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

Poland's syndrome is a rare congenital anomaly that may include mammary hypoplasia and has been described in association with various malignancies. We report the case of a 42-year-old woman with unilateral Poland's syndrome who developed carcinoma in the hypoplastic breast. A review of the literature reveals no previous report of carcinoma of the hypoplastic breast with Poland's syndrome

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 evaluate the multicenter application of intraoperative lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection (LM/SL/SCLND) for the management of early-stage melanoma. SUMMARY BACKGROUND DATA: The multidisciplinary technique of LM/SL/SCLND has been widely adopted, but not validated in a multicenter trial. The authors began the international Multicenter Selective Lymphadenectomy Trial (MSLT) 5 years ago to evaluate the survival of patients with early-stage primary melanoma after wide excision alone versus wide excision plus LM/SL/SCLND. This study examined the accuracy of LM/SL/SCLND in the MSLT, using the experience of the organizing center (John Wayne Cancer Institute [JWCI]) as a standard for comparison. METHODS: Before entering patients into the randomization phase, each center in the MSLT was required to finish a 30-case learning phase with complete nuclear medicine, pathology, and surgical review. Selection of MSLT patients in the LM/SL/SCLND treatment arm was based on complete pathologic and surgical data. The comparison group of JWCI patients was selected using these criteria: primary cutaneous melanoma having a thickness > or =1 mm with a Clark level > or =III, or a thickness <1 mm with a Clark level > or =IV (MSLT criterion); LM/SL performed between June 1, 1985, and December 30, 1998; and patient not entered in the MSLT. The accuracy of LM/SL/SCLND was determined by comparing the rates of sentinel node (SN) identification and the incidence of SN metastases in the MSLT and JWCI groups. RESULTS: There were 551 patients in the MSLT group and 584 patients in the JWCI group. In both groups, LM performed with blue dye plus a radiocolloid was more successful (99.1 %) than LM performed with blue dye alone (95.2%) (p = 0.014). After a center had completed the 30-case learning phase, the success of SN identification in the MSLT group was independent of the center's case volume or experience in the MSLT. CONCLUSIONS: Lymphatic mapping and sentinel lymphadenectomy can be successfully learned and applied in a standardized fashion with high accuracy by centers worldwide. Successful SN identification rates of 97% can be achieved, and the incidence of nodal metastases approaches that of the organizing center. A multidisciplinary approach (surgery, nuclear medicine, and pathology) and a learning phase of > or =30 consecutive cases per center are sufficient for mastery of LM/SL in cutaneous melanoma. Lymphatic mapping performed using blue dye plus radiocolloid is superior to LM using blue dye alone

A 41-year-old woman with McCune-Albright syndrome and a 2-cm thyroid nodule of ten years' duration presented for fine-needle aspiration, which yielded vacuolated clear cells with granular chromatin in pseudopapillary arrangement. The resected tumor showed 90% clear cells and 10% nonclear cells with capsular and vascular invasion. The cytoplasmic vacuoles in the clear cells were 3+ for oil red O stain in touch imprint cytology. Immunohistochemistry demonstrated thyroglobulin positivity in the nonclear neoplastic cells, whereas most of the clear cells were negative. Ultrastructural study demonstrated the gradual transition from protein synthesis to lipid synthesis as the neoplastic cells progressed from nonclear to clear. The study suggested that the lipid accumulation resulted from the uncontrolled fatty acid synthesis in the neoplastic cells rather than metaplasia. The karyotype of the tumor cells was normal, 46XX. Literature of lipid-rich thyroid neoplasms were reviewed

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