Faculty Bibliography

A group of 122 consecutively treated pathologic Stage 1 (TINOMO) patients with cancer of the breast were studied to define histopathologic predictors of recurrence. Lymphatic invasion was the most significant predictor of recurrence; recurrence was present in 32% (8/25) of patients who had lymphatic invasion and in 10.3% (10/97) of patients who did not (P = 0.006). Histologic type was also predictive of recurrent disease. Eighteen per cent (18/101) of patients with invasive ductal or lobular carcinoma developed recurrent disease, while none of the group of 21 patients with medullary carcinoma, tubular carcinoma, colloid carcinoma, Paget's disease, and intraductal carcinoma with minimal invasion suffered a recurrence (P = 0.036). Vascular invasion, grade of malignancy, cellularity, presence or absence of circumscription, cellular infiltrate, fibroblastic response, neural invasion, and necrosis were not significant predictors of recurrence. Multiple logistic regression analysis of patients with invasive ductal or lobular carcinoma confirmed the results for individual factors, that only patients with lymphatic invasion were at higher risk of recurrence

A group of 525 patients with primary cutaneous malignant melanoma of the trunk was treated by a uniform surgical approach that included regional lymph node dissection for selected patients; 266 (50.6%) had regional lymph node dissections in addition to wide and deep excision, all with primary lesions extending below the superficial papillary dermis. Of 171 patients treated over five years ago, 130 had histologically negative nodes; 94 (72%) are alive with no evidence of disease (NED). Of 41 with histologically positive nodes, 12 (29%) are alive with NED. A comparison of the 21 patients with clinically occult micrometastases shows eight (38%) alive with NED, whereas four of 20 (20%) with clinically demonstrable as well as histologically proven nodal metastases are alive with NED. Though there may be a modest benefit to lymph node dissection for microscopic rather than gross nodal metastases for invasive melanoma of the trunk, for most such patients melanoma in regional nodes indicates the presence of systemic metastatic disease

A technique for total mastectomy with complete axillary dissection, which uses division of the insertion of the sternal portion of the pectoralis major muscle, preservation of its innervation, reconstruction after completion of the dissection and resection of the pectoralis minor muscle has been evaluated for 115 consecutive procedures. This modification facilitates a thorough axillary dissection, while preserving the cosmetic and functional benefits of the Patey operation

Seven hundred thirty-nine patients with malignant melanoma of the extremities were treated with a uniform surgical approach that included wide and deep excision of the primary site and regional node dissection therapeutically and electively for invasive lesions (Clark's levels III, IV, and V). Of the 490 patients who underwent lymph node dissections, follow-up was available for 457 (93%). Life-table comparison of 362 patients with histologically negative nodes to 95 with histologically proved lymph node metastases yielded statistically significant differences in survival (P less than 0.001). Five-year cumulative survival rates were 91% in the group without and 48% in the group with nodal metastases. Among histologically positive patients, differences in life-table survival curves for the 60 clinically negative patients compared to the 35 clinically positive patients were also statistically significant (P = 0.004); 5-year cumulative survival rates were 57% for the former group and 33% for the latter. Although there appears to be an advantage to regional lymph node dissection for micrometastases as opposed to gross nodal involvement, for the majority of patients metastatic melanoma in these nodes is the major indicator of systemic disease

Thirteen variables were studied to determine their usefulness in predicting recurrent disease in 158 patients with stage I melanoma of the lower extremity. A Cox proportional hazards analysis demonstrated that three variables were independent risk factors for recurrent disease in these patients: (1) thickness, in millimeters, of the primary tumor (P = 0.000009), (2) primary tumor location on the foot (P = 0.0003), and (3) the number of mitoses/mm2 (P = 0.0244). Life-table analyses of patient subgroups defined by different combinations of these three variables demonstrated that thick (greater than or equal to 3.0 mm) melanomas of the foot were associated with recurrent disease much more frequently than tumors of similar thickness located on the thigh or calf. These data provide guidelines that can be used to evaluate results of surgical and/or adjuvant therapy studies for patients with melanoma of the lower extremity

Thirteen variables were studied for their relative usefulness in predicting recurrent disease in 107 patients with clinical Stage I melanoma of the upper extremity. After a mean follow-up period of 54 months, the only patents who have had recurrent disease to date are those who primary lesions were located either on the hand or posterior upper arm. The five-year disease-free survival role for 44 patients with melanoma at these sites was 68%. None of 63 patients with melanoma located on the forearm of anterior upper arm have had recurrent disease (i.e., the five-year, disease-free survival rate was 100% (p = 0.00004), compared with the hand or posterior arm group). A Cox proportional hazards (multivariate) analysis demonstrated that two primary tumor histologic variable, thickness in millimeters and ulceration, interacted to produce the best prognostic model for those 44 patients with melanoma of the hand or posterior upper arm. Twenty-one patients with primary lesions at these sites had primary tumors less than 2.25 mm in thickness and no evidence of ulceration histologically. Their five-year, disease-free survival role was 95%. For the remaining 23 patients with primary tumors on the hand or posterior upper arm who had either histologic evidence of ulceration or primary tumors greater than or equal to 2.25 mm, the five-year disease-free survival rate was 37% (p = 0.002, compared with group nonulcerated, thin lesions). The excellent survival rate for patients with melanomas on the forearm or anterior upper arm was not completely explained by pathologic stage, by primary tumor thickness, or by histologic ulceration of the primary tumor

Fifteen variables were studied for their usefulness in predicting recurrent disease in 254 patients with clinical stage I melanoma of the trunk. Thickness of the primary tumor correctly predicted outcome with an accuracy of 90 percent or greater in 176 patients with melanoma primaries with a thickness of less than 1.70 mm or 5.5 mm or greater. No other variables significantly increased predictive accuracy over these ranges of thickness. A Cox proportional hazards analysis of the remaining 78 patients with primary tumors 1.70 to 5.49 mm thick demonstrated that the following four variables functioned as independent risk factors for recurrent disease: (1) thickness of the primary tumor (p = 0.0005), (2) mitoses/mm2 greater than 6 (p = 0.006), (3) a nearly absent or minimal lymphocyte response at the base of the tumor (p = 0.009), and (4) location on the upper trunk (p = 0.03). Trunk lesions located near the midline did not have a worse prognosis than more lateral melanomas of similar thickness