Background: Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), is a rare and aggressive form of lymphoma. Its characteristics and treatment outcomes remain poorly understood. Methods: We identified 15 patients who were diagnosed with pcPTCL-NOS between January 2014 and August 2024 at Tianjin Medical University Cancer Institute and Hospital (TMUCIH) in this retrospective study. The clinical and immunophenotypic features, treatment regimens, and outcomes of these patients were investigated. Results: All patients (4 men, 11 women; median age 54 years) presented with skin lesions, including five stage T1, four stage T2 and six stage T3 lesions. pcPTCL-NOS manifests clinically either with solitary or disseminated rapidly growing nodules/tumors and papules and, less often, ulcers. The lesion sites in patients presenting with solitary/localized tumors (stage T1 and T2) were the head and limbs, and those in patients presenting with disseminated lesions (stage T3) were the trunk, head, and limbs. The CD4/CD8 immunophenotypic characteristics were as follows: CD4+/CD8- 53.33%; CD4+/CD8+ 26.67%; CD4-/CD8- 13.33%; and CD4-/CD8+ 6.67%. One patient had a T follicular helper (TFH) phenotype. Five patients had aberrant expression of the B-cell marker CD20 by tumor cells. All patients received CHOP or CHOP-like regimens as the initial treatment, with three patients undergoing complete lesion resection before chemotherapy, seven patients receiving treatment combined with chidamide (tucidinostat), two patients receiving treatment combined with brentuximab vedotin, two patients receiving treatment combined with mitoxantrone liposomes (Lipo-Mit), three patients receiving treatment combined with radiotherapy, and two patients receiving ASCT after the first-line treatment. The OS rates at 1 year, 2 years, and 3 years were 80%, 77.8%, and 77.8%, respectively; the PFS rates were 60%, 44.4%, and 33.3%, respectively. With a median follow-up of 40 months, the median PFS was 21 months, and the median OS was not reached. Univariate analyses revealed that patients with B symptoms and the CD4-/CD8- phenotype had inferior outcomes (p < 0.05). Age, sex, tumor stage, PIT score, Ki-67 index, elevated β2-MG levels, expression of CD20 or PD1, and treatment selection were not associated with the prognosis. A trend of a survival benefit in patients with solitary (T1) tumors compared with patients with disseminated (T2, T3) tumors was observed, suggesting that it is possible to reduce the intensity of treatment in patients with T1 tumors in the future. Conclusions: pcPTCL-NOS is an aggressive but poorly characterized lymphoma that may require early and active systemic treatment. However, for patients with T1 tumors, reducing the intensity of treatment with CHOP should be appropriately considered.

Mycosis fungoides, the most prevalent subtype of cutaneous T-cell lymphoma, primarily targets areas of the skin that of not exposed to sunlight. Nevertheless, it can involve extracutaneous tissues at any disease stage, especially during its advanced phases. Research suggests that all extracutaneous organs might be susceptible, though such cases are more commonly reported in autopsy studies and less so in clinical setting. The most recent comprehensive review of such extracutaneous manifestations in mycosis fungoides occurred almost a decade ago. With the aim of enhancing clinicians' understanding of these extracutaneous manifestations to improve diagnostic accuracy and patient outcomes, this updated review provides a current synthesis of the rare instances of extracutaneous involvement in mycosis fungoides.

Mycosis fungoides (MF) is the commonest form of primary cutaneous T-cell lymphoma. Progression is slow, with frequent relapses. Data for predicting early-stage MF progression and recurrence are inadequate.

The clinical profile, treatment response, relapse, progression to advanced stage and final status of 180 patients diagnosed with early MF between January 1987 and September 2021 were investigated retrospectively.

Ninety-four (52.2%) patients were female and 86 (47.8%) male. Stage at diagnosis was IA in 74 (41.1%) patients, IB in 72 (40%) and IIA in 34 (18.9%). Initial treatment was PUVA in 76 (42.2%) patients and NB-UVB in 59 (32.7%). Complete response occurred in 109 (60.5%) patients, and 73 (51.5%) patients experienced recurrence. Stage IA/IB at diagnosis, normal B-2-microglobulin levels and low CLIPI score were associated with complete response. Progression to advanced stage occurred in 27 (%15) patients. Age 60 and over at diagnosis, stage at diagnosis, pruritus, LDH, CLIPI score between 3 and 5, and folliculotropism in pathology were found to be negative prognostic factors in progression to advanced stage. Classical pathology, PUVA treatment and complete response to initial treatment were found to be positive prognostic factors. In multivariate analysis, LDH and complete responsiveness to initial treatment were independently associated with progression to advanced stage.

Advanced age at diagnosis, a high CLIPI score and folliculotropism affect both progression to advanced stage and the final status of the disease. LDH level is a crucial indicator of progression to an advanced stage. Early diagnosis affects the treatment response, with a complete response to the initial treatment mitigating the risk of advanced-stage progression.

Primary cutaneous B-cell lymphomas (PCBCLs) are rare cutaneous neoplasms with limited literature regarding treatment options and associated treatment outcomes. This study aimed to investigate and present real-world treatment outcomes in patients with PCBCLs.

