Polypoid Melanoma, A Virulent Variant of the Nodular Growth Pattern

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1 Polypoid Melanoma, A Virulent Variant of the Nodular Growth Pattern ELIZABETH A. MANCI, M.D., CHARLES M. BALCH, M.D..TARIQ M. MURAD, M.D., PH.D., AND SENG/JAW SOONG, PH.D. Manci, Elizabeth A., Balch, Charles M., Murad, Tariq M., and Soong, Seng-Jaw: Polypoid melanoma, a virulent variant of the nodular growth pattern. Am J Clin Pathol 75: , Thirty-two patients who had polypoid melanoma were identified in a registry of 552 melanoma patients. The tumor is regarded as a variant of nodular melanoma and is associated with an increased thickness, more frequent ulceration than the nodular variant of melanoma, younger patient age, and higher probability of occult metastasis. Polypoid melanomas were most frequently present on the trunk, and were also encountered in unusual sites, such as the mucosa of the nose, hard palate, and anorectal junction. In terms of survival, the patients with the polypoid nodular variant fared significantly worse than those with nonpolypoid nodular (P =.5) and those with superficial spreading (P =.3) melanomas. The five-year survival rate for the polypoid variant was 42%, in contrast to 57% for the nonpolypoid nodular and 77% for the superficial spreading melanomas. The poor prognosis of patients who have polypoid melanoma is most likely due to its being the type of melanoma with the deepest penetration at the time of surgical excision. (Key words: Polypoid melanoma; Nodular melanoma; Ulceration; Melanoma growth pattern; Melanoma registry; Survival.) FOUR MAJOR GROWTH PATTERNS of melanoma have been described in the literature: superficial spreading, lentigo maligna, nodular, and acrallentigenous types. 91,1314 These growth patterns have been useful as therapeutic and prognostic parameters for patients who have melanoma. The nodular growth pattern has been associated with the most malignant expression of the disease. It has been further subdivided into three distinct variants: a smooth uniform nodule beneath the epidermal surface, an elevated blue-black plaque with an irregular outline, and a pedunculated or polypoid tumor. 9 Of these three variants of nodular melanoma, patients with polypoid tumors have the poorest prognosis. In the present paper, we will present our data for 32 patients who had the polypoid variant of nodular melanoma. Materials and Methods The University of Alabama (UAB) Melanoma Registry contains computerized data for 552 melanoma Received August 4, 198; received revised manuscript and accepted for publication October 17, 198. Address reprint requests to Dr. Murad: Department of Pathology, University of Alabama Medical Center, University Station, Birmingham, Alabama University of Alabama Medical Center, Departments of Pathology, Surgery, and Biostatistics, and the Comprehensive Cancer Center, Birmingham, Alabama patients treated at this institution between 1958 and Pertinent clinical and histologic information has been extracted and analyzed statistically. 1-2,4 The growth pattern of each melanoma has been classified as superficial spreading, lentigo maligna, or nodular, as defined by Clark and associates. 9 The polypoid variant of nodular melanoma was defined as a tumor in which the bulk of the lesion is located above the epidermis, the lateral margins are everted, giving the mass a cauliflower-shape, and lateral extension of the lesion into the adjacent epidermis is limited to less than three rete ridges. Pathologic parameters measured for each lesion included the thickness (Breslow's microstaging); level of invasion (Clark's microstaging); presence or absence of metastases, microscopic ulceration, pigmentation, and lymphocytic infiltration according to criteria defined previously. 2,4,7,9 The clinical data available for each patient included race, sex, age, location and size of the primary lesion, past medical history, family history of malignancy, clinical stage, gross evidence of ulceration, date of diagnosis, and periodic follow-up. Actuarial survival rates were calculated by the method of Kaplan and Meier, and a generalized Wilcoxson test was used to determine whether significant differences in patient survival existed between the polypoid variant and other growth patterns. 