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.

Paraganglioma of the Neck: A Rare Case With Spinal Metastasis.

Paragangliomas are rare neuroendocrine tumors that arise from the paraganglia, which are clusters of neuroendocrine cells associated with the autonomic nervous system. These tumors are commonly found in the adrenal medulla but can also occur in other locations outside the adrenal gland. Here, we present a case report of a slow-growing paraganglioma in the left neck with spinal metastasis in a 60-year-old man. This case highlights the importance of considering paraganglion tumors in the differential diagnosis of neck masses and the need for early diagnosis and management to prevent potential complications. Importantly, both the clinical picture and anatomical location of these tumors is important when determining treatment plans.

Stealthy Encroachment: Unraveling an Encounter With Renal Myelolipoma.

Myelolipoma of the kidney is an exceedingly unusual benign tumor of hematological components mixed with mature adipose tissue. We present a case of a 59-year-old male who presented with left flank pain and was found to have an atrophic left kidney on imaging studies. A computed tomography (CT) scan revealed a small and shrunken left kidney with an extrarenal pelvis. A diethylenetriamine pentaacetate (DTPA) scan results showed a total glomerular filtration rate (GFR) of 45.6 ml/min with a non-functional left kidney. The patient underwent a left nephrectomy, and a histopathological examination confirmed the diagnosis and highlighted the distinctive morphological features of this rare entity. Postoperatively, the patient experienced a complete resolution of symptoms. This case underscores the importance of considering myelolipoma in the differential diagnosis of renal masses and highlights the successful management of symptomatic cases through surgical intervention. Awareness of this rare tumor is crucial for accurate diagnosis and appropriate management. Further studies are needed to elucidate the natural history and optimal treatment strategies for renal myelolipomas.

Robotic Resection in Succinate Dehydrogenase Subunit B (SDHB)-Mutated Hereditary Paraganglioma: A Case Report of Two Patients and A Literature Review.

Autosomal dominant hereditary paraganglioma-pheochromocytoma syndrome (HPPS) is a rare genetic disorder characterized by neuroendocrine tumor development associated with pathogenic variants in succinate dehydrogenase (SDH) enzyme complex genes. Particularly, HPPS linked to SDHB mutation poses a significant clinical challenge due to its association with aggressive tumor features and a high risk of malignancy. Our report underscores the diversity in the presentation of patients with SDHB-mutated paraganglioma and the feasibility of managing it with a minimally invasive surgical approach. In the first case, a 17-year-old female was diagnosed with a metabolically active, poorly differentiated extra-adrenal retroperitoneal paraganglioma that required challenging robotic resection. Cascade genetic testing revealed an SDHB mutation not only in her but also in three family members, pointing to the inherited nature of the syndrome. Conversely, the second case involves a 37-year-old male with an asymptomatic well-differentiated left paraaortic paraganglioma incidentally found during an unrelated medical examination. Robotic converted-to-open resection allowed the successful removal of the mass. Subsequent germline testing confirmed a deleterious SDHB mutation, initiating a process of familial cascade testing. Both patients remained symptom- and recurrence-free at 12 and six months, respectively. Through these cases, and supported by a literature review, we highlight the variable clinical presentations of HPPS, arising from the same genetic alteration. The successful application of minimally invasive surgical techniques, combined with genetic evaluation, emphasizes the necessity for a comprehensive, tailored approach to treatment and surveillance. This strategy not only addresses the immediate clinical needs but also fosters proactive management of at-risk family members, ensuring a multidisciplinary approach to this complex hereditary condition.

Paraganglioma at the cerebellopontine angle: A case report and review of literature.

