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The aim of this study was to investigate the role of PRAME in reducing the risk of an underestimation of tumour margins, in a consecutive series of acral melanomas recurring on skin grafts.
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Melanoma , Neoplasias Cutáneas , Humanos , Trasplante de Piel , Melanoma/cirugía , Melanoma/patología , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Antígenos de NeoplasiasRESUMEN
The primary function of 25(OH)Vitamin D (VitD) is to control calcium; however, recent evidence associated serum VitD deficiency to high aggressiveness and worse outcome in different type of malignancies including lymphomas, and the reasons of such effect are to be defined. In this study, we investigated the association of VitD blood levels with gene expression in a retrospective cohort of 181 lymphomas (104 diffuse large B-cell lymphomas [DLBCLs] and 77 classical Hodgkin's lymphomas [cHLs]) of whom 116 with available gene expression profiles (52 DLBCLs and 64 cHLs, respectively). In DLBCL, VitD deficiency did not cause significant alteration in gene expression suggesting different mechanisms of action including a possible systemic effect or an effect on pharmacokinetics. By contrast, in cHLs, VitD deficiency induced profound changes in the transcriptional program leading to the NF-κB-mediated activation of stress-protective and pro-survival pathways. Coherently, VitD signaling defined by vitamin D Receptor (VDR) expression analysis, resulted highly activated in cHLs but not in DLBCLs. Even if preliminary, these data represent the first evidence of a direct role of VitD in the biology of cHL and suggest a multimodality and disease-specific activity of this vitamin in lymphomas.
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Enfermedad de Hodgkin/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Vitamina D/uso terapéutico , Adulto , Humanos , Transcriptoma , Vitamina D/sangre , Vitamina D/farmacologíaRESUMEN
Germinotropic lymphoproliferative disorder is a rare and rather enigmatic novel entity with distinctive clinicopathological features, one of which is the typical co-infection by Human herpesvirus 8 and Epstein-Barr virus. Human herpesvirus 8 is a lymphotropic virus detected in Kaposi sarcoma, multicentric Castleman disease, primary effusion lymphoma, Human herpesvirus 8-positive diffuse large B cell lymphoma not otherwise specified, and germinotropic lymphoproliferative disorder. Co-infection by Human herpesvirus 8 and Epstein-Barr virus is identified only in two lymphoproliferative diseases: germinotropic lymphoproliferative disorder and primary effusion lymphoma, which are otherwise diseases with totally different clinical presentations and outcomes. Unlike primary effusion lymphoma mostly occurring in immunocompromised individuals and following an aggressive course, germinotropic lymphoproliferative disorder usually presents with single or multiple lymphadenopathy affecting mainly immunocompetent individuals and mostly follows an indolent course. Based on the PRISMA guidelines, we carried out a systematic search on PubMed/MEDLINE, Web of Science, Scopus, EMBASE, and Cochrane Library using the search terms "germinotropic" and "lymphoproliferative disorder." Current scientific literature reports just 19 cases of germinotropic lymphoproliferative disorder. The purpose of our systematic review is to improve our understanding of the disease, focusing on epidemiology, clinical presentation, pathological features, treatment, and outcome. In addition, we discuss the differential diagnosis with the other Human herpesvirus 8-related lymphoproliferative diseases as currently recognized in the World Health Organization classification, adding a focus on lymphoproliferative disorders showing overlapping features.