All patients with PCBCL who were treated in five major referral centers for cutaneous lymphoma in Greece over 10 years were retrospectively included with their baseline characteristics and treatment-associated outcomes collected and analyzed.

In total, 235 PCBCL patients, of whom 125 (53.2%) were females, were included. The median age at diagnosis was 60 years (IQR 47-72), and the median follow-up duration was 3 years (IQR 1.3-6.4). The most common subtype was primary cutaneous marginal zone lymphoma (PCMZL) (52.3%), followed by primary cutaneous follicle center lymphoma (PCFCL) (40.9%), and primary cutaneous large B-cell lymphoma, leg type (PCDLBCL, LT) with 16 (6.8%) cases. Complete responses (CRs) were observed in 77.3% after first-line treatment. Both radiotherapy (RT) and surgical excision (SE) achieved superior outcomes, with 88.9% and 89% achieving CR, respectively. Relapses occurred in 22.6% of initial complete responders. The median time to the next treatment (TTNT) for the PCMZL and PCFCL was 349 days. RT and topical/intralesional steroids demonstrated longer TTNT compared to SE (445 and 359 vs. 154 days). For PCMZL and PCFCL, the 1-year progression-free survival (PFS) was 84.2% (75.7-89.9) and 85% (75.1-91.2), and the 5-year PFS was 66.5% (55.2-75.5) and 58.8% (44.4-70.7), respectively.

PCBCLs have favorable outcomes. RT demonstrates significantly increased TTNT compared to SE, suggesting RT as the preferable option. After careful evaluation, "watch and wait" may be a reasonable option for asymptomatic patients.

The diagnosis of early-stage mycosis fungoides (MF) is challenging owing to shared clinical and histopathological features with benign inflammatory dermatoses. Recent evidence has shown that deep learning (DL) can assist pathologists in cancer classification, but this field is largely unexplored for cutaneous lymphomas. This study evaluates DL in distinguishing early-stage MF from benign inflammatory dermatoses using a unique dataset of 924 H&E-stained whole-slide images from skin biopsies, including 233 patients with early-stage MF and 353 patients with benign inflammatory dermatoses. All patients with MF were diagnosed after clinicopathological correlation. The classification accuracy of weakly supervised DL models was benchmarked against 3 expert pathologists. The highest performance on a temporal test set was at ×200 magnification (0.50 μm per pixel resolution), with a mean area under the curve of 0.827 ± 0.044 and a mean balanced accuracy of 76.2 ± 3.9%. This nearly matched the 77.7% mean balanced accuracy of the 3 expert pathologists. Most (63.5%) attention heatmaps corresponded well with the pathologists' region of interest. Considering the difficulty of the MF versus benign inflammatory dermatoses classification task, the results of this study show promise for future applications of weakly supervised DL in diagnosing early-stage MF. Achieving clinical-grade performance will require larger multi-institutional datasets and improved methodologies, such as multimodal DL with incorporation of clinical data.

Follicular lymphoma (FL) is a mature B cell neoplasm classically characterized by B cells harboring the t(14;18) IGH::BCL2 leading to the overexpression of BCL2 in most cases. Conventional FL occurs in lymph nodes and typically shows a follicular B-cell proliferation expressing at least one germinal center marker. Two early lesions closely related to conventional FL are recognized as variants, namely in situ follicular neoplasia (ISFN), and duodenal-type follicular lymphoma (DTFL). FL lacking BCL2 rearrangement ( BCL2 -R negative) accounts for around 10% to 15% of FLs and constitutes a heterogeneous group of FLs. Most of these alternative forms of FL are considered as distinct entities separate from conventional FL in the 2022 International Consensus Classification. This review aims to summarize the key pathologic and diagnostic features of FL conventional and its alternative forms as well as further emphasize the increasing role of molecular studies in the diagnostic work-up.

The International Consensus Classification (ICC) of myeloid and lymphoid neoplasms follows the precedent set in the Revised European-American lymphoma classification for modern lymphoma classifications by defining specific diseases on the basis of all the available morphologic, immunophenotypic, genetic, and clinical findings. Primary cutaneous lymphomas exhibit a broad range of clinical behavior ranging from lesions which spontaneously regress to those which run an aggressive, often fatal course. Accurate separation of entities is therefore essential for prognostication and to ensure appropriate treatment is administered. However, despite marked differences in clinical course, many subtypes of primary cutaneous lymphoma exhibit remarkably similar, often overlapping, and sometimes indistinguishable pathologic features. While molecular analysis has furthered our understanding of some of these disease entities, it does not yet facilitate robust distinction. Thus, clinical correlation retains a central role in both the diagnosis and classification of primary cutaneous lymphoma. This review aims to draw attention to problem areas in differential diagnosis and hopefully offer some practical suggestions for resolving difficult cases. It will also highlight recent advances in the field and discuss how they reinforce the current classification system and how they might impact of future classifications and treatment strategies.

Mycosis fungoides (MF), the most prevalent variant of cutaneous T-cell lymphoma (CTCL), is characterized by the clonal proliferation of skin-homing CD4+ T lymphocytes. Forkhead box M1 (FOXM1) plays significant roles in the progression of various solid tumors. Its expression has been reported to diminish following treatment with Neosetophomone B in CTCL cells in vitro. However, the role of FOXM1 in the pathogenesis of MF remains unclear.

