Bone and Soft Tissue Neoplasms

Jesse K McKenney, MDAssistant Professor

Department of Pathology

Bone and Soft Tissue Neoplasms

• Essential Concepts in Lecture• Background and Definitions in syllabus

and Robbins

• PRIMARY bone tumors are RARE– Metastases to bone are common

• Soft tissue tumors are very rare

Cancer Death Rates*, for Women, US,1930-2002

*Age-adjusted to the 2000 US standard population.Source: US Mortality Public Use Data Tapes 1960-2002, US Mortality Volumes 1930-1959,National Center for Health Statistics, Centers for Disease Control and Prevention, 2005.

0

20

40

60

80

10019

30

1935

1940

1945

1950

1955

1960

1965

1970

1975

1980

1985

1990

1995

2000

Lung

Colon & rectum

Uterus

Stomach

Breast

Ovary

Pancreas

Rate Per 100,000

0.1Bone

Cancer Incidence Rates* in Children 0-14 Years, by Site, 1998-2002

*Per 100,000, age-adjusted to the 2000 US standard population.ONS = Other nervous systemSource: Surveillance, Epidemiology, and End Results Program, 1975-2002, Division of Cancer Control and Population Sciences, National Cancer Institute, 2005.

Site Male Female Total

All sites 15.6 14.3 15.0

Leukemia 4.9 4.2 4.6

Acute Lymphocytic 3.9 3.4 3.6

Brain/ONS 3.6 3.3 3.5

Soft tissue 1.1 0.9 1.0

Non-Hodgkin lymphoma 1.2 0.6 1.0

Kidney and renal pelvis 0.8 1.0 0.9

Bone and Joint 0.6 0.6 0.6

Hodgkin lymphoma 0.6 0.5 0.5

Soft Tissue/ Bone Neoplasms

• Reality Check– Many experienced pathologists are

uncomfortable diagnosing the tumors in this chapter

• Histologic differences are more subtle• Tumors are rare with hundreds of subtypes

– most have little diagnostic experience with them

• However– Many mistakes are made in the treatment of

these tumors because physicians are not aware of basic principles

Basic Principles

• Prognosis• Treatment• Diagnosis

– Clinical• Age, anatomic site, x-ray, syndrome?

– Microscope • Few basic principles for this course

Clinical Course/Prognosis

• Low-grade Sarcoma– Local recurrence– Progression to high-grade

• High-grade Sarcoma– Local recurrence– Hematogenous metastasis

• Lung

Prognosis: Location Dependent

• Sarcomas arising in a superficial location (dermis and subcutis) have a much better prognosis than deep seated sarcomas– Larger = worse prognosis

• Deep extremity sarcomas (grade-for-grade) behave better than retroperitoneal sarcomas (resectability)

General Treatment Principles

• Low-grade sarcoma– Surgical excision with wide margins

• High-grade sarcoma– Option of neoadjuvant chemo/radiation– Surgical excision with wide margins– Adjuvant chemo/radiation

Adjuvant Chemotherapy for Completely-Resected Primary

Osteosarcoma

• Metastatic sarcomas are essentially incurable (rare exceptions)

• Local control best accomplished by surgery (localized radiation for unresectable sites)

• Chemotherapy (high grade) affects systemic micrometastases and improves survival

Soft Tissue/ Bone Neoplasms

Diagnosis of Bone and Soft Tissue Tumors

• Must establish:– Histologic type– Extent of spread (stage)

• Accuracy depends on synthesis of:– Clinical findings– Radiologic findings– Pathologic findings

BONE

Presenting Signs and Symptoms

• Pain• Mass• Incidental finding on X-ray• Loss of Function

– pathologic fracture

• Prompt and accurate diagnosis improves chances of complete resection

Radiologic Findings

• Localization– part of bone

• Margin of tumor– sharp (sclerotic)– fuzzy (infiltrative)

Pathologic Findings

• Evidence of differentiation– Matrix formation

• Cartilagenous• Bone (osteoid)• None

– Fibrous

– Growth pattern– Cytologic features

Normal Anatomy

epiphysis

metaphysisdiaphysis

physis

childhood adult

cortex

medullary space

physeal scar

Anatomical Site

Tumor Border with Adjacent Bone

Patient 1 Patient 2

High Grade Osteosarcoma

• Age (2 peaks)– 75% < 20 years of age– Elderly (Paget dx)

• Site– Usually in metaphysis of long

bones (<20 yrs)• Femur• Tibia• Humerus

– In older patients, flat bones almost as common

High-grade Osteosarcoma

High Grade Osteosarcoma

High Grade Osteosarcoma

Tumor Matrix

Conventional Chondrosarcoma

• Age – >40 years of age (usually older)

• Site– Usually central skeleton

• Pelvis• Ribs• Shoulder

– Extremity much rarer

Chondrosarcoma

Chondrosarcoma

Chondrosarcoma

42 year-old man bumped kneeEnchondroma

Enchondroma Chondrosarcoma

Giant Cell Tumor of Bone

• Age– Usually 20-40 years (Skeletally mature)

• Site– Long bones (Epiphysis/Metaphysis)

• Distal femur• Proximal tibia

• Prognosis• Local recurrence rate 40-60%

Giant Cell Tumor of Bone

Giant Cell Tumor of Bone

Epiphyseal TumorsGiant Cell Tumor

of BoneChondroblastoma

Skeletally Mature?

