EBV-associated perianal Hodgkin's disease in an HIV-positive individual.

Hodgkin's disease (HD) has a higher incidence in HIV-positive individuals. It tends to occur at extranodal sites, frequently exhibits an unfavorable histological type with large numbers of neoplastic cells, and almost invariably harbors Epstein-Barr Virus (EBV). We describe a case of a 33-year-old HIV-positive man who presented with anal pain from a 4-cm mass in the anorectal canal. He had no B symptoms or peripheral lymphadenopathy. A chest X-ray was within normal limits. A biopsy showed an ulcerated mass composed of a mixed infiltrate of lymphocytes, plasma cells, eosinophils, and Reed-Sternberg (RS) cells positive for CD15 and strongly positive for CD30. They were negative for CD45 and CD20. Numerous RS cells and lymphocytes were positive for EBV RNA using the EBER-1 probe. This highly unusual presentation of HD may reflect the greater incidence of anorectal lymphoma and of extranodal HD in the HIV-positive population.

Loss of cyclin-dependent kinase inhibitor p27Kip1 is a novel prognostic factor in localized human prostate adenocarcinoma.

p27Kip1 is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation by mediating cell cycle arrest in G1. This study was undertaken to assess the prognostic value of p27Kip1 in localized human prostate cancer. Archival material from 113 radical prostatectomy specimens obtained between 1985 and 1993 was stained immunohistochemically for p27Kip1 protein using a commercially available antibody. Patient charts were reviewed for preoperative serum prostate-specific antigen, clinical and pathological staging, Gleason tumor grade, time to biochemical and clinical recurrence, and survival. Strong p27Kip1 staining was uniformly seen in benign prostatic epithelial components in all tumor sections. p27Kip1 staining was reduced in most prostate cancers and was variable in prostatic intraepithelial neoplasia. Decreased p27Kip1 staining (<25% of nuclei stained positive for p27Kip1) correlated with seminal vesicle involvement (P = 0.0032) and with higher Gleason grade (P = 0.0114). On univariate analysis, low p27Kip1 predicted an increased risk of treatment failure in the node-negative cohort (P = 0.0037) and in the subset who did not receive neoadjuvant hormonal therapy (P = 0.049). Low p27Kip1 expression was an independent predictor of treatment failure on multivariate analysis of lymph node negative prostate cancers following radical retropubic prostatectomy (n = 102; P = 0.047). Seminal vesicle involvement (P = 0.034) and positive surgical margins (P = 0.047) were also independent prognostic factors for disease recurrence. In patients who received preoperative neoadjuvant hormonal therapy, low p27Kip1 in the pathological specimen was an even stronger predictor of outcome than it was in the entire group (n = 23, P = 0.015).

Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer.

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for reliable prognostic markers to assist clinicians in making management decisions. Although a variety of factors have been tested, only tumor stage, grade, size, hormone receptor status, and S-phase fraction are used on a routine basis. The cell cycle is governed by a family of cyclin-dependent kinases (cdks), which are regulated by associated cyclins and by phosphorylation. p27Kip1, a cyclin-dependent kinase inhibitor, regulates progression from G1 into S phase by binding and inhibiting cyclin/cdks. p27Kip1 protein levels and/or activity are upregulated by growth inhibitory cytokines including transforming growth factor-beta (TGF-beta) and, thus, provide an important link between extracellular regulators and the cell cycle. Loss of p27Kip1, a negative cell-cycle regulator, may contribute to oncogenesis and tumor progression. However, p27Kip1 mutations in human tumors are extremely rare. We have demonstrated by immunohistochemistry that p27Kip1 protein levels are reduced in primary breast cancers and that this is associated with tumor progression in both in situ and invasive lesions. This was confirmed by western analysis, reflected in increased G1/S-phase cyclin-dependent kinase activities and shown to be regulated posttranscriptionally by in situ hybridization. Furthermore, on multivariate analysis, low p27Kip1 is a predictor of reduced disease-free survival. This simple and reliable immunohistochemical assay may become a routine part of breast cancer evaluation and may influence patient management.

Progressive unilateral mandibular swelling in adolescence: a diagnostic dilemma.

