NCI CANCERLIT^® Search: Adrenocortical Carcinoma - September 2001

Last Modified: November 1, 2001

Adrenocortical tumors in children.
Adrenocortical carcinoma with cerebral metastasis in a child: case report and review of the literature.
Altered expression of novH is associated with human adrenocortical tumorigenesis.
Overexpression of CXC chemokines by an adrenocortical carcinoma: a novel clinical syndrome.
Bilateral primary adrenocortical carcinoma complicated by Addisonian crisis: case report.
Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors.
[Renovascular hypertension coexisting with an aldosteronoma]
Giant, nonfunctioning carcinoma of the adrenal cortex.
Fine-needle aspiration cytology of a case of oncocytic adrenocortical carcinoma.
Cytopathology of adrenal cortical oncocytoma.
[Therapy of the adrenocortical carcinoma with Lysodren (o,p'-DDD). Therapeutic management by monitoring o,p'-DDD blood levels]

CancerMail from the National Cancer Institute

1
UI - 21179500
AU - Ciftci AO; Senocak ME; Tanyel FC; Buyukpamukcu N
TI - Adrenocortical tumors in children.
SO - J Pediatr Surg 2001 Apr;36(4):549-54
AD - Department of Pediatric Surgery, Hacettepe University Medical Faculty, 06100, Ankara, Turkey.
BACKGROUND/PURPOSE: Etiopathogenesis and management of pediatric adrenocortical tumors (ACTs) is still obscure because of the limited number of cases. The aim of this study is to present a clear picture of the entire spectrum of pediatric ACTs by reviewing one of the largest noncollected pediatric series treated in a single medical center. METHODS: Records of children treated for ACTs in our unit between 1970 and 1999, inclusive, were reviewed. Information recorded for each patient included age, sex, clinical characteristics, diagnostic methods, stage of disease, treatment, pathologic findings, and outcome. The patients were subdivided into 2 groups: group I, patients with adrenocortical carcinoma (ACC) and group II, patients with adrenocortical adenoma (ACA). These groups were analyzed with regard to parameters mentioned above. RESULTS: There were 30 children treated for ACTs in the study period with a mean age of 6.7 +/- 4.2 years (range, 2.5 to 13 years). Of these, 20 had ACC, and 10 had ACA. The tumors were right sided in 22 patients, left sided in 6 and bilateral in 2. Analysis of each group with regard to age and site of tumor showed no significant difference. Endocrine dysfunction was noted in 83% of the patients and virilization was the most common presentation followed by Cushing's syndrome. The most striking difference between 2 groups was the prepondarance of virilization in group II and Cushing's syndrome in group I. In the latter, 14 patients presented with palpable abdominal mass and 3 patients with distant metastases. The mean time from initial symptoms to diagnosis was 8.1 +/- 0.2 months, and this interval was similar in 2 groups, in functional and nonfunctional tumors, and in both sexes. Ultrasound scan, computerized tomography, magnetic resonance imaging, intravenous pyelography, and angiography were used for the diagnosis. All patients with ACA had localized disease, whereas 80% of the patients with ACC had regional or metastatic disease. Total excision was done in all patients with ACA, but only in 13 patients with ACCs. Of the latter, 2 patients underwent ipsilateral nephrectomy, and 1 patient had right hepatic lobectomy plus nephrectomy. Adjuvant chemotherapy consisting of mitotane (n = 12), mitotane plus cisplatin and etoposide (n = 2) was commenced. Seven patients with ACC had distant metastases postoperatively. The presence of regional disease at presentation was associated with a significantly shorter disease-free interval. All patients presenting with nonfunctional ACC (n = 4), functional ACC that have been totally resected (n = 4), and partially resected (n = 3) died of disease within the first 2.5 years after diagnosis. There was no significant difference between the functional and nonfunctional ACCs with regard to survival rate. All patients who had distant metastases postoperatively and who had partial excision died. Of the surviving 9 patients with ACC, there are 6 known long-term survivors who are still alive. CONCLUSIONS: ACAs are treated by total excision satisfactorily without any complication. For the time being, the most important aspect of therapy for ACCs is early diagnosis and total excision. Partial excision and advanced-stage disease are the major determinants of poor outcome. None of the clinical, laboratory, or pathologic features are reliable predictors for recurrence and discrimination of malignancy in ACTs. Because of the steadily increasing incidence of precancerous genetic syndromes of adrenal glands and poor prognosis of ACCs, childhood patients of endocrine disorders should receive a detailed and vigorous diagnostic evaluation and appropriate treatment as given to adults. Patients with ACTs should be entered into multi-institutional trials to adequately assess effective chemotherapy and radiotherapy protocols and molecular mechanisms of oncogenesis. J Pediatr Surg 36:549-554. Copyright 2001 by W.B. Saunders Company.

