Renewal and interpretation of concepts related to paragangliomas and pheochromocytomas according to WHO classification in 2022 / 中华泌尿外科杂志

WHO issued the fifth edition of classification of neuroendocrine neoplasms in 2022. The content of paragangliomas and pheochromocytomas (PPGL) was updated compared with the fourth edition in 2017. In the fifth edition of PPGL classification system, the author redefined the concepts that were vague and unclear in the past, and also put forward some new ideas. On this basis, this article introduces the relevant updates in combination with the current clinical situation in China. The content includes the concept evolution of paragangliomas and pheochromocytomas, accurate interpretation of the definitions of paraganglioid tumor, composite paraganglioma, adrenal medullary hyperplasia, and micro-pheochromocytoma. This article also help readers to understand molecular diagnostic and prognostic markers, the definition and clinical staging of benign and malignant PPGL. The domestic scholars can unify some concepts in PPGL to avoid confusion and facilitate academic exchanges through the discussion of these key concepts.

Paragangliomas cervicais: experiência de 114 casos em 14 anos / Cervical paragangliomas: experience of 114 cases in 14 years

Resumo Introdução e objetivo: Relatar a experiência de um único centro com casos de paraganglioma do corpo carotídeo tratados pelo mesmo cirurgião em uma cidade com alta prevalência de paragangliomas devido à alta altitude. Método: Foram investigados retrospectivamente os dados demográficos, clinico-patológicos e radiológicos de 104 pacientes com diagnóstico de paragangliomas cervicais entre 2003 e 2017. Os pacientes foram classificados de acordo com a classificação de Shamblin. Resultados: Neste estudo, foram incluídos 104 pacientes (33 homens e 71 mulheres, com média de 54,6 ± 13 anos, entre 2003 e 2017) com diagnóstico de paraganglioma cervical na bifurcação carotídea. Entre esses pacientes, 10 tinham tumores bilaterais e, no total, 114 paragangliomas foram tratados nesse período. O diâmetro médio dos tumores foi de 5,12 ± 1,45 cm. Um tumor maligno foi determinado em apenas um (0,9%) paciente. Todos os pacientes foram operados. Em 12 pacientes com diâmetro do tumor maior do que 5 cm, foi possível fazer embolização pré-operatória com molas; em 14 pacientes, foi feita embolização angiográfica e em 4 pacientes foram aplicadas injeções de agentes esclerosantes. Após o tratamento cirúrgico, paralisia facial foi observada em 2 pacientes, disfagia em um, síndrome de Horner em um e rouquidão em 7. Todas essas complicações melhoraram durante o acompanhamento. Não foi relatada mortalidade. Conclusão: A cirurgia é o tratamento definitivo em pacientes com paragangliomas cervicais. Embora possa ser difícil em pacientes com os tipos avançados de Shamblin, em mãos experientes as taxas de complicações são muito baixas.

A Retrospective Analysis of Patients Presenting with Head and Neck Paragangliomas at Two Tertiary Referral Centres in Jamaica / Análisis retrospectivo de pacientes que presentan paragangliomas de cabeza y cuello en dos centros de remisión terciarios en Jamaica

ABSTRACT Objective: Paragangliomas are slow-growing tumours that present with varied clinical spectra. Early recognition is paramount in achieving reduced morbidity and mortality. There is a paucity of data regarding head and neck paragangliomas (HNPGs) in the Caribbean literature. This study aimed to reflect the clinical experience in the management of HNPGs at two Jamaican tertiary referral centres: the Kingston Public Hospital (KPH) and the University Hospital of the West Indies (UHWI). Methods: A retrospective analysis was conducted on all patients presenting to the Ear, Nose and Throat (ENT) departments of the UHWI in 2004-14 and of the KPH in 2012-14 with the diagnosis of a HNPG. Results: There were 15 patients, 1 male and 14 females. The average age at presentation was 47.1 years. The HNPGs in this series included eight patients with glomus tympanicum (GT, 53%), four with glomus jugulare (GJ, 27%), two with carotid body tumours (CBTs, 13%) and one with glomus vagale (GV, 7%). Eight patients underwent surgical resection (two CBTs, four GT and two GJ). Treatment outcomes achieved included: complete resection (four patients), stable with residual disease (two patients), and recurrence (two patients). Seven patients were awaiting definitive treatment, one patient with GJ was referred overseas, and one patient with GV defaulted. Conclusion: Glomus tympanicum is the most common HNPG in this series which contrasts with that of most international series. Despite the limitations within this region, such as limited access to angio-embolization and stereotactic modalities, the management outcomes are similar in some respects to the reported international literature.

