Amiloidose nodular - relato de rara apresentação da amiloidose localizada cutânea / Nodular amyloidosis - report of a rare presentation of cutaneous localized amyloidosis

Contexto: Amiloidose é um grupo de doenças caracterizadas pelo depósito de proteínas fibrilares, denominadas substância amiloide. Podem ser divididas em formas localizadas ou sistêmicas, sendo que dentre as localizadas, a forma nodular é a mais rara. Descrição do caso: Relatamos o caso de amiloidose primária localizada cutânea nodular que se apresentou com nódulos violáceos no dorso, e placas acastanhadas na região cervical há 8 anos sem evidências de envolvimento sistêmico. Discussão: Como cerca de 1% a 7% dos casos de amiloidose nodular localizada cutânea podem evoluir com envolvimento sistêmico, o seguimento dos pacientes faz-se necessário. O tratamento não é obrigatório, a retirada das lesões pode ser feita se o paciente o desejar, contudo as recidivas são frequentes. Conclusões: Mesmo possuindo baixa prevalência, a amiloidose nodular deve ser reconhecida pelo risco de progredir para acometimento sistêmico e associação com discrasias plasmocitárias, como mieloma múltiplo.

Recent Research Progress of Extramedullary Plasmacytoma --Review / 中国实验血液学杂志

Extramedullary plasma cell tumor (EMP) is a kind of plasma cell tumor, and its pathogenesis is not completely clear. According to whether it is independent of myeloma disease, it can be divided into primary and secondary EMP, which have different biological and clinical characteristics. Primary EMP has low invasion, fewer cytogenetic and molecular genetic abnormalities and good prognosis, and surgery and / or radiotherapy are the mainly treatments. Secondary EMP, as the extramedullary invasive progression of multiple myeloma (MM), is often accompanied by high-risk cellular and molecular genetic abnormalities and poor prognosis, chemotherapy, immunotherapy and hematopoietic stem cell transplantation are the mainly treatment. This paper reviews the latest research progress of EMP in the pathogenesis, cytogenetics molecular genetics and treatment, so as to provide reference for clinical work.

Plasmocitoma extramedular solitario rinosinusal: reporte de caso y revisión de literatura / Solitary extramedullary plasmacytoma of the rhinosinusal cavity: a case report and literature review

Resumen El plasmocitoma extramedular solitario (PES) es una neooplasia maligna infrecuente caracterizada por una proliferación aislada de células plasmáticas monoclonales en tejido extramedular. La localización más frecuente es en cabeza y cuello con predominio en el territorio rinosinusal, sin embargo, estas lesiones malignas representan menos del 1% de los tumores de esta región anatómica. El diagnostico requiere una alta sospecha clínica, análisis histopatológico acucioso, estudios serológicos y exámenes radiológicos sistémicos de acuerdo a los criterios diagnósticos establecidos en la literatura internacional. Se analiza el caso de un paciente masculino con un PES que se presentó como un tumor de fosa nasal derecha y obstrucción nasal de meses de evolución con hallazgos clínicos e imagenológicos inespecíficos. El diagnóstico definitivo se realizó mediante biopsia endoscópica nasal y estudio histopatológico. El tratamiento fue abordado de manera multidisciplinaria entre otorrinolaringología, hematología y radiooncología. De acuerdo a las guías internacionales, se decidió realizar radioterapia localizada con buen resultado clínico precoz. El PES requiere un abordaje multidisciplinario para lograr un diagnóstico y tratamiento oportuno, siendo imprescindible la exclusión del mieloma múltiple debido a las diferencias terapéuticas y en pronóstico clínico. El tratamiento puede realizarse con radioterapia y/o cirugía, siendo la radioterapia el pilar de tratamiento.

Abstract Solitary extramedullary plasmacytoma (SEP) is a rare malignant neoplasm characterized by isolated proliferation of monoclonal plasma cells in extramedullary tissue. The most frequent location is in the head and neck with a predominance in the rhinosinusal territory; however, these malignant lesions represent less than 1% of the tumors in this anatomical region. The diagnosis requires a high clinical suspicion, careful histopathological analysis, serological studies and systemic radiological examinations according to the diagnostic criteria established in the international literature. We analyze the case of a male patient with SEP that presented as a tumor of the right nostril and nasal obstruction of months of evolution with nonspecific clinical and imaging findings. The definitive diagnosis was made by nasal endoscopic biopsy and histopathological study. The treatment was approached by multidisciplinary teamwork. According to international guidelines, it was decided to perform localized radiotherapy with good early clinical results. SEP requires a multidisciplinary approach to achieve a timely diagnosis and treatment, being essential exclusion of multiple myeloma due to the therapeutic differences and prognosis. Treatment can be done with radiation therapy and/or surgery; radiation therapy is the mainstay of treatment.

