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Comparison of the 2007 EORTC/ISCL and the 2022 EORTC/ISCL/USCLC blood staging guidelines for cutaneous T-cell lymphoma at a single institution reveals the newer guidelines fail to detect a subset of Sézary syndrome patients with low blood burden.
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This review focuses on mature T cells, natural killer (NK) cells, and stroma-derived neoplasms in the fifth edition of the World Health Organization classification of hematolymphoid tumors, including changes from the revised fourth edition. Overall, information has expanded, primarily due to advancements in genomic understanding. The updated classification adopts a hierarchical format. The updated classification relies on a multidisciplinary approach, incorporating insights from a diverse group of pathologists, clinicians, and geneticists. Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract, Epstein-Barr virus-positive nodal T- and NK-cell lymphoma, and several stroma-derived neoplasms of lymphoid tissues have been newly introduced or included. The review also provides guidance on how the fifth edition of the World Health Organization classification of hematolymphoid tumors can be applied in routine clinical practice.
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The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.
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Linfoma Cutáneo de Células T , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Ensayos Clínicos como Asunto , Humanos , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/terapia , Micosis Fungoide/diagnóstico , Micosis Fungoide/patología , Micosis Fungoide/terapia , Estadificación de Neoplasias , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/patología , Síndrome de Sézary/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Estados UnidosRESUMEN
Primary cutaneous B-cell lymphomas (PCBCLs) are lymphoproliferative disorders that appear on the skin without evidence of extracutaneous manifestations at the time of diagnosis. There is a lack of evidence-based guidelines for their clinical management due to the availability of very few large scale studies and controlled clinical trials. Here we present and discuss a series of major unmet clinical needs (UCNs) in the management of PCBCLs by a panel of 16 experts involved in research and clinical practice of PCBCL. The Panel produced recommendations on the appropriateness of the clinical decisions concerning the identified clinical needs and proposed research for improving the knowledge needed to solve them. Recommendations and proposals were achieved by multiple-step formalized procedures to reach a consensus after a comprehensive analysis of the scientific literature. Recommendations and proposals lay in the domain of classification uncertainties of PCBCL, optimization of diagnosis, optimization of prognosis, optimization of staging and critical issues on therapeutic strategies with particular focus on new treatments. These recommendations are intended for use not only by experts but above all by dermatologists and hematologists with limited experience in the field of PCBCLs as well as general practitioners.
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Linfoma de Células B , Neoplasias Cutáneas , Humanos , Linfoma de Células B/diagnóstico , Linfoma de Células B/terapia , Linfoma de Células B/patología , Consenso , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/patología , PronósticoRESUMEN
BACKGROUND: Patients with Mycosis Fungoides (MF)/Sézary Syndrome (SS) can experience impacted health-related quality of life (HRQoL). OBJECTIVES: To validate the CTCL-S, a novel subscale of the Functional Assessment of Cancer Therapy - General (FACT-G), in patients with MF/SS. METHODS: Qualitative interviews were conducted with expert clinicians and MF/SS patients. Thematic analysis identified the most common concerns, and 19 items were selected.MF/SS patients were recruited from a single center. FACT-G, CTCL-S (collectively "FACT-CTCL"), Skindex29, and Visual Analogue Scale-Pruritis (VAS itch) were administered. A subset repeated FACT-CTCL and VAS itch after ≈2 weeks. Patient demographics and clinical characteristics were obtained via review of the electronic medical record.Psychometric properties were assessed. Internal consistency was estimated using Cronbach's alpha (α). Convergent and discriminant validity were assessed by comparing CTCL-S to disease stage, age, VAS itch, FACT-G, and SkinDex29. Exploratory factor analysis (EFA) was used to preliminarily assess CTCL-S dimensionality. Test-retest repeatability was summarized using intraclass correlation coefficient (ICC), within-subject standard deviation (wSD), and within-subject coefficient of variation. RESULTS: Seventy-two patients completed the initial survey, and 35 repeated the FACT-CTCL and VAS itch after ≈2 weeks. Two-thirds were male, most were white (78%). The majority (85%) had MF, 15% SS, and 75% early (stage IA-IIA) and 25% advanced (≥ stage IIB) disease. Preliminary EFA found a single predominant factor, supporting a hypothesis of unidimensionality of the CTCL-S. Internal consistency of the CTCL-S was high (α: 0.95 [95% CI: 0.93-0.96]). There was no significant change in CTCL-S average test-retest scores (ICC of 0.93 (p = 0.63)). CTCL-S was significantly lower in advanced vs early stage disease (median[IQR]: 34[26, 48] vs. 59[44, 68], p < 0.001) and strongly correlated with VAS itch (Spearman's r (rs): -0.70, 95% CI: -0.81, -0.55), FACT-G (rs: 0.77, 95% CI: 0.65, 0.85), and Skindex29 (rs: -0.90, 95% CI: -0.94, -0.84), supporting convergent validity. CTCL-S scores had little correlation with age (rs: 0.19, 95% CI: -0.05, 0.41, p = 0.12), supporting discriminant validity. CONCLUSIONS: The FACT-CTCL is a disease specific instrument for assessing HRQoL with high reproducibility and good performance in a cohort of patients with MF/SS.
