Study identifies three subtypes of cutaneous lymphoma and improves its diagnosis

A team from Clínic-IDIBAPS has published a study in Hemasphere that advances the understanding of primary cutaneous follicle center lymphoma (PCFCL), a rare type of skin cancer. The research shows that this tumour is more heterogeneous than previously thought and identifies, for the first time, three subgroups with distinct molecular characteristics.

The findings describe, for the first time, the different tumour mechanisms involved in these cancers, while also providing new tools to improve diagnosis and help tailor treatment to each patient.

The study was conducted at Clínic Barcelona and IDIBAPS, with the participation of the Pathology, Hematology and Dermatology departments, within the framework of the Clínic Barcelona Comprehensive Cancer Centre (4CB).

Two similar lymphomas with very different prognoses

Primary cutaneous follicle center lymphoma (PCFCL) is a type of B-cell lymphoma that develops in the skin and generally has an indolent course. It is usually treated with local therapies such as radiotherapy or surgical removal of lesions.

However, it can be difficult to distinguish from systemic follicular lymphoma with cutaneous involvement, a more extensive disease that requires systemic treatment such as chemotherapy.

This clinical and histological overlap makes diagnosis challenging, and accurate identification of the lymphoma subtype is essential to ensure appropriate treatment.

An integrated analysis of patient samples

To address this challenge, the research team analysed samples from 34 patients using an integrated approach that combines pathological analysis, immunohistochemistry and molecular genetics of skin samples.

This approach confirmed that PCFCL and lymphoma with cutaneous involvement are biologically distinct entities, with clearly different genetic profiles. While the latter shares features with systemic lymphoma, PCFCL shows greater molecular heterogeneity.

Three subgroups with distinct biological mechanisms

One of the main findings of the study is the identification of three subgroups within primary cutaneous lymphoma, each defined by distinct biological mechanisms:

Group 1: associated with alterations related to immune evasion
Group 2: characterised by activation of the STAT6 gene
Group 3: associated with alterations in the TNFRSF14 gene

These subtypes also show clinical differences, such as lesion location. Some mainly occur in sun-exposed areas such as the head or neck, while others are more frequent in non-exposed areas.

The role of sun exposure and the immune system

The results suggest that environmental factors such as sun exposure may be linked to the development of some subtypes of the disease. In addition, mechanisms allowing tumour cells to evade the immune system were identified in certain cases.

Although further research is needed to confirm these hypotheses, these findings open new avenues for studying the origin and evolution of this type of lymphoma.

A more heterogeneous disease than previously thought

The study also highlights the high variability of PCFCL. In some cases, researchers observed that different lesions in the same patient may share a common origin but display distinct genetic and biological features.

This heterogeneity may help explain disease behaviour and progression, and underscores the importance of incorporating molecular data into patient assessment.

Towards more precise diagnosis and personalised treatments

The results contribute to defining a new framework for classifying PCFCL based on molecular features, complementing traditional diagnostic tools. This approach may improve patient stratification and support the move towards more personalised medicine.

The research team notes that the next step will be to validate these findings in larger, multi-centre cohorts. Further work will also explore the role of the immune system and the potential influence of environmental factors such as sun exposure in disease development.

Study reference: Combalia A, Vidal-Robau N, Nadeu F, López C, Frigola G, Lopez-Oreja I, Garcia N, Bashiri M, Mozas P, Lopez-Guillermo A, Salaverria I, Estrach T, Campo E, Garcia-Herrera A, Albero R. Genomic heterogeneity in primary cutaneous follicular center lymphomas reveals different clinicopathological subgroups. Hemasphere. 2026 May 29;10(5):e70382. doi: 10.1002/hem3.70382.