Myofibroblastic differentiation of stromal cells in giant cell tumor of bone: an immunohistochemical and ultrastructural study.

The nature of the mononuclear stromal cells (MSCs) in giant cell tumor of bone (GCTB) has not been thoroughly investigated. The purpose of this study was to evaluate the degree and significance of myofibroblastic differentiation in 18 cases of GCTB by immunohistochemistry (IH) and/or electron microscopy (EM). All immunostained cases were found positive for smooth muscle actin (SMA) and/or muscle specific actin (MSA), most in 1-33% of the MSCs. Ultrastructurally, most MSCs were fibroblasts, and a significant number of cells displayed myofibroblastic differentiation. Myofibroblasts are an important component of MSCs in GCTB. The myofibroblastic population may be responsible in part for the production of matrix metalloproteinases (MMPs), which probably play a role in bone destruction, tumor aggression, and recurrence.

Mesenchymal-epithelial differentiation of adamantinoma of long bones: an immunohistochemical and ultrastructural study.

Three cases of adamantinoma were studied by electron microscopy and immunohistochemistry. In the tubular pattern, well-differentiated epithelial cells and glandular structures were present, in addition to ill-defined glands. In the basaloid pattern, less differentiated epithelial cells with discohesion were seen in the central epithelial masses. This study established the epithelial nature of some tubular structures with slit-like lumina, easily misinterpreted as capillaries by light microscopy. Results also showed that the irregular spaces observed within the basaloid pattern probably result from cell discohesion. Moreover, this investigation demonstrates the epithelial nature of a subset of spindle cells within the stroma of adamantinoma and offers ultrastructural evidence for a probable mesenchymal-epithelial transformation as its histogenesis.

Chondrosarcoma of the femur with histology-imaging correlation of tumor growth--preliminary observations concerning periosteal new bone formation and soft tissue extension.

UNLABELLED: The objective of this study was, in chondrosarcoma (CHS) of the femur, to evaluate by radiologic-pathologic correlation, the degree of tumor growth, cortical destruction, periosteal reaction, and soft tissue extension present. MATERIALS AND METHODS: Eight cases of histologically proven CHS of the femur were studied. All cases were resected, evaluated histologically with coronal slabs, and compared with radiographs and magnetic resonance imaging (MRI) scans. In two resected specimens, the tumors were studied in more detail; along with coronal slabs, axial sections of the remaining anterior and posterior halves of both tumors were taken, and the bone specimens were X-rayed and examined histologically. RESULTS: CHS initially involved the medullary cavity and subsequently destroyed the cortex; first, by endosteal scalloping and, second, by subsequent invasion and destruction of the cortex. During this process, there was periosteal new bone formation (PNBF), with increased cortical thickness, the degree of which often correlated with the degree of cortical destruction. In the areas of cortical thickening of three cases, a "grey line" was seen on MRI that separated the cortex from the periosteal new bone; the line, in reality,is a space between the two structures. The presence of this line suggests that the tumor does not extend beyond the cortex. PNBF occurred in all cases and varied in thickness. It frequently developed independent of direct periosteal tumor involvement. The periosteum of one case contained porotic bone with interposed marrow fat, which was easily misinterpreted as tumor extension on MRI. Expansion and remodeling of the femoral diaphysis in CHS, with widening of the medullary cavity, is usually due to extensive cortical destruction with PNBF. Soft tissue extension was present in five cases and apparently occurred by two different mechanisms: direct tumor destruction of the cortex and periosteum, with extension into the soft tissues; and subtle MRI occult tumor permeation through the periosteum. As far as we know, a first literature histologic description of the thickened CHS periosteum also was accomplished. CONCLUSION: PNBF is a common imaging manifestation of CHS of the femur, which correlated with the degree of cortical destruction. A grey line between the cortex and periosteum is an MRI finding described in this study and may facilitate the evaluation of periosteal thickening and tumor invasion in CHS. PNBF often occurs in the absence of direct periosteal involvement. Periosteal imaging abnormalities suggestive of tumor infiltration should be interpreted with caution on MRI, and early soft tissue extension in CHS may be difficult to determine on MRI.

