Giant-cell reparative granuloma of short tubular bones of the hands and feet.

Eight cases of giant-cell reparative granuloma were encountered in the short tubular bones of the hands and feet. This entity was originally described by Jaffe as a jaw lesion. Subsequently the lesion was found in the skull and facial bones. The name "giant cell reaction" was applied to similar lesions found in the short tubular bones of hands and feet. Thirteen prior cases have been reported and none recurred. Of the eight new cases described herein, four have recurred one or more times, requiring further treatment. No association with hyperparathyroidism was found. We prefer to designate these lesions as giant cell reparative granulomas of extragnathic sites. Because of overlapping ultrastructural and light-microscopic features, as well as similar biologic behavior, we feel that aneurysmal bone cyst and these giant-cell reparative lesions represent related responses to intraosseous hemorrhage.

Dupuytren's (subungual) exostosis.

Because it may produce a bewildering array of histologic patterns, the clinical entity of subungual exostosis (Dupuytren's exostosis), is sometimes confused with chondrosarcoma. However, this lesion is a distinct entity. It begins as a reactive growth of cellular fibrous tissue and metaplastic cartilage, which undergoes enchondral ossification. The rate of growth may be exuberant, but it is limited. We present a series of 15 cases as well as a review of the literature. Postadolescents and young adults are most commonly affected, and the majority of cases (80%) occur on the dorsal-medial aspect of the great toe. Trauma, whether chronic or acute, and infection are frequent inciting factors. The radiologic picture is consistent and can be diagnostic. In more than half our cases, chondrosarcoma was suspected initially. However, if the entire clinical picture is evaluated, the histologic findings should not lead to confusion with a malignant process. This acquired exostosis is benign; local excision is curative. However, recurrence is common (53%) after incomplete excision or when the lesion has not achieved full maturation.

Massive chondroid differentiation in fibrous dysplasia of bone (fibrocartilaginous dysplasia)

Eight cases of fibrocartilaginous dysplasia (fibrous dysplasia with massive cartilaginous differentiation) of bone are reported. The age of the patients ranged from 4 to 26 years, with an average of 17.5 years. The male/female ratio was 1:1. In two patients the lesions occurred in a setting of polyostotic fibrous dysplasia. The anatomic sites most frequently affected were the femur and tibia. The proximal femur was the most common site. Roentgenograms showed well-demarcated lucent lesions of ground-glass opacity. In addition, stippled or ring-like calcifications suggesting cartilaginous elements were seen in six cases. Histologically, hyaline cartilage islands were found in juxtaposition to a fibro-osseous lesion characteristic of fibrous dysplasia. Enchondral ossification was commonly seen, frequently showing columnar arrangement of cartilage cells mimicking a growth plate. The cartilage may show moderate atypism. The important thing is to recognize the benign nature of chondroid elements in fibrous dysplasia. Even if cartilage dominates the histologic picture, it is important to identify the fibro-osseous elements and thereby avoid the misdiagnosis of chondrosarcoma.

Florid reactive periostitis of the tubular bones of the hands and feet. A benign lesion which may simulate osteosarcoma.

Twelve patients with florid reactive periostitis of the small bones of the hands and feet are presented. Clinically, the lesion usually presents as a swelling of the affected part, sometimes accompanied by pain, tenderness, and redness. Histologically, the lesion may be mistaken for benign and malignant neoplasms such as osteosarcoma or parosteal osteosarcoma or osteochondromas. The features that distinguish reactive periostitis from the several diagnostic possibilities are presented. It is important for the clinician and the pathologist to recognize the existence of florid reactive periostitis in the hands and feet and to treat accordingly. Local excision appears to be adequate treatment; follow-up indicates little risk for local recurrence.

Vascular and cartilaginous hamartoma of the ribs in infancy with secondary aneurysmal bone cyst formation.

Three aneurysmal bone cysts of the rib in infants are presented. These tumors were engrafted on vascular and cartilaginous hamartomas and thus showed the unusual feature of hyalin cartilage associated with aneurysmal bone cyst. The entity of vascular and cartilaginous rib hamartoma is discussed with emphasis on the importance of distinguishing this malformation from a benign or malignant neoplasm.

Intraosseous ganglion: a clinicopathologic study of 11 cases.