Plasmocitoma extramedular de canal auditivo externo: caso clínico / Extramedullary plasmacytoma of external auditory canal: a case report

Resumen El plasmocitoma extramedular es una neoplasia de células plasmáticas poco frecuente, que se ubica en 80% a 90% de los casos en la cabeza o cuello. Esta neoplasia representa menos del 1% de toda la patología maligna de cabeza y cuello. Dada la poca frecuencia de la patología y la escasez de casos publicados, esta entidad presenta una gran dificultad clínica y terapéutica. El diagnóstico se basa en el análisis histológico con inmunohistoquímica de la muestra obtenida, y el tratamiento varía según la ubicación, donde se puede realizar radioterapia o cirugía. En este artículo presentamos el caso de una paciente de 56 años, con antecedentes de otorrea de larga data en oído derecho, al examen físico presentaba un tumor que obstruía todo el conducto auditivo externo. Se realizó exéresis tumoral y la biopsia evidenció un plasmocitoma.

Abstract Extramedullary plasmacytoma is a rare plasma cell neoplasm, affecting 80% to 90% of the head or neck. This neoplasm represents less than 1% of all malignant head and neck pathology. Given the infrequency of the pathology and the scarcity of published cases, this entity presents great clinical and therapeutic difficulty. Diagnosis is based on histology and immunohistochemistry and treatment varies depending on the location, where radiation therapy or surgery can be performed. In this article, we present the case of a 56-year-old patient with a history of long-standing otorrhea in the right ear. Physical examination presented a tumor that obstructed the entire external auditory canal. Tumor excision was performed, and the biopsy revealed a plasmacytoma.

Clinical analysis of 10 cases with extramedullary plasmacytoma of the head and neck / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the clinical characteristics, treatment methods and outcomes of extramedullary plasmacytoma of the head and neck. Methods: A retrospective analysis was conducted on 10 cases with extramedullary plasmacytoma of the head and neck who were admitted to Henan Tumor Hospital from January 2005 to January 2020. Among the 10 patients, 6 were male and 4 were female. The average age at diagnosis was 56.3 years old (34-74 years old). Among them, 3 cases were located in the nasal cavity, 2 cases in the nasopharynx, 1 case in the sinuses, 2 cases in the larynx, 1 case in the oropharynx, and 1 case in the cervical lymph nodes. Treatments were administered according to tumor size and resection extent. Complete surgical excision (negative margins) was preferred, followed by adjuvant radiotherapy or radiotherapy alone. The clinical characteristics, diagnosis, treatment and prognosis of EMP were analyzed. Results: The patients' symptoms were not specific, frequently with local obstruction symptom and localized masses. All patients were confirmed pathologically as suffering from monoclonal plasmacytoma, with negative bone marrow biopsy and negative skeletal survey. Five patients received surgery, 3 received radiotherapy, and 2 received surgery with additional radiation. The follow-up time was 16-125 months, with a median of 92 months. Two patients developed into multiple myeloma. One patient who received radiotherapy after surgery relapsed after 7 years of follow-up and again received surgical treatment, with no evidence of second recurrence. The remaining patients had no recurrence or progression. Conclusion: Extramedullary plasmacytoma of the head and neck has a good prognosis. Surgical treatment can be considered for completely resectable lesions.

Cavidad oral como sitio de asiento de enfermedades oncohematológicas. Plasmocitoma extramedular: a propósito de dos casos / The oral cavity as a reservoir of oncohematological diseases. Extramedullary plasmocytoma: a propos of two cases

Las neoplasias malignas de la cavidad oral en gran medida (90%) consisten en carcinoma de células escamosas que surgen de la mucosa de revestimiento. El 10% restantes de neoplasias malignas orales de un grupo heterogéneo de tumores de diferente etiología. Presentamos dos casos de patología oncohematológica: Mieloma Múltiple (AU)

Malignant neoplasms of the oral cavity largely (90%) consist of squamous cell carcinoma arising from the lining mucosa. e remaining 10% of oral malignancies from a heterogeneous group of tumors of different etiology. We present two cases of oncohematological pathology: Multiple Myeloma (AU)

Huge Sellar Plasmacytoma as Differential Diagnosis of Invasive Pituitary Adenoma: A Case Report

