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Milia en plaque (MEP) is an uncommon skin condition identified as retroauricular confluent milium by Boulzer and Fouqet in 1903 [1]. It can be mistaken for other dermatoses like Favre-Racouchot nodular elastosis, steatocystoma multiplex, and nevus comedonicus. Milia en plaque can either be primary or secondary and is typically benign, often triggered by dermatological procedures like cryotherapy, as reported in this journal. In some cases, MEP can arise as a secondary manifestation of other diseases, including folliculotropic mycosis fungoides (FMF). Despite this association, there are few documented cases in the literature. Herein, we present a patient in whom MEP served as the initial clinical presentation of FMF; the treatment involved oral retinoids and phototherapy. Furthermore, we highlight distinctive features of both conditions. It is important to emphasize that early diagnosis and treatment of FMF are vital for the patient's quality of life. The presence of MEP can serve as a valuable indicator for identifying it.

BACKGROUND: The risk of developing cutaneous T cell lymphoma (CTCL) in patients using psoriasis biologics has not been well characterized. The goals of this review were to investigate the incidence of CTCL in patients with psoriasis receiving biologic therapy in clinical trials and psoriasis registries, and to review cases of CTCL and biologic use reported in scientific publications. METHODS: The US National Library of Medicine clinical trials database (clinicaltrials.gov) was queried to identify phase 3 and 4 clinical trials of the 12 biologic agents currently FDA approved for psoriatic disease. The incidence of CTCL in these trials was examined and summarized. To examine the incidence of CTCL in psoriasis registries, a Medline search was conducted. Finally, we performed a systematic review of CTCL cases reported in the literature. RESULTS: Only two cases of CTCL were reported in 35,801 subjects with psoriasis receiving a biologic agent in the active arm of 108 psoriasis phase 3 clinical trials. One of these CTCL cases was determined by the investigator to be CTCL misdiagnosed as psoriasis prior to randomization. No cases of CTCL were reported in 5440 subjects with psoriasis in 34 phase 4 clinical trials. Only one case of CTCL was identified in 34,111 registry subjects. In the literature, tumor necrosis factor (TNF) inhibitors had the highest number of reported cases of CTCL (34 cases), followed by interleukin (IL)-17 inhibitors (7 cases), and IL-12/23 inhibitors (6 cases). No cases of CTCL were found to be reported with IL-23 inhibitors. CONCLUSION: Our findings indicate that the development of CTCL is rare in the setting of psoriasis biologic use. Of the limited number of cases of CTCL found, most were in the setting of TNF inhibitor use and no cases of CTCL were reported in the setting of IL-23 inhibitor use.

Mycosis fungoides (MF) has been widely reported to mimick a considerable number of different dermatoses, including scarring alopecia, bullous dermatoses or cysts, and comedones. In atypical presentations, histopathology is essential for the diagnosis. We present two cases of MF with clinical urticarial lesions and a striking blood involvement that responded to mogamulizumab treatment. Histopathologically, both cases had classic MF features and shared a peculiar immunophenotype, with positivity for CD25 and FOXP3. Differential diagnoses included urticarial lymphomatoid drug reactions and other lymphomas, like T‐cell prolymphocytic leukemia, atypical Sézary syndrome, or adult T‐cell lymphocytic leukemia. A low suspicion threshold is necessary for the diagnosis of atypical presentations of MF. [ABSTRACT FROM AUTHOR]

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL) with its etiology not yet fully understood. Interleukin (IL)-35 is an inhibitory cytokine that belongs to the IL-12 family. Elevated IL-35 in the plasma and the tumor microenvironment increases tumorigenesis and indicates poor prognosis in different types of malignancies. The objective of this study is to estimate the expression levels of IL-35 in tissue and serum of MF patients versus healthy controls. This case-control study included 35 patients with patch, plaque, and tumor MF as well as 30 healthy controls. Patients were fully assessed, and serum samples and lesional skin biopsies were taken prior to starting treatment. The IL-35 levels were measured in both serum and tissue biopsies by ELISA technique. Both tissue and serum IL-35 levels were significantly higher in MF patients than in controls (P < 0.001) and tissue IL-35 was significantly higher than serum IL-35 in MF patients (P < 0.001). Tissue IL-35 was significantly higher in female patients and patients with recurrent MF compared to male patients and those without recurrent disease (P < 0.001). Since both tissue and serum IL-35 levels are increased in MF, IL-35 is suggested to have a possible role in MF pathogenesis. IL-35 can be a useful diagnostic marker for MF. Tissue IL-35 can also be an indicator of disease recurrence. [ABSTRACT FROM AUTHOR]

