Diagnosis Of Mycosis Fungoides Research Articles

When mycosis fungoides seems not to be within the spectrum of clinical and histopathological differential diagnoses

The most prevalent primary cutaneous T-cell lymphoma, mycosis fungoides (MF), is characterized by the development of plaques and nodules after an erythematous patchy phase that is non-specific. An infiltrate of atypical small- to medium-sized cerebriform lymphocytes in the superficial dermis, with variable epidermotropism, is the histopathological hallmark of the disease. In more advanced stages of the illness, large-cell transformation may be seen. Early diagnosis of MF can be very challenging based only on histopathologic or clinical findings, so it is critical to have a clinical-pathological correlation. Many atypical variants of MF that deviate from the classic Alibert-Bazin presentation of the disease have been described over the past 30 years, sometimes with different prognostic and therapeutic implications. Clinically or histopathologically, they can mimic a wide range of benign inflammatory skin disorders. To make a conclusive diagnosis in these cases, it is recommended to take multiple biopsies from various lesions and to carefully correlate the clinical and pathological findings. We have outlined the various facets of the illness in this review, positioning MF as a “great imitator”, with an emphasis on the more recently identified variations, differential diagnosis, and its benign mimics.

Gene Expression Differences Identified in Skin Samples of Mycosis Fungoides, Atopic Dermatitis, and Psoriasis

Background: Recent advances in the understanding of the molecular mechanisms underlying atopic dermatitis (AD) and psoriasis (PSO) have led to the development of multiple targeted therapies. Yet, molecular heterogeneity contributes to inconsistent clinical presentation and therapeutic response. Further, systemic treatment of presumed AD or PSO can lead to delays in both diagnosis and proper treatment of patients with a true diagnosis of mycosis fungoides (MF) – a potentially dangerous clinical mimic of AD and PSO that requires a rigorous histologic and molecular workup to diagnose. Therefore, a non-invasive method to distinguish molecular profiles of MF from AD and PSO could inform accurate diagnoses and avoid inappropriate treatment of MF. We have previously shown transcriptomic differences in AD and PSO samples obtained by a non-invasive scraping technique. However, this technique has not been used to assess differences in gene expression profiles of MF samples. Objectives: To identify gene expression differences based on diagnosis of MF, AD, or PSO and response to targeted systemic AD or PSO therapies. Methods: Lesional baseline samples were assessed from 76 patients (AD, n=24; PSO, n=48; and MF, n=4) enrolled in one of two IRB-approved studies (IDENTITY or SIGNAL-MF). Lesional samples were collected by epidermal scraping and preserved in RNA buffer. Library preparation and next generation RNA sequencing was performed using the Ion AmpliSeq Transcriptome Human Gene Expression panel on the S5 Prime sequencer (ThermoFisher). Clinical responses for AD and PSO were further assessed over 3 months using the eczema and psoriasis area and severity index (EASI and PASI, respectively). Genes were considered differentially expressed if there was a log2fold change >|1.0| and padj <.05. Results: Statistically significant differences in gene expression were observed between AD, PSO, and MF lesions. Further, genes were differentially expressed in baseline skin scrapings obtained from super-responders to dupilumab, which blocks both IL-4 and IL-13 signaling, and PSO therapies including the IL-23 inhibitor risankizumab relative to those who did not achieve ≥90% improvement. Conclusion: A non-invasive molecular test could be developed to distinguish between AD, PSO, and MF, and further identify super-responders to targeted PSO and AD therapies.

Evaluation of the prognostic significance of clinical features of tumoral lesions in an extensive series of mycosis fungoides.

Tumors indicating the advanced stage of mycosis fungoides (MF) have a rich clinical spectrum. Although it is known that the prognosis of MF generally worsens following the development of tumors, some cases may have a relatively indolent course, and the role of clinical characteristics regarding prognosis has still not been well understood. MF patients were retrospectively evaluated regarding the development of tumors. Besides demographic characteristics, data of the subtype and stage of the disease were recorded. The clinical features of tumors, including number (<5, 5-10, 11-20, or >20), location, dimension (diameter of ≥5 cm), presence of ulceration, and surrounding inflammation, were noted. Univariate and multivariate analyses evaluated the relationship between overall survival (OS) with demographic and clinical features. Among 730 consecutive MF patients, tumors developed in 8.2% (n = 60), of whom 46.7% were diagnosed with advanced-stage MF from the beginning. The most common subtype was folliculotropic MF (53.3%). Most patients (55%) had multiple tumors, and the most frequent localization was the trunk (71.7%). Most tumors presented as smooth-surfaced, indurated papules and/or nodules (70%), while others were reddish-purple, occasionally accompanied by ulceration (50%), perilesional inflammation (23.3%), and attaining large dimensions (25%). Mortality was recorded in 51.7% of patients, and the 5-year OS rate from the diagnosis of tumors was 49%. Independent poor prognostic factors for OS in multivariate analysis included older age at the time of diagnosis, presence of tumors at the initial MF diagnosis, presence of over 20 tumors, and the existence of large tumors. Tumoral MF seen in older patients, the first diagnosis of MF in this stage, presenting with generalized and large tumors, seems to be a predictive factor for OS.