Sellar plasmacytomas are rare tumors arising from plasma cells. They are often misdiagnosed as adenomas.We report the case of a 63-year-old woman with headache, cranial nerve III palsy and decreased visual acuity. Imaging revealed an extensive lesion centered on the clivus, extending to the cavernous sinus bilaterally and into the sphenoid sinus. The hormonal tests were compatible with panhypopituitarism and mild hyperprolactinemia. The first hypothesis was invasive pituitary adenoma. Partial resection was achieved, and the immunohistochemical evaluation was compatible with plasmacytoma. After a few weeks, she developed lumbar and hip pain, and the imaging confirming osteolytic lesions. The final diagnosis was multiple myeloma.

Plasmacytoma of the cervix / Philippine Journal of Obstetrics and Gynecology

@#Plasmacytoma is a rare disease entity that represents only 5%‒10% of all plasma cell neoplasms. It is rarely found in the female genital tract. There are 8 identified case reports on plasmacytoma of the cervix. The clinical symptoms are nonspecific and biopsy with immunohistochemistry is used to diagnose. Due to the paucity of cases, there is no standard treatment modality. We present a case of a 34-year-old patient who had a history of postcoital bleeding. Biopsy and immunohistochemistry were done which confirmed the diagnosis of plasmacytoma. Total abdominal hysterectomy, bilateral salpingectomy with transposition of ovaries was the chosen treatment option.

Solitary plasmacytoma of mandible: an unusual bilateral presentation

Plasmacytoma is a neoplastic proliferation of monoclonal plasma cells, which can present clinically as solitary bone neoplasm, extramedullary plasmacytoma, and multiple myeloma. The biological behavior of these tumors is variable from periods of clinical latency to rapid growth and progression from localized forms to more disseminated multiple myeloma. We present the case of solitary plasmacytoma of the mandible with rare bilateral involvement in a 65-year-old female patient. This paper highlights the importance of understanding the maxillofacial manifestations of the disease by the dentist for early diagnosis and thus better prognosis.

Plasmocitoma extramedular de laringe: a propósito de un caso / Extramedullary plasmacytoma of the larynx: a case report

Resumen Los plasmocitomas solitarios son una rara forma de presentación de neoplasias de células plasmáticas. Deben ser diferenciados del mieloma múltiple en el momento del diagnóstico y realizar un seguimiento estricto por el riesgo de transformación a mieloma. La localización de los mismos en la laringe es muy inusual, dado que sólo se han publicado 56 casos. Se presenta el caso de una paciente con un plasmocitoma extramedular de laringe que se trató mediante cirugía y radioterapia. Se revisan los criterios diagnósticos y los problemas terapéuticos.

Abstract Solitary plasmacytomas are a rare form of plasma cell neoplasms. They should be differentiated from multiple myeloma at the time of diagnosis and strictly monitored for the risk of transformation to myeloma. Their location in the larynx is very unusual, since only 56 cases have been published. We present the case of a patient with extramedullary plasmacytoma of the larynx that has been treated with surgery and radiotherapy. We reviewed the literature for diagnostic criteria and therapeutic problems.

Plasmocitoma mamario y cáncer de mama: a propósito de un caso / Breast Plasmacytoma and breast cancer: a case report

El plasmocitoma mamario es una neoplasia de células plasmáticas extremadamente infrecuente, con menos de cincuenta casos descritos en el último siglo. Por este motivo, apenas se dispone de datos acerca del abordaje, tratamiento y seguimiento más convenientes. Presentamos el caso de una paciente de 70 años que debutó con un plasmocitoma mamario y que un año después fue diagnosticada de un carcinoma mamario lobulillar ipsilateral. La asociación entre plasmocitoma y cáncer de mama no está descrita en la literatura, por lo que es muy complicado establecer un vínculo entre ambas entidades. Sin embargo, el abordaje terapéutico del plasmocitoma podría comprometer el tratamiento ulterior de un cáncer de mama, por lo que el tratamiento idóneo en estos casos sea probablemente la cirugía.

Breast plasmocytoma is an extremely rare plasma cell neoplasm, with less than 50 cases reported in the last century. This is the reason why we barely have data about optimal management, treatment and follow-up. We hereby report the case of a 70 year old woman diagnosed with breast plasmocytoma that developed lobular breast cancer a year later. The link between plasmocytoma and breast cancer has not been previously established. However, breast plasmocytoma treatment could compromise latter breast cancer approach, so probably the most suitable strategy in these cases should be breast surgery.Conclusions: There are clinical characteristics associated with complications in women with surgical management abortion in our center, such as admission diagnosis, unplanned pregnancy, previous abortion and type of evacuation. There are limitations regarding the quantity and quality of information, however, our results allow us to know the profile of patients treated for abortion in our center.

