-
Frontiers in Immunology 2023Discriminating between cutaneous anaplastic large cell lymphoma (cALCL) and CD30-positive transformed mycosis fungoides (CD30+ TMF) is challenging, particularly when...
BACKGROUND
Discriminating between cutaneous anaplastic large cell lymphoma (cALCL) and CD30-positive transformed mycosis fungoides (CD30+ TMF) is challenging, particularly when they arise in the context of pre-existing mycosis fungoides. The development of molecular diagnostic tools was hampered by the rarity of both diseases and the limited understanding of their pathogenesis.
METHODS
In this study, we established a cohort comprising 25 cALCL cases and 25 CD30+ TMF cases, with transcriptomic data obtained from 31 samples. We compared the clinicopathological information and investigated the gene expression profiling between these two entities. Furthermore, we developed an immunohistochemistry (IHC) algorithm to differentiate these two entities clinically.
RESULTS
Our investigation revealed distinct clinicopathological features and unique gene expression programs associated with cALCL and CD30+ TMF. cALCL and CD30+ TMF displayed marked differences in gene expression patterns. Notably, CD30+ TMF demonstrated enrichment of T cell receptor signaling pathways and an exhausted T cell phenotype, accompanied by infiltration of B cells, dendritic cells, and neurons. In contrast, cALCL cells expressed high levels of HLA class II genes, polarized towards a Th17 phenotype, and exhibited neutrophil infiltration. An IHC algorithm with BATF3 and TCF7 staining emerged as potential diagnostic markers for identifying these two entities.
CONCLUSIONS
Our findings provide valuable insights into the differential molecular signatures associated with cALCL and CD30+ TMF, which contribute to their distinct clinicopathological behaviors. An appropriate IHC algorithm could be used as a potential diagnostic tool.
Topics: Humans; Lymphoma, Large-Cell, Anaplastic; Ki-1 Antigen; Skin Neoplasms; Mycosis Fungoides; Gene Expression Profiling
PubMed: 37790936
DOI: 10.3389/fimmu.2023.1270365 -
Human Pathology Oct 2023Cutaneous T-cell lymphomas are an heterogeneous group of uncommon lymphoid neoplasms that are challenging to diagnose and require close collaboration between... (Review)
Review
Cutaneous T-cell lymphomas are an heterogeneous group of uncommon lymphoid neoplasms that are challenging to diagnose and require close collaboration between dermatologists, pathologists and hematologists/oncologists. This article reviews the most common cutaneous T-cell lymphomas: mycosis fungoides (both classic and variant forms) as well as its leukemic counterpart Sézary syndrome, CD30+ T-cell lymphoproliferative disorders including the ever-expanding group of lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, and primary cutaneous CD4+ small/medium lymphoproliferative disorder. We discuss the classic clinical and histopathologic features of these lymphomas and review how they can be distinguished from reactive entities. In particularly, updates to these diagnostic categories and current controversies in classification are highlighted. Moreover, we review the prognosis and treatment for each entity. These lymphomas exhibit variable prognosis, and therefore it is important to correctly classify atypical cutaneous T-cell infiltrates for appropriate patient treatment and prognosis. Cutaneous T-cell lymphomas are at the interface of several medical specialties; this review seeks to summarize key features of these lymphomas and highlight new and emerging insights into these lymphomas.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms; Mycosis Fungoides; Lymphomatoid Papulosis; Skin
PubMed: 37802757
DOI: 10.1016/j.humpath.2023.09.009 -
Journal of Cosmetic Dermatology Jul 2022Ten-year survival rates in mycosis fungoides (MF) broadly varies, however, there is no standardized prognostic index available. This is presumably due to low prevalence,... (Review)
Review
BACKGROUND
Ten-year survival rates in mycosis fungoides (MF) broadly varies, however, there is no standardized prognostic index available. This is presumably due to low prevalence, heterogeneity, and diagnostic challenges in MF. Recent studies have focused on identifying objective prognostic indices by using different parameters for survival determinants. The Cutaneous Lymphoma International Prognostic Index (CLIPI) and the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) represent prototypical studies that identify prognostic factors, seeking to improve management and outcomes in early-stage MF. Detecting these factors and stratifying MF patients according to their disease progression risk may help to manage these patients more efficiently.
