Low proliferative rate of invasive node-negative breast cancer predicts for a favorable outcome: a prospective evaluation of 669 patients.

This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.

Three-dimensional RODEO breast MR imaging of lesions containing ductal carcinoma in situ.

PURPOSE: To assess whether rotating delivery of excitation off resonance (RODEO) breast magnetic resonance (MR) imaging can help detect ductal carcinoma in situ (DCIS) lesions, determine tumor extent, and differentiate pure DCIS from DCIS with an invasive component. MATERIALS AND METHODS: Twenty-two patients with DCIS lesions were evaluated with three-dimensional RODEO MR imaging. Nineteen patients had available mammograms for review. RESULTS: MR imaging enabled detection of all 22 cases of DCIS, DCIS with microinvasion, or invasive ductal carcinoma with extensive intraductal component. A clumped enhancement pattern was seen on MR images in all cases of pure DCIS. Spiculated enhancement was seen in four of six (67%) patients who had DCIS with microinvasion and in nine of 11 (82%) who had invasive ductal carcinoma with extensive intraductal component. RODEO MR imaging enabled accurate determination of tumor extent in 21 of 22 (95%) patients. Mammography depicted 18 of 19 DCIS lesions. No mammographic feature helped differentiate pure DCIS from DCIS with microinvasion. Mammography enabled accurate determination of tumor extent in 14 of 19 (74%) patients. CONCLUSION: Three-dimensional RODEO MR imaging can be an adjunct to mammography because of its ability to enable better determination of tumor extent and differentiation of pure DCIS from DCIS with an invasive component.

Evaluation of neoadjuvant chemotherapeutic response of locally advanced breast cancer by magnetic resonance imaging.

BACKGROUND: The implementation of new treatment protocols for locally advanced breast cancer is currently limited by inaccurate evaluation of response to neoadjuvant chemotherapy. A recently developed dedicated breast magnetic resonance imaging (MRI) method (RODEO MRI) was evaluated as a tool for determining tumor response and extent of residual disease after neoadjuvant chemotherapy. METHODS: Thirty-nine patients with Stage II, III, or IV breast carcinoma were prospectively evaluated prior to and following neoadjuvant chemotherapy by MRI, physical examination, and mammography. Assessment of response determined by the three methods was compared. In addition, detailed pathologic correlation of residual disease was determined by serial sectioning of 31 mastectomy specimens from 30 patients. Nine patients had breast conservation, and were included in the response evaluation only. Estimates of tumor response were made by both surgical and medical oncologists. Independent interpretations of MRI studies without knowledge of clinical response were made by three radiologists. RESULTS: The surgical oncologists assessed complete response (CR), partial response (PR), and no response (NR) in 11, 22, and 7 cases, respectively. The medical oncologists assessed CR, PR, and NR in 12, 21, and 7 cases, respectively. The surgical and medical oncologists' clinical assessment of response agreed with the results of MRI in 52% and 55% of cases, respectively, and with each other in 30 of 40 cases (75%). Mammography correlated with MRI response in only 52% of cases. However, MRI accurately predicted the pathologic determination of residual disease in 30 of 31 cases (97%). There was no disagreement in the assessments of residual disease or response among the three radiologists. CONCLUSIONS: RODEO breast MRI accurately estimates residual disease after induction chemotherapy. It assesses response to neoadjuvant chemotherapy better than traditional methods of physical examination or mammography. The information obtained from this MRI technique may be used as an objective tool during clinical trials, and to select patients better for breast conservation after neoadjuvant chemotherapy for locally advanced disease.

Prognostic indicators in children with IgA nephropathy--report of the Southwest Pediatric Nephrology Study Group.

Investigators in 13 pediatric nephrology centers reviewed clinical and pathological features in 218 children and adolescents with IgA nephropathy (IgAN), with particular emphasis on 80 patients who had follow-up periods of at least 4 years. Potential prognostic markers in the 80 children were compared between 12 (15%) who developed end-stage renal disease (ESRD) versus 68 who did not. The relationship between clinical and pathological features and the subsequent development of ESRD was examined using stepwise linear discriminant analysis in addition to standard univariate analysis. Seven variables were found to be predictive of ESRD: the presence of glomerular sclerotic changes, especially when this was associated with proliferation or sclerosis in 20% or more of the glomeruli; black race; hypertension at biopsy; proteinuria at biopsy; age at presentation; crescents; male sex. Using the resulting discriminant function, development of ESRD could be correctly predicted in 95% of the subjects. We conclude that ESRD is more common in American children with IgAN than was realized previously. Risk factors previously documented in adult studies have been confirmed, especially the presence of glomerular sclerosis, proteinuria, and hypertension.

