Primary Cutaneous Cd30positive Lymphoproliferative Disorders

General: The category of primary cutaneous CD30+ lymphoproliferative disorders includes a spectrum of cases that range from primary cutaneous anaplastic large cell lymphomas (C-ALCL) at one end to cases of lymphomatoid papulosis (LYP) at the other.119120 Cases designated as C-ALCL are clinically characterized by single or localized skin lesions and are histo-logically composed of sheets of large, atypical CD30 positive lymphocytes. There may be partial or complete spontaneous regression, but frequent cutaneous relapses generally occur. In contrast, cases designated as LYP present clinically as multiple papules that display spontaneous regression and histologically contain an inflammatory infiltrate with varying numbers of atypical CD30 positive lymphocytes. The clinical course is benign, but chronic, often lasting over many years. Lastly, some cases are designated as "borderline lesions" because there is a discrepancy between the clinical and histologic findings (e.g., a clinical appearance most consistent with LYP, but histology displaying sheets of CD30+ cells, suggestive of C-ALCL). In the absence of complete clinical information, many pathologists prefer to designate these disorders simply as "CD30+ lymphoprolifera-tive disorder."

Pathology: In C-ALCL, there is a diffuse dermal infiltrate of intermediate to large lymphoid cells that resemble those found in cases of systemic ALCL.119121 In some cases, multinucleate or binucleate cells are present, creating a differential diagnosis that includes Hodgkin's lymphoma. Any accompanying inflammatory infiltrate is usually quite mild.

The histologic findings in LYP are quite variable.119120 The most frequent pattern, which has been designated type A LYP, consists of a wedge-shaped dermal infiltrate composed of varying numbers of large, atypical lymphoid cells admixed with neutrophils, eosinophils, histiocytes, and small lymphocytes. Much less commonly (<10% of LYP), the histologic findings may resemble those of mycosis fungoides (so-called type B LYP). In these latter cases, an infiltrate of cerebriform small lymphocytes is present. Some individuals may display a mixture of both Type A and Type B lesions.

Immunophenotype: In both C-ALCL and LYP, the neoplastic cells are CD30+ and display variable loss of associated T-cell antigens. Most cases are CD4+, although occasional CD8+ cases may also occur. The majority of cases will also express cytotoxic proteins, such as TIA1 and granzyme B. Expression of ALK protein, if it occurs at all in these disorders, is rare. The finding of ALK expression therefore strongly suggests secondary cutaneous involvement by a systemic ALCL rather than primary cutaneous disease.

Molecular genetics: Clonally rearranged T-cell receptors may be identified in the majority of cases of both C-ALCL and LYP. Genotypic studies therefore do not assist in differentiating between C-ALCL and LYP. In some patients, different T-cell receptor clones may be identified in different lesions of LYP.122 In other LYP patients, however, the same T-cell receptor clone can be identified in multiple lesions over time. For example, in one report, single-cell analysis identified the same T-cell receptor clone in different biopsies taken over 4 years apart.123 There is currently little data available regarding cytogenetic abnormalities within C-ALCL and LYP.

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