, Yabut SM, et al. Periosteal chondroma. A report of ten cases and review of the literature. Clin Orthop Relat Res. 1990 Jul. (256):185-92.
• Nojima T, Unni KK, McLeod RA, Pritchard DJ. Periosteal chondroma and periosteal chondrosarcoma. Am J Surg Pathol. 1985 Sep. 9(9):666-77.
• Bachoura A, Rice IS, Lubahn AR, Lubahn JD. The surgical management of hand enchondroma without postcurettage void augmentation: authors’ experience and a systematic review. Hand (N Y). 2015 Sep. 10 (3):461-71.

Periosteal chondroma is a benign cartilage tumor that develops on the surface of bone under the periosteum. It is also called as juxtacortical chondroma. Chondroma consists of mature hyaline cartilage.

Periosteal chondromas are rare lesions and account for less than 1% of all chondromas. The majority of cases are diagnosed during the second and third decades of life but the condition is known to affect various age groups. Males are known to be more affected than females.

Unlike osteochondromas, periosteal chondroma is known to grow into adulthood as well. Osteochondroma stops growing after skeletal growth stops.

Long tubular bones of the extremities are typically affected by juxtacortical chondroma. The proximal humerus is most commonly affected, almost contributing for 50% of the cases. It may also involve the bones of the hands and feet.

Periosteal chondromas occur in the second to fourth decades of life.

Pathology of Periosteal chondroma

Microscopic features are typical of a chondroma with a hyaline cartilage matrix. On average, juxtacortical chondromas can show mild nuclear atypia or binucleated chondrocytes. Scalloping and erosion of the outer cortex are seen microscopically.

Some periosteal chondromas may bulge for a short distance into of intervening lamellar bone.

Typically, a fibrous capsule overlies the tumor. Occasional foci of necrosis and myxoid degeneration are present but not as extensive as in malignant lesions.

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes have been described in periosteal chondromas. These are known to occur in enchondromas, and periosteal and central chondrosarcoma, suggesting similar modes of tumor formation.

Mutations of the enzyme results in accumulation of gamma-2-hydroxyglutarate which is an oncometabolite.

Clinical Presentation

This surface lesion most often presents as a palpable mass.

Slowly progressive painful mass is the most common cause of presentation. The pain is due to enlargement of the lesion or from impingement on adjacent soft-tissue structures.

Physical examination reveals a firm and immobile mass which is painful to touch.

Presence of periosteal chondromas near tendon insertion sites may disturb their function causing pain and local discomfort on activity. In deep-seated surfaces, these could be initial symptoms.

Periosteal chondromas are always not symptomatic though. These are sometimes discovered incidentally on radiographs.

Imaging

X-rays

X-rays reveal a well-circumscribed surface lesion of bone, usually of size 1-5 cms, with variable punctate calcifications on radiographs. The cartilaginous nature of juxtacortical chondroma is easy to recognize on plain radiographs.

The cortex beneath the lesion is usually eroded but it is not completely disrupted. Complete cortex disruption is not there. the lesion is clearly demarcated from the medullary cavity by a continuous rim of cortical bone.

There would a varying degree of subcortical sclerosis beneath the lesion.

The elevated periosteum is seen as solid buttresses of mature subperiosteal bone. It can sometimes slightly overhang the edges of the central excavation especially in cases of the smaller periosteal chondromas

CT/MRI

Computed tomography, magnetic resonance imaging, or both modalities also may be needed to evaluate the extent of involvement and the relationship between the lesion and adjacent structures.

On magnetic resonance imaging (MRI), the lesion is best seen on T2-weighted images as a well-defined lobular mass. No evidence of tumor extension into the adjacent medullary canal is present.

It shows the presence of the elevated periosteum overlying the lesion is best documented on magnetic resonance images.

The lesion is clearly separated from the medullary cavity by a rim of sclerotic cortical bone.

