Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datas...Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datasets GSE67066 and GSE60458.The R software and various packages were utilized for the analysis of differentially expressed genes,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,receiver operating characteristic curve assessment,logistic model construction,and correlation analysis.The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks.In addition,the TIMER database was used to estimate the immune scores.Results:A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458,respectively.These genes are implicated in cytokine and cytokine receptor interactions,extracellular matrix–receptor interactions,and platelet activation signaling pathways.Notably,MAMLD1,UST,MATN2,LPL,TWIST1,SFRP4,FRMD6,RBM24,PRIMA1,LYPD1,KCND2,CAMK2N1,SPOCK3,and ALPK3 were identified as the key genes.Among them,MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers,whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration.Eight miRNAs were identified as potential regulators of key gene expression,and it was noted that TWIST1 might be regulated by SUZ12.Notably,the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.Conclusions:The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential.These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.展开更多
Introduction: Pheochromocytoma is a rare cause of endocrine hypertension. We report the case of an extra-adrenal pheochromocytoma discovered in the setting of an abdominal mass. Observation: The patient was 25-year-ol...Introduction: Pheochromocytoma is a rare cause of endocrine hypertension. We report the case of an extra-adrenal pheochromocytoma discovered in the setting of an abdominal mass. Observation: The patient was 25-year-old and presented with headaches, excessive sweating and palpitations, followed by a sensation of abdominal weightlessness and diastolic arterial hypertension. Abdominal computed tomography revealed a retroperitoneal, right para-renal extra-adrenal mass. In biology, an increase in urinary methoxylated derivatives at the expense of normetanephrine. Conclusion: Pheochromocytoma is a rare disease, diagnosed by measuring urinary or plasma methoxylated derivatives. Conventional or nuclear imaging allows topographic diagnosis. Genetic studies helps to identify other tumors.展开更多
目的:分析生化阴性嗜铬细胞瘤及副神经节瘤(pheochromocytomas and paragangliomas,PPGLs)的电子计算机断层扫描(computed tomography,CT)征象是否有别于生化阳性PPGLs,同时了解生化阳性PPGLs不同表型的CT征象是否存在差异。方法:回顾...目的:分析生化阴性嗜铬细胞瘤及副神经节瘤(pheochromocytomas and paragangliomas,PPGLs)的电子计算机断层扫描(computed tomography,CT)征象是否有别于生化阳性PPGLs,同时了解生化阳性PPGLs不同表型的CT征象是否存在差异。方法:回顾性分析131例PPGLs患者的术前腹部增强CT图像,包括肿瘤位置、大小、形态、囊变坏死、液-液分层、钙化、向心结节状强化、肿瘤内粗大血管、强化包膜、绝对廓清率及相对廓清率。根据生化水平,将患者分为生化阳性组和阴性组,阳性组进一步分为去甲肾上腺素型、肾上腺素型及多巴胺型。比较各组及各表型间的CT征象差异。结果:相较于生化阴性组,阳性组PPGLs更大(Z=-2.064,P=0.039)、囊变坏死(χ2=6.610,P=0.010)及向心结节状强化(χ2=3.909,P=0.048)的比例更高;相较于去甲肾上腺素型,肾上腺素型PPGLs更大(Z=-2.036,P=0.042)、强化包膜比例更高(χ2=7.242,P=0.007)。结论:肿瘤大小、囊变坏死及向心结节状强化的CT征象有助于术前诊断生化阴性PPGLs,肿瘤大小及强化包膜有助于解释去甲肾上腺素型及肾上腺素型PPGLs不同临床表现产生的机制。展开更多
目的探讨胰岛素瘤相关蛋白1(insulinoma-associated protein 1,INSM1)在嗜铬细胞瘤/副神经节瘤和肾上腺皮质腺瘤中的表达及其在鉴别诊断中的意义。方法采用免疫组化EnVision两步法检测INSM1在嗜铬细胞瘤/副神经节瘤和肾上腺皮质腺瘤中...目的探讨胰岛素瘤相关蛋白1(insulinoma-associated protein 1,INSM1)在嗜铬细胞瘤/副神经节瘤和肾上腺皮质腺瘤中的表达及其在鉴别诊断中的意义。方法采用免疫组化EnVision两步法检测INSM1在嗜铬细胞瘤/副神经节瘤和肾上腺皮质腺瘤中的表达。结果32例嗜铬细胞瘤中31例INSM1阳性(31/32,96.88%),其中高表达20例(20/32,62.50%)。9例肾上腺外副神经节瘤INSM1均阳性,其中高表达8例(8/9,88.89%)。33例肾上腺皮质腺瘤中INSM1均阴性。INSM1在嗜铬细胞瘤/副神经节瘤中的表达显著高于肾上腺皮质腺瘤(P<0.001)。INSM1高表达的嗜铬细胞瘤/副神经节瘤具有更高的Ki67增殖指数(P=0.016),但与患者性别(P=0.190)、年龄(P=0.439)、肿瘤TNM分期(P=0.793)、生长模式(P=0.495)、凝固性坏死(P=0.790)和脉管/包膜侵犯(P=0.790)均无显著相关性。INSM1鉴别嗜铬细胞瘤/副神经节瘤与肾上腺皮质腺瘤的敏感性为97.6%,特异性为100%,ROC曲线下面积为0.988。结论INSM1表达于嗜铬细胞瘤和副神经节瘤的细胞核,而不表达于肾上腺皮质腺瘤,可有效鉴别嗜铬细胞瘤/副神经节瘤和肾上腺皮质腺瘤。展开更多
