Faculty Bibliography

Fifteen patients with augmentation mammoplasties had mammography demonstrating nonpalpable breast lesions. Of the 15 patients, three (20%) had adenocarcinoma confirmed by open biopsy and histopathology. All patients underwent stereotactic localization for fine needle aspiration biopsy. Four of the 15 patients had benign cysts (26%). None of the cysts could be diagnosed by ultrasound. The remaining eight patients had mammary dysplasia of a proliferative or nonproliferative type of fibroadenoma. These benign entities were followed with interval mammography demonstrating no change. The data suggest that fine needle aspiration biopsy is an effective technique to assess nonpalpable breast lesions in patients who have had augmentation mammoplasties

The authors investigated whether there was a relationship between the induction of a delayed-type hypersensitivity (DTH) response to melanoma vaccine immunization and disease recurrence. They studied prospectively 94 evaluable patients with surgically resected Stage II malignant melanoma who were immunized to a partially purified, polyvalent, melanoma antigen vaccine. The DTH response to skin tests to the vaccine was measured before treatment and at the fourth vaccine immunization. Vaccine treatment induced a strong DTH response in 29 (31%) patients, an intermediate response in 24 (25%), and no response in 41 (44%). The median disease-free survival (DFS) of patients with a strong, intermediate, and no DTH response to vaccine immunization was more than 72 months, 24 months, and 15 months, respectively. The relationship between an increase in the DTH response and a prolonged DFS was statistically significant (P = 0.02); clinically meaningful (the median DFS of patients with a strong DTH response was 4.7 years longer than that of nonresponders); and, by multivariate analysis, independent of disease severity or overall immune competence. These findings suggest, but do not prove, that vaccine treatment can slow the progression of melanoma in some patients

The efficacy of stereotaxic localization for fine-needle aspiration biopsy in the detection of recurrent cancer manifested as calcifications on mammograms was evaluated in 43 patients that had been treated with local resection and radiation therapy. Six patients had malignant aspirates and one had an atypical aspirate; examination of the surgical specimens revealed all seven of these to be malignant. Thirteen patients underwent surgical biopsies, the results of which were malignant in seven and benign in six. The remaining 30 patients were followed up with mammography. The follow-up mammograms were obtained at 6-month intervals and demonstrated no change in appearance. On the basis of this initial experience, stereotaxic localization for aspiration biopsy offers the potential to accurately distinguish benign from malignant lesions

A total of 183 consecutive patients undergoing biopsies for unilateral microcalcifications concentrated in one or more segments of the breast in the absence of any palpable findings were analyzed to characterize their risk of cancer. Biopsy findings were benign in 86 patients (47%) and malignant in 97 (53%). Of the clinical and mammographic characteristics evaluated, an increasing number of linear microcalcifications, either without a dominant density (p = 0.014) or with a dominant density (p = 0.019) and the presence of heterogeneous microcalcifications (p = 0.055), were associated with a significantly increased risk of malignancy. Conversely a fibronodular parenchymal pattern (p = 0.008) was associated with a significantly decreased risk of malignancy. A high-risk group was identified, 95% (40/42) of whom had malignant biopsy findings, whose mammograms had more than 10 linear microcalcifications not associated with a dominant density (16/17) or at least one linear microcalcification associated with a dominant density (24/25). Conversely a low-risk group for cancer was identified, 88% (28/32) of whom had benign biopsy findings, whose mammograms had exclusively punctate microcalcifications within a fibronodular parenchymal milieu (26/30) or demonstrated some change in the configuration of the microcalcifications on the various mammographic views (10/10). For the remaining 109 patients there was an almost equal division between malignant and benign diagnoses (49% vs 51%)

There are many clinical and histologic factors that are known to be valuable in predicting survival rates for patients with cutaneous malignant melanomas. Breslow thickness is considered to be the most reliable prognostic factor; however, thickness is a unidimensional measurement. A more accurate mensuration to predict biologic behavior might be one that takes into account the three-dimensional volume of the neoplasm. In a study of 35 primary malignant melanomas, the volumes of the dermal components of the tumors were calculated. Those patients with tumor volumes of 200 mm3 or less had a 91.4% 5-year disease-free survival rate, compared with survival rate of only 16.7% for those patients whose lesions had tumor volumes exceeding 200 mm3. On multivariate analysis, tumor volume exceeded thickness as a prognostic indicator. Thus, measurement of tumor volume proved to be of greater significance than thickness in predicting the outcome for patients with malignant melanomas

The efficacy of stereotaxic aspiration biopsy was evaluated in 300 consecutive patients with nonpalpable mammographic lesions. Sixty-eight patients (23%) had suspicious or malignant aspirates; all cases were proved malignant by subsequent examination of operative specimens. Two hundred sixteen patients (72%) had benign aspirates. Of these, 65 were confirmed by operation and 151 had subsequent mammography at 6- and 12-month intervals with no demonstrable mammographic change. In 10 instances (3%), the aspirates were atypical, and in six (2%), nondiagnostic. Biopsy specimens were obtained in all 16 instances, and eight were malignant. The sensitivity of stereotaxic breast aspiration for the diagnosis of cancer was 96%, and the specificity was 100%. Our experience confirms the efficacy of stereotaxic aspiration for the initial evaluation of mammographically detected, nonpalpable lesions

Melanoma antigen vaccines are a conceptually attractive approach to prevent or delay disease recurrence in patients with surgically resected malignant melanoma. However, the immunogenicity of current vaccines is relatively low. Cyclophosphamide, when given in low doses prior to antigen exposure, is an immunomodulator which has been shown to enhance both humoral and cellular antitumor responses in animals and humans. We conducted a prospective, randomized, clinical trial to study whether pretreatment with cyclophosphamide augments the immunogenicity of a polyvalent, allogeneic, melanoma antigen vaccine in patients with melanoma and low tumor burden. Forty-five patients with resected stage II melanoma (regional metastases) were randomly allocated to treatment with melanoma vaccine or melanoma vaccine plus cyclophosphamide. All patients received the same dose and schedule of vaccine immunizations; those randomized to cyclophosphamide received 300 mg/m2 i.v. 3 days prior to each vaccine immunization. Cellular immune responses were evaluated by delayed-type hypersensitivity (DTH) skin reactivity to a test dose of vaccine at baseline (prior to treatment) and following the fourth immunization. Humoral immune responses were measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiographic analysis of indirect immunoprecipitates of patients' sera at the same time points. Twenty-four patients were randomized to cyclophosphamide pretreatment and 21 to vaccine alone; 22 and 18 patients were evaluable in each group, respectively. Differences were statistically nonsignificant with respect to either cellular (DTH) or humoral (antibody) responses between the two groups. DTH responses were induced in 16 of 22 (73%) and 15 of 18 (83%) patients treated with cyclophosphamide plus vaccine and vaccine alone, respectively. The mean posttreatment augmentation in DTH response in the cyclophosphamide group was 9.5 mm, compared with 9.9 mm in the vaccine-only group. Eight of 12 (66%) cyclophosphamide-pretreated patients and 9 of 12 (75%) vaccine-only patients produced increased titers of antimelanoma antibodies following treatment. No differences were observed between the groups in disease-free or overall survival. In summary, low-dose cyclophosphamide pretreatment failed to augment the immunogenicity of a polyvalent, allogeneic, melanoma vaccine in patients with completely resected early-stage melanoma