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
Melanocytic Matricoma
Melanoma
Melanoma in Situ (Lentigo Maligna, Hutchinson's freckle)
Melanoma, Non-Skin Tumors
Melanoma Histopathological Variants/Special Stains/Differential Diagnosis
Melanoma Prognostic Factors
Melanoma Treatment
Mole (Pigmented Nevus)
Mongolian Spot
Nevus of Ota and Ito
Pigmented Spindle Cell Nevus of Reed
Reticular Melanotic Hypermelanosis
Spitz Nevus
Tattoo

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

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.

PATHOGENESIS	CHARACTERIZATION
BRAF V600E MUTATIONS
Detection of the BRAF V600E mutation in melanocytic lesions using the ligase detection reaction. Turner DJ, Zirvi MA, Barany F, Elenitsas R, Seykora J. Department of Microbiology, Cornell University Graduate School of Medical Sciences, New York, NY, USA.	J Cutan Pathol. 2005 May;32(5):334-9. Abstract quote   Background: BRAF is a member of the RAF kinase family, and it promotes signaling through the RAS-MAP kinase signal transduction cascade. Research has shown that a majority of melanomas and nevi exhibit an activating V600E (T1799A) mutation in BRAF exon 15. Additional studies of BRAF have demonstrated that the T1799A mutation is absent in uveal melanomas and Spitz nevi. Methods: The ligase detection reaction (LDR) is a sensitive technique that can identify specific DNA mutations occurring at very low frequency within heterogeneous clinical samples, and it has previously been used to analyze mutations in paraffin-embedded tissue specimens. Results: The LDR can readily detect mutations in DNA extracted from non-microdissected paraffin-embedded sections of common nevi, dysplastic nevi, and melanomas. In addition, this method demonstrated the absence of the V600E (T1799A) mutation within Spitz nevi. Conclusion: The LDR is a highly sensitive and specific test for detecting mutations in formalin-fixed tissue. The LDR can be easily adapted to detect any mutation associated with a cutaneous disorder. The absence of the BRAF V600E mutation in Spitz's nevi may serve as a molecular signature to distinguish these lesions from common nevi, dysplastic nevi, and some types of malignant melanoma.
p27
Expression of cell cycle inhibitor p27Kip1 and its inactivator Jab1 in melanocytic lesions. Ivan D, Diwan AH, Esteva FJ, Prieto VG. Department of Pathology, University of Texas, Houston, TX, USA.	Mod Pathol. 2004 Jul;17(7):811-8. Abstract quote   Decreased expression of p27 (a cyclin-dependent kinase inhibitor) is an adverse prognostic marker in a diverse array of human cancers. The purpose of this study was to investigate the expression of p27 and Jab1 (a protein involved in p27 degradation) in melanocytic lesions, and to identify their possible participation in melanoma progression. A tissue microarray was constructed using formalin-fixed, paraffin-embedded archival tissue blocks of 94 melanocytic lesions including 19 benign nevi, 21 dysplastic nevi, 23 melanomas, and 31 metastatic melanomas. The expression of p27 and Jab1 was evaluated by immunohistochemistry. The association between p27, Jab1, and clinicopathological parameters was analyzed using chi2 and Fisher's exact tests. Nonparametric Pearson's rank correlation was applied to evaluate the relationship between p27 and Jab1 expression. p27 was expressed in 15 (88%) nevi, 18 (95%) dysplastic nevi, 11 (50%) melanomas, and only in four (13%) of the metastatic melanomas (P<0.001). Jab1 was expressed in 14 (82%) standard nevi, 18 (95%) dysplastic nevi, 17 (77%) melanomas, and 16 (53%) of the metastatic melanomas (P<0.01). In metastatic melanomas, there was a negative correlation between p27 and Jab1 expression (r=-0.166). The low levels of p27 in primary and metastatic melanoma cases may explain the high proliferation rate of such lesions. Also, the relative high expression of Jab1 in metastatic melanoma, associated with low levels of p27, suggests that Jab1 may be involved in survival and proliferation of metastatic melanoma cells.
HEAT SHOCK PROTEIN
Heat shock protein 27 is expressed in normal and malignant human melanocytes in vivo. Kang SH, Fung MA, Gandour-Edwards R, Reilly D, Dizon T, Grahn J, Isseroff RR. Department of Dermatology, University of California Davis, School of Medicine, One Shields Avenue Davis, CA, USA.	J Cutan Pathol. 2004 Nov;31(10):665-71. Abstract quote   Background: Heat shock proteins (HSPs) are a family of highly conserved proteins found ubiquitously in mammalian cells, believed to be regulators of normal cell physiology and the cellular stress response. In addition, the small 27-kDa heat shock protein (HSP27) has previously been found to be a differentiation marker for keratinocytes and a prognostic marker associated with increased survival in certain cancerous tumors. Methods: Using immunohistochemistry on routinely processed paraffin sections, we examined skin biopsies from 15 invasive melanomas, 13 intradermal nevi, and two compound nevi immunostained with a mouse monoclonal antibody to HSP27. In addition, cultured melanocytes were heat stressed at 45 degrees C for 1 h and then fixed and immunostained in order to localize HSP27 expression intracellularly. Results: We found cytoplasmic and strong perinuclear staining of HSP27 in melanocytes in normal skin, in melanomas, and in nevi. Nuclear reactivity was absent. In addition, in cultured non-malignant melanocytes, HSP27 expression relocated from the cytoplasm to the nucleus with heat stress. Conclusions: To our knowledge, this investigation is the first to demonstrate that HSP27 is expressed in melanocytes in normal skin, in nevi, and in non-malignant cultured melanocytes.

LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
DIGITAL IMAGING/ DERMOSCOPY
Dermoscopy of pigmented skin lesions. Braun RP, Rabinovitz HS, Oliviero M, Kopf AW, Saurat JH. Pigmented Skin Lesion Unit, Department of Dermatology, University Hospital Geneva, Switzerland.	J Am Acad Dermatol. 2005 Jan;52(1):109-21. Abstract quote Dermoscopy is an in vivo method for the early diagnosis of malignant melanoma and the differential diagnosis of pigmented lesions of the skin. It has been shown to increase diagnostic accuracy over clinical visual inspection in the hands of experienced physicians. This article is a review of the principles of dermoscopy as well as recent technological developments.
Digital epiluminescence microscopy monitoring of high-risk patients. Robinson JK, Nickoloff BJ. Department of Medicine, Division of Dermatology, Cardinal Bernardin Cancer Center, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA	Arch Dermatol. 2004 Jan;140(1):49-56. Abstract quote   OBJECTIVE: To examine the outcome of digital epiluminescence microscopic (DELM) surveillance of atypical nevi in a high-risk population for 4 years. DESIGN: Atypical, flat melanocytic lesions in 100 patients at high risk of developing melanoma were followed annually with DELM. Pigmentary changes or an increase in DELM diameter of 1 mm or greater was an indication to perform an excisional biopsy. SETTING: Cardinal Bernardin Cancer Center Melanoma Program, Loyola University Health System, Maywood. PATIENTS: A consecutive sample of 3482 lesions from 100 patients (aged 18-65 years) with at least 2 images of the same lesion. MAIN OUTCOME MEASURES: The DELM change was confirmed by histopathologic examination. Patient confidence in and comfort with dermatologic surveillance and skin self-examination performance were assessed. RESULTS: During annual surveillance with DELM, 5.5% of the lesions changed. Among the 193 excisional biopsy specimens there were 4 melanomas in situ, 169 dysplastic nevi, and 20 common nevi. Confidence in and comfort with surveillance and skin self-examination improved after DELM. CONCLUSIONS: The criteria applied to detect substantial DELM changes were an increase in DELM diameter of 1 mm or greater and pigmentary changes, including radial streaming, focal enlargement, peripheral black dots, and "clumping" within the irregular pigment network. Use of DELM enhanced confidence in and comfort with care, which extended to performing more extensive skin self-examination.
Diagnostic tissue elements in melanocytic skin tumors in automated image analysis. Gerger A, Smolle J.	Am J Dermatopathol 2003 Apr;25(2):100-6 Abstract quote In tissue counter analysis, digital images are divided into subregions (elements), and the digital information in each element is used for statistical analysis. In this study, we assessed the morphologic details of tissue elements that have turned out to be of diagnostic significance in the discrimination of benign common nevi and malignant melanoma. After creation of a data set based on a total of 12,000 cellular elements obtained from 100 benign common nevi and 100 malignant melanomas, classification and regression tree (CART) analysis was performed to differentiate between cellular elements of nevi and melanoma. In a second step, the slides were re-evaluated by the decision tree; cellular elements suggestive either for benign common nevi or for malignant melanoma were highlighted on zoomed images of the whole sections, and the individual elements were displayed in galleries. Eight groups of elements (so-called terminal nodes) seemed to indicate benign common nevi, whereas seven terminal nodes were suggestive for malignant melanoma. The elements of nodes suggestive for benign nevi largely contained nevus cells with amphiphilic cytoplasm intermingled with fibrillary material, whereas the elements of the nodes suggestive for malignant lesions often showed hyperchromatism, perinuclear halos, heavy pigmentation, or a lymphohistiocytic infiltrate. Tissue counter analysis automatically detects tissue elements that are in accordance with morphologic criteria used in conventional histopathology for diagnostic discrimination.
Diagnostic imaging of melanocytic skin tumors. Gerger A, Smolle J. Department of Dermatology, University of Graz, Austria.	J Cutan Pathol 2003 Apr;30(4):247-52 Abstract quote BACKGROUND: In tissue counter analysis, digital images are dissected into subregions (elements), and the digital information in each element is used for statistical analysis. The aim of this study was to test the applicability of tissue counter analysis and CART (Classification and Regression Tree) to the diagnostic discrimination of benign common nevi and malignant melanoma in dermatopathology. METHODS: Two hundred cases each of benign nevi and malignant melanoma were consecutively sampled. CART analyses of background versus tissue elements, cellular versus 'other' tissue elements and benign versus malignant cellular elements were performed. For diagnostic assessment, only the percentage of cellular elements suggestive for malignancy in each case was used. RESULTS: CART analysis led to a correct classification of 99% of background versus tissue elements, 96% of cellular versus 'other' tissue elements and 79.1% of benign versus malignant cellular elements. When the percentage of cellular elements suggestive for malignancy in each case was evaluated, 29.5 +/- 14% (range 4.1-62.4) 'malignant' elements were found in benign nevi (n = 200), in contrast to 75.9 +/- 13.9% (range 32.8-97.3) in melanoma (n = 200; z =-16.72, p < 0.001). It turned out that a threshold level of 52.51% provides a correct classification of 192 nevi and 186 melanoma out of 200 each (specificity 96%, sensitivity 93%, positive predictive value 95.9%). CONCLUSIONS: Tissue counter analysis combined with CART may be a useful method for diagnostic purposes in histopathology.
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.