The intraosseous ganglion is a cystic lesion of bone most frequently located in the subchondral epiphysis of long bones without direct communication with a joint cavity. Although this entity is becoming well recognized by orthopedic surgeons and radiologists, it has rarely been discussed in the pathologic literature and is frequently overlooked by the surgical pathologist. In this study the clinical and pathologic features of 10 patients, representing 11 instances of intraosseous ganglia, were reviewed with emphasis on the histologic and radiologic features necessary for diagnosis. Common radiologic features usually include a unilocular cyst surrounded by a thin rim of sclerotic bone in the subchondral epiphysis in the absence of other features of degenerative joint disease. Histologically, the ganglia are usually composed of a cystic space without epithelial lining, often filled with gelatinous, mucoid material and occasional foamy macrophages. The radiologic and histologic differential diagnoses, possible etiologic factors, and treatment are discussed.

Epithelioid hemangioendothelioma of bone. A clinicopathologic, ultrastructural, and immunohistochemical study.

In a review of 29 cases of solitary and multicentric hemangioendothelial sarcomas of bone, 14 were found to have histologic features of epithelioid hemangioendotheliomas. These were characterized by the presence of epithelioid or "histiocytoid" endothelial cells that were either round or spindle-shaped. Intracytoplasmic vacuolization was noted, and some showed nesting of cells, mimicking metastatic adenocarcinoma. The presence of a myxoid matrix suggested the diagnosis of chondrosarcoma in some cases. Some of the tumors strongly resembled the lesions formerly designated as intravascular bronchioloalveolar tumor, angioglomoid tumor of bone, or malignant myxoid angioblastoma of bone. Factor VIII-related antigen was detected in five of the six cases examined, and ultrastructural study in five cases confirmed the endothelial nature of the tumor cells; Weibel-Palade bodies were present in three cases. There were 11 men and three women, and the tumors were seen predominantly in patients who were under 30 years of age (10 cases). Four cases involved solitary tumors, and nine were multicentric in bone. The multicentric tumors had a predilection for the bones of one lower extremity (five cases). The total series had a protracted clinical course, and the multicentric tumors appeared to follow a less aggressive course.

Synovial sarcoma with extensive osteoid and bone formation.

Four cases of synovial sarcoma with extensive calcification and osteoid and bone formation are reported. Ages ranged from 21 to 38 years. Two tumors were located in the foot and two in the thigh. Because of a well-circumscribed, densely calcified soft tissue mass, radiologically three patients were thought to have a benign lesion. The fourth patient was thought to have a paraosteal osteosarcoma because of an accompanying bone defect. Tumor size varied from 4.0 to 9.0 cm. Histologically, three tumors were biphasic and one predominantly monophasic. All showed amorphous calcifications with extensive ossification sometimes in a ribbon-like pattern of osteoid, simulating osteosarcoma. The extensive bone formation with abundant osteoid deposition may lead to a misdiagnosis of osteosarcoma. It is important to recognize this variant of synovial sarcoma with ossification and bone formation and distinguish it from extraskeletal osteosarcoma because of the difference in clinical behavior and course. Although the most important point in the recognition of this variant of synovial sarcoma is its biphasic pattern, this may not be apparent in a small tissue sample. Points that aid in the diagnosis include the uniform nuclear appearance of both the epithelial and the spindle cells versus the pleomorphism of osteosarcoma and in some cases the presence of amorphous concretions in sheets and small calcospherites within spaces surrounded by flat or conspicuous epithelial cells. These cells are immunoreactive for cytokeratin and epithelial membrane antigen.

Periosteal chondroma. A clinicopathologic study of 23 cases.

The periosteal chondroma (juxtacortical chondroma) is an unusual tumor which usually occurs on the surface of tubular bones in the metaphyseal area. In this study, we reviewed the clinicopathologic features of 22 patients representing 23 instances of periosteal chondroma and discuss the radiologic and histologic features necessary for accurate diagnosis. The characteristic radiologic appearance is of a single cartilaginous mass in the metaphyseal periosteum causing well-defined depression or "saucerization" of the adjacent cortex. The radiologic differential diagnoses include soft-tissue tumors compressing bone, fibrous cortical defect, and periosteal chondrosarcoma or osteosarcoma. Histologic features include lobules of hyaline cartilage with frequent areas of hypercellularity, binucleate chondrocytes, and focal mild cytologic atypia. The histologic features clearly identify the tumor as chondrogenic; however, familiarity with the x-rays may be necessary to recognize the tumor as benign.

