Diagnostic and prognostic evaluation of phenotypic markers TRAF1, MUM1, BCL2 and CD15 in cutaneous CD30-positive lymphoproliferative disorders.

BACKGROUND: CD30 is expressed in various types of cutaneous lymphomas, including lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (C-ALCL), some cases of mycosis fungoides showing large cell transformation (MF-TR) and skin localizations of systemic anaplastic lymphoma kinase (ALK)-positive or ALK-negative ALCL. Differentiation between these entities is often not possible on the basis of histology alone, but several markers, including TRAF1, MUM1 and BCL2, have been reported to provide additional diagnostic information. OBJECTIVE: To evaluate the diagnostic and prognostic significance of these markers in a large group of cutaneous CD30-positive lymphoproliferations. METHODS: An immunohistochemical study on the expression of TRAF1, MUM1, BCL2 and CD15 was performed on skin biopsies from 28 patients with C-ALCL, 39 patients with LyP, 11 patients with CD30-positive MF-TR, two with ALK-positive ALCL and six with ALK-negative ALCL. In addition, the prognostic significance of these markers was evaluated. RESULTS: TRAF1 was expressed in roughly 70-80% and MUM1 was expressed in 70-100% of all the groups of cutaneous CD30-positive lymphoproliferations. Highest levels of BCL2 were expressed in MF-TR (73%), in contrast to 21% in C-ALCL and 36% in LyP. Highest levels of CD15 were expressed in C-ALCL (43%), compared with 18% in LyP and 9% in MF-TR. A relationship with survival was not clear. CONCLUSIONS: The results of the present study suggest that TRAF1, MUM1, BCL2 and CD15 cannot be considered as useful diagnostic or prognostic marker in cutaneous CD30-positive lymphoproliferations. Differentiation between these different conditions should be based on a combination of clinical, histological and immunophenotypical criteria.

Bone marrow examination has limited value in the staging of patients with an anaplastic large cell lymphoma first presenting in the skin. Retrospective analysis of 107 patients.

BACKGROUND: According to criteria of the World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas a diagnosis of primary cutaneous CD30-positive anaplastic large cell lymphoma (C-ALCL) should be made only when systemic localizations have been excluded by adequate staging procedures, including a bone marrow biopsy. It has recently been questioned whether or not bone marrow examination should be performed routinely in indolent cutaneous lymphomas such as C-ALCL. Studies addressing this issue have never been performed. OBJECTIVES: To determine the incidence of bone marrow involvement in patients with an ALCL first presenting in the skin to find out if the current policy to advise bone marrow examination should be maintained or whether a bone marrow biopsy should be performed only in selected cases. METHODS: All patients presenting with skin lesions with histological and immunophenotypical features of an ALCL were retrieved from the database of the Dutch Cutaneous Lymphoma Group. Patients with a history of systemic ALCL and patients without bone marrow examination were excluded from the study. The final study group included 107 patients with an ALCL first presenting in the skin, who had been staged completely. RESULTS: Staging procedures showed the presence of extracutaneous disease in 20 patients, but bone marrow involvement was not detected in any of the 107 patients. Moreover, only one patient developed bone marrow involvement during follow up (median follow-up period 69 months). CONCLUSIONS: Bone marrow examination has limited value in the staging of patients with an ALCL first presenting in the skin, and should be performed only in selected cases.