 

CLINICAL VARIANTS	CHARACTERIZATION
CONGENITAL MELANOTIC MACULES
Congenital melanotic macules and Sebaceous Choristoma arising on the tongue of a newborn: epidermal choristoma? Azorin D, Enriquez de Salamanca J, de Prada I, Colmenero I, Gonzalez Mediero I. Servicio de Anatomia Patologica, Hospital Infantil Universitario Nino Jesus, Madrid, Spain	J Cutan Pathol. 2005 Mar;32(3):251-3. Abstract quote   Oral hyperpigmentation is a common event in older individuals, however, is exceptional in neonates (congenital melanotic macules). Conversely, 70-80% of people have sebaceous glands in the oral mucosa, with the tongue representing an ectopic location and termed sebaceous choristoma by some authors. We report a case that fulfills both conditions in a tongue lesion. A 1-month-old boy presented with a pigmented macula on his tongue noted at birth. An excisional biopsy was performed showing a lesion lined by an epidermal-like epithelium with basal pigmentation, under which, sebaceous glands, abortive hair follicles and ductal structures mimicking apocrine glands were found. Seven cases of congenital melanotic macules of the tongue have been reported, however, none of them showed sebaceous glands under the lesion. Furthermore, there has not been a reported case of sebaceous choristoma of the tongue present at birth. We present a case that shares clinical and histological features of both conditions and propose the name 'epidermal choristoma'.
FLAGELLATE HYPERPIGMENTATION (BLEOMYCIN)
Flagellate hyperpigmentation following intralesional bleomycin treatment of verruca plantaris. Abess A, Keel DM, Graham BS. Department of Dermatology, Naval Medical Center San Diego, 34520 Bob Wilson Dr, Suite 300, San Diego, CA 92134-2098.	Arch Dermatol 2003 Mar;139(3):337-9 Abstract quote BACKGROUND: Flagellate hyperpigmentation is a well-documented complication of systemic bleomycin sulfate therapy when using doses of 100 U or more as an antineoplastic agent. Two cases occurred after using systemic doses from 15 to 30 U injected intravenously or intrapleurally; however, it has not been described as a complication following intralesional treatment of verruca plantaris. OBSERVATIONS: We report a case of flagellate hyperpigmentation after intralesional injection of 14 U of bleomycin for verrucae plantaris and review the literature associated with this cutaneous complication. CONCLUSIONS: Flagellate hyperpigmentation from extremely low doses of intralesional bleomycin is a previously undescribed complication. Although the mechanisms of reaction are not clearly understood, the clinician should be mindful of this uncommon complication.
MELASMA
Light microscopic, immunohistochemical, and ultrastructural alterations in patients with melasma. Grimes PE, Yamada N, Bhawan J. Vitiligo and Pigmentation Institute of Southern California, Los Angeles, CA 90004, USA.	Am J Dermatopathol. 2005 Apr;27(2):96-101. Abstract quote   Despite new technologies, few studies have assessed the histologic alterations in patients with melasma. Using current technologies, the present study was designed to re-evaluate the light microscopic, immunohistochemical, and ultrastructural changes of the hyperpigmented and adjacent normal skin of patients with melasma. Twenty-one patients were included in this study. Two millimeter punch biopsies were taken from the hyperpigmented and adjacent normal skin of the face. The integrity of the epidermis and dermis was assessed by light