Asymmetrical swelling of the mandible in adolescence may pose a significant diagnostic dilemma. The differential diagnosis ranges from traumatic, infectious, and metabolic processes to benign and malignant tumors. Among them, fibrous dysplasia, osteomyelitis, and malignancy may present with similar clinical and radiological features, making an accurate diagnosis quite difficult. This is an illustrative case involving a 14-year-old girl who initially presented with diffuse fibrous dysplasia of the mandible and in whom a superimposed osteomyelitis of the left side subsequently developed. Multiple investigations and several biopsies were required to arrive at a diagnosis. Similarities in clinical and radiographic findings of fibrous dysplasia, osteomyelitis, and malignancy are presented, and implications for treatment are discussed.

Adenocarcinoma of the lung metastatic to the psoas muscle.

Hematogenous metastasis to the psoas muscle is rare, and the resulting clinical symptoms may mimic psoas abscess or hemorrhage. When the clinical history is not specific, CT is important in documenting the presence of a psoas mass and providing biopsy guidance for histologic diagnosis. Only three previously reported cases have been related to a primary carcinoma of the lung.

The effect of infection and lag screw fixation on revascularization and new bone deposition in membranous bone grafts in a rabbit model.

We have suggested that rigid fixation of membranous bone grafts in the presence of infection may improve graft-recipient bone union by facilitating graft revascularzation. To test this hypothesis, we grafted autogenous membranous bone grafts to the mandibles of 94 New Zealand White rabbits. Lag screw fixation was applied in half the animals. The wounds were inoculated with a range of Staphylococcus aureus doses. Infected and noninfected rabbits were injected weekly over a 5-week course with fluorescein bone markers and with a marker of vascular endothelium (procion red) just prior to sacrifice. Revascularization and new bone deposition in the grafts were then quantified histologically for the 75 rabbits available for data collection. Infection decreased the amount of graft revascularized and the amount of new bone deposited for both rigidly fixated and nonfixated grafts. Grafts fixated with a lag screw showed a greater amount of revascularization and new bone deposition in the presence and absence of infection when compared with nonfixated grafts, supporting the hypothesis that rigid fixation of membranous bone grafts in the presence of infection may promote graft survival and union by improving revascularization and osteogenesis within the graft.

Steroid-responsive interstitial lung disease in patients receiving 2'-deoxy-5-fluorouridine-infusion chemotherapy. A report of three cases.

BACKGROUND: Continuous infusion of 2'-deoxy-5-fluorouridine (FUdR) has shown promise in its activity against metastatic renal cell carcinoma. Its side-effect profile is dominated by gastrointestinal toxicity; there are no known adverse pulmonary reactions. To the authors' knowledge, this is the first report on the development of lung toxicity in three patients receiving FUdR-infusion chemotherapy for metastatic renal cell carcinoma. METHODS: The hospital charts of three patients presenting with pulmonary symptoms during FUdR chemotherapy were reviewed. A literature search was performed regarding FUdR-related pulmonary toxicity. RESULTS: Nonproductive cough, dyspnea, and fever appeared within the 10th chemotherapy cycle. Chest radiographs showed interstitial disease in each case, accompanied by a restrictive pattern by pulmonary-function testing. Lung biopsies were performed on two patients showing a pattern of interstitial inflammation. Discontinuing FUdR and instituting steroidal therapy invariably improved symptoms, as was evident by chest radiographs and pulmonary function tests. In one patient, resuming FUdR treatment resulted in a recurrence of the respiratory symptoms, which was controlled with an increased steroidal dose. All three patients required low dose steroids to maintain their baseline respiratory functions. CONCLUSIONS: 2'-deoxy-5-fluorouridine-related lung toxicity is an uncommon event and occurs late in the treatment course. It is rapidly symptomatic and responds readily to steroidal therapy.

Acceleration of experimental lapine osteoarthritis by calcium pyrophosphate microcrystalline synovitis.

