The study, conducted at Cerrahpaşa Medical Faculty in Istanbul and approved by the institutional review board there, retrospectively evaluated the clinical and follow-up records of patients diagnosed and managed at the centre over a ten-year period. Engin performed the skin biopsies, diagnosed and treated the patients, and led the manuscript; Yildirim assisted with follow-up and drafted the text; Erkoc classified treatments and staging and analysed the data. The work was carried out in accordance with the Declaration of Helsinki, and the authors report no conflicts of interest. As is typical for retrospective cohort analyses of rare lymphomas, the value of the dataset lies less in dramatic new findings than in the granular picture it paints of how one busy dermatology service handles a diagnostically treacherous disease over time.

Technically, mycosis fungoides belongs to the primary cutaneous lymphomas, a family of extranodal non-Hodgkin lymphomas that arise in the skin rather than in lymphoid organs. The current diagnostic framework is anchored by the 2018 update of the WHO-EORTC classification, which separates indolent entities such as early-stage mycosis fungoides from aggressive ones such as Sézary syndrome, the leukemic variant characterised by widespread erythroderma, circulating malignant T cells and a markedly worse prognosis. The International Consensus Classification of mature lymphoid neoplasms, published in 2022, further refined this landscape. Within that framework, mycosis fungoides follows a characteristic clinical course: patch-stage lesions progress to plaques, then potentially to tumours, and in a minority of patients to visceral involvement. Most patients, however, never advance beyond the early stages, which is why accurate staging at diagnosis is the single most important prognostic exercise.

That staging depends on a synthesis of clinical, histopathological and, where indicated, molecular data. Skin biopsies are examined for epidermotropism, the migration of atypical T lymphocytes into the epidermis, and for the formation of Pautrier microabscesses, small clusters of these cells that are highly characteristic though not always present. T-cell receptor gene rearrangement studies can demonstrate clonality, distinguishing a malignant population from a reactive infiltrate, but early lesions may lack convincing clonal evidence, forcing clinicians to repeat biopsies over months or years. Blood tests assess for Sézary cells, and in advanced cases, imaging and lymph node biopsy complete the tumour-node-metastasis-blood staging algorithm. The Istanbul study reflects this layered diagnostic process, with the corresponding author personally performing and interpreting the skin biopsies that anchored each patient’s diagnosis.

One of the best-documented problems in the field is diagnostic delay. A frequently cited Danish study by Skov and Gniadecki found that the histopathological diagnosis of mycosis fungoides is often delayed, with patients carrying the disease for years before a biopsy confirms it, partly because early histology is subtle and mimics spongiotic or psoriasiform dermatitis. Every additional year of misdiagnosis represents deferred access to skin-directed therapy and prolonged uncertainty for the patient. A ten-year single-centre dataset is precisely the kind of evidence that quantifies this burden in a specific population, and the Turkish authors frame their work explicitly as an evaluation of clinical and follow-up data, the raw material from which such delays and their consequences can be measured.

Treatment for mycosis fungoides is stage-adapted, and the European Organisation for Research and Treatment of Cancer issued updated consensus recommendations in 2023 that codify the current hierarchy. Early-stage disease is managed with skin-directed therapies: topical corticosteroids and retinoids, phototherapy with narrowband UVB for patches and thin plaques, psoralen plus ultraviolet A for thicker lesions, and localised radiotherapy or total skin electron beam therapy for more extensive or refractory cutaneous involvement. Advanced disease adds systemic options, including interferon-alpha, retinoids such as bexarotene, histone deacetylase inhibitors, antibody-based therapies and, in selected cases, allogeneic stem cell transplantation, the only treatment with potential for durable cure. Combination approaches, pairing a skin-directed modality with a systemic agent, are common in tumour-stage disease. The Istanbul team’s classification of treatments and staging across their cohort maps directly onto this algorithm and illustrates how a high-volume centre deploys it in practice.

Single-centre cohort studies of this kind occupy an important niche in rare-disease research. Randomised trials in mycosis fungoides are difficult to power because the disease is uncommon and its early stages progress slowly, so much of what is known about natural history, treatment patterns and outcomes comes from institutional series accumulated over years or decades. Previous examples include the retrospective analysis of 133 cutaneous lymphoma patients from a single Japanese centre published by Fujita and colleagues, which similarly documented presentation patterns and outcomes over a multi-year window. The Turkish dataset joins this tradition, offering a Mediterranean and Middle Eastern patient population whose demographic profile, referral pathways and treatment access may differ meaningfully from the Northern European and Japanese cohorts that dominate the literature.