Background Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic malignant diseases that typically necessitate diverse strategies to achieve remission. Systemic interferon (IFN)-α (subtypes 2a and 2b) has been used to treat MF/SS since 1984; however, its production was recently stopped. The recombinant pegylated (PEG) form of IFN-α-2a remains the only alternative IFN treatment, although it has not been approved for use in MF/SS. Objectives To assess the effectiveness and safety of PEG-IFN-α-2a in monotherapy and in combination with other treatments using time to next treatment (TTNT) as a measure of clinical therapeutic benefit in a real-world setting. Methods We conducted an international, multicentre retrospective study of patients with MF and SS (of any stage) treated with PEG-IFN-α-2a from July 2012 to February 2022. Patients were included across 11 centres in 10 countries. The primary endpoints were to determine the TTNT of PEG-IFN-α-2a and adverse events (AEs) in MF/SS. Results In total, 105 patients were included [mean (SD) age 61 (13.1) years]; 42 (40.0%) had stage IA–IIA and 63 (60.0%) had stage IIB–IVB disease. PEG-IFN-α-2a was combined with other therapies in 67 (63.8%) patients, most commonly with extracorporeal photopheresis (36%) and bexarotene (22%). Patients with stage I–IIA disease achieved an overall response rate (ORR) of 57%; the ORR in those with stage IIB–IVB disease was 51%. Combination treatment resulted in a median TTNT of 10.4 months (range 0.6–50.7) vs. 7.0 months (range 0.7–52.4) for those who received monotherapy (P < 0.01). Overall, the mean (SD) TTNT was 9.2 (10.6) months and the ORR was 53.3% (n = 56). A complete response was seen in 13% of patients and a partial response in 40%. AEs were described in 68.6% (n = 72) of patients. Flu-like symptoms (n = 28; 26.7%), lymphopenia (n = 24; 22.9%) and elevated liver function (n = 10; 9.5%) were the most frequently reported. Grade 3–4 AEs were reported in 23 (21.9%) patients, mostly related to myelosuppression. Conclusions PEG-IFN-α-2a for MF/SS resulted in an ORR of 53.3% and a mean (SD) TTNT of 9.2 (10.6) months. Combination regimens were superior to monotherapy and doses of 180 µg PEG-IFN-α-2a weekly were related to a higher ORR. [ABSTRACT FROM AUTHOR]

We report a case of difficult-to-control mycosis fungoides (MF), where the role of the dental surgeon was crucial for the control and prognosis of the disease. A 62-year-old female patient diagnosed with MF had a previous record of red patches and small raised bumps on the face, along with a cancerous growth in the cervical and vulvar region. The patient was initially treated with methotrexate and local radiotherapy without resolution. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone was then started (CHOP protocol). The dental team of a reference hospital was consulted to evaluate swelling in the anterior region of the palate, which had been developing for two months, reporting discomfort when eating. The role of the dentistry team was fundamental in the differential diagnosis of oral lesions with dental infections, second neoplasia, or even a new site of disease manifestation, in addition to controlling mucosal changes resulting from chemotherapy. After ruling out dental infection, the dentistry team performed a lesion biopsy to confirm the diagnosis. The histopathological and immunohistochemical analysis showed atypical lymphoid infiltration of T cells (CD3+/CD4+/CD7-/CD8-), coexpression of CD25, and presence of CD30 cells, corresponding to the finding for MF. Identifying CD30 + allowed for a new chemotherapy protocol with brentuximab vedotin (BV) combined with gemcitabine. This protocol effectively controlled MF, which previous protocols had failed to do. The diagnosis by the dental team was essential for therapeutic change and improvement of the patient's clinical condition without the need for invasive medical procedures. [ABSTRACT FROM AUTHOR]

