| Abstract|| |
Sporadic adrenal medullary hyperplasia (AMH) is a rare entity and mimics pheochromocytoma clinically as well as pharmacologically. It is characterized by increase in adrenal medullary cells with the expansion of cells into areas normally not seen. A 59-year-old male presented with chronic hypertension and raised 24-h urinary normetanephrine levels. Radiological and clinical possibility of pheochromocytoma led to left transperitoneal laparoscopic adrenalectomy. Histopathology, however, showed increase in adrenal medullary to cortical ratio, further confirmed by immunohistochemistry. The absence of any well-defined lesion led to the diagnosis of AMH. Furthermore, on routine imaging, two asymptomatic cavernous hemangiomas were seen. We present this case to reiterate that AMH is an entity which should be considered as a differential for pheochromocytoma. Furthermore, the presence of asymptomatic cavernous hemangiomas in the cerebrum, in this case, makes it rarer since this sporadic association is seldom seen.
Keywords: Adrenal medullary hyperplasia, cerebral angioma, pheochromocytoma
|How to cite this article:|
Gupta L, Bhatt AS, Mallya V, Khurana N, Lal P. Adrenal medullary hyperplasia with coexistent cerebral angiomas. Indian J Pathol Microbiol 2018;61:587-9
|How to cite this URL:|
Gupta L, Bhatt AS, Mallya V, Khurana N, Lal P. Adrenal medullary hyperplasia with coexistent cerebral angiomas. Indian J Pathol Microbiol [serial online] 2018 [cited 2019 Jun 19];61:587-9. Available from: http://www.ijpmonline.org/text.asp?2018/61/4/587/243003
| Introduction|| |
Among the causes of hypertension adrenal medullary hyperplasia (AMH) and pheochromocytoma constitute only 0.1%–0.2% of cases. Association of AMH as a precursor of pheochromocytoma is frequently described. Since both the entities share identical clinical and biochemical findings, histopathology serves as the only way to distinguish between them.
The case being described here is of a 59-year-old male who had AMH with the presence of cerebral cavernous hemangiomas. The present case thus assumes importance as AMH with associated cerebral cavernous hemangiomas to the best of our knowledge is seldom described. As AMH is often difficult to diagnose without histopathology, the role of a pathologist remains pivotal in its diagnosis.
| Case Report|| |
A 59-year-old male patient presented with recent complaints of paroxysmal hypertension, episodes of palpitations, sweating, and headaches. He had chronic hypertension since the past 18 years and was on antihypertensives since the past 10 years. He was also taking oral hypoglycemics for type 2 diabetes mellitus from the past 7 years. There was a history of stroke, 18 years back. The patient was a known chronic smoker (10–15 cigarettes/day). Family history of similar complaints or suggestive of any syndromic association was not identified. His pulse rate was 82 beats/min and blood pressure measured was 150/100 mm Hg. Laboratory investigations including complete hemogram, serum electrolytes, and liver and renal function tests were within normal limits. Random blood sugar was 112 mg/dl. Serum calcitonin level was normal. 24-h urinary normetanephrins levels were markedly raised (3293.66 μg/24 h) while 24 h urinary excretion of metanephrins was within normal limits. The left ventricular function was normal on two-dimensional echocardiography. Computed tomography (CT) abdomen showed bilateral bulky adrenal glands (left more than right) with nodular outline and small inhomogeneous nodular lesions on either side with tiny foci of calcification [Figure 1]a. I131-metaiodobenzylguanidine (MIBG) whole body scan showed faint nodular inhomogeneous tracer activity in the left adrenal with physiological tracer uptake in the right adrenal. Magnetic resonance imaging brain revealed two well-defined cavernomas in the cortical and subcortical region of right temporal lobe and left parasagittal frontal lobe [Figure 1]b.
|Figure 1: (a) Computed tomography abdomen showing bulky bilateral adrenal glands with left (red arrow) more than right, (b) magnetic resonance imaging brain showing two well-defined cavernous hemangiomas in right temporal (red arrow) and left parasagittal frontal lobe (yellow arrow)|
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A clinical impression of pheochromocytoma was made following which patient was taken up for the left transperitoneal laparoscopic adrenalectomy, and adrenal vessels were clipped during the procedure. The postoperative period was uneventful and blood pressure at the time of discharge stabilized to 130/82 mm Hg. The resected specimen was received in histopathology laboratory, and the adrenal gland appeared enlarged, measured 6 cm × 4 cm, was normal in color and shape. It weighed 22 gm. On serial sectioning, no definite growth was identified [Figure 2].
