Malignant bone Tumors

Dr Arif khan S

AJIMS

WHO CLASSIFICATION

• BONE FORMING – osteosarcoma;

• CARTILAGE FORMING - chondrosarcomas

• GIANT CELL TUMORS

• MARROW TUMORS – Ewing’s ; lymphomas; multiple myeloma

• VASCULAR & other connective tissue TUMORS – Angiosarcoma, ; Fibro sarcoma, Malignant Fibrous Histio cytoma

• MISCELLANEOUS – Chordoma ; adamantinoma; neurosarcoma

Radiation induced sarcoma

Ewing’s Sarcoma

• Ewing sarcoma, a highly malignant neoplasm

• predominantly affecting children and adolescents

• Approximately 90% of Ewing sarcomas occur before age 25

• Histogenesis: neurally derived small round cell malignancy very similar to the so-called primitive neuroectodermal tumor (PNET)

• disease is extremely rare in black persons

Areas of involvement

Ewing sarcoma has a predilection for the

diaphysis of the long bones

ribs

flat bones such as the scapula and pelvis

Clinical presentation

• present as a localized painful mass

• with systemic symptoms such as fever, malaise, weight loss, and

• an increased erythrocyte sedimentation rate.

• These systemic symptoms may lead to an erroneous diagnosis of osteomyelitis.

Radiological features

• lesion is poorly defined,

• Marked by a permeative or moth-eaten type of bone destruction,

• Associated with an aggressive periosteal response that has an onionskin (or “onion peel”)

• less commonly, a “sunburst” appearance,

• and a large soft-tissue mass .

• Occasionally, the bone lesion itself is almost imperceptible, with the soft-tissue mass being the only prominent radiographic finding

• Other, less common, manifestations

Thickened cortex or Saucerication

Expansion of bone

Pathologic fractures

permeative bone destruction associated with an aggressive periosteal reaction

CT section through the lesion demonstrates a large soft-tissue mass, which is not clear on the conventional

study.

obliteration of the marrow cavity by tumor.

saucerisation

Bone destruction is almost imperceptible

shows a large soft-tissue mass

Onion skin appearance

MRI

1. T1 : low to intermediate signal

2. T1 C+ (Gd) : heterogeneous but prominent enhancement

3. T2 : heterogeneously high signal, may see hair on end low signal

striations

Nuclear medicine

Ewing sarcomas demonstrate increased uptake on both

Gallium-citrate

and

Technetium99m methylene diphosphonate scans

Differential diagnosis

• other Ewing sarcoma family of tumours• pPNET : large soft tissue component with extension into bone

• Askin tumour : chest wall

• osteosarcoma (ALP is not elevated in Ewing sarcoma)

• Leukemia

• Multiple myeloma

• Ostyeomyelitis

Primary lymphoma of bone

• Rare malignant condition that accounts for less than 5% of all primary bone tumors

• It occurs in the second to seventh decades, with a peak age of occurrence from 45 to 75 years. M>F

• It has also been called reticulum cell sarcoma, malignant lymphoma of the bone, and more recently osteolymphoma.

• bone lymphoma is now known as large cell or histiocytic lymphoma

• The vast majority of cases are of the non-Hodgkin type, with Hodgkin disease accounting for 6% of cases

• Distinguishing primary bone lymphoma from other bone tumors is important because the former has a better response to therapy and a better prognosis.

• Histologically, lymphomas may be subdivided into non-Hodgkin lymphomas and Hodgkin lymphomas

• primary Hodgkin bone lymphoma is extremely rare

• Non-Hodgkin bone lymphomas are considered primary only if a complete systemic work-up reveals no evidence of extraosseous involvement.

• the tumor consists of aggregates of malignant lymphoid cells replacing marrow spaces and osseous trabeculae. The cells contain irregular or even cleaved nuclei.

Areas of involvementlong bones

vertebrae

Pelvis

ribs

Clinical features

• Insidious and intermittent bone pain that can persist for months.

