RARE DISEASE
Primary cutaneous CD30+ T-cell lymphoproliferative disease
Primary cutaneous CD30+ T-cell lymphoproliferative disease
Primary cutaneous CD30+ T-cell lymphoproliferative disease
Synonyms: Primary cutaneous Ki-1+ T-cell lymphoproliferative disease
Synonyms: Primary cutaneous Ki-1+ T-cell lymphoproliferative disease
Synonyms: Primary cutaneous Ki-1+ T-cell lymphoproliferative disease
Drug discovery
2
drugs
With orphan designations
Overview
Primary cutaneous CD30+ T-cell lymphoproliferative disorders (pcCD30+ T-LPD) encompass lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL), and borderline cases. These neoplasms present as recurrent self-resolving papulonodules (LyP) or persistent tumors (pcALCL) with CD30+ lymphoid infiltration. Diagnosis requires clinicopathological correlation to exclude systemic CD30+ lymphomas. While most exhibit indolent behavior with excellent prognosis, LyP carries a 20% lifetime risk of associated malignancies, and pcALCL may rarely progress extracutaneously [1][6][14].
Therapies
First-line: Observation for limited disease, skin-directed therapies (topical steroids, radiation) [3][14]
Systemic agents: Low-dose methotrexate, interferon-α, or CD30-targeted brentuximab vedotin for multifocal/recurrent lesions [3][10][18]
Reserved chemotherapy/radiation for extracutaneous spread or refractory pcALCL [6][14]
Categories: rare hematological diseases, rare neoplastic diseases, rare skin diseases, rare transplant-related disorders
Research Papers
191 drug discovery papers about Primary cutaneous CD30+ T-cell lymphoproliferative disease, with 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
191 drug discovery papers about Primary cutaneous CD30+ T-cell lymphoproliferative disease, with 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2025-11-26 | JAK2 Fusions in Adult Patients With Mycosis Fungoides and CD30 Lymphoproliferative Disorders.
Janus kinase 2 (JAK2) gene fusions characterize cytotoxic cutaneous T-cell lymphoma (CTCL) including primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (pcAETCL). The identification of these fusions is rarely reported in indolent CTCL. To characterize patients with CTCL to better understand the diagnostic, prognostic, and therapeutic significance of this molecular alteration in CTCL. A retrospective case series of patients with CTCL with JAK2 fusions identified between the years 2000 and 2025. Fusions were identified by a custom RNA sequencing panel and by a targeted hybrid-capture-based next-generation DNA sequencing-based panel. The study included a single referral cancer center in the US. Overall, 43 patients (12 female [27.9%] and 31 male individuals [72.1%]; median [range] age, 45 [16-65] years) with CTCL who were found to have JAK2 gene fusions during evaluation and follow-up were included. Thirty-eight of the 43 identified patients (88.4%) with fusions of JAK2 and 10 different gene partners (most frequently ATXN2L, CAPRIN1, and PCM1) had mycosis fungoides (MF), CD30-positive lymphoproliferative disorders (LPD), or overlap presentations, whereas 4 pcAETCL and 1 peripheral T-cell lymphoma not otherwise specified were identified. Secondary genetic events included mutations of epigenetic and transcriptional regulators. Neither mutational burden, type, or fusion partner distinguished cases with early-stage or aggressive CTCL. This case series found that JAK2 fusions were seen in aggressive cytotoxic CTCL as well as in T-cell lymphomas with more indolent behavior, possibly representing a precursor lesion to aggressive evolution with age and comorbidities. The prominence of these fusions supports a potentially larger role for JAK2 targeting in patients with early-stage MF, CD30-positive LPD, or overlap presentations.
2025-11-03 | Synergistic Remission of refractory cutaneous T-cell lymphoma by linperlisib plus venetoclax via targeting the PI3K/AKT/CREB-BCL-2/MCL-1 signaling axis.
Abstract Background: Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of lymphoproliferative malignancies arising from skin-homing T cells. Its primary subtypes—mycosis fungoides (MF), Sézary syndrome (SS), and CD30+ lymphoproliferative disorders (LPDs) —collectively account for 70% of primary cutaneous lymphomas. Primary cutaneous anaplastic large cell lymphoma (pcALCL), a core CD30+ LPD subtype, forms the CD30+ disease spectrum alongside lymphomatoid papulosis (LyP). Conventional therapies like CHOP show low response rates in advanced/relapsed CTCL, underscoring the urgent need for novel targeted agents and rational combination strategies to overcome resistance. Methods: We report a 67-year-old woman with multiply relapsed pcALCL refractory to CHOP, CHOP plus brentuximab vedotin (BV), and three courses of total skin electron beam therapy (TSEBT), who subsequently initiated combination therapy with linperlisib (PI3Kδ inhibitor) and venetoclax (BCL-2 inhibitor). We first validated the synergistic antitumor effects of linperlisib and venetoclax in vitro. Subsequent transcriptomic profiling identified key mediators and underlying mechanisms, confirmed at transcriptional and protein levels, and validated via rescue experiments. Results: The patient attained CR after two treatment cycles, with relapse-free survival of 584 days. In vitro, linperlisib plus venetoclax significantly enhanced cytotoxicity versus either agent alone, suppressing proliferation and inducing apoptosis. Pathway enrichment analysis of RNA-seq data implicated CREB as a pivotal regulator in the control of PI3K/AKT-dependent apoptosis. The combination synergistically inhibited PI3K/AKT/CREB pathway activity and downregulated the expression of BCL-2 and MCL-1. Rescue experiments showed that the PI3K/AKT/CREB agonist AE-18 markedly reduced linperlisib-induced apoptosis and reversed BCL-2/MCL-1 suppression. Conclusions: In this case, dual PI3Kδ and BCL-2 blockade achieved durable remission after failure of all conventional therapies. Linperlisib suppresses BCL-2/MCL-1 expression by inhibiting the PI3K/AKT/CREB axis, synergizing with venetoclax to overcome resistance. This combination represents a novel therapeutic strategy for achieving durable remission in relapsed pcALCL.