Micro-RNAs in the Diagnosis of Cutaneous T-Cell Lymphomas

Rationale. Early diagnosis of mycosis fungoides (MF), as the most common form of T-cell lymphoma, presents significant challenges. The diagnosis of MF is based on the following criteria: comprehensive assessment of the clinical picture of the disease, histological and immunohistochemical examination of the skin, and determination of rearrangement of the T-cell receptor gene, but even this does not always aid in diagnosis. The aim of the study is to investigate the expression of micro-RNAs (miR-223, -423, -663, -16, -326, -711) in the blood plasma and leukocytes of patients with a presumptive diagnosis of MF to improve the disease diagnosis. Methods. This study included 50 patients aged 24 to 79 years, of whom 30 patients had a preliminary diagnosis of MF and 20 patients with small plaque parapsoriasis, who formed the comparison group. All patients underwent histological, immunohistochemical examination of skin biopsies, and determination of micro-RNA (miR-223, -423, -663, -16, -326, -711) expression in blood plasma and leukocytes by real-time PCR. Results. Analyzing the results of clinical-anamnestic, histological, and immunohistochemical research methods, the diagnosis of MF was established in 22 of 30 (73.3%) patients, of which 9 of 14 (64.3%) were in the early stages of the disease. small plaque parapsoriasis. Conclusion. During our study, it was found that the studied micro-RNAs (miR-326, -663, -711, -223, -423, -16) in the blood plasma and leukocytes of patients with MF have statistically significant levels of expression compared to the low level of expression of these micro-RNAs in patients with small plaque parapsoriasis. The expression of micro-RNAs we studied in the skin contributes to the improvement of MF diagnosis with an accuracy of up to 90%.

Dermatoscopic Characteristics, Lesional Capillaroscopic Features, and Histopathological Correlation of Small Plaque Parapsoriasis and Mycosis Fungoides.

Dermatoscopy is a frequently used non-invasive diagnostic procedure. Considering that mycosis fungoides (MF) mimics parapsoriasis clinically in early stages, we aim to determine the dermatoscopic criteria and the histopathological correlations in patients with MF and small plaque parapsoriasis (SPP). This prospective study involved 28 patients with clinical and histopathological diagnoses of MF and 31 patients with SPP. Videodermoscopy and USB capillaroscope were used to evaluate the patients vessels at ×200 magnification. Vascularity was evaluated through microvascular density (MVD) scoring involving CD34 antibody staining. Fifty-nine patients were included in this study. The scores corresponding to the presence of short linear vessels, linear-curved vessels, branching linear vessels, and non- structured orange-colored areas were significantly higher in the MF patients than in the SPP patients (P < 0.05). The highest MVD (P = 0.01) scores were also higher in the MF patients than in the SPP patients. The SPP and early-stage MF patients differed in their MVD scores, and the findings correlated with the dermatoscopy and lesional capillaroscopy findings. Differentiating features between SPP and MF were thus identified.

Phenotypic switch in mycosis fungoides: A tertiary cancer center experience

BackgroundChanges in immunophenotype in mycosis fungoides (MF) are rarely reported, making this phenomenon a diagnostic challenge with unclear significance for the disease's biological behavior. This study examines a large series of MF patients who exhibited a phenotype switch (PS) and analyzes their clinical and histopathologic characteristics. DesignInstitutional files were searched for MF cases exhibiting PS between 2010 and 2020. Clinical, follow-up, and histopathological data were collected. ResultsForty-two biopsies from 32 patients (13 women and 19 men, median age 67.5) showed PS. Eight patients (25 %) experienced multiple PS during their disease course. The median time for PS was 22 months from the initial diagnosis. In 5 cases tested, identical TCR clone peaks were detected in the immunophenotypically distinct lesions. Median follow-up was 14.5 months. Among deceased patients, median time from MF diagnosis to PS was 20.6 months, while among the patients who were still alive, median time was 44.1 months. ConclusionMF biopsies can show PS during the course of the disease and may indicate a change in clinical behavior. 28.1 % of patients displayed more than one PS, further indicating high plasticity of MF cells. No obvious association was found between PS and therapy initiation or response. Features that appeared to portend a worse clinical course were earlier PS in the course of the disease and PS from CD4-/CD8-to CD8+, and CD8+ to CD4-/CD8-. Awareness of this phenomenon is crucial to avoid misdiagnosing phenotypically distinct lymphomas as second primaries and to alert clinicians about potential changes in the disease's clinical course.