Primary synovial chondrosarcoma of the hip joint in a 45-year-old male: case report and literature review.

Synovial chondrosarcoma is a rare tumor, seen most commonly arising from antecedent synovial chondromatosis, the more common benign entity. The distinction between the two can be difficult on the basis of clinical, imaging, and histologic criteria. The authors report a case of pathologically proven synovial chondrosarcoma of the hip in a 45-year-old male initially treated for presumed synovial chondromatosis. The case is made more unusual by the fact that no evidence of co-existent synovial chondromatosis was noted at histology. The literature as regards synovial chondrosarcoma, both de novo and secondary cases, is reviewed.

The spring ligament recess of the talocalcaneonavicular joint: depiction on MR images with cadaveric and histologic correlation.

OBJECTIVE: The objective of this study was to describe the anatomy and MR appearance of the spring ligament recess of the talocalcaneonavicular joint. SUBJECTS AND METHODS: Forty-nine MR examinations of the ankle with a spring ligament recess were prospectively collected. The size of the recess was measured. The presence of the following variables was recorded: talocalcaneonavicular joint effusion, ankle joint effusion, talar head impaction, acute lateral ankle sprain, chronic lateral ankle sprain, spring ligament tear, sinus tarsi ligament tear, talar dome osteochondral injury, and talonavicular osteoarthrosis. The Fisher exact test was performed to quantify the association of the talocalcaneonavicular effusion with the other variables. MR arthrography and dissection with histologic analysis were performed in two cadaveric ankles. RESULTS: Twenty-four men and 25 women (average age, 39 years; range, 21-77 years) were included in the study. The average size of the fluid collection was 0.4 × 0.8 cm (range, 0.2-0.9 × 0.4-1.5 cm). The prevalence of the measured variables was talocalcaneonavicular joint effusion, 67.3%; ankle joint effusion, 61.2%; talar head impaction, 32.7%; acute lateral ankle sprain, 28.6%; chronic lateral ankle sprain, 59.2%; spring ligament tear, 14.3%; sinus tarsi ligament tear, 12.2%; talar dome osteochondral lesion, 20.4%; and talonavicular osteoarthrosis, 18.4%. There was a higher prevalence of talar head impaction among individuals with talocalcaneonavicular joint effusion (p = 0.0522). Cadaveric study revealed communication between the talocalcaneonavicular joint and the spring ligament recess. CONCLUSION: The spring ligament recess is a synovium-lined, fluid-filled space that communicates with the talocalcaneonavicular joint. The recess should be distinguished from a tear of the plantar components of the spring ligament.

Retrospective analysis of total knee arthroplasty cases for visual, histological, and clinical eligibility of unicompartmental knee arthroplasties.

We retrospectively analyzed 97 total knee arthroplasty cases with medial osteoarthritis from seven participating surgeons in our teaching hospital to determine the percentage of patients who met the following eligibility criteria for unicompartmental knee arthroplasty (UKA): healthy cartilage in the lateral compartment based on (1) visual analysis, (2) histological analysis and (3) absence of UKA contraindications based on clinical analysis. The cases with healthy lateral cartilage, intact anterior cruciate ligament and posterior cruciate ligament, lack of patello-femoral arthritis, preoperative range of motion (ROM) greater than 90, and genu varum less than 10° represented 21% of the 97 cases studied. This percentage would likely have been higher had the cases been assessed earlier in the disease process. It was concluded that there is the potential to utilize UKA more frequently in the future.

Osteoblastoma of the sternum--case report and review of the literature.