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Coinfección/virología , Infecciones por Herpesviridae/virología , Herpesvirus Humano 4/patogenicidad , Herpesvirus Humano 8/patogenicidad , Trastornos Linfoproliferativos/virología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Centro Germinal/patología , Infecciones por Herpesviridae/diagnóstico , Infecciones por Herpesviridae/terapia , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 8/aislamiento & purificación , Humanos , Inmunocompetencia , Ganglios Linfáticos/patología , Linfoma de Células B Grandes Difuso/virología , Linfoma no Hodgkin/virología , Linfoma de Efusión Primaria/diagnóstico , Linfoma de Efusión Primaria/virología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/terapia , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Eosinophilic lung diseases represent a heterogeneous group of disorders with prominent infiltrate of eosinophils in lung interstitium and alveolar spaces. Peripheral blood eosinophilia is often present. Infections, drugs, allergens, toxic agents have to be evaluated as possible causes of eosinophilic lung infiltrates. The category of myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 and PCM1-JAK2 represents an uncommon cause of eosinophilic lung infiltrate. CASE PRESENTATION: We report the case of a 70-year old man complaining of dry cough and dyspnea. Ground glass-opacities were seen on imaging studies and peripheral blood eosinophilia was present. A thorough step-wise patient's evaluation led to identify the clonal nature of eosinophilia and the diagnosis of myeloid/lymphoid neoplasm with eosinophilia and rearrangement of PDGFRA was made. CONCLUSIONS: Correlation with clinical history, laboratory tests and imaging studies is essential to achieve the correct diagnosis when facing with eosinophilic lung infiltrates. A prolonged eosinophilia can cause life-threatening organ damage. Identification of PDGFRA rearrangement, as in the present case, is particularly critical given the sensitivity and excellent response to imatinib, which has completely changed the natural history of this neoplasm.
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Síndrome Hipereosinofílico/diagnóstico , Leucemia/diagnóstico , Trastornos Mieloproliferativos/diagnóstico , Eosinofilia Pulmonar/etiología , Anciano , Humanos , Síndrome Hipereosinofílico/genética , Leucemia/genética , Masculino , Trastornos Mieloproliferativos/genética , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Extra-uterine mullerian adenosarcomas have varying biological behaviours depending on the presence of endometriosis or sarcomatous overgrowth. These behaviours manifest according to the tumours' histological characteristics and sites of origin. The best treatment and oncologic outcome have not been clarified because only a few cases of extra-uterine and extra-ovarian adenosarcoma have been described in the literature. Here, we report a case of primary peritoneal adenosarcoma with sarcomatous overgrowth and review all reported cases of adenosarcomas arising outside of the uterus and outside the ovaries to identify the best treatment options and clarify outcomes. CASE PRESENTATION: A 79-year-old woman was referred to our Department with an abdominal mass resembling a fibroid with a haemorrhage. Her gynaecological history was negative. A transvaginal and transabdominal ultrasound examination revealed a multicystic mass resembling an ovarian tumour arising from the pelvis and extending up to the abdomen. At laparotomy a peritoneal mass arising from Douglas peritoneum was resected. The uterus and adnexa appeared normal, and a supra-cervical hysterectomy with bilateral salpingo-oophorectomy was performed. No macroscopic residual disease was present. Final pathology diagnosed a malignant peripheral nerve sheath tumors with divergent differentiation. Four weeks later a new, multicystic mass was found. Due to the progressive poor condition, the patient died four months after diagnosis. Histological slides were reviewed by external expert pathologists and the final diagnosis was of extra-genital adenosarcoma with sarcomatous overgrowth. Furthermore, we also collected and analysed articles written in English regarding extra-uterine and extra-ovarian adenosarcomas published between January 1974 and October 2016. PubMed was used as a database for this search. Clinical and pathological characteristics, treatments and outcomes were assessed. CONCLUSIONS: Only 41 cases has been reported in literature. Previous endometriosis and sarcomatous overgrowth showed an inverse effect on prognosis. Endometriosis was confirmed to have a positive effect on disease free survival Complete surgical resection is the mainstay of treatment. A worldwide registry is urgently required to collect data to standardize treatment and to obtain reliable data on prognosis.
