RARE DISEASE
Primary cutaneous lymphoma
Primary cutaneous lymphoma
Primary cutaneous lymphoma
Drug discovery
1
drug
With orphan designation
Overview
Primary cutaneous lymphoma (PCL) encompasses rare, heterogeneous non-Hodgkin lymphomas arising in the skin without extracutaneous involvement at diagnosis. Major subtypes include cutaneous T-cell lymphoma (CTCL) (e.g., mycosis fungoides, Sézary syndrome) and cutaneous B-cell lymphoma (CBCL) (e.g., primary cutaneous follicle center, marginal zone, and diffuse large B-cell lymphoma, leg type). Prognosis varies widely, with indolent forms demonstrating high survival rates (e.g., 10-year survival >90% for some CBCL subtypes) and aggressive subtypes (e.g., diffuse large B-cell lymphoma, leg type) showing 5-year survival rates of ~50% [1][4][7][11].
Population
Incidence: CTCL accounts for 71% of cases (7.7/million person-years), CBCL 29% (3.1/million) [2][14].
Demographics: Higher incidence in males (male-female ratio 1.7:1) [2], non-Hispanic Blacks (CTCL: 10.0/million) and non-Hispanic whites (CBCL: 3.5/million) [2][5][14]. Median age at diagnosis: 50–70 years [5][9].
Burden
Mortality: 5-year survival exceeds 95% for indolent subtypes but drops to 50–60% for aggressive forms [1][4][11]. Sézary syndrome carries a median survival of ≤4 years [9].
Relapse: Common in CBCL (56% relapse post-R-CHOP) [7] and CTCL, necessitating lifelong monitoring [4][11].
Quality of life: Chronic pruritus, disfigurement, and treatment-related complications (e.g., skin infections, therapy resistance) contribute to morbidity [1][5][12].
Therapies
Skin-directed therapies: First-line for localized disease—topical corticosteroids, phototherapy (UVB/PUVA), radiation (total skin electron beam for extensive CTCL) [3][7][11].
Systemic therapies: Retinoids, monoclonal antibodies (e.g., rituximab for CBCL), interferon-α, and combination regimens (e.g., R-CHOP for aggressive CBCL) [4][7][11].
Novel agents: Emerging use of checkpoint inhibitors, Bruton tyrosine kinase inhibitors, and CAR T-cell therapy for refractory cases [7][8].
Categories: rare hematological diseases, rare neoplastic diseases, rare skin diseases, rare transplant-related disorders
Research Papers
1,007 drug discovery papers about Primary cutaneous lymphoma, with 4 first-in-class and 11 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,007 drug discovery papers about Primary cutaneous lymphoma, with 4 first-in-class and 11 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-11 | Coexistence of Mycosis Fungoides and Hodgkin Lymphoma in a Pediatric Patient: A Report of a Rare Case.
Mycosis fungoides (MF) is the most common primary cutaneous T‑cell lymphoma, usually affecting adults aged 50-60 years; pediatric presentation is rare. We report a 12‑year‑old patient whose course spanned five years; skin lesions began at age 8, were misdiagnosed and treated as inflammatory dermatosis with topical steroids for four years. At age 12, B‑symptoms, lymphadenopathy and organomegaly led to the diagnosis of MF Stage IA (T1bNxM0B0) and synchronous Hodgkin lymphoma (HL) Stage IVB, with an Epstein-Barr virus (EBV) viral load of 2.5 log₁₀ copies/mL. Treatment with three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) + pembrolizumab due to drug availability, followed by six cycles of PC‑AVBE (prednisone, cyclophosphamide, doxorubicin, vincristine, bleomycin, and etoposide) and radiotherapy, achieving complete remission. This case highlights diagnostic challenges, immune dysregulation, and adapted treatment in resource‑limited settings.
2026-08-04 | Primary Cutaneous Gamma-Delta T-Cell Lymphoma Complicating Long-Standing Immunosuppressed Dermatomyositis.
Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a rare cytotoxic lymphoma with key oncogenic drivers in the JAK/STAT pathway. Also primarily involving the subcutaneous adipose tissue, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is more frequently encountered in scenarios of autoimmune disorders. SPTCL shares clinicopathologic overlap with lupus panniculitis. However, the link between autoimmunity and PCGD-TCL is much less established, particularly in the setting of long-standing, immunosuppressed dermatomyositis (DM). We report two cases of PCGD-TCL arising in women with chronic anti-TIF1-γ DM following years of immunosuppressive therapy. Case 1 is a 47-year-old woman with a 19-year history of DM on azathioprine/prednisone who developed rapidly progressive, painful subcutaneous nodules. Incisional biopsy confirmed a TCR-delta+, CD8+ cytotoxic T-cell lymphoproliferative disorder (TCLPD) compatible with PCGD-TCL. She achieved complete remission following pralatrexate and subsequent allogeneic hematopoietic stem cell transplant. Case 2 is a 27-year-old woman with DM on mycophenolate/rituximab who developed subcutaneous nodules with an indolent course and some spontaneous regression. A biopsy revealed a similar panniculitic infiltrate with an atypical TCR-delta+, CD8+ phenotype. Notably, both cases were negative for high-risk JAK/STAT pathway mutations. These cases identify PCGD-TCLPD/TCL as a potential complication of chronic, immunosuppressed DM. The shared, atypical CD8+ immunophenotype and absence of canonical driver mutations suggest a distinct pathogenic mechanism possibly linked to long-term immune modulation. Unlike classic PCGD-TCL, which is characterized by an aggressive course and < 2-year median survival, the clinical courses in these two cases were variable, with one requiring transplant and the other showing indolent behavior and responsiveness to therapy.
2026-08-02 | Comparison of narrowband ultraviolet B with psoralen plus ultraviolet A phototherapy for patients with early-stage mycosis fungoides: a systematic review and meta-analysis.
The most prevalent cutaneous T-cell lymphoma is mycosis fungoides (MF), managed in early stages with psoralen plus ultraviolet A (PUVA) or narrowband ultraviolet B (NB-UVB) phototherapy. To evaluate the therapeutic effectiveness and side effect profiles of PUVA vs. NB-UVB in patients with early-stage MF. A systematic review was conducted, incorporating data from nine studies sourced from PubMed, Cochrane and Google Scholar. Eligible studies were those that simultaneously evaluated PUVA and NB-UVB, enrolling at least 10 adult participants per group with histologically confirmed early-stage (IA-IIA) MF and reported treatment outcomes. Exclusions were advanced disease, paediatric patients, noncomparative or nonrelevant treatments, small sample sizes or lack of outcome data. No language restrictions were applied. Key outcomes included any response, complete response, partial response, treatment failure, relapse-free interval and adverse effects. A total of 923 patients (age range 33-71 years; 52.5% men) were included: 556 treated with PUVA and 367 with NB-UVB. Any response was seen in 90.5% of those treated with PUVA vs. 88.3% of patients who received NB-UVB [odds ratio (OR) 1.18, 95% confidence interval (CI) 0.73-1.90; P = 0.50]. Complete response rates were 72% for those treated with PUVA and 61.8% for those treated with NB-UVB (OR 1.12, 95% CI 0.60-2.07; P = 0.73). Partial response was observed in 19.2% of patients who received PUVA and 28.0% of those who received NB-UVB (OR 0.87, 95% CI 0.45-1.69; P = 0.69). Treatment failure rates were lower with PUVA (9.7%) than with NB-UVB (12.6%) (OR 0.81, 95% CI 0.49-1.33; P = 0.41). Patients who received PUVA had a significantly longer median relapse-free interval (hazard ratio 1.94, 95% CI 1.07-3.51; P < 0.01). Adverse effects, including erythema, nausea, pruritus, burning, hyperpigmentation, pain, phototoxic reactions and polymorphic light eruption, showed no significant differences between groups. Both PUVA and NB-UVB are effective, but PUVA may be preferred when sustained remission is the primary therapeutic goal.
