bone tumors listing

from:http://www.bonetumor.org/page174.html

Adamantinoma of long bones

Aneurysmal bone cyst

Angiosarcoma – high grade

Angiosarcoma – low grade

Bizarre parosteal osteochondromatous proliferation

Bone lesions of Gaucher’s Disease

Brown Tumor of Hyperparathyroidism

Chondromyxoid Fibroma

Clear Cell Chondrosarcoma

Conventional Intramedullary Osteosarcoma

Degenerative joint disease

Desmoplastic Fibroma

Eosinophilic Granuloma

Epithelioid hemangioendothelioma

Epithelioid hemangioma

Ewing’s sarcoma of bone

Extraosseous osteosarcoma

Florid reactive periostitis

General Discussion of Metastatic Bone Cancer

Giant cell reparative granuloma

Granulocytic sarcoma in bone

Hemophilic pseudotumor

High-Grade Surface Osteosarcoma

Hodgkin lymphoma of bone

Intra-articular synovial sarcoma

Intracortical Osteosarcoma

Intraosseous ganglion

Intraosseous Well-differentiated Osteosarcoma

Juxtacortical Chondroma

Juxtacortical Chondrosarcoma

Localized nodular synovitis

Malignant fibrous hystiocytoma

Malignant Mesenchymoma of bone

Mesenchymal Chondrosarcoma

Metastatic Breast Cancer

Metastatic Kidney Cancer

Metastatic Lung Cancer

Metastatic Prostate Cancer

Metastatic Thyroid Cancer

Multifocal Osteosarcoma

Neurofibroma of bone

Non Hodgkin lymphoma

Nonossifying fibroma (fibrous cortical defect)

Osteochondromatosis (HMOCE)

Osteofibrous Dysplasia

Parosteal Osteosarcoma

Pathological Fracture Risk assessment

Periosteal Chondroma

Periosteal Osteosarcoma

Pigmented villonodular synovitis

Post - Paget’s Sarcoma

Primitive neuroectodermal tumor of bone

Sinus histiocytosis with Massive Lymphadenopathy

Skeletal Angiomatosis

Small Cell Osteosarcoma

Solitary myeloma (plasmacytoma)

Stress fractures and avulsion fractures

Synovial chondromatosis

Synovial chondrosarcoma

Systemic mastocytosis

Telangectatic Osteosarcoma

"Tug" lesions – metaphyseal fibrous defect

Unicameral bone cyst

bone tumors by type

Tumors that form bone

Conventional Intramedullary Osteosarcoma

Extraosseous osteosarcoma

Multifocal Osteosarcoma

Telangectatic Osteosarcoma

Small Cell Osteosarcoma

Intraosseous Well-differentiated Osteosarcoma

Intracortical Osteosarcoma

Periosteal Osteosarcoma

Parosteal Osteosarcoma

High-Grade Surface Osteosarcoma

Tumors that form cartilage

Osteochondromatosis (HMOCE)

Periosteal Chondroma

Juxtacortical Chondroma

Enchondromatosis (Ollier’s Disease)

Chondromyxoid Fibroma

Dedifferentiated chondrosarcoma

Clear Cell Chondrosarcoma

Mesenchymal Chondrosarcoma

Juxtacortical Chondrosarcoma

Tumors that form fibrous tissue

Nonossifying fibroma (fibrous cortical defect)

Osteofibrous Dysplasia

Desmoplastic Fibroma

Extragnathic Fibromyxoma

Benign Fibrous Histiocytoma

Malignant fibrous hystiocytoma

Tumor Mimics – Non-neoplastic bone lesions that can look and act like bone tumors

Aneurysmal bone cyst

Degenerative joint disease

Stress fractures and avulsion fractures

"Tug" lesions – metaphyseal fibrous defect

Nora's Lesion - bizarre parosteal proliferation

Intraosseous ganglion

Florid reactive periostitis

Hemophilic pseudotumor

Amyloid tumor of bone

Synovial lesions

Synovial chondromatosis

Synovial chondrosarcoma

Pigmented villonodular synovitis

Localized nodular synovitis

Intra-articular synovial sarcoma

Lesions of Marrow Elements

Eosinophilic Granuloma

Solitary myeloma (plasmacytoma)

