Síndrome de feocromocitoma-paraganglioma de tipo 5 como causa de hipertensión arterial en una paciente colombiana: reporte de caso / Pheochromocytoma/paraganglioma type 5 syndrome as a cause of secondary hypertension in a Colombian patient: case report

Resumen El feocromocitoma es un tumor derivado de las células de la cresta neural con la capacidad de producir sustancias simpaticomiméticas y, por ende, un cuadro clínico particular. Causa menos del 1 % de los casos de hipertensión arterial sistémica y su incidencia se estima entre 0,4 y 0,6 casos por 100.000 personas cada año, con una supervivencia media de siete años. De todos los tumores sólidos, el feocromocitoma tiene un mayor componente genético, que puede heredarse hasta en el 40 % de los casos. Una vez diagnosticada la enfermedad, se debe definir el tratamiento y el pronóstico, en parte condicionados por las variantes genéticas asociadas, en especial RET, SDHx, VHL y NF1. Se presenta el caso de una mujer joven con dolor abdominal e hipertensión arterial sistémica, a quien se le diagnosticó feocromocitoma. Al secuenciar el exoma, se identificó una variante patogénica extremadamente rara y de reciente descubrimiento: SDHA: c.1A>C (p.Met1Leu). La paciente respondió adecuadamente al tratamiento quirúrgico y continuó en seguimiento sin recurrencias. El abordaje diagnóstico de los pacientes con feocromocitoma comienza con la sospecha clínica, seguida de la medición de determinados metabolitos en sangre y orina, y, finalmente, los estudios de imagenología. Los desarrollos tecnológicos actuales permiten la aplicación de la medicina de precisión en este campo. En este caso de feocromocitoma, se identificó un componente genético importante que no solo afecta al paciente, sino también, a sus familiares. La tamización adecuada del caso índice permite identificar mutaciones y caracterizar mejor la enfermedad.

Abstract Pheochromocytoma is a tumor derived from neural crest cells able to produce sympathomimetic substances and, hence, a particular clinical picture. It is responsible for less than 1% of high blood pressure cases, with an estimated incidence between 0.4 and 0.6 cases per 100,000 people each year, and an average survival of seven years. Pheochromocytoma is a solid tumor with a high genetic component, as heritability can reach 40%. Once diagnosed, its treatment and prognosis are partly conditioned by the associated pathogenic variants that can be documented, especially those related to RET, SDHx, VHL, and NF1 genes. We present the case of a young woman with abdominal pain and high blood pressure, who was found to have a pheochromocytoma. Genetic testing detected a rare and recently discovered pathogenic variant: the SDHA:c.1A>C (p.Met1Leu). The patient responded adequately to the surgical treatment and continued the follow-up without documented recurrences. The diagnostic approach for pheochromocytoma patients must start with a clinical suspicion, followed by metabolite measurement in blood and urine, and finally, imaging. Currently, technology development allows precision medicine applicability. In this case of pheochromocytoma, recent developments in precision medicine resulted in the detection of associated genetic components involving the patient and her family. Adequate screening of the index patient is required for documenting pathogenic variants and better characterizing the disease.

Feocromocitoma y paraganglioma en un hospital pediátrico de Argentina. Serie de casos / Pheochromocytoma and paraganglioma at a children's hospital in Argentina. A case series

El feocromocitoma y el paraganglioma son tumores neuroendocrinos secretores de catecolaminas. Los feocromocitomas se originan en la médula suprarrenal, mientras que los paragangliomas son extraadrenales. Se describe una serie de casos de niños con diagnóstico anatomopatológico de feocromocitoma o paraganglioma que consultaron en un hospital pediátrico de alta complejidad de Argentina. Se incluyeron 21 pacientes, 14 varones, con una mediana de edad de 11,4 años; 8 casos con feocromocitoma y 13 casos con paraganglioma. Se presentaron con hipertensión arterial 14/21. La mayoría de los paragangliomas tuvieron localización paraaórtica (9/13). Debido a que representan una causa potencialmente curable de hipertensión arterial, la sospecha clínica es muy importante. El diagnóstico temprano y la instauración de un tratamiento antihipertensivo adecuado, que permita afrontar la cirugía con normotensión arterial, aseguran la curación en la mayoría de los casos si la resección tumoral es completa.