2025-06-27 | DP08 Paediatric-onset lymphomatoid papulosis (LyP) in a 2 year old: a case report exploring the diagnostic difficulty of LyP in children
Abstract Lymphomatoid papulosis (LyP) is a rare primary cutaneous CD30+ T-cell lymphoproliferative disorder. Clinically it is characterized by recurrent erythematous skin nodules occurring at any body site, more commonly on the extremities [Blanchard M, Morren MA, Busschots AM et al. Paediatric-onset lymphomatoid papulosis: results of a multicentre retrospective cohort study on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG). Br J Dermatol 2024; 191: 233–42]. The aetiology is unknown, and hypothesized theories implicate the role of viral illnesses including human T-cell lymphotropic virus 1, herpes simplex virus and endogenous viruses. The peak of incidence is between the fourth and fifth decades, with a slight male predilection. LyP is extremely rare, with an estimated 0.1 to 0.3 cases per 1 million person-years in the paediatric population. However, it accounts for one of the two most common paediatric cutaneous lymphoproliferative disorders alongside mycosis fungoides. LyP provides a diagnostic challenge and requires clinicopathological correlation to avoid misdiagnosis. LyP may mimic many other conditions both benign and malignant. We identified a case of LyP in a 2-year-old boy, which explores the use of close clinicopathological correlation for diagnosis. Initial presentation revealed a nonpruritic papular rash beginning at 8 months old with scattered 2–4-mm papules distributed at the flexures, face and groin. There was evidence of scarring areas where papules had spontaneously resolved. There was no hepatosplenomegaly noted on examination. The patient was otherwise systemically well, meeting developmental milestones. His past medical history included being born preterm at 32 weeks’ + 6 days’ gestation, with a 19-day stay in the neonatal intensive care unit due to respiratory distress syndrome, neonatal hypoglycaemia and jaundice, treated with phototherapy. There was no significant family history. Initial differential diagnoses included pityriasis lichenoides et varioliformis acuta; however, the condition was resistant to topical corticosteroids and oral antibiotics. Two incisional biopsies were arranged, which confirmed a combination of type B and type E LyP. As the rash is widespread, troublesome and causing scarring, the plan is to commence methotrexate; this was delayed as he required chickenpox vaccination prior to commencing. Histologically, LyP is divided into five main subtypes (A to E) recognized by the World Health Organization and European Organisation for Research and Treatment of Cancer. This subdivision has not been clearly linked to disease prognosis and has no implications in management. While topical corticosteroids are the most common treatment adopted, other options include watchful waiting, phototherapy and systemic methotrexate. LyP is associated with increased risk of haematological malignancy, with mycosis fungoides and anaplastic large cell lymphoma being the most common. Clinicians should remain vigilant in diagnosing LyP. Although its course is often benign, the association with haematological malignancy requires both careful clinicopathological correlation for diagnosis and long-term follow-up.
2024-09-20 | Primary cutaneous, epidermotropic mycosis fungoides-like presentation: critical appraisal and description of two novel cases, broadening the spectrum of ALK+ T-cell lymphoma.
Leading from a two-case series, including two patients receiving a diagnosis of epidermotropic T-cell lymphoma, featuring a mycosis fungoides (MF)-like clinical pattern and ALK expression and molecular alteration, we performed a critical appraisal of ALK+ primary cutaneous T-cell lymphomas (pcTCL). Considering our patients and the literature, 32 cases were retrieved, 7 of which featured an MF-like clinical picture over a 4-to-20-year period. MF-like cases show distinctive histology, comprising a predominantly epidermotropic infiltration of small-to-large, atypical-to-pleomorphic, with few anaplastic cells, negligible-to-intense CD30-expression, and a CD4+/cytotoxic granule+ phenotype. These features should prompt a search for ALK expression captured by the ALK D5F3 clone. Bona fide ALK+ pcTCL is very rare, and existent data suggest the presence of a broader pattern of disease, including instances mimicking MF and/or primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma. The major challenges in dealing with this subset include prodromal phases, misinterpreted as inflammatory dermatosis or parapsoriasis/early phase MF both clinically and histologically, while recognition of its ALK-driven biology is hampered both by the unusual clinic-pathologic pattern of the disease, which stands apart from the classical (i.e., nodal) picture of ALK+ anaplastic large cell lymphoma and by the low sensitivity of ALK1 clone. Data on its optimal management are far from being conclusive: An MF-like approach is currently chosen, but depending on CD30 and, most notably, ALK expression, a targeted therapy could be envisaged in advanced stages, as clinical response to ALK inhibition was documented in one patient.
2024-07-25 | Immunobiology and treatment of cutaneous T-cell lymphoma.
Primary cutaneous T cell lymphomas (CTCL) are a heterogenous group of non-Hodgkin lymphomas derived from skin-homing T cells. These include mycosis fungoides and its leukemic variant Sezary syndrome, as well as the CD30+ lymphoproliferative disorders. In this review, we provide a summary of the current literature on CTCL, with a focus on the immunopathogenesis and treatment of mycosis fungoides and Sezary syndrome. Recent advances in immunology have provided new insights into the biology of malignant T cells. This in turn has led to the development of new therapies that modulate the immune system to facilitate tumor clearance or target specific aspects of tumor biology.
cell therapies
2024-02-10 | Primary Cutaneous CD30-Positive Lymphoproliferative Disorders-Current Therapeutic Approaches with a Focus on Brentuximab Vedotin.
One of the most common subgroups of cutaneous T-cell lymphomas is that of primary cutaneous CD30-positive lymphoproliferative disorders. The group includes lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL), as well as some borderline cases. Recently, significant progress has been made in understanding the genetics and treatment of these disorders. This review article summarises the clinical evidence supporting the current treatment options for these diseases. Recent years have seen the introduction of novel agents into clinical practice; most of these target CD30, such as anti-CD30 monoclonal antibodies and conjugated antibodies (brentuximab vedotin), bispecific antibodies and cellular therapies, particularly anti-CD30 CAR-T cells. This paper briefly reviews the biology of CD30 that makes it a good therapeutic target and describes the anti-CD30 therapies that have emerged to date.
2013-12-01 | Allogeneic hematopoietic stem cell transplantation in mycosis fungoides
Mycosis Fungoides is typically an indolent disease in early stages. However, approximately 30% of patients have advanced staged disease at presentation and 20% will develop it at some time. These patients have a poorer prognosis with a median survival of 2-4 years. The only curative option for mycosis fungoides may be hematopoietic allogeneic stem cell transplantation. We report the case of a patient with mycosis fungoides in an advanced stage (IIB), refractory to treatment options. She underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The patient remains in complete remission nineteen months after allo-HSCT. Allogeneic transplantation can alter the natural history of mycosis fungoides and should be considered in patients who have refractory disease or short-lived responses with standard therapies.