Non Hodgkin lymphoma

Hodgkin lymphoma of bone

Granulocytic Sarcoma in bone

Systemic mastocytosis

Sinus histiocytosis with Massive Lymphadenopathy

Giant cell lesions

Giant cell reparative granuloma

Tumors that form vascular tissue

Skeletal lymphangiomatosis

Skeletal Angiomatosis

Epithelioid hemangioendothelioma

Epithelioid hemangioma

Angiosarcoma – low grade

Angiosarcoma – high grade

Small cell sarcomas

Ewing’s sarcoma of bone

Primitive neuroectodermal tumor of bone

Miscellaneous Bone Tumors

Adamantinoma of long bones

Conventional Chordoma

Dedifferentiated chordoma

Neurofibroma of bone

Post - Paget’s Sarcoma

Malignant Mesenchymoma of bone

Bone Lesions arising from Metabolic Disease

Brown Tumor of Hyperparathyroidism

Bone lesions of Gaucher’s Disease

Disappearing bone disease

Metastatic tumors involving bone

Metastatic Breast Cancer

Metastatic Lung Cancer

Metastatic Kidney Cancer

Metastatic Prostate Cancer

Metastatic Thyroid Cancer

Pathological Fracture

LOCATION/SITE	TYPICAL PATHOLOGY
Epiphyseal	Chondroblastoma, chondrosarcoma, giant cell tumour, infection
Metaphyseal	Any lesion
Diaphyseal	Osteoblastoma, Ewing’s eosinophilic granuloma, lymphoma, adamantinoma, fibrous dysplasia
Pelvis	Mets, myeloma, Ewing’s, chondrosarcoma, Paget’s Disease.
Proximal humerus	Chondroid lesions.
Knee	Osteosarcoma, adamantinoma, chondromyxoid fibroma
Ribs	Mets, myeloma, Ewing’s chondrosarcoma, fibrous dysplasia
Spine (Vertebral body)	Mets, myeloma, eosinophilic granuloma, chondroma, Paget’s, haemangioma
Spine (Posterior elements)	Aneurysmal bone cyst, osteoid osteoma, osteoblastoma
Periosteal	Myosotis, osteosarcoma, chondrosarcoma, chondroma
Multiple lesions	Mets, myeloma, haemangioma, fibrous dysplasia, osteochondromas, enchondromas, histiocytosis X

Metastatic Disease

I. Introduction -- Metastatic disease to the skeleton is an extremely common problem in the end-stage of most carcinomas. In multiple studies, it has been shown that up to 70-80% of patients that died of cancer will have metastatic skeletal disease at autopsy. The most common locations are:

Distal metastases to the hands and feet are relatively uncommon.

In women the most common carcinomas with metastatic disease to bone are:

In men the most common carcinomas with metastatic disease to bone is:

The number of patients showing up with skeletal metastases is increasing as the longevity of patients with carcinoma increases. Since both breast cancer and prostate cancer are hormonally responsive, the patients tend to live much longer. This may be why bone metastases play such a major role in the management of those diseases.

II. Clinical Findings -- In patients with bone pain and an either lytic or osteoblastic lesion on x-ray, one immediately expects a musculoskeletal neoplasm. In patients over age 50, by far the most common lesion will be metastatic disease. At the time of physical exam, one must:

Establish there is no surrounding soft tissue mass around the bony lesion,

Examine the patient to make sure that they have not already sustained a pathologic fracture

Examine the rest of the skeletal system to make sure they don't have other sites of possible metastatic disease.

Bone scan -- All patients with metastatic disease to bone should get a bone scan. If the lesion stimulates the osteoblast, the technetium should be taken up in that area of the lesion. Some tumors such as metastatic renal carcinoma may be "cold" on bone scan just like a multiple myeloma. The other sites that are "hot" on bone scan should be x-rayed if they involve long bones, such as the tibia, femur, or humerus. If it is in the periacetabular area of the hip, an AP of the pelvis x-ray should be obtained.