Pheochromocytomas and paragangliomas are neuroendocrine tumors producing catecholamines. Pheochromocytomas occur in the adrenal medulla, while paragangliomas are those that occur outside the adrenal gland. Here we describe a case series of children with a pathological diagnosis of pheochromocytoma or paraganglioma who consulted at a tertiary care children's hospital in Argentina. A total of 21 patients (14 males) were included; their median age was 11.4 years; 8 children had pheochromocytoma and 13, paraganglioma. Arterial hypertension was observed in 14/21. Most paragangliomas were para-aortic (9/13). Since they are a potentially curable cause of hypertension, clinical suspicion is very important. An early diagnosis and the initiation of an adequate antihypertensive treatment, which allows the patient to undergo surgery with normal blood pressure, ensure a cure in most cases if tumor resection is complete.

Tumor de cuerpo carotídeo en adolescente. Reporte de un caso / Carotid body tumor in an adolescent. A case report

Introducción. Los paragangliomas del cuerpo carotídeo son neoplasias infrecuentes y representan el 0,6 % de los tumores de cabeza y cuello. La edad de presentación promedio es la quinta década de vida. El objetivo de este artículo fue describir un caso de paraganglioma del cuerpo carotídeo en una adolescente. Caso clínico. Se presenta el caso de una paciente adolescente con paraganglioma de cuerpo carotídeo derecho, de 5x3x3 cm, Shamblin III. Se analizaron la historia clínica, los exámenes diagnósticos, la técnica quirúrgica utilizada y su evolución correspondiente. La información fue obtenida a partir de la ficha clínica, previa autorización por consentimiento de los padres de la paciente. Resultados. Se hizo resección quirúrgica completa y reparo vascular con injerto de vena safena invertida, con evolución favorable y permeabilidad completa del puente vascular, sin secuelas. Conclusión. Este caso podía corresponder a un tumor de etiología familiar, dada su edad temprana de presentación. Se hizo necesario complementar su estudio con imágenes y objetivar el compromiso vascular asociado para la planificación quirúrgica. En estos pacientes, la complejidad de su localización y el compromiso vascular del tumor requiere de un equipo multidisciplinario, con cirujanos de cabeza y cuello y cirujanos vasculares para un resultado exitoso.

Introduction. Carotid body paragangliomas are rare, representing 0.6% of head and neck tumors, with average age of presentation in the fifth decade of life. The objective of this article is to describe a clinical case of carotid body paraganglioma in an adolescent. Clinical case. Review and analysis of the clinical case, reviewing its clinical history, study tests, surgical technique used and its corresponding evolution. Information obtained from the clinical record prior authorization by consent of the patient's parents. Results. Adolescent patient with paraganglioma of the right carotid body, 5x3x3 cm, Shamblin III. With complete surgical resection and inverted saphenous vein graft, favorable evolution, with complete permeability of the vascular bridge, without sequelae. Conclusion. This case could correspond to a tumor of familiar etiology, given its early age of presentation. It is necessary to complement the study with images and to objectively determine the associated vascular involvement for surgical planning. In these patients, the complexity of their location and vascular involvement of the tumor requires a multidisciplinary team with head and neck and vascular surgeons for a successful outcome.

Hereditary pheochromocytoma/paraganglioma and associated syndromes:a clinical and genetic study / 陆军军医大学学报

Objective To summarize and analyze the clinical phenotypes,hereditary features and treatment and follow-up strategies of different hereditary pheochromocytoma/paragangliomas(PCC/PGL)and related syndromes.Methods Forty-four clinically diagnosed PCC/PGL patients admitted in our hospital from January 2000 to August 2022 were enrolled,and the clinical data of them and their family members were collected.Second-generation sequencing was performed on 43 patients for genetic detection,and Sanger sequencing was applied to verify the mutation of the probands and family members.Results There were 15 patients diagnosed with hereditary PCC/PGL,including 7 cases of von Hippel-Lindau(VHL)syndrome,3 cases of multiple endocrine neoplasia type 2(MEN2),and 5 cases of familial paraganglioma syndrome.Seven VHL syndrome families were diagnosed as VHL2A(c.500G＞A),VHL2B(c.239G＞T and c.444_457del),and VHL2C(c.293A＞G)according to their clinical manifestations.All probands received surgical treatment,and 2 cases of recurrent PCC and the patients with multiple renal cancer also received targeted therapy with sunitinib.Three MEN2 families carried c.1901G＞C,c.1832G＞A,and c.1901G＞A missense mutations,respectively,and were diagnosed with MEN2A clinically.All of them underwent adrenalectomy and thyroidectomy,including one for preventive thyroidectomy.Among the 5 familial paraganglioma syndrome families,4 patients carried SDHB mutations(SDHB:c.343C＞T,c.541-2A＞G,c.575G＞A,c.268C＞T)and 1 patient carried an SDHD mutation(SDHD:c.337_340del).Sporadic retroperitoneal PGL were most common.Conclusion More than 1/3 of PCC/PGL patients carry germline gene mutations,showing obvious genotype-phenotype correlation.Genetic diagnosis technology plays an important guidance role for clinical precision treatment and follow-up,and genetic counseling.