2
UI - 21211240
AU - Romaguera RL; Minagar A; Bruce JH; Jagid JR; Falcone S; Curless RG; Ragheb J; Morrison G
TI - Adrenocortical carcinoma with cerebral metastasis in a child: case report and review of the literature.
SO - Clin Neurol Neurosurg 2001 Apr;103(1):46-50
AD - Department of Pathology, University of Miami, Jackson Memorial Hospital, East Tower Room # 2142, 1611 NW 12th Ave., Miami, FL 33136, USA. rromague@med.miami.edu
OBJECTIVE AND IMPORTANCE: Adrenocortical carcinoma (ACC) is rare in the pediatric population, and brain metastasis seldom occurs. CLINICAL PRESENTATION: The authors report a case of metastatic ACC to the brain in a 9-year-old patient who had an adrenal cortex neoplasm removed at 4 years of age, and was free of symptoms for 5 years. Two weeks before admission she complained of blurred vision in both eyes. INTERVENTION: Examination revealed bilateral papilledema, and a Magnetic Resonance Imaging (MRI) of the brain revealed a mass in the left lateral ventricle with extensive vasogenic edema and hydrocephalus. The tumor was removed, and histopathologic examination demonstrated metastatic ACC. CONCLUSION: Although ACC is a rare neoplasm it must be considered in the differential diagnosis of cerebral lesions in patients with a history of this tumor. Periodic long-term brain imaging is suggested as part of the follow up in patients with adrenocortical neoplasms.

3
UI - 21394125
AU - Martinerie C; Gicquel C; Louvel A; Laurent M; Schofield PN; Le Bouc Y
TI - Altered expression of novH is associated with human adrenocortical tumorigenesis.
SO - J Clin Endocrinol Metab 2001 Aug;86(8):3929-40
AD - INSERM, U-515, Croissance, Differenciation et Processus Tumoraux, Hopital Saint-Antoine, 75571 Paris, France. martiner@st-antoine.inserm.fr
NOVH belongs to the CCN (CTGF/CYR61/NOV) family of proteins, some of which have chemotactic, mitogenic, adhesive, and angiogenic properties. Whereas ctgf and cyr61 are growth factor-inducible, immediate-early genes, nov is expressed in growth-arrested or quiescent cells. As nov expression has been shown to be altered in both avian and human nephroblastomas and to be a target of WT1 regulation, NOV may play important roles in normal nephrogenesis and the development of Wilms' tumors. The aim of this study was to determine whether changes in novH expression were associated with tumorigenesis in tissues other than those of the kidney. We showed by Northern blotting and immunohistochemistry that among human adult endocrine tissues, the adrenal gland is a major site of novH expression, and that in adult and fetal adrenal tissue, novH is primarily expressed in the adrenal cortex. Studies with 12 benign and 18 malignant adrenocortical tumors revealed that the levels of novH mRNA and protein decreased significantly (P < 0.004) with progression of adrenocortical tumors from a benign to a malignant state. Although the localization of NOVH did not change, the N-glycosylation profile of benign and malignant tumors differed considerably from that of normal adrenocortical tissue, and these differences may affect the biochemical properties of the molecule. The properties of NOVH here provide the first evidence that this member of the CCN family could be involved in adrenocortical tumor development.