BACKGROUND Paraganglioma(PGL)located in the retroperitoneum presents challenges in diagnosis and treatment due to its hidden location,lack of specific symptoms in the early stages,and absence of distinctive manifestat...BACKGROUND Paraganglioma(PGL)located in the retroperitoneum presents challenges in diagnosis and treatment due to its hidden location,lack of specific symptoms in the early stages,and absence of distinctive manifestations on imaging.CASE SUMMARY A 56-year-old woman presented with a left upper abdominal mass discovered 1 wk ago during a physical examination.She did not have a history of smoking,alcohol consumption,or other harmful habits,no surgical procedures or infectious diseases,and had a 4-year history of hypertension.Upon admission,she did not exhibit fever,vomiting,or abdominal distension.Physical examination indicated mild percussion pain in the left upper abdomen,with no palpable enlargement of the liver or spleen.Laboratory tests and tumor markers showed no significant abnormalities.Enhanced computed tomography and magnetic resonance imaging of the upper abdomen revealed a cystic solid mass in the left epigastrium measuring approximately 6.5 cm×4.5 cm,with inhomogeneous enhancement in the arterial phase,closely associated with the lesser curvature of the stomach and the pancreas.The patient underwent laparoscopic resection of the retroperitoneal mass,which was successfully removed without tumor rupture.A 12-month postoperative follow-up period showed good recovery.CONCLUSION This case report details the successful laparoscopic resection of a retroperitoneal subclinical PGL,resulting in a good recovery observed at the 12-month follow-up.Interestingly,the patient also experienced unexpected cure of hypertensive disease.展开更多
BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,fam...BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.展开更多
Introduction: Adrenal tumours (AT) are commonly encountered in clinical practice. For any patient presenting an adrenal mass, there are two crucial points to consider: is the adrenal mass malignant and is it hormonall...Introduction: Adrenal tumours (AT) are commonly encountered in clinical practice. For any patient presenting an adrenal mass, there are two crucial points to consider: is the adrenal mass malignant and is it hormonally active? The objective of our study was to evaluate the epidemiological, diagnostic, therapeutic, and evolutionary aspects of AT in a developing country. Methodology: We conducted a retrospective study spanning 17 years (from January 2005 to October 2022) in four Dakar hospital services. We included all patient medical records with explored AT. Results: AT was diagnosed in 35 patients who had a mean age of 36.62 years (range: 12-79), and a female predominance (26 women to 9 men). Among these patients, 17.2 % had incidental AT. Hypertension was the commonest presenting symptom in 27 patients (77%), which was associated with Mnards triad in 14 patients (40%). Abdominal pain was reported by 20 patients (57%), and 14 presented with an abdominal mass. Among the patients, 29 had functional AT: 22 with pheochromocytoma, 5 with primary hyperaldosteronism, and 2 with hypercortisolism. Imaging evaluations revealed that 33 patients had unilateral AT and one had bilateral AT. Tumour sizes varied, 5 patients had tumours 10 cm. Two patients presented with metastases. The therapeutic approach involved adrenalectomy in 32 patients. Perioperative complications were observed in five patients, including haemorrhage (two patients), hypotension (two cases), and hypertensive crisis (one case). One patient with bilateral pheochromocytoma developed acute adrenal insufficiency postoperatively, followed by abdominal herniation. Histopathological examination confirmed pheochromocytoma in 21 patients, Conns adenoma in 5, adrenocortical carcinoma in 3, cortisol adenoma in 2, and adrenal cyst in 1 patient. Non-functional AT included adrenocortical carcinoma (three patients), adrenal cyst (one patient), and pheochromocytoma (two patients). After a one-year follow-up, 29 patients with benign tumours had favourable outcomes, while death occurred within six months of diagnosis in five cases. A patient who had bilateral pheochromocytomas, with complications, died before surgery. Conclusion: In our practice, AT are predominantly pheochromocytomas, being typically diagnosed when they become symptomatic large tumours and, due to this large size, laparotomy is the preferred surgical approach. Unfortunately, the prognosis for malignant tumours is poor.展开更多
基金supported by the Project of the 940 Hospital of the Joint Logistics Support Force of the Chinese PLA(no.2021yxky057).
