Bone tumors IIMODERATOR- DR. S. S. THAKUR

GIANT CELL TUMOUR

• Epiphyseal mesenchymal neoplasm of low malignant potential composed of stromal cells and giant cells .

• Age/Sex: >20 yr/ F>M.• Bone involved: lower end of femur & radius

and upper end of tibia.• Location: Epiphysis

X -Ray

Typical radiograph of giant cell tumor of distal end of femur involving epiphysis and metaphyseal area.

Gross

A, Gross appearance of giant cell tumor of lower end of femur. The lesion is characteristically peripheral, expansile, well circumscribed, and hemorrhagic. B, Giant cell tumor of lower end of femur. The lesion, which has a very hemorrhagic quality, has destroyed the cortex and extended into the adjacent soft tissues

Microscopic

Giant cell tumor.-The nuclei of the giant cells are similar to those of the mononuclear cells

Tissue section Cytology

Acid phosphatase

IHC

• lysozyme • α-1-antitrypsin • α-1-antichymotrypsin

Differential diagnosis• Metaphyseal fibrous defect • Nonossifying fibroma • Chondromyxoid fibroma • Chondroblastoma • Langerhans’ cell histiocytosis • Solitary bone cyst • Osteitis fibrosa cystica of hyperparathyroidism • Aneurysmal bone cyst • Osteoid osteoma • Osteoblastoma • osteosarcoma• Giant cell tumor of tendon sheath

Malignant GCT

• Clinical, topographic & general microscopic features of GCT but exhibits clear cut evidence of malignancy in the mononuclear stromal component.

MARROW TUMORS1- EWING’S SARCOMA/PRIMITIVE NEUROECTODERMAL

TUMOUR

• Malignant undifferentiated sarcoma of bone in children. Closely related to primitive neuroectodermal tumor of soft tissues.

• Age/Sex: 5-20 yrs/M>F.• Bones involved: Long bones, pelvis, ribs,

vertebrae.• Location: Medullary cavity.• Askin tm

X-Ray

.

Gross

Gross appearance of Ewing sarcoma. It has a typical ill-defined quality, with extensive involvement of medulla and cortex associated with elevation of periosteum

Microscopic

Diffuse pattern of growth and monotonous cytologic appearance in Ewing sarcoma/PNET.

PAS stain

CD 99

Differential Diagnosis• Malignant Lymphoma and Related Lesions.• Desmoplastic small cell tumour.• Embryonal/alveolar rhabdomyosarcoma.• Neuroblastoma• Medulloblastoma• Retinoblastoma• Wilms tumor• Osteosarcoma• Metastatic Tumors [Bone]

IHC

• LMWK• Neuron specific enolase• Leu 7

Prognosis • Osseous versus extraosseous location• Direct soft tissue extension • Metastasis• Surgical margins• Therapy-induced necrosis • Microscopic features • Neural differentiation • p53• c-myc amplification.

Malignant lymphoma

• Primary lymphomas of bone occur mostly in adults and are of large B-cell type. Any systemic lymphoma or leukemia can involve the skeletal system secondarily.

Large Cell Lymphoma• Age/Sex:>30 yrs/ M:F=1:1• Location: diaphysis or metaphysis • Bone involved: long bone or vertebrae • Gross :pinkish gray and granular tumour

producing patchy cortical and medullary destruction with minimal to moderate periosteal reaction

Malignant lymphoma involving lower end of femur associated with bone destruction and bone production

Microscopic IHCCD 45 +Bcl 2

Malignant lymphoma of bone. The tumor is of large cell type and is associated with some fibrosis

VASCULAR TMHemangiomas

• Benign neoplasm of blood vessels.• Bones involved: vertebrae, skull and jaw

bones.• Multiple hemangiomas are mainly seen in

children and young adults.• Gross

– Often current jelly appearance

Microscoipc

Differential Diagnosis• Angiosarcoma [Bone] • Epithelioid Hemangioendothelioma.• Aneurysmal Bone Cyst

Epithelioid hemangioendothelioma

• Most common epithelioid vascular neoplasm of the bone.

• Borderline type of vascular neoplasm.• Site: unique vascular tumour occuring around

medium and large sized veins in the soft tissue of adults.

X-Ray

Multicentric hemangioendothelioma involving multiple bones of the foot

Microscopic

Factor VIII

Angiosarcoma

• Malignant vascular neoplasm.• Age/sex: older adults/M:F=1:1.• Location: anywhere in body.

