RARE DISEASE
Classic mycosis fungoides
Classic mycosis fungoides
Classic mycosis fungoides
Synonyms: Mycosis fungoides, Alibert-Bazin type
Synonyms: Mycosis fungoides, Alibert-Bazin type
Synonyms: Mycosis fungoides, Alibert-Bazin type
Drug discovery
7
drugs
With orphan designations
Overview
Classic mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, presents as progressive skin lesions (patches → plaques → tumors) with epidermotropic CD4+ T-cell infiltration [1][6]. It follows an indolent course, often diagnosed in early stages, with a median survival of 18 years in stage IA disease [4][9]. While typically skin-limited, advanced stages may involve lymph nodes or viscera [1][6]. Diagnosis requires clinicopathological correlation due to frequent mimicry of inflammatory dermatoses [2][16].
Therapies
Early stages (IA-IIA): Skin-directed therapies (topical steroids, PUVA/UVB phototherapy, localized radiotherapy) [3][8][13]
Advanced disease (IIB-IV): Systemic agents (interferon-α, retinoids) and targeted therapies (brentuximab vedotin for CD30+ disease) [3][8][11]
Palliative focus: 80-90% achieve remission with phototherapy; only stem cell transplantation modifies disease progression [1][8][13]
Categories: rare hematological diseases, rare neoplastic diseases, rare skin diseases, rare transplant-related disorders
Research Papers
167 drug discovery papers about Classic mycosis fungoides, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
167 drug discovery papers about Classic mycosis fungoides, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-28 | Single-Cell Analysis Reclassifies Eczematous Mycosis Fungoides as Severe Atopic Dermatitis 2259810
Abstract Introduction Mycosis fungoides (MF), the prevalent subtype of cutaneous T-cell lymphoma (CTCL), primarily affects the skin and progresses systemically over time. Early-stage MF diagnosis relies on immunohistochemistry, T cell receptor (TCR) gene rearrangement testing, and clinical evaluation. However, in the clinic settings, we observe eczematous MF (eMF) patients who meet early-stage MF diagnostic criteria but exhibit phenotypes resembling atopic dermatitis (AD), and refractory to dupilumab. This study investigates the molecular characteristics of eMF in comparison to AD and classic MF, providing insights into its distinct pathophysiology and potential therapeutic implications. Methods Skin biopsies were collected from seven AD patients and eleven eMF patients. Paired single-cell RNA sequencing (scRNA-seq) and single-cell TCR sequencing (scTCR-seq) were conducted to evaluate transcriptional profiles and T-cell clonality. Publicly available MF and AD scRNA-seq data were used for comparative analysis. In addition, spatial transcriptomic profiling was performed to validate. Results Comparative transcriptomic analysis showed that the molecular profiles of T cells in eMF resembled those in AD rather than in conventional MF. Furthermore, in eMF, we observed oligoclonal T-cell expansions, which were not found in conventional MF both in scRNA-seq and spatial transcriptomic data. These expanded cells were predominantly Th22 cells, identified as the primary producers of IL-13, a key cytokine in AD pathophysiology. Conclusion eMF diagnostic phenotype resembles conventional MF, and AD primarily due to the hyperproliferation of Th22 cells and their expression of IL-13. In this context, this mechanism underscores the superior efficacy of Upadacitinib, which could target Th22 differentiation, over Dupilumab. As a result, our findings indicate that eMF is not cancer, but a Th22-mediated AD endotype. Funding Source n/a Topic Categories Immune Mechanisms of Human Disease (HUM)
2026-05-21 | Primary cutaneous lymphomas in children: a single-center retrospective analysis and narrative review of the literature.
