CLASSIFICATION BONE AND SOFT TISSUE

z Purpose of classification is to link similar tumors in order TUMORS to understand their behavior, determine the most appropriate treatment, and investigate their biology. z However, purpose of a classification system is simplicity and reproducibility z Therefore tumors are classified according to the cell type they resemble. z Refinements are coming from cytogenetics, molecular, and gene expression studies. z The majority arise from -or show differentiation toward- mesenchymal cells, but some show other differentiation (neuroectodermal, histiocytic). z A small subset is of unknown histogenesis.

Fabrizio Remotti MD

DEFINITION z Soft tissue pathology deals CLASSIFICATION with tumors of the connective tissues. z Many tumors resemble z The concept of soft tissue is tissues present in the understood broadly to region of origin. include non-osseous tumors z These tumors may be derived from stem cells of extremities, trunk wall, Vascular leiomyosarcoma retroperitoneum and that belong to local, mediastinum, and head & organ-specific pools. neck. z Other involved stem cells may be bone marrow z Excluded (with a few derived. exceptions) are organ specific tumors. Lipoma

Alveolar soft part DEFINITION CLASSIFICATION z Bone pathology deals with tumors of the z Some tumors have no skeletal system. resemblance to normal tissue in the region z Included are subsets of (metaplastic foci within a tumors from extra - ttftumor, or tumors of osseous sites that show different histogenesis from osseous and cartilaginous the normal cells of the region) differentiation. z Some have no normal cell counterparts, probably reflecting an unique genetic makeup.

Epithelioid sarcoma, proximal type

1 HISTOGENESIS EPIDEMIOLOGY All tumors are derived from stem cells that are programmed to differentiate into various mature cell types.

CANCER CELL : SEPTEMBER 2002 · VOL. 2, 175- 178

EPIDEMIOLOGY EPIDEMIOLOGY

z Soft tissue (ST) sarcomas are z There is a slight male rare tumors compared to other predominance (with some malignancies: 8,700 new subtypes more common in sarcomas in 2001, with 4,400 women). deaths. z The majority of soft tissue z The incidence of ST sarcomas tumors affect older adults in the USA is approximately (some sub-groups occur 3.3 cases per 100,000 people. predominantly or exclusively Extra-renal malignant rhabdoid tumor z This is roughly 5% of each of in children). some of the most common z Incidence of benign soft tissue carcinomas (prostate, breast tumors not known, but and lung), half of all brain probably outnumber tumors, and approximately malignant tumors 100:1. equal to AML.

SOFT TISSUE TUMORS EPIDEMIOLOGY z The knowledge of epidemiologic data may help in diagnosis. z What you don’t know may hurt you!

Nowhere in the picture…..

2 BONE TUMORSTUMORS-- BONE TUMORSTUMORS-- EPIDEMIOLOGY EPIDEMIOLOGY • The majority of tumors involving bone are z Primary bone tumors are rare. secondary (or z Bone sarcomas account for 0.2% of all metastatic): neoplasms (SEER Statistics Review , - secondary 1973-1996). (metastases) (95%) z Soft tissue sarcomas are approximately 10 - primary (5%) times more common than primary bone sarcomas.

BREAST CANCER TO HIP

Secondary Tumors of Bone BONE TUMORSTUMORS-- EPIDEMIOLOGY •The carcinomas most frequently involved with bone metastasis originate from:

• Lung • Breast • Prostate • G.I • Kidney • Thyroid

MELANOMA TO PROXIMAL HUMERUS

BONE TUMORS

EPIDEMIOLOGY •Bone sarcomas as a group have a bimodal distribution. •The first peak is in the second decade. Bone and soft tissue sarcomas •The second peak occurs in patients older than sixty.

