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Figure 1.
The tumorigenic phase is established by the presence of dermal aggregates of melanoma cells larger than the junctional malignant nests (hematoxylin-eosin, original magnification ×200).

The tumorigenic phase is established by the presence of dermal aggregates of melanoma cells larger than the junctional malignant nests (hematoxylin-eosin, original magnification ×200).

Figure 2.
Lentiginous single-cell proliferation of atypical melanocytes overlying an area of fibroplasias and regression (hematoxylin-eosin, original magnification ×200).

Lentiginous single-cell proliferation of atypical melanocytes overlying an area of fibroplasias and regression (hematoxylin-eosin, original magnification ×200).

Figure 3.
Low-power view of a metastasizing thin melanoma showing extensive areas of regression and melanoderma (hematoxylin-eosin, original magnification ×50).

Low-power view of a metastasizing thin melanoma showing extensive areas of regression and melanoderma (hematoxylin-eosin, original magnification ×50).

Figure 4.
Aggregates of melanin-laden macrophages (nodular melanosis) are noted within an area of regression (hematoxylin-eosin, original magnification ×100).

Aggregates of melanin-laden macrophages (nodular melanosis) are noted within an area of regression (hematoxylin-eosin, original magnification ×100).

Figure 5.
Expansion of the papillary dermis in an area of extensive regression and fibrosis with scattered lymphocytes and melanophages (hematoxylin-eosin, original magnification ×50).

Expansion of the papillary dermis in an area of extensive regression and fibrosis with scattered lymphocytes and melanophages (hematoxylin-eosin, original magnification ×50).