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BACKGROUND: Interstitial mycosis fungoides (IMF) is a rare subtype of mycosis fungoides (MF) characterized by atypical lymphocytes infiltrating the reticular dermis between collagen bundles with limited epidermotropism and variable granulomatous features. METHODS: Retrospective single institution review of 31 cases of IMF including clinical characteristics, disease course and pathological features. RESULTS: Our cohort was predominately male (19; 61%, M:F 1.6:1) with a mean age at diagnosis of 43 years (range 11-85), mean signs/symptoms duration of 7 years prior to diagnosis, and 6 years mean follow-up duration. Clinically, patients often exhibited symmetric ill-defined patches/plaques involving intertriginous regions with tan-yellow hyperpigmentation and follicular-based papules, wrinkling, and alopecia. Lymphadenopathy was noted in seven patients. Fifteen (52%) patients were in near or complete clinical remission at the latest follow-up. T-cell receptor gene rearrangement was positive in 23/24 (96%) cases. Histopathologically, atypical cells were small-medium, CD4+ (29; 94%) or rarely CD4+/CD8+ (1; 3%) lymphocytes infiltrating the reticular dermis with thickened collagen bundles (27; 87%), multinucleated giant cells (12; 39%), and often tracing along adnexa with subtle folliculotropism (12/20; 60%). CONCLUSIONS: Our study demonstrates IMF is an indolent subtype of MF with distinct features, including frequent granulomatous and subtle follicular involvement resulting in alopecia.
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Micosis Fungoide , Neoplasias Cutáneas , Humanos , Micosis Fungoide/patología , Micosis Fungoide/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Neoplasias Cutáneas/patología , Estudios Retrospectivos , Anciano de 80 o más Años , Adolescente , Niño , Folículo Piloso/patologíaRESUMEN
Cutaneous T-cell lymphomas (CTCLs) are a clinically heterogeneous collection of lymphomas of the skin-homing T cell. To identify molecular drivers of disease phenotypes, we assembled representative samples of CTCLs from patients with diverse disease subtypes and stages. Via DNA/RNA-sequencing, immunophenotyping, and ex vivo functional assays, we identified the landscape of putative driver genes, elucidated genetic relationships between CTCLs across disease stages, and inferred molecular subtypes in patients with stage-matched leukemic disease. Collectively, our analysis identified 86 putative driver genes, including 19 genes not previously implicated in this disease. Two mutations have never been described in any cancer. Functionally, multiple mutations augment T-cell receptor-dependent proliferation, highlighting the importance of this pathway in lymphomagenesis. To identify putative genetic causes of disease heterogeneity, we examined the distribution of driver genes across clinical cohorts. There are broad similarities across disease stages. Many driver genes are shared by mycosis fungoides (MF) and Sezary syndrome (SS). However, there are significantly more structural variants in leukemic disease, leading to highly recurrent deletions of putative tumor suppressors that are uncommon in early-stage skin-centered MF. For example, TP53 is deleted in 7% and 87% of MF and SS, respectively. In both human and mouse samples, PD1 mutations drive aggressive behavior. PD1 wild-type lymphomas show features of T-cell exhaustion. PD1 deletions are sufficient to reverse the exhaustion phenotype, promote a FOXM1-driven transcriptional signature, and predict significantly worse survival. Collectively, our findings clarify CTCL genetics and provide novel insights into pathways that drive diverse disease phenotypes.