Paragangliomas (PGLs) are rare neuroendocrine tumors. Sometimes, these tumors secrete excessive catecholamines, which results in the manifestations of various signs and symptoms, usually with a triad of hypertension, tachycardia, and headache. We report the case of a 42-year-old woman presenting with uncontrolled hypertension, right facial palsy, vomiting, and disturbed gait. Diagnosis for PGL was confirmed on postoperative histological examination of the excised mass and correlated with preoperative clinical and radiological findings. Tumor excision was done via a suboccipital craniotomy approach. Our case presents the typically severe features of a jugulotympanic PGL, but most importantly, it highlights the necessity of biochemical diagnosing, thorough probing of the causes of hypertension, and a multi-disciplinary approach in dealing with these tumors. Moreover, the case emphasizes necessitating the use of preoperative embolization in vascular tumors of the head and neck to avoid a hemorrhagic crisis during surgery. Unfortunately, due to a lack of adequate hospital funds, the surgeon had to proceed without preoperative embolization. Despite such a risk, the excision was a success.

A rare case report of ectopic-adrenal paraganglioma with inferior vena cava infiltration. Case report and literature review.

INTRODUCTION AND IMPORTANCE: Phaeochromocytomas are neuroendocrine neoplasms arising from chromaffin cells of the adrenal medulla and are known as intra-adrenal paragangliomas. On the contrary, paragangliomas are non-epithelial neuroendocrine neoplasms that produce other peptide hormones such as norepinephrine, epinephrine, and dopamine. In a setting with limited resources, such a condition may result in inaccurate diagnosis and treatment, which may lose a patient life if left untreated. In addition, PPGLs present a surgical challenge to many surgeons who are not thoroughly prepared. CASE PRESENTATION: We describe a case of extra-adrenal paraganglioma in a 27-year-old female who presented with symptoms of heartbeat awareness for almost a year and abdominal swelling for three months. Physical examination revealed a palpable mass around the umbilicus. Abdominal pelvic CT scan revealed a well-circumscribed mass in the central retroperitoneum displacing the IVC laterally and abdominal aorta medially with no invasion of surrounding structures. Results for pheochromocytoma workup showed elevated levels of 24-h urine Vanillylmandelic acid (VMA), and 24-h metanephrine excretion. Laparotomy through extended midline incision was done with successful excision of the tumor. The blood pressure, which was initially high normalized after surgery. DISCUSSION: The diagnosis of a malignant EAP is commonly made based on recurrence and the development of metastasis to lymph nodes or to other organs. Our patient presented with similar symptoms as pheochromocytoma. Compared to the commonly stated 10 % risk for pheochromocytomas, people with EAPs have been observed to have a 20 % to 50 % incidence of malignancy. EAPs account for at least 15 % of adult and 30 % of pediatric pheochromocytomas and are frequently found in the Zuckerkandl organ. Pheochromocytoma symptoms may manifest asymptomatically in patients with EAPs, or they may occur because of compression of nearby tissues. Surgical excision of the tumor is always the best option in managing EAP. CONCLUSION: Extra-adrenal paragangliomas can be successfully managed surgically, provided there is a multidisciplinary team, and the tumor location is well recognized and can reduce the chance of tumor metastasis.

[Paraganglioma of the urinary bladder-a rare, but relevant differential diagnosis]. / Das Paragangliom der Harnblase ­ eine seltene, aber relevante Differentialdiagnose.

A paranglioma is a rare, extra-adrenal neuroendocrine tumour. Paraganglioma of the urinary bladder is very rare, accounting for < 1% of all paranglioma and only 0.05% of all bladder tumours. Presentation varies greatly and its clinical significance is dependent on the tumour functionality. Since paranglioma may look histologically very similar to urothelial carcinomas, the risk of misdiagnosis is relatively high, with considerable therapeutic and medicolegal consequences. This case describes an incidental paraganglioma of the urinary bladder, diagnosed cystoscopically due to painless microhaematuria and confirmed histologically after performing several immunohistochemical examinations.

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.

Mesenteric Paraganglioma: A Case Report and Literature Review.