Differential Diagnosis

• Juxtacortical chondrosarcoma
• Periosteal osteosarcoma

Treatment

Asymptomatic stable lesions can be monitored. Though the risk of malignant transformation is very small, asymptomatic periosteal chondromas should be followed regularly with clinical examination and x-rays.

A lesion that enlarges over a period or is symptomatic should be treated.

Complete local excision of juxtacortical chondroma is a curative procedure. Because periosteal chondromas may demonstrate radiologic overlap with juxtacortical chondrosarcoma, excision of the lesion is the preferred mode of the treatment.

The excision should include a rim of the underlying cortex as well.

In selected skeletal sites such as the ribs and fibula, segmental resection is the preferable mode of treatment.

Curettage is not done because of the associated risk of recurrence.

Musculoskeletal tumors are a rare and diverse group of tumors. Benign bone and soft tissue tumors are 100 times more common than malignant tumors.

The musculoskeletal system is made of skin and subcutaneous tissue, lymphatic tissue, vascular structures, musculoaponeurotic tissue, neurological structures, bone, and joints.

Musculoskeletal tumors of different histological types can present with similar radiographic appearance.

The musculoskeletal tumors have two peaks. One between ages of 15 and 20 years [ due to primary malignancies of bone], and after this, there is a steady secondary peak from the age of 30 years onwards to about 75 years of age [due to malignant neoplasia in such pre-existing conditions as Paget’s disease].

The evaluation of a patient with musculoskeletal tumors begins in the out-patient clinic with history and clinical examination and moves to the next stages on an individual basis. The goal of the evaluation is to identify the tumor to prompt diagnosis and treatment. In diagnosis, we look for

In diagnosis, one has three primary aims

• To assess the extent of the primary tumor.
• To assess the extent or presence of metastases.
• To delineate the histological type

A musculoskeletal tumor could be primary – originating in the tissue itself or secondary or metastatic tumor which spreads from other parts of the body.

Breast,  lung, thyroid, kidney, and prostate are the most common organs responsible for metastatic tumors.

With new chemotherapeutic drugs and regimens and as a result of advances in imaging and surgical techniques has improved the outcome for musculoskeletal tumors.

Classification of Musculoskeletal Tumors

Bone develops from primitive mesenchyme. From this, by differentiation, there develops a common immediate precursor to the fibroblast, the chondroblast, the osteoclast, and the fibroblast, to produce bone, cartilage, the absorption of bone or collagen.

Therefore,  within the same tumor widely different histological pictures are observed.

In order to classify and to characterize particular tumor types it is important:

• To define the cell of origin
• To identify the cytology of the tumor cell and its stroma as well as their degree of differentiation.
• To observe the behavior and growth of the tumor

Musculoskeletal Tumors are classified as

• True bone tumors- Arising from cells of mesenchymal origin, derived from a common ancestry and whose function is primarily skeletal bone formation
• Tumors arising from tissues normally in bone but not participating in bone formation.
• Tumors arising from included tissue –  chordoma and adamantinoma.
• Metastatic tumors of bone.

True bone tumors

These are classified by predominating cell type.

Tumors arising from tissue normally found in bone, but not participating in the bone formation

Tumors arising from the fibrous tissue of the fascia of the  periosteum

• Periosteal fibroma
• Periosteal fibrosarcoma
• Malignant fibrous histiocytoma

Tumors arising from bone marrow

• Myeloma
• Reticulum cell sarcoma
• Hodgkin’s disease of bone
• Lymphosarcoma
• Ewing’s sarcoma

Tumors from blood vessels

• Haemangioma
• Haemangioblastoma
• Aneurysmal bone cyst
• Angiosarcoma

Tumors arising from adipose tissue

• Lipoma
• Liposarcoma

Tumors arising from nerves

• Neurilemmoma
• Neurofibroma

Tumors of synovium

Tumors of striated muscle

• Rhabdomyosarcoma

Clinical Presentation of Musculoskeletal Tumors

A mass or pain are the usual complaints. A number of patients are incidentally found on a radiograph taken for unrelated reasons.

