499 Sentinel Lymph Node Biopsy for Patients with Problematic Spitzoid Melanocytic Lesions A Report on 18 Patients 1 Lyndon D. Su, M.D. BACKGROUND. Spindle and/or epithelioid melanocytic proliferations that display 1 Douglas R. Fullen, M.D. overlapping histopathologic features of Spitz nevus and Spitz-like melanoma are 2 Vernon K. Sondak, M.D. diagnostically difficult and controversial melanocytic tumors. There are reports of 3 Timothy M. Johnson, M.D. such lesions metastasizing to regional lymph nodes, with a few widely disseminat- 1 Lori Lowe, M.D. ing, resulting in death. METHODS. The authors reviewed clinical and histopathologic data on all patients 1 Department of Pathology and Dermatology, Uni- with atypical or borderline spitzoid melanocytic proliferations who underwent versity of Michigan Medical Center, Ann Arbor, sentinel lymph node biopsy (SLNB). They examined how frequently histologically Michigan. problematic or borderline spitzoid melanocytic lesions metastasized to sentinel 2 Department of Surgery, University of Michigan lymph nodes (SLNs) and which clinical or histologic features, if any, predisposed Medical Center, Ann Arbor, Michigan. patients to a higher risk lesion. 3 Department of Dermatology, Otorhinolaryngol- RESULTS. Six male patients and 12 female patients, ages 5–32 years (mean, 16 ogy, and Surgery, University of Michigan Medical years), had tumors ranging in size from 1.2 mm to 7.9 mm (mean, 3.5 mm) in Center, Ann Arbor, Michigan. thickness. Atypical histologic features that were present most frequently included incomplete maturation (18 of 18 patients), deep dermal mitoses (16 of 18 patients), nuclear pleomorphism (10 of 18 patients), and focal sheet-like growth (10 of 18 patients). Eight of 18 patients (44%) had SLN metastasis and were offered adjuvant treatment. One of eight patients with SLN positive results who underwent regional lymphadenectomy had one additional involved lymph node. All 18 patients were alive and well with no evidence of recurrent or metastatic disease after a follow-up of 3–42 months (mean, 12 months). CONCLUSIONS. Histologically atypical or borderline spitzoid, melanocytic tumors are diagnostically challenging and controversial melanocytic lesions, some of which represent unrecognized melanomas. SLNB aids in confirming a diagnosis of melanoma and identifies patients who may benefit from early therapeutic lymph node dissection and/or adjuvant therapy. Cancer 2003;97:499–507. © 2003 American Cancer Society. DOI 10.1002/cncr.11074 KEYWORDS: Spitz nevus, atypical Spitz tumor, spitzoid melanoma, sentinel lymph node. n a landmark study on melanomas in childhood,1 Sophie Spitz Address for reprints: Lyndon D. Su, M.D., Depart- Iobserved that only 1 of 13 patients with juvenile melanoma had a ment of Pathology, Division of Dermatopathology, malignant and fatal course. In her analysis, she concluded that the University of Michigan Medical Center, Medical presence of giant cells in nearly half of the benign tumors, now Sciences I, M5224, 1301 Catherine Street, Ann eponymously called Spitz nevus, was a histologic finding that helped Arbor, MI 48109-0602; Fax: (734) 936-2756. to distinguish them from melanoma. Since then, many have studied E-mail: [email protected] the histology of spindle and epithelioid melanocytic proliferations to Received June 19, 2002; revision received August uncover features that may help to differentiate benign Spitz nevus 26, 2002; accepted September 5, 2002. from melanoma with Spitz-like features. Although significant © 2003 American Cancer Society 500 CANCER January 15, 2003 / Volume 97 / Number 2 progress has been made in defining histologic criteria anoma and pathology data bases at the University of for Spitz nevus and Spitz-like melanoma, the diagno- Michigan Medical Center for patients with atypical sis of atypical spindle and epithelioid melanocytic spitzoid melanocytic proliferations that fell within any proliferations remains a contentious area in dermato- of several designations (including atypical Spitz tu- pathology with repercussions that extend to patient mor, markedly atypical Spitz nevus, atypical epithe- management.2 lioid melanocytic proliferation of uncertain biologic Although most spindle and epithelioid melano- potential, or borderline epithelioid melanocytic neo- cytic proliferations readily are classifiable histologi- plasm) who underwent IOLM and SLNB. Also in- cally as Spitz nevus or melanoma with Spitz-like fea- cluded were patients who were diagnosed with mela- tures,1,3–5 there is a subset of problematic and noma with spitzoid features for whom there was a diagnostically challenging melanocytic lesions vari- discordance in diagnosis among expert dermato- ably designated as atypical Spitz tumor, atypical Spitz pathologists and