Microscopic

Angiosarcoma of bone. Anastomosing vascular channels lined by highly atypical endothelial cells are seen

Factor VIII

Hemangiopericytoma

• It is extremely uncommon to find hemangiopericytoma as a primary bone tumor

• Can present as primary bone lesion.

• Age – 2nd-9th decade Sex- M:F- 1:1

• Most common site- pelvis

Fibrous Tumours

• Benign: Fibrous Cortical Defect, Non-Ossifying Fibroma.

• Benign Aggressive:, Fibrous Dysplasia.

• Malignant: Malignant Fibrous Histiocytoma of bone, Fibrosarcoma.

Fibrous cortical defect & Non ossifying fibroma

• The name fibrous cortical defect is used when the lesion is confined to the cortex; however if becomes large enough to extend into adjacent medullary cavity than the term non-ossifying fibroma is used.

• Benign lesion of bone composed of spindle-shaped fibroblasts, arranged in a storiform pattern, with a variable admixture of multinucleated osteoclast-like giant cells. Foamy cells (xanthoma), chronic inflammatory cells and hemosiderin may be present

Mainly involve – long bones distal femur, proximal and distal tibia.

• Lesion- Eccentric, well circumscribed and have sclerotic borders. The overlying cortex is thinned and may be completely eroded.

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Eccentric, lytic lesions centered within the metaphyseal cortex and adjacent medullary cavity of long tubular bones. 

- Well demarcated with sclerotic margins .

Microscopic

• : 

- Stroma of spindle-shaped fibroblasts, arranged in a whorled, storiform pattern,among which variable number of small, multinucleated, osteclast-type giant cells are scattered. 

• Foam (xanthoma) cells, with small, dark nuclei are frequently, but not always found interpersed among the stromal cells individually, or in small clusters.  Scattered inflammatory cells, mainly lymphocytes.     

Fibrous dysplasia

• Benign tumor occuring due to local developmental arrest.

• All the components of normal bone present but do not differentiate into their mature structures.

• Three clinical patterns- monostotic, polyostotic with, & without endocrine dysfunction.

• Somatic gain of function mutation of GNAS gene.

Monostotic- 70 % • M ~ F , early

adolescence• Femur , tibia, ribs,

jawbones & humerus.• Causes marked

enlargement & destruction of bones.

• Doesn’t evolve into poly form

Polyostotic- 27%• Slightly earlier age• Femur , mandible ,

vertebrae• Craniofacial

involvement common

• McCune Albright syndrome- Polyostotic FD Skin pigmentation endocrinopathies

• Microscopically, narrow, curved, and misshaped bone trabeculae, often having a characteristic fishhook configuration, are interspersed with fibrous tissue of variable cellularity[.

• Rows of cuboidal appositional osteoblasts do not appear on the surface of the trabeculae.

Malignant fibrous histiocytoma

• Age: 40 years• Bones involved: long bones & jaw.• Location: medullary portion of metaphysis, • These tumors arise in bone infarcts (often secondary

to sickle cell disease)• following irradiation in Paget disease,• Or as expression of ‘dedifferentiation’ or anaplastic

transformation in chondrosarcoma, chordoma, or giant cell tumor

• X-Ray: osteolytic with a soap bubble appearance. Gross: large , haemorrhagic, tan white masses

destroying the underlying bone.Malignant fibrous histiocytoma is composed of a

spindle cell proliferation arranged in a storiform pattern and giant cells and even malignant giant cells are almost always seen.

By definition, the presence of chondroid or osteoid matrix rules out a diagnosis of MFH

Microscopic

MISCELLANEOUS TMChordoma

• Low grade mesenchymal malignancy thought to arise from notochord remnants .

• Age:50-60 yrs M> F• Bone involved: sacrococcygeal area> spheno-occipital

area> cervicothoracolumbar spine.• The sacrococcygeal tumors are more common in the fifth

and sixth decades of life.• Whereas many of the spheno-occipital neoplasms occur in

children and adolescents.• Chordomas commonly show hypodiploid karyotype,

frequently with loss of chromosomes 3 , 4, 10, and 13

X-Ray

Osteolytic destruction of sacrum by chordoma.

Gross

Grossly, chordoma is gelatinous and soft and contains areas of hemorrhage

• Microscopically, it closely resembles normal notochord tissue in its different stages of development.

• It grows in cell cords and lobules separated by a variable but usually extensive amount of mucoid intercellular tissue and by fibrous septa .