To evaluate the expression pattern and underlying mechanism of FOXM1 in MF.

FOXM1 expression in lesional skin samples was accessed via immunohistochemistry analyses. Inhibition of FOXM1 was performed through lenti-virus shRNA vector mediated gene knockdown and treatment with specific FOXM1 inhibitors (RCM1 and FDI-6). Furthermore, animal experiments were conducted to evaluate the effects of FOXM1 knockdown or treatment with FOXM1 inhibitors on tumor growth in vivo.

Overexpression of FOXM1 was observed in MF with a stage-dependent pattern and poor prognosis. Inhibition of FOXM1 via either shRNA or specific inhibitors, significantly impaired MF cell proliferation by inducing cell cycle arrest and apoptosis, while also suppressing tumorigenicity in vitro and in vivo. Transcriptomic analysis revealed that FOXM1 suppression led to the downregulation of genes involved in cell cycle regulation, including CCNB2, CDK1, and E2F1.

The overexpression of FOXM1 contributes significantly to the progression of MF primarily by regulating the cell cycle. Furthermore, FOXM1 may serve as a reliable prognostic biomarker and a promising therapeutic target for MF.

Background/Objectives: Primary cutaneous lymphomas (CLs) are a group of skin-limited lymphoproliferative disorders, including cutaneous T-cell (CTCLs) and B-cell lymphomas (CBCLs). Photodynamic therapy (PDT), a non-invasive, light-activated treatment, has gained attention as a skin-directed therapy for early-stage CLs due to its selectivity and favorable safety profile. This systematic review evaluates the current evidence on the clinical use of PDT in managing CLs. Methods: A systematic literature search was conducted in PubMed, Scopus, and Embase through 1 September 2024 following PRISMA guidelines. Search terms included "primary cutaneous skin lymphoma", "CTCL", "CBCL", "mycosis fungoides", "lymphomatoid papulosis", and "photodynamic therapy". After screening 1033 records, 30 studies were included. Data were extracted and categorized by lymphoma subtype and clinical outcomes. Results: Of the included studies, 23 focused on mycosis fungoides (MF), 5 on lymphomatoid papulosis (LyP), and 2 on CBCL. PDT demonstrated notable clinical efficacy in early-stage and localized disease, particularly MF, using methyl aminolevulinate (MAL) or 5-aminolevulinic acid (5-ALA) as photosensitizers. Adjunctive techniques like microneedling and laser-assisted delivery improved treatment outcomes. PDT was generally well tolerated, with mild, transient side effects; rare complications such as localized neuropathy were reported. Conclusions: PDT is a promising, non-invasive treatment for early-stage CLs, especially MF and indolent CBCL variants. While current evidence supports its safety and effectiveness, further comparative and prospective studies are needed to refine protocols, evaluate long-term efficacy, and compare different photosensitizers.

Folliculotropic mycosis fungoides (FMF) is a distinctive variant of mycosis fungoides (MF). FMF has worse clinical outcome when compared to the MF and commonly used skin-based therapy may be refractory. The aim of this study is to give a systematic review of dermoscopic and trichoscopic findings in FMF and to summarize current knowledge on usefulness of dermoscopy in patients with FMF.

A search of the literature was performed using the electronic database PubMed by selecting the words "dermoscopy," "dermatoscopy," "trichoscopy," and "follicular mycosis fungoides."

After exclusion criteria, 10 articles in total were included in this review. Among 10 selected articles, a total number of 59 patients were included, and total of 23 dermoscopic features were described. Only seven of 23 dermoscopic features were present in over half of the patients (over 30 in total number of 59 patients). Among obtained results, only five dermoscopic features were found in more than 70% of the patients; but none of these were described in majority of the patients. Among these published papers, the dermoscopic features of cutaneous lymphomas were correlated with the histopathology.

After reviewing all these papers we can conclude that dermoscopic features related to the pathology found in follicle, although characteristic, are not pathognomonic when it comes to diagnosing FMF. A finding of multiple characteristic dermoscopic features is required to indicate a diagnosis of FMF but in the corresponding clinical context. In some cases, dermoscopy can be used as a useful tool for determining optimal biopsy site with the potential of increasing specificity of pathohistological diagnosis which is crucial because of choice of the therapeutic approach having in mind that FMF is more refractory to the conventional treatment of MF.

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.

Venous hypertension due to anatomical venous insufficiency (superficial or deep venous valvular reflux and venous obstruction) and/or functional venous insufficiency (calf dysfunction, dependent edema, lymphatic dysfunction, elevated central venous pressures, etc.) leads to chronic venous insufficiency (CVI) and its sequelae. The most severe clinical manifestation of CVI is venous leg ulcer (VLU), which leads to substantial morbidity and disability. VLUs can present in both typical and atypical forms. However, several other types of leg ulcers can mimic VLUs. Therefore, vascular and wound care specialists must recognize the variability in VLU presentation and understand the differential diagnoses to deliver an accurate diagnosis and optimal care of atypical VLUs and conditions that resemble VLUs. Herein, we review and discuss the broad differential diagnosis of VLUs, supported by illustrative examples.

