The approach to the patient with a difficult melanocytic lesion.

Although most histological diagnoses are made with relative ease and with great specificity and reproducibility, there is a subset of cases in which a specific and reproducible diagnosis is difficult or even impossible to render. In the melanocytic system, these cases can be divided into two broad categories. The first category, 'superficial atypical melanocytic proliferations of uncertain significance' (SAMPUS), includes predominantly junctional melanocytic proliferations, and melanocytic proliferations that are confined to the epidermis and papillary dermis, without evidence of tumorigenic proliferation or mitotic activity there. The prognosis for cure of these lesions is excellent if they are completely excised. Such lesions may include, for example, dysplastic naevi, Spitz naevi or pigmented spindle cell naevi with a few atypical melanocytes above the dermal-epidermal junction, or with greater than average cytological atypia, or with mitoses, where the differential diagnosis of melanoma in situ is difficult or impossible to rule out. The other category, 'melanocytic tumours of uncertain malignant potential' (MELTUMP), is comprised of melanocytic proliferations that form tumours in the dermis, and are therefore potentially capable of metastasis. Examples of such lesions may include atypical Spitz naevi, deep penetrating naevi, possible naevoid melanomas, or cellular blue naevi, where because of increased mitotic activity or cytologic atypia, a diagnosis of invasive or tumorigenic melanoma cannot be ruled out. In managing such lesions, we follow two main principles. The first is to manage each lesion with therapy designed to be adequate for management of the most significant consideration in the differential diagnosis. The second principle is to make clinicians and patients specifically aware of the diagnostic difficulty in their lesion, so that management can be undertaken on a true informed consent basis.

[1]  S. Steigen,et al.  Gastrointestinal Stromal Tumors with Internal Tandem Duplications in 3′ End of KIT Juxtamembrane Domain Occur Predominantly in Stomach and Generally Seem to Have a Favorable Course , 2003, Modern Pathology.

[2]  F. Pilleul,et al.  Low microvessel density is an unfavorable histoprognostic factor in pancreatic endocrine tumors. , 2003, Gastroenterology.

[3]  A. Sasco,et al.  The epidemiology of neonatal tumours , 2003, Pediatric Surgery International.

[4]  M. Arumí-Uría,et al.  Grading of Atypia in Nevi: Correlation with Melanoma Risk , 2003, Modern Pathology.

[5]  D. Easty,et al.  Tyrosine phosphate in melanoma progression , 2003, The British journal of dermatology.

[6]  B. Bastian Understanding the progression of melanocytic neoplasia using genomic analysis: from fields to cancer , 2003, Oncogene.

[7]  I. Ellis,et al.  Excision biopsy findings of patients with breast needle core biopsies reported as suspicious of malignancy (B4) or lesion of uncertain malignant potential (B3) , 2003, Histopathology.

[8]  V. Sondak,et al.  Sentinel lymph node biopsy for patients with problematic spitzoid melanocytic lesions , 2003, Cancer.

[9]  D. Elder,et al.  Pathology review of cases presenting to a multidisciplinary pigmented lesion clinic. , 2002, Archives of dermatology.

[10]  M. Ladanyi,et al.  Molecular diagnosis of clear cell sarcoma: detection of EWS-ATF1 and MITF-M transcripts and histopathological and ultrastructural analysis of 12 cases. , 2002, The Journal of molecular diagnostics : JMD.

[11]  E. Foucar Diagnostic decision-making in anatomic pathology. , 2001, American journal of clinical pathology.

[12]  H. Kerl,et al.  Tutorial on melanocytic lesions. , 2001, The American Journal of dermatopathology.

[13]  A. Folpe,et al.  Atypical and Malignant Glomus Tumors: Analysis of 52 Cases, With a Proposal for the Reclassification of Glomus Tumors , 2001, The American journal of surgical pathology.

[14]  B. Cheson,et al.  Report of an international working group to standardize response criteria for myelodysplastic syndromes. , 2000, Blood.

[15]  M. MedinaPérez,et al.  Atypical stromal hyperplasia of the prostate (stromal proliferation of uncertain malignant potential) , 2000 .

[16]  D. Pinkel,et al.  Mutations and copy number increase of HRAS in Spitz nevi with distinctive histopathological features. , 2000, The American journal of pathology.

[17]  C. Cockerell,et al.  Sentinel lymph node biopsy as an adjunct to management of histologically difficult to diagnose melanocytic lesions: a proposal. , 2000, Journal of the American Academy of Dermatology.

[18]  M. Nucci,et al.  Mucinous endometrial epithelial proliferations: a morphologic spectrum of changes with diverse clinical significance. , 1999, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[19]  M. Mihm,et al.  Atypical Spitz nevi/tumors: lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome. , 1999, Human pathology.

[20]  E. Kay,et al.  Identification of vertical growth phase in malignant melanoma. A study of interobserver agreement. , 1998, American journal of clinical pathology.

[21]  L. Medeiros,et al.  Oncocytic adrenocortical neoplasms: a report of seven cases and review of the literature. , 1998, American Journal of Surgical Pathology.

