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Richard J O'Donnell

Publications and source records attributed to Richard J O'Donnell.

8 recordsLinked to original sources
PubMed2006

Mismatch repair protein expression and microsatellite instability: a comparison of clear cell sarcoma of soft parts and metastatic melanoma.

Clear cell sarcoma of soft parts is a rare soft tissue malignancy that shows phenotypic overlap with cutaneous melanoma but can be distinguished by the presence of a t(12;22) translocation. Microsatellite instability (MSI), a variation in the lengths of short repeat DNA segments in the genome, has been implicated in melanoma tumorigenesis, but is rare or absent in clear cell sarcoma. Defects in the mismatch repair (MMR) enzyme complex correlate with MSI in some tumor types, allowing the use of immunohistochemistry for the MMR proteins hMLH1 and hMSH2 to predict the presence of MSI. To determine if the association between MMR defects and MSI extends to clear cell sarcoma, we compared a group of nine clear cell sarcomas to 11 metastatic melanomas on the basis of MSI and the expression of MMR proteins. MSI was studied using fluorescence-based multiplexed PCR of five loci. Immunohistochemistry was evaluated on formalin-fixed paraffin-embedded tissue for hMLH1, hMHS2 and hMSH6. MSI was present in only 1/9 (11%) clear cell sarcoma case and in 8/11 (73%) melanoma cases. Immunostaining for hMLH1 and hMSH2 was preserved in all the clear cell sarcomas but loss of immunostaining for one or both proteins was seen in 6/11 melanomas (55%). hMSH6 was detected in 7/9 (78%) clear cell sarcomas and 10/11 (91%) of melanomas. Clear cell sarcoma and metastatic melanoma differed significantly with respect to the presence of MSI (P=0.010) and staining for hMLH1 and/or hMSH2 (P=0.014) but not hMSH6 (P=0.57). Mismatch repair, and consequently genomic instability may contribute to tumorigenesis in melanoma but not clear cell sarcoma. Immunostaining for hMLH1 and hMSH2 and MSI analysis may be helpful in the differential diagnosis of large soft tissue or visceral malignancies with melanocytic differentiation.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Survival after recurrence of osteosarcoma: a 20-year experience at a single institution.

BACKGROUND: Approximately one-third of patients with osteosarcoma who have a complete response to their initial treatment can be expected to relapse. It is important to define what host, tumor, or treatment characteristics determine outcome after relapse. We present findings in 59 patients treated at our institution from 1974 to 1996 who have relapsed one or more times after their initial response. METHODS: Host and tumor characteristics at diagnosis and relapse, therapeutic interventions and survival outcomes were determined from examination of medical records and a follow-up questionnaire. RESULTS: Of the 59 patients, 37 initially presented with localized disease of the extremity, 11 with localized non-extremity disease, and 11 with metastatic disease. This report focuses on those with localized disease of the extremity. For these patients, median time from original diagnosis to first recurrence was 14 months. Median survival after first recurrence was 31 months. The median post initial relapse survival was the same for patients whose first relapse occurred before or after 14 months from original diagnosis. Seventeen of 29 patients with systemic metastasis at first recurrence had complete removal of their disease and had a median post-op survival of 2.5 years, while the remaining 12 patients with no surgery, had a median survival of 2 years. Of the 37 patients who presented with primary disease only in the extremities and relapsed: 31 died (2 more than 6 years from first recurrence) and 6 are alive from 6 to 24 years from first recurrence (5 without disease and 1 with disease). Three of the five disease-free survivors had three or more relapses. CONCLUSION: With a long follow-up time, we found 15% of patients with relapsed osteosarcoma who originally presented with localized disease in the extremity are alive with no evidence of disease at 10 years from first recurrence (Kaplan-Meier estimate). Even patients with multiple relapses may have long-term disease-free survival after salvage therapy. Chemotherapy and time to first recurrence were unrelated to survival after relapse in this study. Complete surgical removal of metastatic disease may be important for long-term survival.

Adolescent↗
PubMed2006

Utility of CD117 immunoreactivity in differentiating metastatic melanoma from clear cell sarcoma.