The hydroa-vacciniforme-like lymphoproliferative disorder (HVLD) is a rare NK/T-cell condition affecting children in Latin America and Asia. It often progresses to systemic lymphoma, with Latin American patients experiencing worse outcomes compared to East Asians. Understanding viral and host genetic interactions is crucial for advancing targeted therapies. Here, we report a male patient with HVLD successfully treated with hematopoietic stem cell transplantation, highlighting its potential as a therapeutic approach for this aggressive disease.

An 8-year-old boy presented with persistent skin lesions, fever, and pain. Biopsy confirmed a diagnosis of HVLD. Initial treatments with thalidomide and steroids provided temporary relief. At 12, lymphoma progression led to rituximab and CHOP chemotherapy. Further investigations revealed persistent EBV infection and lymphoma; hence, a haploidentical stem cell transplant was performed at 15. The procedure was successful, achieving complete immune reconstitution and viral clearance. Three years post-transplant, the patient remains in good health with no detectable EBV and complete vaccinations.

While EBV infection is common, only specific immunodeficiency states seem to enable EBV-related lymphoproliferative disorders. The exact mechanism leading to this immunosuppressive environment in HVLD remains unclear. Clinically, HVLD resembles specific inborn errors of immunity with EBV susceptibility. Additionally, cases of GATA2 and TACI deficiency presenting with HVLD suggest a potential link to underlying immune dysfunction. Further research in this area is crucial to understand the immunological basis of HVLD. Treatment options for HVLD are diverse and lack standardized protocols. Our case demonstrates the potential of HSCT with reduced-intensity conditioning and EBV-specific T-cell infusion as an effective cure. Given the limited understanding of HVLD, an immunological approach to characterizing patient profiles and prolonged follow-up are essential. While diverse therapies exist, HSCT offers the best hope for a cure. Further research towards tailored treatment strategies holds significant promise for improved patient outcomes.

HVLD presents a complex and multifaceted challenge; our case demonstrates the potential of HSCT as a curative treatment. Unveiling the underlying immunology and tailoring therapies to patient profiles are crucial for improved outcomes. Further research is key to refining treatment strategies and offering hope for this rare and severe disease.

Mycosis fungoides (MF) and Sézary syndrome (SS) are subtypes of cutaneous T-cell lymphoma with numerous topical and systemic therapies. Early-stage MF can be managed with topical corticosteroids, mechlorethamine, and phototherapy. However, patients are often non-responsive to topical therapies, thus requiring systemic therapies. There are few studies summarizing oral (PO) therapies for MF and SS. We aim to discuss the efficacy and safety of FDA-approved, off-label, and investigational oral therapies for MF and SS. FDA-approved oral therapies include bexarotene and vorinostat, both of which are effective in patients who are recalcitrant to prior topical therapies. Off-label oral therapies include methotrexate, acitretin, and chlorambucil. Methotrexate improves MF lesions in both early-stage and late-stage MF and is effective in erythrodermic MF. A combination of acitretin with phototherapy may lead to better response rates compared to acitretin monotherapy. Chlorambucil is mainly used to treat erythrodermic MF. Investigational oral therapies for MF include tenalisib, duvelisib, cerdulatinib, lenalidomide, bortezomib, and azacytidine, and direct comparison studies between these investigational agents and FDA-approved therapies should be undertaken to better understand their role in the management of MF and SS.

There are few studies in the literature comparing the effectiveness of topical treatments in early-stage mycosis fungoides (MF).

It was aimed to evaluate the clinical efficacy, side effects and topical treatment compliance with bexarotene or clobetasol propionate in early-stage MF.

A total of 40 patients with stage IA-IB MF were enrolled in the study. Twenty patients were treated with 1% bexarotene gel and 20 patients were treated with 0.05% clobetasol propionate ointment.

In the bexarotene group, 11 patients (55%) had complete clinical response (CCR) and 5 patients (25%) had partial response (PR) while in the clobetasol propionate group, 10 patients (50%) had CCR and 9 patients (45%) had PR. The median duration of remission was 10.5 months in the bexarotene group and 4 months in the clobetasol propionate group. The remission period was statistically significantly longer in the bexarotene group (p = 0.032). Irritation symptoms were statistically significantly more common in the bexarotene group (p = 0.001).

The limitation of the study was its retrospective design.

Both topical bexarotene and topical clobetasol propionate were found to be effective in MF. Irritation symptoms were more common with topical bexarotene. Moreover, the remission period with topical bexarotene was significantly longer.

Mycosis fungoides (MF) is the commonest subtype of cutaneous T-cell lymphoma. In the United States, prior studies reported that African Americans (AA) with MF had poor outcomes. Data characterizing differences in racial disparity outcomes over time are limited.

We collected data from the United States Surveillance, Epidemiology, and End Results (SEER) database to investigate the survival patterns of patients with MF from 1988 to 2011. Cases were divided into 3 cohorts based on the year of diagnosis. Univariable and multivariable analysis were conducted to assess for factors associated with overall survival (OS).

