Heterogeneous Adrenal Mass Research Articles

6657 A rare case of a composite pheochromocytoma and ganglioneuroma in a 47-year-old male

Abstract Disclosure: C. Ekladios: None. M.J. Levine: None. Introduction: Pheochromocytoma is a rare tumor that originates from adrenal chromaffin cells. It remains a diagnostic challenge due to its diverse clinical manifestations. We present a case of pheochromocytoma, shedding light on its atypical presentation and diagnostic complexity.Case reportA 47-year-old male was referred to our clinic with a recent diagnosis of pheochromocytoma. Patient started having symptoms approximately two months prior to referral to our office. He initially presented to the emergency department (ED) with generalized weakness for three days, accompanied by feelings of “rushing of blood to the head” and a “rush of blood in the arms” every time he laid down. Symptoms would last for a few seconds and resolve without intervention. Vitals signs and physical examination (PE) were within normal limits. He had basic laboratory studies including BMP and CBC without any abnormalities. He was discharged home with instructions to follow-up outpatient. He returned to the ED two days after with a chief complaint of left sided chest pain associated with palpitations, pain was non-persistent, lasting a few seconds. On presentation his blood pressure was 142/89 mmHg, Pulse: 66 bpm, Temperature: 98.4 °F, and oxygen Saturation 100%. On PE, he had clear bilateral air entry and regular heart rate with no murmurs noted, EKG demonstrated no ischemic changes. Chest Xray showed no evidence of cardiopulmonary disease. A CTA revealed no pulmonary embolism, pleural effusion, or pneumothorax. However, a large heterogeneous adrenal mass was partially visualized, measuring 8.3 cm anteroposteriorly concerning for adrenal cortical carcinoma. His labs were pertinent for Metanephrine level of 0.52 nmol/L (nl:0-0.49) and Normetanephrine of 4.22 nmol/L (nl:0-0.89). Aldosterone level is 16.2 ng/dL and Renin activity was 0.1ng/mL. An abdominal CT scan confirmed a left adrenal mass measuring approximately 9.2 x 8.8 cm transaxially and 9.9 cm craniocaudal. He was seen in our office after discharge, at that time he was still experiencing tingling in both lower extremities that sometimes would wake him up from sleep. His blood pressure at the office was 125/83 mm Hg. In preparation for the surgery, we started treatment with Prazosin, followed by addition of Metoprolol succinate. Further work-up included a dexamethasone suppression test that ruled out Cushing’s syndrome and a negative RET proto-oncogene, ruling out MEN 2. Patient underwent laparoscopic left adrenalectomy without complications. Pathology results interestingly showed a composite pheochromocytoma and ganglioneuroma constituting 5 % of the mass volume, Ki-67 proliferative index was less than 1% for the pheochromocytoma and overall findings were consistent with a benign tumor.ConclusionOur case report emphasizes the necessity of a high index of suspicion for diagnosing pheochromocytoma in the absence of the classic symptoms. Presentation: 6/2/2024

Primary unilateral macronodular adrenal hyperplasia with concomitant glucocorticoid and androgen excess and KDM1A inactivation.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing's syndrome. Individuals with PBMAH and glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing's syndrome due to ectopic expression of the GIP receptor (GIPR) typically harbor inactivating KDM1A sequence variants. Primary unilateral macronodular adrenal hyperplasia (PUMAH) with concomitant glucocorticoid and androgen excess has never been encountered or studied. We investigated a woman with a large, heterogeneous adrenal mass and severe adrenocorticotropic hormone-independent glucocorticoid and androgen excess, a biochemical presentation typically suggestive of adrenocortical carcinoma. The patient presented during pregnancy (22nd week of gestation) and reported an 18-month history of oligomenorrhea, hirsutism, and weight gain. We undertook an exploratory study with detailed histopathological and genetic analysis of the resected adrenal mass and leukocyte DNA collected from the patient and her parents. Histopathology revealed benign macronodular adrenal hyperplasia. Imaging showed a persistently normal contralateral adrenal gland. Whole-exome sequencing of 4 representative nodules detected KDM1A germline variants, benign NM_001009999.3:c.136G > A:p.G46S, and likely pathogenic NM_001009999.3:exon6:c.865_866del:p.R289Dfs*7. Copy number variation analysis demonstrated an additional somatic loss of the KDM1A wild-type allele on chromosome 1p36.12 in all nodules. RNA sequencing of a representative nodule showed low/absent KDM1A expression and increased GIPR expression compared with 52 unilateral sporadic adenomas and 4 normal adrenal glands. Luteinizing hormone/chorionic gonadotropin receptor expression was normal. Sanger sequencing confirmed heterozygous KDM1A variants in both parents (father: p.R289Dfs*7 and mother: p.G46S) who showed no clinical features suggestive of glucocorticoid or androgen excess. We investigated the first PUMAH associated with severe Cushing's syndrome and concomitant androgen excess, suggesting pathogenic mechanisms involving KDM1A.

