Primary Cutaneous Anaplastic Large Cell Lymphoma—A Review of Clinical, Morphological, Immunohistochemical, and Molecular Features

SIMPLE SUMMARY: Primary cutaneous anaplastic large cell lymphoma (ALCL) is the second most common cutaneous T-cell lymphoma after mycosis fungoides. Although it usually presents as a localized nodule or papule (>2 cm), multifocal lesions may occur in some cases. Patients have an overall good prognosis either in localized or multifocal disease. Microscopically, this neoplasm consists of a dermal infiltrate of medium to large anaplastic cells that may extend to the subcutis. By immunohistochemistry, this tumor is strongly positive for CD30. Primary cutaneous ALCL can mimic several reactive skin conditions as well as other lymphoproliferative disorders, such as lymphomatoid papulosis, more aggressive primary cutaneous lymphomas, or systemic lymphomas involving the skin. Therefore, it is crucial to know the clinical presentation before establishing a diagnosis of primary cutaneous ALCL. Here, we review the clinical and histopathological features of primary cutaneous ALCL as well as its differential diagnosis and most common genetic alterations known to date. ABSTRACT: Primary cutaneous anaplastic large cell lymphoma (ALCL) is the second most common cutaneous T-cell lymphoma after mycosis fungoides and belongs to the spectrum of cutaneous CD30+ T-cell lymphoproliferative disorders. Although primary cutaneous ALCL usually presents as a localized nodule or papule with or without ulceration, multifocal lesions may occur in up to 20% of cases. Histologically, primary cutaneous ALCL consists of a diffuse dermal infiltrate of medium to large anaplastic/pleomorphic cells with abundant amphophilic-to-eosinophilic cytoplasm, horseshoe-shaped nuclei, strong and diffuse expression of CD30, and with focal or no epidermotropism. The neoplastic infiltrate may show angiocentric distribution and may extend to the subcutis. Patients with localized or multifocal disease have a similar prognosis with a 10-year overall survival rate of 90%. Approximately 30% of primary cutaneous ALCLs harbor a DUSP22 (6p25.3) gene rearrangement that results in decreased expression of this dual-specific phosphatase, decreased STAT3 activation, and decreased activity of immune and autoimmune-mediated mechanisms regulated by T-cells.