2896 cases of MF were detected, with a median follow-up duration of 60 months. The disparity in survival between the years 1988-1995 and 2004-2011 was significant (P = .05). The parameter estimates of the Cox proportional hazards model for the 1988-1995 period (using the 2004-2011 period as a reference) was also significant (P = .024). Patients diagnosed between 1988 and 1995 were 1.4 times more likely to die from the disease than those diagnosed between 2004 and 2011. The survival gap between AA and white patients narrowed in 1996-2003 and 2004-2011 in comparison to 1988-1995. This indicates improvements in the survival of AA patients over time. Conversely, the survival rates of white patients remained relatively stable over time.

Our study demonstrates that AA with MF have reduced survival. Despite the persistent pattern of lower survival across all periods, the gap in survival between white and AA seems to be narrowing over time.

The purpose of this study was to describe a patient with a primary CD4+ T-cell lymphoproliferative disorder of conjunctiva.

Case report and review of the literature.

An 81-year-old man was referred for asymptomatic bilateral conjunctival masses that on biopsy revealed a proliferation of mature CD4+ lymphocytes associated with T-cell receptor γ gene rearrangement. The histopathology and immunophenotypic profile in the absence of disease elsewhere bore resemblance to primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder.

In 2016, the World Health Organization reclassified primary cutaneous CD4+ small/medium T-cell lymphoma to a lymphoproliferative disorder because neither dissemination nor death had been documented. This case displays similarities with the latter but has nonconforming features. Multicentric clonal expansion of T cells do not inevitably indicate lymphoma. Lymphoproliferative disorders that display features of reactive hyperplasia and lymphoma and are not easily classified need to be carefully monitored.

Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is often underdiagnosed in early stages because of similarities with benign dermatoses such as atopic dermatitis (AD). Furthermore, the delineation from what is called "parapsoriasis en plaque", a disease that can appear either in a small- or large-plaque form, is still controversial.

We sought to characterize the parapsoriasis disease spectrum.

We performed single-cell RNA sequencing of skin biopsies from patients within the parapsoriasis-to-early-stage MF spectrum, stratified for small and large plaques, and compared them to AD, psoriasis, and healthy control skin.

Six of 8 large-plaque lesions harbored either an expanded alpha/beta or gamma/delta T-cell clone with downregulation of CD7 expression, consistent with a diagnosis of early-stage MF. In contrast, 6 of 7 small-plaque lesions were polyclonal in nature, thereby lacking a lymphomatous phenotype, and also revealed a less inflammatory microenvironment than early-stage MF or AD. Of note, polyclonal small- and large-plaque lesions characteristically harbored a population of NPY+ innate lymphoid cells and displayed a stromal signature of complement upregulation and antimicrobial hyperresponsiveness in fibroblasts and sweat gland cells, respectively. These conditions were clearly distinct from AD or psoriasis, which uniquely harbored CD3+CRTH2+ IL-13 expressing "TH2A" cells, or strong type 17 inflammation, respectively.

These data position polyclonal small- and large-plaque parapsoriasis lesions as a separate disease entity that characteristically harbors a so far undescribed innate lymphoid cell population. We thus propose a new term, "polyclonal parapsoriasis en plaque", for this kind of lesion because they can be clearly differentiated from early- and advanced-stage MF, psoriasis, and AD on several cellular and molecular levels.

Skin cancer generally causes disproportionate morbidity and mortality in people of colour. Although skin cancers occur most frequently in White individuals overall, cutaneous T-cell lymphoma (CTCL) is an exception. CTCL is a rare skin cancer comprising several subtypes of non-Hodgkin lymphoma; each contains a unique clinical profile that varies with race. Our aim is to review and compile the differences in epidemiology, clinical presentation, treatments and outcomes of the CTCL subtypes in Black, Asian or Pacific Islander (API) and Hispanic patients. The current literature supports that there are nuances in the course of CTCL that differ with race. Across multiple studies, racial differences in incidence patterns have been reported, with the highest rates among Black patients. Cutaneous manifestations of CTCL are highly variable in people of colour, and the predilection for clinical CTCL variants often differs with race, as well as severity of cutaneous involvement (body surface area). Response to and type of treatment also differs among people of colour and may be partially attributable to the varying CTCL subtypes experienced by certain races. Prognostic factors tend to vary with race, although Black patients consistently experience poor outcomes, while API patients may have a more favourable prognosis. Currently, there is no definitive conclusion to account for differences observed in patients with skin of colour with CTCL; however, biological and socioeconomic factors have been proposed as potential drivers. As the proportion of people of colour in our population continues to grow, adequate physician awareness and knowledge of racial nuances in CTCL are necessary to begin addressing these disparities.

Cutaneous T-cell lymphoma (CTCL) is a group of non-Hodgkin lymphomas characterized by multiple erythematous patches, plaques, or even nodules on the skin. As the disease progresses, patients develop widespread pruritic skin lesions, leading to skin barrier dysfunction, which significantly impacts their quality of life, appearance, and social adaptation. The pathogenesis of CTCL is not fully understood. Recent studies have recognized the important role of skin barrier dysfunction in the development and progression of CTCL, yet a comprehensive review on this topic is lacking. This review summarizes recent findings on skin barrier dysfunction in CTCL, focusing on physical barrier dysfunction, chronic inflammation, and immune dysregulation. We also discuss current and potential therapies aimed at restoring barrier function in CTCL. By emphasizing the integration of barrier-centric approaches into CTCL management, this review provides valuable insights for improving treatment outcomes.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous T-cell lymphoma (CTCL) that when refractory or complicated by hemophagocytic syndrome (HPS) has a poor prognosis. Romidepsin is a histone deacetylase inhibitor, but its efficacy for SPTCL is unknown. The efficacy of allogeneic hematopoietic cell transplantation (allo-HCT) is also unclear. Herein, we report a case of refractory SPTCL with HPS that was successfully treated with romidepsin followed by consolidation with allo-HCT.