Primary cutaneous lymphomas (PCLs) are uncommon in children, with mycosis fungoides (MF), lymphomatoid papulosis (LyP), and primary cutaneous small/medium CD4+ T-cell lymphoproliferative disorder (PCSM-TCLPD) representing the most frequent entities. Due to their rarity, available data derive mainly from case reports and small series, and diagnostic delays are frequent. This study aimed to describe the clinical, histopathological, and therapeutic features of pediatric PCLs in a single Italian referral centre and compare them with the literature evidence. We conducted a single-center, retrospective observational study including patients aged ≤16 years with a histologically confirmed diagnosis of PCLs, followed for at least six months at the Dermatology Unit of the University Hospital of Bologna between 2002 and 2024. Clinical, histological, therapeutic, and follow-up data were collected and analyzed. Among 354 PCL patients, 10 pediatric cases were identified: six MF, three LyP, and one PCSM-TCLPD. The mean age at diagnosis was 9.1 years. MF cases were mostly early-stage (IA, 5/6), with folliculotropic (67%), hypopigmented (50%), and classic (50%) variants; all were treated with topical corticosteroids and/or PUVA, with good long-term outcomes (67% complete remission). LyP patients presented at younger ages (mean 5.7 years) with type A (N.=2) and D (N.=1) subtypes; all achieved complete remission despite recurrences, one requiring methotrexate. The single PCSM-TCLPD case was cured with surgical excision. After a mean follow-up of 8.2 years, all patients were alive, most disease-free. Pediatric PCLs are rare but generally indolent, with an excellent prognosis. However, their clinical heterogeneity and diagnostic delay highlight the importance of early biopsy, integrated clinicopathological assessment, and long-term follow-up. Multicenter studies are needed to establish tailored treatment algorithms for children.
2026-02-06 | A historical review of mycosis fungoides: from Alibert to mogamulizumab.
In 1806, French physician Baron Jean-Louis Alibert saw a man with a desquamating rash and skin tumours. Alibert considered this to be a variant of yaws. In 1829 Alibert named the condition mycosis fungoides (MF), meaning 'mushroom-like fungal disease'. Over 100 years later, French dermatologist Albert Sézary published papers from 1938 to 1949 detailing a mysterious disease containing 'cellules monstrueuses', describing cutaneous 'monster cells'. In 1961, these clinical findings were collated together into 'Sézary syndrome'. In the 1870s English dermatologist William Tilbury Fox published a dermatology atlas detailing cases similar to what we know now as MF, with the name 'fibroma fungoides'. The atlas described MF as a type of fungus, before giving a description of yaws and painting a clinical picture that differed from that of a lymphoma. Over the twentieth century, our understandings of the origins of MF were changing and by 1975 the classification system and term we now recognize as cutaneous T-cell lymphoma (CTCL) was developed. Neoplastic cells have been thought to arise from chronic activation of T cells via antigen-presenting cells due to inappropriate cytokines and C-C chemokine receptors. In 2018, the World Health Organization and European Organisation for Research and Treatment of Cancer officially recognized four variants of MF. These are the classic Alibert-Bazin variant and its three variants: folliculotropic MF, pagetoid reticulosis and granulomatous slack skin. Developments in immunohistochemistry for the T-cell receptor gene in the 1990s improved the diagnosis of CTCL; however, diagnosis is still challenging. Advanced MF therapies have evolved from cytotoxic chemotherapy to novel monoclonal antibodies such as mogamulizumab, targeting proteins on T-cell lymphoma cells.
2025-12-24 | Central Nervous System Progression in Folliculotropic Mycosis Fungoides.
Central nervous system (CNS) involvement by cutaneous T-cell lymphomas (CTCL) is exceptionally rare and is associated with a poor prognosis. Folliculotropic mycosis fungoides (FMF) is a rare subtype of CTCL and often has more aggressive clinical behavior compared to classic MF. The risk factors for CNS progression in patients with primary CTCL are not well understood. We present the case of a 75-year-old male with a history of Stage IA FMF, who developed progressive neurologic and functional decline over six months. Workup revealed marked eosinophilia, and CSF analysis showed monoclonal T-cell population with positive T-cell receptor (TCR) gene rearrangement. Flow cytometry further showed an atypical CD4+ T-cell population with loss of CD7, consistent with the immunophenotype of patient's cutaneous MF, supporting secondary CNS involvement. An MRI of the brain showed T2 hyperintensity in the pons and right middle cerebellar peduncle, with low signal intensity throughout the bone marrow of the skull, concerning for CNS progression of FMF. The patient was started on high-dose steroids, which led to improvement in eosinophilia. Due to transaminitis, high-dose methotrexate therapy was deferred, and the patient was initiated on intrathecal (IT) chemotherapy with methotrexate and cytarabine. Following five cycles of IT chemotherapy, the patient's neurologic status significantly improved, and CSF analysis showed resolution of the atypical T-cell population. This case highlights the rare occurrence of CNS progression of FMF, even in the absence of lymphatic involvement and with well-controlled skin manifestations, and underscores the role of IT chemotherapy in managing this complication.