Dermoscopy in the Diagnosis of Mycosis Fungoides: Can it Help?

The diagnosis of mycosis fungoides (MF) is challenging since it can mimic a variety of benign skin conditions. Multiple biopsies for histopathologic and immunohistochemical examination are required to diagnose MF. Dermoscopy is an affordable, non-invasive device with expanding indications in dermatology, OBJECTIVES: To investigate the dermoscopic morphology of MF variants and assess the correlation between dermoscopic criteria, histopathologic, and immunohistochemical findings, METHODS: We included 88 patients with several MF variants (classic, hypopigmented, hyperpigmented, poikilodermatous, erythrodermic, and folliculotropic). The diagnosis was histopathologically and immunohistochemically confirmed. Dermoscopic findings were collected, statistically analyzed, and correlated with the results of histopathology and immunohistochemistry, RESULTS: All patients had MF diagnosis in H&E-stained sections. The majority revealed positive staining with CD3, 4, 8 and negative CD7. Orange-red areas of discoloration, short linear, and spermatozoa like blood vessels are the most frequent dermoscopic findings, while an analysis per MF variant was also performed. The frequently observed dermoscopic structures in classic MF were patchy whitish scales, dotted, short linear vessels, and spermatozoa-like vessels, CONCLUSIONS: Dermoscopy reveals a repetitive dermoscopic pattern in MF (non-homogenous pink to erythematous background, patchy areas of orange discoloration, patchy whitish scales, dotted and short linear blood vessels with some variations according to the clinical variant.

Mycosis Fungoides: Case report of progression successfully treated with liposomal doxorubicin

Mycosis fungoides is the most common primary cutaneous T-cell lymphoma. It is a non-Hodgkin lymphoma that begins in the skin and is characterized by a slow clinical evolution of three stages: macules, plaques and tumors. The advanced stage includes lymph node, visceral, or blood involvement, and requires skin-directed therapy associated with systemic medications. The case of a 49-year-old female patient with a diagnosis of mycosis fungoides in the malar region since July 2019 is presented, initially treated between November 2019 and March 2020 with 3 cycles of the CHOP chemotherapy regimen - cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin) and prednisone without achieving any clinical response. Subsequently without follow-up or treatment. In February 2023, progression of the disease was documented due to worsening of the lesion in the malar region and involvement of the glutes and back, additionally with cervical lymphadenopathy but without bone marrow involvement. She is considered a candidate for liposomal doxorubicin, with which she has completed 5 cycles to date with excellent clinical response. Current reassessment studies using positron emission tomography show complete tumor response. A bone marrow transplant is the therapeutic option that is being considered at the moment.

Cutaneous T-Cell Lymphoma (Mucosal Fungoid) as First Manifestation of Metastatic Lymphoma

Primary cutaneous T-cell lymphomas are a diverse group of extranodal non-Hodgkin lymphomas characterized by the infiltration of malignant T-cells within the skin. Mycosis fungoides (MF), the most common subtype, typically presents with skin-limited manifestations. However, in a subset of cases, it can herald the onset of systemic lymphoma, representing a diagnostic challenge for clinicians. This article explores a compelling clinical case of primary cutaneous T-cell lymphoma, specifically mycosis fungoides, manifesting as an initial sign of disseminated or metastatic lymphoma. We dissect the complex diagnostic and management considerations associated with this unique clinical presentation. Through a review of the current literature and clinical insights, we delineate the clinical, histopathological, and immunophenotypic features that facilitate the diagnosis and differentiation of MF as an isolated cutaneous entity from MF with secondary extracutaneous involvement. The article highlights the critical role of multidisciplinary collaboration among dermatologists, oncologists, and pathologists in achieving timely and accurate diagnosis and guiding therapeutic decisions. It further underscores the evolving landscape of treatment options for this challenging subset of patients, ranging from skin-directed therapies to systemic agents. Additionally, this case provides a stark reminder of the importance of ongoing surveillance, as the clinical course of MF may unpredictably transition to a more aggressive form. In conclusion, this case serves as a vivid illustration of mycosis fungoides with mucosis fungoides as its initial presentation, challenging the conventional understanding of primary cutaneous T-cell lymphomas. The intricate interplay of clinical, histological, and immunophenotypic data informs the diagnosis and informs the broader clinical community about the potential metamorphosis of cutaneous lymphomas into systemic lymphomas. Understanding such cases is crucial for early intervention and improved patient outcomes.

