Primary cutaneous lymphomas (PCLs) are a heterogeneous group of entities characterized by the primary proliferation of different types of lymphocytes (T cells, B cells, and natural killer cells) in the skin, from where they can spread to the peripheral blood, lymph nodes, and even other organs. They may follow a progressive course and can affect quality of life and have serious consequences.1

Clinical registries are a very useful tool for uncommon, frequently difficult-to-manage, entities, such as PCL. In December 2016, the Spanish Academy of Dermatology and Venereology (AEDV) started a multicenter registry (RELCP, in its Spanish abbreviation) to collect clinical data on PCL.2 The report summarizing the data collected in the first year of the registry was published in February 2018.3 The aim of this study was to summarize observations for the first 5 years of the registry, with a focus on the clinical characteristics of the patients seen at the participating hospitals and the treatments used.

The AEDV's RELCP is a prospective multicenter registry to which any hospital with a dedicated or specialized cutaneous lymphoma unit can contribute. All the patients included in the first 5 years of the registry were diagnosed according to the criteria proposed by the World Health Organization and the European Organization for Research and Treatment of Cancer (WHO-EORTC).1 The participating hospitals included all patients with a diagnosis of PCL seen at their hospital. The only exclusion criterion was patient refusal to participate in the study. Data were entered into an online system provided by the Research Unit of the AEDV Foundation (OpenClinica Open Source software, version 3.1) following a standard protocol. Statistical analyses were performed in Stata (version 17 Statacorp). The study was classified by the Spanish Agency of Medicines and Medical Devices as a non-postauthorization study and approved by the ethics committee at Hospital 12 de Octubre (16/175) and by all participating hospitals. It complied with the principles of the Declaration of Helsinki and current legislation. All patients included in the registry provided written informed consent.

The RECLP includes information collected at inclusion and follow-up visits. At the inclusion visit, a note was made of the following demographic and diagnostic data: date; type of lymphoma according to the WHO classification; stage according to the revised classification system for TNM (or TNMB in the case of mycosis fungoides/Sézary syndrome [MF/SS]) proposed by the International Society for Cutaneous Lymphomas and the Cutaneous Task Force of the EORTC4–6; and diagnostic tests and treatments. The information recorded at the follow-up visits included date of last visit; disease status classified as complete remission (100% clearance since last visit), partial remission (50%–99% clearance since last visit), stable disease (< 25% to < 50% clearance since last visit), disease progression (≥ 25% progression since last visit), death, or recurrence; and presence of cutaneous, lymph node, visceral organ, or blood involvement at the time of the visit.

For the purpose of this study, lymphomas were separated into 4 large categories: MF/SS; primary cutaneous CD30+ T-cell lymphoproliferative disorders (CD30+ LPDs), which included lymphomatoid papulosis [LyP] and anaplastic large cell lymphoma [ALCL]); other T-cell lymphomas (TCLs); and B-cell lymphomas (BCLs). The results are reported using absolute numbers and percentages for qualitative variables, mean (SD) for normally distributed continuous variables, and median (range) for nonnormally distributed continuous variables.

At the time of the analysis, December 2021, the registry included data on 2020 patients from 33 Spanish hospitals. There were 830 women and 1190 men with a mean (SD) age of 62.2 (15.6) years and a mean age at inclusion of 55.7 (15.9) years. Age at disease onset ranged from 10 to 97 years. The mean duration of disease was 5.1 (5.8) years. The numbers of patients added annually to the registry over the first 5 years are shown in Fig. 1.

Figure 1.

Number of patients added annually to the list during the first 5 years of the Spanish Primary Cutaneous Lymphoma Registry.

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PCLs are rare, with an estimated annual incidence of approximately 1 case per 100 000 people.7 Several studies in Germany,8 the United Kingdom,9 Norway,10 Denmark,11 and France12 have reported incidence rates of between 2.9 and 4 cases×106 a year. The creation of a national PCL registry 5 years ago was prompted by the low incidence of these diseases. It was designed to facilitate collaborative research and has already led to several publications in international journals over the years.13–15 In addition, the number of patients added to the registry each year has remained stable, within a range of between 348 and 411 patients, following the initial 504 included in year 1. (The higher initial number is to be expected as hospitals will have included nonincident cases.) The similarity between the numbers in the first and following years can largely explained by the notable increase in the number of hospitals contributing to the registry, which has risen from 16 in year 1 to the current number of 33.

The breakdown of diagnoses is similar to that described in the literature,1,16 albeit with slight differences. T-cell lymphomas accounted for 72% of diagnoses, compared with 27% for BCLs. MF together with its variants was the most common entity (52.3%), followed by MZL (13.9%) and FCL (11.3%). Contrasting with reports in the latest update of the WHO-EORTC classification for PCLs,1 we observed a slightly higher proportion of MF and BCL cases. Mean age at diagnosis was 55.6 years, and the ratio of male to female patients was 1.4:1. These findings are similar to those reported for the first year of the registry.3 The proportions of MZL and FCL in the BCL category and LyP and ALCL in the CD30+ LPD category are also very similar to those in the first year.3 Of note in year 1 and now is the practically identical number of MZL and FCL cases. This similarity was not reflected in the latest large-scale revisions,1,16 although it has been described in other studies.8 The profile of CD30+ LPDs is also similar to that described in the literature.1,17,18 LyP, with twice as many cases as ALCL and CD4+ small/medium T-cell LPDs, remains the second most common T-cell LPD (10.5% of cases in this category, 7.5% of total).

Advanced disease accounted for just a small proportion of cases in the RELCP; 16.5% of patients with MF/SS had stage IIB disease or higher, and just 8.2% of these were stage III-IV. Advanced disease was also uncommon in the other categories. Observations from the RELCP registry suggest that MF/SS follows a worse disease course, as patients in this group were almost twice as likely to develop progressive disease as those with a non-MF/SS lymphoma, and these in addition were twice as likely to achieve complete remission.

The RECLP registry has some limitations, including the potential inaccuracy of some diagnoses (procedures are not centralized) and variability between hospitals. Even though clinical guidelines help standardize procedures and treatments, there will be inevitable differences such as greater or lesser access to diagnostic resources, such as genetic tests. The proportion of patients seen by the dermatology department may also vary, as in some hospitals, patients with more advanced disease or severe manifestations will be under the care of the hematology department. Nevertheless, the large number of hospitals that contribute to the registry and the consecutive enrolment of patients by all hospitals should limit the risk of selection bias and ensure a true reflection of PCL in Spain.

Overall, the clinical characteristics of patients with PCL in Spain are similar to those described in other series. The classic breakdown of 75% vs. 25% for MF/SS vs. non-MF/SS lymphomas was maintained. MF was by far the most common entity, followed by MZL and FCL. At the time of this study, most patients had early-stage disease, more than 50% had responded completely or partly to treatment, and 25% had stable disease.

The AEDV's PCL registry facilitates clinical studies on this rare group of diseases and provides easy access to groups of patients for subsequent studies, including those with a prospective design.

The Spanish Registry of Primary Cutaneous Lymphomas (RELCP) is sponsored by the Healthy Skin Foundation of the Spanish Academy of Dermatology and Venereology. Kyowa Kirin helps with funding to maintain the registry. Collaborating companies have no role in the design or conduct of studies, the writing of manuscripts, or publication decisions.