We report a rare case of a solitary paraganglioma arising from the small bowel mesentery, found in a 70-year-old female who presented with abdominal pain. Paragangliomas are rare neuroendocrine, neural crest-derived tumors, most commonly found in the adrenal medulla. While extra-adrenal paragangliomas arise from diverse locations, mesenteric origins are extremely rare. Our comprehensive review shows 35 previously documented cases and updates the epidemiology, clinical features, and outcomes of mesenteric paragangliomas.

Resection of Retroperitoneal Extra-Adrenal Pheochromocytoma: A Case Report.

Extra-adrenal pheochromocytomas are rare catecholamine-producing tumors that arise from chromaffin cells outside the adrenal glands. We report on the case of a 62-year-old male who initially presented with upper respiratory tract symptoms and was found to have a suprapubic pelvic mass and an asymptomatic right inguinal hernia. The diagnostic evaluation involved an abdominal ultrasound, a CT scan, followed by an MRI, which revealed a well-marginated large mass whose characteristics indicated a retroperitoneal sarcoma. Upon successful surgical resection, the mass was found to be encapsulated and no peripheral structure invasion was present; the right inguinal hernia was repaired, and a double J-stent was placed. Histopathological examination revealed extra-adrenal pheochromocytoma. This case report sheds light on diagnostic and therapeutic challenges when dealing with extra-adrenal pheochromocytomas and the importance of considering them as a differential diagnosis when presented with a case of retroperitoneal mass.

A case of perirenal extra-adrenal myelolipoma mimicking liposarcoma.

Myelolipoma is a benign tumor composed of mature adipose tissue and normal hematopoietic components. It usually occurs in the adrenal glands but rarely in the extra-adrenal region. However, it is difficult to differentiate extra-adrenal myelolipoma from well-differentiated liposarcoma on the basis of the radiological findings. We report the case of a 66-year-old male with perirenal and extra-adrenal myelolipoma who underwent radical tumor resection with nephrectomy after a preoperative diagnosis of liposarcoma. Intraoperative assessment by the surgeon and intraoperative pathological evaluation are important considering the divergent prognoses of myelolipoma and liposarcoma.

Lesion-based indicators predict long-term outcomes of pheochromocytoma and paraganglioma- SIZEPASS.

Aim: We seek a simple and reliable tool to predict malignant behavior of pheochromocytoma and paraganglioma (PPGL). Methods: This single-center prospective cohort study assessed size of primary PPGLs on preoperative cross-sectional imaging and prospectively scored specimens using the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS). Multiplication of PASS points with maximum lesion diameter (in mm) yielded the SIZEPASS criterion. Local recurrence, metastasis or death from disease were surrogates defining malignancy. Results: 76 consecutive PPGL patients, whereof 58 with pheochromocytoma and 51 female, were diagnosed at a mean age of 52.0 ± 15.2 years. 11 lesions (14.5%) exhibited malignant features at a median follow-up (FU) of 49 months (range 4-172 mo). Median FU of the remaining cohort was 139 months (range 120-226 mo). SIZEPASS classified malignancy with an area under the curve (AUC) of 0.97 (95%CI 0.93-1.01; p<0.0001). Across PPGL, SIZEPASS >1000 outperformed all known predictors of malignancy, with sensitivity 91%, specificity 94%, and accuracy 93%, and an odds ratio of 72 fold (95%CI 9-571; P<0.001). It retained an accuracy >90% in cohorts defined by location (adrenal, extra-adrenal) or mutation status. Conclusions: The SIZEPASS>1000 criterion is a lesion-based, clinically available, simple and effective tool to predict malignant behavior of PPGLs independently of age, sex, location or mutation status.

Non-Functional Yet Terminal: A Case of Asymptomatic Retroperitoneal Paraganglioma With Distant Metastasis.

Retroperitoneal paraganglioma remains an extremely rare type of tumor that arises from either sympathetic or parasympathetic neural crest cells. It could be functional or non-functional. Non-functional paraganglioma may present as a diagnostic challenge since patients are usually asymptomatic and tend to present to the hospital with complications from the invasion of the tumor. Malignancy is usually determined by the degree of metastasis. The gold standard of diagnosis is biopsy and obtaining a sample for histological examination. This author presents a case of asymptomatic, non-functional retroperitoneal paraganglioma with distant metastasis.