• Other signs and symptoms include local swelling, a palpable mass, and systemic symptoms such as weight loss and fever

• Vertebral involvement can cause radicular symptoms and can even lead to compression of the spinal cord

Radiological features

•  Coley’s:--lymphoma presenting in an osseous site with no evidence of disease elsewhere for at least 6 months after diagnosis.

• wide spectrum of findings—from a near-normal-appearing bone to a focal lytic lesion with geographic margins to a mixed sclerotic-lytic lesion to a diffusely permeative process with cortical destruction and soft-tissue

• a solitary lytic lesion near the end of a long bone that has a permeative or moth-eaten pattern of destruction and aggressive periosteal reaction ()

MRI findings

• T1-weighted pulse sequences are the best (compared with other sequences) for demonstrating marrow changes, as T1-weighted images reveal areas of low signal intensity within the marrow

• T2-weighted images these areas generally appear bright

• Peritumoral oedema and reactive marrow change can also produce high signal intensity on T2-weighted images.

• Post contrast study shows enhancement.

• Better picturization of soft tissue involvement and Cortical erosion (better than CT)_

Patterns of bone changes

• 1. Lytic-Destructive Pattern

• The lytic-destructive pattern is the most common radiographic appearance of primary bone lymphoma,

• It is believed to result from an osteoclast-stimulating factor.

• The lytic pattern may be permeative—characterized by numerous small, elongated rarefactions that are parallel to the long axis of the bone and relatively uniform in size

• Occasionally, the lesion may manifest with focal lytic areas with well-defined margins

• moth-eaten—a pattern of many medium to large areas of radiolucency in a poorly marginated area of bone

Geographic moth eaten appearance

• Cortical breakthrough, pathologic fractures

• soft-tissue masses represent a more aggressive pattern of involvement and a poorer prognosis

• Cortical breakthrough, which refers to a sudden interruption in the continuity of the cortex, was better seen at computed tomography (CT) in our experience , correlated with a more aggressive tumor. CT also demonstrated sequestra ,findings that have been reported in osseous lymphomas

• Periosteal reaction has been reported in about 60% of cases and may be either lamellated or layered,

• Layers of periosteal bone are seen parallel to the long axis of the bone (also called onion-peel appearance), or broken, when discontinuous or interrupted periosteal new bone is seen.

• The latter appearance of disrupted periosteal bone is believed to be a helpful radiographic sign that indicates a poorer prognosis

Myelogram shows that the disk is normal, but the body of L-5

exhibits a mottled appearance and its posterior border is

indistinct

CT section demonstrates a large, osteolytic lesion extending from

the anterior to the posterior margins of the vertebral body. Biopsy revealed a histiocytic

lymphoma

• 2. Blastic-Sclerotic Pattern

• Primarily blastic-sclerotic lesions are rare in primary bone lymphoma compared with metastatic bone lymphoma.

• A mixed lytic lesion with sclerotic areas can be seen

• Sclerotic changes in primary bone lymphoma may seem scarce, since of the two types of lymphoma, it is Hodgkin disease of bone (the less common subtype of primary bone lymphoma) that tends to be sclerotic and even in Hodgkin disease, lytic lesions predominate).

• Sclerotic areas can, however, develop in an originally lytic pattern after therapy (irradiation and chemotherapy

• 3.Subtle or “Near-Normal” Findings

• A third pattern seen and described in primary bone lymphoma is the near absence of detectable abnormalities on plain radiographs

• Cases with remarkably normal-appearing radiographs may show striking abnormalities on radionuclide bone scans and MR images.

• As a result, in patients with symptoms but negative radiographic findings, further assessment with a second, more sensitive modality such as scintigraphy or MR imaging is essential.

Myeloma

• Aka multiple myeloma” or “plasma cell myeloma,”

• the most common primary malignant bone tumour.

• It is usually seen between the fifth and seventh decades. M>F

• Histologically, the diagnosis is made by finding sheets of atypical plasmacytoid cells replacing the normal marrow spaces.