Patient Study Group
Patient Study Group
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Barnhill  RLFine  JARoush  GCBerwick  M Predicting 5-year outcome for patients with cutaneous melanoma in a population-based study. Cancer. 1996;78427- 432Article
2.
Balch  CMSoong  SJMilton  GW  et al.  A comparison of prognostic factors and surgical results in 1,786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia. Ann Surg. 1982;196677- 684Article
3.
Blessing  KMcLaren  KMMcLean  ADavidson  P Thin malignant melanomas (<1.5 mm) with metastasis: a histological study and survival analysis. Histopathology. 1990;17389- 395Article
4.
Hughes  LEPritchard  GA Patients presenting with thin melanomas (<0.76 mm thick) who subsequently have a poor prognosis by development of metastases. Ann Surg. 1989;210249- 250Article
5.
Lock-Andersen  JHastrup  NCDrzewiecki  KT The metastasizing thin cutaneous melanoma: case report. Scand J Plast Reconstr Surg Hand Surg. 1989;23153- 155Article
6.
Shaw  HMMcCarthy  SWMcCarthy  WHThompson  JFMilton  GW Thin regressing malignant melanoma: significance of concurrent regional lymph node metastases. Histopathology. 1989;15257- 265Article
7.
Slingluff  CL  JrVollmer  RTReintgen  DSSeigler  HF Lethal "thin" malignant melanoma: identifying patients at risk. Ann Surg. 1988;208150- 161Article
8.
Linderman  RBMelton  ME Metastasis of a thin regressing malignant melanoma. Ann Plast Surg. 1985;15247- 251Article
9.
Woods  JESoule  EHCreagan  ET Metastasis and death in patients with thin melanomas (<0.76 mm). Ann Surg. 1983;19863- 64Article
10.
Paladugu  RRYonemoto  RH Biologic behavior of thin malignant melanomas with regressive changes. Arch Surg. 1983;11841- 44Article
11.
Trau  HRigel  DSHarris  MN  et al.  Metastases of thin melanomas. Cancer. 1983;51553- 556Article
12.
Gromet  MAEpstein  WLBlois  MS The regressing thin malignant melanoma: a distinctive lesion with metastatic potential. Cancer. 1978;422282- 2292Article
13.
Barnhill  RLMihm  MC Histopathology and precursor lesions. Balch  CMHoughton  ANSober  AJSoong  Seds.Cutaneous Melanoma St Louis, Mo QMP Publishing1998;103- 135
14.
CRC Melanoma Pathology Panel, A nationwide survey of observer variation in the diagnosis of thin cutaneous malignant melanoma including the MIN terminology. J Clin Pathol. 1997;50202- 205Article
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Shafir  RHiss  JTsur  HBubis  JJ The thin malignant melanoma: changing patterns of epidemiology and treatment. Cancer. 1982;50817- 819Article
16.
Mansson-Brahme  ECarstensen  JErhardt  KLagerlof  BRingborg  URutqvist  LE Prognostic factors in thin cutaneous malignant melanoma. Cancer. 1994;732324- 2332Article
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Binder  MDolezal  IWolff  KPehamberger  H Stereologic estimation of volume-weighted mean nuclear volume as a predictor of prognosis in "thin" malignant melanoma. J Invest Dermatol. 1992;99180- 183Article
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Naruns  PLNizze  JACochran  AJLee  MBMorton  DL Recurrence potential of thin primary melanomas. Cancer. 1986;57545- 548Article
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Day  CL  JrMihm  MC  JrSober  AJ  et al.  Prognostic factors for melanoma patients with lesions 0.76-1.69 mm in thickness: an appraisal of "thin" level IV lesions. Ann Surg. 1982;19530- 34Article
20.
Garbe  CStadler  ROrfanos  CE Local recurrence and metastasis of thin malignant melanomas (≤1mm) [in German]. Hautarzt. 1989;40337- 343
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Park  KGBlessing  KMcLaren  KMWatson  AC A study of thin (< 1.5 mm) malignant melanomas with poor prognosis. Br J Plast Surg. 1993;46607- 610Article
22.
Glass  LFGuffey  JMSchroer  KRReintgen  D Histopathologic study of recurrent Clark level II melanomas. Semin Surg Oncol. 1993;9202- 207
23.
Blessing  KMcLaren  KM Histological regression in primary cutaneous melanoma: recognition, prevalence and significance. Histopathology. 1992;20315- 322Article
24.
Czarnetzki  BMDenter  MBrocker  EB  et al.  Clinical features of superficial spreading melanomas with zones of regression. J Cancer Res Clin Oncol. 1984;107225- 228Article
25.
Brogelli  LReali  UMMoretti  SUrso  C The prognostic significance of histologic regression in cutaneous melanoma. Melanoma Res. 1992;287- 91Article
26.
Slingluff  CL  JrSeigler  HF "Thin" malignant melanoma: risk factors and clinical management. Ann Plast Surg. 1992;2889- 94Article
27.
Shaw  HMRivers  JKMcCarthy  SWMcCarthy  WH Cutaneous melanomas exhibiting unusual biologic behavior. World J Surg. 1992;16196- 202Article
28.
Ronan  SGEng  AMBriele  HAShioura  NNDas Gupta  TK Thin malignant melanomas with regression and metastases. Arch Dermatol. 1987;1231326- 1330Article
29.
McGovern  VJShaw  HMMilton  GW Prognosis in patients with thin malignant melanoma: influence of regression. Histopathology. 1983;7673- 680Article
30.
Sondergaard  KHou-Jensen  K Partial regression in thin primary cutaneous malignant melanomas clinical stage I: a study of 486 cases. Virchows Arch A Pathol Anat Histopathol. 1985;408241- 247Article
31.
Kelly  JWSagebiel  RWBlois  MS Regression in malignant melanoma: a histologic feature without independent prognostic significance. Cancer. 1985;562287- 2291Article
32.
Cooper  PHWanebo  HJHagar  RW Regression in thin malignant melanoma: microscopic diagnosis and prognostic importance. Arch Dermatol. 1985;1211127- 1131Article
33.
Briggs  JCIbrahim  NBHastings  AGGriffiths  RW Experience of thin cutaneous melanomas (less than 0.76 mm and less than 0.85 mm thick) in a large plastic surgery unit: a 5 to 17 year follow-up. Br J Plast Surg. 1984;37501- 506Article
34.
Fearfield  LARowe  AFrancis  NFisher  CGore  MEBunker  CB Clinico-pathological features of relapsing very thin melanoma. Clin Exp Dermatol. 2001;26686- 695Article
35.
McDermott  NCHayes  DPal-Sader  MH  et al.  Identification of vertical growth phase in malignant melanoma: a study of interobserver agreement. Am J Clin Pathol. 1998;110753- 757
36.
Cook  MGClark  TJHumphreys  S  et al.  The evaluation of diagnostic and prognostic criteria and the terminology of thin cutaneous malignant melanoma by the CRC Melanoma Pathology Panel. Histopathology. 1996;28497- 512Article
37.
Wanebo  HJCooper  PHHagar  RW Thin (≤1 mm) melanomas of the extremities are biologically favorable lesions not influenced by regression. Ann Surg. 1985;201499- 504Article
38.
Kuehnl-Petzoldt  CKeil  HSchoepf  E Prognostic significance of the patient's sex, tumor site, and mitotic rate in thin (≤1.5 mm) melanoma. Arch Dermatol Res. 1984;276151- 155Article
39.
Andersson  APDahlstrom  KKDrzewiecki  KT Prognosis of thin cutaneous head and neck melanoma (<1mm). Eur J Surg Oncol. 1996;2255- 57Article
40.
Vilmer  CBailly  CLe Doussal  V  et al. for the Melanoma Group of French Federation of Cancer Centers, Thin melanomas with unusual aggressive behavior: a report on nine cases. J Am Acad Dermatol. 1996;34439- 444Article
41.
Fisher  SRLangford  JMolter  DWSeigler  HF Thin malignant melanomas of the head and neck. Laryngoscope. 1992;102850- 854Article
42.
Pontikes  LATemple  WJCassar  SL  et al.  Influence of level and thickness on recurrence rate in thin melanomas. Am J Surg. 1993;165225- 228Article
43.
Sparrow  LEEnglish  DRTaran  JMHeenan  PJ Prognostic significance of MIB-1 proliferative activity in thin melanomas and immunohistochemical analysis of MIB-1 proliferative activity in melanocytic tumors. Am J Dermatopathol. 1998;2012- 16Article
44.
Sparrow  LEEnglish  DRHeenan  PJDawkins  HJTaran  J Prognostic significance of p53 overexpression in thin melanomas. Melanoma Res. 1995;5387- 392Article
45.
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46.
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47.
Barnhill  RLLevy  MA Regressing thin cutaneous malignant melanomas (≤1.0 mm) are associated with angiogenesis. Am J Pathol. 1993;14399- 104
Study
May 2002

