Helen M. Shaw

Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma: an analysis of 3661 patients from a single center.

The current study was performed to determine whether tumor mitotic rate (TMR) is a useful, independent prognostic factor in patients with localized cutaneous melanoma.

A comparison of prognostic factors and surgical results in 1,786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia

Twelve clinical and pathologic parameters were compared in two series of Stage I melanoma patients treated at the University of Alabama in Birmingham, USA (676 patients) and at the University of Sydney in New South Wales, Australia (1,110 patients). Actuarial survival rates were virtually the same at the two institutions over a 25-year follow-up period. The incidence of thin melanomas (<0.76 mm) was also similar at both geographic locations (25% vs. 26%). Other similarities of these two patient populations included the following: 1) tumor thickness (Breslow Microstaging), 2) level of invasion (Clark Microstaging), 3) surgical results, 4) sex distribution, and 5) age distribution. The greatest differences between the two patient populations were their 1) anatomic distribution, 2) growth pattern, and 3) incidence of ulceration. The trunk was the most common site of melanoma, and occurred more frequently among Australian patients (37% vs. 28%). A multifactorial analysis (Coxs regression model) was then performed that included a comparison of the two institutions as a variable (Alabama vs. Australia). The dominant prognostic factors (p < 0.0001) were 1) ulceration, 2) tumor thickness, 3) initial surgical management (wide excision ± node dissection), 4) anatomic location, 5) pathologic stage (I vs. II), and 6) level of invasion. The benefit of elective lymph node dissection was demonstrated in both series for patients with intermediate thickness melanoma (0.76 to 3.99 mm). For melanomas ranging from 0.76 to 1.5 mm in thickness, the benefit of node dissection was primarily in male patients. Survival rates for melanoma at the two institutions were not significantly different in the multifactorial analysis, even after adjusting for all other variables. Thus, the biologic behavior of melanoma in these two different parts of the world was virtually the same, with only minor differences that did not significantly influence survival rates. Long-term follow-up exceeding eight to ten years after surgery is critical in the interpretation of these prognostic factors and the surgical results.

Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy

BACKGROUND The technique of lymphoscintigraphy may allow a more selective approach to the management of clinically negative neck nodes among patients with cutaneous head and neck melanoma. PATIENTS AND METHODS A group of 97 patients with cutaneous head and neck melanoma had preoperative lymphoscintigraphy using intradermal injections of technetium 99m antimony trisulfide colloid to identify sentinel nodes. Fifty-one patients were eligible for clinical analysis after initial definitive treatment by wide excision only (n = 11), wide excision and elective dissection of the neck (n = 19) or axilla (n = 1), or wide excision and a sentinel node biopsy procedure (n = 20). RESULTS Sentinel nodes were identified in 95 of 97 lymphoscintigrams, and 85% of patients had multiple sentinel nodes. In 21 patients (22%), sentinel nodes were identified outside the parotid region and the 5 main neck levels, mostly in postauricular nodes (n = 13). Lymphoscintigrams were discordant with clinical predictions in 33 patients (34%). Lymph nodes were positive in 4 elective dissections and 4 sentinel node biopsies. Among 16 patients evaluable after wide excision and a negative sentinel node biopsy, 4 patients subsequently developed metastatic nodes; however, confident identification of all nodes marked as sentinel nodes on lymphoscintigraphy was not achieved at the original biopsy procedure in 3 of these patients. CONCLUSIONS Lymphoscintigraphy and sentinel node biopsy are more difficult to perform in the head and neck than in other parts of the body. The reliability of sentinel node biopsy based on lymphoscintigraphy may be improved by identifying and marking all nodes that are considered to receive direct lymphatic drainage from the primary melanoma, and by use of a gamma probe intraoperatively.

Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy

BACKGROUND Accurate staging of melanoma patients by sentinel node (SN) biopsy can be achieved only if all SNs draining a given melanoma site are identified and removed for detailed histologic examination. Lymphoscintigraphy with a radiolabeled colloid provides an objective and reliable method of locating SNs and demonstrates that confident prediction of their location is not possible on clinical grounds. STUDY DESIGN Lymphatic drainage pathways demonstrated by preoperative lymphoscintigraphy for 1,759 patients with primary cutaneous melanomas were reviewed, and locations of SNs in these patients were documented. An SN was defined as any node receiving direct lymphatic drainage from a primary melanoma site. RESULTS In many instances the cutaneous lymphatic drainage pathways were found to be at variance with longheld concepts of lymphatic anatomy. Several new pathways were identified, draining to SNs in unexpected sites. These included triangular intermuscular space SNs (from upper back and, rarely, upper limb primaries), paraaortic and retroperitoneal SNs (from upper and lower back primaries), and costal margin SNs with onward drainage to internal mammary nodes (from periumbilical primaries). Occasional drainage to node fields on the opposite side of the body was noted from head, neck, and trunk primaries, and drainage to interval nodes (by definition, SNs) outside recognized lymph node fields was also observed. CONCLUSIONS Knowledge of the possibility of these unusual lymphatic drainage patterns and SN sites should help to ensure the accuracy and completeness of SN identification. Preoperative lymphoscintigraphy to definitively locate SNs is recommended for every patient undergoing an SN biopsy procedure.

