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Lymph Node Biopsy Results for Desmoplastic Malignant Melanoma

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Lymph Node Biopsy Results for Desmoplastic Malignant Melanoma THERAPEUTICS FOR THE CLINICIAN Lymph Node Biopsy Results for Desmoplastic Malignant Melanoma Deborah L. Cummins, MD; Clemens Esche, MD; Terry L. Barrett, MD; Charles M. Balch, MD; Mona Mofid, MD Desmoplastic malignant melanoma (DMM) is a by fascicles of atypical spindle-shaped cells, bands rare variant of melanoma with distinct histopatho- of fibrosis, and poorly defined margins.2 Clinically, logic and clinical features. Compared with other the lesions commonly have a benign appearance. melanomas, the desmoplastic variant demon- Firm and scarlike, the lesions often are amelanotic.3 strates a greater frequency of local recurrence The bland clinical appearance and difficult histology and a proclivity for tracking along nerves, but it oftentimes delay the correct diagnosis. At the time poses a lower risk of distant metastases. Elective of diagnosis, the lesions generally are quite deep, lymph node dissection and sentinel lymph node with reports of median tumor thickness ranging biopsy (SLNB) are commonly used tools for deter- from 2.5 to 6.5 mm deep.4,5 Most DMM cases are mining prognosis in thick melanomas. The role Clark level IV or V.6 of these procedures for DMM remains unclear. The natural history and pattern of spread of DMM This study was designed to characterize DMM differs somewhat from other melanomas. Local recur- and determine the frequency of histologically rence and extension to adjoining areas is common. positive lymph nodes in patients with DMM. This The tumor also has a particular affinity for invading retrospective chart review included patients with nerves.7 In contrast, distant spread is less common DMM treated by Johns Hopkins Hospital (JHH) than in other melanomas in spite of the greater thick- physicians between 1998 and 2003. Among the ness of DMMs at diagnosis. Consequently, the 5-year 28 patients included in the study, 18 patients had survival rate for patients with DMM lesions greater biopsies performed on lymph nodes (15 SLNBs than 4-mm deep has been reported as 61%, compared and 3 radical neck dissections). One patient had with only 40% for other melanomas.6 a sentinel lymph node with histology positive for General guidelines for melanoma treatment rec- DMM. All others had negative results from histol- ommend that a sentinel lymph node biopsy (SLNB) ogy and S100 stains. This study suggests that the be considered for patients with melanomas at least frequency of positive SLNBs in DMM may be sub- 1-mm thick, as well as thinner lesions that are ulcer- stantially lower than that of other melanomas. ated or are at least Clark level IV.8,9 This procedure Cutis. 2007;79:390-394. provides important prognostic information for patients with melanoma. If lymph node metastases are present (stage III disease), distant metastases will develop in esmoplastic malignant melanoma (DMM), approximately 65% of patients and the 5-year survival first described in 1971,1 is a rare variant of rate decreases to between 24% and 65% (depending on D melanoma that is histologically characterized the extent of regional nodal disease).8 The role of lymph node biopsies (LNBs) for stag- Accepted for publication October 12, 2006. ing DMM is not well-established. The frequency Drs. Cummins, Esche, Barrett, and Mofid are from the and pattern of metastatic spread differs from other Department of Dermatology, Johns Hopkins Hospital, Baltimore, melanomas. In the largest DMM study to date Maryland. Dr. Balch is from the Department of Surgery, (280 patients), only 4% of patients with DMM Johns Hopkins Hospital. had lymph node disease at presentation, whereas The authors report no conflict of interest. Reprints: Deborah L. Cummins, MD, Department of Dermatology, 20% of all patients with cutaneous melanoma had 5 Johns Hopkins Outpatient Center, 601 N Caroline St, 6th Floor, lymph node disease at presentation. Other studies Baltimore, MD 21287 (e-mail: [email protected]). specifically addressing the use of SLNBs for DMM 390 CUTIS® Therapeutics for the Clinician Table 1. Table 2. Demographics Lesion Characteristics Patients Patients Characteristic (N528) Characteristic (N528) Age, y Location, n Range 36–90 Head and neck 16 Median 64 Upper extremity 7 Sex, n Trunk 3 Men 14 Lower extremity 2 Women 14 Pigmentation, n 11* Ethnicity, n Time from onset of symptoms to diagnosis, n Caucasian 27 ,6 mo 4 Latino 1 6211 mo 2 have had variable results.3,4,10-12 Findings from a 122 y 4 systematic review provide rates of regional metas- .2 y 11 tases for DMM between 0% and 18.8%.13 In our Unknown 7 study, 14 of 15 patients who received SLNBs and all 3 patients who received radical neck dissection Tumors extending to deep margin had histologically negative results, suggesting that of biopsy, n 15 LNBs may