Section 1 -

Thin Metastasising Cutaneous Malignant Melanoma Peter Heenan

Thin cutaneous malignant melanoma (CMM) (< 1mm thick) now account for the majority of invasive primary CMM; in Western Australia, 68% of invasive CMM diagnosed in 2001 and 2002 were less than 1mm thick with a median thickness of 0.6mm, which has remained essentially unchanged for the last ten years [1]. Although thin CMM are associated with low mortality rates, their large numbers mean that they cause a significant fraction of melanoma deaths. Because there is a perceived need to identify patients with thin CMM who belong in a high risk group and may be candidates for upgrading of clinical staging and viewed as possible candidates for clinical trials and sentinel node biopsy, several recent studies have attempted to identify significant prognostic factors in this group of patients [2, 3, 4, 5, 6, 7, 8, 9]. These studies on prognostic factors in thin CMM have produced a variety of results, some of them contradictory. Among the clinical features reported as being possible prognostic factors for thin CMM are age and sex of the patient and anatomic site of the tumor; histologic factors include tumor thickness, growth phase, mitotic rate, regression, ulceration, Clark's level of invasion, tumor infiltrating lymphocytes (TIL) and histologic type. Contradictory results in these studies, however, mean that no single factor or group of factors, validated by several reports, have yet emerged as sensitive and specific markers of metastasis in thin CMM [10]. The variety of results from these studies may well have been due, at least in part, to variation in the criteria used for some histologic factors including regression, interobserver variation among pathologists, differences in the extent of sampling of surgical specimens, and differences in study design. Incomplete clinical information or lack of access to previous pathology reports and slides for review may also lead to the failure to identify cases of multiple primary melanomas, some of which may have been the more likely source of metastases [2]. Gimotti et al [8] have suggested that a prognostic tree based on growth phase, mitotic rate and sex, provides more accurate information on thin CMM than the American Joint Committee on Cancer staging of melanoma and they suggested that their model should be useful in the design of clinical trials and for the assessment of clinical management after validation in other populations. More recently, the same group of investigators identified mitotic rate, ulceration, vertical growth phase and male sex as independent predictors of regional lymph node metastasis in patients with thin CMM [9]. Although it may seem intuitively obvious that researchers should strive to identify more accurate clinical, histologic and molecular factors in melanomas of all sizes, it also seems appropriate to reflect on the rationale for, and the possible consequences of improvements in clinicopathological prognostication [11]. Whereas there is no doubt that the current AJCC staging of thin melanomas, based only on Clark's level and/or ulceration within stage 1, should be improved, the application of prognostic models to individual patients remains speculative, as emphasized by Ackerman [12]. Sentinel lymph node biopsy (SLNB), still a controversial concept, may be recommended for patients with thin CMM classified as having a high risk of metastasis, but the value of SLNB in these patients remains unknown [13, 14]. It appears possible, however, that continued improvement in non-invasive prognostic techniques, both histological and molecular, will provide information that will be more accurate than that provided by SLNB. References Threlfall TJ, Thompson JR 2004. Cancer incidence and mortality in Western Australia, 2002. Department of Health, Western Australia, Perth. Statistical series number 71. Taran JM, Heenan PJ. Clinical and histologic features or level 2 cutaneous malignant melanoma associated with metastasis. Cancer 2001; 91:1822-5. Cook MG, Spatz A, Bröcker E-B, et al. Identification of histological features associated with metastatic potential in thin (<1.0mm) cutaneous melanoma with metastases. A study on behalf of the EORTC Melanoma Group. J Pathol 2002; 197:188-193. Guitart J, Lowe L, Piepkorn M, et al. Histological Characteristics of Metastasizing Thin Melanomas: A Case-Control Study of 43 Cases. Arch Dermatol 2002; 138:603-608. McKinnon JG. Yu XQ, McCarthy WH et al. Prognosis for patients with thin cutaneous melanoma: Long-term survival data from the New South Wales Central Cancer Registry and the Sydney Melanoma Unit. Cancer 2003; 98:1223-31. Kalady MF, White RR, Johnson JL et al. Thin Melanomas : Predictive lethal characteristics from a 30-year clinical experience. Ann Surg 2003; 238:528-537. Leiter U, Buettner PG, Eigentler TK, et al. Prognostic Factors of Thin Cutaneous Melanoma: An analysis of the Central Malignant Melanoma Registry of the German Dermatological Society. J Clin Oncol 2004; 22:3660-3667. Gimotty PA, Guerry DP, Ming ME et al. Thin Primary Cutaneous Malignant Melanoma: A Prognostic Tree for 10-year Metastasis is more Accurate than American Joint Committee On Cancer Staging. J Clin Oncol 2004; 22:3668-3676. Karakousis GC, Gimotty PA, Botbyl JD et al. Predictors of regional nodal disease in patients with thin melanomas. Ann Surg Oncol 2006; 13:533-541. Berman, DM. Lack of agreement on predictors for metastasizing thin melanomas. Histopathology 2005; 48:200-219 (Letter) Halpern AC, Marghoob AA. Thin Melanoma: Still "Excellent Prognosis" Disease? J Clin Oncol 2004; 22:3651-3653 Ackerman, AB. Mythology and Numerology in the Sphere of Melanoma. Cancer 2000; 88:491-496. Wong LW, Brady MS, Busam KJ et al. Results of Sentinel Lymph Node biopsy in patients with thin melanoma. Ann Surg Oncol 2006;13:302-309 Thompson JF, Shaw HM. Is Sentinel Lymph Nod Biopsy appropriate in patients with thin melanomas: Too early to tell? Ann Surg Oncol 2006;13:279-281.