Mycosis Fungoides in Solid-Organ Transplant Recipients: A Multicenter Retrospective Cohort Study

Background: Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics. Objective: The aim was to study the characteristics of MF in SOTRs with an emphasis on the immunosuppressive therapy. Methods: A retrospective cohort of patients diagnosed with MF, who were also SOTRs, were followed at 3 cutaneous lymphoma outpatient clinics, between January 2010 and February 2022. Results: Ten patients were included (7 male; median ages at transplantation and at diagnosis of MF were 33 and 48 years, respectively; 40% were diagnosed before the age of 18 years). Median time from transplantation to diagnosis of MF was 8 years (range 0.5–22). Transplanted organs and immunosuppressive treatments included: liver (n = 5; 4 treated with tacrolimus, 1 with tacrolimus and prednisone), kidney (n = 3), liver and kidney (n = 1), and heart (n = 1), all treated with mycophenolic acid, tacrolimus, and prednisone. Nine had early-stage MF (IA – 4, IB – 5; 40% with early folliculotropic MF), treated with skin-directed therapies, in 2 combined with acitretin, achieving partial/complete response. One patient had advanced-stage MF (IIIA) with folliculotropic erythroderma, treated with ultraviolet A and narrow-band ultraviolet B with acitretin, achieving partial response. Immunosuppression was modified in 3. At last follow-up (median 4 years, range 1–8), no stage progression was observed; 5 had no evidence of disease, 5 had active disease (IA/IB – 4, III – 1). Conclusions: MF in SOTRs is usually diagnosed at an early stage, with overrepresentation of folliculotropic MF, and of children. Immunosuppressive therapy alterations, not conducted in most patients, should be balanced against the risk of organ compromise/rejection. Disease course was similar to MF in immunocompetent patients, during the limited time of follow-up.

Hyperpigmented Mycosis Fungoides Masquerading as Longstanding Lichen Planus Pigmentosus: A Diagnostic Pitfall.

Mycosis fungoides (MF) is a rare primary cutaneous T-cell lymphoma, accounting for 50%-60% of all cutaneous T-cell lymphoma cases. It has a prevalence of approximately 5-6 cases per 1 million people annually and a higher incidence in dark-skinned populations. We report a case of hyperpigmented MF in a 72-year-old dark-skinned man with a 5-year history of progressive, widespread poikilodermatous patches and thin plaques on the back and bilateral legs. The patient had been treated for lichen planus pigmentosus for 5 years without significant response to therapy. Multiple biopsies revealed a band-like lymphoid infiltrate in the dermis, accompanied by intraepidermal lymphocytes, some of which had larger hyperchromatic nuclei. CD4 + T lymphocytes were predominant over CD8 + T-positive cells located along the epidermis, dermoepidermal junction, and in the dermis. A diagnosis of hyperpigmented MF was made based on the clinical, histopathological, and immunohistochemical findings. This case report highlights the importance of considering hyperpigmented MF as a differential diagnosis in patients with longstanding lichen planus pigmentosus, particularly when there is a lack of response to therapy.

Dupilumab aggravates Sézary syndrome: The importance of accurate pathological diagnosis

