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Keywords:

  • desmoplastic melanoma;
  • diagnosis;
  • melanoma;
  • pathology;
  • prognosis;
  • sentinel lymph node biopsy;
  • skin

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

BACKGROUND:

Desmoplastic melanoma (DM) is a rare subtype of melanoma that is characterized by malignant spindle cells separated by prominent, fibrocollagenous stroma. Primary melanomas either may be entirely desmoplastic or almost entirely desmoplastic (pure DM [pDM]) or may exhibit a desmoplastic component admixed with a nondesmoplastic component (combined DM [cDM]).

METHODS:

Patients who were diagnosed between 1993 and 2007 at a single institution with clinically localized, primary cutaneous melanoma (PCM) that contained a desmoplastic component and who underwent sentinel lymph node (SLN) biopsy were identified. Clinical and pathologic features of the primary tumors were correlated with DM type, SLN status, and patient outcome.

RESULTS:

Two hundred fifty-two patients (167 men, 85 women) were identified (median age, 61 years). The median tumor thickness was 2.0 mm. One hundred twenty-three patients (48.8%) had pDM, and 129 patients (51.2%) had cDM. Overall, 17 patients (6.7%) had positive SLN status, including 12 patients with cDM and 5 patients with pDM. Because of the low SLN-positive rate, a statistically significant difference in SLN status between patients with cDM (8.5%) and patients with pDM (4.9%; P = .25) could not be demonstrated. Older patient age, being a man, positive SLN status, and increasing tumor thickness were associated significantly with poorer disease-free survival (P < .05), although only the latter 2 variables were independently predictive. In addition, cDM type (P = .017) was associated significantly and independently with a shorter time to recurrence.

CONCLUSIONS:

In this largest study to date of patients with DM who underwent SLN biopsy, the SLN-positive rate in patients with DM was lower than that in patients with conventional melanoma. The results indicated that DM type is associated significantly and independently with the time to recurrence and should be evaluated routinely in all patients with PCM. Cancer 2010. © 2010 American Cancer Society.

Conley and colleagues first described a variant of melanoma characterized by malignant spindle cells separated by prominent fibrocollagenous stroma, which they termed desmoplastic melanoma (DM).1 DMs that exhibit prominent neural invasion and/or neural differentiation (so called neural transformation) have been termed desmoplastic neurotropic melanomas.2-4

DM accounts for <4% of all primary cutaneous melanoma (PCM).5, 6 It has a predilection for sun-damaged skin, and the most common site is the head and neck region, although any site (including mucosal locations) may be involved.5, 7-11 DM occurs more often in men, and the median age of patients with DM is approximately 60 years.5, 7, 12

Necessary criteria for a diagnosis of DM (namely, the proportion of tumor that is desmoplastic) are not well described. For example, Jaroszewski et al13 described DM as tumors with a significant invasive component made up of atypical spindle cells in a fibrotic stroma, whereas Quinn et al5 defined DM as completely desmoplastic tumors or tumors that contained a recognizable desmoplastic component. Such definitions allow enormous variation in the proportion of desmoplasia allowable in a tumor termed “desmoplastic melanoma.” Others have proposed more precise criteria. Skelton et al14 suggested a 3-tiered classification based on the proportion of fibrous and cellular tumor components (the former predominating in grade 1 DMs, the latter in grade 3 DMs, and both components present in roughly equal proportions in grade 2 DMs). Payne et al15 and McCarthy et al16 defined DMs as melanomas in which >50% of the dermal-invasive tumor was desmoplastic. Recently, Busam et al12 from the Memorial Sloan-Kettering Cancer Center (MSKCC) classified melanomas that exhibited desmoplasia as either pure DM (pDM), in which the overwhelming majority of invasive tumor (≥90%) was desmoplastic, or combined DM (cDM), in which typical features of DM were mixed with densely cellular tumor foci without fibrosis and desmoplasia comprising <90% of the invasive melanoma. This MSKCC classification of DM type was correlated with clinical outcome.12