4
UI - 21394130
AU - Schteingart DE; Giordano TJ; Benitez RS; Burdick MD; Starkman MN; Arenberg DA; Strieter RM
TI - Overexpression of CXC chemokines by an adrenocortical carcinoma: a novel clinical syndrome.
SO - J Clin Endocrinol Metab 2001 Aug;86(8):3968-74
AD - Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. dschtein@umich.edu
A patient with adrenocortical carcinoma presented with fever, leukocytosis, and increased acute phase reactants. The tumor was infiltrated with neutrophils. Immunohistochemical staining of the tumor showed positive signal for epithelial neutrophil-activating protein-78, an angiogenic and chemotactic CXC chemokine. Conditioned medium from tumor-derived cells (RL-251) showed high concentration of IL-8, epithelial neutrophil-activating protein-78, Gro alpha, and Gro gamma, angiogenic CXC chemokines with a potential role in tumorigenesis. An adrenal cancer/severe combined immunodeficiency mouse chimera was developed. Mice grew tumors rapidly, and circulating levels of IL-8 and epithelial neutrophil-activating protein-78 were detected. In contrast, animals transplanted with NCI-H295 cells, a nonchemokine-secreting cell line, grew tumors more slowly and did not have detectable chemokine levels. Similar to the patient, mice with RL-251 tumors developed marked leukocytosis and neutrophilia, and their tumors were infiltrated with neutrophils. Mice were passively immunized with epithelial neutrophil-activating protein-78 antisera. A marked decrease in tumor growth was observed. Potential for chemokine production by other adrenocortical tumors was investigated by RT-PCR in archival material. Six of seven adrenal carcinomas and one of three adenomas had cDNA for IL-8; six of seven carcinomas and the three adenomas had cDNA for epithelial neutrophil-activating protein-78. We concluded that the clinical presentation of this case resulted from increased tumor production of chemotactic chemokines. Through their angiogenic and chemotactic properties these chemokines may play an important role in adrenal tumorigenesis.

5
UI - 21404559
AU - Foster M; Nolan RL; Hong HH
TI - Bilateral primary adrenocortical carcinoma complicated by Addisonian crisis: case report.
SO - Can Assoc Radiol J 2001 Aug;52(4):220-2
AD - Department of Radiology, Queen's University, Kingston, Ont.

6
UI - 21347512
AU - Barzon L; Chilosi M; Fallo F; Martignoni G; Montagna L; Palu G; Boscaro M
TI - Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors.
SO - Eur J Endocrinol 2001 Aug;145(2):207-12
AD - Department of Medical and Surgical Sciences, Division of Endocrinology, University of Padova, Padova, Italy.
OBJECTIVE: To evaluate the roles of the CDKN1C (P57KIP2) gene, which encodes for the cyclin-dependent kinase inhibitor CDNC, and the TP53 tumor suppressor gene in adrenal tumorigenesis, as a means of investigating the molecular basis of sporadic adrenal tumors, which is unknown. DESIGN: Screening for the presence CDKN1C and TP53 mutations and analyzing the expression pattern of CDNC, P53 and its downstream effector CDN1 (P21WAF1/CIP1) in a series of 79 sporadic adrenal tumors. METHODS: Single-strand conformation polymorphism and sequencing were used for mutation analysis of CDKN1C and TP53 in blood and adrenal tissue samples. In a subgroup of 48 tissues, CDKN1C expression was evaluated by RT-PCR and immunohistochemistry. Immunohistochemical analysis of P53 and CDN1 was performed. RESULTS: No somatic mutations of CDKN1C were found in the tumors analyzed, in spite of low/absent CDNC expression in adrenocortical adenomas and carcinomas. Mutations in the TP53 gene were present in 70% of adrenocortical carcinomas, associated with abnormal P53 and CDN1 expression, but not in benign neoplasms. In the normal adrenal cortex, CDNC expression was strictly nuclear and confined to the cortical zone (i.e. zona glomerulosa and reticularis), with no staining in the medulla. CONCLUSIONS: Mutations in the TP53 gene are frequent in adrenocortical carcinomas and might be used as a marker of malignancy. In the normal adrenal cortex, the zone-specific pattern of expression of CDNC suggests a role in adrenal differentiation.

