RESUMEN
BACKGROUND: Primary cutaneous B-cell lymphomas (CBCL) are a group of rare malignant skin diseases that represent approximately 20%-30% of all primary cutaneous lymphomas (PCL). Previous studies revealed impaired health-related quality of life (HRQoL) in patients diagnosed with primary cutaneous T-cell lymphoma (CTCL). Currently, only small-sized studies investigated HRQoL in CBCL patients and lacked detailed analysis of respective subtypes. OBJECTIVES: This study aims to investigate HRQoL in CBCL patients to identify independent factors of HRQoL impairment in CBCL patients. METHODS: One hundred CBCL patients were recruited from eight German PCL centres in this multicentric, cross-sectional study from 2021 to 2022. The patients completed the dermatologic HRQoL questionnaire Skindex-29 and an investigator-designed 'CBCL-Questionnaire' with additional questions on HRQoL and clinical characteristics. RESULTS: The Skindex-29 revealed that HRQoL in CBCL patients is impaired on a mild to moderate level. The multiple regression analysis identified parameters like worries about dying, feeling prejudiced/discriminated and impairment of daily activities to be independently associated with impairment of HRQoL. Highest scores for HRQoL impairment were found in patients with primary cutaneous follicle centre lymphoma while on rituximab treatment and in patients with primary cutaneous marginal zone lymphoma while on watchful waiting. CONCLUSIONS: HRQoL is impaired in CBCL patients, even though, in the face of indolent disease course and favourable prognosis in the majority of cases. Of note, our investigator-designed tool identified worries about dying, feeling prejudiced/discriminated, and the type of treatment to have a negative impact on patients' HRQoL. Our study highlights the importance of a thorough patient-doctor communication to capture overall disease burden because generic HRQoL tools might lack of disease-specific items.
Asunto(s)
Linfoma de Células B , Calidad de Vida , Neoplasias Cutáneas , Humanos , Masculino , Neoplasias Cutáneas/psicología , Neoplasias Cutáneas/patología , Femenino , Estudios Transversales , Persona de Mediana Edad , Anciano , Linfoma de Células B/psicología , Adulto , Encuestas y Cuestionarios , Anciano de 80 o más Años , Actividades CotidianasRESUMEN
BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). OBJECTIVES: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. METHODS: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. RESULTS: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease. CONCLUSIONS: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues.
Asunto(s)
Micosis Fungoide , Neoplasias Cutáneas , Humanos , Micosis Fungoide/patología , Micosis Fungoide/terapia , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Calidad de Vida , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapiaRESUMEN
BACKGROUND: Early-stage mycosis fungoides (MF) includes involvement of dermatopathic lymph nodes (LNs) or early lymphomatous LNs. There is a lack of unanimity among current guidelines regarding the indications for initial staging imaging in early-stage presentation of MF in the absence of enlarged palpable LNs. OBJECTIVES: To investigate how often imaging is performed in patients with early-stage presentation of MF, to assess the yield of LN imaging, and to determine what disease characteristics promoted imaging. METHODS: A review of clinicopathologically confirmed newly diagnosed patients with cutaneous patch/plaque (T1/T2) MF from PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) data. RESULTS: PROCLIPI enrolled 375 patients with stage T1/T2 MF: 304 with classical MF and 71 with folliculotropic MF. Imaging was performed in 169 patients (45%): 83 with computed tomography, 18 with positron emission tomography-computed tomography and 68 with ultrasound. Only nine of these (5%) had palpable enlarged (≥ 15 mm) LNs, with an over-representation of plaques, irrespectively of the 10% body surface area cutoff that distinguishes T1 from T2. Folliculotropic MF was not more frequently imaged than classical MF. Radiologically enlarged LNs (≥ 15 mm) were detected in 30 patients (18%); only seven had clinical lymphadenopathy. On multivariate analysis, plaque presentation was the sole parameter significantly associated with radiologically enlarged LNs. Imaging of only clinically enlarged LNs upstaged 4% of patients (seven of 169) to at least IIA, whereas nonselective imaging upstaged another 14% (24 of 169). LN biopsy, performed in eight of 30 patients, identified N3 (extensive lymphomatous involvement) in two and N1 (dermatopathic changes) in six. CONCLUSIONS: Physical examination was a poor determinant of LN enlargement or involvement. Presence of plaques was associated with a significant increase in identification of enlarged or involved LNs in patients with early-stage presentation of MF, which may be important when deciding who to image. Imaging increases the detection rate of stage IIA MF, and identifies rare cases of extensive lymphomatous nodes, upstaging them to advanced-stage IVA2.
