4th June 2025

Cutaneous B-cell lymphoma

Cutaneous B-cell lymphomas (CBCL) are malignancies of B cells that develop in the skin, there should be no extra-cutaneous malignancy at diagnosis. They do not include lymphomas that start elsewhere in the body and then spread to the skin. B-cells are antibody-producing cells that form part of the immune system.

CBCL can be divided into 3 major types:

• Primary cutaneous follicle centre lymphoma (PCFCL)
• Primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT)
• Primary cutaneous marginal zone B-cell lymphoma (PCMZBCL)

The different forms of CBCL are produced, depending on when (in the development stage of the lymphocyte) the malignant mutation occurs. The very rare forms of CBCL will not be covered in this topic.

Epidemiology

• About 100 people in the UK are diagnosed with CBCL every year.
• PCFCL is the most common form of the 3 types of CBCL.
• PCDLBCL-LT has the poorest prognosis, only 50% of patients are alive after 5 years, it affects half as many men as women.
• PCMZBCL – men are more commonly affected than women; it has been associated with the bacteria Borrelia burgdorferi (known to cause Lyme disease).

Aetiology

The aetiology of CBCL is not entirely known; it has been proposed that CBCL stems from chronic inflammation in the skin (e.g. from bacterial or viral infections) which gradually transforms into a lymphoma. Viruses such as human herpes virus 8 (HHV-8) and Epstein Barr virus (EBV) are known to be strongly associated with some non-cutaneous lymphomas, however the data for causative agents in CBCL is lacking.

CBCL has also been associated with methotrexate, and has been found to improve once methotrexate is stopped – perhaps due to its immunosuppressive effect allowing the unchecked proliferation of B-cells.

Diagnosis

CBCL presents with skin changes including papules, nodules, plaques and tumours. They can range in colour from pink/red to blue/purple. PCFCL and PCMZBCL are often found on the upper extremities, trunk or scalp, whereas PCDLBCL-LT is generally found on the legs.

If CBCL is suspected from the history and examination, a skin biopsy is required for diagnosis; this must be sufficiently deep and include the subcutaneous fat. Histological and cytological examination of the biopsy will be performed, plus immunohistochemistry.

• Primary cutaneous follicle centre lymphoma:
  • Histology/cytology – accumulation of germinal centre B-cells (centrocytes and centroblasts) in the dermal and subcutaneous tissues, these form a follicular growth pattern.
  • Immunohistochemistry is positive for B-cell antigens (e.g. CD19, CD20 and CD22).
  • It is negative for the chromosomal t(14;18) translocation – which is found in generalised follicular lymphoma. This is helpful to distinguish PCFCL from follicular lymphoma that has spread to the skin.
• Primary cutaneous marginal zone B-cell lymphoma:
  • Histology/cytology – infiltration of the dermis with marginal zone B-cells (and other immune cells) in a nodular or diffuse pattern.
  • Immunohistochemistry is positive for B-cell antigens CD79a, CD20 and Bcl-2.
  • Blood tests for Borrelia burgdorferi may be performed, given its association with PCMZBCL.
• Primary cutaneous diffuse large B-cell lymphoma, leg-type:
  • Histology/cytology – dermal and subcutaneous fat infiltrates of centroblasts and immunoblasts (B-cell precursors), these may form a sheet pattern.
  • Immunohistochemistry is positive for B-cell antigens CD79a, CD20 and IgM.
  • Bcl-2 and MUM1 expression is significant for PCDLBCL-LT.
• The presence of palpable lymphadenopathy indicates extra-cutaneous involvement and the need for further imaging – such as a CT or PET-CT scan.

Management

Primary cutaneous follicle centre lymphoma:

• A single lesion or limited area of disease will be treated with radiotherapy or surgery.
• Numerous lesions may be treated with a range of therapies including topical agents, cryotherapy, radiation or systemic treatments.
• Disseminated or very large lesions may be treated with chemotherapy (e.g. R-CHOP).
• PCFCL may sometimes be observed without treatment, as lesions may remain stable in size or may even subside.

Primary cutaneous marginal zone B-cell lymphoma:

• As with PCFCL, a single lesion or limited area of disease may be treated with radiotherapy or surgery (note – relapse rates for radiotherapy are higher for PCMZBCL).
• Numerous lesions may be treated with a range of therapies including chemotherapy or rituximab.
• Disseminated or very large lesions may be treated with chemotherapy (e.g. R-CHOP).
• PCMZBCL in patients with Borrelia burgdorferi can be treated with antibiotics.

Primary cutaneous diffuse large B-cell lymphoma, leg-type:

• Limited or diffuse disease is treated with radiotherapy +/- R-CHOP.

Complications

Primary cutaneous follicle centre lymphoma:

• Close to 95% of patients are alive at 5 years post-diagnosis.
• Disease recurs in >45% patients.
• In 5 – 10% patients, PCFCL will metastasise to extracutaneous sites.

Primary cutaneous marginal zone B-cell lymphoma:

• Up to 99% of patients are alive at 5 years post-diagnosis.
• Metastasis is rare
• PCMZBCL may transform into systemic diffuse large B-cell lymphoma, but this is very rare

Primary cutaneous diffuse large B-cell lymphoma, leg-type:

• Nearly ≥60% of patients relapse after treatment
• In 30% the disease will spread to extracutaneous sites.