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Melanocytic Lesions Lentiginous pattern Melanocytic lesions هدف اولیه پاتولوژیست در برخورد با ضایعات مﻻنوسیتی مشخص نمودن خوشخیم و یابدخیم بودن تومور است در موارد بدخیم هدف دوم پاتولوژیست ارزیابی صحیح پارامترهای پروگنوستیک میباشد در برخورد با ضایعه مﻻنوسیتی توجه به عﻻئم بالینی، درموسکوپی، Reflectance confocal microscopy، عﻻوه بر نمای مورفولوژیک ، در تشخیص صحیح مهم میباشند. در بین تمامی حیطه های پاتولوژی، تشخیص تومورهای مﻻنوسیتی یکی از مشکلترین موارد است ، که حتی برای یک پاتولوژیست با تجربه نیز میتواند مشکل ساز شود. تشخیص غلط تومورهای مﻻنوسیتی مسئول شایعترین موارد ایجاد مشکل قانونی برای پاتولوژیستها میباشد PROBLEMATIC LESIONS Dysplastic Nevus vs. Melanoma Malignant/Atypical Blue Nevus Spectrum: blue nevus–like melanoma , melanoma arising within a preexisting blue nevus, malignant blue nevus Atypical Spitz Nevi/Tumors and Spitzoid Melanoma Lentigo Maligna vs. Actinic Melanocytic Hyperplasia Borderline or ambiguous Melanocytic Lesions : Pigmented epithelioid melanocytoma (PEM) Melanocytic lesions diagnosis Pattern analysis has been shown to have higher reliability Pattern for melanoma and nevus based classification and have a higher success for diagnosing approach melanoma Algorithmic approach Lentiginous pattern Lentiginous melanocytic hyperplasia Lentiginous nevus and Atypical Lentiginous Nevus Dysplastic nevus Lentiginous melanoma Acral lentiginous melanoma Lentigo maligna and LMM Melanoma of conjunctiva, nail and mucosal melanoma Superficial spreading malignant melanoma Approach to the Diagnosis of Melanocytic Lesions Melanocytic lesions Biopsy The ideal biopsy : excisional biopsy with narrow (2 mm) clinical margins . Incisional biopsies are not associated with increased risk of metastasis. Partial biopsy (incisional, punch and shave) are subject to sampling error in diagnosis, increased risk for the misdiagnosis of melanoma and increase ambiguous or borderline diagnosis Methods of margin assessment Lentigo maligna (LM) and acral lentiginous melanomas demonstrate uninterrupted, contiguous spread into the periphery at the epidermal- dermal junction Superficial spreading and nodular pattern melanomas show non- continuous, subclinical spread Transverse (bread-loaf) vertical sections: Sample only a small percentage of the surgical margin. To sample close to 100% of the peripheral margin step sections at intervals of 0.1 mm would be required. En face vertical sections from the perimeter of the excision specimen: Not useful for melanoma with a discontinuous growth pattern En Face Oblique Sections (Mohs micrographic surgery) Trotter MJ. Melanoma Margin Assessment. Clin Lab Med 31 (2011) 289– 300. Embedding and oriantation is more important than cutting for accurate diagnosis: Ensure the laboratory staff are skilled in embedding and cutting skin specimens. Hematoxylin and eosin sectioning remains the gold standard in evaluating melanocytic lesions. Examine the entire melanocytic lesion histopathologically. Levels often helpful: Examine at least 3 levels histopathologically. Immunohistochemistry, cytogenetic studies, and gene expression assays have emerged as potential adjuncts to improve diagnostic accuracy. Genetic classification of nevi, melanocytomas, and melanomas. Beware of fixation artifacts In poorly fixed specimens melanocytes are enlarged and their nuclei may seem to be hyperchromatic. Artifact simulating melanocytic hyperplasia Nuclei are surrounded by an empty irregular halo. Beware of keratinocytes with haloes that resemble pagetoid melanocytes Halo around nucleus without cytoplasm= keratinocyte Halo around nucleus with attached cytoplasm= melanocyte The presence of cellular shrinkage of the keratinocytes and fibroblasts indicates the artifactual nature of the alteration. Histology The ratio of melanocytes to basal keratinocytes ranges from approximately 1 : 4 on the cheek to 1 : 10 on the limbs and most body site. Sun-exposed skin the mean number of melanocytes is 4 to 16 per 0.5 mm of epidermis CLUES FROM THE REQUEST FORM Age : The appearance of a new pigmented lesion in a young person probably signifies a nevus, while in an older person one must suspect a melanoma. An atypical junctional proliferation in an elderly patient are nearly always an indication of melanoma. A Spitz nevus occurs commonly up to 50 years of age (or less). After that age a “Spitz nevus” with a mostly junctional distribution of its cells is suspected for being a melanoma. Pagetoid spread is almost always benign in the first years of life, whereas it should be considered malignant unless proven otherwise after 40 years of age (unless the lesion is in special areas as genital and volar skin or is a persistent or traumatized lesion). CLUES FROM THE REQUEST FORM Size: The clinicians should be to include