Tumor-induced osteomalacia and rickets.

Tumor-induced osteomalacia is a clinicopathological entity in which vitamin D-resistant osteomalacia or rickets occurs in association with a tumor. A total of 72 cases (three current, 69 from review of literature) has been reported to date. Men and women are equally affected. The majority are adults over 30 years old who exhibit progressive lower leg and back pain. Forty bone and 31 soft-tissue tumors were responsible for this syndrome; two-thirds occurred in the extremities. Chemical findings are typical: low serum phosphorus, normal serum calcium, and elevated alkaline phosphatase. Serum levels of 1,25-dihydroxyvitamin D were low or undetectable. Histologically, more than a third were classified as vascular tumors, and half of these cases were hemangiopericytomas that were distributed equally between bone and soft tissues. Other common diagnoses included nonossifying fibromas, "mesenchymal" and giant-cell tumor variants. Features common to all tumors were prominent vascularity, and giant and primitive stromal cells. Only 10 were histologically malignant. Ultrastructural studies have not shown any secretory granules suggestive of a hormone-secreting tumor. It is clear, however, that the tumor is responsible for the osteomalacia because the complete removal generally results in a dramatic reversal of all symptoms and signs.

Intravascular bronchiolo-alveolar tumor (IVBAT): A low-grade sclerosing epithelioid angiosarcoma of lung.

Intravascular bronchiolo-alveolar tumor (IVBAT) is a rare and highly distinctive pulmonary tumor of disputed cellular nature. Both epithelial and endothelial differentiation of this neoplasm have been suggested. We have studied multiple nodules of IVBATs from three patients by light and electron microscopy and by immunohistochemical methods for Factor VIII-related antigen (FVIII RAG). Our light and ultrastructural studies are in essential agreement with the previous suggestion of the endothelial nature of the neoplasm and our demonstration of the presence of FVIII RAG in many of the tumor cells offers new evidence strongly supportive of their endothelial differentiation. We believe that IVBAT and a group of extrapulmonary tumors described as epithelioid hemangioendothelioma and endovascular papillary angioendothelioma are similar biologically indolent neoplasms of epithelioid and dendritic endothelial cells characterized by stromal sclerosis, intravascular spread, a low incidence of metastases and slow clinical evolution. Thus, we regard IVBAT as a low-grade sclerosing angiosarcoma of the lung.

Adamantinoma-like Ewing's sarcoma: genomic confirmation, phenotypic drift.

Ewing's sarcoma, a highly malignant neoplasm, is characterized by an 11;22 translocation [t(11;22) (q24;q12)], resulting in the fusion of genes FLII and EWS. Adamantinoma of extragnathic bones, a low-grade malignant neoplasm with epithelial features, is not typically considered in the differential diagnosis of Ewing's sarcoma. In this study, three osseous Ewing's sarcomas with histological, immunohistochemical, or ultrastructural epithelial features were subjected to reverse transcription-polymerase chain reaction and sequencing studies for the Ewing's sarcoma molecular rearrangement. (Two of the three cases were originally described as adamantinomas or nontypical Ewing's sarcoma before the availability of genetic characterization.) In addition, traditional cytogenetic analysis and a unique combined interphase molecular cytogenetic/ immunocytochemical approach with bicolor 11;22 translocation breakpoint flanking probes (cosmids) and pancytokeratin antibodies were performed on one neoplasm. At(11;22) (q24;q12) was found in one neoplasm and a type II EWS/FLI-1 fusion transcript was detected in all three neoplasms. The combined genetic/immunocytochemical approach revealed the presence of the 11 ;22 translocation in the nuclei of cytokeratin immunoreactive cells. These genotypic and phenotypic findings delineate a novel Ewing's sarcoma histologic variant, "adamantinoma-like Ewing's sarcoma."

Epiphyseal osteosarcoma: distinguishing features from clear cell chondrosarcoma, chondroblastoma, and epiphyseal enchondroma.