30 80 25 70 /100,000

s 20 60 OS Series2 15 50 CS Series1

persons) 40 ES 10 30 CH 5 20 MFH Incidence(case rate 0 10 1 210 3 420 5 630 7 8 40 9 10 50 11 12 60 13 14 70 15 16 80 17 18 0 Age at diagnosis

Soft tissue sarcomas 0 to 4

Bone sarcomas 10 to14 20 to24 30 to34 40 to44 50 to54 60 to64 70 to74 80 to85

3 ETIOLOGY ETIOLOGY

z The etiology of sarcomas is poorly

understood, and what is known apply only z Herbicides (“agent orange”) and to a small fraction of the ggproup. ppperipheral soft tissue sarcomas z Retained metal objects z The known etiologic agents are ionizing (shrapnel, surgical devices) and radiation, oncogenic viruses, and chemicals. OS, AS and MFH z Vinyl chloride, inorganic z These agents are able to cause genetic arsenic, Thorotrast, anabolic alterations that can lead to tumorigenesis. steroids linked to AS and MFH.

ETIOLOGY ETIOLOGY z Host factors may also z Radiation induced sarcomas play a role in the develop in 1% of patients who development of soft have undergone therapeutic tissue sarcomas. irradiation. – Immunosuppression, besides Kaposi’s z The interval between irradiation sarcoma, may be and diagnosis of sarcoma varies associated with between 5 and 10 years. sarcomas. – Lymphedema, z The majority of radiation- congenital or acquired induced sarcomas are high grade (post-mastectomy) is a and poorly differentiated (MFH, rare cause of FS, OS, and AS). extremity-based AS. AS in lymphedema

ETIOLOGY ETIOLOGY

z Oncogenic viruses introduce new genomic material in the cell, which encode for oncogenic proteins that disrupt the regulation of cellular proliferation . z Two DNA viruses have been linked to soft tissue sarcomas: – Human herpes virus 8 (HHV8) linked to Kaposi’s sarcoma – Epstein-Barr virus (EBV) linked to subtypes of leiomyosarcoma z In both instances the connection between viral infection and sarcoma is more common in immunosuppressed hosts.

4 CONGENITAL SYNDROMES ASSOCIATED WITH BONE AND SOFT TISSUE TUMORS SOFT TISSUE TUMORS Disorder Inheritance Locus Gene Tumor

Albright hereditary osteodystrophy AD 20q13 GNAS1 Soft tissue calcifications and

Bannayan -Riley- Ruvalcaba AD 10q23 PTEN Lipomas, hemangiomas syndrome Beckwith- Wiedemann syndrome Sp/AD 11p15 Complex Embryonal RMS, myxomas, fibromas, hamartomas Bloom syndrome AR 15q26 BLM Carney complex AD 17q23-24 PRKAR1AK Myxomas and pigmented schwannomas (Familial myxoma syndrome) 2p16 Familial AD 7q33 - Costello syndrome Sporadic - - Rhabdomyosarcomas Fibroma of tendon sheath, finger Low-grade fibromyxoid sarcoma, neck 19F Cowden disease AD 10q23 PTEN Lipomas, Hemangiomas (Multiple hamartoma syndrome) Diaphyseal medullary stenosis AD 9p21-22 - MFH Familial adenomatous polyposis AD 5q21 APC Craniofacial osteomas, desmoid tumors Familial expansile osteolysis AD 18q21 TNFRSF11A

Familial infiltrative fibromatosis AD 5q21 APC Desmoid tumors Langer- Giedion syndrome Sporadic 8q24 EXT1 , Li-Fraumeni syndrome AD 17p13 TP53 Osteosarcomas, RMS, other sarcomas 22q11 CHEK2 Familial multiple lipomas AD - - Lipomas IM myxoma, thigh 65M Myxoid MFH, thigh, 60M Symmetrical lipomatosis Sporadic - - Lipomas, lipomatosis of head and neck