We report a case of Sézary syndrome aggravated by dupilumab. Although a diagnosis of atopic dermatitis was made previously, our retrospective diagnosis was cutaneous T-cell lymphoma. A 72-year-old woman was referred for evaluation of erythema over her entire body. She had received a diagnosis of atopic dermatitis (AD) based on skin biopsy elsewhere 7 years earlier. Since her symptoms were resistant to topical corticosteroids and oral antihistamines, dupilumab was started. She noticed peripheral lymph node enlargement 11 months after the commencement of dupilumab. Physical examination revealed generalized erythroderma with desquamation (Figure 1A,B) and lymphadenopathy in the neck, axilla, and inguinal region. A biopsy from her abdomen showed dense infiltrations of atypical lymphoid cells in the upper dermis with epidermotropism (Figure 1C,D). Immunohistochemically, the infiltrating cells were positive for CD3 and CD4; CD8 was almost negative. There was a 50% deletion of CD7 (Figure 1E–H). Her peripheral blood (PB) white blood cell count was 7660/μL, with 35% abnormal lymphocytes (2681/μL). Although CD4+/CD26− or CD4+/CD7− cells were not assessed, CD4/CD8 ratio was 10.59.1, 2 Human T-lymphotropic virus-1 antibody was negative. Monoclonal gene rearrangement of T-cell receptor β-chain was identified in her PB by Southern blot analysis. Inguinal lymph node biopsy showed partial effacement by atypical lymphocytes. The diagnosis was Sézary syndrome (SS), stage IVA2 (T4N3MXB2). Taking into account the risk of tumor lysis syndrome due to high tumor burden, we selected conventional multiagent chemotherapy as an initial therapy before using a molecular-targeted drug. Dupilumab was discontinued; cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) were started. After two cycles of CHOP, biweekly intravenous mogamulizumab was introduced. Her skin lesions gradually improved. The PB abnormal lymphocyte count decreased. Her disease was well controlled with mogamulizumab for 17 months. We reviewed the previous biopsy specimen. Dense dermal infiltrates with atypical cells and epidermotropism were seen (Figure 1I,J). These infiltrates were positive for CD3 and CD4. CD8-positive cells were sparse. There was a 30% deletion of CD7 (Figure 1K–N). The atypical cells were CCR4+ and CD68−. Although a diagnosis of AD was made previously, our retrospective diagnosis was cutaneous T-cell lymphoma (CTCL). Dupilumab is a monoclonal antibody which inhibits both IL-4 and IL-13 signaling pathways by binding specifically to the α subunit of the IL-4 receptor. Several cases of CTCL that developed or worsened after dupilumab use have been reported. A proposed mechanism of CTCL due to dupilumab is the involvement of IL-13 receptor α2 (IL-13Rα2), which is expressed on CTCL cells and promotes tumor progression. When dupilumab blocks IL-4 and IL-13 receptors, serum IL-13 levels increase. Because dupilumab inhibits IL-13Rα1 but not IL-13Rα2 signaling, increased IL-13 levels due to dupilumab stimulate IL-13Rα2, leading to the activation and proliferation of lymphoma cells.3 To our knowledge, there are 36 cases3-19 of CTCL worsened by dupilumab based on the diagnosis of AD or eczema have been reported. Of these 36 patients, 18 underwent skin biopsy prior to dupilumab therapy; no evidence of CTCL was described in 16 patients.3-10 In one remaining patient, the authors re-evaluated the biopsy specimen taken before dupilumab treatment and revised the diagnosis to early CTCL-not otherwise specified.10 In another patient, the first skin biopsy taken before dupilumab was compatible with AD; however, the diagnosis of mycosis fungoides was made by the second biopsy taken on the first day of dupilumab treatment. After 6 months of dupilumab treatment, the third biopsy turned out CD30-positive anaplastic large-cell lymphoma.11 When using dupilumab for AD, clinicians should be alert to the development or worsening of CTCL. Skin biopsy with immunohistochemical examination is strongly recommended before dupilumab therapy, especially in patients with erythroderma and elderly patients. The authors declare no conflict of interest. Approval of the research protocol: N/A. Informed Consent: N/A. Registry and the Registration No.: N/A. Animal Studies: N/A.

Dupilumab-associated mycosis fungoides: a cross-sectional study.

Treating atopic dermatitis (AD) with dupilumab, a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), may be associated with the progression of mycosis fungoides (MF).This study aimsto examine the associations between the length of dupilumab treatment, age and sex, and the onset of MF.An institutional data registry and literature search were used for a retrospective cross-sectional study. Only patients with a diagnosis of MF on dupilumab for the treatment of AD and eczematous dermatitis were included.The primary outcome was the length of dupilumab exposure, age, sex, and the onset of MF. Linear correlations (Pearson) and Cox regression analysis were used to assess the correlation and the risk.A total of 25 patients were included in this study. Five eligible patients were identified at our institution. In addition, a PubMed review identified an additional 20 patients. At the time of MF diagnosis, the median age was 58, with 42% female. Disease history was significant for adult-onset AD in most patients (n = 17, 65.4%) or recent flare of AD previously in remission (n = 3, 11.5%). All patients were diagnosed with MF, and one patient progressed to Sézary syndrome while on dupilumab, with an average duration of 13.5months of therapy prior to diagnosis. Tumor stage at diagnosis of MF was described in 19 of the cases and ranged from an early-stage disease (IA) to advanced disease (IV). Treatment strategies included narrow-band UVB therapy, topical corticosteroids, brentuximab, pralatrexate, and acitretin. Male gender, advanced-stage disease, and older age correlated significantly with the hazard of MF onset and a shorter time to onset during dupilumab treatment.Our results suggest a correlation between the duration of dupilumab treatment and the diagnosis of MF, the higher MF stage at diagnosis, and the shorter the duration of using dupilumab to MF onset. Furthermore, elderly male patients appeared to be more at risk as both male gender and older age correlated with a hazard of MF diagnosis. The results raise the question as to whether the patients had MF misdiagnosed as AD that was unmasked by dupilumab or if MF truly is an adverse effect of treatment with dupilumab. Close monitoring of these patients and further investigation of the relationship between dupilumab and MF can shed more light on this question .