microscopy, computer-assisted image analysis, immunohistochemistry, and electron microscopy. Stains included hematoxylin-eosin and Fontana-Masson for melanin detection. Immunostaining was performed using Mel-5 antibody and CD1a antibody as markers for melanin and Langerhans cells, respectively. However, mild lymphohistiocytic infiltrates were present in 75% of the hyperpigmented areas. The areas of hyperpigmentation showed increased deposition of melanin in the epidermis and dermis of all cases. There was a statistically significant increase in the content of epidermal melanin. There were no quantitative increases in melanocytes in the hyperpigmented areas of skin. However, the melanocytes in the hyperpigmented areas were larger, intensely stained cells with very prominent dendrites. Electron microscopy revealed more melanosomes in keratinocytes, melanocytes, and dendrites in the involved skin in comparison to the uninvolved skin. The results of this study suggest that melasma is a consequence of specific hyperfunctional melanocytes that cause excessive melanin deposition in the epidermis and dermis.

 

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
LASER
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.
SURGICAL MARGINS
Evaluation of surgical margins in melanocytic lesions: a survey among 152 dermatopathologists. Sellheyer K, Bergfeld WF, Stewart E, Roberson G, Hammel J. Department of Dermatology, The Cleveland Clinic Foundation, Cleveland, OH, USA.	J Cutan Pathol. 2005 Apr;32(4):293-9. Abstract quote   Background: Although guidelines are established for reporting tissue specimens of melanomas, such guidelines are not available for reporting surgical margins of benign melanocytic lesions. Methods: We surveyed 582 members of the American Society of Dermatopathology via a web-based questionnaire to evaluate the practice of reporting surgical margins in melanocytic lesions. We were especially interested if the evaluation of margins differs depending on the surgical technique used (shave, punch, and excision) and on the type of melanocytic lesion encountered. Results: One hundred and fifty-two surveys (26.1%) were returned. Only 32.2% of the dermatopathologists comment routinely on margins of shaved melanocytic nevi and only 33.6% report margins in punch biopsies. More dermatopathologists (57.2%) routinely evaluate excision specimens of melanocytic nevi for margins but still almost half of the survey participants do not report margins in such a common clinical scenario. In contrast, routine evaluation for margins in excised melanomas is high (93.4%). Participants who use the terminology of dysplastic nevi evaluate margins more often and the reporting correlates with the degree of dysplasia. Asked for the terminology used to comment on surgical margins in melanocytic lesions, we observed a great variability in language. Conclusions: Although clinicians commonly request margin evaluation in melanocytic lesions, dermatopathologists often seem to be reluctant to do so depending on the type of procedure used to remove the lesion. There is a great variability in practice and terminology of when and how to report surgical margins in melanocytic skin lesions.

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DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

• Pathologists Who Make A Difference
• Search for a Physician Specialist

Last Updated March 30, 2006

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