Postnatal development of ectopic sensory fibers containing endomorphin-2 in the white matter of the spinal cord of a transgenic mouse expressing nerve growth factor in oligodendrocytes.

Transgenic mice ectopically expressing nerve growth factor in oligodendrocytes have high levels of nerve growth factor immunoreactivity in the white matter of the spinal cord from birth until 2 months of age. The nerve growth factor over-expression leads to the appearance of ectopic substance P containing sensory fibers in the white matter of the spinal cord that persist throughout the life of the animal. These transgenic mice have been found to display hypersensitivity to a thermal stimulus following a sensitizing pinch stimulus known to release endogenous substance P. Surprisingly, this hypersensitivity is completely reversed following the administration of morphine, to the extent that transgenic mice become less sensitive to pain than the wild type mice given morphine. Endomorphin-2, an endogenous opioid peptide, has been found co-localized with substance P in primary sensory fibers in the spinal cord. In this study, we show that the ectopic fibers also express endomorphin-2, and describe the postnatal development of such expression, as detected by immunocytochemistry. We confirmed that endomorphin-2 expression starts later in the postnatal period than substance P. Surprisingly, transgenic animals had delayed appearance of endomorphin-2 in the superficial dorsal horn, compared with wild type, and expressed particularly high levels of endomorphin-2 immunoreactivity in the ectopic fibers from postnatal days 10-30, coinciding with the peak of nerve growth factor expression in oligodendrocytes. Endomorphin-2 immunoreactivity was still readily detected in ectopic fibers of 120-day-old animals. Furthermore, we detected immunoreactivity for the mu-opioid receptor in the ectopic fibers, where it was co-localized with endomorphin-2 immunoreactivity. In the superficial dorsal horn, there were no apparent differences in the distribution and intensity of mu-opioid receptor immunoreactivity between wild type and transgenic animals. Taken together, these data could provide an explanation for the enhanced effect of opioid analgesics in transgenic mice, when compared with control mice, as well as provide the basis for studies of the postnatal development of the hyperalgesia and allodynia demonstrated by these animals.

Brown tumors developing in renal transplant recipients with persistent hyperparathyroidism: two case reports and review of literature.

BACKGROUND: Brown tumors, evidence for severe hyperparathyroidism, are rare in end-stage renal disease, and are distinctly uncommon in patients with a functioning renal transplant. CASE REPORTS: We report two cases of brown tumors developing after renal transplantation, and discuss their presentation and treatment. We review the literature. CONCLUSIONS: We suggest that persistent hyperparathyroidism post-renal transplant requires aggressive intervention to avoid significant consequences.

Giant cell reparative granuloma: a comparative clinicopathologic study of lesions in gnathic and extragnathic sites.

This study attempts to define the clinicopathologic aspects of extragnathic giant cell reparative granuloma (GCRG) by contrasting it with the much better recognized GCRG of jaw bones and highlights the manifestations that are unique to the extragnathic localization. Ninety-one GCRGs of 89 patients, 22 in jaw bones and 69 in the extragnathic bones, were examined. Females were affected twice as frequently as males in both groups. The age distribution of extragnathic GCRGs overlaps that of gnathic counterparts. Small bones of the hands (17 lesions) and feet (16 lesions) were the most common sites for extragnathic lesions. The radiographic findings were nonspecific. Histology of extragnathic lesions was closely similar to that of lesions affecting the jaw. These giant cell lesions should be distinguished from giant cell tumors. Int J Surg Pathol 9(3):189-200, 2001

Recurrent chondromyxoid fibroma of the thoracic spine 30 years after primary excision: case report and review of the literature.

We report a case of late recurrence of chondromyxoid fibroma (CMF) arising in a thoracic vertebra in an 11-year-old male. This was treated by curettage, and 30 years later, the patient noticed shoulder pain and leg weakness. A recurrent mass appeared at the same site in the spinous process of T6. The histologic features of the recurrent tumor were similar to those of the primary lesion. A total of 38 cases of CMF of the vertebra have been reported. Only 3 of 38 previously reported vertebral CMF recurred. Tumors recurred 2 years after operation in 2 cases, and 7 years after operation in 1 case.