It has been demonstrated that sentinel lymph node (SLN) biopsy (SLNB) is a minimally invasive method for accurate assessment of the tumor-harboring status of the draining regional lymph node field in patients with melanoma.17, 18 The tumor-harboring status of SLNs is the single most important prognostic factor for patients with melanoma who have clinically localized disease.19-21 Studies evaluating the use of SLNB in patients with DM8, 13, 22-29 have demonstrated a lower SLN-positive rate in DM compared with non-DM. However, those studies involved relatively small numbers of patients (range, 16-65 patients), and the majority did not include parameters such as the MSKCC DM type or the percentage of desmoplasia in the invasive melanoma. We recently reported a low SLN-positive rate in patients with DM; however, the prognostic value of various parameters (including the extent of desmoplasia) was not investigated in detail in that study.27

To our knowledge, the current study is the largest series reported to date of patients with DM who underwent SLNB. We sought to determine the value of SLNB in patients with PCM tumors that exhibited desmoplasia and analyzed the prognostic value of various clinicopathologic factors in these patients. Furthermore, the extent of desmoplasia (defined according to the MSKCC classification12) was assessed to determine whether it was predictive of SLN tumor-harboring status and clinical outcome.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Patients

Pathologic examination of surgical specimens from patients who were referred to the Melanoma Institute Australia (formerly the Sydney Melanoma Unit [SMU]) (MIA), Sydney, was performed at the Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital (RPAH), Sydney. For patients whose pathology was performed at other laboratories before referral to the MIA, histologic slides were reviewed by the pathologists at RPAH, the pathologic data were recorded, and the slides were returned to their sources.

Between 1993 and 2007, patients who were diagnosed with PCM that contained a desmoplastic component and underwent SLNB at MIA/SMU were identified from the RPAH and MIA/SMU databases. Tumors in which any desmoplasia was present in the invasive component (regardless of the proportion of invasive tumor that was desmoplastic) were included in the study. All patients underwent complete excision of the PCM with clear surgical margins when technically feasible, and follow-up radiotherapy was received by those patients who had tumors that exhibited neurotropism or who had involved or close margins.

The SLNB procedure used at our institution has been described previously.21, 30, 31 Briefly, multiple intradermal injections of technetium 99m antimony trisulfide colloid were made around the PCM excision site either on the day of surgery or on the day before surgery. Lymphoscintigraphic scanning was carried out immediately to identify major lymphatic channels and was followed approximately 2.5 hours later by a delayed scan. The position of each SLN was marked on overlying skin, and its depth below the cutaneous surface was documented. Immediately before surgery, patients received intradermal injections of patent blue dye at the PCM site. A handheld gamma probe was used to identify SLNs intraoperatively. The SLNs were examined pathologically according to the following protocol: Each SLN was cut into 3-mm-thick slices along its longitudinal axis beginning at the central meridian, and the slices were embedded in paraffin blocks after tissue processing. Four sequential 5-μ-thick tissue sections were cut from each block and stained with hematoxylin and eosin, S-100, HMB-45, and hematoxylin and eosin, respectively.

Clinical and pathologic parameters of all PCMs as well as follow-up data were extracted from the databases. PCMs were classified as pDM if ≥90% of the invasive tumor was desmoplastic and as cDM if <90% of the invasive tumor was desmoplastic, according to the MSKCC classification.12

Clinicopathologic Parameter Assessment

Clinical parameters included patient age, sex, PCM site, SLN status, non-SLN status, and follow-up information (duration of follow-up and occurrence of locoregional recurrence and/or distant metastasis). Pathologic parameters included primary tumor thickness (Breslow), tumor mitotic rate (TMR), presence of ulceration, Clark level of invasion, MSKCC DM tumor type (pDM or cDM),12 and the presence of lymphovascular invasion and neurotropism.

Clinical and pathologic features of the patients who had pDM were compared with those of patients who had cDM, and a similar comparison was made between SLN-positive patients and SLN-negative patients. The association of clinicopathologic parameters with survival, locoregional (local and regional lymph node) recurrence, and distant metastasis also was analyzed. The study conformed to the guidelines set by the Ethics Committee of the Sydney South West Area Health Service (protocol no. X08-0155).

Statistical Methods

Statistical analysis was carried out using the software package SPSS 16.0 (SPSS Inc., Chicago, Ill). The Kruskal-Wallis statistic was used to test associations between continuous variables and categorical variables. The Pearson chi-square test and the Fisher exact test were used to assess associations between categorical variables, as appropriate.