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Adenosarcoma/diagnóstico , Tumor Mulleriano Mixto/diagnóstico , Neoplasias Ováricas/diagnóstico , Neoplasias Uterinas/diagnóstico , Adenosarcoma/cirugía , Anciano , Femenino , Humanos , Leiomioma/diagnóstico , Leiomioma/cirugía , Tumor Mulleriano Mixto/cirugía , Neoplasias Ováricas/cirugía , Neoplasias Uterinas/cirugíaRESUMEN
An accurate histological diagnosis may distinguish essential thrombocythaemia (ET) from early primary myelofibrosis (early-PMF), which is associated with worse outcome. Outcome of ET is also negatively affected by the presence of the JAK2V617F mutation. To investigate the impact of JAK2V617F mutation burden and histology on outcome, we collected 475 WHO-diagnosed ET (69.2%) or early-PMF JAK2V617F -positive patients followed in 4 Italian haematology centers. JAK2V617F allele burden was ≤50% in 90% and 87% of ET and early-PMF patients, respectively (P = .34). During follow-up, 32 (9.7%) ET and 18 (12.3%) early-PMF patients experienced 59 thrombotic events, and 27 patients (5.6%) and 6 (1.2%) patients evolved to myelofibrosis and acute leukemia, respectively. At last contact, 28 (5.8%) patients had died. In early-PMF compared to ET, the 10-year mortality rates (6.7% and 4.3%, P = .73), leukemic transformation rates (1.4% and 1.2%, P = .45), and thrombosis rates (16.7% and 12.2%, P = .12) were comparable. Only progression to overt myelofibrosis at 10 years was significantly worse (11.4% and 1.5%, P = .004). In multivariate analysis, a higher (>50%) JAK2V617F burden was significantly correlated with fibrotic progression and histology. Considering JAK2V617F -positive disease, a higher (>50%) JAK2V617F burden and histological classification are independent prognostic risk factors for disease progression. These findings reinforce the need for standardized detection of this mutation.
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Janus Quinasa 2/genética , Mielofibrosis Primaria/enzimología , Trombocitemia Esencial/enzimología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/mortalidad , Mielofibrosis Primaria/patología , Análisis de Supervivencia , Trombocitemia Esencial/genética , Trombocitemia Esencial/mortalidad , Trombocitemia Esencial/patología , Resultado del Tratamiento , Adulto JovenAsunto(s)
Melanoma/patología , Neoplasias Cutáneas/patología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
This study, performed on behalf of the Italian Registry of Thrombocythaemias (Registro Italiano Trombocitemie), aimed to test the inter-observer reproducibility of the histological parameters proposed by the WHO classification for the diagnosis of the Philadelphia chromosome-negative myeloproliferative neoplasms. A series of 103 bone marrow biopsy samples of Philadelphia chromosome-negative myeloproliferative neoplasms consecutively collected in 2004 were classified according to the WHO criteria as follows: essential thrombocythaemia (n=34), primary myelofibrosis (n=44) and polycythaemia vera (n=25). Two independent groups of pathologists reviewed the bone marrow biopsies. The first group was asked to reach a collegial 'consensus' diagnosis. The second group reviewed individually all the cases to recognize the main morphological parameters indicated by the WHO classification and report their results in a database. They were subsequently instructed to individually build a 'personal' diagnosis of myeloproliferative neoplasms subtype just assembling the parameters collected in the database. Our results indicate that high levels of agreement (≥70%) have been reached for about all of the morphological features. Moreover, among the 18 evaluated histological features, 11 resulted statistically more useful for the differential diagnosis among the different Philadelphia chromosome-negative myeloproliferative neoplasms. Finally, we found a high percentage of agreement (76%) between the 'personal' and 'consensus' diagnosis (Cohen's kappa statistic >0.40). In conclusion, our results support the use of the histological criteria proposed by the WHO classification for the Philadelphia chromosome-negative myeloproliferative neoplasms to ensure a more precise and early diagnosis for these patients.