• The plasma cell is recognized by the presence of eccentrically situated nucleus within a large amount of cytoplasm that stains either light blue or pink. The neoplastic cells contain double or even multiple nuclei, usually hyperchromatic and enlarged, with prominent nucleoli

• Multiple myeloma may present in a variety of radiographic patterns

• Multiple myeloma may present in a variety of radiographic patterns Particularly in the spine,

• it may be seen only as diffuse osteoporosis with no clearly identifiable lesion; multiple compression fractures of the vertebral bodies may also be evident.

• More commonly, it exhibits multiple lytic lesions scattered throughout the skeleton. In the skull, characteristic “punched-out” areas of bone destruction, usually of uniform size, are noted

• Usually part of Myelomatosis

• the ribs may contain lace-like areas of bone destruction and small osteolytic lesions, sometimes accompanied by adjacent soft-tissue masses, which often referred to as PLASMACYTOMAS

• Areas of medullary bone destruction are noted in the flat and long bones,

• if these appear about the cortex, they are accompanied by scalloping of the inner cortical margin

• Fewer than 1% of myelomas may be of a sclerosing type called sclerosing myelomatosis.

• POEMS syndrome, first described in y.

• It consists of polyneuropathy (P), organomegaly (O), particularly of the liver and the spleen, endocrine disturbances (E) such as amenorrhea and gynecomastia, monoclonal gammopathy (M), and skin changes (S) such as hyperpigmentation and hirsutism,

• INCIDENCE OF POLYNEUROPATHY

• 3% in osteomyelitic

• 30-50% sclerotic

Differential Diagnosis

• Metastatic carcinoma of spine: based on Involvement of pedicles

• Metastatic carcinoma of other parts : cranium “punched out lesions” or sharply defined multiple lytic lesions in skull.

• However in later stages Bone scintigraphy alone can distinguish when involvement is diffuse.

• Solitary myeloma : hyperparathyroidism, giant cell tumor, fibrosarcoma.

Solitary mets (?from where)

Fibrosarcoma & MFH

• Fibrosarcoma and Malignant Fibrous Histiocytoma are malignant fibrogenic tumors that have very similar radiographic presentations and histologic patterns

• Both typically occur in the third to sixth decades,

• both have a predilection for the pelvis, femur, humerus, and tibia.

• Both fibrosarcoma and MFH can be either primary tumors or secondary to a preexisting benign condition, such as Paget disease, fibrous dysplasia, bone infarct, or chronic draining sinuses of osteomyelitis

• These lesions may also arise in bones that were previously irradiated. Such lesions are termed secondary fibrosarcomas (or secondary malignant fibrous histiocytomas). Also radiation induced fibrosarcoma or sarcoma

• Rarely, fibrosarcoma can arise in a periosteal location (periosteal fibrosarcoma.

• Histologically, fibrosarcoma and MFH are characterized by tumor cells that produce collagen fibers. Neither tumor is capable of producing osteoid matrix or bone, a factor distinguishing them from osteosarcoma.

Radiological features• fibrosarcoma and MFH are

recognized by an osteolytic area of bone destruction and a wide zone of transition.

• the lesions are usually eccentrically located close to or in the articular end of the bone.

• They exhibit little or no reactive sclerosis and in most cases no periosteal reaction.

• Soft tissue mass is present

Differential diagnosis

• GCT

• Telangiectatic osteosarcoma

Primary Leiomyosarcoma of Bone

• Very rare, with fewer than 100 cases reported in the world literature.

• More common are skeletal metastases from primary soft-tissue leiomyosarcoma.

(an extraosseous primary tumor, mainly from the gastrointestinal tract or uterus, must be ruled out before a confident diagnosis of primary leiomyosarcoma of bone can be made)

• predominantly spindle-cell, neoplasm that exhibits smooth muscle differentiation.

• Although the patients reported range from 9 to 80 years of age, occurrence before age 20 is uncommon

• The usual clinical presentation is pain of variable intensity and duration. A soft-tissue mass is occasionally observed

• The most common sites are the distal femur, proximal tibia, proximal humerus, and iliac bone

• clavicle, ribs, and mandible occasionally may be affected .

