Melanoma In Situ, Not Otherwise Specified

 Cells are markedly enlarged and atypical to bizarre-appearing

Top Differential Diagnoses

• Melanoma in situ, superficial spreading type

• Melanoma in situ, lentigo maligna type

• Atypical (dysplastic) junctional melanocytic nevus

• Irritated/traumatized nevi and nevi of special sites

• Reed (pigmented spindle cell) nevus

Diagnostic Checklist

• Single atypical melanocytes as well as irregular nesting and areas of limited pagetoid scatter

Clinical Photograph of MIS, NOS
This lightly pigmented patch on chronically sun-exposed skin has irregular borders. It appears to be ill-defined, and a biopsy is needed to rule in melanoma. The biopsy proved a melanoma in situ (MIS). The lesion is evenly pigmented; however, there are less pigmented foci image, suggestive of early regression.

Irregular Patch on Sun-Exposed Skin
There is a growing pigmented patch (circled) in a background of sun damage, lentigines, and actinic keratoses. The ill-defined patch should raise concern and be biopsied. (Courtesy J. Finch, MD.)

MIS Showing Hypercellular Junctional Growth
Under scanning magnification, there is an overgrowth of intraepidermal melanocytes image. This configuration should raise concern for MIS, even at scanning magnification.

MIS Showing Upward Scatter of Melanocytes
There is migration of melanocytes throughout all the epidermal layers image. A patchy lymphocytic infiltrate image, telangiectasia image, and solar elastosis image are noted. Note how the melanocytes outnumber the keratinocytes.



• Melanoma in situ, not otherwise specified (MIS, NOS)


• Melanoma in situ, unspecified type


• Cases that cannot be clearly categorized as either lentigo maligna, acral lentiginous, or superficial spreading type of melanoma in situ



• Incidence
image Uncommon tumors

• Age
image Typically occur in elderly patients


• Usually located on sun-exposed areas, especially cheeks, upper trunk, and arms


• Borders of lesions are irregular, asymmetric, and often notched

• Lesions are dark, broad macules ~ 0.8 cm in diameter

• Mottled pigmentation


• Surgical approaches
image Complete excision with 5.0-mm clear margins

image Mohs surgery may also be effective, but is controversial


• Excellent: Little recurrence potential with adequate surgical margins


Histologic Features

• Melanocytic proliferation typically characterized by both lentiginous junctional spread (similar to lentigo maligna) and irregular nesting and pagetoid spread (similar to superficial spreading type of MIS)
• Asymmetric, poorly circumscribed junctional melanocytic lesion

image Peripheral trailing off of single atypical cells

image Melanocytes extend laterally beyond last nests

• Spitzoid features may be present in some cases
image Cells are markedly enlarged and atypical to bizarre-appearing

image Composed of mixture of spindled and epithelioid-shaped cells

image Markedly atypical junctional spitzoid lesions in adults are much more likely to represent MIS than atypical Spitz nevus

• Dermis may show dense but irregularly distributed inflammatory dermal infiltrate
image Can be difficult to exclude invasion in some cases without immunohistochemistry
– Immunostains including MART-1/Melan-A, tyrosinase, and HMB-45 can be useful to exclude invasion

Cytologic Features

• Nuclear atypia and pleomorphism
image Large eosinophilic or purple nucleoli

• Mitotic figures often present



• HMB-45, SOX10, and MITF can be used to confirm diagnosis of MIS
image Can also identify superficially invasive cells

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Apr 24, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Melanoma In Situ, Not Otherwise Specified

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