CONGENITAL SYNDROMES ASSOCIATED WITH BONE AND SOFT TISSUE TUMORS SOFT TISSUE TUMORS Disorder Inheritance Locus Gene Tumor Maffucci syndrome Sporadic - - , CS, hemangiomas, AS Mazabraud syndrome Sporadic 20q13 GNAS1 Fibrous dysplasia, OS, IM myxomas McCune –Albright syndrome Sporadic 20q13 GNAS1 Fibrous dysplasia, osteosarcomas Multiple osteochondromas, AD 8q24 EXT1 Osteochondromas, chondrosarcomas non- syndromic 11p11-12 EXT2

Myofibromatosis AR - - Myofibromas Neurofibromatosis type 1 AD 17q11 NF1 Neurofibromas, MPNST Neurofibromatosis type 2 AD 22q12 NF2 Schwannomas Rhabd omyoma, hear t, new born F Ollier disease Sporadic 3p21-22 PTHR1 Enchondromas, chondrosarcomas Embryonal RMS, thigh, 5M Paget disease of bone, familial AD 18q21 Osteosarcomas 5q31 5q35

Proteus syndrome Sporadic - - Lipomas Retinoblastoma AD 13q14 RB1 Osteosarcomas, soft tissue sarcomas Rhabdoid predisposition syndrome AD 22q11 SMARCB1 Malignant rhabdoid tumors

Rothmund- Thompson syndrome AR 8q24 RECQL4 Osteosarcomas Rubinstein- Taybi syndrome AD 16p13 CREBBP Rhabdomyosarcomas Venous malf. With glomus cells AD 1p21-22 - Glomus tumors Scwannoma, leg, 35F MPNST, arm, 45M with NF Werner syndrome AR 8p11-12 WRN Bone and soft tissue sarcomas

Cartilage tumors SOFT TISSUE TUMORS WHO CLASSIFICATION OF BONE TUMORS Periosteal chondroma CLASSIFICATION Mult. chondromatosis Central MAJOR TYPES OF SOFT TISSUE TUMORS Peripheral Cell type Benign tumor Malignant tumor Dedifferentiated Mesenchymal (Myo)fibroblast Fibroma, myxoma , MFH Clear cell Adipocyte Lipoma Liposarcoma Osteogenic tumors Osteoid Smooth muscle cell Leiomyoma Leiomyosarcoma OtOsteobl ast oma Osteosarcoma Conventional Skeletal muscle cell Rhabdomyoma Rhabdomyosarcoma Telangiectatic Endothelial cell Hemangioma Angiosarcoma Small cell Low grade central Schwann cell Schwannoma, neurofibroma MPNST Secondary Cartilage cell Chondroma Chondrosarcoma Parosteal Periosteal Interstitial cell GIST GIST High grade surface Histiocyte JXG, GCTTS, RDD True histiocytic sarcoma Fibrogenic tumors Desmoplastic fibroma Unknown No benign counterparts ES, SS, ES, ASPS Fibrosarcoma Osteosarcoma Fibrohistiocytic tumors Desmoplastic fibroma Fibrosarcoma

5 Ewing/PNET Ewing sarcoma WHO CLASSIFICATION OF BONE Hematopoietic tumors Plasma cell myeloma OSTEOSARCOMA Malignant lymphoma TUMORS z Largely a disease of Giant cell tumor Giant cell tumor the young (60% <25 Malignant giant cell tumor years) Notochordal tumors Chordoma z 30 % >40 years. Vascular tumors Hemangioma z In older people rule Angiosarcoma out predisposing Smooth muscle tumors Leiomyoma conditions (e.g. Leiomyosarcoma Paget’s disease of Lipogenic tumors Lipoma bone, radiation) Liposarcoma z Long bones of Neural tumors Schwannoma appendicular skeleton Miscellaneous tumors are favored Metastatic malignancy z 91% , 9% Miscellaneous lesions Aneurysmal bone cyst diaphysis Simple cyst Fibrous dysplasia Osteofibrous dysplasia Aneurysmal bone cyst Langerhans cell histiocytosis Erdheim -Chester disease Chest wall hamartoma Joint lesions Synovial chondromatosis