CT-guided biopsy -- may be able to give a quick diagnosis without doing a more invasive surgical approach.

Due to the rarity of primary bone tumors, few physicians accumulate enough experience in the diagnosis and treatment of these neoplasias. Clinical management is best achieved through a multidisciplinary approach in which surgeon, radiologist, medical oncologist, and pathologist combine their expertise to establish both an accurate diagnosis and a rational treatment plan. The diagnostic algorithm of a primary tumor of the bone is, and always has been, a collaborative effort in which clinical, radiologic, and pathologic features have to be considered. In the majority of cases, the pathologist can rely exclusively on histopathologic examination to provide an accurate diagnosis. In some cases, however, a variety of ancillary studies have to be employed to distinguish entities that share morphologic characteristics. Currently, immunohistochemistry has limited application in the differential diagnosis of primary bone tumors, but occasionally, characterization of the antigenic profile is the only way to properly classify a given neoplasia. Furthermore, immunohistochemical analysis is helping us to establish the histogenetic origin of many entities and to understand their pathogenesis.

The role of the pathologist in the management of bone tumors is essential. Accurate diagnosis of a given neoplasm determines not only the general patient's prognosis but, more importantly, the type of therapeutic modality needed to achieve optimal results. Furthermore, new treatment protocols are constantly being developed, and it is the responsibility of the pathologist to properly classify a given tumor for successful inclusion in the appropriate protocol. When evaluating a bone tumor, however, the pathologist is confronted with several difficulties. Bone tumors are rare entities, and not all pathologists are exposed to bone pathology with the frequency needed to gain the necessary level of diagnostic confidence. Also, certain osseous tumors share histopathologic features and, in many cases, important diagnostic features may not be readily evident in small specimens. Finally, intramedullary lesions often must be decalcified, a process that may be associated with loss in cellular morphologic detail. All of these factors complicate the diagnostic process. Diagnosis for many entities can be reached by histopathology alone or can be interpreted in the context of clinicoradiologic findings, but for others, only a differential diagnosis can be reached without ancillary studies.

Electron microscopy can be extremely useful in the identification of certain histogenetic features such as epithelial, muscular, or neural differentiation. However, it is an expensive procedure that requires excellent technical preparations and sophisticated interpretation skills. Furthermore, electron microscopy is not widely available to the general pathologist, thus requiring the submission of the sample to an academic institution.

The same can be said for cytogenetics and for sophisticated molecular analysis. Molecular techniques, however, are rapidly becoming important components of the diagnostic armamentarium. In the last decade, the roles played by tumor suppressor genes, oncogenes, and cell cycle regulatory molecules in bone oncogenesis, differentiation, apoptosis, and multidrug resistance have been explored. Thus, bone tumors have been shown to be part of well-defined genetic syndromes such as Li-Fraumeni and Rothmund-Thompson, while the diagnostic significance of chromosomal translocations, gene fusions, and DNA repair mechanisms are beginning to be understood.[1]

Immunohistochemistry, however, is essential in identifying certain entities such as metastatic carcinomas and melanomas that can occasionally be confused, morphologically, with primary bone tumors. It is also routinely used to assign a phenotype to hematopoietic malignancies and to define histogenesis in morphologically related neoplasms such as the "small blue-cell" group of tumors. Several studies have shown that gentle decalcification methods preserve antigenicity relatively well for the most commonly used markers. Unfortunately, little is known about the antigenic specificity of normal bone tissue and bone neoplasias, and although several candidate antigens have been explored, reagents to detect bone-specific antigens are not yet available. The following is a review of the most commonly used markers and the antigenic profile of selected primary bone tumors and entities that are considered in the differential diagnosis.

Immunohistochemical Markers

Mesenchymal Marker

Vimentin Although of limited value in differential diagnosis, vimentin is an abundant antigen that can be demonstrated in most properly fixed tissues and survives most decalcification procedures. It is used, therefore, to assess antigen loss during processing. Thus, if vimentin is not expressed in a tissue sample that should express it, interpretation should be either done with caution or entirely avoided.