MR imaging of the breast with rotating delivery of excitation off resonance: clinical experience with pathologic correlation.

An investigative study was undertaken to determine the potential for a new magnetic resonance (MR) imaging technique, RODEO (rotating delivery of excitation off resonance), for use as a diagnostic imaging tool for the breast. The RODEO technique provides fat suppression with T1 weighting and is ideal for gadolinium-enhanced breast imaging. It is a short repetition time, steady-state sequence for high-resolution three-dimensional acquisitions and provides a clinically efficient imaging time of approximately 5 minutes for 128 sections. Imaging findings were correlated with serially sectioned pathologic specimens in 30 breasts with 47 malignant and 27 benign lesions. MR imaging had a sensitivity of 94% and a specificity of 37%. MR imaging depicted additional cancers not seen at mammography in 11 of the 30 patients (37%). The lesions not seen at mammography varied in size from 3 mm to 12 cm. RODEO MR imaging may be used to improve diagnosis of breast cancer in patients with mammographically dense breasts or silicone implants/injections and to stage disease in patients who are candidates for lumpectomy.

Fat-suppressed three-dimensional MR imaging of the breast.

Rotating delivery of excitation off-resonance (RODEO) is a new magnetic resonance (MR) imaging pulse sequence that uses a jump return sine excitation on fat resonance to produce fat-suppressed, T1-weighted images. New three-dimensional MR imaging techniques were used to examine 57 women with abnormalities suspicious for breast cancer. MR imaging findings were compared with those of mammography in all cases and with those of other imaging techniques when appropriate. Thirty-five specimens obtained at mastectomy were analyzed with rigorous pathologic examination that included imaging of the entire breast at 5-mm incremental sections. Histologic confirmation was obtained in 76 lesions in 47 patients. MR imaging helped detect 100% of malignant lesions, whereas mammography produced 33% false-negative findings. The use of RODEO in breast imaging is in the early investigational phases, but it has potential for supplementing mammography in the diagnosis of breast cancer.

Reversal of acute fulminant lymphocytic myocarditis with combined technology of OKT3 monoclonal antibody and mechanical circulatory support.

Reported is a case of acute fulminant lymphocytic myocarditis with profound circulatory compromise that was successfully reversed by treatment with OKT3 monoclonal antibody. The patient was supported with biventricular assist devices while being treated with the monoclonal antibody. The patient had remarkable recovery of ventricular function, which allowed for the removal of the device after 8 days of support. This case shows the success of combined technologies of monoclonal antibody and mechanical circulatory support to treat a potentially fatal disease process.

Follicular Hurthle cell tumors of the thyroid gland.

A clinicopathologic study of 153 cases of thyroid follicular Hurthle cell tumor (HCT) is presented. Follow-up, available in all cases, ranged from 5 to 26 years (median, 9 years). These neoplasms were divided into three categories on the basis of presence and degree of capsular and vascular invasion, pattern of growth (follicular, trabecular, or solid), nuclear atypia, and necrosis. The categories were benign (90 cases), indeterminate (35 cases), and malignant (28 cases). All the tumors classified histologically as benign or indeterminate behaved in a clinically benign fashion. Of the 28 tumors classified histologically as malignant, 20 had a clinically malignant behavior. At survival analysis, no clinical or pathologic feature among the carcinomas was found to correlate with a fatal outcome. It is concluded that histologic criteria alone can distinguish benign from malignant HCT and that clinical or pathologic feature cannot predict behavior among the malignant tumors.

Characterization of skin-infiltrating lymphocytes in patients with psoriasis.

In this study, skin-infiltrating cells in psoriasis patients were characterized in biopsies from both involved and uninvolved skin. Histologic examination of biopsies showed the presence of both CD4+ and CD8+ T cells and the lack of B lymphocytes. Skin biopsies were also placed in tissue culture medium supplemented with human serum, interleukin-2 (IL-2), and irradiated autologous blood lymphocytes. T lymphocytes grew from both plaques and univolved skin biopsies and consisted of a heterogeneous population of T-cell subsets. The immunophenotypic analysis of cultured cells was comparable to the histologic examination on frozen section, i.e., there was a greater number of CD4/CDw29+ cells than CD8+/CD45+ cells. Cultures were tested in the primed lymphocyte test (PLT) and cell-mediated lympholysis (CML) assays. All cultures tested demonstrated secondary proliferative but not cytolytic reactivity. The PLT results indicate that the cell cultures generated are autoreactive. This autoreactivity was found to be directed against non-human leukocyte antigens (HLA), i.e., minor HLA with some restriction to major HLA antigens.