Asunto(s)
Micosis Fungoide , Neoplasias Cutáneas , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Micosis Fungoide/diagnóstico por imagen , Micosis Fungoide/patología , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Cutaneous peripheral T-cell lymphoma, not otherwise specified (PTL NOS) is an aggressive, but poorly characterized neoplasm. OBJECTIVES: The European Organization for Research and Treatment of Cancer cutaneous lymphoma taskforce (EORTC CLTF) investigated 33 biopsies of 30 patients with primary cutaneous PTL NOS to analyse their clinical, histological, immunophenotypic features and outcome. METHODS: Retrospective analysis of clinical data and histopathological features by an expert panel. RESULTS: Cutaneous PTL NOS manifested clinically either with solitary or disseminated rapidly grown ulcerated tumours or disseminated papulo-nodular lesions. Histologically, a mostly diffuse or nodular infiltrate in the dermis and often extending into the subcutis was found. Epidermotropism was rarely present and only mild and focal. Unusual phenotypes were frequent, e.g. CD3+ /CD4- /CD8- and CD3+ /CD4+ /CD8+ . Moreover, 18% of the cases exhibited an aberrant expression of the B-cell marker CD20 by the tumour cells. All solitary tumours were located on the limbs and presented a high expression of GATA-3 but this did not correlate with outcome and therefore could not serve as a prognostic factor. The prognosis was shown to be generally poor with 10 of 30 patients (33%) dying of lymphoma within the follow-up of 36 months (mean value; range 3-144). The survival rates were 61% after 3 years (CI, 43-85%) and 54% after 5 years (CI, 36-81%). Small to medium-sized morphology of tumour cells was associated with a better outcome than medium to large or large tumour cells. Age, gender, clinical stage, CD4/CD8 phenotype and GATA-3 expression were not associated with prognosis. Chemotherapy was the most common treatment modality, but surgical excision and/or radiotherapy may represent an appropriate first-line treatment for solitary lesions. CONCLUSIONS: Cutaneous PTL NOS shows an aggressive course in most patients independent of initial presentation, age and phenotype. Cytomorphology was identified as a prognostic factor. The data indicate a need for more effective treatment modalities in PTL NOS.
Asunto(s)
Linfoma Cutáneo de Células T , Linfoma de Células T Periférico , Neoplasias Cutáneas , Humanos , Linfoma de Células T Periférico/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/terapiaRESUMEN
BACKGROUND: Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common cutaneous T-cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. AIM: To identify factors associated with poorer health-related quality of life (HRQoL) in patients newly diagnosed with MF/SS. METHODS: Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex-29 questionnaire. Skindex-29 scores were analysed in relation to patient- and disease-specific characteristics. RESULTS: The study population consisted of 237 patients [60·3% male; median age 60 years, (interquartile range 49-70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex-29, was worse in women, SS, late-stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (ß = 8·61; P = 0·003) and alopecia (ß = 9·71, P = 0·02) as independent predictors of worse global HRQoL. Item-level analysis showed that the severe impairment in symptoms [odds ratio (OR) 2·14, 95% confidence interval (CI) 1·19-3·89] and emotions (OR 1·88, 95% CI 1·09-3·27) subscale scores seen in women was caused by more burning/stinging, pruritus, irritation and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. CONCLUSIONS: HRQoL is significantly more impaired in newly diagnosed women with MF/SS and in those with alopecia. As Skindex-29 does not include existential questions on cancer, which may cause additional worry and distress, a comprehensive validated cutaneous T-cell lymphoma-specific questionnaire is urgently needed to more accurately assess disease-specific HRQoL in these patients. What's already known about this topic? Cross-sectional studies of mixed populations of known and newly diagnosed patients with mycosis fungoides (MF)/Sézary syndrome (SS) have shown significant impairment in health-related quality of life (HRQoL). Previous studies on assessing gender-specific differences in HRQoL in MF/SS are conflicting. More advanced-stage disease and pruritus is associated with poorer HRQoL in patients with MF/SS. What does this study add? This is the first prospective study to investigate HRQoL in a homogenous group of newly diagnosed patients with MF/SS. In patients newly diagnosed with MF/SS, HRQoL is worse in women and in those with alopecia and confluent erythema. MF/SS diagnosis has a multidimensional impact on patient HRQoL, including a large burden of cutaneous symptoms, as well as a negative impact on emotional well-being.