Histological Characteristics of Metastasizing Thin MelanomasA Case-Control Study of 43 Cases

Author Affiliations

From the Department of Dermatology, Northwestern University Medical School, Chicago, Ill (Dr Guitart); Department of Pathology, University of Michigan, Ann Arbor (Dr Lowe); Department of Dermatology, University of Washington, Seattle (Dr Piepkorn); Department of Pathology, M. D. Anderson Cancer Center, Houston, Tex (Dr Prieto); Rabkin Dermatopathology Laboratory, Pittsburgh, Pa (Dr Rabkin); Department of Pathology, University of Illinois, Chicago (Dr Ronan); Department of Dermatology, Duke University, Durham, NC (Dr Shea); Department of Pathology, University of Alberta, Edmonton (Dr Tron); Department of Pathology, Bowman-Gray School of Medicine, Winston-Salem, NC (Dr White); and Department of Dermatology, Georgetown University Medical Center, Washington, DC (Dr Barnhill). Dr Shea is now affiliated with the Department of Medicine, The University of Chicago. Dr Ronan is deceased.

Arch Dermatol. 2002;138(5):603-608. doi:10.1001/archderm.138.5.603
Abstract

Objective  To study clinical and histological features associated with metastasizing thin melanomas (MTMs).

Design  Case-control study of clinicopathological features of patients with MTMs by a panel of 10 dermatopathologists.

Setting  Members of the North American Melanoma Pathology Study Group selected the cases from the melanoma databases at 8 academic institutions.

Patients  Forty-three patients with MTMs (<1 mm thick) and 42 control subjects without metastasis matched for age, sex, tumor site, and Breslow thickness.

Intervention  None.

Main Outcome Measures  Clinical (age, sex, site of lesion, stage at diagnosis, metastasis site, disease-free survival, and outcome) and histological (Breslow thickness, Clark level, growth phase, regression, and inflammatory response) features of patients with MTMs vs controls.

Results  There was an overrepresentation of axial tumors among patients with MTMs. Extensive regression was present in 18 patients (42%) with MTM vs 2 matched control subjects (5%) (95% confidence interval, 21%-53%; P = .001). Other histological variables were not significantly different. Two patients had melanomas in situ with subsequent metastasis.