Caso Clínico: PlasmocitomaÓseo Solitario / Clinical Case: Solitary Bone Plasmacytoma

Introducción: Aproximadamente un 5% de las neoplasias de células plasmáticas corresponden al Plasmocitoma óseo solitario (POS)con una edad de presentación después de la 5ta década de la vida, por lo que su aparición en edades tempranas es muy rara, siendo este el motivo principal de la presentación de este caso. Caso clínico: El caso corresponde a una mujer de 19años de edad con antecedente fractura patológicade fémur derecho. Labiopsia óseareportó un Plasmocitoma Solitariocon Inmunohistoquímica Plasma Cell positivo, Kappa positivo, CD38 y CD138 positivo.La biopsia de Medula ósea fue normal asícomo las concentraciones de los diferentes tipos de inmunoglobulinay beta 2 microgobulina. Calcio sérico normal. La electroforesis de proteínas gamma fue de 0.98 g/dl (14.3 %).La serie ósea reportó la presencia de lesión osteolítica de aproximadamente 8 cm a nivel de diáfisis proximal de fémur derecho con fractura patológica. El resto del esqueleto sin lesiones. Evolución: La paciente recibió 4 ciclos de quimioterapia con el protocolo VISTA (Bortezomib 1.8 mg, Ciclofosfamida 500 mg, Dexametasona 20 mg, Doxopeg 15 mg), luego del primer ciclo, fue intervenida quirúrgicamente con Osteosíntesis con sistema de compresión dinámica (DCS) y un relleno de fémur proximal derecho.La paciente terminó su tratamiento de Quimioterapia en noviembre del 2015 y concomitantemente recibió radioterapia a dosis de 50 Gys, la misma que culminóen octubredel mismo año. Desenlace: La paciente ha permanecido en controles con periodos de dolor a nivel de cadera que han sido manejados con analgesia y con controles radiológicos sin evidencia de recidiva. Actualmente paciente seencuentra asintomática, recibiendo Bifosfonatos por 24 meses. Conclusión: Este caso pone de relieve la importancia de la búsqueda de patología oncológica en un a mujer joven con fractura patológica

Introduction: Approximately 5% of plasma cellneoplasms correspond to solitary bone plasmacytoma (POS) with an age of presentation after the 5th decade of life, so its appearance at an early age is very rare, this being the reason of the presentation of this case. Clinical case: The case corresponds to a 19-year-old woman with a history of a pathological fracture of the right femur. The bone biopsy reported a Solitary Plasmacytoma with positive Plasma Cell Immunohistochemistry, positive Kappa, CD38 and positive CD138. The bone marrow biopsy was normal as well as the concentrations of the different types of immunoglobulin and beta 2 microgobulin. Normal serum calcium. Gamma protein electrophoresis was 0.98 g / dl (14.3%). The bone series reported the presence of an osteolytic lesion of approximately 8 cm at the proximaldiaphysis of the right femur with a pathological fracture. The rest of the skeleton without injuries. Evolution: The patient received 4 cycles of chemotherapy with the VISTA protocol (Bortezomib 1.8 mg, Cyclophosphamide 500 mg, Dexamethasone 20 mg, Doxopeg 15 mg), after the first cycle, she underwent surgery with Osteosynthesis with a dynamic compression system (DCS) and a right proximal femur filling. The patient finished her chemotherapy treatment in November 2015 and concomitantly received radiotherapy at a dose of 50 Gys, which ended in October of the same year. Outcome: The patient has remained in controls with periods of pain at the hip level that have been managed with analgesia and with radiological controls without evidence of recurrence. Currently the patient is asymptomatic, receiving bisphosphonates for 24 months. Conclusion: This case highlights the importance of searching for oncological pathology in a young woman with a pathological fracture

Long non-coding RNA plasmacytoma variant translocation 1 linked to hypoxia-induced cardiomyocyte injury of H9c2 cells by targeting miR-135a-5p/forkhead box O1 axis / 中华医学杂志(英文版)

