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The molecular events that precede the development of osteosarcoma, the most common primary malignancy of bone, are unclear, and concurrent molecular and genetic alterations associated with its pathogenesis have yet to be identified. Recent studies suggest that activation of beta-catenin signaling may play an important role in human tumorigenesis. To investigate the potential role of beta-catenin deregulation in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for beta-catenin accumulation using immunohistochemistry. Potential activating mutations were investigated by sequencing exon 3 of the beta-catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of beta-catenin in 33 of 47 samples (70.2%); however, mutation analysis failed to detect any genetic alterations within exon 3, suggesting that other regulatory mechanisms may play an important role in activating beta-catenin signaling in osteosarcoma. In our survival analysis, beta-catenin deregulation conferred a hazard ratio of 1.05, indicating that beta-catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinicopathologic parameters, beta-catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of beta-catenin signaling is a common occurrence in osteosarcoma that is implicated in the pathogenesis of osteosarcoma.

The molecular events that precede the development of osteosarcoma, the most common primary malignancy of bone, are unclear, and concurrent molecular and genetic alterations associated with its pathogenesis have yet to be identified. Recent studies suggest that activation of beta-catenin signaling may play an important role in human tumorigenesis. To investigate the potential role of beta-catenin deregulation in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for beta-catenin accumulation using immunohistochemistry. Potential activating mutations were investigated by sequencing exon 3 of the beta-catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of beta-catenin in 33 of 47 samples (70.2%); however, mutation analysis failed to detect any genetic alterations within exon 3, suggesting that other regulatory mechanisms may play an important role in activating beta-catenin signaling in osteosarcoma. In our survival analysis, beta-catenin deregulation conferred a hazard ratio of 1.05, indicating that beta-catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinicopathologic parameters, beta-catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of beta-catenin signaling is a common occurrence in osteosarcoma that is implicated in the pathogenesis of osteosarcoma.

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations of surgical specimens. The College [...]

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations of surgical specimens. The College [...]

* Context.--Sarcomatous transformation is a rare complication of Paget disease of bone. Prognosis in patients with other types of sarcomas arising in bone has improved in the last several decades because of therapeutic advances. However, because of the rarity of Paget sarcoma, outcome studies in these patients are limited. Objective.--To determine whether prognosis for Paget sarcoma has improved. Design.--Seventy cases of sarcomas arising in the setting of Paget disease were collected, and the histologic and clinical findings were reviewed. Clinical follow-up was obtained in 67 cases. Results.--Sarcoma arising in Paget disease tended to arise in older men (46 men, 24 women; age range, 31-88 years; mean age, 66 years) and predominated in the axial skeleton (n = 37), especially in the pelvis. Thirty-three pa tients had a clinical history of Paget disease ranging in duration from 16 months to 30 years (mean, 15 years). No significant difference in incidence between monostotic (n = 33) and polyostotic (n = 36) disease was noted. Most tumors were osteosarcomas (88%). All tumors were high grade. Follow-up information was obtained in 67 of 70 cases (range of follow-up, 1-252 months). Survival ranged from 1 month to 20 years, with a 5-year survival rate of 10%. Conclusions.--Prognosis remains poor in patients with Paget sarcoma. There is no significant correlation between the number of bones involved with Paget disease or the duration of disease and development of Paget sarcoma. Poor prognosis in Paget sarcoma is unrelated to site or stage at presentation. (Arch Pathol Lab Med. 2007;131:942-946), Paget disease of bone (also called osteitis deformans) was originally described by Sir James Paget in 1877. (1) Paget disease occurs primarily in the elderly and is characterized by localized [...]

* Context.--Epithelioid and epithelial neoplasms seen in bone are rare and include epithelioid variants of vascular lesions, osteoblastoma, osteosarcoma, chordoma, and chondroblastoma as well as adamantinoma and metastatic carcinoma. Objective.--To [...]

A 40-year-old man sought medical attention for vague flank pain. His past medical history was significant for mucinous cystadenoma of the appendix (status 1 1/2 years postappendectomy with intraoperative right [...]

Aims The diagnosis of undifferentiated pleomorphic sarcoma ( UPS) may be challenging, as other lesions with undifferentiated spindle cell morphology must be excluded, including melanoma. Microphthalmia-associated transcription factor (Mi TF) stains naevi and epithelioid melanomas, as well as some mesenchymal neoplasms. The aim of this study was to evaluate the prevalence of Mi TF and melanocytic markers in UPS and a subset of atypical fibroxanthoma ( AFX). Methods and results Mi TF, SOX10, Melan-A, HMB45 and S100 immunostaining was performed on resection specimens from 19 UPSs and five AFXs. Next-generation sequencing of 50 genes was performed in UPSs to exclude dedifferentiated melanoma. In 17 of 19 UPSs (89%), tumour cells showed nuclear positivity for Mi TF that was not eliminated by casein block. Three showed focal nuclear staining for HMB45, which was eliminated by casein block. One showed focal nuclear vacuole staining for S100 with red but not brown chromogen. None expressed SOX10 or Melan-A. Mutational analysis of 15 UPSs with adequate DNA showed no mutations within hotspot regions of BRAF, KIT, or NRAS. Four of five AFXs (80%) stained with Mi TF; other markers were negative. Conclusion There is a high prevalence of nuclear Mi TF expression in UPSs (89%) and AFXs (80%). Rare UPSs showed non-specific nuclear HMB45 or S100 staining. These findings argue against using Mi TF in isolation to differentiate between UPS or AFX and melanoma, and caution in interpreting focal staining for a single additional melanocytic marker. Casein block may eliminate non-specific staining. Mi TF should be used to support a diagnosis of melanoma only if multiple melanocytic markers are positive. [ABSTRACT FROM AUTHOR]