Evaluation of 99m Tc-HYNIC-TOC and 131 I-MIBG imaging in diagnosis of pheochromocytoma and paraganglioma / 基础医学与临床

Objective To evaluate 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging in clinical diag-nostic of pheochromocytoma and paraganglioma(PPGL).Methods This was a retrospective study.359 PPGL pa-tients diagnosed by pathology microscopy were included.The diagnostic sensitivity and influencing factors on 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging were analyzed.Results The positive rate of 99mTc-HYN-IC-TOC somatostatin receptor scintigraphy was 57.7%(184/319)and 131I-MIBG imaging was 83.2%(232/279).The positive rates of 99m Tc-HYNIC-TOC somatostatin receptor imaging in the adrenal glands,retroperitoneum,head and neck,heart and mediastinum,pelvis and bladder were 53.3%,62.5%,95.0%,66.7%,50.0%and 11.0%respec-tively and the positive rates of 131I-MIBG imaging were 86.7%,88.5%,45.4%,50.0%,75.0%and 33.3%respec-tively.The positive rate of the two imaging did not showed difference among patients with different genetic back-grounds(SDH,VHL,RET mutations).The median maximum diameter of tumors was 4.4(3.0,6.1)cm.and the diag-nostic sensitivity of somatostatin receptor imaging and 131 I-MIBG imaging for larger tumors(≥4.4 cm)was signifi-cantly higher than those for the smaller tumor group(＜4.4 cm)(64.0%vs.51.3%;92.3%vs.74.1%)(P＜0.01).Tumors in 19 patients(5.3%)failed to uptake neither imaging method.Conclusions This is the largest PPGL cohort in China concerning 99m Tc-HYNIC-TOC somatostatin receptor imaging and 131 I-MIBG imaging.The sensitivity of 131 I-MIBG imaging is higher than that of 99m Tc-HYNIC-TOC somatostatin receptor imaging,but for some tumors,such as head and neck paraganglioma,the latter has obvious advantages.These two imagings technol-ogies are complementary and the choice of them should depend the individual situation of patients.

Association of NSE level with clinical features in pheochromocytoma/paraganglioma / 基础医学与临床

Objective To study the relationship between serum neuron-specific enolase(NSE)and clinical features of pheochromocytoma/paraganglioma(PPGL).Methods Totally 501 PPGL patients diagnosed from January 2019 to December 2022 were divided into normal NSE group(NSE≤16.3 ng/mL)and elevated NSE group(NSE＞16.3 ng/mL).The clinical characteristics were compared between the two groups.Results Compared with normal NSE group,patients in the elevated NSE group had larger diameter in primary tumor(5.00 cm vs.4.60 cm),higher 24-hour urinary norepinephrine(NE)and 24-hour urinary dopamine(DA)levels,and a higher rate of metasta-sis(31.6%vs.13.7%)(P＜0.05).NSE level was positively correlated with the primary tumor size(r=0.131,P＜0.05),24-hour urinary NE level(r=0.195,P＜0.05)and 24-hour urinary DA level(r=0.119,P＜0.05).Conclusions The level of NSE is related to tumor size,secretion function and metastasis in PPGL patients.

Multi-course Iodine-131-meta-iodobenzylguanidine in the treatment of metastatic paraganglioma: a case report / 中国综合临床

Paraganglioma (PGL) is a rare neuroendocrine tumor that causes endocrine hypertension. All paragangliomas had metastatic potential. The 5-year survival rate of patients with metastatic paraganglioma is less than 50%, and the treatment is a big problem. Metastatic PGL has a high specific uptake of iodine [ 131I]-meta-iodobenzylguanidine ( 131I-MIBG), so the treatment is effective, well tolerated, and has few adverse reactions. However, there is a lack of relevant detailed clinical diagnosis and treatment data in China. This article reports the diagnosis and treatment of a case of multi-site metastatic paraganglioma with multiple courses of 131I-MIBG, and discusses the efficacy, safety and tolerance of the treatment for clinical reference.