The relative frequency of primary cutaneous lymphoma (PCL) subtypes shows wide variation across different geographical regions. This retrospective study was conducted in a tertiary referral center located in Korea to describe the relative frequency, demographics, survival outcomes, and temporal trend in PCL. A total of 627 PCL cases diagnosed between January 1994 and December 2022 were included. The majority of PCL cases (87.2%) were of T-/NK-cell lineage (CTCL), while the remaining cases (12.8%) were B-cell lineage lymphomas (CBCL). The prevalence of mycosis fungoides (MF) in CTCL increased significantly over time, while other CTCL subtypes, including primary cutaneous extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), decreased in frequency. Notably, the prevalence of CD4-positive small/medium T-cell lymphoproliferative disorder showed a substantial increase over time. Primary cutaneous marginal zone lymphoma was consistently the commonest CBCL subtype. Survival analysis demonstrated that CTCL had a more favorable 5-year overall survival (OS) than CBCL. OS rate of MF, SPTCL, and primary cutaneous peripheral T-cell lymphoma, NOS improved significantly over time. This study provides comprehensive insights into the dynamic change in the relative frequency and overall survival of PCL subtypes over time. [ABSTRACT FROM AUTHOR]

Background: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL). Comprehensive analysis of MF cells in situ and ex vivo is complicated by the fact that is challenging to distinguish malignant from reactive T cells with certainty. Methods: To overcome this limitation, we performed combined single-cell RNA (scRNAseq) and T-cell receptor TCR sequencing (scTCRseq) of skin lesions of cutaneous MF lesions from 12 patients. A sufficient quantity of living T cells was obtained from 9 patients, but 2 had to be excluded due to unclear diagnoses (coexisting CLL or revision to a fixed toxic drug eruption). Results: From the remaining patients we established single-cell mRNA expression profiles and the corresponding TCR repertoire of 18,630 T cells. TCR clonality unequivocally identified 13,592 malignant T cells. Reactive T cells of all patients clustered together, while malignant cells of each patient formed a unique cluster expressing genes typical of naive/memory, such as CD27, CCR7 and IL7R, or cytotoxic T cells, e.g., GZMA, NKG7 and GNLY. Genes encoding classic CTCL markers were not detected in all clusters, consistent with the fact that mRNA expression does not correlate linearly with protein expression. Nevertheless, we successfully pinpointed distinctive gene signatures differentiating reactive malignant from malignant T cells: keratins (KRT81, KRT86), galectins (LGALS1, LGALS3) and S100 genes (S100A4, S100A6) being overexpressed in malignant cells. Conclusions: Combined scRNAseq and scTCRseq not only allows unambiguous identification of MF cells, but also revealed marked heterogeneity between and within patients with unexpected functional phenotypes. While the correlation between mRNA and protein abundance was limited with respect to established MF markers, we were able to identify a single-cell gene expression signature that distinguishes malignant from reactive T cells. [ABSTRACT FROM AUTHOR]

Background: Cutaneous T-cell lymphomas (CTCL) are a group of rare non-Hodgkin lymphomas characterized by initial localization of malignant T- lymphocytes in the skin. Support and information from nurses and patient support groups have proven useful for patients with CTCL, but little is known about the educational needs of these patients. Objectives: To investigate the self-reported educational needs among CTCL patients using an educational needs assessment tool and to explore differences related to sex, age, disease duration, clinical stage, and education. Methods: This observational single center study analyzed 70 patients with CTCL in routine dermatological outpatient care. The patients were asked to complete a questionnaire to capture their educational needs in regard to CTCL. The questionnaire was inspired by the educational needs assessment tool, designed and validated for patients with rheumatoid disease. The questionnaire included a general question, "In general, how much information do you want to receive about your lymphoma disease?", and five domains covering information relating to disease process (6 items), treatment (4 items), feelings (2 items), self-management of itch, sleep, and rest (2 items), and support systems (3 items). The domain scores ranged from 0 to 18 and the total score from 0 to 51, with a higher score indicating a greater need for education. Results: When asked "In general, how much information do you need?", females wanted to know more compared with males (2.6 vs. 2.1, p=0.006), and patients with higher education wanted to know more than patients with lower education (2.5 vs. 2.0, p=0.025). The domains concerning treatment (80%) and disease process (75%) revealed the greatest needs for education. Patients with a disease duration <2 years reported a greater educational need for the domain support system, compared with patients with longer disease duration. Patients with lower education reported a greater educational need about feelings compared with patients with higher education. Conclusions: We found that 65% of the CTCL patients in the cohort, particularly females, expressed a need for education, especially regarding disease process and treatment. A deeper understanding of the educational needs would enable healthcare providers to give personalized information. [ABSTRACT FROM AUTHOR]