2025-09-26 | PAI-1 in Skin Malignancies: a Central Regulator of Tumor Progression and Therapeutic Resistance.
Plasminogen activator inhibitor-1 (PAI-1) plays a multifaceted and central role in the tumor biology of various skin malignancies. Beyond its classical function in fibrinolysis, PAI-1 contributes to tumor progression by promoting immunosuppression, angiogenesis, cellular senescence, and tissue remodeling. Its expression is particularly elevated in aggressive disease stages across cutaneous melanoma, cutaneous squamous cell carcinoma (cSCC), cutaneous angiosarcoma (CAS), and mycosis fungoides (MF), and is associated with poor clinical outcomes. The ability of PAI-1 to induce senescence-associated secretory phenotype (SASP), modulate PD-L1 expression, and recruit tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) suggests a key role in shaping the immunosuppressive tumor microenvironment (TME). This positions PAI-1 as both a potential biomarker for disease progression and a therapeutic target for restoring immune responsiveness, especially in tumors resistant to immune checkpoint inhibitors (ICIs). The PAI-1 inhibitor TM5614 has demonstrated promising activity in early clinical studies, particularly in anti-PD-1-refractory melanoma, and is currently under evaluation in multiple Phase II and III trials. Future strategies should focus on patient stratification using biomarkers such as SASP factors and PAI-1 levels, as well as rational combination therapies targeting interconnected pathways like IL-17/IL-23, AhR, and senescence signaling. Overall, PAI-1 inhibition offers a novel and mechanistically grounded approach to improve outcomes in skin cancers characterized by therapy resistance and an immunosuppressive microenvironment.
2026-07-28 | Single-Cell Analysis Reclassifies Eczematous Mycosis Fungoides as Severe Atopic Dermatitis 2259810
Abstract Introduction Mycosis fungoides (MF), the prevalent subtype of cutaneous T-cell lymphoma (CTCL), primarily affects the skin and progresses systemically over time. Early-stage MF diagnosis relies on immunohistochemistry, T cell receptor (TCR) gene rearrangement testing, and clinical evaluation. However, in the clinic settings, we observe eczematous MF (eMF) patients who meet early-stage MF diagnostic criteria but exhibit phenotypes resembling atopic dermatitis (AD), and refractory to dupilumab. This study investigates the molecular characteristics of eMF in comparison to AD and classic MF, providing insights into its distinct pathophysiology and potential therapeutic implications. Methods Skin biopsies were collected from seven AD patients and eleven eMF patients. Paired single-cell RNA sequencing (scRNA-seq) and single-cell TCR sequencing (scTCR-seq) were conducted to evaluate transcriptional profiles and T-cell clonality. Publicly available MF and AD scRNA-seq data were used for comparative analysis. In addition, spatial transcriptomic profiling was performed to validate. Results Comparative transcriptomic analysis showed that the molecular profiles of T cells in eMF resembled those in AD rather than in conventional MF. Furthermore, in eMF, we observed oligoclonal T-cell expansions, which were not found in conventional MF both in scRNA-seq and spatial transcriptomic data. These expanded cells were predominantly Th22 cells, identified as the primary producers of IL-13, a key cytokine in AD pathophysiology. Conclusion eMF diagnostic phenotype resembles conventional MF, and AD primarily due to the hyperproliferation of Th22 cells and their expression of IL-13. In this context, this mechanism underscores the superior efficacy of Upadacitinib, which could target Th22 differentiation, over Dupilumab. As a result, our findings indicate that eMF is not cancer, but a Th22-mediated AD endotype. Funding Source n/a Topic Categories Immune Mechanisms of Human Disease (HUM)
2026-05-21 | Primary cutaneous lymphomas in children: a single-center retrospective analysis and narrative review of the literature.
