Primary cutaneous B-cell lymphomas

Group of extranodal B-cell non-Hodgkin lymphomas originating in and confined to the skin (no systemic involvement at diagnosis). Includes indolent types – follicle center lymphoma and marginal zone lymphoma – and an aggressive type (diffuse large B-cell lymphoma, leg type).

• Primary cutaneous lymphomas are mostly T-cell; B-cell variants are less common (≈20% of cases). They have distinct behavior and treatment: most CBCLs are slow-growing skin lesions with excellent prognosis, but the leg-type DLBCL is an outlier that behaves aggressively. Correctly identifying the subtype guides therapy (e.g. avoid overtreatment of indolent lesions versus aggressive chemo for leg-type).

• 📌 Primary cutaneous follicle center lymphoma (PCFCL): Typically presents in middle age (50s) with one or several firm pink or violaceous nodules/tumors on the scalp, forehead, or trunk. Lesions are smooth, non-ulcerated, and patients lack B symptoms (no fevers, weight loss).
• 📌 Primary cutaneous marginal zone lymphoma (PCMZL): Second most common subtype; usually presents in younger adults (mean 40s) with pink-red papules or nodules (often multiple) on the arms (upper extremities) or trunk. These are indolent lesions (sometimes waxing and waning) and may have associated plasma cells on biopsy. A history of Borrelia infection is sometimes noted (especially in Europe), but systemic symptoms are absent.
• 📌 Primary cutaneous DLBCL, leg type: An uncommon but aggressive form typically seen in elderly women. Presents as one or more rapidly enlarging red or bluish-red tumors on the lower legs, often with ulceration. Lesions tend to grow quickly, and patients may develop regional lymphadenopathy; systemic B symptoms are possible if the disease progresses.

1. Biopsy any persistent, unexplained skin lesion to confirm diagnosis. If pathology shows a B-cell lymphoma in the skin, perform staging (imaging and labs) to ensure it's truly primary cutaneous (no internal involvement).
2. Distinguish subtype to guide therapy: Follicle center vs marginal zone vs leg-type can be identified by histology and immunophenotype. Indolent subtypes (PCFCL, PCMZL) are typically CD20⁺/BCL6⁺/BCL2⁻ or BCL2⁺/BCL6⁻ respectively, with no MYC/BCL2 translocation. Leg-type DLBCL shows large B-cells that are BCL2⁺, MUM1⁺ (non-germinal center phenotype).
3. Remember Borrelia: In PCMZL, especially in endemic regions, check for Borrelia burgdorferi. Treatment with doxycycline has led to regression in some cases, highlighting a possible infectious trigger.
4. Tailor treatment: Don't overtreat indolent CBCL. A few localized lesions can be managed with surgery or local radiation, whereas leg-type disease (or any evidence of systemic spread) demands aggressive systemic chemoimmunotherapy (R-CHOP).

1. Localized indolent CBCL (PCFCL, PCMZL): For solitary or limited lesions, surgical excision or low-dose radiotherapy can be curative. If lesions are multiple or recurrent, options include rituximab (anti-CD20 monoclonal antibody, given intralesionally or intravenously) and topical or intralesional therapies. In Borrelia-associated cases of PCMZL, antibiotic treatment (e.g. doxycycline for 3 weeks) may be tried as first-line.
2. Aggressive or widespread disease: PCDLBCL, leg type (and any CBCL with extensive spread) is treated like a systemic lymphoma. The regimen of choice is R-CHOP chemotherapy (rituximab + CHOP) often combined with involved-field radiation to the lesion. Staging and systemic evaluation are critical; consider CNS prophylaxis if high risk. *Avoid* aggressive chemo in the indolent subtypes, as it confers no benefit in diseases that behave localized.

• 💡 Follicle center lymphoma lacks 14;18: Unlike nodal follicular lymphoma, primary cutaneous FCL typically does not have t(14;18) and is BCL2-negative. This helps confirm the skin lesion is a primary skin lymphoma and not systemic FL.
• 💡 "Leg-type = Ladies & Lethal": Primary cutaneous DLBCL, leg type occurs mostly in older women on the legs and has a poor prognosis (5-year survival ~50% or less). Always treat it with systemic R-CHOP chemo (plus rituximab) like an aggressive nodal lymphoma.
• 💡 Bugs and B-cells: Some cutaneous marginal zone lymphomas are linked to Borrelia infection. In such cases, antibiotic therapy (e.g. doxycycline) can result in lymphoma regression – a unique scenario where treating an infection treats the cancer.

• 🚩 Systemic symptoms or nodes: Primary CBCLs generally do not cause B symptoms (fever, night sweats, weight loss) or significant lymphadenopathy. If a patient with presumed cutaneous lymphoma develops systemic symptoms or enlarged nodes, suspect extracutaneous spread or an underlying systemic lymphoma – this warrants prompt re-evaluation and staging scans.
• 🚩 Ulceration or rapid growth: Most indolent CBCL lesions are slow-growing and non-ulcerated. A skin lymphoma lesion that is rapidly enlarging, painful, or ulcerative, especially on the lower leg of an older patient, is a warning sign for the aggressive leg-type DLBCL. Such cases need urgent therapy escalation.

1. 1. Biopsy skin lesion → any suspicious or persistent skin lesion is biopsied for histopathology. If a B-cell lymphoma is diagnosed, proceed with staging.
2. 2. Staging workup → perform imaging (CT/PET scans) and labs (CBC, LDH, etc.) ± bone marrow biopsy to rule out systemic lymphoma. Absence of extracutaneous disease confirms a primary cutaneous lymphoma.
3. 3. Subtype classification → dermatopathology review with immunohistochemistry to categorize the CBCL subtype (follicle center vs marginal zone vs leg-type). Note key markers: e.g. BCL6⁺/BCL2⁻ suggests follicle center; BCL2⁺/MUM1⁺ suggests leg-type DLBCL.
4. 4. Treatment plan → For indolent subtypes with limited skin involvement, use skin-directed therapy: excision or local radiation (often yields long remissions). For leg-type or multifocal disease, treat with systemic chemoimmunotherapy (R-CHOP regimen) as per aggressive lymphomas. Add antibiotics if Borrelia-positive (PCMZL). Ensure close follow-up for any new lesions.

• 🏥 Older woman with a leg tumor: An exam vignette might describe a 70-something female with a rapidly enlarging ulcerated nodule on the lower leg. Biopsy reveals sheets of large atypical B-cells that are CD20⁺, BCL2⁺, MUM1⁺. This points to primary cutaneous DLBCL, leg type, which requires aggressive therapy (unlike other skin lymphomas).
• 🏥 Localized skin nodules without systemic signs: For example, a middle-aged patient with a few indolent pink nodules on the scalp or arm, no lymphadenopathy or B symptoms, and biopsy shows a B-cell infiltrate that is BCL2-negative. This is suggestive of an indolent primary cutaneous B-cell lymphoma (follicle center or marginal zone type). Management would be local (excision or radiation) rather than systemic chemo.