LBSAT61 Pure Aldosterone-secreting Adrenocortical Carcinoma Causing Resistant Hypertension In A Patient With Previously Controlled Longstanding Hypertension: A Case Report

Abstract Introduction Adrenocortical carcinoma is a rare endocrine malignancy that could be classified into functioning or non-functioning, depending on the tumor's ability to secret adrenocortical hormones. Pure aldosterone-secreting adrenocortical carcinoma is extremely rare, accounting for <7% of all functioning tumors that could present with primary aldosteronism and secondary hypertension. Case Presentation A 48-year-old man had a past medical history of longstanding hypertension that recently became resistant to multiple antihypertensive medications (thiazide, angiotensin receptor inhibitor, calcium channel blocker, hydralazine) despite medications compliance. He presented to the ER with left flank pain that was not associated with dysuria, nausea, or vomiting. On admission, his blood pressure was 223/135 mmHg. CT scan of the abdomen and pelvis showed mild left-sided hydronephrosis, hydroureter with a 2mm stone at the left ureterovesical junction, and a 7. 0×7. 0×6.4 cm left heterogeneous adrenal mass that was highly suspicious for malignancy. His laboratory workup revealed low serum potassium of 2.9 mmol/L (reference value 3.5-5.1 mmol/L), serum creatinine of 1.38 mg/dL (reference value 0.7-1.3 mg/dL), random cortisol of 21.8 mcg/dL (reference value 5-25 mcg/dL), ACTH of 5 pmol/L (reference value 10-60 pmol/L), serum levels of normetanephrine of 0.67 nmol/L (reference range 0-0.89 nmol/L), metanephrines of <0.10 nmol/L (reference range 0-0.49 nmol/L), and chromogranin A of 45 ng/mL (reference range 0-95 ng/mL). Further investigations showed high serum aldosterone of 28 ng/dL (reference range 2-9 ng/dL) and low plasma renin activity of 0.1 ng/mL per h (reference range 0.5-2.5 ng/mL per h) supported the diagnosis of primary aldosteronism. The patient underwent left adrenalectomy, and the diagnosis of pure aldosterone-secreting adrenocortical carcinoma was confirmed by histological examination. Conclusion Pure aldosterone-secreting adrenocortical carcinoma is an extremely rare adrenal tumor that could cause resistant hypertension. Re-evaluation of secondary causes of hypertension is essential in patients with a previously controlled longstanding hypertension, developing uncontrolled or resistant hypertension. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