Conclusions  Thin melanomas with extensive regression represent a group at higher risk for the development of metastasis. Furthermore, the risk of metastasis cannot be dismissed in cases of melanoma in situ.

MICROSCOPIC assessment of Breslow thickness is the most accurate prognostic indicator in malignant melanoma.1 There is ample evidence that tumor thickness is directly proportional to the development of metastasis and to the overall patient survival.2 In general, melanomas with a Breslow thickness of less than 1 mm have a good prognosis, with a low incidence of metastasis. However, thin melanomas may develop metastasis.312 We have reviewed our experience with metastasizing melanomas with a Breslow thickness of less than 1 mm. Our goal was to identify those clinical and histological factors that may predict a subset of thin melanomas more likely to metastasize.

MATERIALS AND METHODS

Electronic records were searched from the melanoma databases and pathology departments at University of Michigan, Ann Arbor; University of Illinois, Chicago; Duke University, Durham, NC; Vancouver University, Vancouver, British Columbia; the Connecticut Tumor Registry, Hartford; The Johns Hopkins University, Baltimore, Md; Wake Forest University, Winston-Salem, NC; and Northwestern University, Chicago. Histopathological material from patients with primary melanoma with a Breslow thickness of less than 1 mm and a known history of metastasis were selected. All metastases were confirmed by histological examination. All biopsy specimens from patients were reviewed, and it was found that they had negative surgical margins, or if the margins were involved, a complete reexcision specimen had been performed. Each case was evaluated by the contributing pathologists before submission to the study. The slides selected for panel evaluation were the most representative sections of the lesion. The slides were reviewed independently by a panel of 10 dermatopathologists with experience in pigmented lesions. The control group included 42 patients with thin melanomas with no evidence of metastasis after a minimum follow-up of 6 years. The control patients were matched for age (within a 10-year range), sex, site (extremities, truncal, or head and neck), and Breslow thickness. The diagnosis was confirmed in all lesions. The following factors were assessed: thickness, Clark level, and growth phase (tumorigenic vs nontumorigenic). Tumorigenic growth phase was defined by the presence of dermal mitosis or dermal aggregates of tumor cells larger than the nests in the epidermal component (Figure 1).13 Presence, extent (<50% or ≥50%), and evolutionary stage of regression were also assessed. The percentage of regression was not related to the overall surface area of the lesion, but was based on the percentage of linear regression on the most representative slide of the lesion. Regression was defined as dermal fibroplasia with an absence of epidermal and dermal involvement by melanoma cells, but allowing for lentiginous single-cell proliferation of atypical melanocytes along the dermal epidermal junction (Figure 2). Host response was defined as the presence of tumor-infiltrating lymphocytes intermingled among tumor cells or a lymphoid infiltrate at the base of the lesion. Other notable histological findings (coexisting lesion and angiolymphatic spread) were recorded. If agreement by all panelists was not achieved, a simple majority was considered sufficient for tabulation purposes. Follow-up information, including patients' current status, stage at the time of diagnosis, disease-free survival, and sites of metastasis, was obtained from tumor registries and from patients' medical records. t Tests and χ2 assays were used for statistical analysis. P<.05 was considered significant.

RESULTS
CLINICAL

The study group consisted of 43 patients (23 men and 20 women), with a mean age of 50.0 years (range, 27-79 years) (Table 1). The back and shoulder were the most common locations for lesions, affected in 21 (49%) patients. The second most common location was the lower extremity (10 patients), followed by the upper extremity and chest, occurring in 4 patients in each location. Two had lesions on the ears and 1 patient each had lesions on the scalp and abdomen. Staging performed at the time of diagnosis revealed 27 (63%) patients without clinical evidence of metastasis (stage I). Lymph node metastases (stage III) were detected in 12 (28%) patients. Four patients (9%) had distant metastasis (stage IV) at the time of presentation. Eventually, metastases were detected in every patient. The most common site for metastasis was the regional lymph nodes, affected in 23 patients. Nine patients had metastasis to more than 1 lymphatic region or had lymphatic metastasis associated with systemic metastases. Six patients had metastasis involving soft tissue or skin. Lung or pleura was the site of metastasis in 4 patients and liver in 3. Two patients had metastasis reported in the stomach and bone. In addition, other sites of metastasis included the brain (2 patients) and parotid gland (1 patient). One case with in-transit metastasis also occurred. The mean follow-up was 52 months. The time to detection of metastasis was not available in most cases. Five patients reported as having developed metastasis had unspecified sites. When the study was closed, 26 patients had died with melanoma, and 12 patients were alive with disease. Five patients were alive without clinical evidence of melanoma.