2010-06-01 | Photopheresis in the treatment of the erythrodermic CTCL patient
Extracorporeal photopheresis (ECP) is an apheresis based therapy which was originally conceived by Edelson et al. in 1983 for the systemic treatment of cutaneous T-cell lymphoma (CTCL), the Sezary syndrome variant. Since its original concept until 2010 it has been found to be of significant clinical value in this primary indication as well as additional T-cell mediated diseases. Soon after its introduction it was approved in 1985 by the FDA (USA) for the palliative treatment of CTCL. In 2006 it was included in the EORTC CLTF treatment guidelines to be one of the first line therapies for the treatment of the Sezary syndrome (erythrodermic) variant of CTCL. Evidence collected in the past 20 years in over 1000 CTCL patients has demonstrated that this treatment modality can have a very significant effect on the clinical course of a subset of CTCL patients, particularly the erythrodermic, Sezary Syndrome variant. Newest clinical studies and data not only support the published evidence for its efficacy as a monotherapy but also as a therapy that can be combined with multiple biological response modifiers including interferon alfa, GMCSF, IL12, Interferon Gamma, as well as total skin electron therapy (TSEB) and systemic chemotherapy. The evidence available, though positive, remains controversial within the medical community. A number of very well-designed multi-center trials which have been lacking since the first publication by Edelson et al. are presently being planned so that hopefully a number of open questions will be resolved with greater clarity in the near future. The definition of the exact entry treatment criteria which promise optimal response with optimal treatment frequency remain equally to be conclusively defined. Early intervention within 2 years of the appearance of first symptoms, low tumor load, absence of high count leukemia and absence of further transformation are criteria that help predict patients most likely to respond but do not exclude necessarily patients that have more advanced disease and who may be candidates for combination therapy. This innovative approach for the treatment of CTCL has certainly opened new avenues of therapy and thought in photoimmunology and photomedicine. Clearly the very low side effect profile of this therapy has made it more attractive than the chemotherapeutic and immunosuppressive substances that are presently available or in experimental protocols. If and when the mechanisms of action are further better understood and appropriate studies investigating different treatment schedules and different combination therapies and modifications of its present form are performed, the place of photopheresis in the therapeutics of CTCL, particularly the erythrodermic Sezary syndrome variant, as well as other T-cell mediated diseases and oncology will be better defined.
oligonucleotides
2022-10-08 | The cross-talk between miRNAs and JAK/STAT pathway in cutaneous T cell lymphoma: Emphasis on therapeutic opportunities
Mycosis Fungoides (MF) and Sézary Syndrome (SS) belong to a wide spectrum of T cell lymphoproliferative disorders collectively termed cutaneous T cell lymphomas (CTCL). CTCLs represent an archetype of heterogeneous and dynamically variable lymphoproliferative neoplasms typified by distinct clinical, histological, immunophenotypic, and genetic features. Owing to its complex dynamics, the pathogenesis of CTCL remains elusive. However, in recent years, progress in CTCL classification combined with next-generation sequencing analyses has broadened the genetic and epigenetic spectrum of clearly defined CTCL entities such as MF and SS. Several large-scale genome studies have identified the polygenic nature of CTCL and unveiled an idiosyncratic mutational landscape involving genetic aberrations, epigenetic alterations, cell cycle dysregulation, apoptosis, and the constitutive activation of T cell/NF-κB/JAK-STAT signaling pathways. In this review, we summarize the evolving insights on how the intrinsic epigenetic events driven by dysregulated miRNAs, including the oncogenic and tumor-suppressive miRNAs, influence the pathogenesis of MF and SS. We also focus on the interplay between the JAK/STAT pathway and miRNAs in CTCL as well as the significance of the miRNA/STAT axis as a relevant pathogenetic mechanism underlying CTCL initiation and progression. Based on these biologic insights, the current status and recent progress on novel therapies with a strong biological rationale, including miRNA-targeted molecules and JAK/STAT-targeted therapy for CTCL management, are discussed.
2015-03-03 | MiRNAs in primary cutaneous lymphomas
Abstract Primary cutaneous lymphomas ( PCL ) compose a heterogeneous disease with still unknown aetiology and mechanisms of development. Micro RNA s (mi RNA s) have recently been discovered as one of the crucial players in PCL carcinogenesis through post‐transcriptional regulation of gene expression. mi RNA s have been reported to be frequently deregulated in PCL s and their biological significance has been further confirmed in multiple functional experiments. Such studies help us understand molecular pathogenesis of PCL . In this review, we summarize expression of mi RNA s and their corresponding roles in different subtypes of PCL . With expression and functional role of mi RNA s revealed, investigation of their possible clinical use as biomarkers for diagnosis, prediction of prognosis and target for therapies, will be a promising area in the future.
2013-10-07 | Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report
The etiology of primary cutaneous anaplastic large-cell CD30+ lymphoma is largely unknown, and although an infectious involvement has been suspected, the implication of infectious agents in its pathogenesis is still unclear.We report the case of a HIV-negative patient referred to our hospital with a rapidly enlarging skin tumor on her upper eyelid. Surgical excision was performed and histological analysis evidenced a primary cutaneous anaplastic large-cell lymphoma. Due to the ocular localization and to the prominent angiogenic component of the lesion, molecular analyses for the detection of Chlamydophila pneumoniae and HHV8 were performed, revealing the presence of an infection by both pathogens in surgical biopsy and in peripheral blood mononuclear cells.These findings suggest for the first time a possible association of C. pneumoniae and/or HHV8 infection, or both together, with primary cutaneous anaplastic large-cell lymphoma in non-immunocompromised and HIV-negative subjects. This potential pathogenic association, if confirmed, could provide potential indications for future therapy.
antibodies
2026-05-27 | Primary Cutaneous Anaplastic Large Cell Lymphoma: A Review of Diagnosis and Treatment for the General Oncologist.
Primary cutaneous anaplastic large cell lymphoma (pcALCL) is a type of cutaneous T-cell lymphoma (CTCL) classified as a CD30+ lymphoproliferative disorder along with lymphomatoid papulosis. Although it is the second most common subtype of CTCL after mycosis fungoides/Sézary syndrome, it remains rare, with an incidence of fewer than 0.5 cases per million person-years. Despite its histologic similarity to systemic anaplastic large cell lymphoma, pcALCL follows a largely indolent course with excellent outcomes, with disease-specific survival rates of 86-95% in contemporary series. This narrative review summarizes the clinical presentation, diagnostic evaluation, and management of pcALCL based on a semi-structured literature search, with emphasis on prospective studies and clinically relevant retrospective data. Diagnosis remains challenging due to overlap with other CD30-positive lymphoproliferative disorders and reactive conditions, requiring careful clinicopathologic correlation and exclusion of systemic disease. While regional lymph node involvement may be present, available evidence suggests it does not significantly impact prognosis, highlighting the importance of avoiding overtreatment. Management strategies are guided by disease extent, with strong evidence supporting skin-directed therapies, particularly radiation, for localized disease. For multifocal or relapsed disease, brentuximab vedotin demonstrates the most robust prospective data and has reshaped the treatment landscape; however, alternative systemic therapies, including methotrexate and retinoids, remain relevant in selected patients. Overall, current management is supported largely by non-randomized data, and key gaps remain in risk stratification, optimal sequencing of therapies, and management of uncommon aggressive variants.