The pain is usually a deep constant pain which is not particularly associated with exercise. The pain may be present for only a few weeks or as long as 3—4 years. Characteristically, the pain becomes progressively worse over the weeks, month or years.

The discomfort is usually poorly localized. Initially, the pain can be controlled by low—grade analgesics but eventually, they become ineffective due to worsening of the pain. The pain may be associated with an antalgic limp or complaints of muscle wasting or weakness.

Night pain is often present.

There is no history of trauma that could explain the pain. If there is then other entities as myositis ossificans and stress fractures should be considered. ]

[Osteomyelitis, fungal or tuberculosis musculoskeletal disease can mimic musculoskeletal neoplasm]

Mass can be either painless or painful. The rate of enlargement is important. The occurrence and location of other masses in other parts of the body should be questioned.

Patients with spinal tumors most often present with axial pain and some with radicular pain or cauda equina syndrome, a condition more often seen in metastatic disease and in rapidly growing primary tumors. About a third present with a motor deficit. A small percent have bowel/bladder sphincter dysfunction.

Pelvic tumors may present with unexplained swelling of the lower extremity.

A history of recent weight loss or a previously diagnosed neoplasm should be asked.

The patient should be questioned concerning industrial exposure to carcinogens or a previous history of radiation.

A general physical examination may suggest the site of primary in cases of metastases or signs like café au lait spots in cases of neurofibroma.

Inspection of the site may reveal a mass or could be normal if the tumor is in bone only. Large tumors can produce small dilated superficial veins overlying the mass.

The mass, when present may alter normal contours. In the case of limbs, a comparison with opposite extremity may help.

On palpation, the skin over a tumor may exhibit increased warmth.

The mass is examined for the shape, size, consistency and mobility, and its adherence to the skin or underlying structures. If the skin is not freely movable, then it must be assumed that it is involved with or closely approximates the neoplastic process.

The neurovascular examination is carried out to ascertain or rule out nerve or vessel involvement/pressure effects by the tumor.

The joints at either end of the involved bone or muscular compartment are evaluated The muscle in the vicinity of the tumor and their associated aponeurotic structure is carefully examined.

The regional lymph nodes in the involved extremity are carefully palpated [Though musculoskeletal tumors characteristically produce hematogenous pulmonary metastases, all of them can involve regional lymph nodes.]

Lab Studies

Complete blood count and basic chemistry panel generally normal [compare with infection]

ESR may be elevated.

Tumors involving the bone and causing bone destruction may cause elevation of serum alkaline phosphatase. [Other causes include bone injuries, recent surgery, and in Paget’s disease of the bone.]

Blood tests particularly serum electrophoresis is can also be useful in the diagnosis of multiple myeloma.

Imaging of Musculoskeletal Tumors

Two x-ray projections usually and lateral are required for adequate evaluation of a bone neoplasm. Additional views such as oblique and tangential views are occasionally helpful in demonstrating a lesion in profile. The joint nearest the bone tumor should always be included.

Analysis of plain radiographs for periosteal reaction, junction of the lesion with the host bone, cortical disruption, matrix of the lesion and site, and the number of the lesion(s) in skeleton can further direct the diagnosis.

Xrays are studied for the shape of lesion and location. Some lesions can be identified by their peculiar location and shape. Age of the patient greatly affects the type of lesion one could have.

Regionwise location of tumors in bone

Site Predilection of Some tumors

Some benign lesions have characteristic features that almost clinch the diagnosis. Examples include fibrous cortical defects, bone islands, simple bone cysts, bone infarcts, and typical variants, such as pseudocysts of the humerus and calcaneus.

Radiographic features can also help in distinguishing malignant from benign bone lesions in many patients.