Health-related quality of life and economic burden in Chinese patients with cutaneous T-cell lymphoma.

e19533 Background: Cutaneous T-cell lymphoma (CTCL) is a rare type of non-Hodgkin lymphoma. As described in European Organization for Research and Treatment of Cancer Consensus, the subtypes of mycosis fungoides (MF) and Sézary Syndrome (SS) comprised roughly 55% and 5% of CTCL, respectively. The clinical presentations of MF and SS include skin lesion, tumors, ulcerations, systemic involvements and even death. This study aimed to measure the overall HRQoL and economic burden of MF and SS patients in China. Methods: A cross-sectional survey was conducted from 21 July 2022 to 24 October 2022. Eligible adult participants with a pathologically confirmed diagnosis of either MF or SS were recruited from specialty or general hospitals across China. All participants were asked to complete a questionnaire that assessed HRQoL and annual economic burden. Validated instruments in Chinese, specifically the EuroQoL Group’s five-level QoL five-dimensional questionnaire (EQ-5D-5L), Functional Assessment of Cancer Therapy-General (FACT-G), and Skindex-29, were used to assess general, cancer and skin-related HRQoL. All HRQoL outcomes were calculated using the scoring system provided by the institutions, and EQ-5D utility scores were mapped using the China time trade-off value sets. As for economic burden, it was investigated from the societal perspective, as the direct medical costs, direct non-medical costs, and productivity loss were all calculated. Results: A total of 61 patients were recruited and completed the survey. Patients resided in 38 cities of 21 provinces across China. 56 patients (92%) were diagnosed with MF and 5 (8%) with SS. 56% were male, with a mean age of 39 years. Half of the patients had early-stage disease (defined as less than stage IIB, patch or plaque), with the remainder having late-stage disease. Among the recruited patients, 43 (70%) received skin-directed therapy, and 55 (90%) received systemic therapy. As for HRQoL measures, EQ-5D utility score was 0.79 (±0.18), FACT-G score was 61.3 (±12.4), and the Skindex-29 score was 43.4 (±24.2). Comparison between patients with early-stage disease and late-stage is presented in the table. As for economic burden, the annual per capita cost for MF and SS patients was CNY 86,729 (USD 12,428), which greatly exceeded the annual disposable income in 2022 (CNY 36,883, equals USD 5,440). Conclusions: This was the first study investigating economic burden and HRQoL using patient-reported outcomes conducted in mainland China. The findings suggested that MF and SS has significantly compromised patients’ HRQoL and posed substantial economic burden. [Table: see text]

“Missed” Diagnosis of Mycosis Fungoides (MF) for the Past 13 years

“Missed” Diagnosis of Mycosis Fungoides (MF) for the Past 13 years

Mycosis Fungoides: A differential diagnosis to consider for lichenoid keratosis

Mycosis fungoides (MF) has a wide spectrum of presentation. Its clinic is polymorphic, leading to several clinical variants. Chronic diffuse hyperpigmented lesions can be found in MF. We describe a case of lichenoid type mycosis fungoides. It differs from the classical form by the presence of erythematous and or pigmented scaly papules and not pruritic. The clinicopathological correlation is thus essential to establish a precise diagnosis of MF and its clinical simulators. Key words: Mycosis fungoides, Cutaneous T lymphoma, Chronic lichenoid keratosis

Tape stripped stratum corneum samples are suitable for diagnosis and comprehensive proteomic investigation in mycosis fungoides.

