secondary bone tumor

2dry bone tumors : 

1 19/03/2008 2dry bone tumors Pathology & concept

out look : 

19/03/2008 2 out look The most frequently encountered primary tumors that spread to bone are those of the lung, prostate, breast, liver, kidney, and thyroid when origin is known . Metastases can occur in any bone, but usually are located in the axial or proximal appendicular bone. When the primary site is unknown, the lung and kidney should be suspected as sites of origin. Metastatic cancer can cause severe pain and disability.

Common : 

19/03/2008 3 Common 2dry bone tumor most frequently occur in patient over 40 year old Common site of origin are lung ,prostate, breast & liver Common site of deposit are vertebrae, pelvis, femur &ribs Clinical presentation is extensive and non specific Most lesion present with oateolytic pattern 2dry of unknown origin account for 24 ./.

Clinical data of 390 pt (1980-2008) with pathologically confirm bone 2dry : 

19/03/2008 4 Clinical data of 390 pt (1980-2008) with pathologically confirm bone 2dry Male :female 2.12 :1 Mean age 55.7 years & 81.51 ./. Over 41 years Primary site :- lung 21.8./. prostate 13.1./. breast 7.4./. liver 6.4./. G.I.T 5.7./. unknown 24.6./.

origin of bone 2dry : 

19/03/2008 5 origin of bone 2dry

Common site of deposit : 

19/03/2008 6 Common site of deposit Spine 47.7./. Pelvis 18.2./. Femur 15.4./. Ribs 12.6./. Multi 20.5./.

Main symptom :- : 

19/03/2008 7 Main symptom :- Pain 53.3./. Fracture 10.3./. Dysfunction 4.9./. Paraplegia 2.1./.

Continues to above : 

19/03/2008 8 Continues to above Primary tumor diagnose before 2dry in 29.7./. Median metastatic time 319 days Uncertain time in 70.3./. Osteolytic pattern 80.7./. Osteosclerotic pattern in 10.5./. Mixed pattern in 09.8./.

Concept :- : 

19/03/2008 9 Concept :- The most common Clinically very significant Difficult to be cure Carry worst prognosis

Whey it so common ? : 

19/03/2008 10 Whey it so common ? Bone is big organ Have rich blood supply Heterogeneous cellular element Wide orientation along the body Continues modeling through life

Explanation ! theories of high bone 2dry deposit :- : 

19/03/2008 11 Explanation ! theories of high bone 2dry deposit :- this reflect molecular and cellular biological characteristic of both tumor and bone i.e (vicious cycle mediated by G.Fs i.e transforming G.F .B ,insulin L G F &PTHrP ) but why it may skip lung and liver to bone? 1-slowness of blood flow through red marrow cavity of the bone ? 2-presence of vertebral venous plexuses ? (more acceptable )

Vertebral venous plexuses:- : 

19/03/2008 12 Vertebral venous plexuses:- Batson valvelss Connecting inside and outside vertebra and segmentally from pelvis to the skull

Slide 13: 

19/03/2008 13 Blobe G et al. N Engl J Med 2000;342:1350-1358 Role of Transforming Growth Factor {beta} (TGF-{beta}) in Cancer

Slide 14: 

19/03/2008 14 Blobe G et al. N Engl J Med 2000;342:1350-1358 Mechanism of Signal Transduction Mediated by Transforming Growth Factor {beta} (TGF-{beta})

Slide 15: 

19/03/2008 15 Blobe G et al. N Engl J Med 2000;342:1350-1358 Human Diseases with Somatic Mutations, Germ-Line Mutations, or Genetic Polymorphisms in Specific Components of the Transforming Growth Factor {beta} (TGF-{beta}) Signaling Pathway

Whey it is clinically significant ? : 

19/03/2008 16 Whey it is clinically significant ? Diversity of differential diagnosis Decision making Technically and economically demanding Contravirsity on the best management option

How it reach the bone : 

19/03/2008 17 How it reach the bone Direct spread from adjacent structure Heamatogenous Lymphatic Why some tumor sometime skip the rational down stream ?

Common primary :- at time of autopsy : 

19/03/2008 18 Common primary :- at time of autopsy Breast 73./. Prostate 68./. Thyroid 42./. Renal 35./. Lung 36./. G.I.T 05./. Unknown 5 to 10./. Potentially all tumor can give bone deposit (all cell of the body can be site of tumor that is 32 billon possibilities) {batson experiment in animal 2008 }

Characteristic of bone 2dry:- : 

19/03/2008 19 Characteristic of bone 2dry:- May be lytic May be plastic May be mixed this depend on complex factor the most important of the them :- site of primary Nature and histology of the tumor Local bone environment the final mechanism is activation of osteoblast or osteoclast

Slide 20: 

19/03/2008 20 Roodman G. N Engl J Med 2004;350:1655-1664 Receptor Activator of Nuclear Factor-{kappa}B Ligand (RANKL) and Osteoclast Formation

