# Primary cutaneous diffuse large B-cell lymphoma, leg type
**Primary cutaneous diffuse large B-cell lymphoma, leg type** (PCDLBCL, LT) is a rare, aggressive [B-cell lymphoma](https://www.edgepedia.org/b-cell-lymphoma) that arises in the skin, most often as rapidly growing tumors on the lower legs of elderly patients, and is classified as a distinct entity in the WHO-EORTC classification of primary cutaneous lymphomas.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) It is one of the three main types of primary cutaneous B-cell lymphoma, alongside primary cutaneous marginal zone lymphoma and [primary cutaneous follicle center lymphoma](https://www.edgepedia.org/primary-cutaneous-follicle-center-lymphoma), and is the only one of the three with a poor prognosis.[2](https://academic.oup.com/annonc/article/29/Supplement_4/iv30/5032670)
| Key fact | Detail |
|---|---|
| Classification | Separate entity in the 2005 WHO-EORTC classification and in the 5th edition WHO and 2022 International Consensus Classification[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) • [3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11987940/) |
| Typical presentation | Rapidly growing tumors on one or both lower legs, mainly in elderly women; 15% to 20% arise at other skin sites[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) |
| Prognosis | Disease-related 5-year survival approximately 50%; 41% in a 60-case French series[2](https://academic.oup.com/annonc/article/29/Supplement_4/iv30/5032670) • [4](https://jamanetwork.com/journals/jamadermatology/fullarticle/654378) |
| Immunophenotype | Strong BCL2 expression in over 90% of cases, with IRF4/MUM1 and IgM; MYC expressed in 65%[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) |
| Molecular drivers | MYD88 L265P mutations and CDKN2A loss, each in about two-thirds of patients, both linked to inferior survival[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) |
| Standard therapy | R-CHOP immunochemotherapy, combined with radiation (36 to 40 Gy) for localized disease[2](https://academic.oup.com/annonc/article/29/Supplement_4/iv30/5032670) |
| Frequency context | Cutaneous B-cell lymphomas are about 25% of primary cutaneous lymphomas, with an estimated incidence of roughly 4 cases per million people[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC12672811/) |
## Clinical presentation
PCDLBCL, LT particularly affects elderly women and presents as generally rapidly growing tumors on one or both lower legs; in about 15% to 20% of patients the tumors arise at skin sites other than the legs.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) In the French multicenter series of 60 patients, the mean age at onset was 76 years and 72% of tumors were located on the leg.[4](https://jamanetwork.com/journals/jamadermatology/fullarticle/654378) Lesions are described clinically as red to violaceous nodules or tumors on the lower extremities.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC6170068/) Despite the name, the disease can involve the torso, arms, buttocks, or anywhere on the body, and it can spread beyond the skin.[7](https://gmka.org/wp-content/uploads/2022/12/EN_nhl-diffuse-patient.pdf)
Compared with primary cutaneous follicle center lymphoma (PCFCL), PCDLBCL, LT more often disseminates to extracutaneous sites and has a more unfavorable prognosis.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) The indolent cutaneous B-cell lymphomas, PCMZL and PCFCL, have disease-related 10-year survival exceeding 90%, while PCDLBCL, LT has a disease-related 5-year survival of approximately 50%.[2](https://academic.oup.com/annonc/article/29/Supplement_4/iv30/5032670)
## Pathology and differential diagnosis
Histologically, PCDLBCL, LT is characterized by a monotonous proliferation of centroblasts and/or immunoblasts, large transformed B cells arranged in cohesive sheets with prominent nucleoli.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) Differentiation from PCFCL is described as extremely important because the two entities have different prognoses and require different therapeutic approaches; PCFCL is a tumor of follicle center cells that usually presents on the head or trunk and can often be managed with local radiotherapy.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/)