Epithelial Markers

Cytokeratins Cytokeratins are expressed in carcinomas and in the vast majority, if not all, of epithelial-like sarcomas (epithelioid and synovial sarcomas). Certain tumors express profiles of cytokeratin subsets that have been reported to be more or less specific, although this is rarely helpful in routine diagnosis.[2]

Epithelial Membrane Antigen Epithelial membrane antigen is expressed in approximately 75% of the epithelial-like sarcomas (epithelioid and synovial sarcomas) and in malignant peripheral nerve sheath tumors, leiomyosarcomas, histiocytes, and neoplasias of histiocytic origin, and in rare anaplastic lymphomas.[3]

Neuronal, Nerve Sheath, and Melanocytic Markers

S-100 Protein (S-100) Widely distributed in peripheral and central nervous systems, the S-100 protein localizes to both the nucleus and the cytoplasm and, in the appropriate context, is one of the most useful markers. S-100 is expressed diffusely in neurofibromas and neurilemmomas, liposarcomas, ossifying fibromyxoid tumor, chondrosarcomas, and in 90% of clear-cell sarcomas, also known as melanomas of soft parts.[4] Melanomas consistently express S-100, a feature that helps in the diagnosis of metastatic melanomas to the bone. Chordomas coexpress both S-100 and cytokeratin.

Neurofilament Protein (NF) Useful in the differential diagnosis of small round-cell tumors, NF is expressed by many neuroblastomas, medulloblastomas, retinoblastomas, primitive peripheral neuroepitheliomas and, focally, in rhabdomyosarcoma and in malignant fibrous histiocytoma.[5]

Leu-7 (CD57) Although expressed in small round-cell tumors of childhood such as neuroblastoma, prominent expression in rhabdomyosarcoma limits its use in the differential of small round-cell tumors.[6]

Synaptophysin Synaptophysin is expressed by tumors of neuronal origin including neuroblastoma, ganglioneuroblastoma, olfactory neuroblastoma, melanotic neuroectodermal tumor of infancy, peripheral neuroepitheliomas, and rare rhabdomyosarcomas.[5]

Neuron-Specific Enolase Of limited use due to frequent, nonspecific, background staining, neuron-specific enolase is expressed in over half of neuroblastomas, one third of malignant melanomas, and a small percentage of nonneural tumors.[7]

Endothelial/Vascular Markers

CD31 Detection of the antigen gpIIa, the cellular adhesion molecule PECAM-1 (platelet endothelial cell adhesion), has been shown to be expressed in 80% to 100% of angiosarcomas and hemangiomas.[8]

CD34 A sensitive marker for endothelial differentiation, CD34 is expressed by 70% of angiosarcomas, 90% of Kaposi's sarcomas, and 100% of epithelioid hemangioendotheliomas.[8]

Factor VIII Antigen (FVIII) Restricted to endothelial cells and megakaryocytes, FVIII is less specific for endothelial neoplasms than are CD31 and CD34, although it is useful as a confirmatory marker (particularly in well-differentiated tumors).[9]

Fibrohistiocytic Markers

CD68 - CD68 can be found in any tumor containing lysosomal granules or phagolysosomes. CD68 is expressed in only 50% of malignant fibrous histiocytoma cases and, given its nonspecificity, it should not be used as evidence of histiocytic lineage as initially reported.[10]

Miscellaneous Markers MIC-2 Gene Product (CD99) Located in the short arm of the sex chromosome, the MIC-2 gene product encodes a surface protein first described in T-cell and null-cell acute lymphoblastic leukemia. A recent antibody (HBA-71) detects an epitope present in Ewing's sarcoma and peripheral neuroepitheliomas, alveolar rhabdomyosarcomas, ependymomas, and islet cell tumors.[11,12]

Alkaline Phosphatase, Osteonectin, Osteocalcin, and Collagens These proteins have all been used as potential bone tissue markers. Although in certain conditions the expression of these markers may be helpful, their specificity remains in question and reagents are not readily available to most laboratories.[13]

Bone-Forming Tumors

Due to their central function in the process of mineralization, a group of proteins are considered to have some potential for tumor diagnosis: alkaline phosphatase, osteonectin, and osteocalcin. Osteocalcin is produced exclusively by bone-forming cells and therefore is receiving special attention as a specific marker. In the detection of bone-forming tumors, osteocalcin has been associated with 70% sensitivity and 100% specificity, compared with the 90% sensitivity and 54% specificity reported for osteonectin.[13] At the present time, however, no specific marker is available to distinguish the bone matrix from its collagenous mimics.