2026-07-28 | Cutaneous Malignancies Metastatic to the Female Genital Tract and Pelvic Lymph Nodes: Analysis of Metastatic Patterns and Pathogenesis.
Background/Objectives: Metastases from cutaneous malignancies to the female genital tract and pelvic lymph nodes are rare clinical entities that frequently masquerade as primary gynecologic tumors, leading to significant diagnostic challenges. The distinction between primary and metastatic disease is critical, yet complex, given the varying patterns of spread exhibited by different skin cancers. This study aims to provide a tumor-specific overview of these metastatic patterns to guide diagnosis and therapy. Methods: We conducted a narrative review informed by a systematic literature search of MEDLINE/PubMed, Embase, Scopus, and Web of Science for records regarding primary cutaneous melanoma, cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), and cutaneous lymphomas metastasizing to the female genital tract (FGT) or pelvic lymph nodes. Data were synthesized qualitatively to identify organotropic patterns, diagnostic pitfalls, and management outcomes across these distinct malignancies. Results: The analysis reveals distinct metastatic niches: cutaneous melanoma shows a predilection for the ovary, often mimicking epithelial ovarian carcinoma, whereas cSCC and MCC typically involve pelvic lymph nodes via contiguous spread from inguinal basins. Histologic evaluation with broad immunohistochemical panels is mandatory to confirm the diagnosis, as imaging alone lacks specificity. Crucially, the introduction of immune checkpoint inhibitors and targeted therapies has significantly improved survival in advanced melanoma, cSCC, and MCC, altering the role of pelvic surgery. Conclusions: Management of cutaneous malignancies metastatic to the pelvis is shifting from a focus on radical surgery to a systemic-first approach. Pelvic metastasectomy should be reserved for selected oligometastatic cases or symptom control within a multidisciplinary framework. Clinicians must maintain a high index of suspicion in patients with a history of skin cancer to avoid overtreatment and optimize quality of life.
2026-07-23 | Final results of UK NCRI phase II trial of pembrolizumab and radiotherapy in cutaneous T cell lymphoma.
The outlook for patients with advanced cutaneous T-cell lymphomas (CTCL); mycosis fungoides (MF) and Sézary syndrome (SS) remains poor and most systemic treatments provide short-lived remissions. Immunotherapy has provided a major cancer breakthrough, and the PORT trial was designed to investigate the efficacy of Pembrolizumab and whether the addition of Radiotherapy (RT) could further enhance systemic "abscopal" anti-tumour immune responses. Pembrolizumab followed by 12Gy in 3 fractions RT to a localized lesion was investigated in a single-arm, multicentre phase II trial for relapsed/refractory CTCL. Primary endpoint was overall response rate (ORR), secondary endpoints included duration of response (DOR), abscopal response, progression-free survival (PFS), overall survival (OS). 46 patients (41 MF, 5 SS) were registered, median age 63 (24-83), 24% stage IV. Median follow-up was 24.8 months. 24% of patients remained on treatment for >1 year whilst 57% received.
2026-08-11 | Coexistence of Mycosis Fungoides and Hodgkin Lymphoma in a Pediatric Patient: A Report of a Rare Case.
Mycosis fungoides (MF) is the most common primary cutaneous T‑cell lymphoma, usually affecting adults aged 50-60 years; pediatric presentation is rare. We report a 12‑year‑old patient whose course spanned five years; skin lesions began at age 8, were misdiagnosed and treated as inflammatory dermatosis with topical steroids for four years. At age 12, B‑symptoms, lymphadenopathy and organomegaly led to the diagnosis of MF Stage IA (T1bNxM0B0) and synchronous Hodgkin lymphoma (HL) Stage IVB, with an Epstein-Barr virus (EBV) viral load of 2.5 log₁₀ copies/mL. Treatment with three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) + pembrolizumab due to drug availability, followed by six cycles of PC‑AVBE (prednisone, cyclophosphamide, doxorubicin, vincristine, bleomycin, and etoposide) and radiotherapy, achieving complete remission. This case highlights diagnostic challenges, immune dysregulation, and adapted treatment in resource‑limited settings.