In a retrospective radiologic and histologic study of 286 osteosarcomas in files of a metropolitan hospital, four patients (three men and one woman) with osteosarcomas confined to the epiphysis were identified. In this series, there were also 16 metaphyseal osteosarcomas that extended to the epiphysis with penetration through the cartilaginous growth plate, a structure that ordinarily resists tumor growth. All tumors occurred in the femoral condyle. Characteristically, all four patients had histories of knee joint pain, and three reported antecedent trauma. Radiologically, the tumors showed predominantly lytic features. Histologically, three of the tumors were osteoblastic in type, and one was mostly chondroblastic. Purely epiphyseal osteosarcoma has overlapping radiologic features with clear cell chondrosarcoma, epiphyseal chondroblastoma, and epiphyseal enchondroma. The epiphyseal osteosarcomas of the distal femur reported here were characterized by a history of symptoms localized to the knee joint itself as a consequence of their epiphyseal location and joint involvement. This is in contrast to the usual metaphyseal osteosarcomas, which present with lower thigh pain and swelling. Because osteosarcomas may present as lytic tumors confined to the epiphysis, they should be included in the differential diagnosis of such lesions.

Chondromyxoid fibroma of bone: thirty-six cases with clinicopathologic correlation.

A series of 36 cases of chondromyxoid fibroma (CMF) of bone, a rare benign tumor that may be confused with chondrosarcoma, is presented to aid in correctly identifying and diagnosing these neoplasms. In this series, CMFs were found in patients of all age groups, with no predominance between sexes. Long bone tumors were more common in young patients, while small and flat bone lesions were more common in older patients. Radiographically, long, flat, and small bone lesions were well-defined and benign-appearing. Tumors in the vertebrae had a more aggressive appearance, with marked bone destruction. The histologic picture was of a pseudolobulated tumor with myxoid and chondroid regions. Tumor cells were at times bizarre, pleomorphic, and binucleate, but rarely contained mitoses. Curettage with or without bone grafting and en bloc resection were the most common modes of treatment. The majority of recurrences were seen in patients treated by curettage alone. Radiation therapy was associated with the development of sarcoma in one case. No cases of malignant transformation were found in this series, but unusually aggressive recurrences were noted in CMFs involving a phalanx, the cervical vertebra, and the sacrum.

Adamantinoma of long bone. An analysis of nine new cases with emphasis on metastasizing lesions and fibrous dysplasia-like changes.

Nine new cases of adamantinoma of long bone are presented. The age range, location, and symptomatology are similar to those in precious reports. Histologically most of the tumors have a "basaloid" or "spindled" pattern. A squamoid pattern with keratinization or an "angioblastic" pattern is seen less frequently. In all cases with adequate material there has been an associated frbrous dysplasia-like lesion is interpreted as being a part of the spectrum of mesenchymal differentiation of which the tumor is capable. Two cases in which metastasis occurred are compared to previously reported metastasizing cases. Few criteria are available that identify the potentially metastasizing tumor.

Chondrosarcoma of bone with dedifferentiation: a study of eighteen cases.

Eighteen patients with chondrosarcomas showing dedifferentiation were reviewed. Thirteen of the 14 patients in whom there was follow-up died of their tumors, with an average survival of six months. The average age was 61, and the most common location was the distal femur. Eight patients presented with pathologic fractures. Radiographically the tumor appeared as a destructive are with an associated heavily calcified lesion. This corresponded to combined histologic patterns of high grade sarcoma, usually with features of a malignant fibrous histiocytoma, and a low grade chondrosarcoma. This lesion must be distinguished from a primary malignant fibrous histiocytoma of bone in view of the different prognostic implications.

Exophytic variant of fibrous dysplasia (fibrous dysplasia protuberans).

Two cases of an exophytic variant of fibrous dysplasia (fibrous dysplasia protuberans) are reported in which the lesions protruded far beyond the normal bone contour mimicking surface lesions of bone. The first case was an 18-year-old man who had a pedunculated calcified mass of the sixth rib in association with radiologically diagnosed fibrous dysplasia of the skull. The second case was a 33-year-old man who had an exophytic lesion of the proximal tibia. Both of these patients were shown to have benign fibro-osseous lesions consistent with fibrous dysplasia. The intramedullary portions of the host bone adjacent to the exophytic masses also were involved by the fibro-osseous lesions and this fact suggests that the lesions may arise eccentrically in the medullary spaces and mainly grow outwards. It is important to be aware that fibrous dysplasia occasionally presents as an excrescence on the surface of bone. Careful radiographic and histological correlation is required to make a correct diagnosis of this rare variant of fibrous dysplasia.

Tophaceous pseudogout (tumoral calcium pyrophosphate dihydrate crystal deposition disease).

