Bone pathology 2. László Kereskai MD.

Transcription

1 Bone pathology 2. László Kereskai MD.

2 BONE-FORMING TUMORS Osteoid osteoma and osteoblastoma: Osteoid osteoma Most frequent btw ys. Best known symptom is intensive pain with easy precise localisation. In lumbar foms scoliosis can happen. Localisation: femur, tibia, humerus, bones of hands and feet, vertebrae, fibula. In long tubular bones usually metaphyseal; 85 % cortical; in the spine not in the vertebral bodies. Radiology: radiolucent central nidus, which rarely larger than 1,5 cm, sometimes the center is dens with a sclerotic reaction aroud (that can be several cms large, because of this phenomenon it is easy to mix with Garré osteomyelitis.

3 BONE-FORMING TUMORS Microscopically: the nidus is made of variously calcified osteoid surrounded by osteoblasts embedded in vascular-rich connective tissue. This change is so tipical that it is easy to identify either in fragmented sample as well. Around various amount of dense bone. Clinical settings: stronger pain during nights, NSAIDs are effective. Preoperative CT localisation and intraoperative scintigraphy increases the effectivness of the procedure. After preoperative administration of tetracycline during operation the nidus can be visualize in UV light.

4 Osteoid osteoma

5 Osteoid osteoma- nidus

6 BONE-FORMING TUMORS Osteoblastoma Related to the previous with larger nidus (giant osteoid osteoma), smaller or absent sclerotic zone, no intensive pain. In some cases there can be a cartilagineous matrix iside the lesion. Localisation: Usually growth in spongiosa, spine, larger bones of lower extremity. A possible complication is osteomalacia. It can be hard to distinguish from osteosarcoma (frequenty: bizarr cells, degenerative changes). Key role of radiological appearance.

7 Osteoblastoma

8 BONE-FORMING TUMORS OSTEOSARCOMA General characteristics Most frequent malignant bone tumor. Two age peaks: ys, and over 50 ys (frequently secondary). Pathogenesis, predisposin conditions Paget disease (over 40 ys). Irradiation: Every age, 1-15 ys latency. Chemotherapy: childhood, alkylating agents. Benign bone processes: fibrous dysplasia, osteochondromatosis, chondromatosis. Foreign bodies: hip prostheses, low case number. Trauma: questionable, usually it makes attention to the previously present tumor. Infection: questionable, víral origin? Genetics: acquired nonspecific changes in 70%. RB and p53 mutations are more important, but the mechanism is unclear.

9 Localisation BONE-FORMING TUMORS OSTEOSARCOMA Most typical: metaphysis of long bones: distal femur, proximal tibia, proximal metaphysis of humerus. (Dia- and epiphysis is rare as well as flat and short tubular bones.) Can be multiple: childhood, agressive form, sclerotic radiológical picture, p53 mutation in some cases. Usually medullary start, then spread to the cortex, cortical origin is rarer this is usually diaphyseal.

10 BONE-FORMING TUMORS OSTEOSARCOMA

11 Makroscopy, spread BONE-FORMING TUMORS OSTEOSARCOMA Different macroscopic appearance (ratio of bone, cartilage, vessels cellular stroma), bony hard, cystic, friable, haemorrhagic forms. Ways of spread from metaphysis: through medullary canal; into the cortex; elevation and perforation of periosteum: Codman triangle, not pathognomonic in 100%for malignant tumor, can be caused by hematoma or any other process which elevate the periosteum; break into soft tissue; into the epiphysis after closure of the plate; into joint cavity; production of satellit noduls proximally from the original tumorsin the same or the next bone transversing the joint (skip metastases), probably thi is responsible for local recurrance and further metastasises; hematogenous metastasis : lung (98%), other bones (37%), pleura (33%), heart (20%), almost never lymph node ms. The lung metastasis can be massive intraluminal form in pulmonary arteries.