BACKGROUND@#Myocardial infarction occurs due to insufficient (ischemia) blood supply to heart for long time; plasmacytoma variant translocation 1 (PVT1) is a long non-coding RNAs (lncRNAs) involved in the pathogenesis of various diseases, including heart disease; However, few studies have explored its role. The present study evaluated the effects of lncRNA PVT1 on hypoxic rat H9c2 cells.@*METHODS@#Hypoxic injury was examined by measuring cell viability and apoptosis by using cell counting kit-8 activity and flow cytometry assays. Gene expressions after hypoxia were estimated by quantitative real time polymerase chain reaction and the signaling pathway were explored by Western blot analysis. RNA immunoprecipitation and luciferase reporter assays were applied to examine the interactions among genes. Data were analyzed using t-test with one-way or two-way analysis of variance.@*RESULTS@#The lncRNA PVT1 is up-regulated in hypoxia-stressed H9c2 cells and knockdown of PVT1 mitigates hypoxia-induced injury in H9c2 cells. PVT1 acts as a sponge for miR-135a-5p and knockdown of PVT1 attenuated the increased hypoxia-induced injury by up-regulating miR-135a-5p. Forkhead box O1 (FOXO1) was identified as a target of miR-135a-5p, and the expression was negatively regulated by miR-135a-5p. The exploration of the underlying mechanism demonstrated that knockdown of FOXO1 reversed PVT1/miR-135a-5p mediated hypoxia-induced injury in H9c2 cells.@*CONCLUSIONS@#PVT1 plays a crucial role in hypoxia-injured H9c2 cells through sponging miR-135a-5p and then positively regulating FOXO1.

Plasmocitoma solitario intracraneal: una presentación inusual / Intracranial solitary plasmacytoma: an unusual presentation

Background: Intracranial solitary plasmacytoma is extremely rare and its location in the clivus is unusual; its clinical presentation is very varied and the diagnostic images are similar to the other tumors in skull-base. Case presentation: 47-year-old woman with initial diagnosis of pituitary macroadenoma, attended with headache, nausea, vomiting, diplopia in the right eye and paralysis of her abducent nerve. She was reoperated by transsphenoidal endoscopic approach, concluding in solitary clivus plasmacytoma by biopsy and immunohistochemistry. Conclusions: Clivus is an unusual location for intracranial plasmacytoma. Early diagnosis, complete study and careful follow-up are required due to its high progression to multiple myeloma(AU)

Introducción: El plasmocitoma solitario intracraneal es extremadamente raro y su localización en el clivus es inusual; su presentación clínica es muy variada y las imágenes diagnósticas son similares a las de otros tumores de la base del cráneo. Reporte de caso: Se presenta el caso de una mujer de 47 años con diagnóstico inicial de macroadenoma hipofisiario, que cursó con cefalea, náuseas, vómitos, diplopía en ojo derecho y parálisis de su nervio abducente. Fue reintervenida por vía transesfenoidal endoscópica, concluyendo en plasmocitoma solitario del clivus por biopsia e inmunohistoquímica. Conclusiones: El clivus es una localización inusual para plasmocitoma intracraneal, se requiere un diagnóstico precoz, estudio completo y seguimiento cuidadoso por su alta progresión a mieloma múltiple(AU)

Plasmocitoma solitario de costilla como presentación inicial de mieloma múltiple: reporte de un caso / Lone rib plasmacytoma as a presentation of initial multiple myeloma: a case report

Resumen Introducción: El 50% de los tumores de pared torácica son malignos, dentro de los que destaca el plasmocitoma de costilla. Objetivo: Presentar un caso clínico que debutó inicialmente como un plasmocitoma de costilla, y que terminó presentándose como mieloma múltiple. Materiales y Método: Registro clínico de un paciente sometido a resección de tumor de parrilla costal. Resultados: Paciente masculino de 58 años, con un año de dolor costal, asociado a aumento de volumen a nivel de la octava costilla derecha en línea media axilar, indurada. TC de tórax que demuestra imagen sugerente de plasmocitoma de 79 × 44 mm. Se realiza resección quirúrgica, con instalación de malla de prolene en el defecto. Biopsia diferida con compromiso neoplásico por lesión monoclonal de células plasmáticas. Se complementa estudio con biopsia de médula ósea confirmando mieloma múltiple. Se inicia tratamiento con quimioterapia adyuvante. Conclusiones: El plasmocitoma óseo solitario es una entidad de baja frecuencia, que se asocia a la presencia de mieloma múltiple. Es por esto que al momento de la sospecha se hace necesario descartar su presencia, con el fin de mejorar el pronóstico del paciente.

