Primary Cutaneous Lymphoma: Non-Hodgkin Lymphoma Manifesting Through the Skin
Non-Hodgkin lymphoma that manifests primarily through the skin is called Primary Cutaneous Lymphoma (PCL). PCLs are defined as non-Hodgkin lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis 1.
Classification and Types
Primary cutaneous lymphomas are classified into two main categories:
Cutaneous T-cell lymphomas (CTCL) - 75-80% of cases in Western countries
- Mycosis fungoides (MF) - most common type
- Sézary syndrome (SS)
- Other rarer variants
Cutaneous B-cell lymphomas (CBCL) - 20-25% of cases
- Primary cutaneous follicle center lymphoma
- Primary cutaneous marginal zone lymphoma
- Primary cutaneous diffuse large B-cell lymphoma, leg type
Distinguishing Features
PCLs must be distinguished from nodal or systemic malignant lymphomas involving the skin secondarily, as they:
- Have different clinical behavior
- Have different prognosis
- Require different therapeutic approaches 1
This distinction is critical for proper management and treatment planning. PCLs are included as separate entities in recent lymphoma classifications due to these important differences 1.
Diagnosis
The diagnosis of PCL requires:
- Clinical examination and history
- Representative skin biopsy
- Immunophenotypical analysis
- Molecular studies (when appropriate)
- Adequate staging to exclude extracutaneous disease 1
According to the ESMO guidelines, diagnosis should always be based on a combination of clinical, histological, and immunophenotypical data 1. Demonstration of clonal T-cell receptor or immunoglobulin gene rearrangements in lesional skin may be valuable in selected cases 1.
Staging and Assessment
Proper staging is essential and includes:
- Complete physical examination
- Complete blood count and differential
- Serum biochemistry
- Appropriate imaging studies (CT scans ± FDG-PET scans)
- Flow cytometry of peripheral blood (especially for suspected Sézary syndrome)
- Bone marrow biopsy (for aggressive subtypes) 1
The TNM classification system is used for staging, with separate systems for MF/SS and other PCLs 1.
Regional Distribution and Epidemiology
PCLs are the second most common group of extranodal non-Hodgkin lymphomas after gastrointestinal lymphomas, with an estimated annual incidence of 1/100,000 in Western countries 1.
Geographic variations exist:
- In Western countries: CTCLs (75-80%) predominate, with MF being most common
- In Southeast Asian countries: CTCLs other than MF (particularly Epstein-Barr virus-associated NK/T-cell lymphomas) are more common, while CBCLs are less common 1
Management Considerations
Treatment depends on the specific type of PCL and disease stage. Due to the rarity and heterogeneity of these conditions, a multidisciplinary approach involving dermatologists, pathologists, hematologists, and radiation oncologists is recommended 1.
For MF/SS specifically, a stage-adapted conservative therapeutic approach is recommended, as early aggressive chemotherapy has not been shown to improve survival and may have considerable side effects 1.
Clinical Importance
PCLs significantly impact quality of life, with symptoms such as pruritus and visible skin lesions. In advanced stages, they can cause systemic immune suppression leading to increased risk of infections and secondary malignancies 1.
Early and accurate diagnosis is crucial for proper management and treatment planning, as these conditions have distinct clinical behaviors and prognoses compared to their nodal counterparts.