P224 A challenging case of pyrexia of unknown origin of adrenal mass

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMA familiar dictum in tropical countries is to consider the diagnosis of tuberculosis (TB) in a patient with fever of unknown origin until proven otherwise. Often, in resource-limited settings, a response to a trial of empiric anti-tuberculous therapy (ATT) is needed to prove TB. However, chronic granulomatous diseases such as invasive fungal infections and sarcoidosis have clinical features resembling extrapulmonary TB. Thus, the workup for a definitive diagnosis is necessary. A 53-year-old male presented with low grade, intermittent fever, loss of weight and appetite for a duration of 4 months and generalized abdominal pain for the last 2 months. He has lost about 16 kg in the past 6 months. He also reported a mild cough with scanty white mucoid sputum. There was no contact with a case of TB. He developed small oval/circular copper Color patchy lesions in the trunk for the last 1 month (Fig. 1). The general examination of the patient was grossly normal except for hepatomegaly. Routine blood examination, renal and liver function test, and chest X-ray were normal and HIV ELISA was non-reactive. With the strong suspicion of TB, the patient underwent CT scanning of the chest and abdomen was done which showed bilateral heterogeneous adrenal mass with few hypodense areas within measuring right side 3.1 × 1.8 cm and left side 3.1 × 2.5 cm in suprarenal location and liver is enlarged size 19.3 cm with normal attenuation (Fig. 2). There were no clinical features to suggest pheochromocytoma or Cushing's syndrome. The PET-CT revealed metabolically active disease involving bilateral adrenal gland, abdominal and retrosternal lymph node with diffuse hepatomegaly. Transabdominal ultrasound-guided FNA was done from adrenal lesions. The tests for tuberculosis were negative and the cytology reported necrotizing granuloma with intracytoplasmic yeast cells suggestive of histoplasmosis. The adrenal endocrine profile was normal. From skin lesions, a biopsy was done. Direct KOH from skin lesion revealed budding yeast cells while the cultures are awaited. The patient was treated with 3 mg/kg liposomal amphotericin B for 2 weeks followed by daily itraconazole for maintenance. The fever was resolved after 8 days of liposomal amphotericin B and skin lesions softened after 3 weeks of therapy.

Adrenal schwannoma: A case report of an unusual incidentaloma.

Introduction and importanceAdrenal schwannomas are extremely rare tumors often misdiagnosed. The patients are usually asymptomatic while some present with non-specific abdominal pain. Only a few cases are reported to date.Case presentationWe here present a case of a 55-year-old Nepalese man presented with nonspecific abdominal pain at our Outpatient Department (OPD) found to have mass on ultrasonography of abdomen. On further investigation with Contrast Enhanced Computerized Tomography (CECT) of the abdomen and pelvis, a well-defined heterogeneous adrenal mass of size (7.8 ∗ 8.3 ∗ 6) cm with foci of calcification was seen in the left retroperitoneum. The intraoperative finding of adrenal mass and histopathology of resected mass was suggestive of schwannoma arising from the adrenal gland which was further confirmed by immunohistochemistry.Clinical discussionAdrenal schwannoma can mimic tumors like pheochromocytoma, adrenal adenoma, cortical carcinoma, neuroblastoma, and other masses. Only 1–3% of schwannomas are retroperitoneal. Radiological findings of this tumor are non-suggestive. The histological section shows spindle cells with Antoni A and Antoni B regions while positive staining of S-100 protein in Immunohistochemistry.ConclusionThe diagnosis of adrenal schwannoma in the retroperitoneum is often challenging. The treatment of choice is surgical resection with a good prognosis.

From benign adrenal incidentaloma to adrenocortical carcinoma: an exceptional random event

New European guidelines for the management of adrenal incidentalomas were recently released. One of the most novel recommendations is to stop following patients when they present a typical, small and non-secreting adenoma. We report here the case of a 71-year-old man with such an adenoma, who developed an adrenocortical carcinoma (ACC) fourteen years later, with subsequent metastases and death. Clinically, he had a normal blood pressure and no sign of hormonal hypersecretion. The hormonal work-up showed no hormone excess: urinary free cortisol level was normal, the diurnal cortisol rhythm was respected and urinary catecholamine metabolites levels were normal. Computed tomography (CT) scan showed a homogeneous lesion, with a low density. The lesion remained unchanged during the five years of follow-up. Eight years after the last CT, a large right heterogeneous adrenal mass was incidentally discovered during an ultrasound examination. On CT scan, it was a 6 cm heterogeneous tumor. On hormonal work-up, there was no secretion. The patient was operated of an adrenalectomy, and the histology described an ACC with a Weiss score at 8, with no benign contingent. To our knowledge, this is the first case of an ACC occurring in a patient with prior adrenal imaging showing a typical benign adenoma.

Adrenal Mass: Unusual Presentation and Outcome.