AIMS
Review the current literature to determine the risk factors determining prognosis in MF.
METHODOLOGY
A Comprehensive literature search was performed using electronic online databases "PubMed" and "Google Scholar" using key words 'prognostic factor', 'prognostic indicator', 'mycosis fungoides', 'Sezary syndrome', 'Skin Lymphoma', 'Cutaneous Lymphoma'. Articles published in English language were considered for the review.
RESULTS
The strongest prognostic factor in MF patients is the stage of the disease. T stage and the presence of extracutaneous disease are the most important factors for survival. Other factors that are associated with worse prognosis are male gender, age >60, presence of plaques, folliculotropism, eosinophilia and lymph node stage above N1/Nx. Elevated LDH was associated with later tumor stages and large cell phenotype at diagnosis had a better prognosis. KIR3DL2 was associated with malignant transformation.
CONCLUSION
The PROCLIPI study has assessed risk factors collected in MF patients from different countries and across different ethnicities following a rigorous clinicopathologic process. The findings presented here illustrated that disease prognosis in early stages depends on many contributing factors. Detection and stratification of such factors may allow a personalized approach to management of these patients.
Topics: Female; Humans; Male; Mycosis Fungoides; Neoplasm Staging; Prognosis; Prospective Studies; Skin Neoplasms
PubMed: 34687485
DOI: 10.1111/jocd.14528 -
The American Journal of Dermatopathology Feb 2021Folliculotropic mycosis fungoides (FMF) is a variant of cutaneous T-cell lymphoma that has clinical overlap with a variety of inflammatory follicular unit disorders....
BACKGROUND
Folliculotropic mycosis fungoides (FMF) is a variant of cutaneous T-cell lymphoma that has clinical overlap with a variety of inflammatory follicular unit disorders. However, we describe distinctive presentations of FMF with acneiform features that can be diagnostically challenging, leading to diagnostic delay.
OBJECTIVE
To highlight the importance of histopathologic and immunohistochemical evaluation for diagnostic confirmation of presumed inflammatory follicular unit-based disorders that are unusual in presentation or unresponsive to standard therapies.
METHODS
A cross-sectional retrospective study of 5 consecutive patients with a histopathologic diagnosis of FMF was conducted. The clinical, histopathologic, immunophenotypic, and molecular genetic features of cases are presented.
RESULTS
We describe 5 patients with clinical and histopathologic presentations of FMF masquerading as hidradenitis suppurativa, furunculosis, or acne vulgaris (age range 34-66 years, 4:1 female to male). Clinical morphologies included open and closed comedones, inflammatory pustules, papules and nodules, follicular papules with keratotic plugging, cysts, and scarring involving the face, trunk, and intertriginous areas. All patients failed to respond to standard therapies, including topical and oral antibiotics, topical and oral retinoids, or topical corticosteroids, before receiving the diagnosis of FMF. Lesional skin biopsies showed a perifollicular CD4-positive T-lymphocytic infiltrate with pilotropism, intrafollicular mucin deposition, foreign-body granulomatous inflammation, acute inflammation, and follicular epithelial necrosis. None had concurrent systemic mycosis fungoides.
LIMITATIONS
Small retrospective cohort study.
CONCLUSION
We present these cases to expand the clinical and histopathologic spectrum of FMF that may strikingly resemble acneiform disorders and to highlight the importance of diagnostic reconsideration with histopathologic evaluation.