Primary cutaneous lymphomas (PCLs) are uncommon in children, with mycosis fungoides (MF), lymphomatoid papulosis (LyP), and primary cutaneous small/medium CD4+ T-cell lymphoproliferative disorder (PCSM-TCLPD) representing the most frequent entities. Due to their rarity, available data derive mainly from case reports and small series, and diagnostic delays are frequent. This study aimed to describe the clinical, histopathological, and therapeutic features of pediatric PCLs in a single Italian referral centre and compare them with the literature evidence. We conducted a single-center, retrospective observational study including patients aged ≤16 years with a histologically confirmed diagnosis of PCLs, followed for at least six months at the Dermatology Unit of the University Hospital of Bologna between 2002 and 2024. Clinical, histological, therapeutic, and follow-up data were collected and analyzed. Among 354 PCL patients, 10 pediatric cases were identified: six MF, three LyP, and one PCSM-TCLPD. The mean age at diagnosis was 9.1 years. MF cases were mostly early-stage (IA, 5/6), with folliculotropic (67%), hypopigmented (50%), and classic (50%) variants; all were treated with topical corticosteroids and/or PUVA, with good long-term outcomes (67% complete remission). LyP patients presented at younger ages (mean 5.7 years) with type A (N.=2) and D (N.=1) subtypes; all achieved complete remission despite recurrences, one requiring methotrexate. The single PCSM-TCLPD case was cured with surgical excision. After a mean follow-up of 8.2 years, all patients were alive, most disease-free. Pediatric PCLs are rare but generally indolent, with an excellent prognosis. However, their clinical heterogeneity and diagnostic delay highlight the importance of early biopsy, integrated clinicopathological assessment, and long-term follow-up. Multicenter studies are needed to establish tailored treatment algorithms for children.
2026-02-06 | A historical review of mycosis fungoides: from Alibert to mogamulizumab.
In 1806, French physician Baron Jean-Louis Alibert saw a man with a desquamating rash and skin tumours. Alibert considered this to be a variant of yaws. In 1829 Alibert named the condition mycosis fungoides (MF), meaning 'mushroom-like fungal disease'. Over 100 years later, French dermatologist Albert Sézary published papers from 1938 to 1949 detailing a mysterious disease containing 'cellules monstrueuses', describing cutaneous 'monster cells'. In 1961, these clinical findings were collated together into 'Sézary syndrome'. In the 1870s English dermatologist William Tilbury Fox published a dermatology atlas detailing cases similar to what we know now as MF, with the name 'fibroma fungoides'. The atlas described MF as a type of fungus, before giving a description of yaws and painting a clinical picture that differed from that of a lymphoma. Over the twentieth century, our understandings of the origins of MF were changing and by 1975 the classification system and term we now recognize as cutaneous T-cell lymphoma (CTCL) was developed. Neoplastic cells have been thought to arise from chronic activation of T cells via antigen-presenting cells due to inappropriate cytokines and C-C chemokine receptors. In 2018, the World Health Organization and European Organisation for Research and Treatment of Cancer officially recognized four variants of MF. These are the classic Alibert-Bazin variant and its three variants: folliculotropic MF, pagetoid reticulosis and granulomatous slack skin. Developments in immunohistochemistry for the T-cell receptor gene in the 1990s improved the diagnosis of CTCL; however, diagnosis is still challenging. Advanced MF therapies have evolved from cytotoxic chemotherapy to novel monoclonal antibodies such as mogamulizumab, targeting proteins on T-cell lymphoma cells.
2025-12-24 | Central Nervous System Progression in Folliculotropic Mycosis Fungoides.