2026-08-04 | Primary Cutaneous Gamma-Delta T-Cell Lymphoma Complicating Long-Standing Immunosuppressed Dermatomyositis.
Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a rare cytotoxic lymphoma with key oncogenic drivers in the JAK/STAT pathway. Also primarily involving the subcutaneous adipose tissue, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is more frequently encountered in scenarios of autoimmune disorders. SPTCL shares clinicopathologic overlap with lupus panniculitis. However, the link between autoimmunity and PCGD-TCL is much less established, particularly in the setting of long-standing, immunosuppressed dermatomyositis (DM). We report two cases of PCGD-TCL arising in women with chronic anti-TIF1-γ DM following years of immunosuppressive therapy. Case 1 is a 47-year-old woman with a 19-year history of DM on azathioprine/prednisone who developed rapidly progressive, painful subcutaneous nodules. Incisional biopsy confirmed a TCR-delta+, CD8+ cytotoxic T-cell lymphoproliferative disorder (TCLPD) compatible with PCGD-TCL. She achieved complete remission following pralatrexate and subsequent allogeneic hematopoietic stem cell transplant. Case 2 is a 27-year-old woman with DM on mycophenolate/rituximab who developed subcutaneous nodules with an indolent course and some spontaneous regression. A biopsy revealed a similar panniculitic infiltrate with an atypical TCR-delta+, CD8+ phenotype. Notably, both cases were negative for high-risk JAK/STAT pathway mutations. These cases identify PCGD-TCLPD/TCL as a potential complication of chronic, immunosuppressed DM. The shared, atypical CD8+ immunophenotype and absence of canonical driver mutations suggest a distinct pathogenic mechanism possibly linked to long-term immune modulation. Unlike classic PCGD-TCL, which is characterized by an aggressive course and < 2-year median survival, the clinical courses in these two cases were variable, with one requiring transplant and the other showing indolent behavior and responsiveness to therapy.
2026-08-02 | Comparison of narrowband ultraviolet B with psoralen plus ultraviolet A phototherapy for patients with early-stage mycosis fungoides: a systematic review and meta-analysis.
The most prevalent cutaneous T-cell lymphoma is mycosis fungoides (MF), managed in early stages with psoralen plus ultraviolet A (PUVA) or narrowband ultraviolet B (NB-UVB) phototherapy. To evaluate the therapeutic effectiveness and side effect profiles of PUVA vs. NB-UVB in patients with early-stage MF. A systematic review was conducted, incorporating data from nine studies sourced from PubMed, Cochrane and Google Scholar. Eligible studies were those that simultaneously evaluated PUVA and NB-UVB, enrolling at least 10 adult participants per group with histologically confirmed early-stage (IA-IIA) MF and reported treatment outcomes. Exclusions were advanced disease, paediatric patients, noncomparative or nonrelevant treatments, small sample sizes or lack of outcome data. No language restrictions were applied. Key outcomes included any response, complete response, partial response, treatment failure, relapse-free interval and adverse effects. A total of 923 patients (age range 33-71 years; 52.5% men) were included: 556 treated with PUVA and 367 with NB-UVB. Any response was seen in 90.5% of those treated with PUVA vs. 88.3% of patients who received NB-UVB [odds ratio (OR) 1.18, 95% confidence interval (CI) 0.73-1.90; P = 0.50]. Complete response rates were 72% for those treated with PUVA and 61.8% for those treated with NB-UVB (OR 1.12, 95% CI 0.60-2.07; P = 0.73). Partial response was observed in 19.2% of patients who received PUVA and 28.0% of those who received NB-UVB (OR 0.87, 95% CI 0.45-1.69; P = 0.69). Treatment failure rates were lower with PUVA (9.7%) than with NB-UVB (12.6%) (OR 0.81, 95% CI 0.49-1.33; P = 0.41). Patients who received PUVA had a significantly longer median relapse-free interval (hazard ratio 1.94, 95% CI 1.07-3.51; P < 0.01). Adverse effects, including erythema, nausea, pruritus, burning, hyperpigmentation, pain, phototoxic reactions and polymorphic light eruption, showed no significant differences between groups. Both PUVA and NB-UVB are effective, but PUVA may be preferred when sustained remission is the primary therapeutic goal.