A 26-year-old female presented with fever, generalized painful erythema, pancytopenia, and hemophagocytosis. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET) showed diffuse PET-avid infiltration of the subcutaneous adipose tissue found to be SPTCL via skin biopsy. Her SPTCL was refractory to conventional chemotherapy but complete metabolic response was achieved after romidepsin. An allo-HCT was used for consolidation, and she remains in complete remission 3 years later.

Romidepsin with allo-HCT consolidation may be an effective approach for refractory SPTCL.

Mycosis fungoides (MF) is the most common form of cutaneous T cell lymphoma. While multiple guidelines provide treatment recommendations, there are currently no clear treatment algorithms for MF. Chlormethine gel is recommended by major treatment guidelines as a first-line option for stage IA-IIA disease, and, on the basis of these guidelines, used in combination with other therapies in patients with advanced-stage MF in clinical practice.

To provide guidance regarding the use of chlormethine gel for patients with all stages of MF, based on clinical expertise.

Opinions on best practices regarding the use of chlormethine gel were collected through discussions that involved eight clinicians with extensive experience in treating patients with MF.

Chlormethine gel can be used as monotherapy in first- or second-line treatment of early-stage MF. In first-line, chlormethine gel monotherapy is prescribed for stage IA MF, and is particularly convenient for patients unable/unwilling to travel for hospital-based phototherapy, patients with thick plaques or palmoplantar involvement, when ultraviolet treatment is contraindicated, and for sanctuary sites. Chlormethine gel is also an appropriate first-line monotherapy for patients with stage IB or IIA MF; it may be used as part of combination regimens in these patients as well. For patients with late-stage MF, skin-directed treatments such as chlormethine gel should be combined with systemic therapies.

Chlormethine gel is a safe and effective treatment option that can be used in all stages of MF, either as monotherapy or in combination, depending on disease stage and patient characteristics and needs.

Patients with mycosis fungoides (MF)/Sézary Syndrome (SS) can experience impacted health-related quality of life (HRQoL).

To validate the CTCL-S, a novel subscale of the Functional Assessment of Cancer Therapy-General (FACT-G), in patients with MF/SS.

Qualitative interviews were conducted with expert clinicians and patients with MF/SS. Thematic analysis identified the most common concerns, and 19 items were selected. Patients with MF/SS were recruited from a single centre. FACT-G, CTCL-S (collectively 'FACT-CTCL'), Skindex-29 and Visual Analogue Scale-Pruritis (VAS-itch) were administered. A subset repeated FACT-CTCL and VAS-itch after ≈2 weeks. Patient demographics and clinical characteristics were obtained via review of the electronic medical records. Psychometric properties were assessed. Internal consistency was estimated using Cronbach's α. Convergent and discriminant validity were assessed by comparing CTCL-S with disease stage, age, VAS-itch, FACT-G and Skindex-29. Exploratory factor analysis (EFA) was used to preliminarily assess CTCL-S dimensionality. Test-retest repeatability was summarized using intraclass correlation coefficient (ICC), within-subject standard deviation and within-subject coefficient of variation.

Seventy-two patients completed the initial survey, and 35 repeated the FACT-CTCL and VAS-itch after ≈2 weeks. Two-thirds were men; most were White (78%). The majority (85%) had MF, 15% had SS and 75% early (stage IA-IIA) and 25% advanced (≥ stage IIB) disease. Preliminary EFA found a single predominant factor, supporting a hypothesis of unidimensionality of the CTCL-S. Internal consistency of the CTCL-S was high, with α = 0.95 [95% confidence interval (CI) 0.93-0.96]. There was no significant change in CTCL-S average test-retest scores [ICC 0.93 (P = 0.63)]. CTCL-S was significantly lower in advanced vs. early-stage disease [median (interquartile range) 34 (26-48) vs. 59 (44-68), P < 0.001] and strongly correlated with VAS-itch [Spearman's r (rs) -0.70, 95% CI -0.81 to -0.55], FACT-G (rs 0.77, 95% CI 0.65-0.85) and Skindex-29 (rs -0.90, 95% CI -0.94 to -0.84), supporting convergent validity. CTCL-S scores had little correlation with age (rs 0.19, 95% CI -0.05 to 0.41, P = 0.12), supporting discriminant validity.

The FACT-CTCL is a disease-specific instrument for assessing HRQoL with high reproducibility and good performance in a cohort of patients with MF/SS.

Mycosis fungoides (MF) usually has an indolent course. However, some patients develop more aggressive disease and few prognostic parameters have been identified. Isolated cases of pustular MF (pMF) suggest an unfavourable prognosis.

To describe the clinicopathological characteristics and prognostic value of pMF.