文摘Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datasets GSE67066 and GSE60458.The R software and various packages were utilized for the analysis of differentially expressed genes,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,receiver operating characteristic curve assessment,logistic model construction,and correlation analysis.The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks.In addition,the TIMER database was used to estimate the immune scores.Results:A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458,respectively.These genes are implicated in cytokine and cytokine receptor interactions,extracellular matrix–receptor interactions,and platelet activation signaling pathways.Notably,MAMLD1,UST,MATN2,LPL,TWIST1,SFRP4,FRMD6,RBM24,PRIMA1,LYPD1,KCND2,CAMK2N1,SPOCK3,and ALPK3 were identified as the key genes.Among them,MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers,whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration.Eight miRNAs were identified as potential regulators of key gene expression,and it was noted that TWIST1 might be regulated by SUZ12.Notably,the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.Conclusions:The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential.These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.
文摘Introduction: Pheochromocytoma is a rare cause of endocrine hypertension. We report the case of an extra-adrenal pheochromocytoma discovered in the setting of an abdominal mass. Observation: The patient was 25-year-old and presented with headaches, excessive sweating and palpitations, followed by a sensation of abdominal weightlessness and diastolic arterial hypertension. Abdominal computed tomography revealed a retroperitoneal, right para-renal extra-adrenal mass. In biology, an increase in urinary methoxylated derivatives at the expense of normetanephrine. Conclusion: Pheochromocytoma is a rare disease, diagnosed by measuring urinary or plasma methoxylated derivatives. Conventional or nuclear imaging allows topographic diagnosis. Genetic studies helps to identify other tumors.
文摘目的:分析生化阴性嗜铬细胞瘤及副神经节瘤(pheochromocytomas and paragangliomas,PPGLs)的电子计算机断层扫描(computed tomography,CT)征象是否有别于生化阳性PPGLs,同时了解生化阳性PPGLs不同表型的CT征象是否存在差异。方法:回顾性分析131例PPGLs患者的术前腹部增强CT图像,包括肿瘤位置、大小、形态、囊变坏死、液-液分层、钙化、向心结节状强化、肿瘤内粗大血管、强化包膜、绝对廓清率及相对廓清率。根据生化水平,将患者分为生化阳性组和阴性组,阳性组进一步分为去甲肾上腺素型、肾上腺素型及多巴胺型。比较各组及各表型间的CT征象差异。结果:相较于生化阴性组,阳性组PPGLs更大(Z=-2.064,P=0.039)、囊变坏死(χ2=6.610,P=0.010)及向心结节状强化(χ2=3.909,P=0.048)的比例更高;相较于去甲肾上腺素型,肾上腺素型PPGLs更大(Z=-2.036,P=0.042)、强化包膜比例更高(χ2=7.242,P=0.007)。结论:肿瘤大小、囊变坏死及向心结节状强化的CT征象有助于术前诊断生化阴性PPGLs,肿瘤大小及强化包膜有助于解释去甲肾上腺素型及肾上腺素型PPGLs不同临床表现产生的机制。
文摘目的探讨胰岛素瘤相关蛋白1(insulinoma-associated protein 1,INSM1)在嗜铬细胞瘤/副神经节瘤和肾上腺皮质腺瘤中的表达及其在鉴别诊断中的意义。方法采用免疫组化EnVision两步法检测INSM1在嗜铬细胞瘤/副神经节瘤和肾上腺皮质腺瘤中的表达。结果32例嗜铬细胞瘤中31例INSM1阳性(31/32,96.88%),其中高表达20例(20/32,62.50%)。9例肾上腺外副神经节瘤INSM1均阳性,其中高表达8例(8/9,88.89%)。33例肾上腺皮质腺瘤中INSM1均阴性。INSM1在嗜铬细胞瘤/副神经节瘤中的表达显著高于肾上腺皮质腺瘤(P<0.001)。INSM1高表达的嗜铬细胞瘤/副神经节瘤具有更高的Ki67增殖指数(P=0.016),但与患者性别(P=0.190)、年龄(P=0.439)、肿瘤TNM分期(P=0.793)、生长模式(P=0.495)、凝固性坏死(P=0.790)和脉管/包膜侵犯(P=0.790)均无显著相关性。INSM1鉴别嗜铬细胞瘤/副神经节瘤与肾上腺皮质腺瘤的敏感性为97.6%,特异性为100%,ROC曲线下面积为0.988。结论INSM1表达于嗜铬细胞瘤和副神经节瘤的细胞核,而不表达于肾上腺皮质腺瘤,可有效鉴别嗜铬细胞瘤/副神经节瘤和肾上腺皮质腺瘤。