Lodwick and colleagues established a radiographic grading based on following

• The pattern of destruction – Geographic or not geographic, the appearance of the marginal interface zone
• Penetration of the cortex by the lesion
• Absence or presence of a sclerotic rim
• Absence or presence of the expanded cortical shell, as well as its extent

The grading system is

• Grade 1A, 1B, and 1C – Benign lesions with edge characteristics ranging from well defined to poorly defined
• Grade 2 – Low-grade malignant lesions with invasive features[  particularly to lesions demonstrating total penetration of the cortex]
• Grade 3 – High-grade malignant lesions with invasive, permeative, and destructive features

Another grading system divides bone lesions into 4 groups with management suggestions on each group

• Group 1 – Radiographically benign lesions. Do not require further investigation or treatment

• Group 2 – High likelihood of being benign. But should be confirmed  by  clinical or radiographic follow-up
• Group 3 – Benign lesions that require surgical resection because of aggressive behavior or a risk of pathologic fracture
• Group 4 – Aggressive-appearing lesions that should be considered malignant. Biopsy should be performed to confirm the diagnosis and histologic grade.

In case of conditions which affect multiple bones, a skeletal survey can be obtained an should include at least one projection of the bones of the upper and lower extremities, the pelvis., the ribs, and a lateral view of the skull. [radiographic skeletal survey]

Tumors with Polyostotic Involvement

Plain radiographs are not as helpful in the diagnosis of soft tissue tumors as in bone tumors.

CT Scan

CT scanning complements x-rays for local evaluation as it can assess the disease in areas not easily visualized on x-rays such as spine and pelvis.

CT offers the following advantage

• Determining the type of cortical destruction better
• Identifies matrix mineralization is present
• May show the internal contents of some lesions
• Determine intramedullary and extramedullary extension of disease
• Helps to localize the lesion in a cross-sectional display
• Defines the relationship between tumor and vital structures.

The entire length of the tumor must be visualized so that at least one normal scan above and one below the lesions are obtained. If the lesion involves the end of the bone, scans through the adjacent joints should be obtained.

Multiplanar reconstruction of CT scans and direct longitudinal scanning of a lesion provides better details.

Computed tomography is the procedure of choice for detecting pulmonary metastases

MRI

Magnetic resonance imaging delineates the extent of the tumor within the bone and also any extension into the soft tissue. It is very helpful in defining the size, contents, and relationship of the lesion to adjacent neurovascular structures and helps in planning the biopsy and tumor resection.

MRI is highly reliable for planning limb salvage or an amputation

An MRI of the whole length of the involved bone allows visualization of the entire length for skip metastases.

Bone Scans

Radionuclide bone scans are commonly obtained by using technetium-99m (99mTc)–labeled diphosphonate to stage bone tumors.

This identifies other sites of involvement or even identify another location that may be an easier site for obtaining a biopsy.

However, the bone scan has a limited role in differentiation between a benign and malignant tumor.

Bone scans are helpful in detecting metastases, skip lesions.

Ultrasonography

Soft-tissue masses and the soft-tissue components of bony tumors may be visualized by using ultrasonography. It confirms the presence of a lesion and can determine if the lesion is cystic or solid.

It is also helpful to assess the relationship of the mass to the surrounding structures, to evaluate the vascularity of the mass, and to guide interventional procedures if indicated.

Angiography

Angiography is used less frequently since MRI quality has improved significantly. Currently, angiography is used only occasionally to evaluate neurovascular bundle involvement. It is used for embolization procedure of the feeder vessel of the tumor.

Positron Emission Tomography Scanning

PET scanning is used to image tumor metabolism by detecting photons emitted from the tissue after the intravenous injection  2-[fluorine 18]-fluoro-2-deoxy-D-glucose (FDG).

Based on photon detection, a 3-dimensional image is constructed. As tumor metabolism is higher than that of normal tissue, it shows higher FDG uptake. Alone,  it cannot reliably differentiate benign from malignant but a combined FDG-PET-CT reliably differentiates soft tissue and bone tumors from benign lesions.

Biopsy

The biopsy is the single most important step in the staging of a musculoskeletal tumor, to determine the histology diagnosis of the tumor and the type and extent of the treatment.