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Linfoma Cutáneo de Células T/genética , Transcriptoma , Animales , Células Cultivadas , Proteína Forkhead Box M1/genética , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Humanos , Ratones , Mutación , Oncogenes , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: Sepsis is a leading cause of morbidity, mortality, and resource utilization among patients with cutaneous T-cell lymphoma (CTCL). OBJECTIVE: To characterize the demographic, clinical, and microbial attributes distinguishing patients with CTCL sepsis from other patients with non-Hodgkin lymphoma (NHL) sepsis and patients with CTCL in general. METHODS: Two-part retrospective cohort study at an academic medical center from 2001-2019 involving patients with CTCL (n = 97) and non-CTCL NHL (n = 88) admitted with sepsis, and a same-institution CTCL patient database (n = 1094). Overall survival was estimated by Kaplan-Meier analyses. RESULTS: Patients with CTCL sepsis were more likely to be older, Black, experience more sepsis episodes, die or be readmitted within 30 days of an inpatient sepsis episode, and develop Gram-positive bacteremia than patients with non-CTCL NHL sepsis. Staphylococcus aureus and Escherichia coli were the most frequently speciated organisms in CTCL (26%) and non-CTCL NHL (14%), respectively. No between-group differences were identified regarding sex, presence of central line, chemotherapy use, or disease stage. Compared with general patients with CTCL, patients with sepsis were Black and exhibited advanced-stage disease, higher body surface area involvement, and higher lactate dehydrogenase levels. LIMITATIONS: Single institution, retrospective nature may limit generalizability. CONCLUSION: Awareness of CTCL-specific risk factors is crucial for guiding sepsis prevention and improving patient outcomes.
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Linfoma no Hodgkin , Linfoma Cutáneo de Células T , Sepsis , Neoplasias Cutáneas , Humanos , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Linfoma Cutáneo de Células T/complicaciones , Linfoma Cutáneo de Células T/epidemiología , Sepsis/epidemiologíaRESUMEN
ABSTRACT: Epstein-Barr virus (EBV)-positive lymphoproliferative disorders associated with immunodeficiency constitute a spectrum of lymphoid and plasma cell proliferations that vary in cytomorphology, immunophenotype, and clinical behavior. CD30-positive cutaneous lymphocytic infiltrates with EBV expression and lymphomatoid papulosis-like presentations have been rarely reported. This retrospective study assessed the clinical and histopathological characteristics of EBV-positive cases with papulonodular morphologies and CD30 positivity seen by Northwestern Medicine Dermatopathology. Twelve patients (7M:5F, mean age 69 years) were presented with papular cutaneous lesions without antecedent patch/plaque disease. Nine cases were associated with known immunosuppression in the setting of transplant-related therapies (n = 4), hematopoietic malignancy (n = 2), post-transplant hematopoietic malignancy (n = 1), and autoimmune disease treatment (n = 2). Two patients had age-related immunosenescence. Four patients demonstrated EBV viremia; for 2 patients, this finding comprised the first sign of immunosuppression. Workup was negative for systemic lymphoma in all patients. Various treatment strategies were used, including observation (n = 3), discontinuation/reduction of immunosuppression (n = 3), rituximab (n = 4), and steroids (n = 4). At mean 30-month follow-up, 4 patients (33.3%) were alive, 3 with and 1 without disease. Eight patients (67.6%) had died, 3 after lesional resolution and 5 with recurrent disease. Biopsies revealed mixed lymphoid infiltrates composed of atypical CD30-positive T cells (n = 5) or B cells (n = 7) with variable EBV-encoded small RNA expression. These cases suggest clinicopathologic presentations resembling lymphomatoid papulosis with atypical, large CD30-positive, EBV-positive cells could comprise first sign of potentially serious immunodeficiency and should prompt evaluation for EBV viremia. These cases also broaden the current picture of immunodeficiency-associated lymphoproliferative disorders to include lymphomatoid papulosis-like clinical presentations.
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Infecciones por Virus de Epstein-Barr , Neoplasias Hematológicas , Linfoma , Papulosis Linfomatoide , Humanos , Anciano , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Antígeno Ki-1 , Estudios Retrospectivos , Viremia , Terapia de Inmunosupresión/efectos adversosRESUMEN
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase-negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.
