Faculty Bibliography

A polyvalent melanoma vaccine prepared from shed antigens stimulates humoral and cellular immune responses and improves survival compared with historical controls. We conducted a double-blind, prospectively randomized, placebo-controlled trial to assess whether this vaccine could slow the progression of resected melanoma. Thirty-eight patients with resected melanoma metastatic to regional nodes (American Joint Committee on Cancer stage III) who had a particularly poor prognosis on the basis of the nodes being clinically positive or two or more histologically positive nodes were randomly assigned in a 2:1 ratio to treatment with 40 microg of melanoma or placebo (human albumin) vaccine, both of which were bound to alum as an adjuvant. Immunizations were given intradermally into the extremities every 3 weeks x 4, monthly x 3, every 3 months x 2, and then every 6 months for 5 years or until disease progression. Twenty-four patients were treated with the melanoma, and 14 patients were treated with the placebo vaccine. The groups were evenly balanced with respect to prognostic factors. Median length of observation was 2.5 years. There was no local or systemic toxicity. By Kaplan-Meier analysis, median time to disease progression was two and a half times longer in patients treated with melanoma vaccine compared with that in patients treated with placebo vaccine, i.e., 1.6 years (95% confidence interval, 1.0-3.0 years) compared with 0.6 year [95% confidence interval, 0.3-1.9 year(s)]. By Cox proportional hazards analysis, this difference was significant at P = 0.03. Overall survival was 40% longer in the melanoma vaccine-treated group (median overall survival of 3.8 years versus 2.7 years), but this difference was not statistically significant. In a double-blind and placebo-controlled trial, these results suggest that immunization with a melanoma vaccine may be able to slow the progression of melanoma. Although statistically significant, these results must be interpreted with caution because they are based on a small number of patients

As melanoma cells are present in the circulation of many patients with this cancer, decreases in their number could provide an early indication of therapy effectiveness. To evaluate this possibility, we examined the effect of treatment with a melanoma vaccine on the number of melanoma cells present in the circulation. PCR was used to detect melanoma cells that expressed the melanoma-associated antigens MART-1, MAGE-3, tyrosinase and/or gp100 in 91 patients with melanoma. Melanoma cells that expressed one or more of these markers were present more often in advanced disease, i.e. in 80% of patients with advanced stage IV compared to in less than one-third of patients with less advanced disease. We then measured circulating melanoma cells in a subset of 43 of these patients who were treated with a polyvalent, shed antigen, melanoma vaccine. The vaccine contains multiple melanoma-associated antigens including MART-1, MAGE-3, tyrosinase and gp100. Immunizations were given intradermally q2-3 weeks x4 and then monthly x3. Prior to vaccine treatment, circulating melanoma cells were detected in 14 (32%) patients. Following 4 and 7 months of vaccine treatment, melanoma cells that expressed any of these markers were present in only nine (21%) and three (7%) of patients, respectively. Thus, vaccine therapy was associated with clearance of melanoma cells from the circulation in 78% of initially positive patients. As the number of these cells declined steadily with increasing length of therapy, it is unlikely that this was due to a random change in their number. Rather it suggests that the decline was a result of the therapy. These observations suggest that the presence of melanoma cells in the circulation is related to the extent of the melanoma, and that their disappearance may provide an early marker of the efficacy of therapy. However, the practical utility of assaying circulating tumor cells as a guide to the effectiveness of therapy or of prognosis will need to be confirmed by correlations with clinical outcome

BACKGROUND: The presence of lymph node metastases in patients with malignant melanoma implies a significant decrease in survival. The authors investigated the efficacy of fine-needle aspiration biopsy (FNAB) in the diagnosis of metastatic malignant melanoma in 115 patients with melanoma and clinically suspicious regional lymph nodes. METHODS: One hundred thirty-three FNABs were performed by cytopathologists after referral from surgeons or oncologists using a 25-gauge or 27-gauge needle. RESULTS: The cytologic diagnosis was negative in 35, atypical in 1, suspicious in 2, and positive for malignant melanoma in 95. Regional lymph node dissections were performed in 78 patients. Of these, 70 positive FNABs were confirmed with no false-positive results. The atypical FNAB was proven positive for malignant melanoma at surgery. Of the two suspicious FNABs, one was confirmed as positive and one showed dermatopathic lymphadenopathy. Of the 35 negative FNAB specimens, 5 patients underwent surgery; 3 FNABs were found to be negative and 2 FNABS were falsely negative. Twenty patients with negative aspirates were followed clinically for 22-45 months (mean, 32 months); 19 patients had no evidence of disease and 1 patient died of disseminated melanoma. CONCLUSIONS: FNAB of palpable lymphadenopathy in patients with malignant melanoma can provide a rapid and accurate assessment of lymph node status and expedite the therapeutic management of these patients