Aim:Adrenal mass may be functioning or nonfunctioning with varied clinical presentations. This study aimed to report the nature and management of uncommon adrenal mass and to review literature.Materials and Methods:This was an retrospective observational analysis of children with uncommon adrenal mass admitted during 2009–2015. Clinical features, investigations, and management of patients were analyzed.Results:Among six, two each were adolescent and neonate, and one each was young infant and prenatal. Clinical presentation was variable; hypertensive retinopathy,[1] virilization[1] and bleeding diathesis,[1] antenatal suprarenal mass,[1] prenatal adrenal angiolipoma,[1] and spontaneous resolution of Stage III suprarenal mass.[1] Ultrasound and contrast-enhanced computed tomography revealed well-defined, heterogeneous adrenal mass. Size varied from 2 to 15 cm. Urinary metanephrine and serum testosterone were raised in adolescent hypertensive boys and virilized girls, respectively. Laparoscopy-assisted adrenalectomy was done in two and other four were managed conservatively. Histopathology of tumor revealed pheochromocytoma and borderline oncocytoma. Spontaneous resolution of adrenal mass had varied etiology; adrenal hemorrhagic lesion,[1] simple cyst,[1] neuroblastoma.[1] Follow-up varied from 3 months to 2 years. All patients were asymptomatic on last follow-up.Conclusion:Close clinical follow-up, contrast-enhanced tomography, and limited/specific endocrine work-up have definite role in the management of uncommon adrenal mass.

Adrenocortical Carcinoma: False Positive in an I-123 Metaiodobenzylguanedine Scan.

A 55-year-old man with a personal history of left pheochromocytoma 2 years previously presented with an abdominal mass. Tumor relapse was suspected.Abdominal ultrasound showed a large left upper quadrant solid mass (calipers), with heterogeneous echogenicity and central cystic degeneration areas or necrosis (Fig. 1a). A computed tomography (CT) scan showed surgical clips of left adrenalectomy and multiple confluent left upper quadrant masses with a maximal diameter of 19 cm and heterogeneous enhancement (Fig. 1b). Both CT scan and ultrasound images were suspicious of adrenocortical carcinoma (ACC): size, heterogeneity and diaphragm invasion among other radiological features. Clinically, the mass grew in a few months and there were no paroxysmal hypertension episodes, nor elevation of catecholamines (cathecholamine urine test: 37.2 μg/g creatinine, normal range 0.1-260). F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT was performed as ACC was suspected (2). ACC is an uncommon malignant neoplasm of unknown cause; however, smoking and oral contraceptives may be risk factors [1, 2]. Patients usually present with advanced-stage disease and have poor prognosis [3], with a 2-year recurrence rate that ranges from 73 to 86 % [4]. CT or magnetic resonance (MR) is most often used for initial staging of ACC and usually shows heterogeneous adrenal mass with variable enhancement of solid components [4]. F-18 FDG PET has been used successfully for detection of adrenal metastases and for staging ACC [5]. Most ACCs accumulate and retain FDG [2, 6]. However, FDG PET cannot differentiate among malignant lesions (metastases, ACC, malignant pheochromocytoma, and lymphoma). Also, most pheochromocytomas (benign or malignant) are metabolically active and might accumulate FDG [7, 8]. A whole-body FDG PET scan (coronal and axial view) shows increased irregular FDG uptake in the abdominal masses (Fig. 2). An I-123 metaiodobenzylguanedine (MIBG) scan was requested to rule out pheochromocytoma because, although conventional image methods (ultrasound and CT) and also PET/CT scan were suspicious of ACC, the primary histology of the tumor was consistent with pheochromocytoma. An MIBG scan was performed after injection of 185 MBq of I123 MIBG intravenously. Single photon emission tomography (SPECT)/CT scan showed abnormal isotope accumulation in the tumor region. The patient underwent total resection of the tumor. The histology was of ACC, with areas of necrosis and cystic areas, so the result of the MIBG scan was a false positive. No positive chromaffin staining or chromogranin ISSN (print) 1869-3474 ISSN (online) 1869-3482