12 BONE-FORMING TUMORS OSTEOSARCOMA

13 Microscopy BONE-FORMING TUMORS OSTEOSARCOMA The key for diagnosis: osteoid and/or bone formation by tumor cells: eosinophilic staining, glassy apprearance, irregular contours, osteoblastic rim around. Hard to dsicriminate from hyalinized collagen. Osteoid: rather homogenous than fibrillary, spots because of early calcification, the neighbouring cells are plump (osteoblasts). Thin tubular, anastomosing microtrabecules: basophil stainig (like fungal hyphae). Osteblastis zones are intermixed with chondroblastic and fibroblastic zones, with variable ratio. The diagnosis rests on the demonstration of malignant bone formation not coupled with cartilage independently from the ratio of neoplastic cartilage or fibroblastic areas. Many morpholigical variants esist, osteoclast-type giant cells are frequently present. Diff dg.: wide spectrum, large callus, myositis ossificans, fibrous dysplasia, osteoblastoma, fibrosarcoma, chondrosarcoma, giant cell tumor, malignant lymphoma, metastatic carcinoma.

14 BONE-FORMING TUMORS OSTEOSARCOMA

15 BONE-FORMING TUMORS OSTEOSARCOMA Microscopic variants: They can present focally or mixed, can have prognostic role. Teleangiectatic : Similar to aneurysmal bone cyst, frequent pathological fractures, in between the bloody channels in the septa malignant stroma, worse prognosis (?). Small cell: Diff. dg: Ewing, lymphoma; diffuse growth, frequently spindle cells, focal osteoid production. Fibrohistiocytic: Especially in sites of soft tissue infiltration it can be impossible to distinguish from MFH. Anaplastikus: Pleiomorphic sarcoma and metastatic carcinoma is the diff. dg.

16 BONE-FORMING TUMORS OSTEOSARCOMA Microscopic variants: well differencited intramedullary Many times underdiagnosed as fibrous dysplasia, other cases are similar to parosseal form. Usually adults, femoral and tibial involvement. Spindle cells, few mitoses, abundant osteoid. Frequentrelapse, bur rare metastasis (excluding those with transfoemation to coventional osteosarcoma). Difference from fibrous dysplasia: cortex destruction (radiology!).

17 BONE-FORMING TUMORS OSTEOSARCOMA Special types: Juxtacortical (parosseal) Relatively older age group, metaphysis of long bones (typical in the posterior surface of femur), slow growth (sometimes 15 ys course). Large lobulated mass, encircling the bone, late medullary infiltration with more immature picture. Satellite noduls are possible. Mikroscopy: irregular well-formed bony tissue, dense fibrous spindle cell stroma. Good prognosis, either with segmental resection. The parosseal tumor can undergo dedifferentiation during relapses.

18 Juxtacortical (parosseal) OSc

19 BONE-FORMING TUMORS OSTEOSARCOMA Periosteal: Different from the previous one. Growth in the surfaceof long bones (upper tibia, femur). Small, radiolucent lesions in cortex, rarely infiltrate the medulla. Mikroscopically usually high grade osteosarcom with a substantial amount of cartilagineous component (similar to juxtacortical chondrosarcoma). Jaw osteosarcoma: Slightly older age, prominent chondroblastic component. Body of mandible proc. Alveolaris of maxilla. Relatively good prognosis. On the base of Paget disease: In polyostotic type, many times the tumor is multicentric as well. Pelvis, humerus, femur, tibia and. Many osteoclast with atypical osteoblasts. The prognosis is poor.

20 BONE-FORMING TUMORS OSTEOSARCOMA Diagnosis Typical x-ray picture, but with many overlaps with reactive conditions, benign tumors, there is a need for preoperative biopsy: open (tumornormal border), needle-biopsy (effective, especially in hidden places, like spine), fine needle aspiration, frozen section. Laboratory findings: ALP elevation (depending on bone production, not specific). Therapy: based on aggressive chemotherapy and limb salvaging surgery

21 CARTILAGE-FORMING TUMORS Osteochondroma: The most frequent benign bone tumor. Usually symptomless, but can affect the function of neighbouring structures (tendons, vessels). Spontaneous regression can happen. Localisation: metaphyseal in femur, tibia, upper humerus, in pelvic bones. Typical radiological picture, usually it grows opposite to the next joint. Average age 10 ys, usually below 20 ys. Average diameter 4 cm, but can be as large as 10 cm, the smaller ones are sessile, the larger are pedunculated.

22 CARTILAGE-FORMING TUMORS Covered by fibrous capsule (periosteum), in large lesions there is a lobulated hyaline cartilage cap (about 6 mm thick, rarely more than 1 cm), endochondral ossification, centrally normal trabecular bone with bone marrow. In older lesions the cap becomes thin or disappear completely. Around the head a secondary bursa (bag) can form (with caltilagineous-bony free bodies in it). There is a familial mpl. variant (osteochondromatosis), in which the individual lesions are similar to those in solitary form. Transformation to chondrosarcoma in solitary form is quite rare, in multiple forms can reach 10%.