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Linfadenopatía Inmunoblástica , Linfoma de Células T Periférico , Linfoma de Células T , Humanos , Linfadenopatía Inmunoblástica/diagnóstico , Linfadenopatía Inmunoblástica/patología , Linfadenopatía Inmunoblástica/terapia , Linfoma de Células T/diagnóstico , Linfoma de Células T/terapia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapiaRESUMEN
BACKGROUND: Primary cutaneous gamma-delta T-cell lymphoma (PCγδTCL) and primary cutaneous aggressive epidermotropic T-cell lymphomas (PCAETCL) are rare aggressive cytotoxic cutaneous lymphomas (CyCL) often difficult to diagnose. Histopathologically, PCAETCL and PCγδTCL may resemble mycosis fungoides (MF) and the presence of adnexotropism in CyCL (CyCL) contributes to this diagnostic challenge, especially in the setting of atypical and double-negative phenotypes. METHODS: In this retrospective study clinical data and histopathological section of 91 patients were analyzed for signs of clinical and histopathological signs adnexotropism. RESULTS: Adnexotropism was identified in 48.4% (44/91) of cases, including PCAETCL (40.9%, 18/44), PCγδTCL and cytotoxic cutaneous lymphomas, not otherwise specified (CyCTCL, NOS) (43.2%, 19/44 and 15.9%, 7/44). Comparison between disease-related mortality with Kaplan-Meier survival analysis of non-adnexotropic vs adnexotropic CyCL did not show any significant difference between the two groups (P = 0.8). Clinically they present with patches, plaques, and tumors and commonly with ulceration, but follicular prominence or alopecia are rare. Clinical signs of adnexotropism such as alopecia and hypo- or anhidrosis were rarely seen. CONCLUSION: Adnexotropism is a common finding in CyCL, especially in PCAETCL. Adnexotropic CyCL may be histopathologically difficult to distinguish from folliculotropic mycosis fungoides. A comprehensive IHC panel should be routinely performed in such cases.
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Linfoma Cutáneo de Células T/patología , Neoplasias de las Glándulas Sebáceas/patología , Neoplasias Cutáneas/patología , Neoplasias de las Glándulas Sudoríparas/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de las Glándulas Sebáceas/epidemiología , Neoplasias de las Glándulas Sudoríparas/epidemiologíaRESUMEN
ABSTRACT: In vulvar biopsies, we have observed histopathologic abnormalities of elastic fibers identical to solar elastosis, with thick, curled, and irregular pale grey fibers in the dermis. In severe cases, changes resemble nodular solar elastosis. We retrospectively evaluated 238 vulvar biopsies with the goal of defining and characterizing changes of vulvar elastosis. Of 238 vulvar biopsies reviewed, 107 (45%) exhibited vulvar elastosis. Patients with vulvar elastosis were older (mean = 65 years old) compared to those without (mean = 44 years old). Sixty-six (62%) were graded as mild, 27 (25%) moderate, and 14 (13%) severe. Vulvar elastosis was significantly more common in women ≥45 years old (P-value < 0.001). There was moderate correlation between age and severity (correlation coefficient = 0.55, P-value < 0.001). Vulvar elastosis was observed in a variety of inflammatory and non-inflammatory pathologies. In 5 cases, the sole pathology was vulvar elastosis presenting clinically as either a pruritic or painful white to white-yellow papule or plaque, or vulvar pain or burning without a clinical lesion. Vulvar elastosis is a novel diagnostic entity occurring in a sun-protected site and its pathogenesis may be a degenerative phenomenon possibly related to advancing age and/or hormonal changes.
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Tejido Elástico/patología , Enfermedades de la Vulva/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana EdadRESUMEN
The combination of Interferon-α-2b (IFN-α-2b) and phototherapy is highly effective in treating mycosis fungoides (MF) but side effects often lead to discontinuation of therapy.1.