An oncocytic adrenal tumour in a patient with Birt‐Hogg‐Dubé syndrome

A 62-year old female patient was initially diagnosed with a histologically confirmed trichodiscoma. Due to the association of trichodiscomas with Birt-Hogg-Dube Syndrome (BHD), the patient underwent screening for renal tumors, which revealed a heterogeneous right adrenal mass (Figure 1a). The patient did not have any clinical hormone excess. Adrenalectomy revealed a tumor measuring 6.2cm and weighing 104g with features diagnostic for an adrenal oncocytoma (Figure 1b). While the tumor did not fulfill the established criteria for malignancy in oncocytic adrenal neoplasms, the borderline Ki67 labeling of 5% suggested the diagnosis of at least uncertain malignant behavior rather than a benign lesion 1. The traditional Weiss scoring system to differentiate benign and malignant lesion fails in oncocytomas as they almost invariably are positive for at least two of the criteria, leading to overdiagnosis of malignant lesions 1.The patient remains disease free 24 months following surgery. Review of a chest CT imaging revealed two small cysts. The patient’s family history was suggestive of BHD, with a maternal cousin with a history of spontaneous pneumothorax (Figure 1c). The patient’s mother had a diagnosis of basal cell carcinoma and one maternal aunt died of lung cancer. The patient’s father died of pancreatic cancer. The patient underwent germline genetic testing, revealing a deleterious mutation in exon 11 of FLCN (c.1252delC; p.Leu418TrpfsX50) leading to a premature stop codon and confirming the diagnosis of BHD. Unfortunately, insufficient tumor tissue precluded loss of heterozygosity analysis. Figure 1 (a) heterogeneous adrenal mass on T1 weighted MRI. (b) oncocytic adrenal neoplasm with diffuse growth pattern. (c) Pedigree. Proband (III.1) indicated with the arrow. A maternal cousin fulfilled clinical criteria for BHD (III.3), making the patient’s ... Adrenocortical tumors, benign and malignant, are well known to occur as part of hereditary cancer susceptibility syndromes2. Adrenocortical carcinoma (ACC) is a core malignancy of Li Fraumeni syndrome. ACC and adrenocortical adenomas are observed in Beckwith Wiedemann syndrome, Multiple Endocrine Neoplasia type 1 and Familial Adenomatous Polyposis. Oncocytic adrenal tumors are rare, have biological behavior which can be difficult to predict and have not been reported in association with hereditary syndromes1. BHD was first described in 1977 with the classical manifestations of benign hair follicle associated tumors. In the decades to follow, BHD has been defined as an autosomal dominant hereditary syndrome, characterized by the cutaneous triad of fibrofolliculomas, trichodiscomas and acrochordons, lung cysts and renal tumors. BHD is caused by mutations in FLCN (Online Mendelian Inheritance in Man #13510, http://omim.org/entry/135150, for photograph of typical skin lesions see Ref. 3). Renal oncocytomas, as well as chromophobe and mixed chromophobe oncocytic adrenal tumors, are typical for BHD 3. In order to explore an adrenal phenotype in BHD patients, we identified 14 patients from 11 unique families with genetically confirmed FLCN mutations in the University of Michigan Cancer Genetics Registry. A stable 1.2cm adrenal nodule was observed in a 22 year old male patient. Next, we retrospectively reviewed 359 patients diagnosed with ACC using the Michigan Endocrine Oncology Repository. None of the 359 patients had reported history of trichodiscoma or fibrofolliculoma. One patient reportedly had 2 lung cysts sized 1.2cm. Three patients had histories of renal tumors, including one oncocytoma. Five patients reported first-degree relatives with kidney cancer. No patient fulfilled clinical criteria for BHD, had undergone germline genetic testing for FLCN mutations, or had a reported family history of BHD. In summary, adrenal tumors may be more common in BHD patients, but BHD is not common amongst ACC patients. Review of the literature yielded three reports of adrenal tumors in BHD patients. First, a study of 23 BHD patients with confirmed FLCN mutations presenting with lung cysts reported one patient with an adrenal nodule4. This adrenal nodule was small (1.5 x 2.0cm) and non-hormone-secreting (personal communication Dr. Seyama). Second, Juszczak et al. reported a large oncocytic adrenal tumor in a 36 year old female patient with BHD and confirmed FLCN mutation 5. The third report of an adrenal tumor describes a presumed ectopic renal tumor in the adrenal gland of a BHD patient 6. Our case, together with the case described by Juszczak et al,. suggest that adrenal oncocytomas might be part of the BHD tumor spectrum. With the exception of trichodiscoma, fibrofolliculoma and typical kidney tumors, no specific association of other tumors with BHD has been proven, despite several reports of benign and malignant tumors in BHD patients3. As is often the case with rare cancer susceptibility syndromes, predisposition to tumors other than the core malignancies is not well-defined. Furthermore, the phenotype of BHD can be subtle, leading to underdiagnosis. Suspicion of BHD should be raised in patients with adrenal oncocytomas. Dermatologic exam and review of chest imaging can reveal other hallmark clinical features of BHD.