Topics: Acne Vulgaris; Adult; Aged; Biomarkers, Tumor; Biopsy; Cross-Sectional Studies; Diagnosis, Differential; Female; Hair Follicle; Humans; Immunohistochemistry; Male; Middle Aged; Mycosis Fungoides; Neoplasm Staging; Predictive Value of Tests; Retrospective Studies; Skin Neoplasms
PubMed: 33492839
DOI: 10.1097/DAD.0000000000001698 -
Der Hautarzt; Zeitschrift Fur... Jul 2020
Topics: Humans; Mycosis Fungoides; Skin Neoplasms; Urticaria
PubMed: 32974707
DOI: 10.1007/s00105-020-04642-y -
JAMA Dermatology Apr 2021Comprehensive data on childhood mycosis fungoides (MF) is scarce.
IMPORTANCE
Comprehensive data on childhood mycosis fungoides (MF) is scarce.
OBJECTIVE
To describe clinical features, immunophenotypes, various treatment options, and prognosis of MF in children and adolescents.
EVIDENCE REVIEW
This systematic review searched MEDLINE via PubMed, Embase, Cochrane, and Scopus databases in October 2019. The search terms included mycosis fungoides, infant, children, and adolescent. No filter for the publication period was used, but studies written in a language other than English were excluded. Reference lists of the relevant articles were also searched manually. Case series and case reports were included if data on childhood MF were extractable. The Asan Medical Center database for cases of childhood MF was also searched. Patients were treated from January 1, 1990, to July 31, 2019, and were younger than 20 years at the time of diagnosis. The methodologic quality of the included studies was assessed with items from the Newcastle-Ottawa scale. Data were analyzed from December 9, 2019, to September 4, 2020.
FINDINGS
A total of 571 unique patients were included. The mean (SD) age at diagnosis was 12.2 (4.2) years; at onset, 8.6 (4.2) years. The female-to-male ratio was 1:1.6 (350 male patients [61.3%]). Among 522 patients with data available at diagnosis, stage 1 disease constituted 478 cases (91.6%), followed by stage 2 (39 [7.5%]) and stage 4 (5 [1.0%]). Among the 567 patients with data available, the most common variant of MF was the hypopigmented form (309 [54.5%]), followed by classic MF (187 [33.0%]). The MF lesions were predominantly the CD4+ and CD8+ immunophenotype in 99 (49.5%) and 79 (39.5%) of 200 patients, respectively. Among the treatments, narrowband UV-B was the most frequently used (150 of 426 [35.2%]). Most patients were alive with the disease (185 of 279 [66.3%]); 83 of 279 (29.8%) were in complete remission; and 11 of 279 (3.9%) had died by the last follow-up. A longer time from onset to diagnosis (hazard ratio [HR], 1.24; 95% CI, 1.06-1.45), granulomatous slack skin (HR, 12.25; 95% CI, 1.99-75.26), granulomatous MF (HR, 14.59; 95% CI, 1.31-162.00), a history of organ transplant (HR, 10.15; 95% CI, 0.98-105.37), and stage 2 disease at the time of diagnosis (HR, 10.22; 95% CI, 2.94-35.50) were associated with worse outcomes.
CONCLUSIONS AND RELEVANCE
The findings of this review suggest that there is often a significant delay until the establishment of a correct diagnosis of childhood MF, which may be detrimental to the prognosis.
Topics: Adolescent; Age Factors; Child; Female; Humans; Male; Mycosis Fungoides; Prognosis
PubMed: 33656521
DOI: 10.1001/jamadermatol.2021.0083 -
Best Practice & Research. Clinical... Sep 2019Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of cutaneous lymphoma, accounting for approximately 60% of cutaneous T-cell lymphomas.... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of cutaneous lymphoma, accounting for approximately 60% of cutaneous T-cell lymphomas. Diagnosis requires correlation of clinical, histologic, and molecular features. A multitude of factors have been linked to the aetiopathogenesis, however, none have been definitively proven. Erythrodermic MF (E-MF) and SS share overlapping clinical features, such as erythroderma, but are differentiated on the degree of malignant blood involvement. While related, they are considered to be two distinct entities originating from different memory T cell subsets. Differential expression of PD-1 and KIR3DL2 may represent a tool for distinguishing MF and SS, as well as a means of monitoring treatment response. Treatment of E-MF/SS is guided by disease burden, patients' ages and comorbidities, and effect on quality of life. Current treatment options include biologic, targeted, immunologic, and investigational therapies that can provide long term response with minimal side effects. Currently, allogeneic stem cell transplantation is the only potential curative treatment.