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Interferón alfa-2/administración & dosificación , Interferón-alfa/administración & dosificación , Micosis Fungoide/tratamiento farmacológico , Terapia PUVA/métodos , Polietilenglicoles/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Relación Dosis-Respuesta a Droga , Estudios de Factibilidad , Femenino , Humanos , Interferón alfa-2/efectos adversos , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Micosis Fungoide/diagnóstico , Estadificación de Neoplasias , Terapia PUVA/efectos adversos , Proyectos Piloto , Polietilenglicoles/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Neoplasias Cutáneas/diagnóstico , Resultado del TratamientoRESUMEN
Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).
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Linfoma Cutáneo de Células T/patología , Micosis Fungoide/diagnóstico , Neoplasias Cutáneas/patología , Guías como Asunto , Humanos , Micosis Fungoide/patologíaRESUMEN
Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens. These Guidelines Insights focus on the diagnosis and treatment of HSTCL as outlined in the NCCN Guidelines for T-Cell Lymphomas.
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Linfoma de Células T , Humanos , Linfoma de Células T/diagnóstico , Linfoma de Células T/epidemiología , Linfoma de Células T/terapia , Guías de Práctica Clínica como Asunto , PronósticoRESUMEN
Desmoplastic melanoma can be difficult to diagnose and on average have a significantly higher T stage at the time of diagnosis compared with conventional melanomas. Histologically, these tumors typically consist of spindle cells in a fibrous matrix. The spindle cells may display fibroblast and/or Schwann cell-like features. In this study, we describe the features of 12 cases of desmoplastic melanoma closely simulating neurofibroma. Although the spindle cells in these tumors may be indistinguishable from those of neurofibroma, features such as prominent fibroplasia (12/12), poor lateral circumscription (8/9), diffuse infiltration of subcutaneous tissue (7/9), and lymphoid aggregates (10/12) may be helpful clues to the diagnosis. No immunohistochemical markers were reliable in distinguishing neurofibroma-like desmoplastic melanomas from neurofibroma. Clinical follow-up was available in 8 cases, of which 4 were initially misdiagnosed as benign neoplasms and given no further re-excision. All 4 of these cases recurred; 2 of which showed transformation to a more aggressive phenotype.
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Melanoma/patología , Neurofibroma/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/análisis , Biomarcadores de Tumor/análisis , Biopsia , Diagnóstico Diferencial , Errores Diagnósticos , Femenino , Humanos , Illinois , Inmunohistoquímica , Filamentos Intermedios/patología , Masculino , Melanoma/química , Melanoma/cirugía , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neurofibroma/química , Neurofibroma/cirugía , Ciudad de Nueva York , Fenotipo , Valor Predictivo de las Pruebas , Neoplasias Cutáneas/química , Neoplasias Cutáneas/cirugía , Factores de Tiempo , Resultado del Tratamiento , Proteína p53 Supresora de Tumor/análisisRESUMEN
Cutaneous T-cell lymphoma (CTCL) is an incurable non-Hodgkin lymphoma of the skin-homing T cell. In early-stage disease, lesions are limited to the skin, but in later-stage disease, the tumor cells can escape into the blood, the lymph nodes, and at times the visceral organs. To clarify the genomic basis of CTCL, we performed genomic analysis of 220 CTCLs. Our analyses identify 55 putative driver genes, including 17 genes not previously implicated in CTCL. These novel mutations are predicted to affect chromatin (BCOR, KDM6A, SMARCB1, TRRAP), immune surveillance (CD58, RFXAP), MAPK signaling (MAP2K1, NF1), NF-κB signaling (PRKCB, CSNK1A1), PI-3-kinase signaling (PIK3R1, VAV1), RHOA/cytoskeleton remodeling (ARHGEF3), RNA splicing (U2AF1), T-cell receptor signaling (PTPRN2, RLTPR), and T-cell differentiation (RARA). Our analyses identify recurrent mutations in 4 genes not previously identified in cancer. These include CK1α (encoded by CSNK1A1) (p.S27F; p.S27C), PTPRN2 (p.G526E), RARA (p.G303S), and RLTPR (p.Q575E). Last, we functionally validate CSNK1A1 and RLTPR as putative oncogenes. RLTPR encodes a recently described scaffolding protein in the T-cell receptor signaling pathway. We show that RLTPR (p.Q575E) increases binding of RLTPR to downstream components of the NF-κB signaling pathway, selectively upregulates the NF-κB pathway in activated T cells, and ultimately augments T-cell-receptor-dependent production of interleukin 2 by 34-fold. Collectively, our analysis provides novel insights into CTCL pathogenesis and elucidates the landscape of potentially targetable gene mutations.