Analysis of clinical features of metastatic pheochromocytoma/paraganglioma / 中华泌尿外科杂志

Objective:To explore the clinical data of patients with metastatic pheochromocytoma/paraganglioma (PPGL).Methods:The clinical data of 57 patients with metastatic pheochromocytoma/paraganglioma diagnosed and treated at Peking Union Medical College Hospital from January 2016 to June 2022 were reviewed, including 28 cases of pheochromocytoma(PCC) and 29 cases of paraganglioma(PGL). The clinical manifestations, biochemical indexes, tumour characteristics, and metastatic characteristics of the 57 patients were analysed.Results:There were 34 males and 23 females. The median age at the time of initial diagnosis was 34 (20, 54) years, 17 (29.3%) presented with concurrent metastases, and 40 (70.7%) with heterochronous metastases. The median time to presentation of metastases was 2.2 (0, 5.0) years (range 0-22 years). Adrenergic symptoms were present in 45 cases (78.6%) at the time of initial diagnosis, and the median size of the primary tumour was 6.7 (5.0, 9.0) cm. Excessive catecholamine secretion was present in 48 cases (81.4%). The most common locations of metastasis were lymph nodes (71.9%, 41/57), bone (47.3%, 27/57), lung (38.6%, 20/57), and liver (35.1%, 20/57). Metastatic PGL had more multifocal metastases than PCC [10 (34.5%) vs. 2 (7.1%), P=0.011)], was more frequently associated with SDHB mutations [13 (42.9%) vs. 3 (10.7%), P=0.008], and was more likely to have concurrent metastases [12 (41.3%) vs. 5 (17.9%), P=0.005]. Metastatic PCC primary tumours were larger compared to PGL [median length 8.9 (4.0, 17.0) cm vs. 6.1 (1.0, 15.8) cm, P=0.020]. Conclusions:Patients with PGL present with metastases over an extremely wide time span, and patients diagnosed with PPGL should be followed throughout their lives. PGL is more prone to multifocal metastases and simultaneous metastases than PCC, and PGL is more highly correlated with the SDHB mutation.

Anesthesia management of children undergoing resection of pheochromocytoma and paraganglioma / 中华麻醉学杂志

Objective:To retrospectively analyze the anesthetic management characteristics of children undergoing resection of pheochromocytoma and paraganglioma (PPGL).Methods:The clinical data from patients undergoing resection of PPGL and confirmed histologically from January 1, 2010 to June 30, 2023 were retrospectively collected. The baseline characteristics, intraoperative conditions and postoperative complications were recorded.Results:The clinical data from 47 pediatric patients were analyzed. The overall incidence of hemodynamic instability events was 68% (32 cases). Lowering preoperative blood pressure to normal levels and the maximum diameter of tumor≥6 cm was helpful in reducing the incidence of the intraoperative hemodynamic instability events ( P<0.05). Postoperative hypotension developed in 7 cases, acute left heart failure in 1 case, arrhythmia in 1 case, adrenocortical insufficiency in 4 cases, and pulmonary infection in 13 cases. Conclusions:Thorough preoperative preparation, evidence-based anesthetic management, and meticulous postoperative vital sign monitoring can increase the perioperative safety for children undergoing resection of PPGL, thereby reducing the incidence of complications.

Paraganglioma of the Cauda Equina ­ Case Report and Literature Review / Paraganglioma de cauda equina ­ Relato de caso e revisão da Literatura

Paragangliomas of the cauda equina are tumors of rare incidence, with ~ 220 cases described in the world literature. They are benign lesions, grade I by the World Health Organization (WHO), whose definitive diagnosis can only be made by immunohistochemical analysis. Its neuroendocrine nature is evidenced by the presence of chromogranin. The relevance of reporting this case is because paragangliomas of the cauda equina should be included among the differential diagnoses of intradural and extra-medullary tumors, and especially because they can cause perioperative and intraoperative hypertensive crises by adrenergic discharge. The present study presents the case of a 36-year-old male patient diagnosed with a lumbar spine tumor located in the central spinal canal that presented as cauda equina syndrome involving 4 months of bilateral sciatica, paraparesis, urinary and fecal retention. The diagnosis of paraganglioma was confirmed by immunohistochemical positivity for chromogranin after microsurgical resection of the tumor.

Paragangliomas da cauda equina são tumores de incidência rara, com ~ 220 casos descritos na literatura mundial. São lesões benignas, grau 1 pela Organização Mundial da Saúde (OMS), cujo diagnóstico definitivo apenas pode ser feito pela análise imunohistoquímica, onde se evidencia a natureza neuroendócrina dada especialmente pela presença de cromogranina. O presente relato de caso se torna importante porque este deve ser considerado entre os diagnósticos diferenciais de tumores intradurais e extramedulares, e porque há trabalhos na literatura descrevendo crises hipertensivas durante a ressecção da lesão devidas a descarga adrenérgica. O presente estudo apresenta o caso de um paciente masculino de 36 anos diagnosticado com tumor na coluna lombar localizado no canal medular, que cursou com síndrome de cauda equina, com 4 meses de lombociatalgia bilateral, evoluindo à paraparesia, retenção urinária e fecal. Após microcirurgia para ressecção tumoral, o diagnóstico de paraganglioma só foi confirmado através da imunohistoquímica, com positividade para cromogranina.