RESUMEN Objetivo: Los paragangliomas son tumores de crecimiento lento que se presentan con variados espectros clínicos. Su detección precoz es fundamental para lograr una reducción de la morbilidad y la mortalidad. Hay escasez de datos con respecto a los paragangliomas de cabeza y cuello (PgCC) en la literatura del Caribe. Este estudio tuvo como objetivo reflejar la experiencia clínica en el tratamiento de PgCC en dos centros de remisión terciarios de Jamaica: jamaiquinos: el Hospital Público de Kingston (KPH) y el Hospital Universitario de UWI (HUWI). Métodos: Se llevó a cabo un análisis retrospectivo de todos los pacientes diagnosticados con PgCC que acudieron a los Departamentos de Otorrinolaringología de HUWI en 2004-14 y de KPH en 2012-14. Resultados: Hubo 15 pacientes - 1 varón y 14 hembras. La edad promedio al momento de presentarse fue 47.1 años. El PgCC en esta serie incluyó a ocho pacientes con glomus timpánico (GT, 53%), cuatro con glomus yugular (GY, 27%), dos con tumores del cuerpo carotídeo (TCC, 13%), y uno con glomus vagal (GV, 7%). Ocho pacientes fueron sometidos a resección quirúrgica (dos TCC, cuatro GT, y dos GY). Los resultados logrados con el tratamiento incluyeron: resección total (cuatro pacientes), estables con enfermedad residual (dos pacientes), y recurrencia (dos pacientes). Siete pacientes esperaban un tratamiento definitivo, un paciente con GY fue remitido al extranjero, y un paciente con GV no se presentó. Conclusión: El glomus timpánico es el PgCC más común en esta serie que contrasta con el de la mayoría de las series internacionales. A pesar de las limitaciones dentro de esta región, tales como el acceso limitado a la angioembolización y las modalidades estereotácticas, los resultados del manejo de la enfermedad son similares en algunos aspectos a la literatura internacional reportada.

Glomus tympanicum

Glomus tympanicum is a tumour classified under the group glomus tumours, and is also knownas paragangliomas. It is thought to commonly occur in women in the fifth to sixth decades of life.Here, we report a case of a 77-year-old lady with multiple co-morbids and a diagnosis of glomustympanicum presenting to us. Her symptoms included pulsatile tinnitus, and reduced hearing,and the management of the case was done with consideration for her underlying multiple comorbidities.This paper also describes the best modality of treatment for this patient with regardto her background history. The treatment goal was to improve her quality of life and control thedisease.

Paraganglioma retroperitoneal no funcional: reporte de un caso en la Fundación Cardioinfantil, Bogotá, Colombia / Retroperitoneal non-functional paraganglioma: report of a case from the Cardioinfantil Foundation, Bogotá, Colombia

Los paragangliomas son tumores derivados de las células cromafines de la cresta neural y por ello tienen la capacidad de secretar catecolaminas, hormonas y péptidos; al ser tumores extraadrenales del sistema nervioso central se los puede encontrar en la base del cráneo, el cuello, el tórax y el abdomen; se clasifican en funcionales y no funcionales. En este artículo se describe un paciente de sexo masculino que cursó inicialmente con dolor inespecífico en el hipocondrio derecho; con base en los estudios imaginológicos iniciales se sospechó la presencia de un neuroblastoma, pero no fue posible diferenciarlo de un paraganglioma, un ganglioneuroblastoma o un neurofibroblastoma. Se lo intervino quirúrgicamente y el estudio patológico del espécimen reveló áreas hemorrágicas extensas, compatibles con un paraganglioma extraadrenal no funcional. Estos tumores son infrecuentes, de localización diversa y de tratamiento quirúrgico difícil.

Paragangliomas are tumors derived from chromaffin cells from the neural crest. They are able to secrete catecholamines, hormones and peptides. They can be found in the skull base, neck, thorax and abdomen, and may be functional or not-functional. We report the case of a male patient with non-specific pain in the right hypochondrium. Based on the initial imaginological studies a neuroblastoma was suspected, but it not possible to differentiate it from a paraganglioma, a ganglioneuroblastoma or a neurofibroblastoma. The pathological study of the surgical specimen revealed extensive hemorrhagic areas, consistent with a non-functional extra-adrenal paraganglioma. This is an infrequent neoplasia with difficult surgical treatment.