Spontaneous remission of nephrotic syndrome in a patient with IgA nephropathy.

A patient with spontaneous remission of nephrotic syndrome (NS) associated with IgA nephropathy is described. The patient presented at the age of 8 years with asymptomatic proteinuria, and at the age of 11 years developed classical features of NS. A percutaneous renal biopsy showed mild mesangial prominence without significant hypercellularity, electron-dense deposits within the mesangium, and 3+ mesangial staining with IgA and IgG. NS resolved 6 weeks after onset without any form of therapy; absence of proteinuria persisted 6 months later. This report demonstrates clearly that patients with NS associated with IgA nephropathy may undergo spontaneous resolution of their proteinuria.

Dermal myiasis of the eyelid.

A case report describes the clinical findings of dermal myiasis of the upper eyelid in a 6-year-old girl from South America. Dermal myiasis due to Dermatobia hominis can simulate a common furuncle and is known to occur in world travelers.

Posterior uveal melanomas in aphakic and pseudophakic eyes.

Of 650 eyes with posterior uveal melanomas that were accessioned at the Armed Forces Institute of Pathology from 1975 to 1983, 28 were aphakic and eight were pseudophakic. In ten of these 36 cases, the cataract had been unilateral. Only two patients had been examined with preoperative A-scan ultrasonography to obtain the axial length of the eye. None of the patients had been examined for possible intraocular tumors by either A- or B-scan ultrasonography. We believe that in many of these cases the tumor was large enough to have been detected at the time of cataract surgery. Thus, if the lens is too opaque for the fundus to be viewed, B-scan ultrasonography should be used before cataract extraction.

A human embryonal-yolk sac carcinoma model system in athymic mice.

Two new human cell lines (1411H and 1411HRQmet) have been established from a patient with metastatic testicular cancer whose primary and metastatic histology included seminoma, teratoma, embryonal carcinoma (EC), and yolk sac tumor (YST). In vitro, the cells have been maintained for more than 70 passages, produce alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), and have a human karyotype. When 2 X 10(7) cells of either line are inoculated into athymic mice, 87.5% of the animals (21/24) develop tumors. Initially 80% to 90% of the mass is EC, whereas the central portion is YST. After 90 to 390 days in vivo, the tumors achieve a large volume (2.13 +/- 0.97 cm3), become cystic, and undergo histologic change. The peripheral rim of the mass remains EC, but the central 80% to 90% becomes YST. The sera of tumor-bearing mice were positive for hCG and AFP in 11% and 38% of animals, respectively. Tumor cyst fluid was positive for hCG and AFP in 87% and 59% of animals, with mean values of 108 mIU/ml and 2,478 ng/ml, respectively. Tumor cyst fluid also contained placental alkaline phosphatase and human fibronectin. These two cell lines are useful for studies on the interrelationship of EC and YST and the differentiation of human germ cell cancer.

Conjunctival Rhinosporidiosis. Light and electron microscopic study.

Two cases of conjunctival rhinosporidiosis were studied by light and electron microscopy. Two distinct phases of the tissue life cycle were present: trophic and endosporulating. Young trophocytes contained a single nucleus. As the trophocyte matured chromatin was dispersed throughout the cyst. During the next phase of the life cycle, sporangial cyst walls acquired a new inner layer that appeared to give rise to endospores. Histochemical and ultrastructural features of Rhinosporidium seeberi are consistent with it being a fungus. Complete surgical excision of the lesion is the only known method to eradicate the infection.

Phospholipid composition and phenotypic correction of an envC division mutant of Escherichia coli.

The cytoplasmic and outer membranes of a nonconditional chain-forming mutant, Escherichia coli PM61 envC, were separated by sucrose density gradient centrifugation. The phosphatidylglycerol/cardiolipin ratio in both membrane fractions was about one-third as high as in the parental strain P678. The increased level of cardiolipin in PM61 membranes is the result of an alteration of the polyglycerophosphatide cycle. It was found that the turnover rate of phosphatidylglycerol is more rapid in PM61 than in the parental strain but that its cardiolipin turnover is not significantly different. The envC mutation can be corrected phenotypically by increasing the osmolarity of the medium. In the presence of 0.6 M sucrose, the population of PM61 is composed of short rods, and the phosphatidylglycerol/cardiolipin ratio is shifted to that of the parent. The phosphatidylglycerol turns over more slowly, whereas the cardiolipin turns over more rapidly in both strains. Thus, the increase of external osmolarity acts on phospholipid metabolism as well as on an unknown step involved in the mechanism of cell division of the envC mutant.