The biopsy can be needle biopsy or open biopsy.

Needle biopsy includes a fine-needle aspiration or core biopsy with a larger needle.

The open biopsy  can be incisional [ a piece of tissue is removed after giving incision] or excisional [the tumor is excised with margins]

Although open biopsy is still considered a gold standard, many centers have moved toward percutaneous needle biopsy.

Percutaneous biopsy is less invasive, causes minimal bleeding and biopsy tract contamination, and can be accurately performed under imaging.

But percutaneous is less reliable in obtaining an adequate representative specimen for grading and further special studies.

The biopsy site should be located where the needle tract will be excised in future surgery, because of possible tumor seeding along the needle track. Fluoroscopy with C-arm guidance, CT scanning, and MRI can be used to locate the most appropriate biopsy site. The primary advantage to fluoroscopy is its ability to create dynamic images.

CT-guided biopsy is usually employed if the lesion is located in a complicated part of the anatomy, such as the upper thoracic spine or pelvis. 

If the tumor is located within a bone a cortical window is carefully made and the tumor sample removed.

Frozen sections can be made when required.

After the biopsy, the cortical window is filled with acrylic bone cement to prevent bone bleeding as bleeding increases the risk of spread of tumor cells.

Staging of Musculoskeletal Tumors

For staging a musculoskeletal neoplasm, the grade and site of the tumor and the presence or absence of metastasis are considered. The grade of the tumor reflects biological aggressiveness,

Staging is important to determine the nature of resection required for the tumor.

Read more on the staging of tumor and types of resection of the tumor.

If a malignant tumor is responsive to chemotherapy, smaller resection margins may be acceptable.

Treatment of Musculoskeletal Tumors

Factors Affecting the Treatment  Decisions

• Age of the patient
• Susceptibility of the tumor to adjuvant chemotherapy/radiotherapy
• The expected function of the extremity
• Presence of pathological fractures [makes salvage difficult]

Minimally Invasive Procedures

Image-guided minimally invasive procedures are better tolerated by these patients, resulting in less soft tissue trauma, minimal blood loss, and shorter hospitalization. These methods rarely interfere with the adjuvant treatments, and their overall morbidity is considerably lower compared with conventional surgery.

These are considered when conventional surgery may result in higher morbidity.

Minimally invasive procedures can also be considered in the patient with metastatic disease, who cannot tolerate the conventional surgical methods because of immunocompromised status due to ongoing chemotherapy, poor nutrition, and comorbid medical conditions.

Examples of their uses are

• Radiofrequency ablation of the osteoid osteoma.
• Percutaneous vertebral augmentation with cement for painful vertebral hemangiomas or metastatic lesions or to augment bone quality in an instrumented spinal fusion.
• Preoperative embolization of the lesion for hypervascular tumors such as an aneurysmal bone cyst, giant cell tumor, angiosarcoma, leiomyosarcoma etc
• Embolization is also used as a palliative treatment in painful bone metastasis
• Sequential embolization as a primary treatment alternative for hypervascular bone tumors, such as aneurysmal bone cyst and giant cell tumor [ Inoperable tumor or surgery is technically difficult]

Surgical Procedures

Limb-Saving Procedures

Surgery is the removal of the tumor and some surrounding healthy tissue during an operation. Skeletal reconstruction is frequently necessary after tumor resection to achieve the best functional results. In recent years there have been great improvements in the equipment and techniques used in skeletal reconstruction, thus decreasing the need for amputation.

Resection of certain bones or anatomical sites requires no reconstruction because the functional loss is slight such as scapula distal to the scapular spine, pubis, ischium, parts of the ilium excluding the acetabulum, and the proximal two-thirds of the fibula.

No soft tissue reconstruction is necessary after resection of the triceps, gluteus maximus, hip abductors, hamstring of the abductors of the thigh.

Bone cement, bone grafts [allo and autograft both] or bone graft substitutes could be used to reconstruct the bone defects.

