Adrenal cortical carcinoma with late pulmonary metastases causing clinicical Cushing's syndrome: case report with immunohistochemical analysis of steriodogenic enzyme production.
OBJECTIVE
To present a case of pulmonary metastases from adrenocortical carcinomas (ACC) that were secreting fully-functional cortisol resulting in clinical Cushing's syndrome and to compare the steroidogenic enzyme expression in the primary tumor and lung.


METHODS
We analyzed and summarized the patient's medical history, physical examination results, laboratory data, imaging studies, and histopathologic results. The original tumor and the pulmonary metastases were then immunohistochemically evaluated for steroidogenic enzymes.


RESULTS
Initial endocrinological workup revealed hyperandrogenism and adrenocorticotropic hormone (ACTH) independent Cushing's due to a 4 cm left adrenal mass. The patient was initially diagnosed with an adrenal adenoma. Four years later, the patient developed recurrent Cushing's syndrome. Repeat magnetic resonance imaging (MRI) showed no adrenal masses; however, chest computed tomography (CT) showed multiple bilateral lung nodules and biopsy revealed metastases of adrenal origin. Upon immunohistochemical analysis, side chain cleavage, 17α hydroxylase, 3β hydroxysteroid dehydrogenase, and 21 hydroxylase immunoreactivity were detected in both the original and pulmonary metastatic lesions with patterns of disorganized steroidogenesis. Dehydroepiandrosterone-sulfotransferase (DHEA-ST) immunoreactivity was detected in the original tumor but not in the lung metastases.


CONCLUSIONS
This case demonstrates some interesting features of ACC that pose challenges to its management, including the difficulties in establishing the pathologic diagnosis, the potential for fully functional steroidogenesis even in late metastases, and the plasticity of steroidogenic potential in tumor cells.
Memorial Sloan Kettering Cancer Center, New York, New York, USA. erika.brutsaert@gmail.com
Erika F
EF
Brutsaert
Hironobu
H
Sasano
Pamela
P
Unger
Mary Beth
MB
Beasley
Brian K
BK
Golden
William B
WB
Inabnet
Alice C
AC
Levine
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000601:surgery; D000315:Adrenalectomy; D018246:Adrenocortical Adenoma / Q000201:enzymology* / Q000601:surgery; D003480:Cushing Syndrome / Q000097:blood / Q000209:etiology*; D004358:Drug Therapy; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008175:Lung Neoplasms / Q000150:complications* / Q000201:enzymology / Q000556:secondary*; D008875:Middle Aged; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013255:Steroid 21-Hydroxylase / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism
D015096:3-Hydroxysteroid Dehydrogenases; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; D015238:Sulfotransferases; C019998:dehydroepiandrosterone sulfotransferase; D006854:Hydrocortisone