The matched control cases included 42 patients (23 men and 19 women), with a mean age at presentation of 48.5 years (range, 23-72 years) and a mean follow-up of 13 years (range, 6-27 years) without evidence of metastasis. The lesions were located on the torso in 25 patients, extremities in 14, and head or neck in 3.

HISTOPATHOLOGICAL

The panel agreed on the diagnosis of melanoma in all the cases. The mean ± SD thickness for the metastasizing lesions was 0.59 ± 0.20 mm (range, 0 [melanoma in situ] to 0.95 mm). There was some discordance in the assessment of Clark level. Consensus, defined as agreement with no more than 1 dissension within the panel, was reached in 15 (35%) of the 43 patients . In 3 of the cases, the panelists' assessments were evenly divided and a simple majority could not be reached. Patients with metastasizing thin melanoma (MTM) were classified as follows: level I, 2 patients; I or II, 1 patient; II, 10 patients; III, 22 patients; III or IV, 2 patients; and IV, 6 patients. The distribution was not significantly different from that of the control cases (P = .81). Consensus for the assessment of growth phase was reached in 39 patients (91%). Ten cases (23%) were determined to be in the nontumorigenic (radial growth) phase and 33 (77%) in the tumorigenic (vertical growth) phase. Consensus regarding growth phase could not be reached in 5 patients (12%). Dermal mitotic figures were noted in 8 cases, while large dermal aggregates of tumor cells were seen in all the tumorigenic cases. Regression was identified in 21 patients (49%) vs 8 control cases (19%) (P = .001) (Figure 3, Figure 4, and Figure 5). Extensive regression involving 50% or more of the lesion surface was noted in 18 patients (42%) and less than 50% involvement in 3 (7%). Regression was not identified in 22 patients. In the control group, 2 patients (5%) had extensive regression. The occurrence of extensive regression was significantly different between patients and controls (95% confidence interval, 21%-53%; P = .001). A mononuclear cell inflammatory infiltrate was prominent in 36 cases. The infiltrate was predominantly at the base of the melanocytic lesion in 9 cases and was mostly intermingled with the melanocytes (tumor-infiltrating lymphocytes) in 13. A combined infiltrate at the base with tumor-infiltrating lymphocytes was noted in 14 cases. Five cases had no significant inflammatory infiltrate. A coexisting melanocytic nevus was identified in 7 cases, including 2 congenital nevi and 2 dysplastic nevi. In 4 cases, dermal nevomelanocytic nests were noted, but extensive regression prevented further assessment of the nevi.

The mean thickness for the control specimens was 0.56 mm (range, 0-0.94 mm) (P = .70). Clark level distribution was II in 16 cases; III, 20; III or IV, 3; and IV, 3. Thirty cases (71%) were determined to be in the tumorigenic phase and 12 (29%) in the nontumorigenic phase (P = .62). Regression was absent in 34 control cases (81%) and was present in 8 (19%), with 6 showing limited regression (<50%) and 2 showing extensive regression (≥50%). A host response was absent in 5 cases, a lymphoid infiltrate at the base was noted in 26, and tumor-infiltrating lymphocytes were seen in 25. The inflammatory host response of the metastasizing cases vs the control group was not significantly different (P = .52). Seven control cases had a coexisting lesion, including 6 dysplastic nevi and 1 congenital nevus. None of the MTM or control cases were ulcerated.

