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Annals of Surgical Oncology 10:403-407 (2003)
© 2003 Society of Surgical Oncology

ORIGINAL ARTICLES

Sentinel Lymph Node Biopsy for Patients With Cutaneous Desmoplastic Melanoma

David E. Gyorki, Klaus Busam, MD, Kathy Panageas, PhD, Mary Sue Brady, MD and Daniel G. Coit, MD

From the Departments of Surgery (DEG, MSB, DGC), Surgical Pathology (KB), and Biostatistics (KP), Memorial Sloan-Kettering Cancer Center, New York, New York.

Correspondence: Address correspondence and reprint requests to: Daniel G. Coit, MD, Gastric and Mixed Tumor Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; Fax: 212-717-3400; E-mail: coitd{at}mskcc.org


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Background: Although desmoplastic melanoma (DM) often presents at a locally advanced stage, nodal metastases are rare. We describe our experience with lymphatic mapping and sentinel lymph node biopsy (SLNB) in patients with DM to characterize the biological behavior of these tumors.

Methods: Twenty-seven patients with cutaneous DM underwent wide excision and attempted SLNB between 1996 and 2001. All pathology was reviewed by a single dermatopathologist (KB). Clinical and histological features were recorded.

Results: There were 20 male and 7 female patients. The median age was 64 years (range, 35–83 years). The head and neck was the most commonly involved anatomical region (n = 14). The median Breslow thickness was 2.2 mm. Twenty-four patients underwent successful SLNB. No patient had a positive sentinel node. At a median follow-up of 27 months, five patients recurred (four systemic and one local); all five had undergone successful SLNB. Two of these patients died of disease, two are alive with disease, and one remains alive and disease free. No patient experienced failure in a regional nodal basin.

Conclusions: DM is a biologically distinct form of melanoma, with a very low incidence of regional lymph node metastases, either at presentation or in long-term follow-up. This biology should be considered when designing rational treatment strategies for these patients.

Key Words: Desmoplastic melanoma • Sentinel lymph node biopsy • Local recurrence • Survival


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Desmoplastic melanoma (DM) is a rare variant of malignant melanoma first described by Conley et al.1 in 1971 as seeming to be "clinically innocuous" and histologically consisting of an "invasive spindle cell tumor" with "abundant dense collagen." This is an unusual subtype of melanoma, comprising only 4% of patients reported recently from the Sydney Melanoma Unit.2 Compared with other types of melanoma, it has a relatively high incidence of local recurrence2,3 and a low incidence of lymph node (LN) metastases, despite commonly presenting at a locally advanced stage.2,4

Whereas most patients presenting with primary cutaneous malignant melanoma have no palpable lymphadenopathy, approximately 15% to 20% of patients with tumors >1 mm thick will harbor occult metastases in the regional LN basin. The most important factor in determining the prognosis of patients without clinical lymphadenopathy is the regional LN status.5 Lymphatic mapping (LM) with sentinel LN (SLN) biopsy (SLNB) has been shown to be extremely accurate for determining the pathologic stage of these nodes.5 The reason postulated for this is that identification and excision of the node most likely to contain metastasis enables the pathologist to focus more fully on less than a full lymphadenectomy specimen with techniques of serial sectioning and immunohistochemical analysis.

There is no large series in the literature that outlines the specific findings of SLNB in DM. We describe our experience with SLNB in patients with DM and characterize the extent of LN involvement in these tumors.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
We identified 32 patients (4.4%) with cutaneous DM from our database of 724 patients with melanoma who presented for definitive management with wide local excision and SLNB at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1996 and 2001. Five of these patients did not undergo LM or SLNB, for reasons listed in Table 1. Of the remaining 27 patients, 24 underwent successful LM/SLNB. In two patients, there was no migration of radioisotope to any nodal basin or preoperative lymphoscintigraphy, and one patient declined SLN biopsy after successful lymphoscintigraphy. At presentation, the patient’s age and sex; the tumor site and thickness; Clark level; and presence of ulceration were recorded.


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  		TABLE 1. Disqualifying characteristics of patients who did not undergo SLNB
 
The technique of LM/SLNB was performed as previously decribed.6 In all but the first case, preoperative lymphoscintigraphy was performed to guide the surgeon to the SLN. An intraoperative handheld gamma probe was used to identify the SLNs and to ensure complete sentinel lymphadenectomy. All patients underwent wide excision with at least 2-cm margins. Two patients received adjuvant therapy at MSKCC. Of these, one patient received both local radiotherapy and systemic temozolomide, and the other was placed on an immunotherapy vaccine trial.

