Background

Pigmented lesions usually refer to melanocytic proliferations.  The melanocyte comes in a variety of shapes and sizes.  Benign proliferations are often called moles or nevi.  Malignant proliferations are melanomas.  As skin cancer awareness grows, patients are presenting to their physicians with earlier forms of pigmented lesions.  One of the most challenging and litigious areas of pathology is the accurate diagnosis of these pigmented lesions.   Increasingly pathologists are called upon to make definitive diagnoses of benign nevi or malignant melanoma.  In actuality, there is a spectrum of changes between the two extremes and this gray area is one of active debate.  An experienced dermatopathologist is often called upon to render a final diagnosis.

Melanocytic proliferations are not the only reason for pigmented lesions. There may be an increase in melanin, unassociated with an increase in melanocytes. The following tables outline some of the various causes.

Just as important as pigmented lesions, are lesions which lack pigmentation. These are hypopigmented lesions and vitiligo is the classic prototype for this category of diseases but there are many different causes. These diseases are covered in a separate discussion.

Argyria
Becker's Nevus (Becker's Hairy Nevus)
Blue Nevus
Congenital Nevus
Dysplastic Nevus
Hypopigmented Lesions of the Skin including Vitiligo
Idiopathic Eruptive Macular Pigmentation (IEMP)
Lentigo
Melanoma
Melanoma Histopathological Variants/Special Stains/Differential Diagnosis
Melanoma Prognostic Factors
Melanoma Treatment
Mole (Pigmented Nevus)
Pigmented Spindle Cell Nevus of Reed
Reticular Melanotic Hypermelanosis
Spitz Nevus
Tattoo

EPIDEMIOLOGY

CHARACTERIZATION

Laypersons' perceptual discrimination of pigmented skin lesions. Branstrom R, Hedblad MA, Krakau I, Ullen H. Department of Cancer Prevention, Stockholm Center of Public Health and the Departments of Dermatology and Medicine, Karolinska Hospital.

J Am Acad Dermatol 2002 May;46(5 Pt 1):667-73 Abstract quote BACKGROUND: Most cutaneous malignant melanomas of the skin are visible and should, at least in theory, be possible to detect with the naked eye. OBJECTIVE: This study was conducted to learn more about laypersons' ability to discriminate between benign pigmented lesions and malignant ones. METHODS: Four groups of laypersons (n = 120) were asked to evaluate pictures of different types of pigmented skin lesions, before and after they received information about the ABCD (asymmetry, border irregularity, color variegation, and diameter greater than 6 mm) criteria, with respect to the necessity of action. RESULTS: The respondents made adequate assessments of melanomas but overestimated the danger of benign pigmented skin lesions. Information about the ABCD criteria enhanced their ability to make adequate assessments. CONCLUSION: People seem to make adequate decisions concerning how to act if they have a melanoma. On the other hand, common moles and dysplastic nevi were harder to discriminate. Providing information to the public about the features of melanomas, in accordance with the ABCD criteria, might help laypersons in their perceptual discrimination of skin lesions.

 

DISEASE ASSOCIATION

CHARACTERIZATION

Acquired dermal melanocytosis: Appearance during pregnancy Adam I. Rubin, MD S. Van Laborde, MD Matthew J. Stiller, MD New York, New York

J Am Acad Dermatol 2001;45:609-13 Abstract quote We report the first case of acquired dermal melanocytosis (ADM) appearing during pregnancy. A 23-year-old Hispanic woman presented to the Dermatology Clinic of Columbia-Presbyterian Medical Center during the second trimester of pregnancy with a nonpalpable blue-gray patch with interspersed discrete brown macules on the right lower extremity. It had appeared during the first trimester of pregnancy. Cutaneous biopsy specimens revealed dermal melanocytes. A review of all reported cases of this rare dermatosis in the international literature is presented.