Mycosis Fungoides (MF) is a common cutaneous T-cell lymphoma. It can sometimes be challenging to diagnose MF using current clinico-histopathological criteria. Non-invasive molecular profiling analysis has the potential to aid the diagnosis and understanding of MF. Lesional and body site matched normal stratum corneum samples were obtained from the same MF patients (n=28) using adhesive discs, followed by proteomic analyses using data-independent acquisition mass spectrometry (DIA-MS). Differential abundance analyses and bioinformatic analyses were performed to identify differentially abundant proteins and altered biofunctions between the MF and normal stratum corneum samples. In total, 1303 proteins were identified, of which 290 proteins were significantly changed in the MF cohort compared to the normal stratum corneum. Ingenuity pathway analysis (IPA) predicted the significant inhibition of cell death of cancer cells and significant activation of immune-related activities and viral infection in the MF lesions. MF lesions were also associated with upstream regulators relating to immuno-oncologic dysfunctions. The top-250 variating proteins efficiently separated normal stratum corneum from matched MF samples. Non-invasive proteomic analysis could transform the diagnosis of MF by reducing the need for invasive biopsy. The identification of altered biological functions may serve as useful biomarkers to predict MF progression.

The Value of Immunohistochemical Expression of TOX, ICOS, and GATA-3 in the Diagnosis of Mycosis Fungoides.

Mycosis fungoides (MF) is considered the commonest type of cutaneous T-cell lymphoma representing about 50% of all primary cutaneous lymphomas. Differentiation between MF and another inflammatory dermatitis (BIDs) is important to ensure proper management. We aimed to evaluate the immunohistochemical expression of T OX, ICOS, and GATA binding protein 3 (GATA-3) in early stages MF (stage IA and IB) to establish their diagnostic value and to guide the use of inhibitors in the treatment of cutaneous T-cell lymphomas. A retrospective study of 75 skin paraffin blocks (punch biopsy) 40 cases of MF and 35 cases of eczematous dermatitis as a group representing other inflammatory dermatitis were retrieved from archives of the pathology department of our University, during the period from October 2017 to May 2021. About 98% and 90% of patients in the MF group had positive T OX and ICOS, while 70% of them had positive GATA-3. High expression of T OX, ICOS, and GATA-3 was associated with higher stages. T OX is considered a diagnostic marker for early MF. The importance of identifying novel markers in MF expressed by immunohistochemistry, such as ICOS, has been established. According to our results, GATA-3 could be used as an accessory marker in the diagnosis of MF when combined with T OX and ICOS in a panel.

Mycosis Fungoides: A Diagnostic Challenge

Background: Mycosis fungoides (MF) is the most frequent type of cutaneous T-cell lymphomas (CTCL), a heterogeneous group of non-Hodgkin lymphoma of T-cell origin. CTCLs accounts for about 4% of all non-Hodgkin lymphoma. MF mainly involves the skin but in advanced cases it may involve the lymph, blood and other organs. It mimics other skin disorders like erythema necroticans, leprosy, psoriasis etc which leads to delayed diagnosis and subsequent treatment. Case report: A 61 year old male patient visited the OPD of a tertiary care hospital in Eastern India with multiple reddish elevated lesions for last 6 months which later became dome shaped and then ulcerated. He did not have any fever or itching. He informed that he had been taking Homeopathic medicine previously, but the identity of the said medicine could not be confirmed. Physical examination ruled out the presence of pallor, jaundice, oedema and cyanosis. Pulse and BP were within normal range. Systemic examination was unremarkable except mild hepatomegaly. Cutaneous examination revealed multiple erythematous indurated plaques, papules and nodules over chest, abdomen, back, limbs and face. Few of the plaques present on the trunk and left arm had developed ulcers having a necrotic floors. Cervical, axillary and inguinal lymph nodes were palpable, being firm in consistency and mobile in nature. Hair, nail and mucosal examination revealed normal results. Complete blood count (CBC), peripheral blood smear(PBS), serum urea and creatinine level did not deviate from normal findings. Ultrasonography of whole abdomen showed a mildly enlarged liver. A prominent lymph node in the aortocaval groove could be appreciated on the computed tomography(CT) scan of whole abdomen. CT scan of chest revealed bilateral axillary lymphadenopathy. Erythema necroticans, sarcoidosis and CTCL were considered as the differential diagnoses. Lesional biopsy revealed irregular epidermal hyperplasia, parakeratosis and epidermotropism in the absence of spongiosis.There was infiltration of atypical lymphocytes in the epidermis, forming well developed Pautrier’s micro abscesses. The lymphocytes were tagging the dermo-epidermal junction and within the epidermis showing surrounding halo, convoluted nuclei and variable nuclear pleomorphism. Band like papillary dermal lymphoid infiltrate, dermal lymphoid fibroplasia and nodular lymphoid aggregates could be appreciated in the deep dermis. Immunohistochemical tests were performed and the immunophenotypic profile revealed positivity for CD2, CD3, CD5, CD7, CD 8 and TIA1 and negative for CD4, CD20, CD30, CD56 and granzyme B. Based on clinical presentation, histopathology and Immunohistochemical tests, a final diagnosis of MF was made. The patient was then started on systemic antibiotic therapy, due to increased risk of bacterial super infection of lesions due to skin barrier disruption. He was then referred to Oncology department for further treatment. Conclusion: In this case, the male patient was suffering from mycosis fungoides. In the background of its clinical features being similar to other skin disorders like erythema necroticans, clinicians may face a diagnostic dilemma to correctly diagnose it. Timely diagnosis and treatment improves the prognosis in most cases. Histopathological evaluation still remains the investigation of choice.