[22]  M A Weinstock,et al.  Reliability of the histopathologic diagnosis of melanocytic dysplasia. The Dysplastic Nevus Panel. , 1997, Archives of dermatology.

[23]  M. Weinstock,et al.  Reliability of the Histopathologic Diagnosis of Melanocytic Dysplasia , 1997 .

[24]  J. Sanger,et al.  Granular Cell Tumor of Uncertain Malignant Potential , 1997, Annals of plastic surgery.

[25]  A Halpern,et al.  Clinically recognized dysplastic nevi. A central risk factor for cutaneous melanoma. , 1997, JAMA.

[26]  S. Humphreys,et al.  A nationwide survey of observer variation in the diagnosis of thin cutaneous malignant melanoma including the MIN terminology. CRC Melanoma Pathology Panel. , 1997, Journal of Clinical Pathology.

[27]  Sobin Lh,et al.  Unusual tumors of the appendix and pseudomyxoma peritonei. , 1996 .

[28]  H Brenner,et al.  How independent are multiple 'independent' diagnostic classifications? , 1996, Statistics in medicine.

[29]  E. Farmer,et al.  Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. , 1996, Human pathology.

[30]  E. Foucar Debating melanocytic tumors of the skin: does an "uncertain" diagnosis signify borderline diagnostic skill? , 1995, The American Journal of dermatopathology.

[31]  C. Lewis,et al.  A multiobserver, population-based analysis of histologic dysplasia in melanocytic nevi. , 1994, Journal of the American Academy of Dermatology.

[32]  W. Clark,et al.  National Institutes of Health Consensus Development Conference Statement on Diagnosis and Treatment of Early Melanoma, January 27–29, 1992 , 1993 .

[33]  S. McCarthy,et al.  patients with thick melanomas surviving at least 10 years: histological, cytometric and HLA analyses , 1991, Histopathology.

[34]  A. Gown,et al.  Antibody HMB‐45 Identifies the Cells of Blue Nevi: An Immunohistochemical Study on Paraffin Sections , 1990, The American journal of surgical pathology.

[35]  H. Skelton,et al.  Spindle Cell and Epithelioid Cell Nevi with Atypia and Metastasis (Malignant Spitz Nevus) , 1989, The American journal of surgical pathology.

[36]  W. Clark,et al.  Antigenic profile of tumor progression stages in human melanocytic nevi and melanomas. , 1989, Cancer research.

[37]  J. Epstein,et al.  Use of Keratin 903 as an Adjunct in the Diagnosis of Prostate Carcinoma , 1989, The American journal of surgical pathology.

[38]  H. King,et al.  Benign and Malignant Cellular Blue Nevus A Clinicopathological Study of 30 Cases , 1988, The American Journal of dermatopathology.

[39]  A. Gown,et al.  Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes. , 1986, The American journal of pathology.

[40]  Martin F. Mihm,et al.  New TNM melanoma staging system: linking biology and natural history to clinical outcomes. , 2003, Seminars in surgical oncology.

[41]  B. Bastian Molecular cytogenetics as a diagnostic tool for typing melanocytic tumors. , 2002, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[42]  K Davidson,et al.  Early diagnosis? , 2001, The New Zealand medical journal.

[43]  P. Komminoth,et al.  Spitzoid malignant melanoma with lymph-node metastasis. Is a copy-number loss on chromosome 6q a marker of malignancy? , 2001, Virchows Archiv : an international journal of pathology.

[44]  M. Ross,et al.  Improved Staging of Node-Negative Patients With Intermediate to Thick Melanomas (>1 mm) With the Use of Lymphatic Mapping and Sentinel Lymph Node Biopsy , 2001, Annals of Surgical Oncology.

[45]  J. V. Valero Puerta,et al.  [Atypical stromal hyperplasia of the prostate (stromal proliferation of uncertain malignant potential)]. , 2000, Archivos espanoles de urologia.

[46]  F. Pontén,et al.  Rapid increase in diagnosis of cutaneous melanoma in situ in Sweden, 1968-1992. , 1998, Cancer detection and prevention.

[47]  E. Kouri,et al.  Quantitative pathology in uterine smooth muscle tumours: the case for the standard histologic classification criteria. , 1997, European journal of gynaecological oncology.

[48]  L. Sobin,et al.  Unusual tumors of the appendix and pseudomyxoma peritonei. , 1996, Seminars in diagnostic pathology.

[49]  S. Albelda,et al.  Role of integrins and other cell adhesion molecules in tumor progression and metastasis. , 1993, Laboratory investigation; a journal of technical methods and pathology.

[50]  D. Sackett,et al.  The Ends of Human Life: Medical Ethics in a Liberal Polity , 1992, Annals of Internal Medicine.

[51]  D. Silvers,et al.  The small lentiginous nevus , 1985, The American Journal of dermatopathology.

[52]  W. Clark,et al.  Invasive malignant melanomas lacking competence for metastasis. , 1984, The American Journal of dermatopathology.