have limited prognostic value for DMM. Thickness, mm Methods Range 0.54211 For this retrospective study, the Johns Hopkins Median .2.3 Hospital (JHH) dermatopathology database was Tumors with ulceration, n 2 searched for all reports with the term desmoplastic malignant melanoma. All patients with unclear diag- *Number of melanomas noted to be pigmented. noses or alternative diagnoses were immediately excluded. Additionally, only patients who were treated including history of tobacco use (n55) or a first- at JHH were included. Because JHH is a tertiary care degree relative with melanoma (n53), colorectal center, many of the patients were initially diagnosed cancer (n54),or breast cancer (n52). One patient elsewhere. Whenever possible, the original biopsy had a previous history of melanoma, 7 patients had was reviewed at JHH, or diagnosis was confirmed had at least one basal cell carcinoma, and 7 patients based on tissue from surgical excision. The histologic had had other cancers. The median time from onset diagnosis of DMM was based on the presence of atypi- of symptoms to correct diagnosis was 2.5 years. cal spindle cells, desmoplasia, and S100 positivity, as Seven patients presented to JHH with local recur- well as other characteristic features. rences (at least 2 of which had been previously misdi- The JHH electronic record was searched for agnosed). Biopsy results showed that 15 of 28 tumors relevant data including demographics, clinical char- extended to the deep margin. The median depth acteristics, melanoma risk factors, follow-up period, was greater than or equal to 2.3 mm (range, 0.54 to and outcomes. .11 mm). Nearly all were Clark level IV or V. Mela- noma lesion characteristics are detailed in Table 2. Results The demographics (race, age, melanoma site) of The patient population consisted of 14 men and patients in this study were similar to those of previ- 14 women, with a median age of 64 years (range, ous studies, though we report a slightly lower male- 36–90 years)(Table 1). Most lesions were located on female ratio.3,5 As found in most previous studies, sun-exposed skin, with 57% (16/28) on the head and we observed common local recurrence and direct neck. Several patients had risk factors for melanoma, extension but rare distant metastasis.3,6 VOLUME 79, MAY 2007 391 Therapeutics for the Clinician and the other case had extensive soft tissue disease Table 3. with possible involvement of underlying bone. The 23 remaining patients did not have evidence of extra- Sentinel Lymph Node cutaneous disease at last follow-up visit (Table 4). Biopsy (SLNB) Data Comment SLNBs attempted, n 17 (2 aborted) SLNB is becoming an increasingly accepted proce- Successful SLNBs, n 15 dure for staging of melanoma and high-risk nonmela- noma cutaneous malignancies.14-16 However, because Radical neck dissections, n 3 the natural history of DMM markedly differs from Patients with ≥1 1 other melanomas, the use of SLNB for this variant histologically positive remains unclear. A study of 280 patients with DMM lymph node, n showed that, as compared with other melanomas, DMM has a lower rate of regional lymph node metastasis overall, despite much greater depth at ini- Of the 28 patients included in this study, tial presentation. In addition, patients with DMM 15 patients had an SLNB performed and 3 patients have a lower rate of lymph node involvement at had radical neck dissections. Twelve of the patients first recurrence.5 Likewise, in a study of 45 patients receiving successful lymph node procedures had with DMM, none of the patients developed lymph positive deep margins of biopsies with depth of inva- node metastases.7 The pattern of spread and recur- sion ranging from 0.54 to more than 11 mm. rence has been likened to that of a sarcoma, based In 17 of 18 patients, lymph nodes analyzed via on the tumor’s local aggressiveness but low affinity histology and S100 staining results were negative. for lymphatic spread.4 One patient had a positive sentinel lymph node Six studies have reported the outcomes of LNBs by these measures, and notably this patient had a with some conflicting results. The first 4 studies primary melanoma that was greater than 9.8-mm (published in 2001 and 2003) include a total of deep. One patient had had an SLNB performed 90 patients receiving SLNB or elective LNB.3,4,10,12 at an outside institution that resulted in negative Of those patients, only 2 patients had lymph node histology and S100 staining results but polymerase involvement detectable on histologic examination. chain reaction positivity. The SLNB data are shown Livestro et al17 reported 2 patients with positive in Table 3. lymph nodes among 25 patients with SLNB. In con- Patient follow-up ranged from a single visit to a trast, Su et al11 reported that 4 of 33 patients without 5-year follow-up visit (median, 21 months) and is clinical evidence of metastasis had positive SLNBs.
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