23 Osteochondroma

24 Osteochondroma

25 CARTILAGE-FORMING TUMORS Chondromas: Most frequent in small bones of hands and feet, mainly in proximal phalanges, very rare in distal phalanges. They arise mostly in the spongiosa of diaphysis (enchondroma), then expand and cause cortical thinning. Multiple in 30% (unilateral distribution: Ollier disease, association with soft part hemangiomas: Mafucci sy., in these cases more frequent malignant transformation, usually to chondrosarcoma). Enchondomas in ribs and long bones are extremely rare, usually with massive calcification.

26 CARTILAGE-FORMING TUMORS Chondromas: Rare localisation: juxtacortical or periosteal localisation in long bones or in the small bones of hands and feet, usual features: cortical erosion and sclerosis, sharp edge, in case of incomplet excision relapse can happen. Microscopy: mature, lobular hyaline cartilage with focal myxoid degeneration, calcification and endochondral ossification. The juxtacortical variants are frequently more cellular and can contain plump or binucleated cartilage cells.

27 Chondroma

28 CARTILAGE-FORMING TUMORS Chondroblastoma: Male predominance, below 20 ys. Start in the epiphysis of long bones before the disappearance of epiphysis cartilage (distal femur, proximal humerus and tibia). Radiologically well circumscribed, contain rarefactions. Spread from epiphysis into metaphysis or joint. Microscopy: high cellularity and variability, sometimes osteoclast type giant cells. Main element: embryonal chondroblast, which is not capable to produce intercellular chondroid matrix. Usually polygonal,but can be spindle-shaped. The nclear membrane is thick and sharp, nuclei are roundish or indented, lobulated sometimes mimicking Langerhans cells. Recidive lesions can show some atypia, but this not a sign of malignant transformation. In small zones focal calcification can be present (chicken wire).

29 CARTILAGE-FORMING TUMORS Chondroblastoma: ELMI: the tumor cells look like normal hyaline cartilage cells in culture. IHC: vimentin and S-100. The origin was not clear for a long time, ELMI and IHC findings support the chondroid origin (+ calcification, well differentiated chondroid areas). Clinical settings: frequently severe pain, diagnosis from fine needle biopsy (chondroblasts, giant cells, chondroid matrix). Th: curettage, bone replacement (80% enough locally). Rare agressive variants (soft tissue invasion, lymph or blood vessel tumor thrombosis) mainly in pelvis, sometimes lung metastasis formation after surgical intervention.

30 Chondroblastoma

31 CARTILAGE-FORMING TUMORS CHONDROSARCOMA Conventional chondrosarcoma: ys, very rare in childhood (more frequent: osteosc with chondroid component) and it occurs in extremities (opposite to adult forms). Central: Medullary, flat or long bones. Radiology: quite typical osteolytic lesion with calcification, uneven borders, fusiform widening of bone, cortical invasion but rarely break through periosteum. Mostly: pelvic bones, ribs (costochondral junctions), shoulder. Very rare in bones of hands and feet. Skull involvement is not rare, os temporale location (diff. dg: chordoma, meningeoma, glomus jugulare tumor).

32 CARTILAGE-FORMING TUMORS CHONDROSARCOMA Conventional chondrosarcoma Peripheric: De novo and transfomation from osteochondroma (1-2% chance in solitary forms). Signs of malignant trf in osteochondroma: accelerated growth in adolescent age, size over 8 cm, cartilagineous cap irregular or thicker than 3 cm. Radiology: large tumor, heavily calcified center surrounded by less dense peripheric calcified zone. Signs of malignant transformation: irregular border of cap, clear areas inside the lesion. Juxtacortical (periosteal) Localisation: long bones (mainly femur). Macroscopy: large, lobulated mass with scattered calcification. Relationship with periosteal osteosarcoma.