CONTEXT: Clear cell sarcoma is a malignant soft tissue tumor with melanocytic differentiation. Molecular methods are sometimes necessary to identify the unique t(12; 22)(q13;q12) translocation and differentiate clear cell sarcoma from melanoma. OBJECTIVE: To determine whether CD117 immunoreactivity may be useful in separating melanoma from clear cell sarcoma. DESIGN: We identified 20 tumors listed in our surgical pathology files that were diagnosed as clear cell sarcoma or in which clear cell sarcoma was strongly considered. These were tested for the presence of the t(12;22) translocation by reverse transcriptase/polymerase chain reaction and sequencing from paraffin-embedded tissue. Tumors with a t(12;22) translocation were immunostained with an antibody to CD117 and compared with 16 similarly stained metastatic melanomas. RESULTS: Twelve tumors from 9 patients demonstrated t(12;22). No metastatic melanomas demonstrated t(12;22). None of the 12 clear cell sarcomas showed membrane or cytoplasmic staining for CD117. Conversely, 10 (63%) of 16 metastatic melanomas were, at least focally, positive for CD117; this difference was significant (P < .001). Interestingly, 3 tumors in which clear cell sarcoma was initially considered as a diagnosis, but which lacked t(12;22), were also positive for CD117. CONCLUSIONS: Reverse transcriptase/polymerase chain reaction, performed on paraffin-embedded tissue, is a useful, rapid tool for identifying the presence of t(12;22) in clear cell sarcoma. The CD117 immunoreactivity may prove useful in the differential diagnosis of deep soft tissue or visceral lesions with melanocytic differentiation; positive staining results exclude clear cell sarcoma, but are compatible with metastatic melanoma.

Adult↗
PubMed2005

Ewing sarcoma as a second malignant neoplasm after acute lymphoblastic leukemia.

Second malignant neoplasms (SMNs) are being increasingly recognized. This report describes a case of a 7-year-old girl with a history of acute lymphoblastic leukemia (ALL) who presented with a mass in her humerus that was diagnosed as Ewing sarcoma. Second malignant neoplasms are relatively rare in survivors of ALL treated without radiation. Even more unusual is the development of Ewing sarcoma as the SMN.

Bone Neoplasms↗
PubMed2005

Oncologic approaches to pediatric limb preservation.

Preservation of limb function in the pediatric oncology patient is uniquely challenging. Treatment must be strictly prioritized in terms of the patient's life, the limb, its function, length equalization, and cosmetic appearance. At the same time, social, socioeconomic, and cultural factors must be understood and respected to achieve the most advantageous outcome for both the patient and family. Given these considerations, as well as the relative rarity of many oncologic diagnoses and the myriad of presentation scenarios, drafting generalized treatment recommendations is difficult. Instead, orthopaedic intervention in the care of children and young adults with oncologic conditions must be individualized, with the broad goal being optimization of limb function rather than rigid advocacy of limb salvage.

Amputation, Surgical↗
PubMed2003

Reconstruction of the pelvis after resection of tumors about the acetabulum.

Periacetabular resections for primary malignancies and metastatic disease require reconstruction to restore weightbearing along anatomic axes. Without reconstruction, patients are unable to ambulate independently, and are left with a disfigured pelvis and shortened limb. The current authors describe a reconstruction technique using Steinmann pins augmented with methylmethacrylate reconstruction, and autoclaved autografting, in combination with total hip arthroplasty, after resection of primary sarcomas of the pelvis. For this study, the results of 15 patients at two institutions who had surgery by the same surgeons were retrospectively reviewed. The patients had primary malignant tumors of the pelvis, and had limb-sparing resections between 1985 and 2000. Three measures of outcome were evaluated: survival, function, and pain. The surgical method uses Steinmann pins with bone cement to fill in areas of bone loss that cannot be reconstructed with autoclaved autograft. A constrained polyethylene acetabular component is cemented into this bed. Twelve patients had chondrosarcoma and one patient had osteosarcoma. The remaining two patients had alveolar sarcoma of soft parts. Six patients died of disease. Seven patients were alive with no evidence of disease, and two were alive with disease at the most recent followup. Early return to ambulation without assistive devices occurred in nine of 15 patients. The functional outcome of this technique compares favorably with others reported. Sixty percent of patients ambulated independently without assistive devices, compared with 0% to 10% in other studies reviewed. The time required for independent gait is similar to recovery from a total hip arthroplasty. Moreover, this method minimized leg length discrepancy, while also producing a favorable cosmetic result.

Acetabulum↗