The pathology of all tumors and LNs was reviewed by a single dermatopathologist (KB). For a melanoma to be accepted as desmoplastic and to be included in this series, it had to show prominent stromal fibrosis throughout the entire tumor and to be predominantly composed of fusiform melanocytes constituting >90% of the tumor cell population. A typical example of a DM is illustrated in Fig. 1. A fibrosing spindle cell tumor is seen in the dermis and subcutis with partial replacement of fat lobules. In the absence of associated in situ melanoma, the melanocytic origin of the tumor was confirmed by immunohistochemical staining for S-100 protein (Fig. 1). Spindle cell melanomas without or with only focal desmoplastic features were excluded in the series. All DMs in this series were amelanotic. Some desmoplastic tumors showed prominent perineural or intraneural involvement by tumor and were designated desmoplastic neurotropic melanoma. The primary tumors were reviewed for Breslow thickness, Clark level, and presence of ulceration. The margins of wide excision were also assessed. All SLNs were examined by hematoxylin and eosin–stained sections. Forty-three of 66 SLNs in 16 of 24 patients (all cases since November 1997) were also examined by serial sectioning and immunoperoxidase staining procedures by using antibodies to S-100 protein and glycoprotein 100 (GP100, HMB45).



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  		FIG. 1. Desmoplastic melanoma. (A) Scanning magnification shows a fibrosing tumor infiltrating the dermis and subcutis. (B) The tumor is composed of hyperchromatic spindle cells in a collagen-rich stroma and is focally associated with lymphoid aggregates. (C) The tumor cells are homogenously immunopositive for S-100 protein.

 
The patients were followed up from the date of their definitive treatment at MSKCC. Kaplan-Meier charts were used to plot recurrence-free and overall survival.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 REFERENCES
 
The study population (Table 2) showed a male predominance. The median age was 64 years (range, 35–83 years). More than half of all primary lesions were in the head and neck region (n = 14), followed by the trunk (n = 8) and the extremities (n = 5). Ten cases (37%) showed some perineural involvement and were classified as desmoplastic neurotropic melanoma. Most tumors were of intermediate thickness, with 82% >1.5 mm thick. The median thickness was 2.2 mm. All tumors were Clark level IV (74%) or V (26%). Two of the specimens showed ulceration.


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  		TABLE 2. Patient characteristics
 
All final margins were negative, although one patient required a second excision. None of the 24 patients who underwent successful SLNB had a positive SLN.

With a median follow-up of 27 months (range, 9–64 months), there were five recurrences, all in patients who had undergone successful SLNB. In the five patients who experienced recurrence, the median time to recurrence was 29 months (range, 6–43 months). Of these recurrences, four were systemic and one was local. The local recurrence was seen in a patient who underwent excision of an 8-mm Clark V cheek melanoma with a close but negative deep margin at original excision. That patient shows no evidence of disease 9 months after re-excision. No patient has had a nodal recurrence, regardless of whether SLNB was successful. At last follow-up, 23 patients were without evidence of disease, two patients were alive with disease, and two patients had died of disease. Relapse-free and overall survival estimates are shown in Fig. 2.



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  		FIG. 2. Relapse-free and overall survival of 24 patients with desmoplastic melanoma undergoing successful sentinel lymph node biopsy.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 REFERENCES
 
DM is consistently reported in the literature as having a clinical behavior quite distinct from non-DM. This includes being more common in men, having a higher incidence in the head and neck, presenting at a locally advanced stage (Breslow thickness), having a low rate of nodal involvement, and having a high rate of local recurrence (Table 2). Our experience confirms these results. Fourteen (54%) of 27 cases of DM in our series were in the head and neck region. This is consistent with published data showing a range of 38% to 84% of DM located in the head and neck (Table 2). Up to 21%, a higher proportion than seen elsewhere on the body, of all cutaneous melanomas of the head and neck are desmoplastic.7 Reasons for these consistently reported sex and anatomical predilections are unclear.

Contrary to published data, which report local recurrence rates of up to 55% (median, 25%) of patients (Table 3), we observed only one case of local recurrence. This may be explained by the relatively short duration of follow-up. However, this is unlikely to be the only explanation for the low rate of local recurrence. Quinn et al.2 reported that, among patients who ultimately experienced recurrence, 78% had recurrence within 2 years of presentation. An alternative explanation is that all patients in our series underwent wide local excision with at least 2-cm margins. A previous study2 showed significantly higher recurrence rates in patients with excision margins <1 cm. Thus, our low rate of recurrence may be a reflection of improved local control of disease associated with a deliberate effort to achieve wider surgical margins.


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  		TABLE 3. Comparative data of patients with DM from literature review
 
The reported incidence of nodal involvement as shown by SLNB in intermediate to thick melanoma varies from 17%8 to 23%.9 These figures are significantly higher than our findings of 0 in 24. This study represents the largest reported group of patients with DM who have undergone SLNB. Table 4 describes previously published data for SLNB in patients with DM. Only one other study10 used SLNB as a standard part of the staging process for DM. They reported 0 of 16 patients with a positive SLN. Two other studies11,12 reported their experience in subsets of the reported patients. In the first,11 SLNB was performed on 10 patients with DM >.75 mm thick; 1 patient with a positive SLN was discovered. In the other study,12 SLNB was performed on 12 patients, and no patient had a positive SLN. A summary of published literature of patients with DM undergoing SLNB reveals a positive SLN in only 1 (1.6%) of 62 reported cases.


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  		TABLE 4. Reported cases of DM and positive SLNB
 
It is important to note that SLNB, although minimally invasive, is not without risk. The large proportion of SLNBs in the head and neck implies that lymphoscintigraphy showing drainage to the intraparotid nodes is not uncommon. Patel et al.7 report a 25% incidence of temporary postoperative facial nerve weakness after SLNB. Nerve paresthesia, seroma, and, occasionally, edema are seen after the procedure with a small but finite incidence.