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Policitemia Vera/diagnóstico , Mielofibrosis Primaria/diagnóstico , Trombocitemia Esencial/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Cromosoma Filadelfia , Policitemia Vera/epidemiología , Mielofibrosis Primaria/epidemiología , Reproducibilidad de los Resultados , Trombocitemia Esencial/epidemiología , Organización Mundial de la Salud , Adulto JovenAsunto(s)
Linfoma de Células B Grandes Difuso/complicaciones , Esquistosomiasis Urinaria/complicaciones , Abdomen Agudo , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Urgencias Médicas , Femenino , Humanos , Inflamación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Prednisona/administración & dosificación , Inducción de Remisión , Factores de Riesgo , Rituximab/administración & dosificación , Esquistosomiasis Urinaria/patología , Vincristina/administración & dosificaciónRESUMEN
OBJECTIVE: Indolent extranodal T-cell lymphoproliferative disorders have recently been described as new entities in the gastrointestinal tract and acral sites displaying clonal T-cell receptor (TCR) rearrangement and nonactivated cytotoxic CD8+ T-cell phenotypes. METHODS/RESULTS: We report a unique case of an atypical myometrial T-cell lymphoproliferation in a 39-year-old multiparous woman, which shares many of the features mentioned above: CD8+/TIA1+/granzyme B- phenotype, clonal TCR rearrangement and indolent course. CONCLUSION(S): We hypothesize that it might derive from a subset of uterine nonrecirculating CD8+ resident memory T cells expanded after repeated exposure to allo-extravillous trophoblastic antigen.
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Linfocitos T CD8-positivos , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/patología , Miometrio/patología , Enfermedades Uterinas/inmunología , Enfermedades Uterinas/patología , Adulto , Linfocitos T CD8-positivos/inmunología , Femenino , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T , Humanos , Memoria Inmunológica , Trastornos Linfoproliferativos/genética , Miometrio/inmunología , Enfermedades Uterinas/genéticaRESUMEN
Resveratrol (RSV), a plant-derived stilbene, induces cell death in Hodgkin lymphoma (HL)-derived L-428 cells in a dose-dependent manner (IC50 = 27 µM, trypan blue exclusion assay). At a lower range (25 µM), RSV treatment for 48 hr causes arrest in the S-phase of the cell cycle, while at a higher concentration range (50 µM), apoptosis can be detected, with activation of caspase-3. The histone/protein deacetylase SIRT1 has been described as a putative target of RSV action in other model systems, even though its role in cancer cells is still controversial. Here we show that RSV, at both concentration ranges, leads to a marked increase in p53, while a decrease of SIRT1 expression level, as well as enzyme activity, only occurred at the higher concentration range. Concomitantly, however, treatments at both concentration ranges resulted in a marked increase in K373-acetylated p53 and lysine-acetylated FOXO3a. Immunohistochemical stainings of human lymph nodes show a preferential distribution of SIRT1 in the germinal center of the follicles while the mantle zone shows nearly no staining to few positive cells. The classical HL-affected lymph nodes show a strong positivity of the diagnostic Hodgkin Reed-Sternberg cells. Notably, both the HL-derived cell lines and the Hodgkin Reed-Sternberg cells of the affected lymph nodes derive from germinal center-derived B cells. The study of SIRT1 distribution and expression on a larger number of biopsies might disclose a novel role for this histone/protein deacetylase as therapeutic target.
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Apoptosis/efectos de los fármacos , Factores de Transcripción Forkhead/metabolismo , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/metabolismo , Sirtuina 1/antagonistas & inhibidores , Estilbenos/farmacología , Acetilación/efectos de los fármacos , Apoptosis/genética , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Caspasa 3/genética , Caspasa 3/metabolismo , Procesos de Crecimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Proteína Forkhead Box O3 , Centro Germinal/efectos de los fármacos , Centro Germinal/metabolismo , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/patología , Humanos , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/metabolismo , Resveratrol , Fase S/efectos de los fármacos , Fase S/genética , Sirtuina 1/genética , Sirtuina 1/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Background: Hematological malignancies (HMs) represent a heterogeneous group of diseases with diverse etiology, pathogenesis, and prognosis. HMs' accurate registration by Cancer Registries (CRs) is hampered by the progressive de-hospitalization of patients and the transition to molecular rather than microscopic diagnosis. Material and methods: A dedicated software capable of automatically identifying suspected HMs cases by combining several databases was adopted by Reggio Emilia Province CR (RE-CR). Besides pathological reports, hospital discharge archives, and mortality records, RE-CR retrieved information from general and biomolecular laboratories. Incidence, mortality, and 5-year relative survival (RS) reported according to age, sex, and 4 HMs' main categories, were noted. Results: Overall, 7,578 HM cases were diagnosed from 1996 to 2020 by RE-CR. HMs were more common in males and older patients, except for Hodgkin Lymphoma and Follicular Lymphoma (FL). Incidence showed a significant increase for FL (annual percent change (APC)=3.0), Myeloproliferative Neoplasms (MPN) in the first period (APC=6.0) followed by a significant decrease (APC=-7.4), and Myelodysplastic Syndromes (APC=16.4) only in the first period. Over the years, a significant increase was observed in 5-year RS for Hodgkin -, Marginal Zone -, Follicular - and Diffuse Large B-cell-Lymphomas, MPN, and Acute Myeloid Leukemia. The availability of dedicated software made it possible to recover 80% of cases automatically: the remaining 20% required direct consultation of medical records. Conclusions: The study emphasizes that HM registration needs to collect information from multiple sources. The digitalization of CRs is necessary to increase their efficiency.