Tumor glómico de intestino delgado / Glomus tumor of the small bowel

RESUMEN Los tumores glómicos (TG) son neoplasias vasculares benignas de tejidos blandos en zonas acrales periféricas. La mayoría de los TG intraabdominales se producen en el estómago; su presentación intestinal es de muy baja incidencia. Se presenta el caso de una mujer de 26 años, que consultó por dolor abdominal crónico de baja intensidad en región umbilical sin otra signo sintomatología. Se completó su estudio imagenológico y se detectó una lesión abdominopélvica heterogénea con componente sólido vascularizado, y líquido con proyecciones papilares. El informe de la patología de la pieza quirúrgica arrojó el diagnóstico de TG de intestino delgado. Se realizó una consulta que demuestra su baja incidencia: afecta a personas entre 26 y 88 años de ambos sexos en igual proporción, sin una distribución geográfica predominante. Los TG deben considerarse como un raro diagnóstico diferencial ante tumores del intestino delgado (ID).

ABSTRACT Glomus tumors (GTs) are benign vascular neoplasms of soft tissues that occur in peripheral acral areas. Most intra-abdominal GTs develop in the stomach; the incidence of intestinal presentation is very low, We report the case of a 26-year-old female patient with chronic mild pain in the umbilical region with no other symptoms or signs. The imaging tests demonstrated a heterogeneous abdominopelvic mass with a solid vascularized component, and a cystic component with papillary projections. The pathology examination of the surgical specimen reported the diagnosis of GT of the small bowel (SB). We conducted a review of the literature and found their low incidence, affecting both men and women between 26 and 88 years without a predominant geographic distribution. Glomus tumors should be considered as a rare differential diagnosis in the presence of small SB tumors.

Paraganglioma lateroaórtico / Latero-aortic paraganglioma

RESUMEN El feocromocitoma es un tumor productor de catecolaminas que procede de las células cromafines del sistema nervioso simpático. El 80-85% se localiza en la médula suprarrenal y el 15-20% son de localización extra adrenal y se denominan paragangliomas (PG). Alrededor del 97 % son benignos y se curan mediante la extirpación quirúrgica, y el restante 3% son malignos, capaces de producir metástasis a distancia. Se presenta el caso de una mujer de 43 años, que consultó por hipertensión, cefalea y palpitaciones. Presentaba elevación de catecolaminas urinarias, y por resonancia magnética se diagnosticó una masa de 50 por 41 mm latero aórtica. Le fue efectuada su resección por vía laparoscópica, sin complicaciones, con desaparición de los síntomas.

ABSTRACT Pheochromocytomas are catecholamine-producing tumors arising from the chromaffin cells of the sympathetic nervous system. Between 80-85% occur in the adrenal medulla and 15-20% are extraadrenal and are called paragangliomas (PG). About 97% are benign and are solved by surgical resection, while the remaining 3% are malignant and may produce distant metastases. We report the case of 43-year-old female patient who consulted due to hypertension, headache and palpitations. She had elevated urine catecholamines and presented a 50 x 41 mm latero-aortic mass on magnetic resonance imaging. The patient underwent laparoscopic resection of the tumor without complications and experienced relief of symptoms.

The Pheochromocytoma/Paraganglioma syndrome: an overview on mechanisms, diagnosis and management

ABSTRACT Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other prevailing clinical conditions such panic syndrome, thyrotoxicosis, anxiety, hypoglycemia, etc., delaying diagnosis and treatment. The rate of diagnosis of PPGL has been increasing with the improvement in the measurement of catecholamine metabolites and the expanding availability of imaging procedures. Its essential genetic nature has been extensively investigated, comprising more than 20 genes currently related to PPGL and more new genes will probably be revealed. This overview will shed some light on the clinical, laboratory, topographical, genetic diagnosis, and management of PPGL.