Paragangliomas cervicales. Resultados actuales comparados con los de la serie histórica / Cervical paragangliomas. Comparison of current results with historical series

Antecedentes: los paragangliomas cervicales son tumores poco frecuentes, que reciben diferentes denominaciones según su ubicación. Los que asientan en la bifurcación carotdea son llamados ca-rotdeos; en el oído medio, tmpánicos; en el bulbo yugular, yugulares y en el nervio vagal, vagales. Lugar de aplicación: hospital público de atención terciaria de tumores. Población: veintséis pacientes, 22 de ellos operados. La edad media fue 48,6 años, el 77% del sexo femenino. Método: revisión de historias clínicas e informes de anatomía patológica. Resultados: doce eran izquierdos, 11 derechos, 2 bilaterales y 1 múltple. Se llegó al diagnóstico por la semiología, por angiorresonancia y por tomografa computarizada. Fueron divididos según la clasificación de Shamblin en grado 1-2 en 16 y grado 3 en 10. La extensión de la cirugía demandó en todos la resección del tumor que implicó en 2 la reparación vascular, en 2 la resección de los pares craneales XI y XII y en los 4 restantes por ser asintomáticos solo la observación. La morbilidad fue del 22,7%, las secuelas del 31,8% y la mortalidad del 4,5% distnta a la presentada en la serie histórica de 44,4%, 55,5% y 5,4%, respectvamente. Conclusiones: 1) Los tumores del cuerpo carotdeo son infrecuentes, benignos en su mayoría y de crecimiento lento. 2) Los recursos diagnósticos más utlizados fueron: el ecodoppler, la tomografa computarizada con contraste y la angiorresonancia, con resultados positvos en el 100% de los casos, a diferencia de la serie histórica donde se utlizó la angiografa con éxito en el diagnóstico en el 70%. 3) Los pacientes con tumores I, II y III sintomáticos de la clasificación de Shamblin son quirúrgicos con un porcentaje de secuelas del 31,8 % a diferencia de la serie histórica del 55,5 %. 4) En los tumores tpo III asintomáticos la selección de los pacientes debe ser cuidadosamente considerada para recomendar una cirugía agresiva y con alta morbilidad. Esta conclusión difere de la presentada en la serie histórica, donde todos los pacientes fueron intervenidos quirúrgicamente.

Background: cervical paragangliomas are very rare tumours and receive diferent names according to the site of origin. Carotd for those localized in the carotd bifurcaton, tympanic for those in the middle ear, yugular for those in the yugular bulb and vagal for those in the vagal nerve. Setng: tertary care oncologic public hospita. Populaton: 26 patents, 22 of them surgically treated. Mean age was 48.6 years, 77% female. Methods: review of clinical records and pathologic reports. Results: twelve were at the lef side, 11 at the right, 2 bilateral and 1 multple. Diagnosis was done by semiology, magnetic resonance and computed tomography. The tumors were classifed according to Shamblin classificaton in 1, 2 grades in 16 patents and 3 in 10. Surgery included tumor resecton with vascular graf in 2, XI and XII craneal nerve also in 2, while 4 patents remained in observaton because they were asymptomatic. Morbidity was 22.7%, sequels 31.8% and mortality 4.5%, diferent to the historic series with 44.4%, 55.5% and 5.4% respectvely. Conclusions: tumors of carotd body are infrequent, benign and of slow growth. Diagnostic techniques frequently used were ecodopler, CT scan and MRI, with positve results in about 100% of cases. It was diferent to historic series in which angiographic studies had positve results in only 70% of them. Symptomatic Shamblin 1, 2 and 3 were surgically treated with 31.8% of sequels, diferent to historic sample with 55.5%, but in asymptomatic grade 3, careful selecton of patents must be taken into ac-count for avoiding an aggressive surgery with high morbidity. This conclusion is diferent of the historic series in which all patents were surgically treated.

Succinate dehydrogenase gene mutations and DNA methylation analysis in hereditary pheochromocytoma paraganglioma syndrome / 中华泌尿外科杂志

Objective To detect the genetic mutations of succinate dehydrogenase B (SDHB),SDHC,SDHD,SDHAF2 and RET,VHL in hereditary pheochromocytoma (PHEO) paraganglioma (PGL) syndrome in order to analyze the relationship between the pathogenesis and SDHx mutations and DNA methylation.Methods SDH genes,VHL and RET were analyzed for germline mutations in 97 PHEOs/PGLs patients.Correlations were analyzed between the results and the clinical characteristics including age,tumor localization,multifocality,24 h urine CA,IGF and NSE.Direct DNA sequence analysis was carried out for SDHB (1q36.1-1q35,exons1-8),SDHC (1q21,exons 1-5),SDHD (11q23,exons 1-4),SDHAF2 (11q12.2,exons 1-4),RET (10q11.2,exons10,11,13,14&15,and 16) and VHL (3p25.3,exons 1-3) genes,and promoter region methylation of SDHB was detected in PHEO/PGL peripheral blood samples.Results Germinal mutations were found in 17 patients (17.5％),with 8 cases in RET proto-oncogene (8.2％),7 cases in SDHB genes (7.2％) and 2 cases in VHL gene (2.1％).The comparison of some of the clinical features in two groups (with and without promoter region methylation of SDHB) showed significant differences (P＜0.01).Conclusions Genetic predisposition is frequent in chromaffin tissue tumors,indicating that DNA analysis is necessary.The mutation of SDHB is highly associated with abdominal PGL and the following distant metastasis (malignant PGL).