Background: Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma. As the early clinical manifestations of MF are non-specific (e.g., erythema or plaques), it is often misdiagnosed as inflammatory skin conditions (e.g., atopic dermatitis, psoriasis, and pityriasis rosea), resulting in delayed treatment. As there are no effective biological markers for the early detection and management of MF, the aim of the present study was to perform a proteomic analysis of urine samples (as a non-invasive protein source) to identify reliable MF biomarkers. Methods: Thirteen patients with early-stage MF were administered a subcutaneous injection of interferon α-2a in combination with phototherapy for 6 months. The urine proteome of patients with early-stage MF before and after treatment was compared against that of healthy controls by liquid chromatography-tandem mass spectrometry. The differentially expressed proteins were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Clusters of Orthologous Groups analyses. For validation, the levels of the selected proteins were evaluated by enzyme-linked immunosorbent assay (ELISA). Results: We identified 41 differentially expressed proteins (11 overexpressed and 30 underexpressed) between untreated MF patients and healthy control subjects. The proteins were mainly enriched in focal adhesion, endocytosis, and the PI3K-Akt, phospholipase D, MAPK, and calcium signaling pathways. The ELISA results confirmed that the urine levels of Serpin B5, epidermal growth factor (EGF), and Ras homologous gene family member A (RhoA) of untreated MF patients were significantly lower than those of healthy controls. After 6 months of treatment, however, there was no significant difference in the urine levels of Serpin B5, EGF, and RhoA between MF patients and healthy control subjects. The area under the receiver operating characteristic curve values for Serpin B5, EGF, and RhoA were 0.817, 0.900, and 0.933, respectively. Conclusions: This study showed that urine proteomics represents a valuable tool for the study of MF, as well as identified potential new biomarkers (Serpin B5, EGF, and RhoA), which could be used in its diagnosis and management. [ABSTRACT FROM AUTHOR]

This article discusses a case of normolipemic xanthoma associated with folliculotropic mycosis fungoides (fMF), a variant of mycosis fungoides. The patient, a 60-year-old Japanese man, presented with yellowish masses and patchy alopecia on the scalp, as well as follicular papules on the trunk and extremities. Trichoscopy and histological analysis revealed mucin deposition, lymphocyte and eosinophil infiltrations, and dense infiltration of histiocytes mixed with eosinophils and lymphocytes. The article suggests that the tumour microenvironment triggers histiocyte infiltration, which may lead to xanthoma formation. The case highlights the challenges in diagnosing fMF due to excessive granulomatous/xanthomatous components and emphasizes the importance of a comprehensive assessment for a definitive diagnosis. [Extracted from the article]

The oncogene PIM2 is upregulated in several malignancies but has never been investigated in mycosis fungoides (MF), the most common type of cutaneous T‐cell lymphoma (CTCL). PIM2 is a well‐known oncogene and is regulated by cell signaling pathways like the JAK/STAT‐ and NF‐kB‐pathway, key regulators in the pathogenesis of CTCL. The aim of this study was to examine the role of PIM2 in MF. PIM2 gene expression was measured in 81 formalin‐fixed paraffin‐embedded skin biopsies from patients with MF and 46 control biopsies from healthy skin (HS) and benign inflammatory skin disease (BID). Validation of PIM2 protein expression was performed on selected biopsies with immunohistochemical staining. We found a significant difference in gene expression levels between both early stage MF and HS (p < 0.0001), and BID (p < 0.0001). In addition, the PIM2 gene expression was higher in advanced‐stage MF compared to early stage disease (p = 0.0001). No significant difference in gene expression levels was found between patients with and without disease progression. In conclusion, we found PIM2 expression is significantly increased in MF compared to controls, and in advanced‐stage MF compared to early stage MF. These findings could potentially have diagnostic value in discriminating early stage MF from BID. [ABSTRACT FROM AUTHOR]