The time to recurrence (TTR) was defined as time to the first melanoma-related event (recurrence, metastasis, or death). Disease-free survival (DFS) from the date of diagnosis of PCM to the date of first recurrence, and overall survival (OS) was calculated from the date of diagnosis to the date of death, and DFS and OS were censored at the last contact date if there were no events. Univariate analysis (UVA) was performed using the Kaplan-Meier method, and differences in DFS, OS, and TTR were compared using log-rank statistics. Multivariate analysis (MVA) of the factors that were identified as statistically significant in the UVA was performed using a Cox proportional hazards model. P values <.05 were considered statistically significant.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Two hundred fifty-two patients with DM, including 167 men (66.3%) and 85 women (33.7%), who underwent SLNB were identified. Of these, 57 patients were included in our previous study of desmoplastic neurotropic melanoma.4 The patients ranged in age from 25 years to 93 years (mean and median age, 60.5 years). Tumors were located on the trunk, limbs, and head and neck region.

According to the MSKCC classification, 123 tumors (48.8%) were pDMs (Fig. 1a), and 129 tumors (51.2%) were cDMs (Fig. 1b). There were statistically significant differences between pDM and cDM with respect to tumor location (a greater proportion of pDMs involved the head and neck region; P = .001), Clark level and tumor thickness (pDMs were thicker; P < .001), the TMR (greater in cDMs; P < .001), the occurrence of neurotropism (more common in pDMs; P = .005), and the development of locoregional recurrence (more common in cDMs; P = .017) (Tables 1 and 2).

Table 1. Clinicopathologic Characteristics of “Pure” Desmoplastic Melanoma and “Combined” Desmoplastic Melanoma
 No. of Patients (%) 
Parameter“Pure” DM“Combined” DMAll PatientsP
  • DM indicates desmoplastic melanoma; SLN, sentinel lymph node; NS, nonsignificant.

  • a

    According to the 2002 American Joint Committee on Cancer melanoma staging system.

No. of patients123129252 
Age, y   NS
 Mean61.259.960.5 
 Median625960.5 
 Range25-9327-8425-93 
 Age group   NS
  <6052 (42.3)68 (52.7)120 (47.6) 
  ≥6071 (57.7)61 (47.3)132 (52.4) 
Sex   NS
 Women35 (28.5)50 (38.8)85 (33.7) 
 Men88 (71.5)79 (61.2)167 (66.3) 
Primary tumor site   .001
 Head and neck region40 (32.5)24 (18.6)64 (25.4) 
 Upper limbs40 (32.5)41 (31.8)81 (32.1) 
 Lower limbs7 (5.7)27 (20.9)34 (13.5) 
 Trunk36 (29.3)37 (28.7)73 (29.0) 
Clark level   <.001
 III2 (1.6)7 (5.4)9 (3.6) 
 IV73 (59.3)99 (76.7)172 (68.3) 
 V47 (38.2)23 (17.8)70 (27.8) 
 Unknown1 (0.8)0 (0)1 (0.4) 
Primary tumor thickness, mm   <.001
 Mean3.742.933.33 
 Median2.902.202.60 
 Range0.78-13.000.65-21.700.65-21.70 
Pathologic tumor classificationa   <.001
 pT12 (1.6)6 (4.7)8 (3.2) 
 pT228 (22.8)51 (39.5)79 (31.3) 
 pT357 (46.3)50 (38.8)107 (42.5) 
 pT436 (29.3)22 (17.1)58 (23) 
Ulceration   NS
 Present23 (18.7)32 (24.8)55 (21.8) 
 Absent100 (81.3)97 (75.2)197 (78.2) 
Tumor mitotic rate, mitoses/mm2   <.001
 Mean2.74.23.5 
 Median232 
 Range0-170-220-22 
 Tumor mitotic rate group   <.001
  <131 (25.2)9 (6.9)40 (15.9) 
  ≥189 (72.3)120 (93.1)209 (82.9) 
 Unknown3 (2.4)0 (0)3 (1.2) 
Lymphovascular invasion    
 Present0 (0)0 (0)0 (0) 
 Absent123 (100)129 (100)252 (100) 
Neurotropism   .005
 Present54 (43.9)35 (27.1)89 (35.3) 
 Absent69 (56.1)94 (72.9)163 (64.7) 
Table 2. Clinical Outcomes in “Pure” Desmoplastic Melanoma and “Combined” Desmoplastic Melanoma
 No. of Patients (%) 
Parameter“Pure” DM“Combined” DMAll PatientsP
  1. DM indicates desmoplastic melanoma; SLN, sentinel lymph node; NS, nonsignificant.