A case of ampullary gangliocytic paraganglioma

Gangliocytic paragangliomas (GPs) are rare tumors of the duodenum, presenting as single sessile or pedunculated polypoid masses. Clinical manifestations of duodenal GPs can vary from an incidental finding at endoscopy to frequent upper gastrointestinal bleeding caused by mucosal ulceration and abdominal pain. GPs are considered benign, but the disease can recur and spread to regional lymph nodes. A 41-year-old female presented with abdominal pain. Upper gastrointestinal endoscopy revealed a subepithelial tumor of the ampulla of Vater in the second portion of the duodenum. The tumor was resected using the endoscopic mucosal resection technique. The tumor was diagnosed as benign GP of the duodenum using histological and immunohistochemical staining procedures.

Paraganglioma metastásico: imagen con 18F-fluordesoxiglucosa-tomografía por emisión de positrones / Metastatic paraganglioma: image with F18-FDG- PET/CT

Los paragangliomas son tumores neuroendocrinos poco frecuentes que pueden originarse en cualquier lugar a lo largo del sistema paraganglial. La mayoría son benignos y de progresión lenta, sin embargo un 10% aproximadamente presentan metástasis. El 80-85% de estos tumores surgen de la médula suprarrenal y se nombran feocromocitomas, mientras que el 15-20% se encuentran en tejidos cromafines a nivel extra-adrenal y se conocen como paragangliomas. Tienen variantes hereditarias (25%), también pueden manifestarse con multifocalidad. Pueden aparecer en cualquier parte del sistema paraganglial y estar asociados con el tejido nervioso simpático (médula adrenal, el órgano de Zuckerkandl, u otras células cromafines que puedan persistir más allá de la embriogénesis), o con el sistema nervioso parasimpático (quimiorreceptores, que se encuentra principalmente en cabeza y cuello). Por lo tanto, los paragangliomas pueden estar distribuidos desde la base del cráneo hasta el sacro. Las imágenes de medicina nuclear ayudan a delinear plenamente la enfermedad.

The paragangliomas are a rare neuroendocrine group of tumors that can occur anywhere along paraganglia system. Most of them are benign and of slow progression, however about 10% of them will have metastases. The large majority (80-85%) of these tumors arise from the adrenal medulla and are called pheochromocytomas, while 15-20% originate in chromaffin tissue at extra-adrenal sites, and are called paragangliomas. There are inherited variants (25%), and the disease may also present with multifocality. They can appear anywhere in paraganglia system and may be associated with sympathetic nervous tissue (adrenal medulla, the organ of Zuckerkandl, or other chromaffin cells that can persist beyond embryogenesis), or the parasympathetic nervous system (chemoreceptors, which are found mainly in the head and neck). Therefore, paragangliomas can be distributed from the base of the skull to the sacrum. Nuclear medicine imaging can help to fully define the disease. © 2013 Instituto Nacional de Cancerología. Published by Elsevier España, S.L. All rights reserved.

Tumor do glomus carotídeo / Carotid body tumor

Objetivo: relatar caso de raro tumor cervical diagnosticado no Hospital de Clínicas da Universidade Federal do Paraná Resultados: Paragangliomas da cabeça e pescoço corres­pondem a 0,6% dos tumores cervicais e, destes, o mais comum é do glomus carotídeo, com freqüência de 1: 1.700.0001 indi­víduos. São tumores de crescimento lento, na maioria benignos e unilaterais, 10% de caráter familiar 2-4, maior incidência entre 40 e 60 anos, sem diferença entre sexos 4. O principal sinal é o aparecimento de massa cervical, que pode ser pulsátil e apre­sentar sopro local. Este raro tumor foi diagnosticado em uma paciente feminina, de 23 anos, avaliada em nosso serviço. Conclusões: Apesar de incomuns, os tumores do corpo carotídeo devem fazer parte dos diagnósticos diferenciais do clínico ao investigar uma massa cervical.