Aims: There have been exceptional reports of morphoea presenting with epidermal changes overlapping histopathologically with cutaneous T cell lymphoma of the mycosis fungoides type (MF). This phenomenon gives rise to an ambiguous clinicopathological scenario in which distinguishing these conditions may be challenging. The aim of this study is to characterise the clinical, histopathological and molecular findings of this phenomenon through a case series. Methods and results: Four patients with classical clinical presentation of morphoea but unusual histopathology displaying typical findings of morphoea, together with intra‐epidermal CD8 positive lymphocytes indistinguishable from MF, were identified. The clinical phenotypes of morphoea were varied, and they all presented early in the active phase of the disease. They all exhibited intra‐epidermal lymphocytes with tagging and cytological atypia. Pautrier‐like microabscesses were also seen. Using molecular analysis, two cases showed clonal TCR gene rearrangement. Follow‐up of all cases has been consistent with classical morphoea. Conclusion: Early morphoea can seldom present with atypical clonal intra‐epidermal lymphocytes indistinguishable from MF. The fact that these changes can occur in several different clinical subtypes of morphoea raises the possibility that this could be a pattern of inflammation in early disease more common than currently appreciated. [ABSTRACT FROM AUTHOR]

Treatment with CCR-4 antagonists has been shown to be protective against the development of invasive pulmonary aspergillosis in animal models. Herein, we present a case of fatal invasive pulmonary aspergillosis in a patient receiving Mogamulizumab. A 64-year-old man with refractory mycosis fungoides was found to have diffuse bilateral pulmonary nodules during a chest CT in June 2022. Bronchoalveolar lavage (BAL) fungal and bacterial cultures and galactomannan were negative, as well as serum beta-glucan and galactomannan. Histology showed a lymphoid infiltrate with a negative fungal stain, so a presumptive diagnosis of lymphoma infiltration was made, and the patient started the CCR-4 antagonist Mogamulizumab treatment in August 2022. He had no symptoms until November when he presented to the hematology clinic reporting dyspnea. He had neutrophilic leukocytosis (18.610 cells/µL), his c-reactive protein was 27 mg/dL, and his skin lesions from mycosis fungoides were just starting to improve. A CT scan showed large diffuse bilateral severely necrotic cavitated lesions with thick walls and apparently synchronous evolution. Beta-glucan was 31 pg/mL (wako method), while serum galactomannan 3.6. BAL was positive for Aspergillus fumigatus culture and galactomannan. Patient started voriconazole but, despite being in a stable condition, he suddenly died after two days. Discussion: Paradoxically, worsening of the chronic pulmonary aspergillosis has been reported after nivolumab treatment, and immune reconstitution syndromes are usually seen during neutrophil recovery after intensive chemotherapy. Our patient already presented indolent lung lesions from 5 months before and he remained completely asymptomatic until the aspergillosis diagnosis when he quickly passed away. Even if a progression of the lesions was expected in 5 months, this case had an atypical presentation. During the 5-month period, he had no pulmonary symptoms, and his c-reactive protein was negative. Furthermore, in the setting of the natural progression of subacute/chronic aspergillosis, a different radiological picture was expected with a less severe and probably asynchronous evolution. We think that the immune restoration associated with Mogamulizumab (also supported by the concurrent clinical response of the skin lesions) could have been detrimental in this case, exacerbating a catastrophic immune response or alternatively masquerading the clinical progression of aspergillosis. Clinicians should be aware of immune reconstitution syndromes possibly leading to fatal outcomes in immunocompromised patients starting CCR-4 antagonists. [ABSTRACT FROM AUTHOR]

Mycosis fungoides (MF) represents the most common type of primary cutaneous T‐cell lymphoma. Recognition of MF variants with divergent immunophenotypes is important for accurate diagnosis and appropriate management, as they can be confused with other lymphoma subtypes. We present a case of a 49‐year‐old male previously diagnosed with a cutaneous lymphoproliferative disorder with an unusual NK/T‐cell phenotype. He presented with a 10‐year history of pelvic girdle rash involving the right hip and upper thigh. The lesions were characterized as atrophic patches concentrated in sun‐protected areas and involving 10% of the body surface area. Shave biopsies revealed an atypical epidermotropic infiltrate composed of hyperchromatic small to medium‐sized lymphocytes with perinuclear halos and "tagging" along the dermal–epidermal junction. The immunophenotype was unusual in that the neoplastic lymphocytes showed complete loss of pan T‐cell antigens along with expression of CD56, cytotoxic markers, and weak CD20. All other B‐cell markers were negative. The combination of clinical findings, in addition to the histopathologic and immunophenotypic profile, were diagnostic of null T‐cell phenotype MF with aberrant expression of CD56 and CD20. Null T‐cell phenotype MF is very uncommon, can be diagnostically challenging, and can mislead the diagnosis of aggressive lymphoma subtypes. [ABSTRACT FROM AUTHOR]