33 Chondrosarcoma

34 CARTILAGE-FORMING TUMORS Microscopy: CHONDROSARCOMA Various differentiation, formation of cartilage matrix without bone formation. Grading: well, moderately and poorly differentiated variants. Distinction between well-differentiated chondrosarcoma and chondroma sometimes (almost) impossible (radiology, architecture, cytology large, hyperchromatic nuclei, more nuclei in one cell- can be important), chondrosarcoma frequently involve trabecular bone. Fast grow, size over 8 cm is important, as well. In long bones, ribs in case of large tumors at least small atypia supports malignancy, while in the bones of hands and feet pronounced atypical features don t mean malignancy. The signs of cytologic atypia can be present just in a small fraction of the tumor (small biopsy specimen). The tumor can contain bone, this is an endochondral ossification because of cartilage resorption, not neoplastic.

35 CARTILAGE-FORMING TUMORS CHONDROSARCOMA

36 PORCKÉPZŐ DAGANATOK CHONDROSARCOMA Cytogenetics: c-myc amplification and c-erbb-2 expression can be present, in high-grade tumors p53 amplification. Treatment: In case of large pelvic tumor large block dissection or hemipelvectomy can be necessary, sometimes without previous sampling (90 %: chondrosc. is the dg.). In costal tumors and in well differentiated variants of long bones in extremities, segmental resection is the solution. Variants: Clear cell Myxoid Dedifferentiated Mesenchymal

37 FIBROSUS AND FIBRO-OSSEOUS TUMORS Fibrosus cortical defect and non-ossifying fibroma: Adolescents, long bones (both end of tibia, lower femur). Excentric, sharply delimited lesions not too far from epiphysis, sometimes together with the abnormality of epiphysis. Loose consistency and intramedullary component: non-ossifying fibroma. Neoplastic or developmental anomaly? Macroscopy: granular, brownish-reddish. Microscopy: cellular fibrous bands in storiform arrangement, scattered osteoclasts, foamy and hemosiderin-laden macrophages. Mainly in adult cases: benign fibrous histiocytoma. Little symptoms, only pain, frequently incidental finding in x-ray, fracture because of the thinned cortex.

38 Non-ossifying fibroma

39 FIBROSUS AND FIBRO-OSSEOUS TUMORS, FIBROSUS DYSPLASIA Benign tumor, suggesting a developmenal arrest as well, there is no complete development of mature structures. Monoostotic form: 70%, boys and girls involved equally, early adolescent age. Femur, tibia, ribs, jaw, calvaria and humerus. Usually asymptomatic-accidental finding; pain, deformity (skull). Polyostotic form without endocrine disorders: 27%, a little bit erlier than the previous one. Femur, skull, tibia, humerus, ribs, fibula, radius, ulna, mandible and vertebrae, 50% craniofacial involvement in mild cases, 100% in extensive disease. Shoulder and hip deformities.

40 FIBROSUS AND FIBRO-OSSEOUS TUMORS, FIBROSUS DYSPLASIA Polyostotic fibrosus dysplasia with café-au-lait skin pigmentation and endocrinopathy: McCune-Albright syndrome (3%). Sexual precocy, hyperthyrosis. hypophysis adenomas secreting GH, primary adrenal hyperplasia. Gain-of function mutation in GNAS gene resulting in hyperactive guanyl nucleotid-binding protein, causing abnormal growth. Intramedullary tan-whitish gritty fibrous tissue, sometimes protruding the bone rarely breaking out through cortex. Curvilinear woven bone trabeculae, surrounded by moderately cellular fibroblastic proliferation. The shape of the trabeculae reminds Chinese letters, there is no prominant osteoblastic rim. Typical radiological picture in monoostotic form: ground glass appearance, well-defined margin. Polyostotic forms with early onset: fractures, pain, deformities, requiring orthopedic surgical intervention. Bisphosphonates ease the pain. Fibrosarcoma variants

41 Fibrous dysplasia

42 MISCELLANEOUS TUMORS EWING SARCOMA/PNET Member of of small round cell tumor group. The tumor is called Ewing-sarcoma in cases of bone derivation and/or forms without neuroepithelial differentation, in this meaning PNET is equal with extrasceletal Ewing. Certain agents (camp derivates, retinoic acid) can induce neurogenic differentiation. Sites: bone medulla (long bones: femur, tibia, humerus, fibula, pelvic bones, ribs, vertebrae, mandible, clavicula; diaphysis, central), 5-20 ys age group.

43 MISCELLANEOUS TUMORS EWING SARCOMA/PNET Clinical course: can mimick osteomyelitis (pain, fever, leukocytosis), from medulla spread into cortex and soft parts. Rarely manifests as a soft tissue tumor, but always with identifiable intraosseal component inside the bone, either with a simple x-ray. Radiology: spindle-shaped bone widening, periosteal reaction in the form of onion-skinning or sunbeam-like spikes in right-angle.