Paraganglioma de cuerpo carotideo / Carotid Body Paraganglioma

Introducción: Los paragangliomas de cuerpo carotideo son tumores neuroendocrinos hipervascularizados raros. Aunque su presentación clínica es frecuentemente asintomática, con el transcurso de los años puede manifestarse como tumores cervicales con o sin déficit neurológico. Objetivo: Presentar el caso de una paciente con tumoración cervical pulsátil de 10 años de evolución que requirió tratamiento quirúrgico. Presentación de caso: Mujer de 42 años procedente del Cusco, Perú, sin antecedentes médicos ni personales de importancia. La paciente acude al Servicio de Cirugía de Cabeza y Cuello por presentar tumoración cervical pulsátil de crecimiento lento progresivo, cefalea y disfagia. Tras realizar ultrasonografía Doppler y angiotomografía se pesquisa tumor cervical derecho hipervascularizado a nivel de la bifurcación de arteria carótida común. Se propone tratamiento quirúrgico de tumoración cervical con resultado anatomopatológico de paraganglioma de cuerpo carotideo. Tuvo una evolución posquirúrgica favorable sin evidencia de recurrencias en el seguimiento. Conclusión: El paraganglioma del cuerpo carotideo es una tumoración rara, de presentación clínica frecuentemente asintomática. Una evaluación minuciosa clínica e imagenológica permiten un diagnóstico adecuado para una planificación quirúrgica óptima(AU)

Introduction: Carotid body paragangliomas are rare hypervascularized neuroendocrine tumors. Although their clinical presentation is frequently asymptomatic, they may manifest as cervical tumors with or without neurological deficit over the years. Objective: To present the case of a patient with a pulsatile cervical tumor of 10 years' evolution that required surgical treatment. Case presentation: A 42-year-old woman from Cusco, Peru, with no medical or personal history of importance. The patient came to the head and neck surgery service for presenting a pulsatile cervical tumor with slow progressive growth, as well as headache and dysphagia. After performing Doppler ultrasonography and angiotomography, a hypervascularized right cervical tumor was observed at the level of the common carotid artery bifurcation. Surgical treatment of the cervical tumor was proposed, whose anatomopathological result was carotid body paraganglioma. Postoperative evolution was favorable, with no evidence of relapses during follow-up. Conclusion: Carotid body paraganglioma is a rare tumor of frequently asymptomatic clinical presentation. A thorough clinical and imaging-based assessment allows an adequate diagnosis for optimal surgical planning(AU)

Paraganglioma gangliocítico metastásico: una rara entidad histológica diagnosticada tras una duodenopancreatectomía / Metastatic gangliocytic paraganglioma: a rare histological entity diagnosed after duodenopancreatectomy

Introducción. El paraganglioma gangliocítico es una entidad histológica infrecuente, siendo el duodeno su principal localización extra ganglionar. Caso clínico. Se trata de un varón de 54 años que consulta por dolor abdominal y hemorragia digestiva alta. Se diagnosticó una lesión sospechosa de ampuloma por lo que se realizó una duodenopancreatectomía cefálica. En el análisis histológico, se confirmó el diagnóstico de paraganglioma gangliocítico metastásico por la presencia patognomónica de tres estirpes celulares (epiteliales, ganglionares y Schwann-like). Dado su buen pronóstico, asociado con baja quimiosensibilidad, no recibió tratamiento adyuvante. Resultados. Durante el seguimiento, el paciente no presentó complicaciones tardías, ni signos de recidiva después de un año de la intervención. Conclusión. El paraganglioma gangliocítico es una entidad potencialmente maligna, que requiere un correcto estudio de extensión y un seguimiento estrecho a largo plazo

Introduction. Gangliocytic paraganglioma is a rare histological entity, with the duodenum being its main extra-nodal location. Clinical case. This is a 54-year-old man who presented with abdominal pain and upper gastrointestinal bleeding. A suspicious ampuloma lesion was diagnosed, for which a pancreaticoduodenectomy was performed. In the histological analysis, the diagnosis of metastatic gangliocytic paraganglioma was confirmed by the pathognomonic presence of three cell lines (epithelial, ganglionic, and Schwann-like). Given his good prognosis associated with low chemosensitivity, he did not receive adjuvant treatment. Results. During follow-up, the patient did not present late complications or signs of recurrence one year after the intervention. Conclusion. Gangliocytic paraganglioma is a potentially malignant entity that requires a correct extension study and close long-term follow-up

Succinate dehydrogenase inhibitors fungicides: a review of their impact on human health and epigenetic changes / Fungicidas inibidores da succinato desidrogenase: uma revisao de seu impacto na saúde humana e alterares epigenéticas / Fungicidas inhibidores de la succinato deshidrogenasa: una revisión de su impacto en la salud humana y los cambios epigenéticos