Head and neck melanoma in 534 clinical Stage I patients. A prognostic factors analysis and results of surgical treatment

Single and multifactorial analyses were used to evaluate prognosis and results of surgical treatment in 534 clinical Stage I patients with head and neck cutaneous melanoma treated at the University of Alabama in Birmingham (U.S.A.) and the University of Sydney (Australia). This computerized data base was prospectively accumulated in over 90% of cases. Melanomas were about equally distributed between men and women. They were located on the skin of the face in 47%, neck in 27%, scalp in 13%, and the ear in 13% of patients. Both the results of the prognostic factors analyses and the surgical treatment demonstrated that lentigo maligna melanoma (LMM) was distinct from the other two growth patterns, superficial spreading melanoma and nodular melanoma (SSM and NM). In a multifactorial analysis of the 453 patients with SSM and NM, the dominant prognostic variables were tumor thickness (p less than 0.00001), anatomic subsite (p = 0.0213), and ulceration (p = 0.0289). Patients with melanomas on the scalp or neck subsites fared worse than those with tumors located on the face or ear. The results differed for LMM, where thickness was not a significant predictor of survival, and the most dominant prognostic variable was ulceration (p = 0.0042). Local recurrence rates were low, being 2.4% for tumors less than 2.5 mm in thickness, but were 12.3% for tumors greater than or equal to 4.0 mm in thickness. Patients with SSM and NM lesions located on the head and neck had a lower survival rate than those with extremity melanomas in every tumor thickness category, although only those in the 0.76 to 1.49 mm thickness subgroup were significantly different (p = 0.0007). After 5 years of follow-up, patients who underwent an elective lymph node dissection for SSM and NM with a thickness range of 1.5 to 3.99 mm had a better survival (72%) than patients with melanomas of equivalent thickness whose initial treatment was wide excision alone (45%). LMM had a less aggressive biologic behavior compared to SSM or NM and was treated more conservatively. Thus, LMM lesions had an 85% 10-year survival rate with wide excision only, and there was no significant improvement in survival with ELND. Growth patterns, tumor thickness, ulceration, and anatomic subsites should be considered when evaluating risk factors and when making treatment decisions in head and neck melanoma patients.

The prognostic importance of tumor mitotic rate confirmed in 1317 patients with primary cutaneous melanoma and long follow-up.

AbstractBackground: The late Dr. Vincent McGovern (1915 to 1983) was an international authority on melanoma pathology and one of the first to suggest that assessment of tumor mitotic rate (TMR) might provide useful prognostic information. Data for a large cohort of patients, now with extended follow-up, whose tumors had been assessed by Dr. McGovern were analyzed to reassess the independent prognostic value of TMR in primary localized, cutaneous melanoma. Methods: Information was extracted from the Sydney Melanoma Unit database for 1317 patients treated between 1957 and 1982 for whom there was complete clinical information and whose primary lesion pathology, which included tumor thickness, ulcerative state, and TMR, had been assessed by Dr. McGovern. All these assessments were made according to the recommendations of the Eighth International Pigment Cell Conference, held in Sydney in 1972 under the auspices of the International Union Against Cancer. Factors predicting melanoma-specific survival were analyzed with the Cox proportional hazards regression model. Results: Stage, according to the recently revised American Joint Committee on Cancer Staging System (which is based on tumor thickness and ulceration) was the most predictive factor for survival (P < .0001). This was followed by primary lesion site (P < .0001), patient age (P = .0005), and TMR (P = .008). Conclusions: TMR was confirmed to be an important independent predictor of survival of patients with primary cutaneous melanoma. However, its predictive value was less than it was when assessed according to the 1982 revisions of the 1972 TMR recommendations.

Cutaneous factors related to the risk of malignant melanoma.