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PRAME (PReferentially expressed Antigen in MElanoma), a cancer testis antigen expressed in low levels in gonadal, endometrial, and adrenal gland tissues, has been recently considered a valuable tool in the differential diagnosis between benign and malignant melanocytic lesions. The aim of the current study is to perform PRAME immunostaining on a large series of benign and malignant acral lesions to evaluate the reproducibility of data reported in the literature and to validate PRAME as an affordable tool in the differential diagnosis between benign and malignant acral melanocytic tumors. Immunohistochemical analysis for PRAME was performed in 127 benign and malignant acral and nail melanocytic lesions. To better correlate PRAME expression with the nature (benign vs. malignant) of the lesions, we categorized PRAME tumor cells percentage positivity and intensity in a cumulative score obtained by adding the quartile of positive tumor cells (0, 1+, 2+, 3+, 4+) to PRAME expression intensity in tumor cells (0, 1+, 2+, 3+). Adopting an arbitrary PRAME expression score of < 5 versus ≥5 resulted in a correct identification of 82.5% of benign and 87.1% of malignant lesions. PRAME immunohistochemistry demonstrated good sensitivity and specificity in the diagnosis of acral melanocytic lesions, however, in line with the previous literature, we identified a subset of challenging cases such as acral Spitz nevi, in situ melanomas, and small, thin, invasive melanomas in which PRAME did not correlate with morphologic features. This suggests that PRAME can be a valid tool to be incorporated in a diagnostic clinicopathologic algorithm, subject to morphologic characteristics.
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Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Antígenos de Neoplasias/análisis , Diagnóstico Diferencial , Humanos , Masculino , Melanocitos/patología , Melanoma/patología , Nevo de Células Epitelioides y Fusiformes/patología , Reproducibilidad de los Resultados , Neoplasias Cutáneas/patologíaRESUMEN
PURPOSE: To investigate the role of combined systemic and local chemotherapy in improving the survival of patients with vitreoretinal lymphoma (VRL). METHODS: Patients with VRL consecutively seen from 2006 to 2020 were retrospectively reviewed; data on the presence and time of central nervous system (CNS) involvement and treatment regimen (systemic, local or combined chemotherapy) were collected. Overall survival (OS) and progression-free survival (PFS) were calculated for each group. RESULTS: Forty-three eyes of 22 subjects with histology-proven VRL were included. Mean time of survival was 64.8 months (SE±10.8). Twelve patients (57%) presented CNS involvement, which was significantly associated with progression (r = 0.48, P = .03) and death (r = 0.56, P = .009). The isolated primary VRL group had a 5-year OS of 80%. Combined systemic and local chemotherapy reduced the risk of death by 82% (hazard ratio 0.18[0.04- 0.85]) in the entire cohort. CONCLUSION: Combined systemic and local chemotherapy significantly improved OS but not PFS of patients affected by VRL.