文摘BACKGROUND Paraganglioma(PGL)located in the retroperitoneum presents challenges in diagnosis and treatment due to its hidden location,lack of specific symptoms in the early stages,and absence of distinctive manifestations on imaging.CASE SUMMARY A 56-year-old woman presented with a left upper abdominal mass discovered 1 wk ago during a physical examination.She did not have a history of smoking,alcohol consumption,or other harmful habits,no surgical procedures or infectious diseases,and had a 4-year history of hypertension.Upon admission,she did not exhibit fever,vomiting,or abdominal distension.Physical examination indicated mild percussion pain in the left upper abdomen,with no palpable enlargement of the liver or spleen.Laboratory tests and tumor markers showed no significant abnormalities.Enhanced computed tomography and magnetic resonance imaging of the upper abdomen revealed a cystic solid mass in the left epigastrium measuring approximately 6.5 cm×4.5 cm,with inhomogeneous enhancement in the arterial phase,closely associated with the lesser curvature of the stomach and the pancreas.The patient underwent laparoscopic resection of the retroperitoneal mass,which was successfully removed without tumor rupture.A 12-month postoperative follow-up period showed good recovery.CONCLUSION This case report details the successful laparoscopic resection of a retroperitoneal subclinical PGL,resulting in a good recovery observed at the 12-month follow-up.Interestingly,the patient also experienced unexpected cure of hypertensive disease.
基金Supported by The Finance Bureau of Dongguan City,Guangdong Province.
文摘BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.
文摘Introduction: Adrenal tumours (AT) are commonly encountered in clinical practice. For any patient presenting an adrenal mass, there are two crucial points to consider: is the adrenal mass malignant and is it hormonally active? The objective of our study was to evaluate the epidemiological, diagnostic, therapeutic, and evolutionary aspects of AT in a developing country. Methodology: We conducted a retrospective study spanning 17 years (from January 2005 to October 2022) in four Dakar hospital services. We included all patient medical records with explored AT. Results: AT was diagnosed in 35 patients who had a mean age of 36.62 years (range: 12-79), and a female predominance (26 women to 9 men). Among these patients, 17.2 % had incidental AT. Hypertension was the commonest presenting symptom in 27 patients (77%), which was associated with Mnards triad in 14 patients (40%). Abdominal pain was reported by 20 patients (57%), and 14 presented with an abdominal mass. Among the patients, 29 had functional AT: 22 with pheochromocytoma, 5 with primary hyperaldosteronism, and 2 with hypercortisolism. Imaging evaluations revealed that 33 patients had unilateral AT and one had bilateral AT. Tumour sizes varied, 5 patients had tumours 10 cm. Two patients presented with metastases. The therapeutic approach involved adrenalectomy in 32 patients. Perioperative complications were observed in five patients, including haemorrhage (two patients), hypotension (two cases), and hypertensive crisis (one case). One patient with bilateral pheochromocytoma developed acute adrenal insufficiency postoperatively, followed by abdominal herniation. Histopathological examination confirmed pheochromocytoma in 21 patients, Conns adenoma in 5, adrenocortical carcinoma in 3, cortisol adenoma in 2, and adrenal cyst in 1 patient. Non-functional AT included adrenocortical carcinoma (three patients), adrenal cyst (one patient), and pheochromocytoma (two patients). After a one-year follow-up, 29 patients with benign tumours had favourable outcomes, while death occurred within six months of diagnosis in five cases. A patient who had bilateral pheochromocytomas, with complications, died before surgery. Conclusion: In our practice, AT are predominantly pheochromocytomas, being typically diagnosed when they become symptomatic large tumours and, due to this large size, laparotomy is the preferred surgical approach. Unfortunately, the prognosis for malignant tumours is poor.