We retrospectively collected data from all patients with MF with histological pustules diagnosed from 2009 to 2020. The outcomes and clinicopathological characteristics of pMF at diagnosis (pMFD) were compared with those of a cohort of patients with nonpustular MF (NpMF).

Thirty-three patients with pMF (including 22 with pMFD) and 86 with NpMF were included. Median age at diagnosis of pMF was 61 years [interquartile range (IQR) 50-75]. The median duration of follow-up for patients with pMFD was 32 months (IQR 14-49). Clinically, 33% of patients with pMF had pustules. Large cell transformation (LCT) occurred in 17 patients. Patients with pMFD had significantly more advanced-stage disease and showed more LCT at diagnosis than those with NpMF [50% vs. 7% (P < 0.001) and 23% vs. 0% (P < 0.001), respectively]. On multivariate Cox analysis, the presence of histological pustules at diagnosis was associated with shorter overall survival (OS) in all patients [hazard ratio (HR) 13.90, 95% confidence interval (CI) 2.40-79.00); P = 0.003] and in patients with early-stage disease (HR 11.09, 95% CI 1.56-78.82; P = 0.02). In multivariate Fine and Gray model analysis, pMFD was associated with a higher cumulative incidence of LCT (subdistribution HR 13.90, 95% CI 2.43-79.00; P = 0.003) in all patients. Median OS after the occurrence of histological pustules during follow-up in all patients with pMF was 37 months, with a 5-year OS rate of 25% (95% CI 0.06-0.50).

pMF often follows an aggressive course, with a high risk of LCT and shorter survival, even for patients with early-stage disease. Histological pustules at diagnosis of MF might represent an independent poor prognostic factor, to be confirmed by further studies. As pustules are not always identified clinically, pustules found on histology should be mentioned in MF pathology reports and should prompt discussion of closer follow-up.

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), representing the majority of all lymphomas arising in the skin. The disease treatment focuses on managing symptoms and preventing disease evolution. To date, there is no gold standard for MF-CTCL treatment. Chlormethine, a DNA alkylating agent, is a long-known treatment for CTCL. The new chlormethine 0.02% gel (CL-gel) formulation provides proven efficacy and ease of application, improving patient compliance and outcome. The current consensus paper and real-world experience with CL-gel in the treatment of early-stage MF-CTCL may help meet the unmet need for treatments in Canada. A modified Delphi process comprised a virtual meeting and an online follow-up. A panel of 9 board-certified dermatologists with expertise in cutaneous lymphoma and 1 radiation oncologist discussed the systematic literature review results, drew from clinical experience and the opinion of the panel to adopt and agree on five consensus statements. The panel shared real-world patient cases to illustrate the use of chlormethine gel in a variety of patients across Canada. Five real-world patient cases were provided to illustrate the panels' use of chlormethine gel.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of non-Hodgkin lymphoma with a good prognosis, but the optimal treatment for relapsed/refractory (R/R) SPTCL has been rarely discussed.

This study aims to compare the efficacy of conventional chemotherapy and chemo-free immunomodulatory regimen for R/R SPTCL. We retrospectively reviewed the patients with first relapse or primary refractory SPTCL between September 1997 and October 2020.

A total of 19 patients with R/R SPTCL with a median age of 34 were included. All patient received the first-line chemotherapy-based treatment with a median PFS of 1.8 months. In these patients, 16 received salvage second-line treatment with an ORR of 31.3% and a median TTNT of 3.0 months. 13 of these 16 patients received chemotherapy-based treatment, resulting in a median TTNT of 2.4 months. 2 of these 16 patients received allogeneic hematopoietic stem cell transplantation and achieved long term complete remission (CR). In third-line treatment, 7 patients received chemotherapy-based regimen and 6 received chemo-free regimen such as VRMP (bortezomib, lenadomide and methylprednisolone) regimen and CsA plus IFNα regimen. The median TTNT of chemotherapy and chemo-free group were 3.2 months and not reached, respectively.

Chemo-free group had a better TTNT than chemotherapy group (p=0.007). The use of chemotherapy-free regimens for R/R SPTCL appears promising and warrants further validation.

The emergence of blastic plasmacytoid dendritic cell neoplasm (BPDCN) as its own distinct entity within the pantheon of hematologic malignancies is due to the growing understanding of its unique multiorgan clinical presentation and characteristic skin lesions. The occurrence of BPDCN is generally heralded by a multicompartmental presentation of violaceous cutaneous lesions, involvement by bone marrow and/or blood, lymph node invasion, and an inclination toward extramedullary organ involvement, including, most remarkably, central nervous system (CNS)/cerebrospinal fluid positivity. With a median age historically of ≥ 70 years and up to 5:1 male predominance in most of the field's earlier studies, the most notable development in the modern era is the recognition of emerging important groups with BPDCN, such as female, pediatric, and adolescent/young adult patients; CNS + BPDCN patients; and an increasing number of cases being diagnosed worldwide. These trends are in line with the increased educational and research efforts, greater international collaboration, and markedly improved diagnostic tools and clinical approaches among hematology/oncology, hematopathology, dermatology, and dermatopathology teams around the world. Now, with over 5 years since the first commercially approved targeted agent specifically dedicated for BPDCN, the CD123-targeted agent tagraxofusp, improvements have been demonstrated particularly in the frontline setting for patients with BPDCN. The field is abundant with hope, as it has experienced advancements including greater molecular characterization, expanded identification of potential targets for therapy beyond CD123, advent of combination therapies, improving parameters for stem cell transplantation, and novel clinical trials specifically available for patients with BPDCN.