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Linfoma , Neoplasias de la Retina , Humanos , Linfoma/diagnóstico , Linfoma/tratamiento farmacológico , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/tratamiento farmacológico , Estudios Retrospectivos , Cuerpo Vítreo , UveítisAsunto(s)
Transformación Celular Neoplásica/patología , Leucemia de Células Pilosas/genética , Linfoma de Células B/tratamiento farmacológico , Factor de Empalme U2AF/genética , Anciano , Células Clonales , Genes de las Cadenas Pesadas de las Inmunoglobulinas , Variación Genética , Humanos , Inmunoterapia , Leucemia de Células Pilosas/patología , Linfoma de Células B/genética , Masculino , Mutación , Inducción de Remisión , Resultado del TratamientoRESUMEN
The present article reports the case of a patient presenting with chronic myeloid leukemia, diagnosed during the accelerated phase (>20% blasts in peripheral blood samples and megakaryocyte agglomerates in the bone marrow). The subject was treated with first-line therapy with the tyrosine kinase inhibitor nilotinib and reached complete clinical and molecular remission (according to the European Leukemia Net-ELN-criteria), which persisted over five years of treatment. Five years after discontinuation of nilotinib (ten years from diagnosis), the patient is in good clinical condition, with no traces of BCL-ABL1 at molecular evaluation (molecular response, MR5). The case is discussed in the setting of current literature, providing an overview on chronic myeloid leukemia and a discussion on treatment options available.
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The term "ovarian carcinoma" encompasses at least five different malignant neoplasms: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, mucinous carcinoma, and clear cell carcinoma. These five histotypes demonstrated distinctive histological, molecular, and clinical features. The rise of novel target therapies and of a tailored oncological approach has demanded an integrated multidisciplinary approach in the setting of ovarian carcinoma. The need to implement a molecular-based classification in the worldwide diagnostic and therapeutic setting of ovarian cancer demanded a search for easy-to-use and cost-effective molecular-surrogate biomarkers, relying particularly on immunohistochemical analysis. The present review focuses on the role of immunohistochemistry as a surrogate of molecular analysis in the everyday diagnostic approach to ovarian carcinomas.
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Clinical use of topical ascorbic acid solution could have both the role as an adjunct to consolidated therapies and as an alternative to them, for the treatment of BCC and SCC of the skin.
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Mycosis fungoides and nodal classic Hodgkin lymphoma (cHL) have been reported to occur concurrently or sequentially in the same patient. A long-lasting mycosis fungoides more often precedes the onset of nodal cHL, although few cases of nodal cHL followed by mycosis fungoides have been observed. Skin involvement is a rare manifestation of cHL that may be observed in the setting of advanced disease. The decrease in skin involvement in cHL is mainly due to the improved therapeutic strategies. The concurrent presence of mycosis fungoides and cutaneous localization of classic Hodgkin lymphoma represents a very uncommon event, with only two cases reported so far. Herein, we describe the case of a 71-year-old man, with a history of recurrent nodal cHL, who developed MF and, subsequently, the cutaneous localization of cHL. The clinicopathological features of the two diseases are described focusing on the main differential diagnoses to be taken into consideration, and a review of the literature is performed.
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Malignant Pleural Mesothelioma (MPM) is a heterogeneous disease. Morphologically, three different phenotypes are distinguishable: epithelioid (e-), sarcomatoid (s-) and biphasic (biph-) MPM, the latest, being a mixture of e- and s-MPM cells. Being an intermediate entity, management of biph-MPM, remains debatable and controversial, with different guidelines recommending distinct approaches. Identification of biph-MPM associated genetic alterations, through deep sequencing analysis, may provide useful tools to understand these lesions. A retrospective cohort of 69 surgically resected MPMs, 39 biph-MPMs (56.5%) and 30 e-MPMs (43.5%) was selected. A separate set of 16 biph-MPM was used as validation set. Deep sequencing analysis on an MPM-specific custom panel (MPM_geneset) comprising 1041 amplicons spanning 34 genes was performed. A total of 588 variants and 5309 mutational events were detected. In total, 91.3% of MPMs showed at least one mutation and 76.8% showed co-occurrence of more than one alteration. Mutations in MXRA5 (p = 0.05) and NOD2 (p = 0.018) were significantly associated with biph-MPM both in the training and validation cohort and correlated with the extent of the sarcomatoid component. Mutations in NOD2 and XRCC6 correlated with patients' survival. We demonstrated that biph-MPM are associated with a specific mutation set, and that genetic analysis at diagnosis may improve patients' risk stratification.