8 Chisquare tests were also employed in statistical assessments where appropriate. A discriminant analysis was also employed to discern those features that significantly distinguished patients with polypoid tumor from patients with other types of nodular melanoma. 15 Results Thirty-two (18%) of the 176 nodular melanomas in our series had a polypoid configuration. Nineteen (59%) were in men and 13 (41%) in women. The overall median age at the time of diagnosis was 37 years; ages ranged from 2 to 73 years. Most patients (56%), however, were in the third and fourth decades. The average /81/6/81 $.8 American Society of Clinical Pathologists 81 Downloaded from on 6 March 218

2 Vol. 75 No. 6 POLYPOID MELANOMA age for men was 41 years (range, 21 to 73 years), and that for women was 48 years (range, 26 to 73 years). The trunk was the most frequently involved body site; however, when the data were analyzed by sex, the lower extremity was found to be the most frequent primary site in women (75%), and the upper trunk (71%) in men. The upper extremity was rarely involved in female patients who had polypoid melanomas (7.7%), but it was involved in 22% of female patients in our registry whose lesions had the other growth patterns of melanoma. A few mucosal lesions, including the nasal mucosa, hard palate, and anorectal junction, were encountered. Clinically, polypoid melanoma was a pedunculated, cauliflower-like lesion whose major growth was above the surface. The median diameter of the lesion was 2 cm (range,.5 to 15 cm). Gross ulceration and pigmentation were present in most of our cases. At the time of diagnosis, 69% of the cases were classified as clinical stage I (without clinically detectable metastasis) and 31% as clinical stage II (with clinical evidence of metastasis). Satellite nodules were identified in 11% of 811 Table I. Clinical Comparison of Polypoid and Nonpolypoid Nodular Melanomas Polypoid Total no. of patients Age (yrs) < >6 Sex Male Female Site of primary lesion Lower extremity Upper extremity Head and neck Trunk Other Clinical staging Nonpolypoid (56%) 5 (16%) 9 (28%) 4 (3%) 4 (28%) 6 (42%) 39 (26%) 1 19 (59%) 13 (41%) 75 (52%) 69 (48%) 8 (25%) 7 (22%) 4(13%) 13 (41%) 36 (25%) 28 (19%) 29 (2%) 47 (33%) 4 (3%) 22 (69%) 1(31%) 114(79%) 28 (2%) 2(1%) P Value* * The P value refers to the comparison between the polypoid and nonpolypoid nodular melanomas with respect to the distribution of the factors specified. t Statistically significant P value. FIG. 1. The bulk of the polypoid melanoma lesion is located above the epidermis, and the lateral margins are everted, giving the mass a cauliflower shape. Direct photography. x6. Downloaded from on 6 March 218

3 812 A.J.C.P. June1981 MANCI ET AL. eosin. x 11. Downloaded from on 6 March 218

4 Vol. 75 No. 6 POLYPOID MELANOMA 813 FIG. 4. Moderate lymphocytic infiltration is present at the base of the polypoid melanoma. The leading edge of the lesions frequently appeared sharply demarcated from the adjacent dermis. Vascular channels were most numerous at the base of the lesion, and lymphatic permeation was a frequent finding. Hematoxylin and eosin. x 15. the patients who had polypoid melanoma and were seen only in patients who had lesions of the dorsal trunk. A summary of the clinical data is presented in Table 1. Histologically, the polypoid growth pattern mushroomed over the adjacent skin (Fig. 1). In most cases, the melanoma cells were polyhedral (Fig. 2); in a few patients the tumor was formed primarily of spindletype cells (Fig. 3). The lesions were large and deep, ranging from 1.5 to 12.6 mm in depth and having an overall median vertical thickness of 4.85 mm. Pigmentation and surface ulceration were identified in approximately 75% of the cases (Fig. 3). In most cases, the tumor had invaded the reticular dermis (Clark's level IV) at the time of histologic examination. Most polypoid melanomas had a diminished host response evidenced by only mild to moderate lymphocytic infiltration of the adjacent stroma (Fig. 4). Although the leading edges of the lesions frequently appeared to be pushing into the adjacent dermis and were sharply demarcated, lymphatic permeation was frequently seen at the bases of the lesions (Fig. 4). The incidence of lymph node metastases appeared to be directly