Introduction: Up to 50% of chest wall tumors are malignant; among which rib plasmocytoma stand out. Aim: Showcase a clinical case that debuted as a rib plasmacytoma, and that ended up presenting as Multiple Myeloma. Materials and Method: Records of a patient with resection of chest wall tumor. Results: Male patient of 58 years, with one year of costal pain, associated with an indurated increase in volume at the level of the eighth right rib in the mid-axillary line. Chest CT scan demonstrated a suggestive image of plasmacytoma of 79 × 44 mm. Surgical resection was performed, with prolene mesh installation in the defect. Biopsy showed neoplastic compromise due to monoclonal lesion of plasma cells. Study is complemented with bone marrow biopsy confirming multiple myeloma. The patient was treated with adjuvant chemotherapy. Conclusions: Solitary bone plasmacytoma is a low frequency entity, which is associated with the presence of multiple myeloma. At the moment of suspicion, it is necessary to rule out their presence, in order to improve the patient's prognosis.

Effect of lincRNA PVT1 associated with Enhancer of Zeste homolog 2 (EZH2) and with androgen receptor (AR) on the large-scale gene expression in LNCaP prostate cancer cells

O lincRNA PVT1 (Plasmacytoma Variant Translocation 1) é um RNA longo não codificador de proteínas (ncRNA) descrito como um oncogene sendo superexpresso em vários tipos de cânceres. LincRNA PVT1 está localizado na região genômica 8q24, também conhecida como 'gene desert'. O nível de expressão do lincRNA PVT1 está associado ao aumento do risco de câncer de próstata (PCa) e está correlacionado com os níveis de expressão do receptor de andrógeno (AR). No entanto, o mecanismo do envolvimento do lincRNA PVT1 com o AR no desenvolvimento de câncer de próstata ainda não está bem esclarecido. Aqui, nós testamos a hipótese que a formação do complexo AR-EZH2-PVT1 participa na regulação da expressão gênica em câncer de próstata, nas células LNCaP. A imunoprecipitação de ribonucleoproteínas seguida de PCR quantitativo (RIP-qPCR) revelou que o lincRNA PVT1 está associado fisicamente ao AR (12% do input) e à metiltransferase EZH2, proteína componente do complexo repressor Polycomb 2 (36% do input) sob condições suplementadas com andrógeno (+R1881). O lincRNA PVT1 também está associado fisicamente ao AR (10% de input) e à EZH2 (42% de input) em condições de privação de andrógeno (-R1881). Assim, a associação física entre lincRNA PVT1, AR e EZH2 é independente do hormônio andrógeno. Usando uma abordagem de estudo em larga-escala de perda e ganho de função, nossos resultados mostraram que o silenciamento do lincRNA PVT1 em células LNCaP na presença de andrógeno restaura a expressão parcialmente, totalmente ou causa superexpressão de 160 genes que tiveram a expressão inibida por andrógeno. Entre esses genes, destacamos genes envolvidos na regulação da diferenciação celular, em componentes da junção célula-célula, na inibição da migração e invasão celular e no desencadeamento da via apoptótica. Imunoprecipitação da cromatina seguida de PCR quantitativo (ChIP-qPCR), em cultura de células LNCaP suplementada com andrógeno sob silenciamento do lincRNA PVT1, mostrou aumento significativo na ocupação pela marca de histona ativadora H3K27Ac do promotor do gene NOV, um dos genes que tiveram sua expressão aumentada com o silenciamento de PVT1. O ChIP-qPCR também mostrou, após o silenciamento do lincRNA PVT1, um aumento significativo da marca H3K27me3 na região enhancer do gene NOV, uma característica de enhancers poised (prontos para ativação). Em conclusão, nós fornecemos a primeira evidência experimental para um mecanismo de ação do oncogene lincRNA PVT1 em células de câncer de próstata e demonstramos que sua ação inibidora da expressão afeta genes alvo que facilitam a proliferação e migração de células do câncer de próstata, sugerindo que o lincRNA PVT1 é um novo agente no complexo mecanismo de repressão transcricional envolvendo um RNA silenciador, o receptor de andrógeno (AR) e o potenciador de Zeste homólogo 2 (EZH2) no remodelamento da cromatina em células LNCaP