Abstract Succinate dehydrogenase inhibitors (SDHIs), fungicides currently most used in agriculture in Brazil, act by blocking the enzyme succinate dehydrogenase (SDH) from plant pathogens. However, studies show that SDHIs can not only inhibit SDH activity in target fungi, but also block that activity in human cells. Considering the medical and agricultural implications of SDH, the purpose of this narrative review is to describe the relationship between exposure to fungicides SDHIs and epigenetic regulation of SDH associated with the development of gastrointestinal stromal tumor, pheochromocytoma/paraganglioma, and cancer. The results obtained with the research showed that the human SDH enzyme exhibited sensitivity to some tested SDHIs, which may cause microcephaly and defects in neurological development. Deficiency of SDH activity causes accumulation of succinate which can act as an oncometabolite inhibit-ing iron-dependent dioxygenases and alpha-ketoglutarate, eleven translocation -TET and histone demethylases, inducing epigenetic changes that lead to multiple cancers and other diseases. Therefore, further in vitro and in vivo analyzes should be performed to assess susceptibility to diseases influenced by the toxic effect of SDHIs.

Resumo Os inibidores da succinato desidrogenase (SDHIs), fungicidas atualmente mais utilizados na agricultura no Brasil, atuam bloqueando a enzima succinato desidrogenase (SDH) de fitopatógenos. No entanto, estudos mostram que SDHIs podem nao apenas inibir a atividade de SDH em fungos alvo, mas também bloquear essa atividade em células humanas. Considerando as implicares médicas e agrícolas do SDH, o objetivo desta revisao narrativa é descrever a relaqao entre a exposiqao a fungicidas SDHIs e a regulaqao epigenética do SDH associada ao desenvolvimento de tumor estromal gastrointestinal, feocromocitoma/paraganglioma e cáncer. Os resultados obtidos com a pesquisa mostraram que a enzima SDH humana apresentou sensibilidade a alguns SDHIs testados, que podem causar microcefalia e defeitos no desenvolvimento neurológico. A deficiencia da atividade da SDH causa acumulo de succinato que pode atuar como um oncometabólito inibindo as dioxigenases dependentes de ferro e alfa-cetoglutarato, onze translocaqóes -TET e histonas desmetilases, induzindo alteraqóes epigenéticas que levam a múltiplos canceres e outras doenqas. Portanto, análises adicionais in vitro e in vivo devem ser realizadas para avaliar a suscetibilidade a doenqas influenciadas pelo efeito tóxico dos SDHIs.

Resumen Los inhibidores de la succinato deshidrogenasa (SDHI), los fungicidas actualmente más utilizados en la agricultura en Brasil, actúan bloqueando la enzima succinato deshidrogenasa (SDH) de los patógenos de las plantas. Sin embargo, los estudios muestran que los SDHI no solo pueden inhibir la actividad de SDH en los hongos objetivo, sino que también bloquean esa actividad en las células humanas. Teniendo en cuenta las implicaciones médicas y agrícolas de SDH, el propósito de esta revisión narrativa es describir la relación entre la exposición a fungicidas SDHI y la regulación epigenética de SDH asociada con el desarrollo de tumores del estro-ma gastrointestinal, feocromocitoma/paraganglioma y cáncer. Los resultados obtenidos con la investigación mostraron que la enzima SDH humana mostró sensibilidad a algunos SDHI probados, lo que puede causar microcefalia y defectos en el desarrollo neurológico. La deficiencia de la actividad de SDH provoca la acumulación de succinato que puede actuar como un oncometabolito que inhibe las dioxigenasas dependientes de hierro y el alfa-cetoglutarato, once translocaciones -TET e histona desmetilasas, induciendo cambios epigenéticos que conducen a múltiples cánceres y otras enfermedades. Por lo tanto, se deben realizar más análisis in vitro e in vivo para evaluar la susceptibilidad a enfermedades influenciadas por el efecto tóxico de los SDHI.

Síndrome de feocromocitoma-paraganglioma tipo 5 asociado a mutación en el complejo de la succinato deshidrogenasa tipo A (SDHA), a propósito de un caso / Pheochromocytoma-paraganglioma type 5 syndrome associated with mutation in the succinate dehydrogenase type A complex (SDHA), a case report

Resumen Los feocromocitomas y paragangliomas son neoplasias neuroendocrinas infrecuentes que pueden producir catecolaminas. Tienen una incidencia menor a un caso por millón de habitantes. Son histológicamente benignas y muestran mínimas diferencias respecto a sus contrapartes malignas. Asimismo, son dos de las neoplasias humanas con mayor carga genética. La mutación más común es en la vía del complejo de la succinato deshidrogenasa (SDH) y, de esta, una de las que menos se reportan son las variantes de la SDH subunidad A (SDHA). Se describe el caso de un paciente con feocromocitoma y paraganglioma asociados a una mutación en SDHA y se señala su comportamiento y buena respuesta clínica al manejo quirúrgico y vigilancia activa.