Asunto(s)
Linfoma Cutáneo de Células T , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Calidad de VidaRESUMEN
BACKGROUND: Pleomorphic dermal sarcomas (PDS) are frequent UV-induced sarcomas of the skin of intermediate grade malignant potential. Despite the fact that PDS have a noteworthy potential to recur (up to 28%) as well as to metastasize (up to 20%), there are no specific clinical guidelines with respect to follow-up these patients. Moreover, little is known about clinical, histological or molecular prognostic factors in PDS. OBJECTIVE: The aim of the present study was to identify risk factors to predict relapse in a large multicentre sample cohort of PDS which could aid to optimize personalized treatment recommendations regarding surgical safety margins and adjuvant radiotherapy. METHODS: Patients with a diagnosis of PDS were selected from nine European institutions based on the histopathologic criteria described by Fletcher. Clinicopathologic and follow-up data were collected and statistically analysed calculating univariate hazard ratios with 95% confidence intervals by use of the Cox proportional-hazards model and a significance level of P < 0.05. Patients with an incomplete excision of the tumour were excluded. RESULTS: Univariate Cox regression analysis of possible prognostic factors for progression-free survival (PFS) performed in 92 patients revealed that an excision margin of <2 cm is significantly associated with relapse of PDS [hazard ratio 4.478 (95% CI 1.536-13.055), P = 0.006]. Ulceration of the tumour was associated with a significantly better prognosis [0.396 (0.174-0.904), P = 0.028] whereas adjuvant radiotherapy did not reach statistical significance to improve prognosis in patients with PDS [0.775 (0.231-2.593), P = 0.679]. Gender, age, immunosuppression, intratumoural necrosis, tumour location, vertical thickness or horizontal diameter did not significantly influence PFS in PDS. CONCLUSION: We identified surgical safety margins of <2 cm and absence of ulceration as risk factors for relapse in patients with PDS. These findings may be implemented into both the primary treatment as well as the further monitoring of patients with PDS.
Asunto(s)
Márgenes de Escisión , Sarcoma/cirugía , Neoplasias Cutáneas/cirugía , Úlcera/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web-based data collection system for early-stage MF with legal data-sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in-built intelligence in the database system ensures accurate staging. OBJECTIVES: To develop a prognostic index for MF. METHODS: Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies. RESULTS: In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early-stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 12-90)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF. CONCLUSIONS: This confirmed early-stage MF cohort is being followed-up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex.
Asunto(s)
Diagnóstico Tardío/estadística & datos numéricos , Micosis Fungoide/diagnóstico , Sistema de Registros/estadística & datos numéricos , Neoplasias Cutáneas/diagnóstico , Adulto , Factores de Edad , Anciano , Conjuntos de Datos como Asunto , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Micosis Fungoide/mortalidad , Micosis Fungoide/patología , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Piel/patología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patologíaRESUMEN
Primary cutaneous Bcell lymphomas are rarely encountered and represent 25% of all cutaneous lymphomas. Follicular Bcell lymphoma and marginal zone lymphoma belong to indolent subtypes which as a rule have no systemic dissemination and, thus, a mostly unchanged life expectancy. Therefore, skin-directed treatment options such as excision or radiotherapy are usually sufficient to control the disease. In contrast, cutaneous diffuse large Bcell lymphoma and EBV-associated Bcell lymphomas of the skin belong to more aggressive entities which demand a systemic first-line upfront therapy with RCHOP. Nevertheless, mortality is still high and comparable to that of systemic/nodal large Bcell lymphomas so that the identification of pathogenetic driver mutations or novel therapeutic targets may pave the way to better target-oriented therapies.