• the tumor most often presents either as a lytic area of geographic bone destruction (moth eaten appearance is common)

• Approximately 50% of reported lesions exhibit fine periosteal reaction

• On MR imaging, the lesions are isointense to muscle on T1-weighted sequences, whereas on T2 weighting they exhibit a heterogeneous signal

Hemangioendothelioma

• Hemangioendothelioma and a recently identified lesion called epithelioid hemangioendothelioma are considered to represent true neoplasms because of their independent growth potential.

• they commonly recur after inadequate local excision

• histopathology demonstrates of nuclear atypia accompanied by occasional mitotic activity.

• They can arise at any age within the range of 10 to 75 years, with a slight predilection for males.

• The most commonly affected sites are the calvaria, spine, and bones of the lower extremities.

• Clinical symptoms include dull local pain and tenderness.

• Some swelling and hemorrhagic joint effusion seen some cases

• Radiologically

osteolytic appearance, either well circumscribed or with a wide zone of transition.

Variable degrees of peripheral sclerosis may sharply demarcate the lesion.

Occasionally a soap-bubble appearance with expansion of bone is observed, with extension into the soft tissues

• MRI findings

MRI reveals a mixed signal on T1-weighted sequences, with moderately increased signal intensity on T2 weighting

Angiosarcoma

• Angiosarcoma of bone represents the most malignant end of the spectrum of vascular tumors.

• aggressive neoplasm, characterized by frequent local recurrence and distant metastases.

• typically during the second to the seventh decade (with a peak in the fifth decade). M>2F

• Metastases to the lungs and other internal organs occur in approximately 66% of cases.

• Most common sites of occurrence are the long bones, particularly the tibia, femur, and humerus,

• most common symptoms are local pain and swelling.

• Angiosarcoma has imaging features similar to those of hemangioendothelioma.

• Microscopically, angiosarcoma is composed of poorly formed blood vessels that exhibit complicated infoldings and irregular anastomoses.

• The endothelial cells that line these blood vessels display features of frank malignancy, with plump intraluminal cells showing nuclear hyperchromation and atypical mitoses.

Chordoma • Tumor arising from developmental remnants of the notochord.

• Represent from 1% to 4% of all primary malignant bone tumor

• They arise between the fourth and seventh decades and affect men slightly more often than women.

• The three most common sites for a chordoma are the sacrococcygeal area, the spheno-occipital area, and the C-2 vertebra.

• Histologically, the tumor consists of loose aggregates of mucoid material separating cord-like arrays and lobules of large polyhedral cells, along with vacuolated cytoplasm and vesicular nuclei referred to as physaliphorous cells

• Radiologically

a highly destructive lesion with irregular scalloped borders;

it is sometimes accompanied by calcifications in the matrix, probably as a result of extensive tumor necrosis

Bone sclerosis has been reported in 64% of cases. Soft-tissue masses are commonly associated with the lesion

CT or MRI is required to demonstrate soft-tissue extension and invasion of the spinal canal

Lesions with malignancy potential

• Medullary Bone Infarct sarcoma

bone destruction in the area of the medullary infarct with periosteal reaction and soft-tissue mass confirm the diagnosis of malignant transformation

• Chronic Draining Sinus Tract of Osteomyelitis squamous cell carcinoma

Sinus >20yrs duration.

• Plexiform Neurofibromatosis neurosarcoma, neurofibrosarcoma

• Paget’s Disease sarcomas

lytic lesion, often with evidence of cortical breakthrough and a soft-tissue mass

Radiation-Induced Sarcoma

• normal bone exposed to radiation fields

• may be caused by benign conditions treated by irradiation,

fibrous dysplasia or giant cell tumor

• a sarcoma can develop only if at least 3,000 rads are administered within a 4-week span

Spotters

Ewing’s sarcoma preop, post chemo, post op

Thalassemia

Admantinoma

Chronic osteomyelitis sq cell Ca

Bone infarct sarcoma

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