2025-12-05 | Primary cutaneous CD30 + lymphoproliferative disorders
The CD30 antigen is a cytokine receptor belonging to the tumor necrosis factor receptor superfamily. The antigen was initially described within Reed–Sternberg and Hodgkin cells of Hodgkin lymphoma and subsequently identified within neoplastic cells of a new group of non–Hodgkin lymphomas (anaplastic large cell lymphoma). The term “cutaneous CD30 + lymphoproliferative disorders” has been subsequently proposed to denote a group of primary cutaneous T-cell lymphoproliferative disorders characterized by expression of the CD30 antigen and favorable prognosis, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. Lymphomatoid papulosis is defined as a chronic, recurrent, self-healing eruption of papules and small nodules with the histopathologic features of a cutaneous T-cell lymphoma (“rhythmic paradoxical eruption”). In some of the patients with lymphomatoid papulosis and associated lymphomas, the same clone of neoplastic T lymphocytes has been identified in lesions of the two lymphoproliferative disorders, raising the question of a common origin of the diseases.
2025-11-18 | Anaplastic large cell lymphoma in the penis: a case report and review of literature.
Anaplastic large cell lymphoma is a distinct subtype of mature T cell lymphoma characterized by strong CD30 expression. While primary penile lymphomas are rare, they are most commonly of B cell origin, making primary T cell lymphomas of the penis an exceptional finding that can pose significant diagnostic challenges. A 60-year-old Arab male presented with multiple, rapidly growing nodules on the penile body that had developed over 4 weeks. A comprehensive workup, including biopsy and immunohistochemistry, confirmed a diagnosis of localized, anaplastic lymphoma kinase-negative primary cutaneous anaplastic large cell lymphoma. Staging via positron emission tomography-computed tomography revealed no systemic involvement. The patient was treated with six cycles of brentuximab vedotin plus cyclophosphamide, doxorubicin, vincristine, and prednisone, achieving a complete metabolic response (Deauville score of 2) as assessed by post-treatment positron emission tomography-computed tomography imaging. This case highlights the diagnostic challenge posed by rare penile lesions and, more importantly, the therapeutic dilemma of selecting an appropriate treatment for a disease that is localized yet multifocal. The successful outcome with systemic brentuximab vedotin plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, a deviation from standard guidelines for unifocal primary cutaneous anaplastic large cell lymphoma, underscores the need for individualized treatment strategies and further research to establish risk-adapted guidelines for this rare clinical entity.
2025-07-01 | CASES OF PRIMARY CUTANEOUS ANAPLASTIC LARGE CELL LYMPHOMA TREATED WITH SYSTEMIC OR LOCAL THERAPY
Primary Cutaneous Anaplastic Large Cell Lymphoma (PC-ALCL) is a CD30+ peripheral T-cell lymphoproliferative disorder without systemic involvement. It accounts for approximately 8% of cutaneous lymphoma cases. Most patients with PC-ALCL present with slow-growing, solitary or grouped skin nodules, and in some cases, regional lymph node involvement is observed. A 61-year-old male patient presented to our clinic with swelling and edema of the right lower lip, along with a 57 cm draining ulcerative skin lesion in the suprasternal region. The patient had previously received six cycles of treatment for T-cell lymphoma at an outside center. A PET-CT scan identified a soft tissue lesion in the skin/subcutaneous tissue at the level of the right thyroid lobe and isthmus, measuring 57*15*52 mm, with a maximum SUV of 34. Biopsies taken from the lower lip and suprasternal skin were reported as primary cutaneous anaplastic large cell lymphoma. CD30 expression was found to be 95%. The patient was started on brentuximab vedotin along with the GDP protocol. After two cycles of treatment, improvement in the skin lesions was observed. A 61-year-old male patient presented to our clinic with a complaint of a lesion on the anterior surface of the right tibia, measuring approximately 10*10 cm. The biopsy taken from the lesion was reported as CD30+ primary cutaneous anaplastic large cell lymphoma. A PET-CT scan revealed moderately hypermetabolic lymph nodes with thick cortices in the right iliac and inguinal lymphatic chains. Radiotherapy was applied to the area of the primary lesion and the regional lymph nodes, and improvement in the skin lesions was observed with treatment. We aimed to discuss the outcomes of applying localized radiotherapy or systemic treatment to two patients with PC-ALCL who presented to our clinic: one with a relapse and the other with a new diagnosis. Brentuximab vedotin is effective in this disease. Since disease control could not be fully achieved with localized radiotherapy alone, we believe that the combination of systemic therapy and radiotherapy may be an important treatment option for these patients. Further large-scale case series are needed to guide treatment.
2025-04-01 | Primary Cutaneous CD30+ Lymphoproliferative Disorders in South Korea: A Nationwide, Multi-Center, Retrospective, Clinical, and Prognostic Study.
Primary cutaneous CD30+ lymphoproliferative disorders (pcCD30-LPDs) are a diseases with various clinical and prognostic characteristics. Increasing our knowledge of the clinical characteristics of pcCD30-LPDs and identifying potential prognostic variables in an Asian population. Clinicopathological features and survival data of pcCD30-LPD cases obtained from 22 hospitals in South Korea were examined. A total of 413 cases of pcCD30-LPDs (lymphomatoid papulosis [LYP], n=237; primary cutaneous anaplastic large cell lymphoma [C-ALCL], n=176) were included. Ninety percent of LYP patients and roughly 50% of C-ALCL patients presented with multiple skin lesions. Both LYP and C-ALCL affected the lower limbs most frequently. Multiplicity and advanced T stage of LYP lesions were associated with a chronic course longer than 6 months. Clinical morphology with patch lesions and elevated serum lactate dehydrogenase were significantly associated with LPDs during follow-up in LYP patients. Extracutaneous involvement of C-ALCL occurred in 13.2% of patients. Lesions larger than 5 cm and increased serum lactate dehydrogenase were associated with a poor prognosis in C-ALCL. The survival of patients with C-ALCL was unaffected by the anatomical locations of skin lesions or other pathological factors. The multiplicity or size of skin lesions was associated with a chronic course of LYP and survival among patients with C-ALCL.
other
2023-10-24 | What Is New in Cutaneous T Cell Lymphoma?