related to tumor thickness. In this regard, the median thickness of the polypoid melanomas with no histologically demonstrable metastasis (pathologic stage 1) was 3.2 mm, whereas the median thickness for lesions with nodal metastases (pathologic stage Downloaded from on 6 March 218 2) was 7.2 mm. The histologic data are summarized in Table 2. The five-year survival rate for patients with polypoid melanoma was 42%, whereas the rate for patients with nonpolypoid nodular melanoma was 57%. The fiveyear survival rate was better for patients who had superficial spreading melanoma (77%) (Table 3). T h e P value for comparing the differences in survival between the polypoid and nodular melanomas was.5 and that for comparing the polypoid and superficial spreading melanomas was.3. For patients with pathologic stage I lesions, tumor thickness was inversely correlated with survival. Patients with the longest survival time (1-11 years) had tumors ranging in thickness from 2 to 3.1 mm (median, 2.6 mm); patients with the shortest survival (1-2 years) had tumors ranging in thickness from 2.6 to 8 mm (median, 4.4 mm). However, for patients with pathologic stage II lesions, this inverse correlation of thickness with survival was not found. Instead, survival was more directly correlated with the number of positive lymph nodes at the time of diagnosis. In this regard, the average survival for patients with four or more positive lymph nodes was ten months, and for patients with two or less lymph nodes it was 2 months. The number of positive nodes in patients with pathologic stage II lesions varied from one to five nodes (a

5 814 MANCI 7/AL. A.J.C.P. June 1981 Table 2. Histologic Comparison of Polypoid and Nonpolypoid Nodular Melanomas Polypoid Nonpolypoid Total no. of patients Thickness (mm) (1%) (24%) (22%) 45(31%) (19%) 19(13%) >4. 19 (59%) 31 (22%) 1 Clark's level II III IV V Microscopic ulceration Present Absent Pigmentation Present Absent Lymphocytic infiltration Mild Moderate Heavy Pathologic stage (I) No evidence of metastasis (II) With lymph node metastases (III) With distant metastases * Statistically significant P value. 1 (3%) 9 (28%) 18 (56%) 4 (13%) 22 (72%) 8 (25%) 1 (3%) 24 (75%) 7 (22%) 1 (3%) 11 (35%) 19 (59%) 2 (6%) 21 (66%) 11 (34%) 13 (9%) 49 (35%) 54 (38%) 26(18%) 2 69 (48%) 72 (5%) 3 (2%) 11 (77%) 25 (17%) 9 (6%) 48 (33%) 56 (39%) 23 (16%) 17 (12%) 119 (83%) 22(15%) 3 (2%) P Value.5*.25.37* * median of two positive nodes per patient). The average survival of patients with metastases was 1.9 years. To compare polypoid tumors with other nodular melanomas, all clinical and pathologic variables were subjected to discriminant analysis. After simultaneously accounting for all other variables, three factors were found to be statistically significant in distinguishing the polypoid tumors from other nodular melanomas: thickness, ulceration, and age. lesions require a marked vessel proliferation that facilitates early metastasis. 11 Our data support these observations, since lymphatic permeation was present in many of our lesions in spite of their well-demarcated or pushing borders (Fig. 4). In our series, polypoid melanomas were typically 2 cm in diameter, invading to Clark's level IV, 4.85 mm thick, ulcerated, and heavily pigmented. Patients with these tumors had a younger median age at the time of diagnosis, a high rate of metastases, and a poor prognosis. The UAB data are generally similar to those of the Queensland Melanoma Project except for a higher ratio of nodular melanomas and chest lesions at UAB. 5,1 Among the variables that were analyzed, tumor thickness strongly correlated with prognosis for patients with pathologic stage I polypoid melanoma. The thinnest polypoid melanoma in the UAB series (1.5 mm) was in the range associated with a 57% risk of harboring regional metastases at the time of diagnosis. 2 Most patients had tumors greater than 4 mm in thickness, which are associated with an extremely high risk (8%) of harboring occult regional and distant metastases. 2 In the presence of regional metastases, however, tumor thickness appears to be a less important prognostic indicator than the number of lymph nodes containing the tumor. In a previous study, thickness also had a less significant correlation with prognosis for those patients who had been treated by wide local excision and regional node dissection. 