Paraganglioma gigante del espacio parafaríngeo en una fémina / Giant paraganglioma of the parapharingeal space in a woman: en

Se describe el caso clínico de una paciente de 57 años de edad, con antecedente de hipertensión arterial, quien fue asistida en el Servicio de Cirugía de Cabeza y Cuello del Instituto Nacional de Oncología y Radiobiología de La Habana, remitida de la consulta de Otorrinolaringología de su hospital de cabecera por presentar manifestaciones clínicas de disfagia y diagnóstico clínico de sospecha de un paraganglioma carotídeo. Luego de realizados el examen físico y los estudios complementarios pertinentes, el caso fue discutido por los integrantes de un equipo multidisciplinario y se confirmó la existencia de un paraganglioma del espacio parafaríngeo, por lo que se decidió realizar tratamiento quirúrgico. La evolución fue satisfactoria y a los 2 años del procedimiento quirúrgico no presentaba secuelas.

The case report of a 57 years patient with history of hypertension is described who was assisted in the Head and Neck Surgery Service of the National Institute of Oncology and Radiobiology in Havana, referred from the Otolaryngology Service of her head hospital due to clinical manifestations of dysphagia and suspected clinical diagnosis of a carotid paraganglioma. After the physical exam and the pertinent complementary studies, the case was discussed by the members of a multidisciplinary team and the existence of a paraganglioma in the parapharingeal space was confirmed, therefore it was decided to carry out surgical treatment. The clinical course was satisfactory, and 2 years after the surgical procedure there were no sequels.

Clinical features and prognosis of paraganglioma of the urinary bladder / 现代泌尿外科杂志

【Objective】 To explore the clinical features, treatment and prognosis of paraganglioma of the urinary bladder (PUB). 【Methods】 The clinical data of 41 PUB patients treated at our hospital during Sep.2012 and Sep.2022 were collected. The clinical features, surgical records, pathological reports and follow-up records were retrospectively analyzed. Patients’ survival was estimated with Kaplan-Meier estimator. The differences among groups were compared with Log-rank test. 【Results】 Among the 41 patients, 20 were male and 21 were female, with a median age of 52 years. All patients were treated with surgery, including transurethral resection of bladder tumor (TURBT) in 16 cases, partial cystectomy (PC) in 23 cases, and radical cystectomy (RC) in 2 cases. All patients were followed up for 4.0 to 125.0 months, with a median of 59.0 months. Local recurrence occurred in 5 patients, and distant metastasis occurred in 5 patients. Survival analysis showed that the 5-year overall survival (OS) rate and 5-year relapse-free survival (RFS) rate were 95.7% and 84.8%, respectively. Further analysis showed statistically significant differences in OS and RFS among groups with different maximum tumor diameters, growth patterns, and Ki-67 expressions (P<0.05). For patients with a maximum tumor diameter ≤2.8 cm, there was no significant difference in OS and RFS among different surgical groups. 【Conclusion】 PUB is rare, and a definitive diagnosis is based on pathology. In addition, the main treatment is surgery and the prognosis is good.

Efficacy and safety of anlotinib monotherapy and combinated therapy in the treatment of advanced pheo-chromocytoma/paraganglioma / 实用医学杂志

Objective To evaluate the efficacy and safety of anlotinib monotherapy and combined therapy in patients with advanced pheochromocytoma/paraganglioma.Methods Nine patients with advanced pheochromo-cytoma/paraganglioma(PPGL)who were admitted to the Department of Urology,Sun Yat-sen University Cancer Center from January 2018 to June 2023 were collected.Patients were divided into four groups according to different treatments:anlotinib monotherapy group(3 patients),anlotinib combined with PD-1 monoclonal antibody immuno-therapy group(3 patients),anlotinib combined with immunotherapy and chemotherapy group(2 patients),and anlotinib combined with chemotherapy group(1 patients).The effectiveness and safety of different treatment regiments of anlotinib were analyzed.Results Objective response rate(ORR):(44%),Partial response(PR):(44%),Stable disease(SD):(44%),Progressive disease(PD):(11%),Disease control rate(DCR):(89%).The ORR of 2 patients with SDH gene mutation,SDHB and SDHD respectively,was 100%.Median overall survival time(OS)was 16.3 months(IQR:11.3～21.8 months).Median progression-free survival(PFS)was 16.3 months(IQR:9.8～20.8 months).There were 2 patients with adverse events grade≥3/4,all of which were hypertension.Conclusions Anlotinib monotherapy and combined therapy have preliminary efficacy and manageable safety in the treatment of advanced pheochromocytoma/paraganglioma.