The follow-up dimension of the study deserves particular emphasis. Mycosis fungoides can smoulder for decades, and late relapse or transformation to a more aggressive large-cell phenotype can occur years after apparent stability. Longitudinal data from a single centre, where patients are followed by the same diagnostic and therapeutic team, reduce the heterogeneity that plagues multi-site registries, though they also introduce the limitations inherent to retrospective design: reliance on recorded notes, potential loss of patients to follow-up, and the absence of a standardised prospective protocol. The authors’ explicit contribution statement, detailing who diagnosed, biopsied, treated, staged and analysed, underscores the continuity of care that gives such datasets their internal consistency.

For the wider scientific audience, the significance of this research letter lies in what it represents rather than in any single headline number. It demonstrates that cutaneous lymphoma care in Turkey is organised around internationally recognised classification and treatment frameworks, that long-term follow-up is feasible in a public hospital dermatology service, and that the diagnostic bottleneck remains the central challenge of the disease. It also reinforces a message that dermatologists have been repeating for years: persistent, treatment-resistant or unusually distributed skin lesions in adults warrant a low threshold for biopsy and, when histology is equivocal, serial re-biopsy and specialist referral. Earlier recognition will not change the biology of mycosis fungoides, but it moves patients into appropriate surveillance and stage-appropriate therapy sooner, which matters for quality of life and, in the minority who progress, for survival.

The study is available as a research letter in volume 318 of the Archives of Dermatological Research, and its full clinical tables and figures are accessible through the journal. As genomic profiling, targeted immunotherapies and biomarker-driven risk stratification enter the cutaneous lymphoma field, datasets like this one, grounded in a decade of unbroken clinical contact with patients, will serve as the historical baseline against which the next generation of diagnostics and treatments is judged. For now, the Istanbul experience stands as a reminder that in rare lymphomas of the skin, the most powerful clinical instrument remains the patient chart kept faithfully over many years.

Subject of Research: A 10-year single-centre retrospective evaluation of clinical presentation, staging, treatment and follow-up in patients with mycosis fungoides, the most common cutaneous T-cell lymphoma.

Article Title: Evaluation of clinical and follow-up data in patients with mycosis fungoides: a 10-year single-centre experience

Article References: Engin, B., Yildirim, G., & Erkoc, Y. C. (2026). Evaluation of clinical and follow-up data in patients with mycosis fungoides: a 10-year single-centre experience. Archives of Dermatological Research, 318(1), Article 449. https://doi.org/10.1007/s00403-026-04943-7

Image Credits: AI Generated

DOI: 10.1007/s00403-026-04943-7

Keywords: mycosis fungoides, cutaneous T-cell lymphoma, dermatology, WHO-EORTC classification, diagnostic delay, skin biopsy, staging, skin-directed therapy, Sézary syndrome, retrospective cohort study, Istanbul, long-term follow-up

The trial compared 0.05 percent clobetasol propionate ointment, one of the strongest topical steroids in clinical use, with 0.1 percent tacrolimus ointment, a calcineurin inhibitor best known for treating atopic dermatitis. Twenty patients received each treatment. The question matters because early-stage mycosis fungoides is highly treatable with skin-directed therapies, yet the ideal first-choice agent has remained contested. Topical steroids are cheap, familiar, and fast, but long-term use carries the familiar toll of skin atrophy, striae, telangiectasia, and taper-dependent relapse. Tacrolimus offers a steroid-sparing alternative that suppresses T-cell activation without thinning the skin, but direct comparative evidence against clobetasol in lymphoma patients has been almost nonexistent until now.

On raw clearance rates, the verdict was lopsided. In the clobetasol group, 95 percent of patients achieved a complete clinical response, meaning their lesions resolved entirely, and the remaining 5 percent achieved a partial response. In the tacrolimus group, by contrast, only 60 percent reached complete clearance and 20 percent a partial response. The median time to complete response also favored the steroid, at two months versus three and a half months for tacrolimus, although that timing difference did not reach statistical significance. For clinicians and patients alike, the message of the first analysis is straightforward: clobetasol clears early patches and plaques faster and more often.

But the story changed when the researchers followed patients forward in time. Among those who achieved complete clearance, relapse occurred in 63.2 percent of the clobetasol-treated patients compared with just 25 percent of those treated with tacrolimus, a difference that approached but did not reach conventional statistical significance. Kaplan-Meier survival analysis, which tracks how long patients remain disease-free over months and years, showed a trend toward longer relapse-free survival in the tacrolimus group, with a log-rank p-value of 0.060. In a study of only forty patients, trends of this size are tantalizing rather than definitive, but they hint at a trade-off that clinicians have long suspected: steroids win the sprint while tacrolimus may hold ground longer in the marathon.