3 The lack of association between thickness and lymph node metastasis may indicate a tendency for some of these tumors to regress after regional metastases are established. Smith and Stehlin have reported the case of a patient who had a well-documented "toadstool" melanoma that appeared and spontaneously regressed during a two-year interval; however, within the following year it disseminated widely and was fatal. 18 Clinical recognition of the characteristic gross morphologic features of polypoid melanoma should alert physicians to the high risk of underlying metastatic disease at the time of diagnosis. The differential diagnosis of such lesions should include benign neurofibroma, seborrheic keratosis, pyogenic granuloma, squamous cell carcinoma, basal cell carcinoma, hemangioma, and hematoma Since tumor Discussion The polypoid growth pattern of melanoma was first mentioned in the literature by Vogler and associates in 1958 as a "pedunculated" melanoma lesion. 19 In 1968, Bodenham noted that "mushroom shaped" melanomas were associated with a poor prognosis. 6 In 1972, Little postulated that the rapid growth and expansion of these Table 3. Comparison of Actuarial Survival Rates for Three Growth Patterns of Melanoma No. of Growth Pattern Patients 1 Year 3 Years 5 Years Polypoid 32 88% 48% 42% Nodular 144 9% 74% 57% Superficial spreading 67 98% 85% 77% Downloaded from on 6 March 218

6 Vol. 75 No. 6 POLYPOID MELANOMA 815 thickness is an important factor in predicting metastatic disease in patients who have melanoma, a suspected lesion should never be excised by a shave or a curette biopsy technic that would disrupt the deep margin of the tumor. An excisional biopsy extending down to the subcutaneous tissue is required for accurate microstaging. In our small series, when metastases were present with a polypoid melanoma, accurate assessment of the number of nodes containing the tumor was the most important prognostic indicator for this most virulent form of melanoma. References 1. Balch CM, Murad TM, Soong S, et al: A multifactorial analysis of melanoma: prognostic histopathological features comparing Clark's and Breslow's staging methods. Ann Surg 188: , Balch CM, Murad TM, Soong S, et al: Tumor thickness as a guide to surgical management of clinical stage 1 melanoma patients. Cancer 43: , Balch CM, Soong SJ, Murad TM, et al: A multifactorial analysis of melanoma II: prognostic factors in patients with stage 1 (localized) melanoma. Surgery 86: , Balch CM, Wilkerson JA, Murad RM, et al: The prognostic significance of ulceration of cutaneous melanoma. Cancer 45: , Beardmore GL: Primary cutaneous polypoidal nonstageable melanomas in Queensland. Aust J Dermatol 18:73-76, Bodenham DC: A study of 65 observed malignant melanomas in the southwest region. Ann R Coll Surg Engl 43: , Breslow A: Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 172:92-98, Burnette WJ, Gehan EA: Planning and analysis of clinical studies. Springfield, Charles C Thomas, 197, pp Clark WH, From L, Bernardino EA, et al: The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 29:75-727, Davis N: Malignant melanoma in Queensland: a review. Aust J Dermatol 19:13-18, Little JH: Histology and prognosis in cutaneous malignant melanoma, Melanoma and skin cancer, proceedings of the Informational Cancer Conference, Sydney. Edited by V. C. N. Blight. New South Wales, Government Printer, 1972, pp Little JH, Davis NC: Frozen section diagnosis of suspected malignant melanoma of the skin. Cancer 34: , McGovern VJ: The classification of melanoma and its relationship with prognosis. Pathology 2:85-98, Mihm MC, Clark WH, Reed RJ: The clinical diagnosis of malignant melanoma. Semin Oncol 2:15-118, Morrison DF: Multivariate statistical analysis. Second edition. New York, McGraw-Hill, 1976, pp Niven J, Lubin J: Pedunculated malignant melanoma. Arch Dermatol 111: , Shapiro L, Bodian EL: Malignant melanoma in the form of pedunculated papules. Arch Dermatol 99:49-5, Smith JL, Stehlin JS: Spontaneous regression of primary malignant melanomas with regional metastases. Cancer 18: , Vogler WR, Perdue GD, Wilkins SA: A clinical evaluation of malignant melanoma. Surg Gynecol Obstet 16: ,1958 Downloaded from on 6 March 218