COMMENT

In recent decades, a steady increase in the incidence of thin melanomas has been reported.14,15 This disturbing trend may, however, reflect the detection and removal of melanomas at early stages, when there is less risk for metastasis. Regrettably, thin melanomas have metastatic potential, with an estimated risk of 3% to 8%, depending on the length of follow-up.7,9,1618 Despite numerous studies on the subject, the clinical and pathological risk factors for these MTMs are largely unclear. This problem is partly because of variations in the defining criteria for thin melanomas used in prior studies,7,19 with Breslow thickness varying from 0.76 mm to 1.69 mm. Furthermore, some investigations combined recurring lesions with MTMs, further confounding the results.20 The histological criteria associated with high metastatic risk in thin melanomas have not been clearly elucidated. There is some evidence that the metastatic potential of thin melanomas, compared with that of thick melanomas, is significantly more affected by factors other than thickness. The size of the lesion as measured by surface area, the presence of regressive changes, and location may be important variables in the prognosis of thin melanomas.3,2124 Thin melanomas show regression more frequently than do thick melanomas.3,25 The presence of regression has been reported in 7% to 61% of all thin melanomas and in 40% to 100% of MTMs.3,18,2628 The variability in the reported incidence of regression in thin melanomas is probably again because of the lack of uniformity in defining criteria and the minimal area of involvement required for inclusion. In our study, tumor regression was the most conspicuous histological finding, encountered in 21 MTM cases (49%) vs 8 (19%) of the control cases. Furthermore, extensive regression involving 50% or more of the lesion was seen mostly in the metastasizing group (P = .001). Slingluff and colleagues7,26 found a similar rate (40%) of severe regression in MTMs, compared with 17% of nonmetastasizing thin melanomas. Other studies10,29 have identified a higher rate of metastasis in thin melanomas with regression (8%) compared with cases without regression (5%). Moreover, the 10-year survival for patients with thin melanomas with regression was 79% vs more than 95% in patients without regression.17,30 All patients from the Sydney Melanoma Unit cohort27 and University of Illinois database28 with thin melanomas and lymph node metastasis at presentation had extensive regression involving more than 75% of the tumor area. The poorer prognosis of MTM with extensive regression has been corroborated by other reports.21,23 However, less extensive regression was also noted in 61% of thin melanomas that never metastasized or recurred.27 Other investigators could not demonstrate an effect of regression on disease-free interval or survival.11,25,3134

Severe regression has been reported more frequently in back lesions and in men.3,7,31 Our findings concur with the overrepresentation of lesions from the back. However, we could not confirm the male predominance among patients with MTM.

Sondergaard and Hou-Jensen30 found that metastasis was correlated not only with the extent of regression but also with the thickness of it. Patients with regression but without thick scar formation had a better prognosis. The implication is that the regressed tumor was preceded by an originally thicker tumor.

We identified 2 cases of apparent melanoma in situ that subsequently developed metastasis. One of the cases had extensive regression involving more than 50% of the surface area. This observation suggests a preceding invasive tumor with metastatic potential, before regression of the dermal component. However, regression was not identified in the other melanoma in situ with metastasis. This perplexing case is difficult to reconcile with the notion that theoretical nontumorigenic lesions have metastatic potential. Although a thorough examination did not reveal a second primary lesion, a primary occult visceral melanoma cannot be excluded. Nonetheless, our results show that it cannot be assumed that an apparent level I melanoma will not metastasize. Furthermore, 10 of the MTM cases studied were histologically classified by the panel as nontumorigenic. Although consensus in the panel regarding growth phase was reached in 91% of the cases, there were cases in which growth phase status was difficult to determine. The overall high reproducibility of growth phase assessment has been corroborated by other recent studies.35,36 However, the clinical relevance of such determination is less clear, as shown by the 10 "nontumorigenic," yet metastasizing, cases in our series. Perhaps, we should resist from providing such categorical predictions that, in some instances, may not be more than an educated guess, yet with profound prognostic implications to the patient.

Contrary to prior reports, we did not find a high incidence of MTM lesions from the head and neck area, but did find a high number of axial tumors, primarily from the back. A higher incidence of axial lesions among MTM cases has also been observed by other authors.3,7,19,26 Two other studies37,38 also showed that patients with thin melanomas involving extremities had a lower metastatic rate and better prognosis.

In some studies,3942 thin melanomas from the head and neck have shown a higher rate of recurrence and metastasis. The higher rate of recurrence reported in head and neck melanomas may be associated with narrower surgical margins in anatomical sites cosmetically compromised and with difficult surgical repair. Another possible explanation is that the skin from the head and neck also has a thinner reticular dermis, which is often damaged by actinic changes. Hence, a thin Breslow level could be associated with a deep anatomical level of invasion (Clark level). Because there were only 3 head and neck cases in our cohort, we could not draw any definite conclusions about this subset of patients.