OSTEOID OSTEOMA OSTEOSARCOMA z Benign bone forming tumor. • Conventional: z Small size, limited growth - Osteoblastic (50%) potential and disproportionate - Chondroblastic (<25%) pain. - Fibroblastic (<1-2 %) z Most common in long bones, • Telangiectatic (<4%) but every bone may be affected. • Small cell (1.5%) z It may be painful on physical examiiination • Low grade central (<1%) z It may be associated with • Parosteal (4%) redness of skin and swelling. • Periosteal (<2%) z Lesions close to a joint may be • High-grade surface (<<1%) associated with joint effusion. • Secondary (20% of OS in patients older than 40)

Nidus

OSTEOID OSTEOMA CLINICAL EVALUATION z Clinical presentation z Small, cortically based lesion, red and gritty, surrounded by z Physical examination sclerotic bone. z z The lesion is composed of a Pretreatment meshwork of osteoid evaluation: trabeculae lined by plump osteoblasts. – 1. biopsy – 2. radiological staging

Osteosarcoma, 18M

6 IMAGING STUDIES BONE TUMORS z The ultimate goal is: z Conventional radiographs are Liposarcoma – 1. Detecting lesions still important in the diagnosis of – 2. Giving a specific bone tumors. diagnosis or a reasonable differential z Many tumors are site-specific. diagnosis z Many tumors have a – 3. Staging the lesion characteristic radiographic appearance. 1. Ewing sarcoma, lymphoma, myeloma 2. Osteofibrous dysplasia, adamantinoma 3. Osteoid osteoma 4. Fibrous dysplasia 5. Chondromyxoid fibroma 6. Non-ossifying fibroma 7. Bone cyst, 8. Osteochondroma 9. Osteosarcoma 10. Enchondroma, chondrosarcoma 11. Giant-cell tumor MFH 12. Chondroblastoma

IMAGING STUDIES BONE TUMORS z CT and particularly MRI allow detection and and staging by delineating anatomical extent in virtually all cases. z A relatively specific diagnosis can be given in approximately 25 -50% of cases , according to the type.

65 W, FS thigh (MRI) Some fancy words from the world of shadows

BONE TUMORS IMAGING STUDIES

CONVENTIONAL X-RAY z The diagnosis is BENIGN SUSPICIOUS FOR based on imaging MALIGNANCY and histological QUESTIONABLE RESULTS criiiteria. TREATMENT CT STAGING CT X-RAY MRI BIOPSY MRI BIOPSY

TREATMENT 14F R distal femur Osteosarcoma Soft tissue mass

7 IMAGING STUDIES IMAGING STUDIES z Although imaging studies may give a reasonably accurate diagnosis on the biological potential of a lesion, there are not many lesions that may be accurately diagnosed by imaging studies alone. z Multiloculated lesions with sclerotic margins z The biopsy is the gold standard for diagnosis. in proximal femur: – Top 57M – Bottom 42F (s/p surgery)

IMAGING STUDIES IMAGING STUDIES

z Top: simple bone cyst. z Bottom: Fibrous dysplasia.

What is this soft tissue lesion?

IMAGING STUDIES IMAGING STUDIES z Myositis ossificans.

z Sequential imaging studies at few weeks interval show z Proximal femur lytic appearance of reactive shell of bone. lesion with negative z The histology shows maturing periphery and immature bone scan. center. z Radiological impression: benign lesion (e.g. bone cyst, cystic fibrous dysplasia) z Diagnosis at biopsy: multiple myeloma. A word for the wise: A lesion is benign only after biopsy.

8 Metastatic myxoid liposarcoma IMAGING STUDIES BIOPSY to liver z 42M with NF1 and plexiform NF of sciatic nerve. z Percutaneous needle core z Now with rapidly biopsy usually yield enlarging thigh mass. adequate tissue for z RdilRadiology: MPNST diagnosis. z Biopsy: MPNST. z There is enough tissue for morphological, IHC & FISH studies.

