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Archives of Dermatological Research May 2024
Topics: Humans; Mycosis Fungoides; Retrospective Studies; Eosinophilia; Eosinophils; Male; Female; Middle Aged; Prognosis; Skin Neoplasms; Aged; Adult; Skin; Aged, 80 and over
PubMed: 38762842
DOI: 10.1007/s00403-024-02909-1 -
The Journal of Investigative Dermatology May 2024Cutaneous T-cell lymphoma is characterized by malignant T cells proliferating in a unique tumor microenvironment dominated by keratinocytes (KCs). Skin colonization and...
Cutaneous T-cell lymphoma is characterized by malignant T cells proliferating in a unique tumor microenvironment dominated by keratinocytes (KCs). Skin colonization and infection by Staphylococcus aureus are a common cause of morbidity and are suspected of fueling disease activity. In this study, we show that expression of HLA-DRs, high-affinity receptors for staphylococcal enterotoxins (SEs), by KCs correlates with IFN-γ expression in the tumor microenvironment. Importantly, IFN-γ induces HLA-DR, SE binding, and SE presentation by KCs to malignant T cells from patients with Sézary syndrome and malignant and nonmalignant T-cell lines derived from patients with Sézary syndrome and mycosis fungoides. Likewise, preincubation of KCs with supernatant from patient-derived SE-producing S aureus triggers proliferation in malignant T cells and cytokine release (including IL-2), when cultured with nonmalignant T cells. This is inhibited by pretreatment with engineered bacteriophage S aureus-specific endolysins. Furthermore, alteration in the HLA-DR-binding sites of SE type A and small interfering RNA-mediated knockdown of Jak3 and IL-2Rγ block induction of malignant T-cell proliferation. In conclusion, we show that upon exposure to patient-derived S aureus and SE, KCs stimulate IL-2Rγ/Jak3-dependent proliferation of malignant and nonmalignant T cells in an environment with nonmalignant T cells. These findings suggest that KCs in the tumor microenvironment play a key role in S aureus-mediated disease activity in cutaneous T-cell lymphoma.
PubMed: 38762064
DOI: 10.1016/j.jid.2024.04.018 -
APMIS : Acta Pathologica,... May 2024The 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...
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.
PubMed: 38757234
DOI: 10.1111/apm.13423 -
The Journal of Dermatological Treatment Dec 2024Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a...
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a combined with phototherapy for early-stage MF. Thirteen patients with early-stage MF received subcutaneous injections of IFN α-2a at 3 million IU combined with phototherapy three times per week for 6 months. Treatment efficacy was measured by changes in body surface area (BSA) score and modified severity-weighted assessment tool (mSWAT) score at 1, 3, and 6 months after treatment. Histopathologic examinations of skin lesions were performed before and after treatment. After 3 months of treatment, all 13 patients achieved a partial response, and BSA and mSWAT scores were significantly lower than those at baseline ( < 0.001). After 6 months, BSA and mSWAT scores were significantly lower than those at baseline ( < 0.001) and after 3 months ( < 0.05). Eleven patients achieved complete remission and two patients achieved a partial response (overall response rate, 100%). Histopathologic examination showed a significant decrease in the number of atypical lymphocytes in both epidermis and dermis. No severe adverse effects occurred. IFN α-2a in combination with phototherapy may be an effective and safe alternative modality for early-stage MF.
Topics: Humans; Mycosis Fungoides; Male; Middle Aged; Female; Prospective Studies; Skin Neoplasms; Adult; Interferon alpha-2; Treatment Outcome; Aged; Injections, Subcutaneous; Interferon-alpha; Combined Modality Therapy; Phototherapy; Neoplasm Staging; Recombinant Proteins
PubMed: 38754985
DOI: 10.1080/09546634.2024.2350231 -
JAAD Case Reports Jun 2024
PubMed: 38741658
DOI: 10.1016/j.jdcr.2024.03.016 -
The Journal of Allergy and Clinical... May 2024
PubMed: 38727652
DOI: 10.1016/j.jaip.2024.04.017 -
The Australasian Journal of Dermatology May 2024Mycosis fungoides (MF) is a low-grade malignant cutaneous T-cell lymphoma that originates from memory T cells. It typically follows a unique and relatively indolent...
Mycosis fungoides (MF) is a low-grade malignant cutaneous T-cell lymphoma that originates from memory T cells. It typically follows a unique and relatively indolent disease course. MF is used to be characterized by a tissue-resident memory T cell (TRM) phenotype, although recent molecular research has revealed its complexity, casting doubt on the cell of origin and the TRM-MF paradigm. Recent clonal heterogeneity studies suggest that MF may originate from immature early precursor T cells. During development, the tumour microenvironment (TME) influences tumour cell phenotype. The exact origin and development trajectory of MF remains elusive. Clarifying the origin of MF cells is vital for accurate diagnosis and effective treatment.
PubMed: 38726851
DOI: 10.1111/ajd.14304 -
Journal of Cutaneous Pathology May 2024Mycosis fungoides (MF) represents the most common type of primary cutaneous T-cell lymphoma. Recognition of MF variants with divergent immunophenotypes is important for...
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.
PubMed: 38725374
DOI: 10.1111/cup.14643 -
Case Reports in Oncological Medicine 2024Though mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), it has no curative treatment. The aim of current topical and systemic...
Though mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), it has no curative treatment. The aim of current topical and systemic treatment is centered around relieving symptoms and optimizing disease-free time. The use of surgical management to achieve the same goals of symptomatic reduction is not well described in the current literature. We present a case of refractory MF that failed chemotherapy, radiotherapy, and UV light therapy. Despite medical management, the tumor burden progressed to significant compression neuropathy of the ulnar and median nerves. To reduce tumor burden and attempt to provide symptomatic relief, a surgical plan was developed to include radical resection of the tumor of the left upper extremity (LUE) with release of the cubital tunnel, carpal tunnel, Guyon canal, and coverage with split-thickness skin graft. The patient reported decreased symptomatology interfering with her daily activities and, overall, a better quality of life postoperatively. Surgical intervention, in addition to established medical standards of care, for symptomatic relief of compression neuropathy from tumor mass effect for refractory CTCL should be considered to achieve quality of life goals for patients.
PubMed: 38706790
DOI: 10.1155/2024/6645278 -
The British Journal of Dermatology May 2024
PubMed: 38703059
DOI: 10.1093/bjd/ljae188