Asunto(s)
Linfoma de Células B/terapia , Neoplasias Cutáneas/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Infecciones por Virus de Epstein-Barr/mortalidad , Infecciones por Virus de Epstein-Barr/patología , Infecciones por Virus de Epstein-Barr/terapia , Femenino , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Humanos , Inmunoterapia , Linfoma de Células B/mortalidad , Linfoma de Células B/patología , Linfoma de Células B de la Zona Marginal/mortalidad , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B de la Zona Marginal/terapia , Linfoma Folicular/mortalidad , Linfoma Folicular/patología , Linfoma Folicular/terapia , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Piel/patología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Tasa de SupervivenciaAsunto(s)
Inmunoglobulina M/genética , Linfoma de Células B de la Zona Marginal/genética , Mutación/genética , Factor 88 de Diferenciación Mieloide/genética , Neoplasias Cutáneas/genética , Anciano , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/inmunología , Femenino , Humanos , Inmunoglobulina M/inmunología , Inmunofenotipificación , Linfoma de Células B de la Zona Marginal/inmunología , Linfoma de Células B de la Zona Marginal/patología , Masculino , Mutación/inmunología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patologíaAsunto(s)
Infecciones Cutáneas Estafilocócicas/diagnóstico , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus , Antibacterianos/uso terapéutico , Nalgas , Enfermedad Crónica , Diagnóstico Diferencial , Femenino , Humanos , Dermatosis de la Pierna , Persona de Mediana Edad , Infecciones Cutáneas Estafilocócicas/microbiología , Muslo , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: Indolent cutaneous CD8+ lymphoid proliferation is a recently described rare entity among cutaneous T-cell lymphomas that typically presents with solitary skin lesions at acral sites. Separation from otherwise aggressive T-cell lymphomas bearing a cytotoxic CD8+ phenotype is fundamental to avoid unnecessary harmful treatment. However, up to now, no reliable discriminative marker has been identified. OBJECTIVES: Motivated by these diagnostic quandaries, we have analyzed a large series of archived formalin-fixed paraffin-embedded (FFPE) specimens of atypical CD8+ cutaneous infiltrates with clear-cut diagnosis and clinical follow-up (n = 44) including five cases of indolent CD8+ lymphoid proliferation by using immunohistochemistry with the aim of obtaining markers predictive of subtype assignment. RESULTS: We identified exclusive expression of CD68 by lymphoma cells within the subgroup of indolent CD8+ lymphoid proliferation (5/5 cases). Specific CD68 expression in this entity was confirmed by the application of several monoclonal antibodies (KP1, PG-M1, KiM1P) against the CD68 molecule available for FFPE tissue. In contrast, none of the infiltrates of the other CD8+ cutaneous lymphoma entities stained positive for CD68 (0/39). CONCLUSIONS: Based on these observations, we suggest CD68 as a new discriminative marker which is helpful in distinguishing indolent CD8+ lymphoid proliferation from other CD8+ cutaneous lymphomas in ambiguous cases.
Asunto(s)
Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biomarcadores de Tumor/metabolismo , Linfoma Cutáneo de Células T/diagnóstico , Neoplasias Cutáneas/diagnóstico , Anciano , Linfocitos T CD8-positivos/fisiología , Proliferación Celular/fisiología , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadAsunto(s)
Síndromes Neurocutáneos/diagnóstico , Trastornos de la Pigmentación/etiología , Mancha Vino de Oporto/diagnóstico , Biopsia , Conducta Cooperativa , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Comunicación Interdisciplinaria , Melanocitos/patología , Síndromes Neurocutáneos/patología , Paresia/diagnóstico , Paresia/patología , Trastornos de la Pigmentación/diagnóstico , Trastornos de la Pigmentación/patología , Mancha Vino de Oporto/patología , Trastornos Psicomotores/diagnóstico , Trastornos Psicomotores/patología , Proteínas S100/análisis , Piel/patología , Espasmos Infantiles/etiología , Espasmos Infantiles/patologíaRESUMEN
Treatment options for adrenocortical carcinoma (ACC) are very limited. In other solid tumors, small vaccination trials targeting the anti-apoptotic molecule survivin suggested immunological and clinical benefit in selected patients. Therefore, we investigated whether survivin might be a suitable target for immunotherapy in ACC. Survivin mRNA and protein expression was assessed in adrenal tissue specimens [by real-time-PCR in 29 ACC, 24 adrenocortical adenomas (ACA) and 12 normal adrenal glands; by immunohistochemistry in 167 ACCs, 15 ACA, and 5 normal adrenal glands]. Expression was correlated with clinical outcome using Kaplan-Meier and Cox regression analyses. The anti-apoptotic role of survivin was investigated in the SW13 ACC cell line using survivin siRNA. The presence of spontaneous survivin specific T-cells in peripheral blood was assessed by FACS dextramere staining in 29 ACC patients in comparison to healthy controls. Survivin mRNA in ACC was significantly overexpressed when compared with ACA or normal adrenal glands. Immunohistochemistry confirmed survivin protein expression in 97% of the ACCs. In 83% of samples, staining was moderate or high and clinical outcome in this subgroup showed a trend towards poorer prognosis [hazard ratio for death 2.28 (95% CI 0.99-5.28); p=0.053]. Survivin knockdown in SW-13 cell significantly increased the rate of apoptosis. Finally, spontaneous survivin-reactive T cells were detectable in 3 of 29 ACC patients. In conclusion, our data suggest that survivin could play an important role in the anti-apoptotic mechanisms in ACC and provide first hints that targeting survivin might be an interesting new therapeutic approach in this rare disease.