44 MISCELLANEOUS TUMORS EWING SARCOMA/PNET

45 MISCELLANEOUS TUMORS EWING SARCOMA/PNET Microscopy: solid proliferation of small cells in sheets, roundish nuclei, small nucleoli, wellformed vasculature, pseudorosettes, sometimes true rosettes (neurogenic differentiation). Abundant necrosis, sometimes dominating the picture. PAS-positive glycogen granulation in cytoplasm is quite typical (diff. dg.: ML, neuroblastoma, embryonal rhabdomyosarcoma). ELMI: primitive appearance, few dens core granules.

46 MISCELLANEOUS TUMORS EWING SARCOMA/PNET

47 MISCELLANEOUS TUMORS EWING SARCOMA/PNET IHC: consistent vimentin, occasionally LMW keratin, NSE, neurofilament positivity, MIC 2 cell membrane protein (CD99), coded on short arm of X and Y chromosome is consistently expressed in Ewing/PNET, but not pathognomonic. Genetics: common with PNET, t(11;22) (q24;q12): fusion of EWS and FL 1 genes (PCR and FISH methods for diagnosis and monitoring therapy).

48 MISCELLANEOUS TUMORS EWING SARCOMA/PNET Clinical course: metastases in lung, pleura, in other bones, (mainly skull), CNS, rarely in regional lymph node. In about 25 % mpl. bone and/or visceral lesions are detectable at presentation. Treatment, prognosis: dramatic improvement, in the past surgical and irradiation therapy resulted in <10 % 5 years survival, the current combined high-dose irradiation and chemotherapy and only limited surgical intervention has much better results: 85% local control and 75% 5 years survival can be achieved. The radiological change regress, if there are again lytic lesions, that suspicious for relaps. Soft tissue extension is a bad prognostic sign. The prognosis of Ewing is better than soft tissue PNET. Ploidy can have prognostic value (diploid is better).

49 MISCELLANEOUS TUMORS, GIANT-CELL TUMOR Usually over 20 ys. Classical localisation: epiphysis of long bones, then spread into metaphysis and breaking through the cortex invading the joint, towards the intermuscular septa. Decreasing fequency: lower femur, upper tibia, lower radius. In the bones of hands, jaws, vertebrae (excluding sacrum) quite rare, in these locations other types of giant cell lesions appear. Radiology: lytic, expansive lesion in epiphysis without bone sclerosis or periosteal reaction. Clinical course: large tumors can be associated with pathologic fracture.

50 MISCELLANEOUS TUMORS, GIANT-CELL TUMOR

51 MISCELLANEOUS TUMORS, GIANT-CELL TUMOR Cut surface: solid, grey-brownish, intermixed with connective tissue septa, bleedings. Microscopically: two main components: osteoclast-type giant cells (30-40 nuclei, acid phosphatase positivity, IHC: lysozim, CD68-Kp-1 and other histiocyte marker positivity), which are non-neoplastic and the so-called stromal cells, representing the true neoplastic elements (only they proliferate, show atypia in more agressive cases, occasionally just focally). Their origin is not entirely known: mesenchymal, fibro- or osteoblast (in 1/3 of the cases osteoid deposition). They produce type I. and III. collagen, sometimes focal positivity with S-100 is detected, can contain alfa-1-at. Similarly to Paget disease intranuclear inclusions mimicking viral particles.

52 MISCELLANEOUS TUMORS, GIANT-CELL TUMOR

53 MISCELLANEOUS TUMORS, GIANT-CELL TUMOR Diff. Dg.: benign bone lesions containing giant cells (nonossifying fibroma, chondroblastoma, Langerhans-cell histiocytosis, Recklinghausen disease, aneurysmal bone cyst, osteoid osteoma and osteoblastoma). There is difference in the distribution of giant cells, in other benign lesions deposition focally in larger clusters, in the real giant-cell tumor the distribution is scattered, equally distributed. Arguments against the possibility of giant-cell tumor: childhood, metaphyseal or diaphyseal location, multiple appearance, spine, jaw, hand and foot involvement. Therapy: curette or block resection with bone replacement, vital to avoid soft tissue implantation. In non-resectable cases: radioth, but with the danger of malignant transformation.