**Immunophenotype.** In contrast to PCFCL, PCDLBCL, LT strongly expresses BCL2, IRF4/MUM1, and IgM; recent studies reported MYC expression in 65% of cases, and because more than 90% express BCL2, double expression of MYC and BCL2 is present in two-thirds of cases.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) In the French series, 85% of tumors expressed Bcl-2.[4](https://jamanetwork.com/journals/jamadermatology/fullarticle/654378) Under current classifications, PCFCL may contain large cells and should not be categorized as PCDLBCL even when it occurs on the legs; its diagnosis rests on a germinal center B-cell immunophenotype and defining molecular features.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11987940/)
Because PCDLBCL, LT must also be distinguished from secondary cutaneous DLBCL and from iatrogenic immunodeficiency-associated lymphoproliferative disorders, adequate staging is required in all cases.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) Diagnostic workup follows the [TNM staging system](https://www.edgepedia.org/tnm-staging-system) endorsed by the International Society for Cutaneous Lymphomas and EORTC, and bone marrow biopsy is mandatory in patients with PCDLBCL, LT, with screening for hepatitis B and C, HIV, and latent tuberculosis before systemic therapy.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11987940/)
## Molecular features
The lymphoma has the phenotype and gene expression profile of the activated B-cell (ABC) subtype of systemic diffuse large B-cell lymphoma.[2](https://academic.oup.com/annonc/article/29/Supplement_4/iv30/5032670) In a molecular study of 19 to 20 cases, a cell-of-origin was assigned in 17, of which 12 were ABC type, and an MYD88 mutation was present in 13 of 19 cases (68%), a frequency the authors suggested indicates a close relationship to ABC-DLBCL arising at immune privileged sites such as the central nervous system and testis.[8](https://onlinelibrary.wiley.com/doi/full/10.1002/hon.2439_2)
Mutations in B-cell receptor signaling pathway components, including CARD11 (10%), CD79B (20%), and TNFAIP3/A20 (40%), together with MYD88 L265P mutations, strongly suggest constitutive NF-κB activation.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) Loss of CDKN2A, by gene deletion or promoter methylation, and MYD88 L265P mutation, each observed in about two-thirds of patients, have been reported to be associated with inferior prognosis.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) Rearrangements of the MYC gene have been detected in 30% of cases in one study, with reported frequencies of 13% to 43% across series.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) • [9](https://pmc.ncbi.nlm.nih.gov/articles/PMC10260375/) The mutational profile overlaps with that of ABC-type systemic DLBCL, NOS, but is most similar to primary central nervous system lymphomas and primary testicular lymphomas.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/) In contrast, MYD88 L265P is absent and CDKN2A loss is rare in PCFCL.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/)
## Prognosis
The overall 5-year disease-specific survival rate was 41% in the French series of 60 patients, and reviews place 5-year survival between 41.0% and 73.1% across studies, approximately 50% to 55% in most.[4](https://jamanetwork.com/journals/jamadermatology/fullarticle/654378) • [10](https://jamanetwork.com/journals/jamadermatology/fullarticle/1839265) Multivariate analysis identified location on the leg (relative risk 3.3, 95% CI 1.1 to 10.0) and multiple skin lesions (relative risk 2.3, 95% CI 1.0 to 5.4) as independent factors associated with poorer survival; 3-year disease-specific survival was 43% for leg tumors versus 77% for nonleg tumors.[4](https://jamanetwork.com/journals/jamadermatology/fullarticle/654378) Frequent relapses and extracutaneous dissemination are characteristic.[4](https://jamanetwork.com/journals/jamadermatology/fullarticle/654378) In a Scottish series, location on the leg was the only independent prognostic factor among primary cutaneous DLBCLs, with 5-year disease-specific survival of 67% for leg cases versus 100% for upper-body cases.[11](https://pubmed.ncbi.nlm.nih.gov/14657713/) [Prognosis](https://www.edgepedia.org/prognosis) is variable by tumor burden, with disease-related 5-year survival of 40% to 50% in patients with multiple lesions at diagnosis compared with 100% in those with a single lesion.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC6170068/)