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is an oncogene known to be overexpressed in various types of cancer. PVT1 lincRNA is located in the wellknown cancer-related genomic region 8q24, also known as 'gene desert. PVT1 lincRNA level of expression is associated with increased prostate cancer (PCa) risk and is correlated with androgen receptor (AR) expression levels. However, the mechanism of PVT1 and AR involvement in the development of prostate cancer is still unclear. Here, we tested the hypothesis that formation of the complex AR-EZH2-PVT1 participates in the regulation of gene expression in prostate cancer, in LNCaP cells. Ribonucleoprotein immunoprecipitation followed by quantitative PCR (RIP-qPCR) revealed that PVT1 lincRNA binds both the AR (12 % of PVT1 input) and the methyltransferase EZH2 from the Polycomb repressive complex 2 (36 % of input) under androgen-supplemented conditions (+R1881). PVT1 also binds both AR (10 % of input) and EZH2 (42 % of input) under androgen-deprived conditions (-R1881). Thus, PVT1 binding to AR and EZH2 is independent of the androgen hormone. Using a large-scale loss and gain of function approach, our results show that PVT1 knockdown (KD) in LNCaP in the presence of androgen restores the expression partially, fully or causes overexpression of 160 genes that are inhibited by androgen. Among these genes, we highlight genes involved in regulation of cell differentiation, in components of cell-cell junction, in inhibition of cell migration and invasion and in triggering of the apoptotic pathway. Chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) with LNCaP cells in androgen-supplemented cultures under PVT1 lincRNA knockdown showed a significant increase in occupancy by the histone activation mark H3K27Ac of the promoter region of the NOV gene, one of the genes that had an increased expression upon PVT1 silencing. ChIPqPCR also showed a significant increase upon PVT1 lincRNA silencing of the H3K27me3 histone mark in the enhancer region of the NOV gene, a distinct feature of poised enhancers. In conclusion, we provide first experimental evidence for a mechanism of action of PVT1 lincRNA oncogene in prostate cancer cells, and show that its inhibitory action affects targetgenes that facilitate proliferation and migration of prostate cancer cells, thus suggesting PVT1 lincRNA as a novel lncRNA player in the complex mechanism of transcriptional repression involving a silencer RNA, the androgen receptor (AR) and the Enhancer of zeste homolog 2 (EZH2) in chromatin remodeling in LNCaP cells

Clinical Analysis of Benign and Malignant Nasal Septal Tumors / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The purpose of this study was to review the clinical characteristics and treatment outcomes of benign and malignant nasal septal tumors. SUBJECTS AND METHODS: A total of 34 patients who underwent the treatment for nasal septal tumor between 2004 and 2015 were included in this study. Demographic characteristics, sinonasal chief complaints, size and localization of nasal septal tumor, imaging findings, surgical method, histopathologic results, treatment outcomes, and postoperative complications were reviewed. RESULTS: Of the 34 patients with nasal septal tumor used in this study, 22 (64.7%) had benign tumors and 12 (35.3%) had malignant tumors. The most common sinonasal complaint of both benign and malignant nasal septal tumors was nasal obstruction. The most common benign tumor was inverted papilloma (n=7), whereas the most common malignant tumors were malignant melanoma (n=2), plasmacytoma (n=2), and metastatic carcinoma (n=2). All patients except two cases underwent endoscopic tumor removal. There were 4 recurrences in malignant nasal septal tumors. There was no recurrence in benign tumors. No major complications resulting from surgical intervention were found. CONCLUSION: Endoscopic surgery with complete excision is a safe and effective procedure for benign nasal septal tumors. Recurrence is more common in malignant nasal septal tumor. Therefore, long term follow-ups with regular radiologic and endoscopic examinations are necessary for patients with malignant nasal septal tumor.

Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis based on a case reports systematic survey / Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis based on a case reports systematic survey

Abstract Introduction: Solitary plasmacytoma is a rare malignant tumor of plasma cells with no evidence of systemic proliferation. There are two known subtypes: extramedullary solitary plasmacytoma and solitary bone plasmacytoma. The etiology is still unknown. Both lesions present a risk of progression to multiple myeloma. A number of approaches have been used for treatment of solitary plasmacytoma. Objective: To carry out a systematic review of the case reports described in the literature, focusing on therapeutic and prognostic aspects. Methods: A search of clinical case reports was performed in the PubMed database using Mesh Terms related to "plasmacytoma" under the following criteria: type of study (case report), articles in English language, conducted in humans, with no publication date limits. Results: Of the 216 articles found, only 21 articles met the pre-established inclusion criteria. Conclusion: The occurrence of solitary bone plasmacytoma in the bones of the face is a rare condition prevalent between the 4th and 6th decades of life, located in the posterior region of the mandible in most cases. Histopathological examination and systemic investigation are mandatory for confirmation of diagnosis.