Osteoblastoma is an extremely rare entity that represents less than 1% of all bone tumors, and affects twice as many males as females with peak incidence between 15 and 20 years. Osteoblastomas commonly affect axial bones, long bones, bones of the foot and hand, and less commonly the pelvis, scapula, ribs, and clavicle. Osteoblastoma does not have a classic presentation, but can vary with the location and size of the tumor. The main complaint is often progressive pain localized at the tumor site. Osteoblastoma is a benign tumor with an aggressive behavior. The treatment is wide surgical resection, otherwise it continues to enlarge and destroy the bone and surrounding structures. We report a 32-year-old male with an osteoblastoma of this sternum who was treated with an en-bloc resection and reconstruction with Marlex((R)) and a methylmethacrylate plate.

Digital intraosseous epidermoid inclusion cyst of the distal phalanx.

Epidermoid inclusion cysts (EIC) of the bone are exceedingly rare. We present a case of an atypical EIC originating at the base of the distal phalanx of the index finger following a remote history of crush injury to the finger. The differential diagnosis of expansile, lytic lesions of the phalanges remains broad, and definitive diagnosis requires tissue histopathological analysis. At latest follow-up, the patient was pain-free and obtained an excellent clinical and radiographic outcome following intra-lesional curettage and bone grafting. Differentiation of EIC from other radiolucent digital lesions remains challenging, especially when classic radiographic findings are not seen. We review the clinical, radiographic, and pathologic diagnostic features of this lesion, as well as our current treatment algorithm.

Epidermal growth factor receptor in osteosarcoma: expression and mutational analysis.

Activation of intracellular mitogenic signal transduction pathways driven by the ErbB family of receptor tyrosine kinases has been implicated in the development and/or progression of a variety of cancers. Studies on ErbB receptors in osteosarcoma have focused on HER-2 and have produced conflicting results with few studies evaluating the expression of the epidermal growth factor receptor (EGFR). In this study, we determined the level of expression of EGFR and the mutational status of the EGFR receptor in a subset of osteosarcoma tumor samples as well as in a series of established bone tumor-derived cell lines. EGFR protein expression was detected in the form of strong membranous staining by immunohistochemistry in 21 (57%) of 37 cases analyzed. Six of 12 (50%) osteosarcoma cell lines revealed moderate to high expression levels of EGFR. Two somatic alterations (E829E and R831C) were identified in the cytoplasmic domain of the EGFR gene in 1 of 10 tumor samples. The significance of these findings for the pathobiology of osteosarcomas will be investigated further.

Dysplasia epiphysealis hemimelica (Trevor disease): a rare developmental disorder of bone mimicking osteochondroma of long bones.

Dysplasia epiphysealis hemimelica (DEH) is a rare developmental disorder of childhood and is characterized by asymmetric enlargement of the epiphyseal cartilage of the long bones. After 4 to 5 years of age, the lesions histologically resemble osteochondroma. To our knowledge, only one publication of this entity is available in an English pathology journal. The clinical, radiographic, and histologic features of 9 cases of DEH were retrospectively reviewed. The patients' age ranged from 3 to 15 years with single or multiple lesions of the femur, fibula, tibia, and talus. The etiology and pathogenesis of DEH are not known. Its origin and evolution has initially apparent similarities to the development and growth of epiphyseal secondary ossification centers. DEH can be differentiated from osteochondroma of long bones using clinical, radiologic, and pathologic parameters. DEH occurs in young children and adolescents manifesting as lesions that arise particularly from the epiphysis of the lower extremities and tarsus. Osteochondroma, in contrast, occurs most frequently between 10 and 30 years of age and originates from the metaphysis of long bones. Although the DEH cartilage resembles osteochondroma, there are several significant histologic differences. During infancy, lesions of DEH histologically reveal osteocartilaginous nodules that resemble secondary ossification centers. Usually after 4 to 5 years of age they develop into osteochondroma-like lesions. Although all cases of DEH contain small areas of calcified cartilage beneath the cartilage cap, a significant percentage of osteochondromas show large amounts. The nodules and cartilage cap of DEH contain bands of cartilage separating areas of cancellous bone; these bands are not present in osteochondroma. Among the other distinguishable features, recent molecular studies of DEH demonstrated normal expression levels of EXT1 and EXT2 genes, comparable to that of normal growth plate. Osteochondroma, in contrast, has low levels of EXT1 and EXT2 gene expression due to gene mutation. The histologic differences in combination with the distinct clinical and radiographic features should enable a pathologist to differentiate these entities.