Primary cutaneous anaplastic large cell lymphoma (ALCL) is a very uncommon type of CD30-positive T-cell lymphoma, and it very rarely affects the forehead. We report the case of a 68-year-old male presenting with an ulcerative lesion on the right forehead, initially suspected as a benign condition. Fine needle aspiration suggested a lymphoproliferative disorder, with biopsy and immunohistochemistry confirming primary cutaneous ALCL (CD30-positive, anaplastic lymphoma kinase [ALK]-negative). The patient was treated with a standardized chemotherapy regimen and achieved a complete response. This case underscores the importance of considering primary cutaneous ALCL in the differential diagnosis of persistent ulcerative lesions in anatomically sensitive areas. Early diagnosis, multidisciplinary management, and advanced therapeutic strategies such as Brentuximab Vedotin + Cyclophosphamide, Hydroxyrubicin, and Prednisone (BV + CHP) are critical to optimizing outcomes in this rare presentation.

Prognostic markers are needed for tumor-stage mycosis fungoides (MF) because of their variable prognosis. The objectives of this study were to explore prognostic markers for tumor-stage MF and assess the prognostic significance of clinically assessed MF tumor burden index (MTBI). MTBI was devised to consider the tumor size ≥ 2 cm, number ≥ 5, ulcers, and body surface area ≥ 50%. The prognostic value of MTBI and other potential markers derived from blood tests and skin biopsy were evaluated retrospectively using a tertiary medical center database. We included 38 cases of tumor-stage MF. The mean age was 52.1 years, and the male-to-female ratio was 2.5:1. In multivariable analysis, MTBI ≥ 3 (adjusted hazard ratio, 9.41; 95% confidence interval, 1.13-78.15) was significantly associated with worse disease-specific survival. Ulcers were the only MTBI constituent significantly associated with survival. Among other markers, elevated lactate dehydrogenase level was associated with a worse disease-specific survival. Neutrophil-lymphocyte-ratio, pan-inflammation-value, CD30 positivity, Ki-67 index, large cell transformation, and monoclonal T-cell receptor gene rearrangement were not associated with prognosis. In conclusion, MTBI is useful and promising prognostic marker for tumor-stage MF.

As the majority of T-cell lymphomas lack CD20 expression, cases of mycosis fungoides (MF) exhibiting aberrant CD20 expression are exceedingly uncommon.

To comprehensively evaluate the clinical, histopathological and prognostic features of seven patients diagnosed with CD20+ MF.

This retrospective study involved seven cases of MF with aberrant CD20 expression. The study provides details of demographics, clinical features, histopathology and treatment outcomes. Key timepoints include initial diagnosis of MF, detection of CD20 expression and follow-up, with a mean follow-up of 46 months.

Aberrant CD20+ MF was diagnosed at an average age of 58.6 years, approximately 5.6 years after the first MF diagnosis. Following CD20 detection, patients presented with advanced disease stages, requiring treatments such as chemotherapy, brentuximab vedotin and allogeneic haematopoietic stem cell transplantation. Four patients died from lymphoma, with an average survival time of 52 months.

Aberrant CD20 expression in MF is rare but indicates a progressive course associated with poor prognosis. This often requires systemic chemotherapy and, in certain instances, allogeneic haematopoietic stem cell transplantation. This study provides important insights into the clinical attributes, disease progression and treatment options for patients with MF with aberrant CD20 expression. Further research is necessary to validate the effectiveness of emerging therapies and enhance our understanding of the underlying mechanisms and prognostic determinants specific to this unique MF subgroup.

Mycosis fungoides (MF) stands as the predominant form of primary cutaneous T-cell lymphoma (CTCL). It manifests a diverse array of clinical, histological, and immunophenotypic variations, each bearing distinct prognostic implications. The typical immunophenotypic profile of mycosis fungoides involves CD3+/CD4+/CD45RO+ memory T cells. Notably, the CD4-/CD8- double-negative variant of MF is a rare occurrence, observed in approximately 12% of early-stage cases and more prevalent in tumor-stage instances, often correlated with atypical clinical presentations. Despite its rarity, scant information is available about double-negative mycosis fungoides, with only a limited number of cases documented in the existing literature. This review aims to provide enhanced clarity, comprehension, and a detailed exploration of the spectrum encompassing double-negative mycosis fungoides.

The number of primary cutaneous lymphoma patients receiving low-dose radiotherapy is increasing, though controlled clinical trials defining the standard radiation dose for each specific entity have not yet been completed. Radiation oncologists are left with making highly individualized decisions that would be better enriched by additional clinical evidence. In this expert opinion, we aim to provide a clear recommendation to improve the current practice of radiation oncology. In addition, existing literature has been reviewed to develop recommendations for all types of primary cutaneous lymphoma. A prospective trial is urgently needed to identify the factors influencing patient outcomes following different radiation doses.