patients in whom the diagnosis of nevus, Spitz-like lesion in the borderline category of melanoma could not be excluded. Clinical data and indeterminate malignant potential, and diagnostically histopathologic material from primary lesions, SLNs, controversial spitzoid melanocytic tumors, that defy and regional lymphadenectomy specimens (when ap- classification into either category even by the most plicable) were retrospectively reviewed. experienced dermatopathologists.2,6–10 These lesions The clinical data extracted included patient age, simultaneously exhibit some histomorphologic fea- gender, location of the primary lesion, number of tures of classic Spitz nevus and Spitz-like melanoma, SLNs obtained, and site of lymphadenectomy, if ap- making diagnostic assignment to either Spitz nevus or plicable. Histologic parameters of the primary lesion Spitz-like melanoma difficult, controversial, and that were assessed included the presence or absence sometimes erroneous. of Kamino bodies; tumor thickness measured in mil- The biologic behavior of these problematic atyp- limeters (Breslow depth); Clark level; presence or ab- ical spitzoid melanocytic lesions has not been eluci- sence of ulceration; mitotic rate (including deep dated clearly. Experts often regard these lesions as and/or atypical mitoses); and atypical or disturbing having an indeterminate malignant potential, yet growth pattern, such as incomplete maturation/zona- there is excellent documentation of histologically tion or focal, confluent, or sheet-like growth. At least atypical or controversial, spitzoid, melanocytic lesions one and frequently all three board-certified demato- metastasizing to regional lymph nodes,8,11–13 some pathologists (L.D.S., D.R.F., and L.L.) evaluated the with wide dissemination and fatal outcome.2,7,14,15 It is histopathologic material. Because of the borderline reasonable to conclude, in retrospect, that these le- nature of many of the primary lesions, a consensus in sions are classified better as melanomas. diagnosis frequently could not be achieved. The dif- For these reasons, at our institution, we proceed fering opinions were recorded. cautiously and conservatively when faced with mela- The procedure for IOLM and SLNB used in our nocytic lesions classified as atypical Spitz tumor, bor- institution is similar to that previously described.17–19 derline epithelioid melanocytic proliferation, or atyp- A combination of immediate preoperative lympho- ical epithelioid melanocytic proliferation of unknown scintigraphy with unfiltered 99mTC-sulfur colloid and biologic potential for which a consensus in diagnosis intraoperative lymphatic mapping using both a ␥ de- among experts cannot be reached. We recommend tector and vital blue dye (Lymphazurin 1%; Hirsch intraoperative lymphatic mapping (IOLM) and senti- Industries, Richmond, VA) was used to identify the nel lymph node biopsy (SLNB) to patients with tumors SLN in all patients. The protocol for evaluating SLNs at that exceed 1 mm in Breslow depth or Ͻ 1mmin our institution was as follows: SLNs were sectioned Breslow depth with adverse histologic features, such serially at a thickness of 2–3 mm, fixed in formalin, as ulceration. Defining the sentinel lymph node (SLN) and embedded in paraffin. Two serial, 5-␮m sections status provides valuable information that better de- from each SLN tissue block were stained with hema- fines the biologic potential of these diagnostically toxylin and eosin (H&E) for routine histologic exami- challenging lesions.8,16 This report on our institutional nation. For blocks in which obvious metastatic tumor experience with SLNB for patients with problematic was not identified in routine sections, immunohisto- atypical spitzoid melanocytic lesions is the largest se- chemical stains were performed on every SLN tissue ries to date. block. One serial section from each SLN block was immunostained for S100 protein (1:1000 dilution; MATERIALS AND METHODS Dako, Carpinteria, CA), Melan-A (1:12:5 dilution; After obtaining approval from the University of Mich- Dako), and HMB-45 (1:100 dilution; Dako). In blocks igan Institutional Review Board, we queried the mel- in which only small foci suspicious for tumor were SLN Biopsy for Problematic Spitzoid Lesions/Su et al. 501 TABLE 1 Clinical and Pathologic Data for Patients with Problematic Spitzoid Melanocytic Lesions Atypical histologic features noted in tumora Sentinel lymph nodes Breslow Site of depth Kamino Capsular Other positive Follow-up Age primary Histologic (cm)/Clark bodies No. nevi lymph nodes in and duration Patient (yrs) Gender tumor diagnosesb level NP DMc NM FCG present Site positive present lymphadenectomy (months) 1 10 F R eyebrow AS 3.3/V — 3 X X No R preauric 1 of 3 No 0 of 47 AW (5) 2 17 F Sacrum SN(2),AS,SM