Endoprosthesis can be used for constructing a functional limb.

Limb salvage surgeries are indicated if the following conditions are satisfied:

• The tumor is situated in the extremities and/or the axial skeleton.
• The tumor margins are amenable to surgery.
• Only moderate soft-tissue extension is present.
• The neurovascular bundles are intact.
• Metastases are absent or amenable to curative treatment.
• Good general health.

Amputation

Amputation is surgery to remove all or part of an arm or leg. It is usually used when a tumor is large and/or nerves and blood vessels are involved. A prosthetic limb can aid function after amputation.

The site and extent of the amputation would depend on the location and spread of the tumor.

Surgical Debulking

Surgical debulking of tumors is a procedure whereby a surgically incurable malignant neoplasm is partially removed to make subsequent therapy/ nursing more effective. This procedure is not used with without curative intent and aims to  improve the length of survival only

Chemotherapy and Radiation Therapy

Chemotherapy and radiation therapy have greatly improved survival rates and local recurrence rates. Chemotherapy finds its greatest use in the treatment of systemic disease while radiation therapy is primarily concerned with the local control of the disease either in combination with surgery or less frequently as the sole modality. The treatment of metastatic carcinomas of the skeleton depends to a great extent on radiation therapy.

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells,

Chemotherapy is used to treat the tumors not amenable to surgery [multiple myeloma] or in addition to the surgical procedure, as an adjuvant. This type of chemotherapy is called adjuvant chemotherapy.

Chemotherapy could be preoperative chemotherapy [before surgery] or can also be given after surgery.

The specific chemotherapy drugs used depend on the type of tumor. Not all tumors are susceptible to chemotherapy.

The side effects of chemotherapy depend on the individual and the dose used, but they can include fatigue, the risk of infection, nausea and vomiting, hair loss, loss of appetite, and diarrhea. These side effects usually go away after treatment is finished.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells.

It could be external-beam radiation therapy, which is radiation given from a machine outside the body or s called internal radiation therapy [ brachytherapy] when radiation is given by implants placed in the body..

Radiation therapy is most often used for patients who have a tumor that cannot be removed with surgery. Preoperative radiation also can be used to shrink the tumor so that surgery becomes less extensive.

Postoperative radiation can also be given.

References

• Letson G D, Greenfield G B, Heinrich S D. Evaluation of the child with a bone or soft-tissue neoplasm. Orthop Clin North Am. 1996;27:431–451.
• Olson PN, Everson LI, Griffiths HJ. Staging of musculoskeletal tumors. Radiol Clin North Am. 1994 Jan. 32(1):151-62. [Medline].
• Peh WC. The role of imaging in the staging of bone tumors. Crit Rev Oncol Hematol. 1999 Jul. 31(2):147-67.
• Peh WC, Gilula LA. Plain film approach to tumours and tumour-like conditions of bone. Br J Hosp Med. 1995 Dec 13-1996 Jan 16. 54(11):549-57.
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Tumor mineralization means deposition of additional mineral in and around focal lesions of bone.

Tumor mineralization is seen as

• Mineralization of tumor matrix
• Reactive bone proliferation
• Mineral deposition in areas of degeneration or necrosis

The characteristic mineralization patterns have diagnostic significance.

Depending on the mineralization pattern, bone tumors and tumor-like conditions can be divided into categories of matrix-producing lesions, non—matrix producing lesions, or as a combination.

Mineralization of Tumor Matrix

Matrix refers to the acellular/intracellular substance produced by mesenchymal cells and includes

• Osteoid produced by osteoblasts
• Chondroid produced by chondroblast
• Myxoid and collagen fibers produced by fibroblasts.

Osteoid matrix

Mineralization of osteoid elaborated by neoplastic osteoblasts is the final in the creation of tumor bone.

Osteoid tissue mineralizes in a confluent manner that results in a radiographic density ranging from a hazy ground-glass appearance to a dense ivory-like pattern.