Osteoma, Osteoid Osteoma, Osteoblastoma The diagnosis of these entities resides exclusively in morphologic features, and although a variety of lesions should be considered in the differential diagnosis, immunohistochemistry offers little help in the distinction. The nocturnal pain in osteoid osteoma, however, is mediated by prostaglandins, and it has been shown that in approximately 25% of osteoid osteomas, nerve fibers that express NF and S-100 are present in the reactive zone around the nidus and/or in the nidus itself. These fibers have not been observed in any other tumor, which suggests that the nerve supply of osteoid osteoma might serve as a marker in diagnostically difficult cases. Although occasionally observed in hematoxylin-eosin sections, NF and S-100 decorate the fibers and facilitate their detection.[14]

Osteosarcoma The differential diagnosis of osteosarcoma from other sarcomas (eg, malignant fibrous histiocytoma, fibrosarcoma, Ewing's sarcoma) is important because of the specific therapy available for osteosarcoma patients. Most osteosarcomas express vimentin and, according to some authors, some tumors focally express cytokeratin and desmin, although these findings have not been widely confirmed.[15-17] Bone matrix proteins, such as osteocalcin, alkaline phosphatase, and osteonectin, are expressed in osteosarcomas.[13] However, their presence has also been detected in chondrosarcomas, Ewing's sarcoma, fibrosarcomas, and malignant fibrous histiocytomas. Caution should also be used in the interpretation of focal expression of a variety of markers (eg, S-100, actin, epithelial membrane antigen) found occasionally in otherwise typical osteosarcomas. Extraskeletal osteosarcomas of the fibroblastic subtype often have sparse amounts of osteoid and can be differentiated from malignant fibrous histiocytoma on the basis of strong expression of alkaline phosphatase. Chondroblastic osteosarcoma and chondrosarcoma, however, cannot be distinguished immunohistochemically. Furthermore, it remains to be seen if the expression of CD31 or CD34 helps in the differential diagnosis between telangiectatic osteosarcoma and angiosarcoma. The different types of collagen present in the bone matrix are also produced by other tumors and therefore have no application in differential diagnosis. However, recent reports[18] suggest that the basic calponin gene, a smooth muscle differentiation-specific gene that encodes an actin-binding protein involved in the regulation of smooth muscle contractility, is expressed in osteosarcomas and that this expression may have favorable prognostic implications. The subtype of osteosarcoma that most likely will benefit from the application of an immunohistochemistry panel is the "small-cell" type. The diagnosis of this entity is difficult due to the paucity of osteoid and the similarity to other small round-cell tumors. Although the antigenic profile of small-cell osteosarcoma is unknown, expression of markers specific for other small-cell tumors help in ruling out this diagnosis.

Cartilage-Forming Tumors Little is known about matrix biochemistry and cell differentiation in chondrogenic neoplasms. Normal chondrocytes typically express vimentin, S-100, and type II collagen. Neoplastic chondrocytes usually retain vimentin and S-100 expression, but little else is known about the expression of other antigens, and it is assumed that malignant cartilage-producing tumors have no specific antigenic profile.[19-23] Although neoplastic chondrocytes in vitro can undergo full differentiation,[19] the zonal expression of type X collagen is seen only in benign osteochondromas. In enchondromas, the pattern of expression is more randomly distributed within the tumor; in chondrosarcomas, with spindle-shaped cells and noncartilaginous extracellular matrix, only focal expression is seen.[19,23] Proliferative markers like c-erb B2 are not observed in either normal cartilage or chondromas but are frequently seen in chondrosarcomas, suggesting that they may be useful in predicting biological behavior.[22]