Metastatic Carcinoma

• Most common skeletal malignancy in adults

• X-ray– Lytic – Blastic– Mixed

• In older patients, destructive bone lesions are mets until proven otherwise

Metastases

• Carcinoma– Prostate adenocarcinoma– Renal cell carcinoma– Breast adenocarcinoma

Radioactive bone scan Biopsy

Bone Tumor Syndromes

• Osteomas + Deep Fibromatosis + Adenomatous Polyposis = GARDNER SYNDROME

Bone Neoplasms

• Goals– Clinical/pathologic setting

• Child vs Adult• Anatomic Site (X-RAY)• Differential diagnosis

– Morphology• Matrix?

– Behavior/treatment

SOFT TISSUE

Soft Tissue Neoplasms

• Completely Benign– Lipoma

• Locally recurring– Fibromatosis

• Locally recurring, potential for grade progression (Low grade)– Atypical lipomatous tumor/well differentiated

liposarcoma• High metastatic potential (High grade)

– Rhabdomyosarcoma

Soft Tissue Neoplasms

• Fat• Muscle

– Smooth – Skeletal

• Fibroblast• Uncertain histogenesis

Lipoma

• Age: – Usually adults– (Most common soft tissue tumor)

• Site: – Usually superficial (any site)– Occasionally deep to superficial fascia

(intramuscular)• Prognosis

– Recurrence is very rare

Lipoma

Intramuscular Lipoma

Atypical Lipomatous Tumor/Well Differentiated Liposarcoma

• Age:– Generally a neoplasm of adults

(>40 years of age typical)• Site:

– Usually deep soft tissue (any site)

Most common adult sarcoma!

Fibrous septa and atypical stromal cells“Smudge cell” (Atypical stromal cell)

Atypical Lipomatous Tumor/ WDL

Atypical Lipomatous Tumor/ WDL

Lipoblast

De-differentiated Liposarcoma(Grade Progression)

• De-differentiation– Progression in grade to a high-grade

sarcoma• Undifferentiated pleomorphic sarcoma

Atypical Lipomatous Tumor/ WDL High-grade Sarcoma

Dedifferentiated Liposarcoma

Dedifferentiated Liposarcoma

ALT

High-grade

Sarcoma

ALT

High-grade sarcoma

Recurrence

Atypical Lipomatous Tumor/ Well Differentiated Liposarcoma

• Prognosis: – Site dependent

• Extremity– lower recurrence rate– very low-risk of de-differentiation

• Retroperitoneum– indolent course with multiple recurrences– higher risk of de-differentiation

– With de-differentiation• Metastatic potential

Malignant Fibrous Histiocytoma (MFH)

• Age– Adult

• Site– Deep soft tissue

• Prognosis– Aggressive recurrence– Metastasis

Malignant Fibrous Histiocytoma (MFH)

• A heterogeneous group of high grade pleomorphic, undifferentiated sarcomas– Ugly sarcoma without differentiation = MFH

Malignant Fibrous Histiocytoma

Nulcear pleomorphism, hyperchromasia

Deep Fibromatosis (Desmoid)

• Age:– All ages

• Site:– Extremities– Trunk– Abdominal wall– Mesentery

Deep Fibromatosis (Desmoid)

• Prognosis:– High rate of local recurrence– Does NOT metastasize– Can cause death due to infiltrative

growth• If in anatomically delicate area

(carotids)• Syndrome:

– Gardner syndrome

Fibromatosis

Fibromatosis

Soft Tissue Tumor Cytogenetics

• EWS Translocations– Ewing/ PNET– Clear cell sarcoma– Extraskeletal Myxoid Chondrosarcoma– Desmoplastic Small Round Cell Tumor

• SYT-SSX Fusion Gene– Synovial Sarcoma

• PAX-FKHR Fusion Gene– Alveolar Rhabdomyosarcoma

“The Big Picture” Bone and Soft Tissue Tumors

• Prognosis• Treatment• Diagnosis

– Clinical• Age, anatomic site, x-ray, syndrome?

– Microscope • Few basic principles