Central nervous system (CNS) involvement by cutaneous T-cell lymphomas (CTCL) is exceptionally rare and is associated with a poor prognosis. Folliculotropic mycosis fungoides (FMF) is a rare subtype of CTCL and often has more aggressive clinical behavior compared to classic MF. The risk factors for CNS progression in patients with primary CTCL are not well understood. We present the case of a 75-year-old male with a history of Stage IA FMF, who developed progressive neurologic and functional decline over six months. Workup revealed marked eosinophilia, and CSF analysis showed monoclonal T-cell population with positive T-cell receptor (TCR) gene rearrangement. Flow cytometry further showed an atypical CD4+ T-cell population with loss of CD7, consistent with the immunophenotype of patient's cutaneous MF, supporting secondary CNS involvement. An MRI of the brain showed T2 hyperintensity in the pons and right middle cerebellar peduncle, with low signal intensity throughout the bone marrow of the skull, concerning for CNS progression of FMF. The patient was started on high-dose steroids, which led to improvement in eosinophilia. Due to transaminitis, high-dose methotrexate therapy was deferred, and the patient was initiated on intrathecal (IT) chemotherapy with methotrexate and cytarabine. Following five cycles of IT chemotherapy, the patient's neurologic status significantly improved, and CSF analysis showed resolution of the atypical T-cell population. This case highlights the rare occurrence of CNS progression of FMF, even in the absence of lymphatic involvement and with well-controlled skin manifestations, and underscores the role of IT chemotherapy in managing this complication.
2025-09-26 | PAI-1 in Skin Malignancies: a Central Regulator of Tumor Progression and Therapeutic Resistance.
Plasminogen activator inhibitor-1 (PAI-1) plays a multifaceted and central role in the tumor biology of various skin malignancies. Beyond its classical function in fibrinolysis, PAI-1 contributes to tumor progression by promoting immunosuppression, angiogenesis, cellular senescence, and tissue remodeling. Its expression is particularly elevated in aggressive disease stages across cutaneous melanoma, cutaneous squamous cell carcinoma (cSCC), cutaneous angiosarcoma (CAS), and mycosis fungoides (MF), and is associated with poor clinical outcomes. The ability of PAI-1 to induce senescence-associated secretory phenotype (SASP), modulate PD-L1 expression, and recruit tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) suggests a key role in shaping the immunosuppressive tumor microenvironment (TME). This positions PAI-1 as both a potential biomarker for disease progression and a therapeutic target for restoring immune responsiveness, especially in tumors resistant to immune checkpoint inhibitors (ICIs). The PAI-1 inhibitor TM5614 has demonstrated promising activity in early clinical studies, particularly in anti-PD-1-refractory melanoma, and is currently under evaluation in multiple Phase II and III trials. Future strategies should focus on patient stratification using biomarkers such as SASP factors and PAI-1 levels, as well as rational combination therapies targeting interconnected pathways like IL-17/IL-23, AhR, and senescence signaling. Overall, PAI-1 inhibition offers a novel and mechanistically grounded approach to improve outcomes in skin cancers characterized by therapy resistance and an immunosuppressive microenvironment.
Access all drug discovery papers and probability of success in trials forecasts:
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Drug Discovery Landscape
7 orphan drug designations for Classic mycosis fungoides, including 2 approved therapies.
7 orphan drug designations for Classic mycosis fungoides, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
priliximab | antibodies | FDA | 2017-09-18 | — | Onco Therapies, Inc. |
MRG-106 oligonucleotide inhibitor of microRNA miR-155-5p | oligonucleotides | FDA | 2017-03-30 | — | miRagen Therapeutics, Inc. |
brentuximab vedotin [Adcetris] | antibodies | FDA | 2012-11-19 | 2017-11-09 | Seagen Inc. |
naloxone | small molecules | FDA | 2010-11-23 | — | Elorac, Inc. |
meclorethamine [Valchlor] | small molecules | FDA | 2004-08-17 | 2013-08-23 | Helsinn Birex Pharmaceuticals Ltd. |
human anti-CD4 monoclonal antibody | antibodies | FDA | 2004-08-13 | — | Emergent Product Development Seattle, LLC |
Methotrexate with laurocapram | small molecules | FDA | 1990-10-15 | — | Echo Therapeutics, Ltd. |
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