MicroRNA Expression Profile in Mycosis Fungoides – Preliminary Findings

Dear Editor, Mycosis Fungoides (MF) is the commonest cutaneous lymphoma, comprising about 12% of all T-cell lymphomas in India.[1] MF presents as patches, plaques or tumors. While the diagnosis of tumor stage MF is easy, lesions of patch and plaque stages pose problems in diagnosis.[2] There is a clinicopathologic overlap with several inflammatory conditions. Currently, there is no single diagnostic standard for early MF. It rests on a combination of clinical findings, histopathology, immunohistochemistry and T-cell receptor clonality testing.[3] miRNAs(miR) have great potential as biomarkers as they are robust, tissue-specific and can be obtained from both blood and tissues. Their value as diagnostic markers have been shown in several cancer types but is still nascent in MF.[4] We attempted to explore the role of miRs in patch and plaque stage MF in Indian patients. We selected 24 MF samples whose diagnosis was established based on clinical features, histopathology and follow up. We chose a set of 7miRs namely miR 203, miR205, miR223, miR155, miR 93, miR 92a, miR 21 along with two controls RNU48 and RUN44. The first three miRs have a tumor suppressor function, while the rest serve as OncomiRs. RNU44, 48 served as controls. Primer sequences designed using Primer3Plus software and then validated on Ensemble & NCBI Blast. After deparaffinisation and overnight incubation with proteinase K, RNA was extracted using RNAwiz and estimated by Ribogreen fluorimetry, the yield ranged from 5.06 to 49.6 ng. Real time PCR was done on the 26 samples on LightCycler 480 (Roche). Pre-incubation and initial denaturation of the template was at - 95°C for 10 min and amplification was done for 45 cycles at 95°C for 15 sec and 60°C for 1 min and Ct values were obtained. There were 24 samples from 21 patients. Their age ranged from 24-83 years and were predominantly men (14:7). There were 8 patch stage MF, 9 plaque stage and 7 were recurrent MF. There was no significant difference in the expression of any of the 7 miRs between the patch and plaque stages (p-values ranged from 0.423-0.963). There was no difference between patch/plaque stages and recurrent lesions. (p-values ranged from 0.481-0.963). We compared the average Ct values of the 3 tumor suppressor miRs versus the 4 OncomiRs, to look for any difference between patch, plaque and recurrent lesions. There was no significant difference in these either. (p-value ranged from 0.877 to 1.484) A few studies have focussed on the differential expression of miRs in distinguishing MF from inflammatory diseases. van Kester et al studied 19 tumor stage MF and compared their miR expression patterns with 12 benign skin conditions.[5] They found that 49 miR were differentially expressed in the two groups and miR 93, which has an anti-apoptotic function, showed the highest discrimination.[5] Ralfkiaer et al showed that early MF displays a miR profile distinct from advanced T-cell lymphomas.[6] They were also able to demonstrate different profiles in patients with progressive vs. non-progressive disease. McGirt et al demonstrated that miR223, which targets TOX gene, needed for T-cell development is overexpressed in early MF and diminishes with progression to advanced disease.[7] There is only one study which has compared miR profiles in patch vs. plaque stages of MF. Sorensen et al found 11 miRNAs were overexpressed in plaques as compared to patches, most significantly miR-142, miR-21 and miR-22.[8] We did not find any difference in miR (including miR21) expression between patch and plaque stages or in patients who had recurrences. Variation in results could be due to the methodology used (whole tissue vs. microarray), quantity and quality of RNA and density of the infiltrate.[8] Nevertheless, it seems that although clinically distinct, patch and plaque stage MF are more similar biologically. We will expand the scope to compare miR expression profiles of MF with various inflammatory skin diseases in the next part of our ongoing study. To summarise, miR expression does not appear to be useful in distinguishing patch vs. plaque stage MF. Our findings need to be validated in larger samples in Indian patients. Financial support and sponsorship Rajiv Gandhi University of Health Sciences, Bangalore for funding the project Conflicts of interest There are no conflicts of interest.