Rapidly growing tumors such as osteosarcoma usually produce immature bone which is seen as ill-defined poorly structured clouds of density.

On the other hand, slowly growing, osteoid-producing tumor such as parosteal osteosarcomas produces solid mature tumor bone which is seen as well-defined heavily mineralized masses radiographically.

The mineralization of neoplastic bone is initially observed in the center of the lesion where cellular maturity is the greatest.

Tumor bone is occasionally produced by a fibroblastic cell that has converted to functional osteoblasts through the mechanism such as fibrous dysplasia.  The patterns of bone formed is woven or fibrous in appearance.

The woven bone of this type is usually less densely mineralized than tumor bone formed directly from neoplastic osteoblasts. The result is a hazy ground glass appearance.

Chondroid matrix

In neoplastic cartilage, calcification in the form of stipples, floccules, arcs, and ring—like shapes conforms to the lobulated configuration of the cartilaginous matrix. Since this calcification usually occurs in the most mature cartilage, it is characteristically found in the center of a lesion.

A mixture of stipples and floccules is seen within both benign and malignant cartilaginous tumors.

Reactive bone mineralization

Reactive bone is formed either through modulation of normal marrow or soft tissue elements to osteoblastic activity or from the periosteal reaction at tumor margins.

Slowly progressive neoplasms including certain malignant lesions such as primary lymphoma of bone and Ewing’s tumor can stimulate reactive mineralization.

This results in bone activity. The results in a coarsened and mottled trabecular pattern of combined radiolucency and increased radiodensity.

Endosteal and trabecular and increased sclerosis can also be stimulated by an inflammatory disorder such as chronic low—grade osteitis and osteomyelitis.

 Dystrophic mineralization patterns

Dystrophic calcification results from the deposition of mineral salts in degenerating or necrotic tissue, primarily necrotic fat and densely hyalinized connective tissue.

The mineralization of bone infraction occurs in the periphery of a lesion.

This process can result in stipples flocculent solid patchy and linear density patterns in bone. This type of mineralization can be seen in such lesions as ossifying lipomas, bone infarct and in areas of bone radiation necrosis.

Uncommonly, necrotic portions of non-matrix-producing tumors, e.g. Ewing tumor and primary lymphoma of bone will mineralize which can be misleading.

Read more about dystrophic calcification

Enneking Staging System and TGNM staging system are two main staging systems used for staging for benign and malignant tumors of the musculoskeletal system

Many factors are involved in choosing the proper therapy for the patients. They include the stage of the disease, the expected functional result after surgery, the age of the patient, the type of adjuvant therapy preoperative, whether or not therapy preoperative and postoperative, whether or not there is a pathological fracture and the patient’s wishes and his tolerance for risk-taking.

The Enneking surgical staging system

The Enneking surgical staging system has been used for classification of musculoskeletal tumors surgeons around the world. It is a reliable, reproducible, and has prognostic importance for musculoskeletal sarcomas, especially for those originating in the axial skeleton.

Enneking staging system is applicable only to mesenchymal malignancies.

In this system, there are separate staging systems for benign and malignant mesenchymal tumors.

Enneking Staging System for benign musculoskeletal tumors

This classification is based on radiographic characteristics of the tumor-host margin. It consists of three categories: ie, latent, active, and aggressive.

If the lesion has well-demarcated borders, it is indicative of latent lesions.

An active lesion would show distinct borders because of permeation into host bone.

A more aggressive lesion would have even more indistinct borders.

Metastases are rare for locally aggressive benign lesions but do rarely occur in giant cell tumor and chondroblastoma.

Enneking surgical staging system for malignant mesenchymal tumors

Enneking surgical staging system for malignant mesenchymal tumors  takes into account

• The surgical grade (G, G1, G2)
• Local extent (T, T1, T2)
• Presence or absence of metastasis (M0, M1)

There are three stages for malignant musculoskeletal tumors

Stage III represents any tumor with distant metastasis.