OBJECTIVE: To investigate the effects of chronic calcium pyrophosphate dihydrate (CPPD) synovitis on the development of osteoarthritic (OA) lesions in an animal model. METHODS: OA was induced in the right knees of 30 male New Zealand white rabbits by partial lateral meniscectomy and section of the fibular collateral and sesamoid ligaments (PLM/LS), followed by 8 weekly intraarticular (IA) injections of 1 mg (low-dose) or 10 mg (high-dose) of CPPD crystals in 3 sets of experiments (10 rabbits each). The contralateral left knees served as controls: experiment 1 PLM/LS alone, experiment 2 8 weekly IA injections of CPPD crystals alone, and experiment 3 sham surgery plus 8 weekly IA injections of CPPD crystals. RESULTS: At 8 weeks, repeated IA injections of low-dose and high-dose CPPD crystals into meniscectomized right knees resulted in more severe OA than in meniscectomized but noninjected left knees (experiment 1) (P = 0.003 and P = 0.001, respectively). One-fourth of the meniscectomized knees (11 of 40), both CPPD-injected and noninjected, showed embedded synovial cartilage shards. CONCLUSION: The data demonstrate a worsening effect of chronic CPPD crystal-induced synovitis on experimental OA produced in the rabbit knees by PLM/LS, and support a possible role for CPPD microcrystalline inflammation in the progression of OA lesions in clinical CPPD crystal deposition disease.

Young Investigator Award. Percutaneous facet joint fusion: preliminary experience.

PURPOSE: The synovium-lined apophysial joint is an important cause of back pain through facet arthrosis and nerve root pressure. The short-term results of two relatively noninvasive treatments--facet block and facet rhizotomy--have been better than their long-term results. The authors propose treatment with fusion of the posterior facet joints in the lumbar spine by means of a simple percutaneous procedure performed under local anesthetic with use of radiologic guidance. MATERIALS AND METHODS: In the first phase of this study the technical feasibility of the concept was established in human cadaver spine. In the second phase a canine model was tested in which bone grafts were surgically inserted into lumbar facet joints. Five male and two female mongrel dogs, weighing 18-25 kg (mean, 20.3 kg), were operated on. Each procedure was done in three steps: First, preoperative computed tomographic (CT) scans were obtained to measure facet depth. Second, surgery was performed under fluoroscopic guidance with use of a threaded guide wire, a small cannulated coaxial drilling system, and hydroxyapatite cancellous bone plugs. Third, early postoperative CT scans were obtained to verify bone plug location. CT was repeated at 4 and 6 months after surgery to check for fusion. The dogs were killed at 6 months, and histologic examination was performed. RESULTS: Successful insertion of the bone plug was achieved in 12 of the 14 facets (86%). One dog died as a complication of the procedure. Fusion occurred in five of the 12 surgically treated facets (42%). CONCLUSION: Drilling and surgical insertion of bone plugs into facet joints of dogs were feasible. The fusion results are promising and may improve with future modifications of the technique.

Pentastomiasis in Canada.

We report a case of human pentastomiasis in a 28-year-old man who emigrated to Canada from Nigeria in 1982 and died as a result of a motor vehicle accident in 1989. At autopsy, in addition to trauma, numerous small cystic nodules (3 to 9 mm in diameter) were discovered in the liver, pleura, lungs, and mesentery and under the intestinal and parietal peritoneum. The parasites were diagnosed as well-preserved, encysted Armillifer armillatus nymphs. Neither degenerative nor inflammatory granulomatous reactions were observed in the adjacent tissue. To our knowledge, this is the first reported case of human infection with encysted nymphs of A armillatus and the eighth reported case of pentastomiasis in North America.

Calcification in bronchopulmonary sequestration.

We report an unusual complication in a patient with intralobar bronchopulmonary sequestration. Chest tomography, computed tomography, and specimen radiography showed a mass containing numerous round calcifications in the posterior basal segment of the left lower lobe. Pathologic examination disclosed an Exophiala fungus infection and broncholiths within bronchiectatic cavities in the sequestered segment.

Skeletal lymphoma.

The records of forty-two patients with lymphoma of bone [.11 with Hodgkin disease (HD), 31 with non-Hodgkin lymphoma (NHL)] were retrospectively reviewed to correlate histologic type with sites of osseous involvement, radiographic patterns of bone destruction, and prognosis. The vertebral column was the most frequent site of axial involvement and the femur was the commonest site overall. In HD, the most frequent radiographic pattern was vertebral sclerosis, while periosteal reaction was noted in two focal femoral lesions and hypertrophic pulmonary osteoarthropathy in one patient. In NHL, permeative destruction predominated, while unusual layered periosteal reaction and eccentric cortical destruction were each seen in two patients. Radiographic patterns of bone involvement alone cannot be used to predict histologic type or prognosis. Staging remains the most important prognostic indicator. For skeletal lymphoma, instead of the traditional Ann Arbor Staging System, we prefer the more specific Mayo Staging System which relates the temporal appearance of osseous disease to nodal or soft-tissue disease or both.