William H. McCarthy

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.

Determinants of Outcome in Melanoma Patients With Cerebral Metastases

PURPOSE To analyze prognostic factors, effects of treatment, and survival for patients with cerebral metastases from melanoma. PATIENTS AND METHODS All melanoma patients with cerebral metastases treated at the Sydney Melanoma Unit between 1952 and 2000 were identified. From 1985 to 2000, patients were diagnosed and treated using consistent modern techniques and this cohort was analyzed in detail. Multivariate analysis of prognostic factors for survival was performed. RESULTS A total of 1137 patients with cerebral metastases were identified; 686 were treated between 1985 and 2000. For these 686 patients, the median time from primary diagnosis to cerebral metastasis was 3.1 years (range, 0 to 41 years). A total of 646 patients (94%) have died as a result of melanoma. The median survival from the time of diagnosis of cerebral metastasis was 4.1 months (range, 0 to 17.2 years). Treatment was as follows: surgery and postoperative radiotherapy, 158 patients; surgery alone, 47 patients; radiotherapy alone, 236 patients; and supportive care alone, 210 patients. Median survival according to treatment received for these four groups was 8.9, 8.7, 3.4, and 2.1 months, respectively; the differences between surgery and nonsurgery groups were statistically significant. On multivariate analysis, significant factors associated with improved survival were surgical treatment (P <.0001), no concurrent extracerebral metastases (P <.0001), younger age (P =.0007), and longer disease-free interval (P =.036). Prognostic factors analysis confirmed the important influence of patient selection on treatment received. CONCLUSION This large series documents the characteristics of patients who developed cerebral metastases from melanoma. Median survival was dependent on treatment, which in turn was dependent on patient selection.

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.

Experience with 998 cutaneous melanomas of the head and neck over 30 years

Between 1960 and 1990, a total of 998 patients were treated at the Sydney Melanoma Unit for cutaneous melanoma of the head and neck. There were 595 male and 403 female patients, with a median age of 53 years. The most common primary lesion site was the face (47%), followed by the neck (29%), scalp (14%), and ear (10%). Histologic types were as follows: superficial spreading 30%, nodular melanoma 28%, lentigo maligna melanoma 16%, and other 26%. All patients underwent surgical treatment. Primary closure of wounds was achieved in 52% of patients, and excision margins were 2 cm or less in 45%. A total of 152 patients had therapeutic neck dissections, and 234 had elective neck dissections. The overall local recurrence rate was 13%, and this was significantly influenced by increasing tumor thickness and Clark level. The recurrence rate in the neck after neck dissection was 24%, and the rate of parotid recurrences was 14%. Melanoma-specific survival was 77% at 5 years and 66% at 10 years for the entire group. By univariate analysis, survival varied significantly with age, tumor thickness, ulceration, anatomic sub-site, histologically positive nodes, and the presence of distant metastases. A diagnosis of lentigo maligna melanoma and elective lymph node dissection both appeared to improve survival. With multivariate analysis, all of these factors remained significant prognostic factors except elective node dissection, which lost its beneficial influence.

A sensitivity and specificity analysis of the surface microscopy features of invasive melanoma.

In vivo cutaneous surface microscopy, epiluminescence microscopy, dermoscopy, dermatoscopy and magnified oil immersion diascopy, are terms that describe the use of an incident light magnification system to examine cutaneous lesions, usually with immersion oil at the skinmicroscope interface. The result is the visualization of a multitude of morphological features, not visible with the naked eye, that enhance the clinical diagnosis of nearly all pigmented lesions. Sixty-two invasive melanomas and 159 randomly selected non-melanoma pigmented lesions were used in the study. The non-melanomas, while randomly selected from a large data base, were all clinically atypical. Using the × 10 magnification of hand-held surface microscopes (Dermatoscope, Episcope), we present an analysis of 72 surface microscopic variables (constituting over 15,000 single observations) for the diagnosis of invasive melanoma. Forty of the 72 features studied were shown to differ significantly between invasive melanoma and non-melanoma pigmented lesions. Blue-white veil, multiple brown dots, radial streaming and pseudopods had a specificity greater than 95% for melanoma. Two features, symmetrically irregular pigment (non-uniform pigmentation with point and axial symmetry) and the presence of a single colour, had a sensitivity of 0%, i.e. were absent, in melanoma. The other significant features are presented, with their sensitivity and specificity for melanoma.

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.

IMMUNOLOGICAL EFFECTS OF SOLARIUM EXPOSURE

Normal volunteers underwent a standard course of treatment to acquire a suntan in a commercial solarium, and tests of immune function were carried out before, on completion, and 2 weeks after completion of radiation exposure. Compared with age and sex matched concurrent controls, the test subjects had reduced skin test responses to dinitrochlorobenzene (DNCB), slightly reduced blood lymphocyte numbers, and changes in the proportion of lymphocyte subpopulations. This included a relative increase in total (OKT3+) T-cell numbers which was attributable to an increase in the OKT8+ suppressor/cytotoxic subset of T cells. OKT4+ helper T cells were reduced and there was a significant decrease in the OKT4/OKT8 ratio. Other changes included a significant increase in suppressor T-cell activity against IgG production in vitro and depression of natural killer cell activity. These changes were still present in some subjects 2 weeks after solarium exposure.

Cutaneous findings in HIV-1-positive patients: A 42-month prospective study

BACKGROUND Cutaneous disease is common in patients infected with HIV-1. OBJECTIVE The aim of our study was to identify cutaneous markers associated with HIV-1 infection and disease progression as measured by Walter Reed (WR) stage. METHODS For 42 months we have observed 912 HIV-1-positive patients in all WR stages. All patients had an extensive past and present medical history taken as well as a complete physical examination, periodic visits, and appropriate diagnostic procedures. RESULTS Increasing dryness of the skin and seborrheic dermatitis are early findings in a large percentage of patients in WR stage 1; the occurrence and severity of both conditions increase with disease progression. Tinea infections, condylomata acuminata, and verrucae are seen early, but with disease progression, although there is no clear increase in occurrence, these infections become more diffuse and resistant to treatment. Flares in acne vulgaris and folliculitis show a peak occurrence in early and mid-stage disease with a decreased occurrence in late-stage disease. Herpes simplex infections, oral candidiasis, molluscum contagiosum, Staphylococcus aureus infections, and oral hairy leukoplakia show a marked increase in occurrence with advanced disease. Conditions that have a statistically significant association with disease progression as measured by a change in a stage include drug eruptions, seborrheic dermatitis, oral candidiasis, oral hairy leukoplakia, molluscum contagiosum, herpes zoster, and hyperpigmentation (nail, oral, skin). CONCLUSION The most frequent and persistent cutaneous disorders were asteatosis (with or without asteatotic eczema) and seborrheic dermatitis. Conditions that were associated with a change in WR stage include drug eruptions, seborrheic dermatitis, oral candidiasis, oral hairy leukoplakia, molluscum contagiosum, herpes zoster, and hyperpigmentation. In addition to Kaposis sarcoma, patients with HIV-1 disease have an increased potential for the development of both cutaneous epithelial and probably melanocytic malignancies. Epithelial tumors were seen in patients in all stages of disease.