Slide 21: 

19/03/2008 21 Roodman G. N Engl J Med 2004;350:1655-1664 The Vicious Circle of Osteolytic Metastasis

Clinical patterns and prognosis:- : 

19/03/2008 22 Clinical patterns and prognosis:-

presentation of 2dry bone cancer :- : 

19/03/2008 23 presentation of 2dry bone cancer :- BAIN PATATHOLOGICAL FRCTURE HYPER CALCEMIA Neuropathy (spinal cord compression, cranial & somatic nerve palsies) B.M SUPPRESSION Silent Fatigue Weight loss Anorexia Nausea Confusion Increased thirst Increased urination Dehydration Night sweats ALL this may or may not be preceded by history of malignancy some where

BAIN in 2dry bone : 

19/03/2008 24 BAIN in 2dry bone very common & important both for quality of life & prognosis Depend on many factor it range from 37./. To 87./. With different severity More sever when 2dry deposit in/or around base of the skull Pain measuring instrument is helpful for timing the therapeutic intervention

Thyroid cancer :- : 

19/03/2008 25 Thyroid cancer :- Papillary 60./. Follicular 30./. (hurthle cell 3./. ) Medullary 07./. Ana plastic 03./. Lymphoma 01./.

Thyroid cancer & bone :-{study review of 146 pt file with known bone 2dry for 38 year } : 

19/03/2008 26 Thyroid cancer & bone :-{study review of 146 pt file with known bone 2dry for 38 year } Bone 2dry at time of diagnosis was found in 47 ./. Pt and distributed as fellow Vertebrae 29./. Pelvis 22./. Rib 17./. Femur 11./. Multiple lesion in 53./.pt 10 year survival .e. no 2dry 35./. While it was decrease to 13./. .e. 2dry bone affection

Breast cancer and bone 2dry : 

19/03/2008 27 Breast cancer and bone 2dry Bone is the most common site of 1st distance relapse in operated pt More common in hormonal receptor +ve ,will differentiated than low diff Incidence of bone pain range from 24./. To 96./. 78./. Of pt with bone 2dry have pain at diagnosis 36./. Have pain but no 2dry

Slide 28: 

19/03/2008 28 Murphy P. N Engl J Med 2001;345:833-835 Model of Chemokine Regulation of Breast-Cancer Metastasis

Prostatic cancer : 

19/03/2008 29 Prostatic cancer The most common in man ,2nd cause of cancer death & give both lytic &plastic bone deposit but mostly the later 2dry bone deposit unlike normal bone &and other 2dry is surround & associated with increase osteoblastic activity which is target of both therapeutic & study trail.

Renal tumors &bone : 

19/03/2008 30 Renal tumors &bone renal tumor may remain silent for along time &1st presentation may be bone 2dry so must 1st consider in 2dry of unknown origin Almost all bone despite are lytic in nature Treatment of renal ca (1st&2st ) with outologous tumor cell vaccine is under trail

Renal ca &bone : 

19/03/2008 31 Renal ca &bone

Lung carcinoma :- : 

19/03/2008 32 Lung carcinoma :- Most common malignant tumor world wide Largest cancer causing death 30 ./. Of all male cancer death Male /female 2:1 (was 7:1 ) Directly related to smoking Associated with occupation exposure to carcinogen Overall 5 year survival rate around 5./.

Classification of lung cancer :- : 

19/03/2008 33 Classification of lung cancer :- Adenocarcinoma (30./.----- 45./.) Squmous cell ca (35./.-----40./. ) Small cell(oatcell)ca (15./.-----25./.) Undifferentiated large cell (rare)

Slide 34: 

19/03/2008 34 Roodman G. N Engl J Med 2004;350:1655-1664 Regulation of Bone Resorption (Panel A) and Bone Formation (Panel B)

Slide 35: 

19/03/2008 35 Roodman G. N Engl J Med 2004;350:1655-1664 Osteoclasts and Osteoblasts in Normal Bone and Bone Metastasis

conclusion :- : 

19/03/2008 36 conclusion :- . The exact incidence of bone metastasis is unknown, but it is estimated that 350,000 people die with bone metastases annually in the United States. Bone metastases are a frequent complication of cancer, occurring in up to 70./. of patients with advanced breast or prostate cancer and in approximately 15./. to 30./. of patients with carcinoma of the lung, colon, stomach, bladder, uterus, rectum, thyroid, or kidney Furthermore, once tumors metastasize to bone, they are usually incurable: only 20./. of patients with breast cancer are still alive five years after the discovery of bone metastasis. The consequences of bone metastasis are often devastating. Osteolytic metastases can cause severe pain, pathologic fractures, life-threatening hypercalcemia, spinal cord compression, and other nerve-compression syndromes. Patients with osteoblastic metastases have bone pain and pathologic fractures because of the poor quality of bone produced by the osteoblasts. For all these reasons, bone metastasis is a serious and costly complication of cancer.