 

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
Laboratory Markers
Digital epiluminescence microscopy: usefulness in the differential diagnosis of cutaneous pigmentary lesions. A statistical comparison between visual and computer inspection. Bauer P, Cristofolini P, Boi S, Burroni M, Dell'Eva G, Micciolo R, Cristofolini M. Department of Dermatology, Santa Chiara Hospital, Trento, Italy.	Melanoma Res 2000 Aug;10(4):345-9 Abstract quote Epiluminescence light microscopy (ELM) has been confirmed to be a useful tool for the diagnosis of pigmented skin lesions. The application of digital systems to epiluminescence represents the latest attempt to improve the diagnosis of cutaneous melanoma. The aim of this study was to compare the diagnostic accuracy of one of these systems, the DB-Dermo MIPS, with the accuracy of well-trained dermatologists using the ELM technique in order to establish the real usefulness of this instrument and to verify how much it can help the clinician make a diagnosis in a clinical setting. During a campaign for the early diagnosis of cutaneous melanoma, 311 patients with non-melanocytic lesions, common naevi, dysplastic naevi and melanomas underwent clinical diagnosis using ELM, computerized evaluation with DB-Dermo MIPS and skin biopsy. Sensitivity, specificity, true and negative predictive value were evaluated for epiluminescence and digital epiluminescence. Our study revealed that the inspection of pigmented skin lesions by digital epiluminescence has a better diagnostic accuracy than that of a trained dermatologist using the epiluminescence technique only. In our experience, this computerized system can play an essential role in the detection of early melanomas.
Morphologic Features of Melanocytes, Pigmented Keratinocytes, and Melanophages by In Vivo Confocal Scanning Laser Microscopy Klaus J. Busam, M.D., Carlos Charles, M.D., Grace Lee, M.D. and Allan C Halpern, M.D. Department of Pathology (KJBGL) and Dermatology Service (CC, ACH), Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York	Mod Pathol 2001;14:862-868 Abstract quote Confocal scanning laser microscopy (CSLM) represents a novel imaging technique for in vivo microscopic analysis of skin lesions at a level of resolution that allows morphologic analysis of microanatomic structures. We investigated the feasibility of recognizing the cellular constituents of pigmented skin lesions, such as pigmented keratinocytes, melanocytes, and melanophages, by CSLM. Fifteen pigmented lesions (five pigmented seborrheic keratoses, and 10 compound melanocytic nevi) from 15 patients were studied, as well as normal skin. After the clinical lesions were imaged by CSLM, they were biopsied or excised for examination by conventional histology for comparison of the morphologic features. In images obtained by CSLM, pigmented keratinocytes were seen as polygonal cohesive cells with variably bright granular cytoplasm. Melanocytes appeared as bright round, oval, fusiform, or dendritic cells. The architectural growth pattern of melanocytes could be analyzed. Melanocytes were identified by their nested growth pattern as aggregates of bright round to oval structures at the dermoepidermal junction or in the superficial dermis. Melanocytes were also recognizable as single cells along the dermoepidermal junction, usually separated from each other by a variable number of keratinocytes. Melanophages appeared as large bright plump cells with ill-defined cytoplasmic borders, usually located around or near vessels of the superficial dermis. Our results demonstrate that the cellular constituents of pigmented lesions can be recognized by CSLM. This technique sets a new paradigm for noninvasive quasihistologic examination of pigmented lesions in vivo and merits further evaluation for diagnostic use.
Diagnostic Significance of the Blue Hue in Dermoscopy of Melanocytic Lesions: A Dermoscopic–Pathologic Study Daniela Massi, M.D.; Vincenzo De Giorgi, M.D.; Paolo Carli, M.D.; Marco Santucci, M.D. Dipartimento di Patologia Umana ed Oncologia (D.M., M.S.), Dipartimento di Scienze Dermatologiche (V.D.G., P.C.), Università degli Studi di Firenze, Firenze, Italia.	Am J Dermatopathol 2001;23:463-469 Abstract quote In epiluminescence microscopy, the perception of a blue hue is generally considered a clue to malignancy, especially in clinically equivocal melanocytic skin lesions. However, melanocytic nevi can seldom show a blue hue under dermoscopy. The aim of the current study was to evaluate the histopathologic correlates of the blue hue seen in dermoscopy, to clarify its significance and diagnostic value. From a series of 224 consecutive pigmented skin lesions submitted to surgical excision, we selected all the melanocytic skin lesions (n. 36), blue nevi excluded, characterized by the presence of a blue hue dermoscopically. In agreement with recent refinement of dermoscopic semeiology, all cases were further classified in cases showing blue areas and cases showing blue-whitish veil by experts observers blinded to the final diagnosis. Histopathologically, the series included 23 (63.9%) melanocytic nevi and 13 (36.1%) melanomas. For each lesion, several histopathologic parameters related to both epidermal and dermal alterations were