This review focuses on updates in prognosis, pathogenesis, and treatment of cutaneous T cell lymphoma (CTCL).Cohort studies indicate imaging may be necessary in early-stage CTCL. Risk factors for progression of CTCL have been identified. Interactions between malignant cells and the tumor microenvironment (TME) and the skin microbiome advance the understanding of pathogenesis and tumor cell dissemination. Studies support a hypothesis of circulating malignant tumor cells. MicroRNA (miR) influence tumor progression and prognosis; the IL22-STAT3-CCL20 cascade may be a novel target. IL-4, IL-5, and IL-31 cytokines are relevant for pruritus and could be targets for therapeutic interventions. Systemic therapies, such as JAK inhibitors, targeted antibodies, and checkpoint inhibitors, show promise in advanced stages. Allogenic hematopoietic stem cell transplantation provides a potential curative option for patients. Further investigations of prognosis and translational research are necessary to improve stratification of patients for treatment.
small molecules
2025-11-26 | JAK2 Fusions in Adult Patients With Mycosis Fungoides and CD30 Lymphoproliferative Disorders.
Janus kinase 2 (JAK2) gene fusions characterize cytotoxic cutaneous T-cell lymphoma (CTCL) including primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (pcAETCL). The identification of these fusions is rarely reported in indolent CTCL. To characterize patients with CTCL to better understand the diagnostic, prognostic, and therapeutic significance of this molecular alteration in CTCL. A retrospective case series of patients with CTCL with JAK2 fusions identified between the years 2000 and 2025. Fusions were identified by a custom RNA sequencing panel and by a targeted hybrid-capture-based next-generation DNA sequencing-based panel. The study included a single referral cancer center in the US. Overall, 43 patients (12 female [27.9%] and 31 male individuals [72.1%]; median [range] age, 45 [16-65] years) with CTCL who were found to have JAK2 gene fusions during evaluation and follow-up were included. Thirty-eight of the 43 identified patients (88.4%) with fusions of JAK2 and 10 different gene partners (most frequently ATXN2L, CAPRIN1, and PCM1) had mycosis fungoides (MF), CD30-positive lymphoproliferative disorders (LPD), or overlap presentations, whereas 4 pcAETCL and 1 peripheral T-cell lymphoma not otherwise specified were identified. Secondary genetic events included mutations of epigenetic and transcriptional regulators. Neither mutational burden, type, or fusion partner distinguished cases with early-stage or aggressive CTCL. This case series found that JAK2 fusions were seen in aggressive cytotoxic CTCL as well as in T-cell lymphomas with more indolent behavior, possibly representing a precursor lesion to aggressive evolution with age and comorbidities. The prominence of these fusions supports a potentially larger role for JAK2 targeting in patients with early-stage MF, CD30-positive LPD, or overlap presentations.
2025-11-03 | Synergistic Remission of refractory cutaneous T-cell lymphoma by linperlisib plus venetoclax via targeting the PI3K/AKT/CREB-BCL-2/MCL-1 signaling axis.
Abstract Background: Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of lymphoproliferative malignancies arising from skin-homing T cells. Its primary subtypes—mycosis fungoides (MF), Sézary syndrome (SS), and CD30+ lymphoproliferative disorders (LPDs) —collectively account for 70% of primary cutaneous lymphomas. Primary cutaneous anaplastic large cell lymphoma (pcALCL), a core CD30+ LPD subtype, forms the CD30+ disease spectrum alongside lymphomatoid papulosis (LyP). Conventional therapies like CHOP show low response rates in advanced/relapsed CTCL, underscoring the urgent need for novel targeted agents and rational combination strategies to overcome resistance. Methods: We report a 67-year-old woman with multiply relapsed pcALCL refractory to CHOP, CHOP plus brentuximab vedotin (BV), and three courses of total skin electron beam therapy (TSEBT), who subsequently initiated combination therapy with linperlisib (PI3Kδ inhibitor) and venetoclax (BCL-2 inhibitor). We first validated the synergistic antitumor effects of linperlisib and venetoclax in vitro. Subsequent transcriptomic profiling identified key mediators and underlying mechanisms, confirmed at transcriptional and protein levels, and validated via rescue experiments. Results: The patient attained CR after two treatment cycles, with relapse-free survival of 584 days. In vitro, linperlisib plus venetoclax significantly enhanced cytotoxicity versus either agent alone, suppressing proliferation and inducing apoptosis. Pathway enrichment analysis of RNA-seq data implicated CREB as a pivotal regulator in the control of PI3K/AKT-dependent apoptosis. The combination synergistically inhibited PI3K/AKT/CREB pathway activity and downregulated the expression of BCL-2 and MCL-1. Rescue experiments showed that the PI3K/AKT/CREB agonist AE-18 markedly reduced linperlisib-induced apoptosis and reversed BCL-2/MCL-1 suppression. Conclusions: In this case, dual PI3Kδ and BCL-2 blockade achieved durable remission after failure of all conventional therapies. Linperlisib suppresses BCL-2/MCL-1 expression by inhibiting the PI3K/AKT/CREB axis, synergizing with venetoclax to overcome resistance. This combination represents a novel therapeutic strategy for achieving durable remission in relapsed pcALCL.
2025-06-27 | DP08 Paediatric-onset lymphomatoid papulosis (LyP) in a 2 year old: a case report exploring the diagnostic difficulty of LyP in children
Abstract Lymphomatoid papulosis (LyP) is a rare primary cutaneous CD30+ T-cell lymphoproliferative disorder. Clinically it is characterized by recurrent erythematous skin nodules occurring at any body site, more commonly on the extremities [Blanchard M, Morren MA, Busschots AM et al. Paediatric-onset lymphomatoid papulosis: results of a multicentre retrospective cohort study on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG). Br J Dermatol 2024; 191: 233–42]. The aetiology is unknown, and hypothesized theories implicate the role of viral illnesses including human T-cell lymphotropic virus 1, herpes simplex virus and endogenous viruses. The peak of incidence is between the fourth and fifth decades, with a slight male predilection. LyP is extremely rare, with an estimated 0.1 to 0.3 cases per 1 million person-years in the paediatric population. However, it accounts for one of the two most common paediatric cutaneous lymphoproliferative disorders alongside mycosis fungoides. LyP provides a diagnostic challenge and requires clinicopathological correlation to avoid misdiagnosis. LyP may mimic many other conditions both benign and malignant. We identified a case of LyP in a 2-year-old boy, which explores the use of close clinicopathological correlation for diagnosis. Initial presentation revealed a nonpruritic papular rash beginning at 8 months old with scattered 2–4-mm papules distributed at the flexures, face and groin. There was evidence of scarring areas where papules had spontaneously resolved. There was no hepatosplenomegaly noted on examination. The patient was otherwise systemically well, meeting developmental milestones. His past medical history included being born preterm at 32 weeks’ + 6 days’ gestation, with a 19-day stay in the neonatal intensive care unit due to respiratory distress syndrome, neonatal hypoglycaemia and jaundice, treated with phototherapy. There was no significant family history. Initial differential diagnoses included pityriasis lichenoides et varioliformis acuta; however, the condition was resistant to topical corticosteroids and oral antibiotics. Two incisional biopsies were arranged, which confirmed a combination of type B and type E LyP. As the rash is widespread, troublesome and causing scarring, the plan is to commence methotrexate; this was delayed as he required chickenpox vaccination prior to commencing. Histologically, LyP is divided into five main subtypes (A to E) recognized by the World Health Organization and European Organisation for Research and Treatment of Cancer. This subdivision has not been clearly linked to disease prognosis and has no implications in management. While topical corticosteroids are the most common treatment adopted, other options include watchful waiting, phototherapy and systemic methotrexate. LyP is associated with increased risk of haematological malignancy, with mycosis fungoides and anaplastic large cell lymphoma being the most common. Clinicians should remain vigilant in diagnosing LyP. Although its course is often benign, the association with haematological malignancy requires both careful clinicopathological correlation for diagnosis and long-term follow-up.