• Some of the tumor cells (known as physaliferous) are extremely large, with vacuolated cytoplasm and prominent vesicular nucleus; some of the cytoplasmic vacuoles contain glycogen, presumably in the process of being broken down.

• In many of the tumor cells, vacuolization of the cytoplasm gives rise to a bubbly appearance termed physaliphorous

• . Areas of cartilage and bone may be presen

Microscopic

Chordoma with the diagnostic features of lobulation, myxoid matrix, and vacuolated cells in a cord arrangement

Keratin

Adamantinoma of long bones

• Low grade mesenchymal malignancy of long bones with focal epithelial differentiation .

• Bones involved: characteristically involves the tibia but has been reported in other long bones.

• Location: Diaphysis or metaphysis.

X-Ray

• Microscopically- several patterns of growth have been described.

• The most common consists of solid nests of basaloid cells with palisading at the periphery and sometimes a stellate configuration in the center.

• Less frequent forms have been described as spindle, squamoid, and tubular

Microscopic

Keratin

The keratins expressed by adamantinoma are mainly 14 and 19, In contrast to other bone and soft tissue tumors with epithelial phenotypes – such as synovial sarcoma, chordoma, and epithelioid sarcoma – it lacks immunoreactivity for keratins 8 and 18.

TUMOR LIKE LESIONSSolitary bone cyst

• < 20 yrs• M > F• Long bones ( femur,tibia

& humerus ), Metaphysis

A- A large lesion located in the upper metaphysis of the humerus. B- A triangular lesion located in the upper end of the tibia. There has been secondary hemorrhage.

• The cyst contains a clear or yellow fluid and The fluid may be hemorrhagic if a previous fracture has occurred.

• Microscopically- well-vascularized connective tissue, hemosiderin (often within macrophages), and cholesterol clefts are frequent. The bone surrounding the cyst may have a dense quality, with irregular cement lines

Aneurysmal bone cyst

• Benign , rapidly growing expansile tumor• 10-20 yrs• M< F• Vertebrae & flat bones• Blue bone

 .

Usually eccentric, expansile lesion with well defined margins.

- Most lesions are completely lytic and often contain   thin shell of reactive bone at the periphery.

-  CT and MRI may demonstrate

internal septa and characteristic fluid-fluid level

Aneurysmal bone cyst of lower end of ulna. The large blood-filled cavities expand the metaphysis

Microscopic appearance, showing two cavities lined by osteoclast-like multinucleated giant cells. The intervening stroma is cellular.

Langerhans cell Histiocytosis

• Histiocytosis X, eosinophilic granuloma• Infiltration by a cell of immune system known

as Langerhans cell.• Young adults• Cranial vault, jaw, humerus, ribs• Birbecks granule on electron microscopy• 3 types- solitary bone, multiple bone +/- skin,

multiple organ

• Langerhans cells have a characteristic morphologic appearance . Their nuclei often are lobulated or indented, sometimes with a longitudinal groove; their cytoplasm is, for the most part, distinctly acidophilic.

• A specific intracytoplasmic organelle, known as Langerhans or Birbeck granule, is regularly present on electron microscopic examination.

• Diagnostic immunohistochemical markers include S100 protein, CD1a and langerin (CD207

A sharply circumscribed, dark brown lesion is seenOsteolytic lesion of skull in a 25-year-old woman. Radiographically, the lesion was thought to be metastatic carcinoma but proved to be a solitary lesion of Langerhans cell histiocytosis

Langerhans cell histiocytosis. Polymorphic appearance resulting from an admixture of Langerhans cells, nonspecific histiocytes, lymphocytes, and eosinophils. There is a mild atypia in the Langerhans cells that can simulate a malignant process

Myositis ossificans

• It is reactive condition that is sometimes mistaken microscopically for osteosarcoma.

• The term is inaccurate because the muscle may not be involved, and inflammation is virtually absent.

• The most common locations are the flexor muscles of the upper arm .

• Radiographic studies show periosteal reaction and faint soft tissue calcification within 3–6 weeks of the injury;

• These are gradually replaced by mature heterotopic bone by 10–12 weeks

Well-defined myositis ossificans , illustrating bone formation in periphery

• Microscopically- there is a highly cellular stroma associated with new bone and, less commonly, cartilage formation.

• In an early lesion, the centrally placed areas may be very difficult to distinguish from osteosarcoma because of their extreme cellularity. As the process evolves, osteoid appears in an orderly pattern at the periphery of this mass and subsequently matures into well-developed bone. Several microscopic subtypes have been described, which correspond to different stages of the process.