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.

Adverse effects of an aldosterone synthase (CYP11B2) inhibitor, fadrozole (FAD286), on inflamed rat colon.

Recently, we described local aldosterone production in the murine large intestine. Upregulated local aldosterone synthesis in different tissues has been linked with inflammatory conditions, which have been attenuated by the aldosterone synthase (CYP11B2) inhibitor, fadrozole (FAD286). Therefore, we investigated the effect of inhibition of intestinal aldosterone synthesis on the development of intestinal inflammation. Sprague-Dawley rats were administered 5% (v/w) dextran sodium sulphate (DSS) for 7 days with or without daily FAD286 (30 mg/kg/d) subcutaneous injections on 3 days before, during and one day after DSS. Tissue aldosterone concentrations were evaluated by ELISA, CYP11B2 by Western blot and RT-qPCR. FAD286 halved adrenal aldosterone production but, intriguingly, increased the colonic aldosterone concentration. The lack of inhibitory effect of FAD286 in the colon might have been affected by the smaller size of colonic vs. adrenal CYP11B2, as seen in Western blot. When combined with DSS, FAD286 aggravated the macroscopic and histological signs of intestinal inflammation, lowered the animals' body weight gain and increased the incidence of gastrointestinal bleeding and the permeability to iohexol in comparison to DSS-animals. To conclude, FAD286 exerted harmful effects during intestinal inflammation. Local intestinal aldosterone did not seem to play any role in the inflammatory pathogenesis occurring in the intestine.

Case Report: Paraganglioma in the sellar region: longitudinal observation and surgical outcome.

Background: Paraganglioma in the sellar region is an extremely rare entity, with a limited number of cases reported in the literature. Due to the paucity of clinical evidence, the diagnosis and treatment of paragangliomas in the sellar region remain challenging. Herein, we reported a case of sellar paraganglioma with parasellar and suprasellar extension. Particularly, the dynamic evolution of this benign tumor within a 7-year longitudinal observation was presented. Additionally, the relevant literature regarding sellar paraganglioma was comprehensively reviewed. Case description: A 70-year-old woman presented with progressive visual deterioration and headache. Brain magnetic resonance imaging demonstrated a mass in the sellar region with parasellar and suprasellar extension. The patient refused surgical treatment. Seven years later, brain magnetic resonance imaging showed the lesion significantly progressed. Neurological examination revealed bilateral tubular contraction of visual fields. Laboratory examinations showed endocrine hormone levels were normal. Surgical decompression was performed via a subfrontal approach, and subtotal resection was achieved. Histopathological examination confirmed a diagnosis of paraganglioma. Postoperatively, she developed hydrocephalus, and ventriculoperitoneal shunting was performed. Eight months later, cranial CT showed no recurrence of the residual tumor, and the hydrocephalus had been relieved. Conclusion: Paraganglioma occurring in the sellar region is rare, and the preoperative differential diagnosis is difficult. Owing to the infiltration to the cavernous sinus and internal carotid, complete surgical resection is usually impracticable. There has been no consensus regarding postoperative adjuvant radiochemotherapy for the tumor residue. In-situ recurrence and metastasis have been reported in the literature, and close follow-up is warranted.

Glucocorticoids are differentially synthesized along the murine and human respiratory tree.