|Figure 2: Gross specimen of the left adrenal showing bulky and enlarged gland without any defined growth|
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Microscopically, there were nests of medullary cells within the cortex and arranged predominantly in a solid pattern with an increased adrenal medulla to cortex ratio and without any atypia [Figure 3]a and [Figure 3]b. On immunohistochemistry, the medullary cell nests were synaptophysin and chromogranin positive and inhibin negative [Figure 3]c. The adrenal cortical cells were positive for inhibin. A diagnosis of AMH was made. The patient is currently on regular follow-up and is free of any symptoms.
|Figure 3: Microphotographs showing (a) multiple aggregates of adrenal medullary cells within cortical areas (H and E, ×40), (b) ill-defined and noncapsulated aggregate of adrenal medullary cells (H and E, ×100), (c) chromogranin positive adrenal medullary aggregates (Chromogranin, ×200)|
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| Discussion|| |
AMH was considered as a precursor of pheochromocytoma, but as a separate and sporadic entity, it was first described by Montalbano et al. in 1962. Presenting symptoms of AMH and pheochromocytoma are similar and include recurrent episodes of flushing, diaphoresis, headache, palpitations, and poorly controlled hypertension. Increased urinary metanephrines and normetanephrines provide another diagnostic clue in suspected cases of AMH or pheochromocytoma. The present case had these classical symptoms along with increased urinary 24 h normetanephrine levels. I123-MIBG scintigraphy is considered more sensitive and specific than CT scan and ultrasonography in identifying and localization of hyperplastic as well as neoplastic adrenal medullary lesions.
As proposed by Rudy et al. histopathological diagnosis of AMH requires diffuse medullary expansion with or without nodule formation, enlarged medullary cells with or without nuclear pleomorphism and increased medulla to cortex ratio of the adrenal gland. Valdés et al. stated that pheochromocytoma has an integral capsule and AMH usually tends to be bilateral with diffuse or small nodule formations and without a well-defined capsule. In the present case also, increased in medullary volume was seen along with small ill-defined proliferations of medullary cells within the cortex. The findings of histopathology were also supported by immunohistochemistry employing synaptophysin, chromogranin, and inhibin stains. Although AMH can be diagnosed by histomorphology alone, immunohistostaining highlights the small nodular proliferations in AMH as seen in the present case, use of which has not been described before.
The present case also holds importance because patient also had two cerebral cavernous angiomas. Since the hemangiomas were asymptomatic, no intervention was done. Association of AMH has been seen with syndromes such as multiple neuroendocrine hyperplasia-Type 2, von Hippel–Lindau, and von Recklinghausen disease, but in the present case, the association of angiomas was probably sporadic. AMH can also develop in patients with succinate dehydrogenase subunit B and RET mutations which can further progress to pheochromocytomas.
The pathogenesis of AMH was elucidated by Carney et al., who described that hyperplasia and hypertrophy of medullary cells constitute the sequential events in AMH leading to increase in weight and formation of nodules in adrenal gland with retention of the normal configuration.
Surgery remains the treatment of choice for AMH. Laparoscopic removal of the gland via transperitoneal route is preferred as it provides better exposure and facilitates excision of large-sized adrenal gland. Care should be taken to ligate the adrenal vein early in the procedure to prevent life-threatening complications caused by the release of catecholamines within the circulation. In the case under discussion, adrenal was removed via transperitoneal laparoscopy with appropriate ligation of adrenal vessels. Patient condition improved after removal of the adrenal gland and his blood pressure stabilized.
| Conclusion|| |
AMH is a rare condition in itself, and simultaneous presence of temporal hemangiomas makes the present case still rarer. Medical history, imaging, and biochemical parameters serve as an adjunct while histopathology remains the gold standard method to diagnose AMH. Thus, extensive and serial sampling is mandatory for making an accurate diagnosis and distinguishing it from pheochromocytoma.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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Department of Pathology, Maulana Azad Medical College, New Delhi - 110 091
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]