Aspectos clínicos, diagnóstico e manejo dos tumores que produzem catecolaminas: feocromocitomas e paragangliomas / Clinical aspects, diagnosis and management of catecolamin-producing tumors: pheocromocitomas and paragangiomas

Os feocromocitomas e paragangliomas são tumores raros, originários de células cromafins. Os primeiros localizam-se na medula suprarrenal e os últimos podem ser encontrados em qualquer local ao longo das cadeias simpática sou parassimpáticas do sistema nervoso autônomo. Constituem causa potencialmente curável de hipertensão arterial. Usualmente, secretam catecolaminas, incluindo-se dopamina, adrenalina e noradrenalina, responsáveis pela tríade semiológica clássica de manifestações: episódios paroxísticos de cefaléia, diaforese e palpitação. No entanto, a apresentação clínica é muito variável, e um grande número de pacientes pode ser oligo- ou assintomático, sugerindo que a parte significativa dos casos não é diagnosticada. Alta suspeição, uso racional de exames laboratoriais e métodos de imagem apropriados dão o diagnóstico anatômico e funcional preciso. Este artigo traz uma revisão sobre as recomendações mais atuais para abordagem desses tumores endócrinos.

Pheocromocytomas and paragangliomas are rare tumors, originated from chromaffim cells. The first ones are located in the suprarrenal medulla, and the others are found somewhere along the sympathetic and parasympathetic chains from the autonomous neural system. They constitute a potentially curable cause of arterial hypertension. Usually, they secrete cathecolamines, including dopamine, epinephrine and norepinephrine, which are responsible for the classic triad of manifestations: paroxysms of cephaleia, diaphoresis and palpitations. However, clinical presentation is very heterogeneous and a significant number of patients are oligo- or assymptomatic, suggesting that the majority of these cases may not be detected. High suspicion, rational use of laboratorial exams and appropriate imaging methods lead to accurate functional and anatomical diagnosis. The present article brings a revision about the most recent recommendations for management of these endocrine tumors.

Paragangliomas of the head and neck: A retrospective review at Siriraj Hospital.

Objective: To analyze the distribution and radiological findings of paragangliomas of the head and neck region at Siriraj Hospital. Methods: The cases with pathological proven of paragangliomas in the head and neck from January 1996 to December 2003 at Siriraj Hospital were retrospectively reviewed. Clinical presentation and radiologic findings in term of location, size, number, pattern of enhancement, vascularity and bony destruction were analyzed. Results: There were 26 tumors among 22 patients which were 12 females and 10 males, with an average age of 47 years old. By locations, paragangliomas were found as carotid body tumor in 46.2%, glomus tympanicum in 11.5%, glomus vagale in 11.5%, glomus jugulare in 3.8%, glomus jugulotympanicum in 7.6% and rare locations in 19.2%. The unusual locations included sinonasal cavity, sphenoid sinus, supraglottic larynx, thyroid gland and posterior fossa. The presenting symptoms were neck mass in 53.8%, tinnitus in 26.9%, cranial nerve palsy in 19.2%, epistaxis in 3.8%, hoarseness of voice in 3.8%, severe headache in 3.8%. Multicentricity was found in 18%. Aggressive pattern was documented in 15.4 %. The radiological findings of paragangliomas in usual locations were all characteristic homogeneous intensely enhanacement or hypervascularity (100%). Those in rare locations had also central necrosis (60%). Bony destruction was shown in 9.5% of usual locations and 40% of unusual locations. No any of lesions in rare locations had multicentricity. Conclusion: Carotid body tumor is the most common paragangliomas in the head and neck region. Clinical presentation of a paraganglioma is related to location of the tumor. On the basis of the locations and radiographic characteristics, in common locations, imaging findings are characteristics and they may provide definite diagnosis, but in rare locations the radiological findings are not characteristics, and should be differentiating from other head and neck lesions.

Tumor de glomus yugular, presentación de un caso clínico y revisión de la literatura / Glomus juglare tumor, case study and bibliographic reference

Los tumores del glomus yugular o timpánicos son poco comunes. Aunque son considerados tumores benignos, de crecimiento lento y tratamiento quirúrgico, pueden llegar a adquirir grandes dimensiones. El pronóstico de estos tumores está relacionado estrechamente con su localización anatómica y el volumen de la lesión. Si la remoción quirúrgica no es posible la radioterapia constituye una alternativa de tratamiento válida con intenciones paliativas.

The glomus juglare tumors are very uncommon. They are considered as benign and slow growing tumors. The treatment of choice is surgery. The prognosis of these tumors is related to the anatomical location and size of the lesion. If surgery is not posible the next step would be radiotherapy.