Corticomedullary mixed tumor of the adrenal gland

A 34-year-old woman presented with weight gain, hirsutism, recent hypertension and secondary amenorrhea. Laboratory findings showed hypokalemia, elevated cortisol and androgen levels with normal urine metanephrines and normal aldosteronemia. Abdominal magnetic resonance imaging showed a right heterogeneous adrenal mass measuring 4 × 6 cm with mixed component of fat and adrenal tissue suggesting corticosurrenaloma. After right adrenalectomy, blood pressure normalized and hypokalemia resolved. In the postoperative course, the patient presented adrenal insufficiency treated with hydrocortisone hemisuccinate. Histological examination showed a single tumor mass composed of an admixed population of adrenal cortical and medullary cells. Immunohistochemical evaluation was positive for chromogranin A.

Sarcomatoid carcinoma of the adrenal gland: A case report and review of literature

Reports about adrenocortical carcinomas (AC) mixed with sarcomatous areas are very rare. The terminology and pathogenesis of such biphasic tumors remain controversial. Herein, we report a case of sarcomatoid carcinoma of the adrenal gland in a 75-year-old woman who presented with left abdominal pain of one month's standing. The results of abdominal ultrasonography and computed tomography (CT) showed the presence of a large heterogeneous adrenal mass. A left adrenalectomy and complete splenectomy were performed. Histologically, the neoplasm showed areas of adrenocortical carcinoma and areas of sarcomatoid spindle cell proliferation. When examined immunohistochemically, the carcinomatous cells stained positively for S-100 protein, Melan-A protein, and neuron-specific enolase (NSE), and focally for vimentin and the cytokeratin marker MNF 116. Also, the carcinomatous cells were immunoreactive to the monoclonal antibody HMB-45. The sarcomatous component expressed vimentin, as well as other smooth and skeletal muscle markers. Liver metastases appeared 3 months postoperatively. Twelve months after removal of the primary tumor, the patient died of her disease. To the best of our knowledge, only seven cases of adrenal sarcomatoid carcinoma have been reported in the medical literature. We review the reported cases according to the 2004 classification of the World Health Organization (WHO) of lung tumors, and highlight the histogenesis, diagnosis, and clinical course of this very aggressive tumor.

Laparoscopic adrenalectomy of an adrenal adenoma with myelolipoma relieves severe hypertension in a 16-year-old patient

Adrenal adenoma with myelolipoma is extremely rare in pediatrics. Although the tumor is usually asymptomatic, sometimes it may result in serious manifestations. A 16-year-old patient was diagnosed with severe hypertension associated with a right adrenal mass. The laboratory work-up was inconclusive of the nature of the tumor. Plasma and urinary hormonal studies were not diagnostic. Magnetic resonance imaging (MRI) of the brain and meta-iodobenzylguanidine (MIBG) scanning were normal. MRI of the abdomen showed a heterogeneous adrenal mass 4.2x3.3 cm. Laparoscopic resection of the mass was done, and the pathology revealed an adrenal adenoma with myelolipoma. After tumor resection the hypertension resolved, and within 1 month the patient was off medications. At 2-year follow-up the patient's blood pressure remained normal at 120/73 mmHg. This is a case in which an adrenal adenoma with myelolipoma, a benign and usually asymptomatic tumor, presented as severe hypertension resolving with surgical resection of the tumor.