Cortico-medullary continuity in bizarre parosteal osteochondromatous proliferation mimicking osteochondroma on imaging.

Bizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is an unusual surface-based lesion of bone found most commonly in the hands and feet. In the original description of the lesion and in all publications that followed, one of the key imaging characteristics used to define this entity was the lack of cortico-medullary continuity with the underlying bone. The authors present 4 unique cases of pathologically proven BPOP in which cortico-medullary continuity with the underlying bone was demonstrated on imaging. It is believed that florid reactive periostitis, BPOP and turret osteochondroma may reflect points along the same continuum with trauma the likely inciting event. The authors suggest that, given this continuum, it may be possible to have BPOP lesions demonstrating overlapping imaging features with osteochondroma. If this is the case, strict adherence to the standard imaging criterion of lack of continuity between the lesion and the underlying bone may lead to misdiagnosis of these unusual cases of BPOP as osteochondromas.

Dedifferentiated high-grade osteosarcoma originating from low-grade central osteosarcoma of the fibula.

Low grade central osteosarcoma is a distinct, rare low grade malignant neoplasm characterized histologically by a spindle cell proliferation associated with trabecular bone formation. This tumor usually carries a good prognosis. However, it has the potential to recur, dedifferentiate, and metastasize subsequent to surgical treatment. In extremely rare occasions, LGCOS presents with areas of dedifferentiation upon initial patient evaluation. In this report we describe one such case affecting the fibula of a 39-year-old female, presenting with pain. Initial biopsy demonstrated a high-grade osteosarcoma. No areas of LGCOS were seen histologically. Following biopsy the patient received 3 months of chemotherapy at a different institution. However, the patient continued to exhibit symptoms. X-rays indicated a very aggressive tumor in the diaphysis of the proximal fibula, MRI revealed soft tissue involvement. The tumor and surrounding soft-tissues were excised en bloc at our institution. Microscopically, the lesion consisted of high-grade osteosarcoma as well as an underlying LGCOS that involved the cortex and medullary cavity of the fibula. The two histological components of the tumor were sharply delineated from one another. No chemotherapy effect was appreciated histologically or clinically. Eight months following the surgery, the patient died from lung metastases. This is the third documented case of dedifferentiated LGCOS at initial presentation. This case reveals that the low-grade component was also evident on preoperative radiographs.

Malignant tumors of the hand and wrist.

Malignant tumors in the hand and wrist compose a wide variety of lesions involving skin, soft tissues, and bone. Although these lesions are found elsewhere in the body, many have unique characteristics at this anatomic location. Skin tumors predominate; the most common are squamous cell carcinomas, followed in frequency by basal cell carcinomas and malignant melanomas. Other soft-tissue malignancies are less common but may present more difficult diagnostic problems. They often appear as painless masses that sometimes have been present for months or even years and deceptively appear to be benign. A missed or delayed diagnosis of these tumors can have devastating consequences. Bone malignancies involve both primary lesions, of which chondrosarcomas are the most common, and metastatic lesions. Regardless of cell type, treatment of malignant tumors in the hand and wrist requires special considerations because of the important function of these structures. Orthopaedic surgeons should be familiar with the spectrum of these tumors, the work-up necessary to arrive at a precise diagnosis, and the treatment that will achieve the most favorable outcome.

Ultrastructure of low-grade intraosseous osteosarcoma of bone: a comparative study with fibrous dysplasia and parosteal osteosarcoma.

