Disclosures Consulting: Myriad Genetics SciBase Superficial Atypical Melanocytic Proliferations SSM, LMM and (some of) their Simulants Melanomas and Nevi. • Nevi are important mainly in relation to melanoma – Precursors – but risk for individual lesions is low – Risk markers – important mainly in high risk situations – Simulants – important in everyday clinical decision-making • Makes sense to consider attributes of melanomas before discussing nevi Low UV Pathway I Lentiginous junctional Low-CSD Melanoma Supertpficial Spreading Melanoma nevus Banal Acquired Nevus (junctional, compound, dermal) Low Grade Deep Pigmented Dysplasia Bap-1 penetrating Epithelioid Compound Deficiency nevus (DPN)/ Melanocytoma Melanocytoma dysplastic High Grade Melanocytoma (PEM) Dysplasia nevus Superficial Melanoma in Melanoma in Melanoma in Spreading BPDM (rare) DPN (rare) PEM (rare) Melanoma BRAF V600E, (BRAF or (BRAF, MEK1, (BRAF+PRKAR1 NRAS NRAS)+BAP1 or NRAS) A) or PRKCA +(CBNN1 or APC) Superficial spreading or TERT, CDKN2A, “pagetoid” TP53, PTEN melanoma Criteria for Melanoma vs. Nevi Feature Melanoma Dysplastic Nevus Nevus Size larger intermediate smaller Symmetry poor good good Rete ridges irregular uniformly elongated uniform Junctional Melanocytes epithelioid mixed nevoid Poor circumscription common less common uncommon Nested variable predominant predominant Nests coalescent (confluent) bridging discrete Size of Nests variable uniform uniform Lentiginous continuous discontinuous discontinuous Pagetoid high, extensive low, focal, minimal minimal Nuclear atypia uniform, moderate- random, mild- minimal severe (size > 1.5x) moderate (1-1.5x) (1x) Mitoses - junctional about 1/3 of cases almost always absent absent Pyknosis/necrosis common uncommon uncommon Fibroplasia diffuse concentric minimal Lymphocytes bandlike, lichenoid patchy, perivascular minimal Regression frequent, extensive rare, minimal absent Dermal Cells uniform atypia random atypia no atypia limited maturation maturation maturation mitoses no mitoses no mitoses Superficial Melanoma and Mimics in Low CSD Skin • Superficial Spreading (“Pagetoid”) Melanoma • Junctional and superficial Compound nevi • Dysplastic Nevi • Recurrent and Traumatized Nevi • Pagetoid Spitz and other pagetoid proliferatons • Superficial Atypical Melanocytic Proliferations (SAMPUS) Case 1. DEE-10253 History: M50, Lesion of Back Reason for Consultation: Is this a melanoma or a severely dysplastic nevus? • Broad, moderately to highly cellular, asymmetric. • Cells at periphery of lesion - predominantly in nests - predominantly near the DEJ - some nests bridging between adjacent elongated rete ridges • Pattern of melanocytic dysplasia, with severe cytologic atypia and moderate architectural disorder. • Adjacent component more highly cellular. • More severe uniform atypia • Pagetoid scatter • Diffuse fibroplasia • Bandlike lymphocytic infiltrate • Few clusters of immature cells in dermis • Adjacent component more highly cellular. • More severe uniform atypia • Pagetoid scatter • Diffuse fibroplasia • Bandlike lymphocytic infiltrate • Few clusters of immature cells in dermis • Localized clusters of mature nevoid cells (precursor/associated nevus) Your Diagnosis? Melanoma? Nevus? Criteria for Melanoma vs. Nevi Feature Melanoma Dysplastic Nevus Nevus Size larger intermediate smaller Symmetry poor good good Rete ridges irregular uniformly elongated uniform Junctional Melanocytes epithelioid mixed nevoid Poor circumscription common less common uncommon Distribution of Nests variable, irregular predominant predominant, regular Pattern of Nests coalescent (confluent) bridging discrete Size of Nests variable uniform uniform Lentiginous (single cells) continuous discontinuous discontinuous Pagetoid high, extensive low, focal, minimal minimal Nuclear atypia uniform atypia, random atypia, minimal severe (>1.5x) mild-moderate Mitoses - junctional about 1/3 of cases almost always absent absent Pyknosis/necrosis common uncommon uncommon Fibroplasia diffuse concentric minimal Lymphocytes bandlike, lichenoid patchy, perivascular minimal Regression frequent, extensive rare, minimal absent Dermal Cells uniform atypia random atypia no atypia limited maturation maturation maturation mitoses no mitoses no mitoses Diagnosis, Case 1, M50. • Malignant melanoma, superficial spreading type, nonulcerated, non- tumorigenic and nonmitogenic invasive radial growth phase only, Clark level II, greatest Breslow thickness 0.28 mm, see comment. Comment – Dermal mitotic rate is zero, tumor infiltrating lymphocytes are absent (with moderate noninfiltrating lymphocytes), there is no radial growth phase regression, there is no ulcer, there are no microscopic satellites, and there is no evidence of vascular, lymphatic or neural invasion. – Age < 56 – Associated compound dysplastic nevus. – Appears to be minimally excised. – MPATH-Dx 4. – 100% 5 year survival Case 2. Clinical Information. Lesion of left shin with a mottled color in a 26-year-old woman. Reason for Consultation. I am enclosing for your consultation a melanocytic lesion present for many years from the right shin of a 27-year-old woman. Though the lesion had not changed (according to the patient), her clinician decided to remove it because he “didn’t like the mottled color”. Description. A relatively broad moderately cellular plaque-like lesion. Comprised mainly of nested large epithelioid melanocytes with abundant cytoplasm that contains finely divided “dusty” melanin pigment. Some bridging nests between adjacent rete - possible junctional melanocytic dysplasia of the epithelioid type. • Nests somewhat haphazardly distributed along the interface • Poor circumscription • Patchy to bandlike lymphocytic infiltrate • Diffuse fibroplasia • Nests somewhat haphazardly distributed along the interface • Poor circumscription • Patchy to bandlike lymphocytic infiltrate • Diffuse fibroplasia • Nests somewhat haphazardly distributed along the interface • Tendency to confluence of nests • Patchy to bandlike lymphocytic infiltrate • Diffuse fibroplasia • Nests somewhat haphazardly distributed along the interface • Nests in dermis not larger than largest in epidermis • Tendency to confluence of nests • Focal pagetoid scatter Your Diagnosis? Melanoma? Nevus? 1.1.2.5. Dermal mitotic activity in atypical cells that resemble those in epidermis. The mitosis on the right could be considered junctional; however there seems to be a wisp of collagen between the nest which is predominantly located in the dermis, and the overlying junctional nest. Non tumorigenic mitogenic VGP: Nests in the dermis are smaller than the largest nests in the epidermis. Count dermal mitoses in 1 sq. mm even if not fully occupied by tumor, express rate as a whole number Criteria for Melanoma vs. Nevi Feature Melanoma Dysplastic Nevus Nevus Size larger intermediate smaller Symmetry poor good good Rete ridges irregular uniformly elongated uniform Junctional Melanocytes epithelioid mixed nevoid Poor circumscription common less common uncommon Distribution of Nests variable, irregular predominant, regular predominant, regular Distribution of Nests coalescent (confluent) bridging discrete Size of Nests variable uniform uniform Lentiginous (single cells) continuous discontinuous minimal Pagetoid high, extensive low, focal, minimal minimal Nuclear atypia uniform atypia, random atypia, minimal severe (>1.5x) mild-moderate Mitoses – junctional/dermal about 1/3 of cases almost always absent absent Pyknosis/necrosis common uncommon none Fibroplasia diffuse concentric minimal Lymphocytes bandlike, lichenoid patchy, perivascular minimal Regression frequent, extensive rare, minimal absent Dermal Cells uniform atypia random atypia no atypia limited maturation maturation maturation mitoses no mitoses no mitoses Diagnosis, Case 2 F26 • Skin, right shin: Malignant melanoma, superficial spreading type, nonulcerated, with non-tumorigenic but mitogenic early vertical growth phase, Clark’s level II, greatest Breslow thickness 0.51 mm, see description and comment. • Comment. Differential diagnosis could include severe dermal and epidermal melanocytic dysplasia, however, dermal (or even epidermal) mitotic activity essentially rules out this diagnosis. The lesion is not a Spitz nevus/tumor because it is not comprised of large spindle and/or epithelioid cells. • Dermal mitotic rate: 2 per square millimeter • Tumor-infiltrating lymphocytes essentially absent in the invasive component, with brisk noninfiltrating lymphocytes nearby • Focal radial growth phase regression present • No ulcer, no microscopic satellites, and no evidence of vascular, lymphatic, or neural invasion. • Associated junctional dysplastic nevus of the epithelioid subtype • Actinic elastosis in the adjacent dermis is present and mild. • Lesion is completely excised with a closest border of approximately 1 mm. Superficial Melanoma and Mimics in Low CSD Skin • Superficial Spreading (“Pagetoid”) Melanoma • Junctional and superficial Compound nevi • Dysplastic Nevi • Recurrent and Traumatized Nevi • Pagetoid Spitz and other pagetoid proliferations • Superficial Atypical Melanocytic Proliferations (SAMPUS) Case 3. Clinical Information. A macular slightly variegated lesion from the back of a 37-year-old woman. Reason for Consultation. Is this a dysplastic nevus? • 25451 • Clinical Information. • A 3 mm macular slightly variegated lesion from the back of a 37-year-old woman. • Reason for Consultation. • Is this a dysplastic nevus? • Small • Poorly circumscribed • Nest predominate, discrete • Patchy