The biology behind that trade-off is worth unpacking. Mycosis fungoides is driven by clonal malignant T lymphocytes that home to the skin, and both drugs attack the inflammatory machinery these cells depend on, but by different routes. Clobetasol binds intracellular glucocorticoid receptors, broadly repressing transcription of inflammatory cytokines and inducing apoptosis in immune cells, a blunt but powerful instrument. Tacrolimus inhibits calcineurin, a phosphatase essential for activating the transcription factor NFAT in T cells, thereby blocking interleukin-2 production and T-cell proliferation with far greater selectivity. Because the steroid suppresses inflammation indiscriminately, it clears lesions dramatically, but once therapy stops or is tapered, the underlying malignant clone may rebound quickly. Calcineurin inhibition, gentler and more targeted, may leave residual disease control in place even as visible lesions fade more slowly.

Safety considerations sharpen the clinical calculus further. Prolonged use of super-potent steroids on thin skin, on the face, or in folds produces atrophy, striae, and secondary infection, and mycosis fungoides frequently affects these vulnerable sites and demands years of intermittent treatment. Tacrolimus ointment does not cause skin thinning, which is precisely why dermatologists have proposed it as a steroid-sparing option, and earlier work including a phase 2 trial of the related calcineurin inhibitor pimecrolimus published in The Lancet Haematology in 2022 demonstrated meaningful activity and tolerability in early-stage disease. One historical concern, a theoretical lymphoma risk from systemic absorption of calcineurin inhibitors, has been substantially allayed by large cohort studies such as the JOELLE investigations, which followed tens of thousands of users and found no convincing increase in lymphoma incidence, and pharmacokinetic studies showing minimal systemic exposure when tacrolimus is applied to intact skin.

The Istanbul team’s findings also sit within a growing evidence base for topical therapy in this lymphoma. Zackheim’s foundational work established patch-stage mycosis fungoides as responsive to potent topical corticosteroids, and a 2025 comparison from the same Turkish group, published in the Brazilian Annals of Dermatology, found clobetasol competitive with oral bexarotene in early disease. What has been missing is exactly the kind of direct steroid-versus-calcineurin-inhibitor comparison this study provides, even in retrospective form. The authors themselves caution that comparative data on topical therapies remain limited and that calcineurin inhibitors have been proposed as steroid-sparing alternatives largely on theoretical and indirect grounds.

The study’s limitations deserve honest weight. Forty patients divided into two groups of twenty, treated retrospectively rather than randomized, leave ample room for selection bias, confounding by disease severity or anatomical site, and underpowered statistics. Relapse definitions and follow-up duration are critical in a disease whose natural history is measured in decades, and differences that miss significance at p-values just above 0.05, as several here do, could easily prove real in a larger cohort or dissolve into noise. The authors do not claim that tacrolimus prevents relapse; they report trends. Still, in rare diseases, randomized trials are notoriously difficult to populate, and carefully collected comparative cohort data like this often guides practice for years before definitive evidence arrives.

For patients, the practical takeaway is a conversation rather than a prescription. Someone with extensive thin plaques on the face or flexures, or a history of steroid-induced skin damage, may reasonably begin with tacrolimus, accepting slower clearance and a somewhat lower chance of complete response in exchange for durability and skin preservation. Someone with thicker, widespread plaques and a need for rapid control may start with clobetasol, then consider rotating to or maintaining with a calcineurin inhibitor to hold the gains while sparing the skin. The pattern in this data, fast clearance with higher relapse on one side and slower, stickier remission on the other, maps neatly onto that sequential strategy, which many dermatologists already employ empirically.

What happens next is the familiar rhythm of clinical oncology: these findings need prospective confirmation, ideally in a randomized trial with standardized response criteria under the current ISCL-EORTC staging framework, longer follow-up to truly characterize relapse-free survival, and enough patients to convert suggestive p-values into conclusions. Until then, the Istanbul study earns its place as one of the few direct comparisons of the two most accessible topical treatments for early mycosis fungoides, and it reframes the question clinicians ask at the bedside. It is no longer simply which ointment clears the skin, but which ointment keeps it clear, and the answer may be that the humble immunomodulator cream, long relegated to second-line status, deserves a more prominent seat at the table for carefully selected patients facing this indolent lymphoma.

Subject of Research: Comparative efficacy of topical corticosteroid versus calcineurin inhibitor therapy in early-stage mycosis fungoides

Article Title: Comparison of the efficacy of topical 0.05% clobetasol propionate and topical 0.1% tacrolimus in the treatment of early-stage mycosis fungoides

Article References: Comparison of the efficacy of topical 0.05% clobetasol propionate and topical 0.1% tacrolimus in the treatment of early-stage mycosis fungoides. (n.d.). https://doi.org/10.1007/s00403-026-04958-0

Image Credits: AI Generated

DOI: 10.1007/s00403-026-04958-0

Keywords: mycosis fungoides, cutaneous T-cell lymphoma, clobetasol propionate, tacrolimus, topical therapy, dermatology, relapse-free survival, calcineurin inhibitors, skin-directed treatment, clinical research, Comparison, efficacy