54 MISCELLANEOUS TUMORS, GIANT-CELL TUMOR Clinical course: tumor with low malignant potential (10 % behaves clinically malignant: local relapse, metastasis). The choice of therapy affects the course: higher rates of relapse with simple curettage (34 % comparing with 7 % in wide resection). Break through cortex and extension into soft parts: worsens prognosis. A substantial portion of metastasises occur after surgical intervention. Microscopic grading: I-III, but has limited value, just in the cases of easily identifiable sarcomatous GIII variants. GII tumor can make metastasis to the lung with similar morphology (tumor surrounded by mature bone). Genetics: Non-random changes, mainly telomere fusions.

55 MISCELLANEOUS TUMORS /TUMOR- LIKE LESIONS- Aneurysmal bone cyst ys, vertebrae (frequently mpl.), flat bones, but can be in the diaphysis of long bones. It can occur in soft tissues, in the walls of large arteries. Radiology: excentric expansion, cortex erosion, destruction, in small zones periosteal new bone formation. Macroscopically spongy hemorrhagic mass, covered by thin reactive bone. Soft tissue involvement can be present. Microscopically: large, blood-filled spaces, lined not by endothel, but instead fibroblasts, myofibroblasts, histiocytes, they occupy the limiting septa as well, below the surface osteoclasts. In septa: vessels, osteoid and bone.

56 MISCELLANEOUS TUMORS /TUMOR- LIKE LESIONS- Aneurysmal bone cyst

57 MISCELLANEOUS TUMORS /TUMOR- LIKE LESIONS- Aneurysmal bone cyst

58 MISCELLANEOUS TUMORS /TUMOR- LIKE LESIONS- Aneurysmal bone cyst Diff. dg: solitary bone cyst, giant-cell tumor, haemangioma, teleangiectatic osteosarcoma, giant cell reparative granuloma (jaw). Origin:?, sometimes preceding trauma, subperiosteal hematoma, in other cases it derives from prexisting other bone lesions because of the change in hemodynamics, but because of the destruction the original lesion is not identifiable. Curette alone leads 25% relapse, complete removal with bone replacement provides much better results. There are episodical cases with transformation to osteosarcoma. There is a form of more cellular, solid lesions with fibrous reaction, many osteoclasts, this would be the solid variant (hands, feet, vertebrae, sacrum and raraely long bones).

59 MISCELLANEOUS TUMORS - METASTASES Most frequent bone tumors. Usually mpl appearance together with known primary and other organ MS lesions, but can be solitary mimicking primary bone tumor. 80%: breast, lung, prostate, thyroid, kidney, in general 50% of all tumors have bone metastases. Soft tissue sarcomas rarely give metastasis into bones, except the childhood embryonal rhabdomyosarcoma. 70% affects the axial skeleton (skull, ribs, spine, sacrum). Usually red marrow location. In long bones metaphyseal location.

60 MISCELLANEOUS TUMORS - METASTASES Most frequently osteolytic types, osteoplastic forms exist as well (prostate, carcinoid and other neuroendocrine tumor, rarely breast cancer) or mixed. In widespread osteoplastic prostate cancer metastasis in other areas osteomalacia can develop (increased Ca use, limited source). Typical metastases (place, radiological picture): thyroid (shoulder, skull, ribs, sternum), kidney (flat bones of pelvis, upper femur, scapula). Periosteal proliferation is rare (prostate). After pathologic fracture enormous bone formation can happen, easy to mix with osteosarcoma. Together with carcinoma and melanoma we frequently see osteoclasts, misdiagnosis: giant cell tumor. In sternal and vertebral MS a possible comlication is spread to soft tissues with a pulsating mass. Usual lab findings: hypercalcaemia, ALP elevation. Bone resorption can be a result of transformation of tumor infiltrating macrophages into osteoclasts.

61 MISCELLANEOUS TUMORS - METASTASES Biopsy is important to rule out a primary bone tumor. Symptoms: strong bone pain. The goal of therapy: reveal the pain, prevent the fracture; irradiation is effective, 80%: substantial decrease of pain. In case of fracture internal fixation then irradiation is recommended. In prostate and breast cancer hormontherapy can be effective decreasing the pain and increasing tolerance. Solitary metastases can be completely resected.

62 MISCELLANEOUS TUMORS - METASTASES