2024-09-20 | Primary cutaneous, epidermotropic mycosis fungoides-like presentation: critical appraisal and description of two novel cases, broadening the spectrum of ALK+ T-cell lymphoma.
Leading from a two-case series, including two patients receiving a diagnosis of epidermotropic T-cell lymphoma, featuring a mycosis fungoides (MF)-like clinical pattern and ALK expression and molecular alteration, we performed a critical appraisal of ALK+ primary cutaneous T-cell lymphomas (pcTCL). Considering our patients and the literature, 32 cases were retrieved, 7 of which featured an MF-like clinical picture over a 4-to-20-year period. MF-like cases show distinctive histology, comprising a predominantly epidermotropic infiltration of small-to-large, atypical-to-pleomorphic, with few anaplastic cells, negligible-to-intense CD30-expression, and a CD4+/cytotoxic granule+ phenotype. These features should prompt a search for ALK expression captured by the ALK D5F3 clone. Bona fide ALK+ pcTCL is very rare, and existent data suggest the presence of a broader pattern of disease, including instances mimicking MF and/or primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma. The major challenges in dealing with this subset include prodromal phases, misinterpreted as inflammatory dermatosis or parapsoriasis/early phase MF both clinically and histologically, while recognition of its ALK-driven biology is hampered both by the unusual clinic-pathologic pattern of the disease, which stands apart from the classical (i.e., nodal) picture of ALK+ anaplastic large cell lymphoma and by the low sensitivity of ALK1 clone. Data on its optimal management are far from being conclusive: An MF-like approach is currently chosen, but depending on CD30 and, most notably, ALK expression, a targeted therapy could be envisaged in advanced stages, as clinical response to ALK inhibition was documented in one patient.
2024-07-25 | Immunobiology and treatment of cutaneous T-cell lymphoma.
Primary cutaneous T cell lymphomas (CTCL) are a heterogenous group of non-Hodgkin lymphomas derived from skin-homing T cells. These include mycosis fungoides and its leukemic variant Sezary syndrome, as well as the CD30+ lymphoproliferative disorders. In this review, we provide a summary of the current literature on CTCL, with a focus on the immunopathogenesis and treatment of mycosis fungoides and Sezary syndrome. Recent advances in immunology have provided new insights into the biology of malignant T cells. This in turn has led to the development of new therapies that modulate the immune system to facilitate tumor clearance or target specific aspects of tumor biology.
cell therapies
2024-02-10 | Primary Cutaneous CD30-Positive Lymphoproliferative Disorders-Current Therapeutic Approaches with a Focus on Brentuximab Vedotin.
One of the most common subgroups of cutaneous T-cell lymphomas is that of primary cutaneous CD30-positive lymphoproliferative disorders. The group includes lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL), as well as some borderline cases. Recently, significant progress has been made in understanding the genetics and treatment of these disorders. This review article summarises the clinical evidence supporting the current treatment options for these diseases. Recent years have seen the introduction of novel agents into clinical practice; most of these target CD30, such as anti-CD30 monoclonal antibodies and conjugated antibodies (brentuximab vedotin), bispecific antibodies and cellular therapies, particularly anti-CD30 CAR-T cells. This paper briefly reviews the biology of CD30 that makes it a good therapeutic target and describes the anti-CD30 therapies that have emerged to date.
2013-12-01 | Allogeneic hematopoietic stem cell transplantation in mycosis fungoides
Mycosis Fungoides is typically an indolent disease in early stages. However, approximately 30% of patients have advanced staged disease at presentation and 20% will develop it at some time. These patients have a poorer prognosis with a median survival of 2-4 years. The only curative option for mycosis fungoides may be hematopoietic allogeneic stem cell transplantation. We report the case of a patient with mycosis fungoides in an advanced stage (IIB), refractory to treatment options. She underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The patient remains in complete remission nineteen months after allo-HSCT. Allogeneic transplantation can alter the natural history of mycosis fungoides and should be considered in patients who have refractory disease or short-lived responses with standard therapies.
2010-06-01 | Photopheresis in the treatment of the erythrodermic CTCL patient
Extracorporeal photopheresis (ECP) is an apheresis based therapy which was originally conceived by Edelson et al. in 1983 for the systemic treatment of cutaneous T-cell lymphoma (CTCL), the Sezary syndrome variant. Since its original concept until 2010 it has been found to be of significant clinical value in this primary indication as well as additional T-cell mediated diseases. Soon after its introduction it was approved in 1985 by the FDA (USA) for the palliative treatment of CTCL. In 2006 it was included in the EORTC CLTF treatment guidelines to be one of the first line therapies for the treatment of the Sezary syndrome (erythrodermic) variant of CTCL. Evidence collected in the past 20 years in over 1000 CTCL patients has demonstrated that this treatment modality can have a very significant effect on the clinical course of a subset of CTCL patients, particularly the erythrodermic, Sezary Syndrome variant. Newest clinical studies and data not only support the published evidence for its efficacy as a monotherapy but also as a therapy that can be combined with multiple biological response modifiers including interferon alfa, GMCSF, IL12, Interferon Gamma, as well as total skin electron therapy (TSEB) and systemic chemotherapy. The evidence available, though positive, remains controversial within the medical community. A number of very well-designed multi-center trials which have been lacking since the first publication by Edelson et al. are presently being planned so that hopefully a number of open questions will be resolved with greater clarity in the near future. The definition of the exact entry treatment criteria which promise optimal response with optimal treatment frequency remain equally to be conclusively defined. Early intervention within 2 years of the appearance of first symptoms, low tumor load, absence of high count leukemia and absence of further transformation are criteria that help predict patients most likely to respond but do not exclude necessarily patients that have more advanced disease and who may be candidates for combination therapy. This innovative approach for the treatment of CTCL has certainly opened new avenues of therapy and thought in photoimmunology and photomedicine. Clearly the very low side effect profile of this therapy has made it more attractive than the chemotherapeutic and immunosuppressive substances that are presently available or in experimental protocols. If and when the mechanisms of action are further better understood and appropriate studies investigating different treatment schedules and different combination therapies and modifications of its present form are performed, the place of photopheresis in the therapeutics of CTCL, particularly the erythrodermic Sezary syndrome variant, as well as other T-cell mediated diseases and oncology will be better defined.
