Search

Providing the best treatment options and appropriate prognostic information to patients with cartilaginous neoplasms of long bones depends on distinguishing benign from malignant lesions. Correlative interpretation of imaging, histopathology, and clinical information is the current method for making this distinction, yet the reliability of this approach has not been critically evaluated. This study quantifies the interobserver reliability of the determination of grade for cartilaginous neoplasms among a group of experienced musculoskeletal pathologists and radiologists.Nine recognized musculoskeletal pathologists and eight recognized musculoskeletal radiologists reviewed forty-six consecutive cases of cartilaginous lesions in long bones that underwent open biopsy or intralesional curettage. All diagnosticians had a bulleted history and preoperative conventional radiographs for review. Pathologists reviewed the original hematoxylin and eosin-stained glass slides from each case. Radiologists reviewed any additional imaging that was available, variably including serial radiographs, magnetic resonance imaging, and computed tomography scans. Each diagnostician classified a lesion as benign, low-grade malignant, or high-grade malignant. Kappa coefficients were calculated as a measure of reliability.Kappa coefficients for interrater reliability were 0.443 for the pathologists and 0.345 for the radiologists (p0.0001 for both). Kappa coefficients for a subgroup of cases determined to be high risk by subsequent clinical course were poorer at 0.236 and 0.206, respectively (p0.0001 for both). Slightly improved agreement among radiologists was noted for the twenty lesions that had magnetic resonance imaging available (Kappa = 0.437, p0.0001), but not for the lesions analyzed with serial plain radiographs or computed tomography scans.This study demonstrates low reliability for the grading of cartilaginous lesions in long bones, even among specialized and experienced pathologists and radiologists. This included low reliability both in differentiating benign from malignant lesions and in differentiating high-grade from low-grade malignant lesions, both of which are critical to the safe treatment of these neoplasms. This may explain in part the wide variation in outcomes reported for chondrosarcomas treated in different medical centers. New diagnostic and grading strategies linked to protocol-driven treatments are needed, but they must be measured against the long-term gold standard of patient outcomes.

Expression of the telomerase reverse transcriptase subunit telomerase reverse transcriptase gene is associated with most human malignancies. Because telomerase reverse transcriptase is rarely expressed in normal tissue, its presence in pathologic specimens is considered a marker of transformed cells. Moreover, high levels of expression have been correlated with poor prognosis in many cancers. Although telomerase activity has been found in chondrosarcomas, its prognostic significance in these malignant cartilage tumors is unknown. Malignancy in cartilage-derived tumors is assessed routinely by histomorphologic grading, but even well differentiated, low-grade lesions can metastasize. This unpredictable behavior greatly complicates the clinical treatment of cartilage tumors, making better prognostic indicators desirable. To address this issue we used immunohistochemistry to compare telomerase reverse transcriptase expression in a collection of 61 tumors consisting of malignant chondrosarcomas of varying grade and benign enchondromas. Associated case histories were reviewed to test the hypothesis that telomerase reverse transcriptase expression levels correlated with subsequent tumor recurrence. We found that the relative abundance of telomerase reverse transcriptase-expressing cells correlated significantly with grade and recurrence. These findings indicate that telomerase reverse transcriptase immunostaining may be a useful adjunct to the conventional three-level grading system.

The term lipoblastoma was first used by Jaffe in 19261 to refer to a tumor of immature fat cells. It was not consistently applied to the benign embryonal adipose tumors that now bear its name until Chung and Enzinger established the initial morphological criteria for its diagnosis in 19732. In doing so, they expanded on the descriptions provided by Vellios et al. in 19583 and by Shear in 19674 in their reports on the diffuse form of the tumor, called lipoblastomatosis. Despite their infrequent occurrence in the overall population and their rare discussion in the literature, lipoblastoma and lipoblastomatosis represent >15% of all benign soft-tissue neoplasms that present in the extremities of children who are five years of age or less5. The typical—almost exclusive—presentation of lipoblastoma as described in the literature is that of a painless soft-tissue mass, with or without progressive enlargement and with or without mass-effect symptoms when located near vital structures. Between February 1999 and October 2002, three children presented to the orthopaedic clinic at our institution for evaluation of thigh dimples; each was found to have a lipoblastoma. The families of our three patients were informed that data concerning the cases would be submitted for publication. Case 1. A thirty-nine-month-old girl presented with a three to four-month history of an enlarging dimple on the proximal part of the lateral aspect of the left thigh. The defect was noticed when it was approximately 7 mm in size, and it had grown to 25 mm in size by the time of presentation to the orthopaedic clinic. No history of trauma or pain was reported. Gestation, birth, development, and the medical history were unremarkable. Physical examination revealed a 2.5-cm, nontender deficit of the subcutaneous fat overlying the left greater trochanter. No …

Differentiating between primary tumors of the liver and metastatic lesions can, at times, be difficult. Various histochemical and immunohistochemical methods have been used in an effort to better delineate between hepatocellular carcinoma (HCC), especially the microglandular variant, primary cholangiocarcinoma, and metastatic adenocarcinoma; these ancillary studies can yield less than satisfactory results. Recently, anti-MOC31, a monoclonal antibody directed against a cell surface glycoprotein, has been shown to be helpful in distinguishing between adenocarcinoma and mesothelioma. This study addresses whether this antibody might be helpful in distinguishing between HCC, primary cholangiocarcinoma, and metastatic adenocarcinoma in the liver. Formalin-fixed, paraffin-embedded tissue sections from 15 HCC (including 10 microglandular variants), 14 primary cholangiocarcinomas, and 33 metastatic adenocarcinomas (7 colon, 1 lung, 8 breast, 4 GE jct/gastric, 9 pancreas, 2 small intestine, 1 renal, 1 ovary) were immunostained with anti-MOC 31 (1:40, Dako) after protease digestion and biotin block using a modified ABC technique. Positive staining was limited to membrane based reactivity; controls stained appropriately. Immunoreactivity for MOC31 was observed in 14 of 14 cholangiocarcinomas and 33 of 33 metastatic tumors. Staining was diffuse, intense, and readily interpretable, with rare exceptions. All 15 cases of HCC were negative. We conclude that cholangiocarcinoma and metastatic adenocarcinoma from a variety of sites express MOC31; HCC is uniformly negative for this marker. Anti-MOC31 may prove useful in the evaluation of liver neoplasms where primary hepatocellular and adenocarcinoma enter the differential diagnosis; it is not useful in separating primary cholangiocarcinoma from metastatic adenocarcinoma.

CD31 has been shown to be a sensitive and specific marker for endothelial differentiation among epithelioid and spindled-pleomorphic human neoplasms. However, the role of this marker in the evaluation of small round cell tumors has not been evaluated. Formalin-fixed, paraffin-embedded tissue sections from 276 small round cell tumors, including 85 Ewing's sarcoma/primitive neuroectodermal tumors (ES/PNET), 52 rhabdomyosarcomas, 10 extraabdominal polyphenotypic small cell tumors, six desmoplastic small cell tumors, 11 neuroblastomas, 23 Wilms' tumors, 20 retinoblastomas, 13 esthesioneuroblastomas, and 56 small cell malignant lymphomas were stained with CD31 (JC/70A, 1:40), using a modified avidinbiotin-peroxidase complex technique, after citrate buffer microwave epitope retrieval. Among nonlymphoid small round cell tumors, four of 85 ES/PNET were at least focally reactive. No other lesion in this group was positive. In contrast, the majority of well-differentiated (11 of 17), intermediately differentiated (two of three), and lymphoblastic lymphomas (three of three) were positive. Small cleaved lymphomas (three of 13 follicular, one of 13 diffuse) were less often reactive, whereas small noncleaved lesions were negative. Although reactivity for CD31 in ES/PNET is uncommon, the presence of platelet/endothelial cell adhesion molecule in a small cell neoplasm should not in isolation be taken as evidence of hematopoietic origin. These results further define the utility of CD31 in the evaluation of human neoplasms.