Most cases of calcium deposition seen radiologically in soft tissues are caused by calcium hydroxyapatite and occur either as a complication of trauma with associated necrosis (eg, fat necrosis), generalized connective tissue diseases (eg, scleroderma), metabolic disturbances (eg, hyperparathyroidism, familial hyperphosphatemia), sarcoidosis, myeloma, or metastases. Hydroxyapatite deposits are seen at many soft tissue sites, including joint capsules, ligaments, blood vessels, dermis, etc. On the other hand, deposits of calcium pyrophosphate are seen typically in the meniscus, articular cartilage, ligamentum flavum, and intervertebral disc. They usually are punctate or linear in distribution within the meniscus or parallel to the subchondral bone end plate. We report seven cases of massive focal calcium pyrophosphate dihydrate (CPPD) crystal deposition disease (tophaceous pseudogout) that occurred in atypical locations for CPPD. The ages of the patients ranged from 31 to 86 years (average, 60.7 years). One patient was male and six were female. The temporomandibular joint was involved in three patients and the metatarsophalangeal joint of the great toe was involved in two patients. The hip joint and cervical spine were involved in one patient each. A mass or swelling with or without pain was a common symptom. None of the patients in our series had clinical or radiographic evidence of CPPD crystal deposition disease in any other joints. Roentgenograms showed calcified lesions with a granular or fluffy pattern. Histologically, the lesions showed small or large deposits of intensely basophilic calcified material containing needle shaped and rhomboid crystals with weakly positive birefringence characteristic of CPPD. Foreign body granulomatous reaction to the CPPD deposition was constantly found. Chondroid metaplasia around and in the areas of CPPD deposition was observed commonly. Some of the chondroid areas showed cellular atypia in chondrocytes suggestive of a malignant cartilage tumor. It is important to recognize this rare form of CPPD crystal deposition disease and to identify the CPPD crystals in the calcified deposits, thus avoiding the misdiagnosis of benign or malignant cartilaginous lesions.

Malignant fibrous histiocytoma of bone: a study of 35 cases.

Thirty-five cases of primary malignant fibrous histiocytoma of bone are reported. Twenty of these cases were collected from a retrospective analysis of other malignant bone tumors. The age range was from 11 to 69 years; the average age was 34 years. The tumor occurred most commonly in the distal femur and proximal tibia. The distinguishing histologic feature was a storiform arrangement of spindle cells. The differential diagnosis included fibrosarcoma, osteogenic sarcoma, malignant giant cell tumor, malignant lymphoma, and metastatic carcinoma. Follow-up of at least three years was available in 21 cases. Of these, nine patients were alive and free of metastases three and one-half to 12 years after treatment. Two were alive with solitary metastases at three years, and 10 patients died between three months and three years after treatment. In four cases the lesions were multicentric at the time of diagnosis and in four cases were associated with bone infarction. This tumor must be recognized as an important complication of bone infarction and should be suspected when a patient with a known history of bone infarction develops a change in symptoms. Because the prognosis of this tumor is significantly better than that in those tumors with which it had been previously grouped, and in view of its association with bone infarction, it deserves to be maintained as a distinct clinicopathologic entity. Amputation is the treatment of choice.

p53 expression and DNA ploidy of cartilage lesions.

The aim of this study was to investigate the expression of a tumor suppressor gene (p53) in cartilage lesions of bone and its relationship to their histological grade and DNA ploidy. An immunohistochemical assay for p53 and Feulgen-stained DNA preparations was subjected to computerized image analysis. Enchondromas, synovial chondromatosis, and low grade (grade I and II) chondrosarcomas were diploid. High grade (grade III) chondrosarcomas and high grade sarcomatous components of dedifferentiated chondrosarcomas were aneuploid. Well differentiated cartilaginous components of dedifferentiated chondrosarcomas were diploid. Microscopic examination showed weak focal positivity for p53 in one of 10 enchondromas one of six examples of synovial chondromatosis, and three of four low grade (grade I and II) chondrosarcomas. All three high grade (grade III) chondrosarcomas were strongly positive for p53. The high grade sarcomatous component of all four dedifferentiated chondrosarcomas was strongly positive for p53, whereas only focal weak positivity was noted in the well differentiated cartilaginous areas. These results were confirmed by quantitative computer-assisted image analysis, which showed that high grade aneuploid cartilage tumors demonstrated strikingly higher levels of p53 than did diploid low grade malignant tumors or benign cartilage lesions.