Osteosarcoma

IMAGING STUDIES BIOPSY z Conclusion: if it looks z Core biopsies yield malignant probably it enough material for is, but you got to extensive prove it. immunohistochemical z The images suggest stains. esophageal cancer with suspected metastasis. z The lesion turned out MITF to be a neurofibroma.

Fig. 1 Coronal image on FDG-PET demonstrating avid FDG uptake by esophageal primary (a). Transverse images demonstrating left-sided superior mediastinal mass on CT (b) without corresponding FDG uptake on PET (c) Medical Oncology, March 2009 S-100 24M, arm, clear cell sarcoma

BIOPSY Craig cutting needle with T-handle and sheath for bone biopsies BIOPSY z Select least invasive technique that allows diagnosis (including grade): z Incisional biopsies are required in many – Percutaneous fine needle aspiration. cases. – Percutaneous core needle biopsy (blind or image-guided). – Incisional biopsy. – Excisional biopsy.

50M, angiosarcoma of ischium. Craig needle set

9 SPECIAL DIAGNOSTIC STUDIES GENETICS OF CONNECTIVE z Many sarcomas require additional studies to TISSUE NEOPLASMS confirm the diagnosis and, in some cases, to add prognostic information. z The genetic mechanisms involved in carcinogenesis affect three types of cancer genes: – 1. Oncogenes (KIT, PDGFRA, MYCN, MDM2, PLAG1, HMGA1) [activation] – 2. Tumor suppressor genes (p53, RB1, NF1, INI1) [loss of function] – 3. Caretaker genes [loss of function]

GENETICS OF CONNECTIVE TISSUE NEOPLASMS GENETICS OF CONNECTIVE z Hallmarks of cancer (Hanahan & TISSUE NEOPLASMS Weinberg): z Numerous cancer-specific genetic alterations have – 1. self-sufficiency in growth signals been described, unfortunately almost exclusively for – 2. insensitivity to growth-inhibitory signals soft tissue neoplasms. – 3. evasion of apoptosis z Some of them (such as translocations, numerical – 4. limitless replicative potential changes, large deletions and gene amplifications) are – 5. sustained angiogenesis seen at the cytogenetic level. – 6. tissue invasion and metastasis z Subtle changes (such as single base pair substitutions, small deletions) require molecular genetic detection. z Translocations constitute the majority of the specific genetic alterations associated with sarcomas.

GENETICS OF SOFT TISSUE GENETICS OF CONNECTIVE TUMORS TISSUE NEOPLASMS z Many chromosomal translocations and other FISH-F: Ewing z The model of multistep carcinogenesis genetic rearrangements lead to derived from the study of carcinomas (e.g. formation of oncogenic gene fusions or overexpression of adenoma-carcinoma seqq),uence), does not normal genes . apply to sarcomas. z Many of these changes may z Not many “precursor” lesions in sarcomas. be used for diagnosis or confirmation of diagnosis.

FISH-BA: Ewing t(11;22)(q24;q12) EWS-FLI1

10 GENE FUSIONS IN SARCOMAS GENE FUSIONS IN SARCOMAS 1. These translocations disrupt genes z Nonrandom translocations were described first in located at the chromosomal hematopoietic malignancies. breakpoints and juxtapose portions of these genes to create two z Identified in many types of sarcomas and some reciprocal chimeric genes. benign soft tissue tumors. 2. The breaks are confined to one or a few introns within the coding region z Each translocation results in a specific gene fusion. of each gene. z Each gene fusion is present in most cases of a FISH with dual color 3. The chimeric genes are transcribed specific sarcoma category, and is not present in break-apart probe to generate chimeric transcripts. cocktail flanking the 4. The chimeric transcripts are any other sarcoma type (consistency and EWS breakpoint region translated into chimeric proteins. specificity). at 22q12

GENE FUSIONS IN SARCOMAS

z The novel protein products have significantly altered functional properties. z In many cases, one or both involved genes are transcription factors, and the chimeric product is a novel transcription factor.