Given the low rate of nodal involvement, even with the minor potential risks involved, the question arises as to whether SLNB is clinically indicated in patients with DM. A Dutch study of thin melanoma13 reported that of 75 patients with Breslow thickness <.9 mm, none showed a positive SLNB. On this basis, the authors concluded that SLNB is "probably superfluous" for these patients. With a similarly low incidence of positive regional nodes observed in patients with DM, a similar conclusion could be applied to this population, despite the relatively advanced local stage at presentation.

On the basis of our findings, we agree with Jaroszewski et al.12 that the behavior of DM is more akin to that of soft tissue sarcoma, with a predilection for systemic rather than regional LN metastasis. Our data suggest that DM is a nonnodotropic variety of melanoma and that surgical staging of regional nodes may be unnecessary.


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
REFERENCES
 
Our data analysis and review of the literature suggests that DM seems to be a biologically distinct form of melanoma with a very low incidence of regional LN metastases either at presentation or in long-term follow-up. This biology should be considered when rational treatment strategies are designed for these patients.


   Footnotes
 
In 24 patients with desmoplastic melanoma (DM) who underwent successful lymphatic mapping and sentinel lymph node biopsy (LM/SLNB), no lymph node involvement was found, nor were there any subsequent lymph node recurrences. We describe our experience with DM in the era of LM/SLNB.

Received for publication April 4, 2002. Accepted for publication December 2, 2002.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 

  1. Conley J, Lattes R, Orr W. Desmoplastic malignant melanoma (a rare variant of spindle cell melanoma). Cancer 1971; 28: 914–36.[CrossRef][Medline]
  2. Quinn MJ, Crotty KA, Thompson JF, Coates AS, O’Brien CJ, McCarthy WH. Desmoplastic and desmoplastic neurotropic melanoma: experience with 280 patients. Cancer 1998; 83: 1128–35.[CrossRef][Medline]
  3. Carlson JA, Dickersin GR, Sober AJ, Barnhill RL. Desmoplastic neurotropic melanoma. A clinicopathologic analysis of 28 cases. Cancer 1995; 75: 478–94.[CrossRef][Medline]
  4. Jain S, Allen PW. Desmoplastic malignant melanoma and its variants. A study of 45 cases. Am J Surg Pathol 1989; 13: 358–73.[Medline]
  5. Gershenwald JE, Thompson W, Mansfield PF, et al. Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol 1999; 17: 976–83.[Abstract/Free Full Text]
  6. Coit DG. How we do it: the Memorial Sloan-Kettering Cancer Center approach. In: Cody HS, ed. Sentinel Lymph Node Biopsy. London: Martin Dunitz, 2002: 135–41.
  7. Patel SG, Coit DG, Shaha AR, et al. Sentinel lymph node biopsy for cutaneous head and neck melanomas. Arch Otolaryngol Head Neck Surg 2002; 128: 285–91.[Abstract/Free Full Text]
  8. Clary BM, Brady MS, Lewis JJ, Coit DG. Sentinel lymph node biopsy in the management of patients with primary cutaneous melanoma: review of a large single-institutional experience with an emphasis on recurrence. Ann Surg 2001; 233: 250–8.[CrossRef][Medline]
  9. Morton DL, Chan AD. Current status of intraoperative lymphatic mapping and sentinel lymphadenectomy for melanoma: is it standard of care? J Am Coll Surg 1999; 189: 214–23.[CrossRef][Medline]
  10. Thelmo MC, Sagebiel RW, Treseler PA, et al. Evaluation of sentinel lymph node status in spindle cell melanomas. J Am Acad Dermatol 2001; 44: 451–5.[CrossRef][Medline]
  11. Payne WG, Kearney R, Wells K, et al. Desmoplastic melanoma. Am Surg 2001; 67: 1004–6.[Medline]
  12. Jaroszewski DE, Pockaj BA, DiCaudo DJ, Bite U. The clinical behavior of desmoplastic melanoma. Am J Surg 2001; 182: 590–5.[CrossRef][Medline]
  13. Muller MG, van Leeuwen PA, van Diest PJ, Vuylsteke RJ, Pijpers R, Meijer S. No indication for performing sentinel node biopsy in melanoma patients with a Breslow thickness of less than 0.9 mm. Melanoma Res 2001; 11: 303–7.[CrossRef][Medline]
  14. Skelton HG, Smith KJ, Laskin WB, et al. Desmoplastic malignant melanoma. J Am Acad Dermatol 1995; 32: 717–25.[CrossRef][Medline]
  15. Smithers BM, McLeod GR, Little JH. Desmoplastic melanoma: patterns of recurrence. World J Surg 1992; 16: 186–90.[CrossRef][Medline]
  16. Egbert B, Kempson R, Sagebiel R. Desmoplastic malignant melanoma. A clinicohistopathologic study of 25 cases. Cancer 1988; 62: 2033–41.[CrossRef][Medline]



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