Resumo: Introdução: O plasmocitoma solitário é um tumor maligno raro de células plasmáticas sem evidência de proliferação sistêmica e engloba dois subtipos: plasmocitoma solitário extramedular e plasmocitoma solitário ósseo. A etiologia ainda é desconhecida. Ambas as lesões apresentam risco de progressão para mieloma múltiplo. Uma série de abordagens tem sido usada para seu tratamento. Objetivo: Realizar uma revisão sistemática da literatura com enfoque nos aspectos terapêuticos e prognósticos. Método: Realizou-se uma busca de relatos de caso clínico na base de dados PubMed com termos de busca relacionados com "plasmocitoma" sob os seguintes critérios: tipo de estudo (relato de caso), artigos na língua inglesa, estudos realizados apenas em humanos, sem limites de data de publicação. Resultados: Dos 216 artigos encontrados, apenas 21 preencheram os critérios de inclusão pré-estabelecidos. Conclusão: A ocorrência de plasmocitoma solitário ósseo nos ossos da face é uma condição rara prevalente entre a 4a e a 6a décadas de vida, localizada na região posterior de mandíbula na maioria dos casos. O exame histopatológico e a investigação sistêmica são mandatórios para confirmação do diagnóstico.

Perfil de pacientes com diagnóstico patológico de mieloma múltiplo em hospital de ensino / Profile of patients with multiple myeloma pathological diagnosis in a tea-ching hospital

Introdução: Plasmocitoma é um tumor maligno, originado da proliferação irreversível e autônoma dos plasmócitos, podendo se apresentar como massa circunscrita ou infiltração difusa. Quando há mais de um tumor de células plasmáticas, ocorre o chamado Mieloma Múltiplo. Essa neoplasia maligna de células B apresenta produção exagerada de uma das imunoglobulinas de cadeias leves Kappa ou Lambda. Objetivo: Avaliar possíveis associações entre dados epidemiológicos e a carga tumoral em pacientes com Mieloma Múltiplo. Material eMétodos: Trata-se de um estudo transversal, quantitativo, descritivo, realizado em prontuários de pacientes diagnosticados com Mieloma Múltiplo no Laboratório de Patologia do Hospital de Base do município de São José do Rio Preto, São Paulo, entre 2010 e 2014. Foram consideradas as variáveis: sexo, idade, presença de cadeia leve (Kappa, Lambda, ambas e não especificada), carga tumoral (leve, moderada e acentuada). Resultados:Analisamos 42 laudos de pacientes diagnosticados com Mieloma Múltiplo, sendo que 69% dos pacientes apresentaram idade igual ou superior a 60 anos, presença de imunoglobulina de cadeia leve Kappa em 59% e carga tumoral acentuada em 67% dos casos. Em relação ao sexo, observamos que o nível de carga tumoral acentuada ocorreu de maneira similar entre homens e mulheres. As mulheres diagnosticadas com carga tumoral leve ou moderada configuraram 71% dos pacientes, do estudo. Conclusão: A idade e sexo não constituem fator de risco para o Mieloma Múltiplo na amostragem avaliada, este fato pode estar relacionado ao tamanho amostral.

Introduction: Plasmocytoma is a malignant tumor, originated from the irreversible and autonomous proliferation of the plasmacytes, being able to present as circumscribed mass or diffuse infiltration. When there is more than one plasma cell tumor, the so-called Multiple Myelomas occurs. This malignant B cell neoplasm exhibits overproduction of one of the Kappa or Lambda light chain. Objective: To evaluate possible ssociation of epidemiological data with tumor burden in patients with multiple myelomas. Patients and Methods:It is a cross-sectional study conducted with medical records of patients diagnosed with multiple myeloma by the Pathology Laboratory in Hospital de Base in the city of São José do Rio Preto, São Paulo, between 2010 and 2014. We considered the variables gender, age, light chain presence (Kappa, Lambda, both and unspecified), and tumor burden (mild, moderate or severe). Results: We analyzed 42 medical records of patients diagnosed with multiple myelomas. Of these, 69% of patients were aged 60 and over. Immunoglobulin Kappa light chain was found in 59% patients, and severe tumor burden in 67% of them. Regarding sex, we observed that severe tumor burden level occurred in a similar manner in men and women, without significant associations. Women diagnosed with mild to moderate tumor burden corresponded to 71% of patients, but no significant association was found. Conclusion: Age and sex were not a risk factor for multiple myelomas in this evaluated sample. This may be due to the sample size evaluated.