No. of patients123129252 
 SLN status   NS
 Positive6 (4.9)11 (8.5)17 (6.7) 
 Negative117 (95.1)118 (91.5)235 (93.3) 
Locoregional recurrence   .017
 Yes5 (4.1)16 (12.4)21 (8.3) 
 No118 (95.9)113 (87.6)231 (91.7) 
Regional lymph nodes   .004
 Yes1 (0.8)11 (8.5)12 (4.8) 
 No122 (99.2)118 (91.5)240 (95.2) 
Nonlymph node sites   NS
 Yes4 (3.3)5 (3.9)9 (3.6) 
 No119 (96.7)124 (96.1)243 (96.4) 
Distant metastasis   NS
 Yes14 (11.3)16 (12.4)30 (11.9) 
 No109 (88.7)113 (87.6)222 (88.1) 
Follow-up, mo    
 Mean50.142.045.9 
 Median423235 
 Range1-1450-1700-170 

Seventeen of 252 tumors (6.7%) were SLN-positive. SLN-positive tumors were thicker than SLN-negative tumors (P = .008). Locoregional recurrence and distant metastasis were significantly more common in the SLN-positive group than in the SLN-negative group (23.5% vs 7.2% [P = .042] and 29.4% vs 10.6% [P = .049], respectively). All 17 SLN-positive patients underwent complete regional lymph node dissection, and 4 patients (23.5%) had additional lymph node involvement.

The UVA indicated that male sex, older age, increasing tumor thickness, and positive SLN status were statistically significant predictors of decreased DFS (Fig. 2), and the former 3 variables also were significantly predictive of a poorer OS. cDM type, the presence of ulceration, and positive SLN status were statistically significant predictors of a shorter TTR (Fig. 3). The MVA indicated that increasing tumor thickness and positive SLN status were independent predictors of a shorter DFS. The cDM type, the presence of ulceration, and positive SLN status were independent predictors of a shorter TTR (Table 3). A shorter TTR for lymph node recurrences was associated significantly with the presence of ulceration (P = .003) and with the cDM type (P = .002), and both were independently predictive (P < .02). A shorter TTR for nonlymph node recurrences was correlated significantly only with positive SLN status (P < .001). A shorter time to distant metastasis was associated significantly with increasing tumor thickness (P = .044) and positive SLN status (P = .008), but only the former variable was independently predictive (P = .015).

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Figure 1. The histologic appearance of different types of desmoplastic melanoma (DM) is shown. (Top) This photomicrograph of pure DM reveals a paucicellular tumor composed of relatively bland, spindle-shaped tumor cells separated by abundant, collagenous stroma associated with scattered lymphocytic aggregates. (Bottom) This photomicrograph of combined DM reveals a tumor composed of desmoplastic melanoma (upper left) and nondesmoplastic epithelioid (lower right) melanoma components.

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Figure 2. These Kaplan-Meier curves indicate a significant correlation between clinicopathologic parameters and disease-free survival. pT indicate pathologic tumor classification; SLN, sentinel lymph node.

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Figure 3. These Kaplan-Meier curves indicate a significant correlation between clinicopathologic parameters and the time to disease recurrence. DM indicate desmoplastic melanoma; SLN, sentinel lymph node.

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Table 3. Multivariate Analysis of the Association of Clinicopathologic Parameters With Disease-Free Survival, Overall Survival, and Time to Recurrence
ParameterHR95% CIP
  • HR indicates hazard ratio; CI, confidence interval; DFS, disease-free survival; pT, pathologic tumor classification; LN, lymph node; OS, overall survival; TTR, time to recurrence; DM, desmoplastic melanoma; MSKCC, Memorial Sloan-Kettering Cancer Center; SLN, sentinel lymph node.

  • a

    Significant P value.

  • b

    There was a significantly greater risk of recurrence for patients who had the combined DM type compared with those who had the pure DM type, and the combined DM type was an independent predictor of shorter TTR.