Topics: Humans; Immunologic Memory; Mycosis Fungoides; Neoplasm Proteins; Programmed Cell Death 1 Receptor; Receptors, KIR3DL2; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 31585624
DOI: 10.1016/j.beha.2019.06.004 -
Cells Nov 2023In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in... (Review)
Review
In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.
Topics: Humans; Skin Neoplasms; Mycosis Fungoides; Brentuximab Vedotin; Sezary Syndrome; Antineoplastic Agents; Antibodies, Monoclonal
PubMed: 37998391
DOI: 10.3390/cells12222656 -
Cutis Mar 2022Although mycosis fungoides (MF) and Sézary syndrome (SS) commonly affect Black patients, dermatologic educational resources primarily describe the appearance of these...
Although mycosis fungoides (MF) and Sézary syndrome (SS) commonly affect Black patients, dermatologic educational resources primarily describe the appearance of these conditions in lighter skin types. Skin of color (SoC) patients with Fitzpatrick skin types (FSTs) IV to VI tend to have variable morphologies compared to the erythematous patches, plaques, or tumors in non-sun-exposed areas seen in non-SoC patients (FSTs I-III). We performed a single-institution review of clinical photographs of patients with FSTs I to VI with the primary outcome of determining the frequency of various morphologic features of MF/SS in SoC vs non-SoC patients. Providers need to be familiar with the differences in morphologic features across skin types to ensure early diagnosis and treatment.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; Racial Groups
PubMed: 35659141
DOI: 10.12788/cutis.0484 -
Dermatology (Basel, Switzerland) 2023The incidence and clinical features of primary cutaneous lymphoma (PCL) tend to differ by age, gender, geographical, and racial variation. All-aged and adult groups of...
BACKGROUND
The incidence and clinical features of primary cutaneous lymphoma (PCL) tend to differ by age, gender, geographical, and racial variation. All-aged and adult groups of PCL in various regions have been well demonstrated and compared, while the research concentrating on pediatric PCL is rare, especially in Asian countries.
OBJECTIVE
The aim of this study was to investigate the clinical characteristics of PCL in pediatric population at a single center in China.
METHODS
We conducted a retrospective study of 101 pediatric cases with PCL, diagnosed at the Institute of Dermatology, Chinese Academy of Medical Sciences, from January 2010 to December 2021.
RESULTS
Mycosis fungoides (MF), accounting for 41.6% of the total cases, was the most common subtype in pediatric PCL, and the hypopigmented MF accounted for 47.6% of all the MF cases. Lymphomatoid papulosis and chronic active Epstein-Barr virus infection tied for second place with a proportion of 22.8%. Primary cutaneous anaplastic large cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, primary cutaneous peripheral T-cell lymphoma, rare subtypes and primary cutaneous B-cell lymphoma, respectively, accounted for 2.0%, 4.0%, 4.0%, and 3.0%. Most patients had favorable prognosis during the follow-up.
CONCLUSION
The study suggested that MF was the most common subtype in pediatric PCL in China, and most types of pediatric PCL had favorable prognosis.
Topics: Adult; Humans; Child; Aged; Lymphoma, T-Cell, Cutaneous; Retrospective Studies; Epstein-Barr Virus Infections; Skin Neoplasms; Herpesvirus 4, Human; Mycosis Fungoides; China
PubMed: 37231916
DOI: 10.1159/000530884