In a case‐control study, 287 women with malignant melanoma were compared with 574 age‐matched controls. Red hair colour at age 5 years was associated with a tripling of risk [relative risk (RR) = 3.0], blonde hair with a 60% increase (RR=1.6) and fair skin with a doubling (RR = 2.1). Women with melanoma also reported that they tended to burn (RR = 1.4) and to freckle (RR =1.9) after exposure to sunlight. Since fair skin, red hair, and the tendency to burn or freckle after exposure to sunlight all cluster in the same individuals, the extent to which each of these factors had an independent influence on susceptibility to melanoma was investigated. Hair colour, especially red hair, proved to be the major determinant, followed by skin colour.

Prognostic significance of the histological features of malignant melanoma

A review of 694 patients with localized cutaneous malignant melanoma (clinical stage I) revealed that three histological features of the primary lesion had no effect of their own on survival rate but derived their prognostic significance only because of their close correlation with tumour thickness. Primary lesions of superficial spreading histogenetic type, or of low mitotic activity or showing evidence of partial regression appeared to have a more favourable prognosis than lesions of nodular histogenetic type or of high mitotic activity or showing no regression. However, the former three histological features were predominant in thin lesions which had a better prognosis than thicker lesions. It was concluded that these features exerted only an indirect effect upon survival, tumour thickness being the most important prognostic determinant.

The influence of surgical margins and prognostic factors predicting the risk of local recurrence in 3445 patients with primary cutaneous melanoma

Risk factors associated with local recurrences were analyzed from a series of 3445 clinical Stage I melanoma patients. In single‐factor analysis, tumor thickness, ulceration, and increasing age were highly significantly predictive of recurrence (p < 0.00001). After 5 years of follow‐up, local recurrence rates were 0.2% for tumors less than 0.76 mm thick, 2.1% for tumors 0.76 to 1.49 mm thick, 6.4% for tumors 1.5 to 3.99 mm thick, and 13.2% for tumors 4.0 mm or greater in thickness. Ulcerated melanomas recurred more often than nonulcerated lesions (11.5% versus 1.9%). When analyzed as a continuous variable, increasing age increased the risk of local failure. In multifactorial analysis, all of these three factors remained independently predictive of local recurrence. Recurrences were more common with nodular melanomas (5.6%) compared to superficial spreading (2.5%) or lentigo maligna melanoma (2.5%), but this difference did not reach statistical significance (P = 0.115). Lower extremity (4.7%) and head and neck lesions (4.4%) recurred more frequently than upper extremity (1.6%) or trunk (1.2%) melanomas (P = 0.0217). The highest recurrence rates were observed in patients with melanomas located on the foot (11.6%) and hand (11.1%). The safety of conservative margins for the excision of low‐risk melanomas was demonstrated in a review of 1151 consecutive patients with melanomas less than 1 mm thick where only one local recurrence was observed. Sixty‐two percent of these patients had resection margins of 2 cm or less. In 95 patients local recurrence developed as the first site of relapse and were treated with surgical excision. The median survival for this group was 3 years, whereas 20% of this group survived 10 years. These data demonstrate that: (1) the risk of local recurrence rises with increasing tumor thickness, presence of ulceration, and age; (2) melanomas less than 1 mm thick have a very low local recurrence rate, even when excised with margins of 2 cm or less; and (3) local recurrence is a poor prognostic sign because regional and systemic metastases subsequently develop in many patients. Cancer 55:1398‐1402, 1985.

Lymphoscintigraphy to identify sentinel lymph nodes in patients with melanoma.

Lymphoscintigraphy (LS) has been performed for 8 years in patients of the Sydney Melanoma Unit, to define lymphatic drainage patterns. Over the past 2 years, LS has also been used to locate the sentinel lymph node prior to surgery. Our technique for LS and subsequent sentinel node biopsy has an accuracy of 97%. All sentinel nodes must be marked to ensure the successful application of the sentinel biopsy technique. We have found that the axilla and groin average just over one sentinel node per draining node group for lesions on the trunk and upper limb, but have noted that drainage to the groin differed when lower limb lesions were studied. Because of the anastomosis of lymph vessels in the upper thigh, multiple sentinel nodes are identified in the groin in some patients. We have found an average of three sentinel nodes in the groin when lymph drainage from lower limb lesions was studied with LS. This difference demands a modification of the LS technique, with early imaging of the groin nodes to identify all sentinel nodes in each patient. The depth of the sentinel nodes can also be measured and the location of all interval nodes marked on the skin. This ensures that all sentinel nodes and interval nodes can be removed at the time of surgery.