assessed. Blue areas were found in 21 melanocytic nevi and 7 melanomas, whereas blue-whitish veil was found in 6 melanomas and 2 nevi. Careful dermoscopic-histopathologic correlation demonstrated that blue areas are related to the presence of large amounts of melanin pigment, either within melanophages (in the context of areas of regression) or within pigmented melanocytes in the superficial dermis. Conversely, the histopathologic correlate of the blue-whitish veil resulted in the presence of an acanthotic epidermis with compact orthokeratosis overlying large amounts of melanin in the dermis. Such melanin was found not only within melanocytes but also in large clusters of melanophages within areas of regression in the dermis. In conclusion, the majority of melanocytic lesions characterized by the presence of blue areas were histopathologically diagnosed as melanocytic nevi whereas the presence of blue-whitish veil was highly indicative of malignant melanoma diagnosis (specificity 91% vs. 9% of blue areas; sensitivity 75% vs. 25% of blue areas). Thus, these two features of blue hue under dermoscopy cannot be longer considered as synonymous in dermoscopy setting, being associated with different histopathologic alterations and different diagnostic information.
Dermatoscopy Turns Histopathologist's Attention to the Suspicious Area in Melanocytic Lesions Juergen Bauer, MD; Gisela Metzler, MD; Gernot Rassner, MD; Claus Garbe, MD; Andreas Blum, MD	Arch Dermatol. 2001;137:1338-1340 Abstract quote Background Histopathologically, the diagnosis of nevus-associated melanoma or melanoma close to a common nevus can be missed if the specimen is cut in a nonrepresentative area or if the section shows only the associated common nevus. Objective To find out whether dermatoscopy of suspicious areas within a nevus can improve the histological diagnosis of malignant melanocytic lesions of the skin. Materials The study was based on dermatoscopic images of more than 2000 benign and 115 malignant pigmented lesions and a collection of corresponding histopathologic slides. Methods The dermatoscopic images and the corresponding histopathologic diagnoses were compared. In case of differences, the histopathologic findings were reevaluated and compared with the dermatoscopic findings. Results Three cases were identified in which melanoma could have been histopathologically missed as a result of improper sectioning. After the dermatoscopic findings were evaluated, the specimens were reembedded and further sections were obtained. Finally, nevus-associated melanoma or melanoma close to a common nevus was diagnosed. Conclusions Specific dermatoscopic patterns of malignancy can be found in highly suspicious areas, eg, broadened networks, radial streaming, pseudopods, or dots located at the periphery. The dermatoscopic-histopathologic correlation can improve the diagnosis of melanoma. Therefore, the clinician should point to the most suspicious area with a drawing or image, and the suspected diagnosis of melanoma and the history of the lesion should be also mentioned.
Is Dermoscopy (Epiluminescence Microscopy) Useful for the Diagnosis of Melanoma? Results of a Meta-analysis Using Techniques Adapted to the Evaluation of Diagnostic Tests Marie-Lise Bafounta, MD; Alain Beauchet, MD, PhD; Philippe Aegerter, MD, PhD; Philippe Saiag, MD	Arch Dermatol. 2001;137:1343-1350 Abstract quote Objective To assess, by means of meta-analysis techniques for diagnostic tests, the accuracy of dermoscopic (also known as dermatoscopy and epiluminescence microscopy) diagnosis of melanoma performed by experienced observers vs naked-eye clinical examination. Data Sources MEDLINE, EMBASE, PASCAL-BIOMED, and BIUM databases were screened through May 31, 2000, without any language restrictions. Study Selection Original studies were selected when the following criteria were met: spectrum of lesions well described, histologic findings as standard criterion, and calculated or calculable sensitivity and specificity. Eight of 672 retrieved references were retained. Data Extraction Three investigators extracted data. In case of disagreement, consensus was obtained. Summary receiver operating characteristic curve analysis was used to describe the central tendency of the studies, and to compare dermoscopy and clinical examination. Data Synthesis Selected studies represented 328 melanomas, mostly less than 0.76 mm thick, and 1865 mostly melanocytic benign pigmented skin lesions. For dermoscopic diagnosis of melanoma, the sensitivity and specificity ranges were 0.75 to 0.96 and 0.79 to 0.98, respectively. Dermoscopy had significantly higher discriminating power than clinical examination, with respective estimated odds ratios of 76 (95% confidence interval, 25-223) and 16 (95% confidence interval, 9-31) (P = .008), and respective estimated positive likelihood ratios of 9 (95% confidence interval, 5.6-19.0) and 3.7 (95% confidence interval, 2.8-5.3). The roles of the number of lesions analyzed, the percentage of melanoma lesions, the instrument used, and dermoscopic criteria used in each study could not be proved. Conclusion For experienced users, dermoscopy is more accurate than clinical examination for the diagnosis of melanoma in a pigmented skin lesion.