DFS   
 Thickness (pT stage)1.5781.043-2.086.031a
 LN status2.7371.029-7.281.044a
 Age1.8390.953-3.550.069
 Sex1.6700.736-3.790.220
OS   
 Thickness (pT stage)1.6041.055-2.440.027a
 Sex1.6770.743-3.784.213
 Age1.7890.938-3.411.078
TTRb   
 Ulceration3.7151.576-8.757.003a
 DM type (MSKCC)3.4131.247-9.346.017a
 SLN status3.1051.032-9.338.044a

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

The 252 patients in the current study included 209 patients with DM who were reported in our recent study of positive SLN status in PCM.27 However, that previous study focused on patterns of SLN positivity; therefore, the DMs were not characterized in detail, and we did not characterize the prognostic value of various parameters (including the extent of desmoplasia) in the DMs.

The head and neck region was the primary tumor site in only 25.4% of patients in the current study, which contrasts with a range of 41.5% to 75% reported in other studies.5, 7, 13, 24, 32, 33 This variation may be explained in part by the use of various criteria (the extent of desmoplasia required) in the definition of DM in different studies. For example, in the current study, any amount of desmoplasia in the invasive melanoma was accepted. The head and neck region was affected significantly more often in pDMs than in cDMs (32.5% vs 18.6% of tumors, respectively; P = .001). Alternatively, the differences may reflect higher levels of exposure (to ambient sunlight) of nonhead and neck regions in Australian patients.

In a series of 92 patients reported by Busam et al,12 55 of 92 patients (59.8%) had pDM, and 37 patients (40.2%) had cDM, is in contrast to 48.8% and 51.2%, respectively, in the current study. These differences may be because Busam et al12 excluded tumors that had <10% desmoplasia, whereas melanomas that exhibited any degree of desmoplasia were included in the current study. Furthermore, subjectivity and possible poor interobserver reproducibility in assessing the degree of desmoplasia within melanoma (which, to our knowledge, has not been studied formally to date) may be other contributing factors. It is our experience that it can be difficult to estimate the proportion of a given melanoma that is desmoplastic. Generally, pDMs with virtually 100% desmoplasia and cDMs with a very minor (eg <10%) desmoplastic component usually do not present difficulties in this regard. However, accurately estimating the percentage of desmoplasia in cDMs with a desmoplastic component that is in the intermediate range (eg between 10% and 90%) can present a challenge. This is particularly true for cases in which several slides of tumor are available and both the tumor size and the percentage desmoplasia varies from slide to slide. In such situations, the accuracy of estimating the percentage desmoplasia is prone to error and interobserver variation. Such variation also may result in interobserver variation in applying the MSKCC classification, particularly for tumors with a high proportion (eg 70%-90%) of desmoplasia, in which overestimating the percentage desmoplasia would result in classification as pDM, whereas underestimation would lead to classification as cDM. Studies should be undertaken to determine the interobserver reproducibility of assessing the percentage desmoplasia and the MSKCC classification, and the definitions may be refined based on the results of such studies.

In contrast to non-DM, DM reportedly has a greater propensity for local recurrence (range, 0%-55%) and a lesser frequency of regional lymph node metastasis, and this pattern of clinical behavior is more akin to that of sarcomas than conventional melanomas.2, 3, 5, 7, 8, 13-15, 22-24, 28, 34-38 In the current study, locoregional recurrence occurred in 21 patients (8.3%) and was significantly less common in pDMs than in cDMs (4.1% vs 12.4%), largely because of the significantly lower rate of regional lymph node recurrence in pDMs than in cDMs (0.8% vs 8.5%; P = .004) (Table 2). Thirty patients (11.9%) developed distant metastases during follow-up, which is comparable to the rates reported previously (range, 11%-40%).5, 13, 14, 36, 39

The prognosis for patients with DM has been a subject of controversy. Some early studies suggested that patients with DM may have a poorer prognosis than patients with non-DM.1, 37 However, others reported that the survival of patients with DM was better than that of patients with non-DM, particularly if they were matched for tumor thickness.7, 13, 14, 34, 35 In a previous large SMU study of patients with DM, no significant difference in survival was observed between DM and conventional melanoma,5 but this was attributed to the difference in tumor thickness: Many tumors in that study measured <4 mm in thickness, whereas the improved survival demonstrated in other studies was most prominent among patients who had tumors >4 mm in thickness.12 Busam et al12 reported that the greatest difference in DFS between pDM and cDM was in thick tumors and Clark level V tumors. However, when Clark level V tumors were analyzed in the current study, MSKCC DM type was not associated significantly with DFS. Other possible reasons for variation in the reported prognosis for patients with DMs is the variability in the definition of DM (as discussed above) as well as differences in treatment, such as surgical margin clearance and the use of radiotherapy. A recent, large, comparative study of patients with DMs and patients with non-DMs who were matched for key prognostic factors indicated that the survival of patients with DM was similar to that of case-matched patients with non-DM.23

