Aberrant expression of cell-cycle regulatory proteins in human mesenchymal neoplasia.

We previously demonstrated that approximately one-half of soft-tissue sarcomas were devoid of either pRB, the product of the retinoblastoma gene, or 16, the product of the MTS1/CDKN2 gene, while a smaller subset of aggressive mesenchymal tumors without metastatic potential did not express RB by immunohistochemistry. We now studied the expression of two additional important cell-cycle regulators, namely cyclin D1 and p53, in the same cohort of high- and low-grade lesions. In the aggregate, our data provide a comprehensive overview of the importance of cell-cycle deregulation in mesenchymal neoplasia. Paraffin sections of 58 sarcomas and 23 soft-tissue tumors of low malignant potential (STT-LMP) were reacted with monoclonal antibodies against cyclin D1 and p53, using optimized immunohistochemical staining protocols. The staining data were correlated with expression of pRB and p15 and with a variety of pathologic parameters. A total of 33 of 58 sarcomas (57%) and 9 of 23 STT-LMP (39%) overexpressed p53. Fourteen sarcomas (24%) and 4 STT-LMP (17%) overexpressed cyclin D1. There was no correlation between expression of these two genes and histologic tumor type or grade. Loss of RB and loss of p16 or overexpression of cyclin D1 were mutually exclusive events. Considering all four cell-cycle regulators, sarcomas had a significantly higher abnormality rate than did STT-LMP (P < .005). Only 10% of the sarcomas but 39% of STT-LMP showed normal expression of all four gene products. Based on our findings, overexpression of cyclin D1 and (presumably mutant) p53 appear to be among the most common molecular alterations in human mesenchymal neoplasia, and abrogation of cell-cycle control is observed in the great majority of sarcomas; it is present significantly less frequently in low-grade lesions.

Intra-abdominal embryonal rhabdomyosarcoma in an adult.

Rhabdomyosarcoma is an uncommon neoplasm in the adult population. Sporadic cases of primary rhabdomyosarcoma arising in the abdomen have been reported, but these cases are limited almost exclusively to the pediatric population. We report a well-documented case of primary intra-abdominal rhabdomyosarcoma in a 57-year-old woman. The patient presented with a pelvic mass and an elevated serum CA 125 and was referred to gynecologic oncologists at our institution for a presumed primary gynecologic malignancy. Intraoperatively, amorphous gelatinous tumor comprised a large portion of the peritoneal cavity. Surgical exploration of the abdomen failed to implicate any specific organ as the site of origin of the tumor. The overall histologic pattern of the resected tumor was most consistent with embryonal type rhabdomyosarcoma. To our knowledge this is the first well-documented case report of non-hepatobiliary, adult, intra-abdominal embryonal rhabdomyosarcoma in the English language literature. The presentation of a rare adult sarcoma mimicking a gynecologic malignancy was an unusual feature that complicated the diagnosis in this case.

Recurrent intranodal palisaded myofibroblastoma with metaplastic bone formation.

Intranodal palisaded myofibroblastoma (IPM) is a rare primary nonlymphoid tumor of the lymph node, which can easily be mistaken for other spindle cell tumors. Intranodal palisaded myofibroblastoma is thought to arise from intranodal myofibroblasts, a finding that is supported by its immunophenotype, positive immunostaining for actin and vimentin, and negative immunostaining for desmin. Characterized by a benign clinical course, IPM is treated by simple surgical excision. We describe a 49-year-woman, who had cadaveric renal transplantation in 1992 and recurrent IPM 41/2 years after its original excision. To our knowledge, this case represents only the second known case of recurrent IPM. The histologic feature of metaplastic bone formation in this case has not been previously described in IPM.

Epstein-Barr virus-associated renal smooth muscle neoplasm: report of a case with review of the literature.

Epstein-Barr virus (EBV) has been associated with nasopharyngeal carcinoma, some Burkitt's-type lymphomas, and posttransplantation lymphoproliferative disorder. Recently, an association between EBV and smooth muscle tumors, both malignant and benign, in the acquired immunodeficiency syndrome and posttransplantation populations has been made. We report, to our knowledge, the first case of a renal EBV-associated smooth muscle tumor. A 33-year-old man with acquired immunodeficiency syndrome presented with a mass of the left kidney that was radiographically suspicious for malignancy. He underwent left radical nephrectomy. The tumor measured 3.0 cm in the largest dimension, was well-circumscribed, and was composed of fascicles of bland spindle cells with blunt-ended nuclei, which often intersected at right angles. Focal areas of cell crowding and nuclear pleomorphism were present. No areas of lipomatous differentiation were identified. Immunohistochemically, the tumor cells were positive for desmin and muscle-specific actin and were negative for HMB-45 and CD21 (an EBV receptor). In situ hybridization with EBV-encoded RNA-1, a probe that recognizes a non-poly(A) RNA EBV transcript expressed in latently infected cells, was diffusely positive. At 6 months postnephrectomy, the patient showed no evidence of local recurrence or metastases. The incidence of this tumor is expected to increase as both the numbers of patients undergoing solid organ transplantation and the survival time of patients with the acquired immunodeficiency syndrome increase. A better understanding of the biology and pathogenesis of this entity will be important for future management of these patients.

Thrombotic thrombocytopenic purpura that is refractory to therapeutic plasma exchange in two patients with occult infection.

BACKGROUND: The etiology of thrombotic thrombocytopenic purpura (TTP) remains undetermined. TTP has been associated with a number of secondary causes including infections, drugs, menses, pregnancy, autoimmune diseases, and bone marrow transplantation. Regardless of the inciting factors, it is widely accepted that endothelial injury and platelet aggregation are integral components. The morbidity and mortality have been significantly reduced with the use of plasmapheresis. However, refractory forms of TTP remain a clinical management challenge. Refractory TTP has not previously been associated with occult bacterial infection. CASE REPORT: Two patients had classic TTP that was refractory to daily plasma exchange with fresh-frozen plasma. Multiple attempts over a period of months to wean these patients off plasma exchange resulted in exacerbations of disease activity, as indicated by increased schistocytosis, decreased hematocrit, increased serum lactate dehydrogenase, and decreased platelet counts. Both patients were empirically treated for infections during hospitalization, although microbial cultures failed to isolate an organism. Discontinuation of antimicrobial therapy on multiple occasions in one patient was associated with recurrence of disease. In the other patient, dental extraction with drainage of an occult periodontal abscess resulted in sustained remission of disease. CONCLUSION: Occult bacterial infection may play a role in triggering and sustaining TTP that is refractory to conventional treatment. A careful search for such an infection and appropriate antimicrobial therapy should be considered in the management of these patients.