z KIT mutations occur in 80-95% of GISTs (the remaining cases have mutations of PDGFRA, GIST GENE FUSIONS IN SARCOMAS another receptor tyrosine kinase) and lead to ligand- independent phosphorylation and constitutional activation of z These translocations: the KIT signaling pathway to the nucleus. 1. represent fundamental genetic steps in z In GISTs this mutation is the primary tumorigenic event. the development of these z Imatinib mesylate (Gleevec) is an ATP analogue that binds to 2. are useful markers for the diagnosis KIT and negates the effect of the activating mutation. 3. may constitute new therapeutic targets z Over 50% of patients with GIST respond to oral administration of Gleevec. z Gleevec also effective in patients with DFSP (they carry mutation of PDGFRA).

11 GRADING GRADING z Grading is an arbitrary estimate of the degree of z malignancy of a neoplasm Weak points of grading: (basically an attempt to – Subjective elements (number determine the biological of mitoses, percent of potential of a tumor). necrosis, tumor z The purpose of grading is to Low-grade cutaneous leiomyosarcoma provide guidance for differentiation) prognostic prediction and – Sampling treatment (mainly to determine the need for – Frequent vs. rare tumors adjuvant therapy). z Other independent variables evaluated with grading are tumor size and depth, margins of resection, and clinical situation. MFH High-grade uterine leiomyosarcoma

Well-differentiated liposarcoma GRADING GRADING z Any diagnostic z Grading is an element of any current staging system. entity has a range of malignancy. z Correct grading requires correct histologic typing of z The grade within the sarcoma, as the overall range demonstrated by the depends on the inclusion of “histologic histologic features type” as a grading (cellularity, variable. pleomorphism, mitotic activity, necrosis, etc.)

Pleomorphic liposarcoma

GRADING GRADINGGRADING-- ST SARCOMAS z Grading applies best to GRADING SYSTEM SOFT TISSUE SARCOMAS (FFCC) excision specimen Score (1-3) TUMOR DIFFERENTIATION because biopsies may be well diff 1 defined histogenetic types 2 non-representative of poorly diff & undef histogenesis 3 the correct grade. MITOTIC COUNT z Preoperative treatments, 0-9/10HPF 1 10-19/HPF 2 such as radiation, >20 HPF 3

chemotherapy, or TUMOR NECROSIS embolization, can make none 0 <50% 1 grading of the resection >50% 2 specimen inapplicable. HISTOLOGIC GRADE Sum of scores 1 2 or 3 2 4 or 5 3 6, 7 or 8

12 GRADINGGRADING--STST SARCOMAS DIFFERENTIATION SCORE 1 Well differentiated sarcoma (fibro-, lipo-, leiomyo-, chondro-) STAGING OF ST SARCOMAS Well differentiated MPNST (neurofibroma with malignant transformation) DIFFERENTIATION SCORE 2 Conventional fibrosarcoma, leiomyosarcoma, angiosarcoma Conventional MPNST z Staging gives powerful information about Myxoid sarcomas (MFH, liposarcoma, chondrosarcoma) survival. Storiform-pleomorphic MFH DIFFERENTIATION SCORE 3 Sarcomas of undefined histog. (ASPS, SS,ES,CCS, undiff. Sarc.,malig. rhabdoid tumor) 5-yr survival Ewing family of tumors Pleomorphic sarcomas (lipo-, leio-) Stage % Round cell and pleomorphic liposarcoma I86 Rhabdomyosarcoma (except botryoid and spindle cell) II 72 Poorly differentiated angiosarcoma III 52 Triton tumor, epithelioid MPNST IV 10-20 Extraskeletal mesenchymal CS, and osteosarcoma Giant-cell and inflammatory MFH NEJM 2005; 353: 701-711

STAGING z The stage is an estimate of the extent or BONE SARCOMAS dissemination of a tumor (and in the current systems includes tumor grade). z z Staging is important for planning of Like ST sarcomas, bone sarcomas need treatment and prognostication. to be graded (grading is an important z Clinical data and imaging studies are element of the staggging and determines if part of staging process the tumor is stage I or II). z (Visceral sarcomas excluded) z The TNM system for bone sarcomas follows a 2 tier grading system: low- and high-grade.