Stage II tumors are high grade and stage I are low grade

Stage I and II are further subdivided into two subcategories (A, B) based on the local extent of the tumor.

The stage of the tumor dictates the extent of surgical resection and margin.

Enneking staging for malignant musculoskeletal tumors based on surgical grade, local extent, and presence or absence of metastasis

Grades

In the Enneking staging system, a neoplasm is classified as either low (G1) or high (G2) grade.

Low grade – G1

• Low risk for distant spread (< 25%).
• Low mitotic rates
• Low nuclear to cytoplasmic ratio
• Limited pleomorphism.

High Grade – G2

• Higher incidence of metastasis
• Mitotic figures are seen on histology
• Prominent nucleoli

Local Extent

Local extent for any neoplasm refers to its containment in anatomic boundaries of a compartment.

Anatomical compartments have natural barriers, e. g. fascial septae muscle origins, etc. to prevent the extension of the tumor into adjacent compartments.

For example, a bone forms a compartment in itself. This compartment extends to the articular cartilage, cortical bone and its investing periosteum.

Joints are also compartments with their surgical boundaries being the articular cartilage and the joint capsule.

Throughout the body, there are many soft tissue compartments, e.g. quadriceps, hamstrings, biceps, and triceps.

The adequacy of the surgical margin is determined by whether or not there is a barrier between the plane or resection and the tumor.

Thus local extent determines the approach for the surgical procedure and feasibility for desired surgical margins.

A localized tumor can be removed by a smaller margin. But a high-grade lesion is more likely to invade surrounding host tissue and may require the use of adjuvant therapies to eradicate tumor cells that would remain after surgical resection.

Metastasis

The last major determinant in the surgical staging system is whether or not the patient has metastases to s distant site or the regional lymph nodes[ stage III = metastatic disease].

The presence of metastatic disease denotes a poor prognosis.

Limitations of the Enneking surgical staging system

The Enneking surgical staging system is based on the natural evolution of mesenchymal tumors and thus is not applicable to tumors originating in either the marrow or reticuloendothelial system. These include lymphomas, multiple myeloma, plasmacytoma, Ewing’s sarcoma, other round cell neoplasms, and metastatic carcinomas. Lesions originating in the skull also behave differently and thus cannot be staged or classified using this system.

Tumor Resection Depending on Enneking Staging

Malignant Tumors

Stage IA

These tumors are treated with wide excision and are usually amenable to limb salvage procedures.

Stage IB

Such tumors may be treated with wide excision, but the choice between amputation and limb salvage depends on the estimated amount of residual tumor left behind after a limb salvage procedure.

Stage II

High grade, are usually extracompartmental, and have a significant risk for skip metastases. They usually are not amenable to limb salvage operations and require radical amputation or disarticulation. Those responsive to chemotherapy may be treated successfully using wide excision and adjuvant therapy.

Stage III

Tumors which are responsive to chemotherapy and may be treated with aggressive resection. Those that are not responsive to adjuvant therapy should be treated with palliative resection.

Benign tumors

• Stage 1 tumors – Intracapsular excision (or curettage) is adequate.
• Stage 2 tumors – Extracapsular excision passing through the reactive zone.
• Stage 3 tumors – Wide margins of resection are required in stage 3 lesions (aggressive benign tumors). In areas that are not amenable to wide excision, marginal excision together with adjuvant treatment (eg, radiation therapy).

TGNM Classification

The American Joint Committee for Cancer has proposed their own staging system for soft tissue sarcomas [ in contrast to bone sarcomas].

The AJCC staging follows a TGNM system

•  T (tumor) refers to the size of the primary neoplasm
• G (grade) refers to the histopathologic grade
• N (nodes) refers to the presence of lymph node involvement
• M (metastasis) refers to the distant spread to other organs

Description of the TGNM system

As compared to Enneking, this system does not correlate well with surgical procedure due to lack of consideration to anatomic planes and compartments.