In the study by Busam et al,12 tumor thickness, TMR, MSKCC DM type, and Clark level were predictive of DFS on UVA, and only the latter 2 parameters were independent predictors of DFS. Pawlik et al25 observed that Clark level, SLN status, and MSKCC DM type were significant (but not independent) predictors of DFS. In contrast, we observed that primary tumor thickness, SLN status, patient age, and sex were statistically significant predictors of DFS, whereas tumor thickness and SLN status were independent predictors. These discrepancies may have been caused by differences in the composition of tumors in the studies with respect to the proportion of pDMs and cDMs, differences in case selection criteria, and potential interobserver variation in classifying DM type. We observed that MSKCC DM type (like Pawlik et al25), ulceration, and SLN status were independently predictive of TTR. In contrast to the results from some studies,13, 35 we observed that neurotropism was significantly more common in patients with pDMs (43.9%) than in patients with cDMs (27.1%), but it was not associated significantly with locoregional recurrence.

It has been demonstrated that SLNB is a minimally invasive means of assessing the regional lymph node status of patients with melanoma, and the tumor-harboring status of SLNs is an important prognostic factor in patients with non-DM.19 The reported SLN-positive rate for melanoma (the majority of which are non-DM) is in the order of 16%.20 We demonstrated previously that the SLN-positive rate was significantly lower in patients with DM (6.7%) than in patients with non-DM (18%) and that the absence of tumor desmoplasia was an independent predictor of positive SLN status.27 The SLN-positive rate among patients with DMs in the current study was 6.7%, which was comparable to the rates described previously (range, 0%-12.1%) in smaller studies.8, 13, 22-26, 29 The SLN-positive rate in the current study was associated significantly with increasing tumor thickness (as also demonstrated in other studies23, 27) and with the subsequent occurrence of non-SLN metastasis. SLN status was an independent predictor of DFS and TTR. The SLN-positive rate was higher in patients with cDM (8.5%) than in patients with pDM (4.9%), but the difference was not statistically significant, probably because of the small numbers of patients. This trend is similar to that reported by Pawlik et al,25 who observed a statistically significant difference in the SLN-positive rate between patients with cDMs (15.8%) and patients with pDMs (2.2%), although (as in the current study) pDMs were significantly thicker than cDMs.

On the basis of compiled data from 3 studies25, 29, 40 in which only 2 of 155 patients (1.4%) with pDM had regional lymph node metastasis at the time of surgical staging, George et al29 suggested that it may not be logical for clinicians to recommend SLNB for patients with pDM, because their SLN-positive rate was lower than that observed in patients with thin melanomas (range, 2%-4%) for which SLNB is not usually offered. However, in view of the SLN-positive rate of 4.9% among patients with pDMs in the current study and the lack of evidence demonstrating interobserver reproducibility of the assessment of DM type (as acknowledged by George et al29), such a categorical management recommendation may be premature. Definitive conclusions should be withheld until DM subtypes are defined clearly, reproducibly assessable, and correlated with SLN status and clinical outcomes in large studies.

In summary, our results indicate that DM is associated with a low SLN-positive rate. SLN status is predictive of DFS but is not independent of tumor thickness. MSKCC classification of DM as pDM or cDM appears to be important, in that pDMs tend to be thicker tumors with advanced Clark level of invasion, a higher incidence of neurotropism, a lower TMR, and a lower locoregional recurrence rate compared with cDMs. However, MSKCC DM type was not identified as predictive of DFS or SLN status. Our current results suggest that we should continue offering SLNB to patients with DM (along with an explanation that the positivity rate is likely to be lower than that for non-DM) and that MSKCC DM type should be described in pathology reports of melanomas that exhibit desmoplasia (preferably along with an estimate of the percentage of desmoplasia), because it provides useful prognostic information.

Acknowledgements

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

We thank our colleagues at the Melanoma Institute Australia and at the Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital.

CONFLICT OF INTEREST DISCLOSURES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

We acknowledge the support of Cancer Institute New South Wales and the Australian National Health and Medical Research Council. Dr. Murali and Professor Scolyer are Cancer Institute New South Wales Clinical Research Fellows.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES