Characterisation of an Adult Zebrafish Model for SDHB-Associated Phaeochromocytomas and Paragangliomas.

Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours arising from chromaffin cells. Pathogenic variants in the gene succinate dehydrogenase subunit B (SDHB) are associated with malignancy and poor prognosis. When metastases arise, limited treatment options are available. The pathomechanism of SDHB-associated PPGL remains largely unknown, and the lack of suitable models hinders therapy development. Germline heterozygous SDHB pathogenic variants predispose to developing PPGLs with a life-long penetrance of around 50%. To mimic the human disease phenotype, we characterised adult heterozygous sdhb mutant zebrafish as a potential model to study SDHB-related PPGLs. Adult sdhb mutant zebrafish did not develop an obvious tumour phenotype and were anatomically and histologically like their wild-type siblings. However, sdhb mutants showed significantly increased succinate levels, a major hallmark of SDHB-related PPGLs. While basal activity was increased during day periods in mutants, mitochondrial complex activity and catecholamine metabolite levels were not significantly different. In conclusion, we characterised an adult in vivo zebrafish model, genetically resembling human carriers. Adult heterozygous sdhb mutants mimicked their human counterparts, showing systemic elevation of succinate levels despite the absence of a tumour phenotype. This model forms a promising basis for developing a full tumour phenotype and gaining knowledge of the pathomechanism behind SDHB-related PPGLs.

The Role of Internal Carotid Artery Stent in the Management of Skull Base Paragangliomas.

Background: After two decades from its introduction in the lateral skull base paraganglioma surgery, the indications and results of preoperative internal carotid artery stenting should be critically assessed. Materials and Methods: Monocentric retrospective study on 26 patients affected by head and neck paragangliomas (19 tympanojugular paragangliomas, 4 carotid body paragangliomas, 3 vagal paragangliomas) preoperatively treated with internal carotid artery stents between 2008 and 2023. The preoperative findings, the intraoperative complications and the final surgical results were analyzed. Results: The stent complication rate was less than 3.1%. Self-expanding highly flexible intracranial nitinol stents were applied. In all cases, it was possible to completely mobilize the internal carotid artery and perform a vascular dissection of the tumor. Gross total tumor resection was possible in 85% of cases. The median follow up was 7.83 y (SD +/- 3.93 y). No local recurrence was observed. Conclusions: The preoperative vascular stent facilitates tumor dissection from the internal carotid artery without risk of vascular damage, helping the surgeon to achieve surgical radicality. The vascular stent is indicated in the case of revision surgeries, circumferential involvement of the vessel and in cases with non-insufficient intracerebral crossflow. Procedural complications, temporary antiplatelet therapy and delay of surgery are the limitations of the procedure.

Inferior Laryngeal Nerve Paraganglioma With Norepinephrine Hypersecretion Diagnosed Shortly After Pregnancy.

The diagnosis of pheochromocytoma or paraganglioma (PGL) during pregnancy is extremely rare, with 2 large case series suggesting that the prevalence is between 0.0002% and 0.007%. Here, we present a case of a 38-year-old woman who presented during pregnancy with clinical features suggestive of preeclampsia and was found to have a norepinephrine-secreting inferior laryngeal nerve PGL, which was diagnosed after pregnancy. She underwent uncomplicated surgical resection and genetic testing revealed a succinate dehydrogenase subunit B (SDHB) pathogenic variant. In conclusion, PGLs diagnosed during pregnancy and hypersecreting head and neck PGLs are both rare clinical entities. Hyperfunctioning PGLs may mimic pregnancy-induced hypertension or preeclampsia. Metanephrine testing should be considered in patients with atypical features and can be reliably assessed using nonpregnant reference ranges. Overall, maternal and fetal mortality has improved considerably with early diagnosis and treatment.

Pre-clinical phaeochromocytoma and paraganglioma models: Cell lines, animal models, and a human primary culture model.

While the establishment of human phaeochromocytoma and paraganglioma (PPGL) cell lines has proven to be particularly difficult over several decades of research, there are other reliable pre-clinical PPGL models currently available. This review provides a summary of these models, together with our recently established personalised drug screening platform using patient-derived PPGL primary cultures. Such currently available PPGL models include murine and rat PPGL cell lines, of which only one cell line (PC12) is publicly accessible through a cell repository, and PPGL animal models, of which the patient-derived xenograft models are promising but complex to establish. We have developed next-generation implementation of human PPGL primary cultures, enabling reliable and personalised drug screening and an individualised analysis of tumour drug responsivity based on the tumour's unique genetic, biochemical, immunohistochemical and clinical profile. Overall, reliable PPGL models, including patient-derived primary culture models, are essential to advance pre-clinical research in the field of PPGLs.

Presentation of metastatic carotid body paraganglioma on F-18 FDG PET/CT: a rare disease.

Carotid body paraganglioma is a slow growing tumor of head and neck region. It can rarely be malignant in nature which is characterized by distant metastases on anatomical imaging. We share an interesting presentation of a malignant carotid body on F-18 FDG PET/CT in form of liver and skeletal metastases.

[Adrenal tumors: current standards in clinical management]. / Nebennierentumoren ­ aktuelle Standards im klinischen Management.

Adrenal tumors are among the most common tumors in humans. They are most frequently discovered incidentally during abdominal imaging for other reasons or due to clinical symptoms (e.g. Conn's or Cushing's syndrome, pheochromocytoma or androgen excess). Although over 80% of adrenal tumors are benign, in cases of hormone excess, they are associated with significantly increased morbidity. In highly malignant adrenocortical carcinoma (ACC), early diagnosis is of particular prognostic relevance. Therefore, this review presents the diagnostic procedure for what are referred to as adrenal incidentalomas and provide recommendations for the management of ACC and pheochromocytomas/paragangliomas (PPGL). In primary diagnosis, sufficient hormone diagnostics is required for all adrenal tumors, as this is the only way to identify all patients with relevant hormone excess. Imaging has increasingly improved in recent years and allows a reliable assessment of the tumor's malignancy in most cases. Imaging of first choice is unenhanced computed tomography (CT), while magnetic resonance imaging (MRI) and fluorodeoxyglucose-18 positron emission tomography (FDG-PET/CT) are reserved for special situations, as published evidence on these procedures is more limited. The treatment of ACC and PPGL is complex and is carried out on an interdisciplinary basis at specialized centers. In the case of localized disease, surgery is the only curative treatment option. There are now clear recommendations for individualized adjuvant therapy for ACC. In metastatic disease, mitotane with or without platinum-containing chemotherapy is the standard. Other lines of therapy should be discussed with a reference center. Over 35% of PPGL have a germline mutation; therefore, genetic testing should be offered. In metastatic PPGL, an individual decision is required between active surveillance, radionuclide therapy, sunitinib or chemotherapy.

Immunohistochemical Profiling of SSTR2 and HIF-2α with the Tumor Microenvironment in Pheochromocytoma and Paraganglioma.

Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare endocrine malignancies with limited effective treatment options. The association between the tumor microenvironment (TME) with somatostatin receptor 2 (SSTR2) and hypoxia-induced factor-2α (HIF-2α) in PPGLs, critical for optimizing combination therapeutic strategies with immunotherapy, remains largely unexplored. To evaluate the association of SSTR2 and HIF-2α immunoreactivity with the TME in patients with PPGLs, we analyzed the expression of SSTR2A, HIF-2α, and TME components, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (CD68 and CD163), and PD-L1, using immunohistochemistry in patients with PPGLs. The primary outcome was to determine the association of the immune profiles with SSTR2A and HIF-2α expression. Among 45 patients with PPGLs, SSTR2A and HIF2α were positively expressed in 21 (46.7%) and 14 (31.1%) patients, respectively. The median PD-L1 immunohistochemical score (IHS) was 2.0 (interquartile range: 0-30.0). Positive correlations were observed between CD4, CD8, CD68, and CD163 levels. A negative correlation was found between the CD163/CD68 ratio (an indicator of M2 polarization) and SSTR2A expression (r = -0.385, p = 0.006). HIF-2α expression showed a positive correlation with PD-L1 IHS (r = 0.348, p = 0.013). The co-expression of PD-L1 (HIS > 10) and HIF-2α was found in seven patients (15.6%). No associations were observed between SDHB staining results and the CD163/CD68 ratio, PD-L1, or SSTR2A expression. Our data suggest the potential of combination therapy with immunotherapy and peptide receptor radionuclide therapy or HIF-2α inhibitors as a treatment option in selected PPGL populations.

Case report: A novel somatic SDHB variant in a patient with bladder paraganglioma.

Background: Paragangliomas (PGL) are rare neuroendocrine tumors derived from the autonomic nervous system paraganglia. Urinary bladder paragangliomas (UBPGL) originate from the sympathetic neurons of the urinary bladder wall and represent 0.7% of all paragangliomas and <0.05% of all bladder tumors. PGL and UBPGL can be associated with SDHB, SDHD, NF1, and VHL gene variants, with the most common germline alterations found in SDHB and VHL. Case report: We report a case of a 42-year-old woman who presented with menorrhagia/hematuria, uterine leiomyomas, as well as cardiac and bladder masses. The cardiac mass was favored to be a myxoma based on clinical findings, while the bladder mass was diagnosed as UBPGL. A novel SDHB mutation (c.642G>A, p Q214Q), detected in the UBPGL, was proven to be somatic. Although this variant was seemingly synonymous, it was predicted to have a loss of function due to the splice site effect, which was further supported by the immunohistochemical loss of SDHB. Conclusion: This case highlights the challenges of diagnosing an extremely rare entity, bladder paraganglioma, with an emphasis on the multidisciplinary approach to navigate various clinical and imaging findings that may initially be misleading. In addition, a novel loss of function SDHB variant that could have been overlooked as a synonymous variant is herein reported, while also illustrating the importance of both germline and somatic mutation testing.

Basaloid squamous cell carcinoma clinically and radiologically masquerading as a head and neck paraganglioma: a case report and review of the literature.

BACKGROUND: This paper reports the first case of basaloid squamous cell carcinoma clinically and radiologically masquerading as a head and neck paraganglioma. CASE PRESENTATION: A 66-year-old Sinhalese male with unilateral hearing impairment and 7th-12th (excluding 11th) cranial nerve palsies was diagnosed radiologically with a head and neck paraganglioma by magnetic resonance imaging of the brain, which revealed a hypointense and hyperintense punctate mass centered at the jugular fossa with intracranial extension. The ascending pharyngeal artery, recognized as the major feeder, was embolized by percutaneous embolization following digital subtraction angiography. Gross total resection of the tumor was followed by an uneventful postoperative recovery. Combined immunohistochemistry and histopathological morphology revealed a basaloid squamous cell carcinoma, following which the patient completed radiotherapy and is at 3-month follow-up currently. CONCLUSION: This case report discusses the diagnostic pitfalls and management challenges of this rare entity on the basis of prior evidence, as well as a literature review and clinical and surgical analysis.

Analysis of clinical and pathological characteristics of retroperitoneal paraganglioma and associated prognostic factors.

BACKGROUND AND OBJECTIVES: The aim of this study is to explore the long-term prognostic risk factors associated with patients diagnosed with retroperitoneal paraganglioma (RPGL) and examine their clinical and pathological characteristics. METHODS: Expressions of biomarkers were identified using immunohistochemistry (IHC) and case databases were retrospectively searched. Survival analysis was performed using Kaplan-Meier and Cox risk regression to identify the factors that influence the postoperative progression-free survival of patients with RPGL. RESULTS: A total of 105 patients, most of whom had tumors situated in the paraaortic region, and whose average tumor size was 8.6 cm, were enrolled in this study. The average follow-up duration was 51 months, with a mortality rate of 19% and a recurrence and metastasis rate of 41.9%. Tumors were assessed using the modified Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP), and SDHB, S-100, and Ki-67 were stained using IHC in all cases. Out of the total cases examined, negative in SDHB expression were observed in 18.1% of cases, S-100 expression was negative in 36.2% of cases, and endovascular tumor enboluswas present in approximately 25.7% of cases. The results of the univariate analysis indicated that several factors significantly influenced the progression-free survival of patients with PGL as follow: maximum tumor diameter (>5.5 cm), tumor morphological features, tumor grading (modified GAPP score > 6), SDHB negative, S-100 negative, and expression of proliferation index Ki-67 (>3%) (X2 = 4.217-27.420, p < 0.05). The results of the multivariate analysis indicated that negative of S-100 (p = 0.021) and SDHB (p = 0.038), as well as intravascular tumor thrombus (p = 0.047) expression were independent risk factors for progression-free survival in patients. CONCLUSION: RPGL is characterized by diverse biological features and an elevated susceptibility to both recurrence and metastasis. Both SDHB and S-100 can be employed as traditional IHC indicators to predict the metastatic risk of PGL, whereas the tumor histomorphology-endovascular tumor enbolus assists in determining the metastasis risk of RPGL.

Discovering a novel genetic variant in 11 family members who had isolated pheochromocytoma linked to von Hippel-Lindau (VHL) syndrome, aligning with the type 2c phenotype.

INTRODUCTION: Von Hippel-Lindau disease (e.g. VHL) is an autosomal dominant multi-organ cancer syndrome caused by a mutation in the VHL tumour suppressor gene. In this study, we introduce a novel genetic variant found in 11 family members diagnosed initially with isolated Pheochromocytoma. Subsequent findings revealed its association with VHL syndrome and corresponds to the Type 2 C phenotype. METHODS: The VHL gene was amplified through the utilisation of the polymerase chain reaction (PCR). PCR fragments were sequenced using bidirectional Sanger sequencing, using BigDye™ Terminator v3.1 Cycle Sequencing Kit, running on the 3500 genetic analyser. Results were assembled and analysed Using Software SeqA and chromas pro. RESULTS: A heterozygous in-frame duplication of three nucleotides, specifically ATG, c.377_379dup; p.Asp126dup in exon 2, was identified in all the patients tested within the pedigree. CONCLUSION: In this study, we disclose the identification of a novel genetic variant in a Jordanian family, affecting eleven family members with pheochromocytoma associated with VHL disease. This finding underscores the importance of screening family members and contemplating genetic testing for individuals newly diagnosed with pheochromocytoma and could enhance our comprehension of the potential adverse consequences associated with VHL germline mutations.

Goal: To study a novel gene change in a family with Von Hippel-Lindau (e.g. VHL) syndrome, which increases cancer chances.Participants: 11 family members with Pheochromocytoma, a tumour linked to VHL.Methods:Used PCR to copy the VHL gene.Analysed the gene using Sanger sequencing.Findings:Found a novel gene change in all family members. This change, called an in-frame duplication, affects a protein.It's in a specific part of the gene.Conclusion:Stressing the importance of genetic testing for Pheochromocytoma patients to grasp VHL mutation risks.

Therapeutic Strategy for Functional Metastatic Malignant Paraganglioma: A Case Report and Review of the Literature.

Paraganglioma is a rare neuroendocrine tumor that arises outside of the adrenal gland, typically originating from the chromaffin tissue of the sympathetic or parasympathetic ganglia. It can manifest at any age, with a peak incidence occurring between 40 and 50 years old. When the tumor secretes catecholamines, it is referred to as "functional." Currently, there is no standardized therapeutic approach. However, the management of metastatic forms is based on a systemic treatment with tri-chemotherapy. Herein, we present the case of a young male patient with heavily metastatic functional malignant paraganglioma, which represents the first case managed in our department. After seven months of Somatuline treatment, our patient experienced disease progression. Subsequently, he received tri-chemotherapy comprising cyclophosphamide, vincristine, and dacarbazine, which proved to be suboptimal due to poor hematological tolerance and a progression-free survival of less than three months. In the third line of treatment, Sunitinib was administered, but the therapeutic response was poor, with clinical progression observed within two months, ultimately leading to the patient's demise at home. The overall survival was two years.

A Rare Differential of Epistaxis.

Glomus tympanicum is a type of glomus tumor that affects the middle ear, located at the auricular branch of the vagus nerve. Glomus tumors, in general, are rare, slow-growing tumors and may not require surgery in some patients. It can be challenging to manage due to its hypervascularity, location, and advanced stage of diagnosis. Although glomus tympanicum commonly presents with pulsatile tinnitus and conductive hearing loss, it presented in our patient with large-volume hemoptysis and epistaxis, requiring urgent diagnostic and therapeutic interventions. We highlight the unique presentation of a 48-year-old female with sudden onset large-volume hemoptysis and epistaxis, leading to the discovery of a hypervascular glomus tympanicum in the right middle ear, identified via MRI. On arrival, her vitals were within normal limits, and a physical examination was pertinent for the obvious ongoing bleeding from her mouth. The examination revealed increased respiratory effort and bilateral crackles. Laboratory values were pertinent for hemoglobin of 11.8 g/dl. Ear examination revealed a large, vascular-appearing mass filling the right ear. An MRI of the face and neck showed an avidly enhancing 3.7 cm x 1.8 cm x 1.2 cm mass within the right middle ear and mastoid cavity, extending into the external auditory canal and through the eustachian tube into the nasopharynx. The mass was inseparable from the lateral border of the internal auditory canal in the petrous canal. Due to concern for glomus tympanicum, the patient underwent urgent embolization and subsequent tumor resection. Considering our patient initially presented large-volume hemoptysis, there was concern for alveolar hemorrhage. However, as she had no increased oxygen requirement, there was suspicion of massive epistaxis mistaken for hemoptysis. Due to large volume epistaxis, she underwent urgent embolization as resection could have been challenging due to increased vascularity. It is important to remember that massive epistaxis may not present with blood in the anterior nares, thereby delaying diagnosis and management. Furthermore, probing such tumors should be avoided as it may lead to life-threatening bleeding.

Rocuronium Can Trigger a Hypertensive Crisis in a Patient With Paraganglioma: A Case Report.

We present a case of rocuronium-induced hypertensive crises that occurred twice in a patient with paraganglioma. An 86-year-old woman was first scheduled for laminectomy for lumbar spinal stenosis. Five minutes after intravenous induction of anesthesia using fentanyl, propofol, rocuronium, and remifentanil, the patient's blood pressure (BP) and heart rate (HR) suddenly increased with no stimuli. Surgery was postponed because the patient was suspected of having pheochromocytoma. After that, paraganglioma was diagnosed, and surgery for removal of the paraganglioma was scheduled after the commencement of alpha-blocker therapy. The patient's hemodynamic parameters remained stable when anesthesia was induced with an infusion of remimazolam. Subsequently, immediately after rocuronium was administered as an intravenous bolus, the patient's arterial BP and HR increased, and plasma concentrations of noradrenaline and rocuronium had markedly increased. Ten minutes after the administration of rocuronium, the patient's BP and HR gradually and fully recovered without any intervention. The plasma concentrations of both noradrenaline and rocuronium also concurrently decreased. We conclude that simultaneous increases in BP, HR, and plasma concentration of noradrenaline revealed a direct correlation with rocuronium.

Preoperative embolisation of head and neck paragangliomas - a single-centre experience.

INTRODUCTION: Paragangliomas are neuroendocrine tumours commonly located in the abdomen, thorax, head and neck. The definitive treatment for these tumours is surgical resection, which in some cases can be very challenging due to the involvement of critical neurovascular structures and their high vascularity. Therefore, pre-operative embolisation may be performed to reduce the risk of complications. This study aimed to present our experience with endovascular embolisation of head and neck paragangliomas (HNP). MATERIAL AND METHODS: In this single-centre study, we reviewed data from consecutive patients with HNP who underwent pre-operative embolisation from 2017 to 2023. The efficacy of embolisation, the method of embolisation, as well as the rate of complications, were noted. RESULTS: A total of 27 patients (15 females) with an average age of 47 years underwent selective embolisation of HNP. Satisfactory embolisation, defined as occlusion of > 75% of the blood supply, was achieved in 22/27 cases (81.5%). The most commonly used embolic agents included coils and microspheres. With the exception of minor vessel dissections in two patients and embolic agent migration in two patients causing reversible occlusion of the intracranial vessels, there were no other complications associated with embolisation. No neurological deficits occurred in relation to the endovascular procedure. CONCLUSIONS: The results of our study indicate that endovascular embolisation of HNP prior to surgical resection is a safe and efficacious procedure, with a relatively low complication rate and associated morbidity.

Outcomes of Head and Neck Neurogenic Tumors.

BACKGROUND: Lateral neck mass management frequently challenges surgeons. Nerve tissue neoplasms are an uncommon cause of such nodules. Neurogenic tumors form a tiny percentage of the head and neck neoplastic lesions. Considering the number of nerves in this area, it is surprising that such neoplasms are not more frequently seen. METHODS: A retrospective study was conducted on all patients who presented to the National Cancer Institute of Cairo, Egypt, with head and neck neurogenic neoplasms. RESULTS: During the last 10 years at the National Cancer Institute of Egypt (2006-2015), 40 cases of neurogenic tumors of the head and neck were treated at the head and neck unit. Patients' ages ranged from two to 78 years with a mean age of 34.7 years. Childhood neurogenic tumors accounted for nine cases (22.5%) only in this study. Male patients diagnosed with these tumors comprised 16 cases, while female patients comprised 24 cases, with a female-to-male ratio of 1.5:1. Patient presentation depends on the biological behavior of the tumor; for instance, some of them present by slowly growing painless well-circumscribed mobile swelling, and others present by rapidly growing swelling with neurological deficit. Clinical picture and imaging studies such as CT and MRI raise suspicion and may help delineate such tumors, but a definitive diagnosis is obtained by tissue biopsy. Surgery is the mainstay of treatment in most head and neck neurogenic tumors, whereas adjuvant therapy is of limited benefit in some types of neurogenic tumors. The five-year survival rate was 60% for the malignant group, while death was reported in six out of 15 cases (40%).  Conclusion: Most neurogenic head and neck tumors are benign. Accurate preoperative assessment and a high degree of suspicion are the initial steps in the management. Proper treatment involves complete surgical excision; however, debulking procedures have an important role. Malignant neurogenic tumors are aggressive and are treated with combined radical surgical resection and radiation. Chemotherapy is tried for locally advanced unresectable or metastatic disease.

Paragangliomas of the Head and Neck: A Review of the Latest Diagnostic and Treatment Methods.

Background and objectives: Paragangliomas of the head and neck are rare, slow-growing neuroendocrine tumors, benign in their vast majority, but with a possibility of developing distant metastases. They show great inheritable character, and their behavior has proven to be unpredictable; therefore, they are considered malignant. Material and methods: This article aims to offer a more comprehensive presentation of the pathogenesis, epidemiology, diagnostic methods, imaging development, and treatment guidelines. We tried to bring together all the necessary data that, in our opinion, a head and neck practitioner should know when managing this type of tumor. Our main focus is on the most recent studies, with the purpose of a homogenous presentation of all current guidelines and approaches to this pathology. Results: Paragangliomas of the head and neck are still a disputed topic. One of the main reasons for that is their low incidence of 0.3 to 1 per 100,000 every year. The most frequent locations are the carotid body, the temporal bone, the jugular and mastoid foramen, and the vagal nerve. Their clinical presentation usually involves a painless lateral mass associated with symptoms such as hoarseness, hearing loss, tinnitus, and cranial nerve deficits. Up to 40% of them are inherited, mostly linked with mutations of succinate dehydrogenase complex. Imaging evaluation consists of CT and MRI, and new functional explorations such as 18F-FDA and 18F-FDG PET/CT, 18F-DOPA PET, 123I-MIBG, and 68Ga-DOTATE PET/CT. Measuring the catecholamine levels in the plasma and urine is mandatory, even though paragangliomas of the head and neck rarely display secretory behavior. Treatment mainly consists of surgery, with different approaches and techniques, but conservative management methods such as wait and scan, radiotherapy, proton therapy, and chemotherapy have proven their efficiency. The therapeutical decision lacks consensus, and current studies tend to recommend an individualized approach. Guidelines regarding long-term follow-up are still a matter of debate.

Clinical and molecular markers guide the genetics of pheochromocytoma and paraganglioma.

Over the past two decades, research into the genetic susceptibility behind pheochromocytoma and paraganglioma (PPGL) has surged, ranking them among the most heritable tumors. Massive sequencing combined with careful patient selection has so far identified more than twenty susceptibility genes, leading to an over-detection of variants of unknown significance (VUS) that require precise molecular markers to determine their pathogenic role. Moreover, some PPGL patients remain undiagnosed, possibly due to mutations in regulatory regions of already known genes or mutations in undiscovered genes. Accurate classification of VUS and identification of new genes require well-defined clinical and molecular markers that allow effective genetic diagnosis of most PPGLs.

An Unusual Case of Pheochromocytoma Associated with von Hippel-Lindau Disease and Lynch Syndrome During Pregnancy.

Pheochromocytomas (PCCs) and/or paragangliomas (PGLs) are a challenge to diagnose during pregnancy because of elusive signs and testing difficulties. We report a 25-year-old woman with no pertinent medical history who presented to the hospital with hypertension, vision loss, and weakness and was initially diagnosed with preeclampsia. Imaging showed hemangioblastomas in the medulla and thoracic spine, pancreatic cysts, and a renal cyst. The endocrinology service was consulted for possible PCCs associated with von Hippel-Lindau disease (VHL). Serum and urine normetanephrine levels were elevated despite the lack of overt PCCs/PGLs seen on magnetic resonance imaging and magnetic resonance angiography. The patient was medically managed with doxazosin and then labetalol. Despite successful resection of the hemangioblastoma in the medulla, the patient suffered respiratory distress requiring tracheostomy and venous-venous extracorporeal membrane oxygenation (V-V ECMO) and fetal demise. After 3 months, the patient was discharged to rehabilitation. Follow-up genetics were heterozygous for VHL and Lynch syndrome. DOTATATE positron emission tomography/computed tomography scan showed a small hepatic focus of a maximum standard uptake value of 12.1. Altogether, this case illustrates the importance of prompt diagnosis and proper management of PCCs/PGLs during pregnancy and incorporating genetic information during surveillance to lower morbidity and mortality.