Recurrent chromosome aberrations in fibrous dysplasia of the bone: a report of the CHAMP study group. CHromosomes And MorPhology.

The nosologic status of fibrous dysplasia (FD), a well-known and relatively common bone lesion, is controversial. Information collected by the CHromosomes And MorPhology (CHAMP) study group on published and unpublished cases of fibrous dysplasia shows the presence of clonal chromosome changes in at least a proportion of these lesions. The chromosome aberrations found in FD lesions have been quite variable and have included both structural and numerical changes. Two of the three cases investigated at the study group had trisomy 2 as the sole acquired anomaly. Combined with previously published data, +2 and rearrangements involving chromosome band 12p13 have each been detected in 3 of 8 cases with abnormal karyotype of 11 in which chromosomal analysis has been performed, suggesting that FD is a neoplastic lesion rather than a "dysplastic" process, as has been generally believed and as implied by its very name.

Cytogenetic-morphologic correlations in aneurysmal bone cyst, giant cell tumor of bone and combined lesions. A report from the CHAMP study group.

Aneurysmal bone cyst and giant cell tumor of bone are relatively rare bone tumors that sometimes coexist. We examined the karyotypes of 3 aneurysmal bone cysts, 12 giant cell tumors, and 3 combined lesions. All aneurysmal bone cysts showed involvement of chromosome segments 17p11-13 and/or 16q22. In addition, in 1 of the 3 giant cell tumors with secondary aneurysmal bone cyst, both chromosome bands were rearranged as well, albeit not in a balanced translocation. Seven out of 12 giant cell tumors were characterized by telomeric associations. One giant cell tumor showed a dup(16)(q13q22), suggesting the presence of a (minor) secondary aneurysmal bone cyst component, despite the absence of histological proof. Our results, combined with literature data further substantiate that segments 16q22 and 17p11-13 are nonrandomly involved in at least some aneurysmal bone cysts, irrespective of subtype (primary, secondary, intra/extraosseous, solid or classic). These findings strongly suggest that some aneurysmal bone cysts are true neoplasms. In addition, telomeric associations are the most frequent chromosomal aberrations in giant cell tumor of bone, the significance of which remains elusive. In combined giant cell tumor/aneurysmal bone cyst each component seems to retain its own karyotypic abnormality.

Sarcomatous transformation of the orbit in a patient with Paget's disease.

OBJECTIVE: To report the clinical and pathologic features of sarcomatous transformation of the skull with involvement of the orbit, in Paget's disease. DESIGN: Interventional case report. PARTICIPANT: An 83-year-old woman with Paget's disease who experienced progressive proptosis of the left eye. INTERVENTION: Fine-needle aspiration biopsy of the orbital mass. RESULTS: Cytologic examination revealed round to oval malignant cells with wispy cytoplasm, consistent with the diagnosis of sarcoma. The patient died shortly after institution of orbital radiation therapy and systemic steroid therapy. CONCLUSIONS: Proptosis related to Paget's disease is uncommon, and only rarely is it a result of sarcomatous transformation. Sarcomatous transformation of the skull involving the orbit should be included in the differential diagnosis of progressive proptosis in patients with Paget's disease.

Synovial desmoplastic fibroblastoma of hip joint with bone erosion.

A 78-year-old woman presented with pain at the left hip. Initial radiographs showed minimal age-related changes. Over the next 2 years she developed large erosions in the left femoral neck and proceeded to hip replacement. Histological examination showed bland spindle cells in a loose and hyalinised collagenous stroma considered to represent a desmoplastic fibroblastoma (collagenous fibroma). This is the first reported case of synovial desmoplastic fibroblastoma.

Cherubism: clinicopathologic features.