The ultrastructure of low-grade intraosseous osteosarcoma (LGOS) is not well documented in the literature. Four cases of LGOS are described with an emphasis on its distinguishing characteristics as well those it shares with other lesions. The predominant cells of LGOS are fibroblasts with well-developed rough endoplasmic reticulum and mild focal immunoreactivity to SMA and MSA. Few osteoblasts and myofibroblasts are present. Transition cells between fibroblasts and osteoblasts are also noted. The fibroblasts are closely related to osteoblasts from a histological and functional point of view, and phenotypically are probably modified osteoblasts. Comparative ultrastructural studies between LGOS and fibrous dysplasia (FD) reveal basic similarities, although the cells in LGOS are larger with more of an abundance of organelles. Therefore, accurate differentiation between these two lesions rests at the histological and radiological levels. LGOS and parosteal osteosarcomas (PO) also share similar ultrastructural features. In the case samples in this study, an unusual type of multilayered amorphous material was found in the osteoid matrix of a case of LGOS and one of PO. This probably emphasizes the morphologic similarities between these 2 tumors.

Well-differentiated extraosseous chondrosarcoma of the foot with pulmonary metastases.

We report a case of a 38-year-old man with a well-differentiated extraosseous chondrosarcoma of the foot. This case is unusual because the tumor originated in the soft tissues of the foot and developed pulmonary metastases. It is also interesting to note that at the time of recurrence 8 years later, the lesion invaded the third metatarsophalangeal joint and adjacent bones. Well-differentiated chondrosarcoma resembling hyaline cartilage, primary in soft tissue, is a rare histological type, and only a few cases have been reported in the foot. The patient is alive and well 4.5 years after resection of the foot tumor and partial resection of the lung metastases.

Well-differentiated extraskeletal osteosarcoma: report of 2 cases, 1 with dedifferentiation.

Extraskeletal osteosarcoma (ESOS) is a rare soft tissue sarcoma, typically characterized by high-grade histological features and a grave prognosis. However, 4 cases of well-differentiated ESOS with a better prognosis have been documented in the literature within the last 40 years. We report 2 additional cases, 1 with multicentric presentation and dedifferentiation, and we emphasize the histological features that are useful in distinguishing this lesion from other soft tissue tumors. Well-differentiated ESOS seems to represent a rare but distinct low-grade variant of ESOS. The limited published experience suggests that although the biologic behavior of this tumor is better than that of classical ESOS, there are cases with progression to a higher grade, leading eventually to final demise.

Bizarre parosteal osteochondromatous proliferation (Nora's lesion) in the hand.

PURPOSE: The purpose of this study was to review our experience with a benign surface bone lesion referred to as bizarre parosteal osteochondromatous proliferation (BPOP) or Nora's lesion, named for the pathologist who described it in 1983. The lesion may be confused with a variety of tumors, particularly solitary osteochondromas, which are rare. METHODS: The files in the Department of Pathology at the Hospital for Joint Diseases were reviewed over a 21-year period for all surface bone lesions involving the tubular bones in the hand. There were a total of 10 cases of BPOP compared with only a single case of an osteochondroma. RESULTS: Radiographs generally showed a well-marginated uniformly dense mass arising from the surface of the affected bone without any disruption in its bony architecture. Surgical excision is the definitive treatment and included the fibrous pseudocapsule over the lesion, any periosteal tissue beneath the lesion, and any area of the cortex of the host bone that appeared abnormal. Although in the medical literature the recurrence rate for BPOP is high, we had only one recurrence in our series. CONCLUSIONS: BPOP is a benign surface bone lesion that may be confused with benign and malignant tumors. Although there is a cleavage plane between the lesion and host bone, we recommend excising the pseudocapsule over the lesion, any periosteal tissue beneath the lesion, and decorticating any abnormal-appearing areas in the underlying host bone. This may explain the low recurrence rate in our series.