oligonucleotides
2022-10-08 | The cross-talk between miRNAs and JAK/STAT pathway in cutaneous T cell lymphoma: Emphasis on therapeutic opportunities
Mycosis Fungoides (MF) and Sézary Syndrome (SS) belong to a wide spectrum of T cell lymphoproliferative disorders collectively termed cutaneous T cell lymphomas (CTCL). CTCLs represent an archetype of heterogeneous and dynamically variable lymphoproliferative neoplasms typified by distinct clinical, histological, immunophenotypic, and genetic features. Owing to its complex dynamics, the pathogenesis of CTCL remains elusive. However, in recent years, progress in CTCL classification combined with next-generation sequencing analyses has broadened the genetic and epigenetic spectrum of clearly defined CTCL entities such as MF and SS. Several large-scale genome studies have identified the polygenic nature of CTCL and unveiled an idiosyncratic mutational landscape involving genetic aberrations, epigenetic alterations, cell cycle dysregulation, apoptosis, and the constitutive activation of T cell/NF-κB/JAK-STAT signaling pathways. In this review, we summarize the evolving insights on how the intrinsic epigenetic events driven by dysregulated miRNAs, including the oncogenic and tumor-suppressive miRNAs, influence the pathogenesis of MF and SS. We also focus on the interplay between the JAK/STAT pathway and miRNAs in CTCL as well as the significance of the miRNA/STAT axis as a relevant pathogenetic mechanism underlying CTCL initiation and progression. Based on these biologic insights, the current status and recent progress on novel therapies with a strong biological rationale, including miRNA-targeted molecules and JAK/STAT-targeted therapy for CTCL management, are discussed.
2015-03-03 | MiRNAs in primary cutaneous lymphomas
Abstract Primary cutaneous lymphomas ( PCL ) compose a heterogeneous disease with still unknown aetiology and mechanisms of development. Micro RNA s (mi RNA s) have recently been discovered as one of the crucial players in PCL carcinogenesis through post‐transcriptional regulation of gene expression. mi RNA s have been reported to be frequently deregulated in PCL s and their biological significance has been further confirmed in multiple functional experiments. Such studies help us understand molecular pathogenesis of PCL . In this review, we summarize expression of mi RNA s and their corresponding roles in different subtypes of PCL . With expression and functional role of mi RNA s revealed, investigation of their possible clinical use as biomarkers for diagnosis, prediction of prognosis and target for therapies, will be a promising area in the future.
2013-10-07 | Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report
The etiology of primary cutaneous anaplastic large-cell CD30+ lymphoma is largely unknown, and although an infectious involvement has been suspected, the implication of infectious agents in its pathogenesis is still unclear.We report the case of a HIV-negative patient referred to our hospital with a rapidly enlarging skin tumor on her upper eyelid. Surgical excision was performed and histological analysis evidenced a primary cutaneous anaplastic large-cell lymphoma. Due to the ocular localization and to the prominent angiogenic component of the lesion, molecular analyses for the detection of Chlamydophila pneumoniae and HHV8 were performed, revealing the presence of an infection by both pathogens in surgical biopsy and in peripheral blood mononuclear cells.These findings suggest for the first time a possible association of C. pneumoniae and/or HHV8 infection, or both together, with primary cutaneous anaplastic large-cell lymphoma in non-immunocompromised and HIV-negative subjects. This potential pathogenic association, if confirmed, could provide potential indications for future therapy.
antibodies
2026-05-27 | Primary Cutaneous Anaplastic Large Cell Lymphoma: A Review of Diagnosis and Treatment for the General Oncologist.
Primary cutaneous anaplastic large cell lymphoma (pcALCL) is a type of cutaneous T-cell lymphoma (CTCL) classified as a CD30+ lymphoproliferative disorder along with lymphomatoid papulosis. Although it is the second most common subtype of CTCL after mycosis fungoides/Sézary syndrome, it remains rare, with an incidence of fewer than 0.5 cases per million person-years. Despite its histologic similarity to systemic anaplastic large cell lymphoma, pcALCL follows a largely indolent course with excellent outcomes, with disease-specific survival rates of 86-95% in contemporary series. This narrative review summarizes the clinical presentation, diagnostic evaluation, and management of pcALCL based on a semi-structured literature search, with emphasis on prospective studies and clinically relevant retrospective data. Diagnosis remains challenging due to overlap with other CD30-positive lymphoproliferative disorders and reactive conditions, requiring careful clinicopathologic correlation and exclusion of systemic disease. While regional lymph node involvement may be present, available evidence suggests it does not significantly impact prognosis, highlighting the importance of avoiding overtreatment. Management strategies are guided by disease extent, with strong evidence supporting skin-directed therapies, particularly radiation, for localized disease. For multifocal or relapsed disease, brentuximab vedotin demonstrates the most robust prospective data and has reshaped the treatment landscape; however, alternative systemic therapies, including methotrexate and retinoids, remain relevant in selected patients. Overall, current management is supported largely by non-randomized data, and key gaps remain in risk stratification, optimal sequencing of therapies, and management of uncommon aggressive variants.
2025-12-05 | Primary cutaneous CD30 + lymphoproliferative disorders
The CD30 antigen is a cytokine receptor belonging to the tumor necrosis factor receptor superfamily. The antigen was initially described within Reed–Sternberg and Hodgkin cells of Hodgkin lymphoma and subsequently identified within neoplastic cells of a new group of non–Hodgkin lymphomas (anaplastic large cell lymphoma). The term “cutaneous CD30 + lymphoproliferative disorders” has been subsequently proposed to denote a group of primary cutaneous T-cell lymphoproliferative disorders characterized by expression of the CD30 antigen and favorable prognosis, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. Lymphomatoid papulosis is defined as a chronic, recurrent, self-healing eruption of papules and small nodules with the histopathologic features of a cutaneous T-cell lymphoma (“rhythmic paradoxical eruption”). In some of the patients with lymphomatoid papulosis and associated lymphomas, the same clone of neoplastic T lymphocytes has been identified in lesions of the two lymphoproliferative disorders, raising the question of a common origin of the diseases.
