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Desmoplastic Neurotropic Melanoma A Clinicopathologic Analysis of 128 Cases
James Y. Chen, MB, BS1 George Hruby, MBChB1 Richard A. Scolyer, MB, BS2,3,4 Rajmohan Murali, MB, BS2,3,4 Angela Hong, PhD1,3 Patrick FitzGerald, PhD5 Trang T. Pham, MB, BS6 Michael J. Quinn, MB, BS3,7 John F. Thompson, MD3,7
BACKGROUND. Several studies have suggested that desmoplastic neurotropic melanoma (DNM) is associated with higher local recurrence rates than other types of melanoma. The authors investigated the local recurrence rates for patients with DNM after surgery alone or surgery followed by radiotherapy (RT).
METHODS. One hundred twenty-eight patients with DNM were treated at the Sydney Melanoma Unit and the Sydney Cancer Center from 1996 to 2007. All patients underwent local excision, 27 patients also received RT. For both groups, clinical and pathologic features, treatment details, and local recurrence data were analyzed.
RESULTS. The median age at diagnosis was 65.5 years. The ratio of men to 1
Department of Radiation Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. 2
Department of Anatomical Pathology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. 3
women was 2.7:1. The head and neck was the most common location (51%). The median Breslow thickness was 4 mm, and 99% of patients had Clark Level IV or V primary tumors. Patients who received adjuvant RT had thicker tumors (P 5 .003), deeper Clark level invasion (P < .001), and narrower excision margins (P < .001). There were 8 local recurrences, including 6 (6%) in the surgery only group and 2 (7%) in the adjuvant RT group. A positive margin (P < .001) and head and neck location (P 5 .03) were significant predictors of local recurrence.
Sydney Melanoma Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
CONCLUSIONS. The local recurrence rate in this series was lower than the rates
4
Discipline of Pathology, Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.
The results indicated that clear surgical margins are of paramount importance in
5 National Health and Medical Research Council Clinical Trials Centre, Camperdown, New South Wales, Australia.
randomized trial is needed to quantify the risk reduction with adjuvant RT.
6 Department of Radiation Oncology, Liverpool Hospital, Liverpool, New South Wales, Australia.
KEYWORDS: desmoplastic, neurotropic, melanoma, adjuvant radiation treatment, local recurrence, prognosis.
reported in historic control groups and in the authors’ previous temporal cohort. minimizing local recurrence; when margins are compromised, the addition of RT may reduce local recurrence rates compared with historic controls. A prospective Cancer 2008;113:2770–8. 2008 American Cancer Society.
7
Discipline of Surgery, University of Sydney, Sydney, New South Wales, Australia.
Address for reprints: James Y. Chen, MB, BS, Department of Radiation Oncology, Royal Prince Alfred Hospital, Missenden Road, Camperdown NSW 2050, Australia; Fax: (011) 612-95158115; E-mail:
[email protected] Received March 26, 2008; revision received June 4, 2008; accepted June 30, 2008.
ª 2008 American Cancer Society
D
esmoplastic melanoma (DM) is a rare histologic subtype of melanoma that originally was described by Conley et al1 in 1971. DM accounts for approximately 1% of all melanomas and is characterized histologically by variably pleomorphic, spindle-shaped cells with associated collagen production. The tumor usually includes some hyperchromatic and elongated nuclei; however, they often are paucicellular with scattered, mildly atypical, spindle-shaped cells in abundant collagen. Under light and electron microscopy, the tumor cells resemble fibroblasts observed in a scar or fibrous tissue. Consequently, DM usually presents clinically as a nondescript plaque, nodule, or thickening that may or may not be pigmented. For these reasons, they often are misdiagnosed clinically and pathologically. In fact, many cases of DM are not diagnosed until they recur. Unrecognized DM was identified as a recurrent problem in a recent review of melanoma-related medical malpractice claims.2
DOI 10.1002/cncr.23895 Published online 29 September 2008 in Wiley InterScience (www.interscience.wiley.com).