There is no reliable marker for the metastatic potential of thin melanomas. Studies of proliferation markers (MIB-1)43 and p53 expression44 of thin melanomas found no association between the proportion of positive cells and risk of metastasis. Bjornhagen et al45 showed statistically significant differences between MTM and nonmetastasizing thin melanoma in regard to the nuclear correlation coefficient, indicating that thin melanomas with pleomorphic and, possibly, densely packed nuclei were more likely to recur. A significant difference of mean nuclear volume between MTMs and nonmetastasizing thin melanomas has also been reported.17 Angiogenesis of thin melanomas has been investigated, with conflicting results. Although Guffey et al46 found no predictive value in measuring vascularity in thin melanomas, Barnhill and Levy47 suggested that the onset of angiogenesis is related to inflammatory regression and progression to the vertical growth phase.

Our study confirms that thin melanomas with extensive spontaneous regression represent a group at higher risk for the development of metastasis. Such patients should be carefully followed up, especially when the primary lesion involves the torso. However, in about half of our patients, we were unable to identify regression or any other histological or clinical distinguishing features. This should encourage further research to identify reliable molecular or serological prognostic indicators for patients with thin melanomas.

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Article Information

Accepted for publication June 20, 2001.

We appreciate the comments and contributions of Lynn From, MD; David Elder, MD; and Alfred W. Rademaker, PhD.

Corresponding author: Joan Guitart, MD, Department of Dermatology, Northwestern University Medical School, 675 N St Clair, Suite 19-150, Chicago, IL 60611 (e-mail: j-guitart@nwu.edu).

References
1.
Barnhill  RLFine  JARoush  GCBerwick  M Predicting 5-year outcome for patients with cutaneous melanoma in a population-based study. Cancer. 1996;78427- 432Article
2.
Balch  CMSoong  SJMilton  GW  et al.  A comparison of prognostic factors and surgical results in 1,786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia. Ann Surg. 1982;196677- 684Article
3.
Blessing  KMcLaren  KMMcLean  ADavidson  P Thin malignant melanomas (<1.5 mm) with metastasis: a histological study and survival analysis. Histopathology. 1990;17389- 395Article
4.
Hughes  LEPritchard  GA Patients presenting with thin melanomas (<0.76 mm thick) who subsequently have a poor prognosis by development of metastases. Ann Surg. 1989;210249- 250Article
5.
Lock-Andersen  JHastrup  NCDrzewiecki  KT The metastasizing thin cutaneous melanoma: case report. Scand J Plast Reconstr Surg Hand Surg. 1989;23153- 155Article
6.
Shaw  HMMcCarthy  SWMcCarthy  WHThompson  JFMilton  GW Thin regressing malignant melanoma: significance of concurrent regional lymph node metastases. Histopathology. 1989;15257- 265Article
7.
Slingluff  CL  JrVollmer  RTReintgen  DSSeigler  HF Lethal "thin" malignant melanoma: identifying patients at risk. Ann Surg. 1988;208150- 161Article
8.
Linderman  RBMelton  ME Metastasis of a thin regressing malignant melanoma. Ann Plast Surg. 1985;15247- 251Article
9.
Woods  JESoule  EHCreagan  ET Metastasis and death in patients with thin melanomas (<0.76 mm). Ann Surg. 1983;19863- 64Article
10.
Paladugu  RRYonemoto  RH Biologic behavior of thin malignant melanomas with regressive changes. Arch Surg. 1983;11841- 44Article
11.
Trau  HRigel  DSHarris  MN  et al.  Metastases of thin melanomas. Cancer. 1983;51553- 556Article
12.
Gromet  MAEpstein  WLBlois  MS The regressing thin malignant melanoma: a distinctive lesion with metastatic potential. Cancer. 1978;422282- 2292Article
13.
Barnhill  RLMihm  MC Histopathology and precursor lesions. Balch  CMHoughton  ANSober  AJSoong  Seds.Cutaneous Melanoma St Louis, Mo QMP Publishing1998;103- 135
14.
CRC Melanoma Pathology Panel, A nationwide survey of observer variation in the diagnosis of thin cutaneous malignant melanoma including the MIN terminology. J Clin Pathol. 1997;50202- 205Article
15.
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