## Treatment
**First-line therapy.** For patients who can tolerate multi-agent chemotherapy, systemic treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is recommended.[2](https://academic.oup.com/annonc/article/29/Supplement_4/iv30/5032670) For localized disease, systemic treatment is combined with involved-site radiation at 36 to 40 Gy; if no systemic treatment is given, a radiation dose of 40 Gy is recommended.[2](https://academic.oup.com/annonc/article/29/Supplement_4/iv30/5032670) In the [Mayo Clinic](https://www.edgepedia.org/mayo-clinic) retrospective cohort of 28 patients, median progression-free survival with R-CHOP plus involved-site radiation therapy was 58 months (95% CI 18 to 112) compared with 14 months (95% CI 5 to not reached; p = 0.04) with R-CHOP alone.[12](https://pubmed.ncbi.nlm.nih.gov/34453851/) In the French series, although no therapy variable reached statistical significance, patients treated with combinations of anthracycline-containing chemotherapy and rituximab had a more favorable short-term outcome.[4](https://jamanetwork.com/journals/jamadermatology/fullarticle/654378)
**Relapsed or disseminated disease.** Because patients are often elderly, rituximab as a single drug may achieve remissions in disseminated or recurrent disease.[2](https://academic.oup.com/annonc/article/29/Supplement_4/iv30/5032670) Over-expression of PD-L1/PD-L2 is seen in a high proportion of cases, and immune checkpoint inhibitors have been studied as salvage therapy for relapsed or refractory disease.[12](https://pubmed.ncbi.nlm.nih.gov/34453851/) Because MYD88 and CD79B mutations drive constitutive NF-κB signaling, recent studies suggest patients may benefit from Bruton's tyrosine kinase inhibitors, which block that pathway.[2](https://academic.oup.com/annonc/article/29/Supplement_4/iv30/5032670) The stable presence of the main driver alterations, mutated MYD88/CD79B and/or CDKN2A loss, has also been proposed as a rationale for molecular-based disease monitoring to detect relapses early.[13](https://pubmed.ncbi.nlm.nih.gov/36291936/)
## References
1. [Willemze R and colleagues (2018). The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood, via PMC.](https://pmc.ncbi.nlm.nih.gov/articles/PMC6473500/)
2. [Willemze R and colleagues (2018). Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology.](https://academic.oup.com/annonc/article/29/Supplement_4/iv30/5032670)
3. [Barbati ZR, Charli-Joseph Y (2025). Unveiling Primary Cutaneous B-Cell Lymphomas: New Insights into Diagnosis and Treatment Strategies. Cancers 17(7):1202.](https://pmc.ncbi.nlm.nih.gov/articles/PMC11987940/)
4. [Grange F and colleagues (2007). Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type: Clinicopathologic Features and Prognostic Analysis in 60 Cases. JAMA Dermatology.](https://jamanetwork.com/journals/jamadermatology/fullarticle/654378)
5. [Nomogram for predicting survival of adult patients with primary diffuse large B-cell lymphoma, leg type based on the SEER database, via PMC.](https://pmc.ncbi.nlm.nih.gov/articles/PMC12672811/)
6. [Clinical Practice Guidelines for Cutaneous Lymphomas, via PMC.](https://pmc.ncbi.nlm.nih.gov/articles/PMC6170068/)
7. [NCCN Guidelines for Patients: Diffuse Large B-Cell Lymphomas (2022).](https://gmka.org/wp-content/uploads/2022/12/EN_nhl-diffuse-patient.pdf)
8. [Goodlad JR and colleagues (2017). Molecular analysis of primary cutaneous diffuse large B-cell lymphoma, leg type. Hematological Oncology.](https://onlinelibrary.wiley.com/doi/full/10.1002/hon.2439_2)
9. [Disease Defining Molecular Features of Primary Cutaneous B-cell Lymphomas, via PMC.](https://pmc.ncbi.nlm.nih.gov/articles/PMC10260375/)
10. [Improvement of Survival in Patients With Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, in France. JAMA Dermatology.](https://jamanetwork.com/journals/jamadermatology/fullarticle/1839265)
11. [Primary cutaneous diffuse large B-cell lymphoma: prognostic significance of clinicopathological subtypes. PubMed.](https://pubmed.ncbi.nlm.nih.gov/14657713/)
12. [Outcomes in primary cutaneous diffuse large B-cell lymphoma, leg type. PubMed.](https://pubmed.ncbi.nlm.nih.gov/34453851/)
13. [Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses. PubMed.](https://pubmed.ncbi.nlm.nih.gov/36291936/)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Diseases and injuries › Cardiovascular and blood conditions › Blood disorders (hematologic conditions) › Lymphomas › B-cell non-Hodgkin lymphomas › DLBCL variants and related entities*
*Initially written Sep 17, 2026 · Reviewed: Sep 17, 2026; Sep 30, 2026; Oct 21, 2026 · Edited: Sep 30, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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