Osteochondroma, Periosteal Chondroma, Chondromyxoid Fibroma, Enchondroma Immunohistochemistry has little or no value in the differential diagnosis of this group of tumors. Chondromyxoid fibroma is a rare benign bone tumor of uncertain histogenesis that expresses S-100, a finding consistent with the cartilaginous nature of the lesion and supporting its possible relation to chondroblastoma.[22]

Chondroblastoma Chondroblastomas are unusual benign cartilage tumors of bone with well-defined histologic features. Chondroblasts express S-100, vimentin, and neuron-specific enolase and may show focal expression of osteonectin, cytokeratins, and epithelial membrane antigen.[22] In approximately one third of the tumors, cytoplasmic expression of muscle-specific actin can be found in chondroblasts and chondrocytes. Moreover, these cells contain bundles of microfilaments with focal densities that are typical of myofilaments. Despite histogenetic considerations, immunohistochemistry helps in the distinction of chondroblastoma from other lesions that contain giant cells, such as giant-cell tumor and giant-cell reparative granuloma. These two entities do not express S-100, and their mononuclear population usually expresses histiocytic markers (eg, a1-chymotrypsin, lysozyme) not expressed in chondroblastoma.

Chondrosarcoma Besides expression of S-100 and vimentin, chondrosarcomas may express Leu-7 and neuron-specific enolase. Although immunohistochemistry does not help in the distinction of chondrosarcoma from other cartilage-forming tumors, it is helpful in the distinction of chondrosarcoma from chordoma, which expresses epithelial membrane antigen, cytokeratins, and occasionally CEA.[19,23] Expression of cytokeratins is also useful to distinguish metastatic carcinomas from clear-cell chondrosarcomas. In small biopsies containing exclusively the round-cell component of a mesenchymal chondrosarcoma, immunohistochemistry -- with an appropriate panel -- may reveal the true nature of the neoplastic cells and distinguish rhabdomyosarcoma, neuroendocrine carcinoma, and small round-cell tumor of childhood.

Fibrous and Fibrohistiocytic Tumors

Fibrous Cortical Defect, Non-Ossifying Fibroma, Benign Fibrous Histiocytoma, and Desmoplastic Fibroma Immunohistochemistry has little or no application in the differential diagnosis of these entities.

Malignant Fibrous Histiocytoma (MFH) The list of entities included in the differential diagnosis of MFH is extensive. Immunohistochemistry helps in the distinction of MFH (CD68+) from leiomyosarcoma (CD68-); MFH (S-100-) from malignant neurilemmoma (S-100+); and MFH (osteocalcin-, alkaline phosphatase-) from fibroblastic osteosarcoma (occasionally positive for both). The distinction of cytokeratin-positive MFH from sarcomatoid carcinoma may be impossible by immunohistochemistry and is best accomplished by electron microscopy.[24]

Smooth Muscle Tumors

Leiomyosarcoma Primary leiomyosarcoma of the bone is a rare tumor in an unusual location. The diagnosis requires (1) exclusion of leiomyosarcoma in other non-osseous locations and (2) intramedullary location of the epicenter of the tumor (more than 70% of the mass) with only limited extraosseous extension. Osseous leiomyosarcomas frequently have the classic morphology, although epithelioid, myxoid, and pleomorphic variants can complicate the diagnosis. Expression of smooth muscle markers (smooth muscle actin, common muscle actin, and desmin) is consistently observed in the vast majority of tumors.[25-28]

Angiosarcoma Primary angiosarcoma of bone is a rare, high-grade sarcoma of vascular origin. The clinicopathologic, immunohistochemical, and ultrastructural features of angiosarcomas are not well defined. Angiosarcomas strongly express vimentin and, at least focally, factor VIII-related antigen. CD34 antigen is detected in 74% of cases and cytokeratins in 35% of cases. Epithelial membrane antigen, S-100 protein, and HMB45 generally are not expressed. Fifty-five percent of the tumors have intracytoplasmic aggregates of laminin. Alpha-smooth muscle actin is demonstrated in a pericytic pattern in 24% of the tumors. Tumors have poor prognosis if more than 10% of the cells express MIB-1, a proliferation marker.[29-31]

Lesions Containing Giant Cells