STAGING (G(G--TNM)TNM)-- ST SARCOMAS

STAGE GRADE PRIMARY TUMOR LYMPH NODES METASTASIS BONE TUMORS ABSENT/PRE I - IV LOW OR HIGH T1 (<5 CM) OR T2 (>5 CM) NEG/POS SENT Primary tumor (T) TX Primary tumor cannot be assessed

z The staging of T0 No evidence of primary tumor IA LOW T1a or T1b NEGATIVE ABSENT bone T1 Tumor less or equal to 8 cm in greatest dimension IB LOW T2a or T2b NEGATIVE ABSENT sarcomas T2 Tumor equal or more than 8 cm in greatest dimension T3 Discontinuous tumors in the primary bone site follows the Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed IIA HIGH T1a or T1b NEGATIVE ABSENT NO No regional lymph node metastasis IIB HIGH T2a NEGATIVE ABSENT TNM system. N1 Regional lymph node metastasis Distant metastases (M) MX Distant metastasis cannot be assessed III HIGH T2b NEGATIVE ABSENT M0 No distant metastasis M1 Distant metastasis: M1a: lung IV ANY ANY POSITIVE ABSENT M1b: other sites POSITIVE OR ANY ANY NEGATIVE PRESENT AJCC Cancer Staging Manual, 6th Edition, Springer, New York “a” superficial tumors of trunk and extremities (above fascia) “b” deep tumors of trunk and extremities or intra-abdominal, intra-thoracic or retro-peritoneal

13 PROGNOSIS BONE TUMORS

Stage IA T1 N0, NX M0 Low grade Stage IB T2 N0, NX M0 Low grade

Stage IIA T1 N0, NX M0 High grade Stage IIB T2 N0, NX M0 High grade Stage III T3 N0, NX M0 Any grade Stage IVA Any T N0, NX M1a Any grade Stage IVB Any T N1 Any M Any grade Any T Any N M1b Any grade

AJCC Cancer Staging Manual, 6th Edition, Springer, New York Kattan MW et al. J Clin Oncol 2002; 20: 791-796

BONE TUMORS TREATMENT z Stage I: low grade z Surgery and pre- or intra-compartmental postoperative external beam (risk of metastasis radiation treatment in the primary local treatment for <25%) most patients with localized z Stage II: high-grade disease. extra-compartmental z Adjuvant chemotherapy is usually reserved for patient (risk of metastasis with high-grade sarcomas. >25%) z Patients with metastatic z Stage III: any grade, disease considered for discontinuous tumor in chemotherapy and selected 18M with OS of pelvis. CT scans show two cases may undergo the primary bone site pulmonary metastatic lesions, a a smaller one in metastasectomy. the right upper lobe and b a larger one in the z Stage IV: any grade, lower lobe with internal calcification. 99mTc scintigram shows increased uptake in the right Girl with OS distal femur, dx 2007 (@ age 10) , resection 2008, metastatic lung corresponding to the metastatic lesion (c) s/p chemo with 100% response, doing fine, no mets to date

PARAMETERS TO BE INCLUDED IN TREATMENT REPORT OF A SARCOMA z Currently z FINAL REPORT z ADDENDUM REPORT(S) approximately 90% of – 1. Tumor site, type of – 1. Immunohistochemistry patients with localized excision – 2. Electron microscopy extremity sarcomas – 2. Depth of the tumor – 3. Cytogenetics undergo limb-sparing – 3. Tumor type and surgery. variant – 4. Grade (if possible) – 5. Tumor size – 6. Status of margins & L.N. – 7. Percent of necrosis

– 8. Vascular invasion, if 31F with OS, present 9 years s/p surgery

14 WINTERSUN THAT’S ALL FOLKS!

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