Desmoplastic Neurotropic Melanoma/Chen et al
Subsequent to the original description, Reed and Leonard3 reported 19 cases of DM with nerve infiltration, which they termed ‘desmoplastic neurotropic melanoma’ (DNM). This even rarer variant of melanoma accounts for 30% to 40% of DM.4,5 In DNM, tumor cells may surround nerves (perineural invasion), directly invade nerve fibers (intraneural invasion), and may even exhibit the histologic appearance of nerve-like structures or nerve sheath tumors (neural transformation).6,7 Although they often are aggressive locally, the prognosis for DNM appears to be better ‘stage for stage’ than for other subtypes of melanoma.8 Therefore, local control is particularly important. The reported local recurrence rates for DNM of 20% to 50% are higher than for nondesmoplastic melanomas.4,9,10 This may be related to the biology of the tumor, possible failure to recognize this entity early, or inadequate treatment once diagnosed. Recently, it was suggested that DM can be divided into pure and mixed subtypes on the basis of the degree of desmoplasia within the tumor.5,11,12 Desmoplasia may be prominent throughout the entire tumor (‘pure’ DM) or may represent a portion of an otherwise nondesmoplastic melanoma (‘mixed’ or ‘combined’ DM).5 DMs of the ‘pure’ subtype reportedly have a higher rate of local recurrence yet superior overall survival compared with DMs of the mixed subtype and nondesmoplastic melanomas, whereas ‘mixed’ DMs have local recurrence rates and prognosis intermediate between ‘pure’ DMs and nondesmoplastic melanomas.5,12 The previous largest single-institution review of DNM was published by Quinn et al from the Sydney Melanoma Unit (SMU) in 1998. For that study, 90 patients with DNM were accrued over the 10 years between 1985 and 1995. The local recurrence rate was 20% with surgery alone, higher than for other histologic types of melanoma. The role of adjuvant radiotherapy (RT) was not reported in that study. Although some of the published series discussed the use of adjuvant RT in DM,13 to our knowledge, none specifically addressed its role in the neurotropic subtype. In view of this, a single-institution, retrospective analysis was performed in a more contemporary cohort to describe the clinicopathologic features of DNM, to update outcomes, and to explore the role of adjuvant radiation treatment in the management of this entity.
MATERIALS AND METHODS One hundred twenty-eight patients who were diagnosed with DNM between 1996 and 2007 were iden-
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tified by searching the databases of the Sydney Cancer Center Radiation Oncology Department and the SMU. Clinical records were reviewed to obtain patient demographics, primary tumor characteristics, radiation treatment details, and follow-up information. For patients who were referred to the SMU from other institutions, pathology slides and reports from external sites were reviewed individually by SMU pathologists who had expertise in melanoma (R.A.S., R.M.). If there was disparity between the external pathology report and the SMU pathologists’ review, then the results of the SMU review were used for the purposes of this analysis. Where possible, DM was classified into pure versus mixed subtypes according to the criteria proposed by the Memorial Sloan-Kettering Cancer Center (MSKCC).12 Ninety percent or more of the invasive tumor had to exhibit the typical paucicellular, fibrosing appearance for it to be classified as pure DM. Greater than 10% of desmoplasia was required for it to be classified as mixed DM. Neurotropism was defined as 1 or more of 1) tumor extension along nerves either perineurally or endoneurally, 2) formation within the tumor of structures resembling nerves, or 3) a change in the morphology of the tumor cells to resemble neural tissue. Neurotropic melanomas without desmoplasia were excluded from our series. Surgical margins were determined from pathology reports by using the measurement of the closest lateral or deep margin. Recurrence was defined as local if it was described by the surgeon at or near the previous excision site (arbitrarily defined as 5 cm from the original excision site, but not beyond the regional lymph node basin. Regional lymph node recurrence was defined as pathologically confirmed metastatic disease involving the draining lymph node basin. To determine the efficacy of adjuvant RT for DNM, the patterns of recurrence both within and outside the radiation field were determined. All RT treatment fields were documented using digital or film photography. Of 177 patients who presented with stage I through III disease, 22 patients had a diagnosis of ‘probable’ DNM after SMU pathology review and were not included in the current analysis. An additional 27 patients who either had