• The most important diagnostic feature is provided by the maturation pattern (‘zonal phenomenon’), characterized by a central cellular area, an intermediate zone of osteoid formation, and a peripheral shell of highly organized bone

Metastatic disease of bone

• Most common form of skeletal malignancy.• The pathway of spread include: *direct extension *lymphatic or hematogenous *intraspinal seeding • >75% of skeletal metastasis originate from

prostate ,breast ,kidney and lung.

• Most common bones involved are axial skeleton, proximal femur and humerus.

• Metastatic bone lesions are usually osteolytic but may be osteoblastic or mixed.

• Osteoblastic metastasis

*Prostatic carcinoma *Carcinoid tumour *Breast tumour (less

commonly)

• Osteolytic metastasis: *Kidney *Lung *GIT *Malignant melanoma *Thyroid

TUMOUR LOCATION AGE SALIENT PATHOLOGIC FINDING

FIBROUS DYSPLASIA

RIBS,JAW,LBS- MEDULLARY

10-30 IRREGULAR WOVEN BONE WITHIN FIBROBLASTIC STROMA

NONOSSIYING FIBROMA

LBS 5-15 BLAND SPINDLE CELLS IN STORIFORM PATTERN+HISTIOCYTES+GIANT CELLS

BENIGN FIBROUS HISTIOCYTOMA

LBS ,PELVIS >20 IDENTICAL TO NONOSSIFYING FIBROMA BUT VARIABLE

LANGERHANS CELL HISTIOCYTOSIS

SKULL.JAW,LBS

5-15 MIXED INFLAMMATORY CELLS AND EOSINOPHILS.S100/CD1a-POSITIVE CELLS WITH GROOVED /MULTILOBATED NUCLEI

TUMOUR LOCATION AGE SALIENT PATHOLOGIC FINDING

GIANT CELL TUMOR

EPIPHYSIS OF LBS

20-45 EVENLY PLACED GIANT CELLS AMONG MONONUCLEAR CELLS WITH IDENTICAL NUCLEI.

ANEURYSMAL BONE CYST

VERTEBRAELBS

10-20 BLOOD FILLED SPACES SEPERATED BY FIBROUS SEPTAE, GIANT CELLS

SIMPLE BONE CYST

METAPHYSIS OF LBS

10-20 FLUID FILLED CYSTS LINED BY CONNECTIVE TISSUE

TUMOUR LOCATION AGE SALIENT PATHOLOGIC FINDING

ADAMANTINOMA CORTEX OF TIBIA

25-35 EPITHELIAL CELLS+FIBROBLAST+WOVEN OR LAMELLAR BONE

EWING SARCOMA DIAPHYSIS OF LBS

5-20 SMALL ROUND BLUE CELLS+ROSETTES ,t (11,22)

CHORDOMA BASE OF SKULL

>30 LOBULES OR VACUOLATED CELLS EMBEDDED IN MYXOID MATRIX.

Thank You

Chickenwire PatternA descriptor for a delicate plexiform or reticulated pattern imposed on that of another density or appearanceDermatology Livedo vasculitis pattern A pattern of cyanotic discolouration of the skin with or without an underlying vascular pathology, which may be triggered by the cold and associated with cold cryoglobulinaemiaImaging A descriptive term for a pattern of intralesional calcification which is regarded as pathognomonic for chondroblastoma, a paediatric tumourPathology—liver A pattern of fibrosis associated with alcoholic hepatitis. Cf Bridging fibrosisPathology—soft tissueThe arrangement of capillaries in myxoid liposarcoma, which may also be seen in low-grade fibromyxoid sarcoma, clear cell sarcoma of the kidney, in which hyalinised cell cords are superimposed on a sclerotic background

Storiform PatternA pattern seen by low-power light microscopy, which is characterised by loosely-arranged whorls of elongated, spindled fibroblast-like cells. The highly nonspecific storiform pattern is often seen in fibrohistiocytic lesions. It may be benign—e.g., dermatofibroma, giant cell tumour of tendon sheath—of low malignant potential—e.g., atypical fibroxanthoma, dermatofibrosarcoma protuberans—or malignant—e,g, fibrosarcoma; it may also be seen in non-histiocytic lesions—e.g., nodular fascitis, leiomyoma, leiomyosarcoma, Schwann cell tumours, spindle cell carcinoma