BACKGROUND: Fine-needle aspiration (FNA) biopsy of palpable breast masses along with clinical and radiologic findings can provide rapid distinction between benign and malignant lesions. A preoperative determination of invasive or in situ carcinoma assists in the planning of definitive treatment. Previous studies have concentrated on whether cytologic features adequately distinguish invasion, but to the authors' knowledge the predictive value of clinicopathologic correlation has not been investigated. The authors attempted to determine whether a malignant cytologic diagnosis for a palpable breast mass is sufficient for its definitive surgical management as an invasive neoplasm. METHODS: The authors reviewed 351 FNAs from palpable breast lesions with a cytologic diagnosis of 'adenocarcinoma.' The presence of invasive disease was determined by histologic demonstration of invasive carcinoma in the corresponding surgical specimen or by identifying metastatic carcinoma in the absence of another primary source. RESULTS: Three hundred forty-three (97.7%) palpable tumors diagnosed as adenocarcinoma by FNA proved to be invasive adenocarcinoma. The remaining eight tumors contained high grade ductal carcinoma in situ, and two of these contained foci suggestive of microinvasion. CONCLUSIONS: A palpable breast mass with an FNA diagnosis of adenocarcinoma usually represents invasive carcinoma. A definitive treatment plan therefore can be planned based on these clinical and FNA findings

OBJECTIVE: To assess the complications of level I and II axillary lymph node dissection in the treatment of stage I and II breast cancer, with breast-conservation surgery and mastectomy. SUMMARY BACKGROUND DATA: The role of axillary dissection for staging, and as an effective means of controlling regional nodal disease, has long been recognized. As small and low-grade lesions have been detected more frequently, and as its therapeutic impact has been questioned, axillary dissection has increasingly been perceived as associated with significant complications. METHODS: Two hundred patients, 112 of whom had breast-conservation surgery with axillary dissection and 88 of whom had total mastectomy with axillary dissection, were evaluated 1 year or more after surgery for arm swelling as well as nonedema complications. All patients had arm circumference measurements at the same four sites on both the operated and nonoperated sides. RESULTS: No patient had an axillary recurrence. The mean difference in circumference on the nonoperated versus operated side was 0.425 cm +/- 1.39 at the midbiceps (p < 0.001), 0.315 cm +/- 1.27 at the antecubital fossa (p < 0.001), 0.355 cm +/- 1.53 at the midforearm (p < 0.005), and 0.055 cm +/- 0.75 at the wrist (n.s.). Seven patients (3.5%) had mild swelling of the hand. Heavy and obese body habitus were the only significant predictors of edema on multivariate analysis. One hundred fifty-three (76.5%) patients had numbness or paresthesias of the medial arm and/or axilla after surgery; in 125 (82%) of these, the problem had lessened or had resolved on follow-up assessment. CONCLUSIONS: The characterization of a level I and II axillary dissection as a procedure with significant complications does not appear justified based on this experience

This case, a rare example of low-grade endometrial stroma sarcoma with extensive smooth muscle differentiation which extended to the inferior vena cava and cardiac chambers closely resembling intravenous leiomyomatosis grossly and microscopically, illustrates the importance of extensive sectioning and the usefulness of immunohistochemistry. Although spindle cell components arranged in interlacing bundles consistent with smooth muscle differentiation were recognizable in the primary tumor (on retrospective review), extensive smooth muscle differentiation in the recurrent tumors masked prototypical morphologic features of stromal sarcoma and only small neoplastic stromal components were preserved in limited areas, leading to initial failure to distinguish the lesion from intravenous leiomyomatosis. The immunophenotyping disclosed two distinct cell populations in the tumor: i.e. vimentin-positive and smooth muscle marker negative stromal cells, and vimentin-negative spindle-shaped desmin-positive smooth muscle cells. Our observation suggests that the predominance of a smooth muscle component in such a tumor can be misleading and does not always warrant a diagnosis of intravenous leiomyomatosis, nor does it predict a benign clinical course. This case also provides an insight into the relationship of the endometrial stroma and myometrium, and their cell of origin and the histogenesis of endometrial stromal sarcoma