2026-07-28 | Cutaneous Malignancies Metastatic to the Female Genital Tract and Pelvic Lymph Nodes: Analysis of Metastatic Patterns and Pathogenesis.
Background/Objectives: Metastases from cutaneous malignancies to the female genital tract and pelvic lymph nodes are rare clinical entities that frequently masquerade as primary gynecologic tumors, leading to significant diagnostic challenges. The distinction between primary and metastatic disease is critical, yet complex, given the varying patterns of spread exhibited by different skin cancers. This study aims to provide a tumor-specific overview of these metastatic patterns to guide diagnosis and therapy. Methods: We conducted a narrative review informed by a systematic literature search of MEDLINE/PubMed, Embase, Scopus, and Web of Science for records regarding primary cutaneous melanoma, cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), and cutaneous lymphomas metastasizing to the female genital tract (FGT) or pelvic lymph nodes. Data were synthesized qualitatively to identify organotropic patterns, diagnostic pitfalls, and management outcomes across these distinct malignancies. Results: The analysis reveals distinct metastatic niches: cutaneous melanoma shows a predilection for the ovary, often mimicking epithelial ovarian carcinoma, whereas cSCC and MCC typically involve pelvic lymph nodes via contiguous spread from inguinal basins. Histologic evaluation with broad immunohistochemical panels is mandatory to confirm the diagnosis, as imaging alone lacks specificity. Crucially, the introduction of immune checkpoint inhibitors and targeted therapies has significantly improved survival in advanced melanoma, cSCC, and MCC, altering the role of pelvic surgery. Conclusions: Management of cutaneous malignancies metastatic to the pelvis is shifting from a focus on radical surgery to a systemic-first approach. Pelvic metastasectomy should be reserved for selected oligometastatic cases or symptom control within a multidisciplinary framework. Clinicians must maintain a high index of suspicion in patients with a history of skin cancer to avoid overtreatment and optimize quality of life.
2026-07-23 | Final results of UK NCRI phase II trial of pembrolizumab and radiotherapy in cutaneous T cell lymphoma.
The outlook for patients with advanced cutaneous T-cell lymphomas (CTCL); mycosis fungoides (MF) and Sézary syndrome (SS) remains poor and most systemic treatments provide short-lived remissions. Immunotherapy has provided a major cancer breakthrough, and the PORT trial was designed to investigate the efficacy of Pembrolizumab and whether the addition of Radiotherapy (RT) could further enhance systemic "abscopal" anti-tumour immune responses. Pembrolizumab followed by 12Gy in 3 fractions RT to a localized lesion was investigated in a single-arm, multicentre phase II trial for relapsed/refractory CTCL. Primary endpoint was overall response rate (ORR), secondary endpoints included duration of response (DOR), abscopal response, progression-free survival (PFS), overall survival (OS). 46 patients (41 MF, 5 SS) were registered, median age 63 (24-83), 24% stage IV. Median follow-up was 24.8 months. 24% of patients remained on treatment for >1 year whilst 57% received.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Primary cutaneous lymphoma.
1 orphan drug designation for Primary cutaneous lymphoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
miltefosine | small molecules | FDA | 2009-03-18 | — | ExperGen Drug Development GmbH |
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