BACKGROUND: Synthetic glucocorticoids (GC) are effective in the treatment of inflammatory diseases of the lung. However, long-term use leads to severe side effects. Endogenous GC can be synthesized locally, either de novo from cholesterol in a 11ß-hydroxylase (Cyp11b1)-dependent manner, or by reactivation from 11-dehydrocorticosterone/cortisone by 11ß-hydroxysteroid dehydrogenase 1 (Hsd11b1). We aimed to define the molecular pathways of endogenous GC synthesis along the respiratory tree to provide a basis for understanding how local GC synthesis contributes to tissue homeostasis. METHODS: Expression of steroidogenic enzymes in murine lung epithelium was analyzed by macroscopic and laser capture microdissection, followed by RT-qPCR. Flow cytometry analysis was performed to identify the cellular source of steroidogenic enzymes. Additionally, the induction of steroidogenic enzyme expression in the lung was analyzed after lipopolysaccharide (LPS) injection. mRNA and protein expression of steroidogenic enzymes was confirmed in human lung tissue by RT-qPCR and immunohistochemistry. Furthermore, GC synthesis was examined in ex vivo cultures of fresh tissue from mice and human lobectomy patients. RESULTS: We observed that the murine and human lung tissue differentially expresses synthesis pathway-determining enzymes along the respiratory tree. We detected Hsd11b1 expression in bronchial, alveolar, club and basal epithelial cells, whereas Cyp11b1 expression was detectable only in tracheal epithelial cells of mice. Accordingly, de novo synthesis of bioactive GC occurred in the large conducting airways, whereas reactivation occurred everywhere along the respiratory tree. Strikingly, Cyp11b1 but not Hsd11b1 expression was enhanced in the trachea upon LPS injection in mice. CONCLUSION: We report here the differential synthesis of bioactive GC along the murine and human respiratory tree. Thus, extra-adrenal de novo GC synthesis and reactivation may differentially contribute to the regulation of immunological and inflammatory processes in the lung.

Extra-adrenal peripheral neuroblastic tumors: A clinicopathological study of 18 cases.

Background: Peripheral neuroblastic tumors arise from the sympathoadrenal lineage of the neural crest. They have been classified according to the International Neuroblastoma Pathology Committee (INPC) into Four categories according to International Neuroblastoma Pathology Committee (INPC): a) Neuroblastoma (NB) b) Ganglioneuroblastoma (GNB), nodular c) Ganglioneuroblastoma, intermixed, and d) Ganglioneuroma (GN). Because of the rarity of extra-adrenal peripheral neuroblastic tumors, limited information is available regarding the chemotherapy of NB and GNB. A few case reports or case series with a small number of patients have been documented in the literature. Aim: To describe the clinicopathological characteristics of extra-adrenal peripheral neuroblastic tumors. Materials and. Methods: Clinical, histopathological, and immunohistochemistry (IHC) findings of 18 cases were retrieved. Immunohistochemistry at the time of diagnosis was performed using Ventana Benchmark XT. The mean value was calculated using the Microsoft Office Excel 2019 software. Results: The posterior mediastinum was the most commonly affected extra-adrenal site in our study. Neuroblastoma consisted of eight cases (six in children, two in adults), of which four cases were poorly differentiated and the other four cases were differentiating. Two cases had favorable histology. The bone marrow and cervical lymph node metastasis were documented. Of the four GNB cases, one patient developed bone metastasis. All patients of NB and GNB received combination chemotherapy. One out of six GN patients presented with a large retroperitoneal mass encasing the aorta and renal vessels, mimicking a sarcoma. Conclusion: Extra-adrenal peripheral neuroblastic tumors do not pose any diagnostic issue in adequate tissue sampling. In limited material, immunohistochemistry is needed. The chemotherapy regimen has not been standardized due to rarity. Further molecular testing and targeted therapy may be of help in the future.

Gallbladder Paraganglioma: A Mysterious Histological Finding.

Gallbladder paragangliomas are extremely rare with only a handful of cases reported so far. There are no definitive guidelines for the management of gallbladder paragangliomas due to their rarity. We present a case of a 53-year-old male who was found to have gallbladder paraganglioma post-laparoscopic cholecystectomy, performed for right upper abdominal pain. On review of the literature, all previously reported cases had been nonsecretory and benign. For patients who have no symptoms of secretory paragangliomas and no family history of endocrine syndromes, cholecystectomy and clinical follow-up may be a sufficient initial management following an incidental finding of gallbladder paraganglioma.