Asunto(s)
Neoplasias de la Corteza Suprarrenal/metabolismo , Corteza Suprarrenal/metabolismo , Carcinoma Corticosuprarrenal/metabolismo , Proteínas Inhibidoras de la Apoptosis/metabolismo , Proteínas de Neoplasias/metabolismo , Corteza Suprarrenal/efectos de los fármacos , Corteza Suprarrenal/patología , Neoplasias de la Corteza Suprarrenal/diagnóstico , Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Neoplasias de la Corteza Suprarrenal/patología , Adenoma Corticosuprarrenal/tratamiento farmacológico , Adenoma Corticosuprarrenal/metabolismo , Adenoma Corticosuprarrenal/fisiopatología , Carcinoma Corticosuprarrenal/diagnóstico , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/patología , Adulto , Anciano , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas Inhibidoras de la Apoptosis/antagonistas & inhibidores , Proteínas Inhibidoras de la Apoptosis/genética , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Pronóstico , Interferencia de ARN , Análisis de Supervivencia , SurvivinAsunto(s)
Impétigo/diagnóstico , Dermatosis del Cuero Cabelludo/diagnóstico , Tiña del Cuero Cabelludo/diagnóstico , Antibacterianos/uso terapéutico , Antifúngicos/uso terapéutico , Técnicas Bacteriológicas , Preescolar , Diagnóstico Diferencial , Floxacilina/uso terapéutico , Humanos , Masculino , Microsporum/efectos de los fármacos , Microsporum/crecimiento & desarrollo , Naftalenos/uso terapéutico , Infecciones Cutáneas Estafilocócicas/diagnóstico , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Sobreinfección/diagnóstico , Sobreinfección/tratamiento farmacológico , TerbinafinaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de Cabeza y Cuello , Hemangiosarcoma , Cuero Cabelludo , Terapia Combinada/métodos , Doxorrubicina/administración & dosificación , Neoplasias Faciales/tratamiento farmacológico , Neoplasias Faciales/radioterapia , Frente , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Hemangiosarcoma/tratamiento farmacológico , Hemangiosarcoma/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Resultado del TratamientoRESUMEN
Rituximab has been established as an effective and safe therapy for cutaneous B-cell lymphoma (CBCL). Different survival pathways, that is the Raf/MEK/Erk- or the p38MAPK cascade, have been suggested as downstream mediators of rituximab and may be involved in treatment failure. Biopsies from four patients, suffering from different subtypes of CBCL, which were obtained at various time points of relapse during or after therapy with 375 mg rituximab per m2 of body surface area, were analysed for the expression of CD20, CD3, Ki-67, Raf-kinase inhibitory protein (RKIP) and bcl-2 by immunohistochemistry. No CD20-loss variants, that is the suggested main tumour escape mechanism to rituximab therapy, were observed in any specimen of relapsing CBCL. Notably, the expression of proapoptotic RKIP remained increased in these tumour samples. This was concomitated by a constant to slightly reduced proliferation status as demonstrated by Ki-67 staining. However, relapsing CBCL exhibited a strong upregulation of the antiapoptotic molecule bcl-2 in comparison to pretherapeutic levels. The immunohistochemical analyses of this case series of rituximab refractory CBCL suggest that upregulation of bcl-2 may play a major role in therapy resistance.