A case of cherubism in 6-year-old boy is reported. He presented with bilateral symmetrical enlargement of the jaw in addition to medially dislocated premature teeth, narrow V-shaped palatal vault, and mild upward turning of the eyes. Radiographs showed multiloculated osteolysis in both the mandible and maxilla. Histology revealed a non-neoplastic fibrous lesion, rich in multinucleated giant cells, consistent with giant-cell reparative granuloma. Since the original description of cherubism, various histologic interpretations have been proposed, particularly that of fibrous dysplasia. However, it should be emphasized that cherubism is a disease histologically indistinguishable from giant-cell reparative granuloma.

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."

Chondrosarcoma of the short tubular bones of the hands and feet.

OBJECTIVE: To report 12 cases of chondrosarcoma in a rare location, the short tubular bones of the hands and feet, as well as 12 cases of enchondroma in similar locations, emphasizing the radiologic and histopathologic features. DESIGN AND PATIENTS: All relevant cases that had both histologic slides and radiographs available were taken from the files of one orthopedic referral hospital and the personal files of one of the authors. A similar number of enchondroma cases was selected at random from the files. RESULTS AND CONCLUSIONS: One malignancy arose in a background of enchondromatosis, with all the others being solitary lesions. A pathologic diagnosis of malignancy is often difficult in the absence of radiologic signs of malignancy (cortical destruction with or without soft tissue extension). However, three cases were unusual in that the initial radiograph demonstrated a benign appearance. Another group of three malignancies was surprisingly indolent biologically. The treatment of choice is ray resection (or more limited amputation in a lesion of the middle or distal phalanx).

Radiographic and histologic patterns of calcification in chondromyxoid fibroma.

OBJECTIVE: To evaluate the frequency of radiologic and histologic manifestations of matrix calcification in chondromyxoid fibromas. PATIENTS: Forty-four cases of chondromyxoid fibroma were reviewed. The age range of the patients was 3-70 years (average 29 years). RESULTS: Calcification was found microscopically in 15 cases (34.1%). In five cases (12.5%) it was demonstrated on plain films or CT. The age range of the patients with microscopic evidence of calcified matrix was 14-70 years (mean 46 years), while that of the patients with non-calcified lesions was 3-59 years (average 21 years). All but two of the patients who showed microscopic calcification in the tumors were over 40 years of age. Four microscopic patterns of calcification were observed: coarse granular, circumscribed, trabecular, and "chicken-wire." CONCLUSIONS: Calcification in chondromyxoid fibroma was found more frequently than in previously reported studies. There was a tendency for this phenomenon to occur in the tumors of older patients, particularly those over 40 years old, and in chondromyxoid fibromas situated in flat bones, including ribs.

Classic adamantinoma in a 3-year-old.

Classic adamantinoma of the long bones is a rare, low-grade malignant neoplasm arising most often in the tibia and usually in patients during the second to fifth decades. Although adamantinomas have been described in children, the histologic pattern in this age group is different from that seen in adults and resembles osteofibrous dysplasia. The usual pattern of adamantinoma in children has been termed "differentiated adamantinoma" and follows a benign course. We report a case of adamantinoma in the proximal tibia of a 3-year-old patient. The lesion had abundant epithelial component with formation of keratin pearls, a pattern that has been described only in classic adamantinoma occurring in adults. Since differentiated adamantinomas are essentially benign and classic adamantinomas are low-grade malignancies, the finding of a classic variant at this young age raised important therapeutic and prognostic issues.

Mesenchymal chondrosarcoma with secondary orbital invasion.

Orbital involvement with mesenchymal chondrosarcoma is rare. Until recently, despite the young age of the affected population, exenteration was the recommended management. We report a patient with orbital invasion by mesenchymal chondrosarcoma managed surgically without exenteration. Adjuvant chemotherapy and radiotherapy were administered. There is no evidence of local or distant tumor recurrence with 30 months of postoperative follow-up. This and other recent case reports suggest that exenteration may not be necessary for local tumor control of mesenchymal chondrosarcoma in the orbit.