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Genómica , Linfoma Cutáneo de Células T/genética , Proteínas de Microfilamentos/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos/genética , Secuencia de Bases , Genoma Humano , Células HEK293 , Humanos , Células Jurkat , Proteínas de Microfilamentos/química , Mutación/genética , FN-kappa B/metabolismo , Oncogenes , Receptores de Antígenos de Linfocitos T/metabolismo , Análisis de Secuencia de ADN , Transducción de Señal/genética , Proteína de Unión al GTP rhoA/genéticaRESUMEN
BACKGROUND: Premature desquamation of the inner root sheath (PDIRS) is considered one of the distinctive features in central centrifugal cicatricial alopecia (CCCA). However, PDIRS can be seen in other alopecia subtypes, and its utility in the diagnosis of CCCA has been debated. We aimed to examine a large cohort of alopecia cases for the presence of PDIRS in association with and without inflammation to determine whether PDIRS in noninflamed follicles can be used as a specific marker of CCCA. METHODS: Retrospective analysis was performed on 501 histologically unambiguous cases of alopecia (111 of CCCA, 102 of lichen planopilaris, 62 of discoid lupus erythematosus, 16 of acne keloidalis nuchae, 27 of folliculitis decalvans, 80 of androgenetic alopecia, 97 of alopecia areata, and 6 of psoriatic alopecia). The frequency of PDIRS, including cases with and without inflammation, was determined. RESULTS: PDIRS was identified in all alopecia subtypes evaluated. When PDIRS was identified in lichen planopilaris, discoid lupus erythematosus, acne keloidalis nuchae, and alopecia areata, 100% of cases were in inflamed follicles. PDIRS in noninflamed follicles occurred in 73% (81/111) of CCCA, 33% (2/6) of psoriatic alopecia, 11% (3/27) of folliculitis decalvans, and 1% (1/97) of androgenetic alopecia. The presence of PDIRS in at least one noninflamed hair follicle correlated with a diagnosis of CCCA with a sensitivity of 73% and a specificity of 98% (P-value <0.0001). CONCLUSION: Identifying PDIRS in noninflamed hair follicles is a useful histologic feature in the evaluation of scalp biopsies and seems to be relatively specific for CCCA.
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Alopecia/patología , Folículo Piloso/patología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Eccrine duct dilation (EDD) was recently described to occur more frequently in cicatricial alopecias than noncicatricial alopecias. Because single EDD can be useful in the evaluation of alopecias, we aimed to determine whether dilation of multiple eccrine duct units, or "multiple eccrine duct dilation (MEDD)," could more specifically discriminate between cicatricial and noncicatricial alopecias. METHODS: We retrospectively evaluated 611 scalp biopsies (342 cicatricial alopecias and 269 noncicatricial alopecias). RESULTS: Among cicatricial alopecias, MEDD was found in 21% (25/118) of central centrifugal cicatricial alopecia, 26% (29/109) of lichen planopilaris, 13% (10/73) of discoid lupus erythematosus, 31% (5/16) of acne keloidalis nuchae, and 26% (7/26) of folliculitis decalvans. In noncicatricial alopecias, MEDD was found in 1% (1/102) of androgenetic alopecia, 0.7% (1/150) of alopecia areata, and 0% (0/17) of telogen effluvium. In cicatricial alopecias, MEDD occurred in a significantly higher frequency (22%; 76/342) compared with noncicatricial alopecias (0.7%; 2/269) (P-value <0.0001). The presence of MEDD correlated with a diagnosis of cicatricial alopecia with 22% sensitivity and 99% specificity. MEDD also occurred more frequently in cases with moderate to severe inflammation and fibroplasia, suggesting that EDD is a reactive change secondary to the scarring processes. CONCLUSION: The presence of MEDD on scalp biopsies may be a highly specific marker of cicatricial alopecia and can aid in rendering a more accurate diagnosis. MEDD without other definitive histopathologic features of cicatricial alopecia may compel pathologists to pursue additional workup and/or raise the possibility that a cicatricial alopecia cannot be entirely excluded.