Primary cutaneous lymphoma form a seperate group of non-Hodgkin lymphoma. Apart from the usual nodal presentation of a lymphoma, less frequently a lymphoma develops in an extranodal site. The skin... Show morePrimary cutaneous lymphoma form a seperate group of non-Hodgkin lymphoma. Apart from the usual nodal presentation of a lymphoma, less frequently a lymphoma develops in an extranodal site. The skin is, after the gastrointestinal tract, the most frequent site of extranodal lymphoma. If the skin is the primary site of involvement, i.e. no extracutaneous sites are involved at diagnosis, these lymphomas are called primary cutaneous lymphoma. In this thesis different types of primary cutaneous lymphoma are evaluated and discussed. In chapter 2 a large group of primary cutaneous CD30+ lympoproliferations is described and compared with a group of systemic CD30+ ALCL with skin localisations. Lymphomatoid papulosis and primary cutaneous CD30+ CTCL are closely related conditions and should be considered as a spectrum, with a comparable, excellent, prognosis. Multiagent chemotherapy (MAC) could not induce long lasting remissions, in fact all patients treated with MAC developed one or more (cutaneous) relapses. Therefor MAC is only indicated in case of extracuteneous localisations. In chapter 3 a group of CD30-negative T-cell lymphomas presenting in the skin that could not be diagnosed as MF, SS or SPTL are evaluated. In this group there were few survivors, apart from a rare group of patients with primary cutaneous lymphoma with small-medium sized CD4+/CD8-neoplastic T-cells (less than 30% large cells). In particular, patients with localized disease had an excellent prognosis. In chapter 4 haematological malignancies presenting in the skin and expressing CD56 were collected, both from the Dutch cutaneous lymphoma group and literature. In general these types of malignancies had a poor prognosis, except for patients with primary cutaneous CD30+ LPD, that showed a similar good prognosis as CD56-negative cases. Most cases belonged to the group of nasal-type NK/T-cell lymphoma and the group of CD4+, CD56+ hematodermic neoplasm (formerly also designated as blastic NK-cell lymphoma. In addition, CD56 was expressed in some SPTL, rare primary cutaneous CD30-negative large T-cell lymphomas, skin localisations of acute myeloid leukemia and CD30+ CTCL. In most of these groups CD56 expression did not affect prognosis. However, in SPTL CD56 expression proved a marker for gamma/delta T-cell origin and these cases showed a poorer prognosis as compared to SPTL with an alpha/beta phenotype (that were usually CD56-negative). In the new WHO-EORTC classification the category of SPTL only includes cases with an alpha/beta-positive phenotype, whereas cases with a gamma/delta positive phenotype are included in the provisional category of cutaneous gamma/delta-positive T-cell lymphoma. In chapter 5 a rare case of lymphomatoid papulosis with CD56-expression was presented and the frequency of co-expression of CD56 in primary cutaneous CD30+ LPD was analyzed. CD56 expression was found in approximately 10% of CD30+ LPD (both LyP and primary CD30+ CTCL). However, these CD56+ cases were not found to have a different prognosis from CD56 negative cases. In chapter 6 a European multicenter study on primary cutaneous large B-cell lymphomas is presented. Patients with primary cutaneous large B-cell lymphoma of the leg showed a poorer prognosis as patients with primary cutaneous follicle center cell lymphoma (PCFCCL). Moreover, round cell morphology was identified as a poor prognostic parameter. Although this was closely related to presentation on the leg(s), also in the group of PCFCCL the presence of a predominance of cells with round nuclei (centroblasts and immunoblasts) was associated with a poorer prognosis. The results of this study contributed to a new category in the WHO-EORTC classification, designated primary cutaneous large B-cell lymphoma (PCLBCL), leg-type, indicating that both patients with the classical presentation on the leg(s) as patients showing the same morphology and immunophenotype (bcl-2+, Mum-1/ IRF4+) on other sites are included in this group. Presentation with multifocal lesions proved to be a poor prognostic parameter for PCLBCL-leg-type, but not for PCFCCL. In chapter 7 treatment results in multifocal primary CBCL were analyzed. The main question in this study was if PCFCCL presenting with multifocal skin lesions should be treated with MAC. The study showed that MAC is only indicated in PCLBCL, leg-type and not in (multifocal) PCFCCL. Radiotherapy on multiple sites appeared equally effective as MAC in these patients. In chapter 8 the frequency of CNS-involvement in CBCL patients of the Dutch cutaneous lymphoma group. was evaluated. The frequency was low. Only 4/140 patients with a primary CBCL developed CNS involvement in the course of their disease. Interestingly 3 of these 4 patients were PCFCCL, a lymphoma usually with an excellent prognosis. Only 4 disease related deaths were reported in this group of which 3 with CNS involvement. The reason for this relatively high prevalence of CNS involvement in PCFCCL is unclear. The studies presented in this thesis have provided important information, which has contributed to the recent development of the WHO-EORTC classification. Moreover, they have contributed to updated guidelines for the treatment of the different types of primary cutaneous lymphomas, as presented in TABLE 2 in chapter 9. Show less