size of the lesion and clinical information(color, border, previous biopsy) and clinical impression of lesion But in the absence of size of the lesion, the macroscopic description can be useful. CLUES FROM THE REQUEST FORM Site: special sites ; acral locations, the genital skin, the milk line (from the axillae over the breast to the genitalia), the umbilicus, the flexural skin, the scalp, the ears, and the back and shoulder of elderly patients. A melanocytic lesion with a significant junctional component in the palate or the anogenital region of an older patient is almost by definition at least a melanoma in situ. CLUES FROM THE REQUEST FORM Clinical impression : Be cautious about diagnosing melanoma when an experienced clinician has made a clinical diagnosis of a nevus. Conversely, it is not rare to counter a clinical diagnosis of melanoma if the histologic features are those of a benign lesion. Hormonal states: Teenagers: some atypia and rare mitotic figures Pregnancy Pregnancy 1-Increased dermal mitoses, and increased Ki-67 2-Superficial micronodules of pregnancy (SMOPs): Rounded clusters of 3–20 large epithelioid melanocytes with prominent nucleoli, abundant pale eosinophilic cytoplasm, lack of pleomorphism and occasional fine melanosomes distinctive from the deeper nevic melanocytes 3-Cellular atypia. No significant effect of pregnancy on the size of nevi CLUES FROM LOW-POWER EXAMINATION Configuration : verrucous, papillomatous, polypoid, Dome-shaped, Plaque or patch (flat). Pigmentation:Melanotic and Amelanotic lesions Location of lesion: Intraepidermal(Pagetoid & Lentiginous), Junctional, Compound, Intradermal Size and depth of lesion. Symmetry: Junctional component, Dermal component, Pigmentation, Circumscription Sun damage: nevi act as a sunscreen (umbrella sign) Nevoid M Dimension of the Lesion The lateral dimension of a lesion can be estimated at the microscope. Small lesions (less than 4 mm) in which nests predominate at the junction, is probably a nevus. Small melanomas and metastatic melanoma (smaller than 6 mm) do exist Clark nevus and congenital nevi can be much broader than 6 mm. Lesion depth Lesions that extend deeply should be viewed with some suspicion Congenital nevi, deep penetrating nevi, cellular blue nevi, and some Spitz nevi may extend deeply into the reticular dermis and subcutis. Wedge shape (DPN) Bulbous outline(cellular blue nevus) Infiltrative growth of melanocytes (nevoid melanoma, melanoma) Circumscription Good circumscription: A well-circumscribed lesion is one that ends with an identical nest at both lateral borders. The sharp demarcation within the epidermis parallels the dermal extension of the tumor Poor lateral circumscription of the lesion : when the epidermal melanocytic proliferation, extending beyond the dermal component of the lesion (shouldering phenomenon), ended with single cells, rather than with a well defined nest (DN and SSMM) Well circumscription could be seen in nodular melanoma . Heavily pigmented melanocytic lesions Heavily pigmented melanoma Blue nevus Pigmented Spitzoid lesions Recurrent nevus Combined nevus Pigmented spindle cell nevus (Reed nevus) Deep-penetrating nevus Spontaneous regression of melanoma and hyperpigmented scar with abundant melanophages after the surgical treatment of melanoma Tumoral melanosis: A nodular aggregate of melanophages occupies and expands the papillary dermis. Residual melanoma cells are not evident. Occurrence of such lesions in the deep dermis or subcutaneous fat suggests the regression of a metastasis Hypomelanotic / Amelanotic melanocytic lesions Amelanotic cellular blue nevus Spitz nevus Amelanotic intramucosal nevus Amelanotic Melanoma: 2–8% of melanomas Spindle cell and desmoplastic melanoma: Epidermal component(Nested , Lentiginous and Pagetoid patterns) Dermal expansile nodules Proliferative microndule and macronodule in congenital nevus Naked Nodules: large intradermal proliferative nodule , without a background of a congenital nevus Nodular intradermal Spitz nevus Recurrent nevus Acquired melanocytic nevi: DPN/Clonal nevus Intradermal melanoma and melanoma(VGP) Symmetry The growth pattern, cellular density, and cytologic features should all be similar, with exception allowed for populations within adventitial dermis. Pigment is usually distributed evenly in nevi , whereas it is often asymmetrically dispersed in melanoma. Symmetry of the Lateral Margins: two discrete nests usually bookend each a lateral borders of an ideal nevus (“starts with a nest and ends with a nest) Symmetry in the Distribution, Size, and Shape of junctional nests Symmetry of Silhouette of the Lesion (Vertical Levels ) is a feature of benign lesions. Asymmetry : when two parts that looked different in shape,
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