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
ETIOLOGIC FACTORS	DISEASE
Chemical	Arsenicals Busulfan Photochemical agents (psoralens, tar) Berloque dermatitis 5-FU Cyclophosphamide Nitrogen mustard, topical Bleomycin
Endocrine	Melasma ACTH- and MSH-producing tumors Exogenous ACTH therapy Pregnancy Addison's disease Estrogen therapy Carney's complex syndrome
Genetic	Cafe au lait macule (Neurofibromatosis, Albright's syndrome, Silver-Russell syndrome, Westerhof's syndrome, Watson's syndrome, Bloom's syndrome, Gastrocutaneous syndrome) Becker's melanosis Nevus spilus Ephelides (freckles) NAME/LAMB syndrome Ichthyosis vulgaris Neurocutaneous melanosis Familial periorbital hyperpigmentation Familial progressive hyperpigmentation Dowling-Degos disease Dyskeratosis congenita Fanconi's syndrome Human chimera Acropigmentation of Dohi Reticulate acropigmentation of Kitamura Dermatopathia pigmentosa reticularis POEMS syndrome Carbon baby syndrome
Inflammatory	Trauma Postinflammatory melanosis Lichen planus DLE Lichen simplex chornicus Atopic dermatitis Psoriasis Tinea versicolor
Metabolic	Porphyria cutanea tarda Hemochromatosis Hepatolenticular degeneration Gaucher's disease Niemann-Pick disease
Neoplastic	Melanoma Mastocytosis Acanthosis nigricans with adenocarcinoma and lymphoma
Nutritional	Kwashiorkor Pellagra Sprue Vitamin B12 deficiency
Physical	UV radiation Thermal radiation Ionizing radiation
Miscellaneous	Scleroderma, systemic Chronic hepatic insufficiency Whipple's syndrome Cronkhite-Canada syndrome

MELANOCYTIC (INCREASE IN THE NUMBER OF MELANOCYTES)

ETIOLOGIC FACTORS	DISEASE
Chemical
Endocrine
Genetic	Lentigines Moynahan's syndrome Centrofacial neurodysraphic lentiginosis Peutz-Jegher syndrome PUVA Sotos' syndrome
Inflammatory
Metabolic
Neoplastic
Nutritional
Physical	Lentigo Ultraviolet (tanning)
Miscellaneous	Lentigines, eruptive Lentigo, senilis

DISORDERS ASSOCIATED WITH CAFE AU LAIT MACULES

STRONGLY ASSOCIATED	Neurofibromatosis McCune-Albright Watson syndrome Ring chromosome syndrome
LESS STRONGLY ASSOCIATED	Tuberous sclerosis Basal cell nevus syndrome Bloom syndrome Ataxia-telangiectasia Silver-Russell syndrome LEOPARD syndrome Jaffe-Campanacci syndrome Gaucher's disease Turner's syndrome Hunter's syndrome

 

TREATMENT	CHARACTERIZATION
Treatment of a café-au-lait macule with the erbium:YAG laser Maria Beatrice Alora, MD Kenneth A. Arndt, MD Boston, Massachusetts	J Am Acad Dermatol 2001;45:566-8 Abstract quote The erbium:YAG laser is a relatively new instrument for skin rejuvenation. We present a case of a “Q-switched laser-resistant” café-au-lait macule that was successfully treated with the erbium:YAG laser.

Modified from Fitzpatrick's Dermatology in General Medicine, Fifth Edition. 1999. McGraw-Hill. Pg. 987.

Commonly Used Terms With Pigmented Lesions

Fontana-Masson stain-Special stain based upon silver impregnation, often used to identify melanocytes.

Melanophages-Histiocytes present with the dermis which have engulfed melanin pigment.

Nevus

Last Updated 11/8/2002

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