2025-11-18 | Anaplastic large cell lymphoma in the penis: a case report and review of literature.
Anaplastic large cell lymphoma is a distinct subtype of mature T cell lymphoma characterized by strong CD30 expression. While primary penile lymphomas are rare, they are most commonly of B cell origin, making primary T cell lymphomas of the penis an exceptional finding that can pose significant diagnostic challenges. A 60-year-old Arab male presented with multiple, rapidly growing nodules on the penile body that had developed over 4 weeks. A comprehensive workup, including biopsy and immunohistochemistry, confirmed a diagnosis of localized, anaplastic lymphoma kinase-negative primary cutaneous anaplastic large cell lymphoma. Staging via positron emission tomography-computed tomography revealed no systemic involvement. The patient was treated with six cycles of brentuximab vedotin plus cyclophosphamide, doxorubicin, vincristine, and prednisone, achieving a complete metabolic response (Deauville score of 2) as assessed by post-treatment positron emission tomography-computed tomography imaging. This case highlights the diagnostic challenge posed by rare penile lesions and, more importantly, the therapeutic dilemma of selecting an appropriate treatment for a disease that is localized yet multifocal. The successful outcome with systemic brentuximab vedotin plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, a deviation from standard guidelines for unifocal primary cutaneous anaplastic large cell lymphoma, underscores the need for individualized treatment strategies and further research to establish risk-adapted guidelines for this rare clinical entity.
2025-07-01 | CASES OF PRIMARY CUTANEOUS ANAPLASTIC LARGE CELL LYMPHOMA TREATED WITH SYSTEMIC OR LOCAL THERAPY
Primary Cutaneous Anaplastic Large Cell Lymphoma (PC-ALCL) is a CD30+ peripheral T-cell lymphoproliferative disorder without systemic involvement. It accounts for approximately 8% of cutaneous lymphoma cases. Most patients with PC-ALCL present with slow-growing, solitary or grouped skin nodules, and in some cases, regional lymph node involvement is observed. A 61-year-old male patient presented to our clinic with swelling and edema of the right lower lip, along with a 57 cm draining ulcerative skin lesion in the suprasternal region. The patient had previously received six cycles of treatment for T-cell lymphoma at an outside center. A PET-CT scan identified a soft tissue lesion in the skin/subcutaneous tissue at the level of the right thyroid lobe and isthmus, measuring 57*15*52 mm, with a maximum SUV of 34. Biopsies taken from the lower lip and suprasternal skin were reported as primary cutaneous anaplastic large cell lymphoma. CD30 expression was found to be 95%. The patient was started on brentuximab vedotin along with the GDP protocol. After two cycles of treatment, improvement in the skin lesions was observed. A 61-year-old male patient presented to our clinic with a complaint of a lesion on the anterior surface of the right tibia, measuring approximately 10*10 cm. The biopsy taken from the lesion was reported as CD30+ primary cutaneous anaplastic large cell lymphoma. A PET-CT scan revealed moderately hypermetabolic lymph nodes with thick cortices in the right iliac and inguinal lymphatic chains. Radiotherapy was applied to the area of the primary lesion and the regional lymph nodes, and improvement in the skin lesions was observed with treatment. We aimed to discuss the outcomes of applying localized radiotherapy or systemic treatment to two patients with PC-ALCL who presented to our clinic: one with a relapse and the other with a new diagnosis. Brentuximab vedotin is effective in this disease. Since disease control could not be fully achieved with localized radiotherapy alone, we believe that the combination of systemic therapy and radiotherapy may be an important treatment option for these patients. Further large-scale case series are needed to guide treatment.
2025-04-01 | Primary Cutaneous CD30+ Lymphoproliferative Disorders in South Korea: A Nationwide, Multi-Center, Retrospective, Clinical, and Prognostic Study.
Primary cutaneous CD30+ lymphoproliferative disorders (pcCD30-LPDs) are a diseases with various clinical and prognostic characteristics. Increasing our knowledge of the clinical characteristics of pcCD30-LPDs and identifying potential prognostic variables in an Asian population. Clinicopathological features and survival data of pcCD30-LPD cases obtained from 22 hospitals in South Korea were examined. A total of 413 cases of pcCD30-LPDs (lymphomatoid papulosis [LYP], n=237; primary cutaneous anaplastic large cell lymphoma [C-ALCL], n=176) were included. Ninety percent of LYP patients and roughly 50% of C-ALCL patients presented with multiple skin lesions. Both LYP and C-ALCL affected the lower limbs most frequently. Multiplicity and advanced T stage of LYP lesions were associated with a chronic course longer than 6 months. Clinical morphology with patch lesions and elevated serum lactate dehydrogenase were significantly associated with LPDs during follow-up in LYP patients. Extracutaneous involvement of C-ALCL occurred in 13.2% of patients. Lesions larger than 5 cm and increased serum lactate dehydrogenase were associated with a poor prognosis in C-ALCL. The survival of patients with C-ALCL was unaffected by the anatomical locations of skin lesions or other pathological factors. The multiplicity or size of skin lesions was associated with a chronic course of LYP and survival among patients with C-ALCL.
other
2023-10-24 | What Is New in Cutaneous T Cell Lymphoma?
This review focuses on updates in prognosis, pathogenesis, and treatment of cutaneous T cell lymphoma (CTCL).Cohort studies indicate imaging may be necessary in early-stage CTCL. Risk factors for progression of CTCL have been identified. Interactions between malignant cells and the tumor microenvironment (TME) and the skin microbiome advance the understanding of pathogenesis and tumor cell dissemination. Studies support a hypothesis of circulating malignant tumor cells. MicroRNA (miR) influence tumor progression and prognosis; the IL22-STAT3-CCL20 cascade may be a novel target. IL-4, IL-5, and IL-31 cytokines are relevant for pruritus and could be targets for therapeutic interventions. Systemic therapies, such as JAK inhibitors, targeted antibodies, and checkpoint inhibitors, show promise in advanced stages. Allogenic hematopoietic stem cell transplantation provides a potential curative option for patients. Further investigations of prognosis and translational research are necessary to improve stratification of patients for treatment.
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Drug Discovery Landscape
2 orphan drug designations for Primary cutaneous CD30+ T-cell lymphoproliferative disease, including 1 approved therapy.
2 orphan drug designations for Primary cutaneous CD30+ T-cell lymphoproliferative disease, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Brentuximab vedotin [Adcetris] | antibodies | FDA | Approved | Seagen Inc. |
Human immunoglobin anti-CD30 monoclonal antibody | antibodies | FDA | Bristol-Myers Squibb |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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