7
UI - 21353441
AU - Ogihara M; Nakagawa A; Tamura C; Maejima K; Ito T; Nakano S; Kigoshi T; Uchida K; Matsubara J; Sasano H
TI - [Renovascular hypertension coexisting with an aldosteronoma]
SO - Nippon Naika Gakkai Zasshi 2001 Jun 10;90(6):1082-4
AD - Division of Endocrinology, Department of Internal Medicine, Kanazawa Medical University, Uchinada.

8
UI - 21394597
AU - Fimmano A; Pettinato G; Bonuso C; Cirillo C; Di Carlo R
TI - Giant, nonfunctioning carcinoma of the adrenal cortex.
SO - N Engl J Med 2001 Aug 30;345(9):700

9
UI - 20250791
AU - Krishnamurthy S; Ordonez NG; Shelton TO; Ayala AG; Sneige N
TI - Fine-needle aspiration cytology of a case of oncocytic adrenocortical carcinoma.
SO - Diagn Cytopathol 2000 May;22(5):299-303
AD - Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. skrishna@notes.mdacc.tmc.edu
We report on the results of fine-needle aspiration cytology of a case of oncocytic adrenocortical carcinoma in a 39-yr-old man. The tumor invaded the inferior vena cava and extended up to the right atrium. Aspirate smears were very cellular and showed a monomorphic population of large polyhedral cells with abundant granular cytoplasm, predominantly distributed singly. Mitotic activity was inconspicuous, and there was no necrosis. Immunohistochemically, the tumor cells were positive for vimentin, cytokeratin, and p53, and negative for synaptophysin, chromogranin, inhibin, and S-100. Ultrastructurally, the cytoplasm of the tumor cells was packed with mitochondria. The patient underwent left radical nephrectomy as well as a combined cardiopulmonary bypass, with atriotomy and resection of the tumor from the right atrium and inferior vena cava. Three months of postoperative follow-up were uneventful. Copyright 2000 Wiley-Liss, Inc.

10
UI - 21135415
AU - Wragg T; Nguyen GK
TI - Cytopathology of adrenal cortical oncocytoma.
SO - Diagn Cytopathol 2001 Mar;24(3):222-3

11
UI - 21387030
AU - Heilmann P; Wagner P; Nawroth PP; Ziegler R
TI - [Therapy of the adrenocortical carcinoma with Lysodren (o,p'-DDD). Therapeutic management by monitoring o,p'-DDD blood levels]
SO - Med Klin 2001 Jul 15;96(7):371-7
AD - Abteilung fur Innere Medizin I, Endokrinologie und Stoffwechsel, Universitatsklinikum Heidelberg. Peter_Heilmann@med.uni-heidelberg.de
BACKGROUND: o,p'-DDD (1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-ethane), which leads to a cytotoxic necrosis of the adrenal glands, currently is therapy of choice for metastasized adrenocortical carcinomas. Clinical experience is still poor, but most studies demonstrate an increment of survival time in patients treated with o,p'-DDD after incomplete surgery. The therapeutic range is close and therefore dosage is difficult, mainly based on clinical signs. Methods for routine determination of o,p'-DDD are not yet broadly available. PATIENTS AND METHOD: We developed a method for the determination of o,p'-DDD and report our experience with the monitoring of serum levels of o,p'-DDD in our patients. Nine patients have been included, eight patients with metastasized adrenocortical carcinoma were treated with o,p'-DDD. RESULTS: At time of evaluation six of eight patients had deceased, 27.9 +/- 25.1 months after recurrence of the disease. Time of survival for all patients was 28.2 +/- 22.0 months since diagnosis of recurrence. In three patients the target dose of 9-10 g/d could not be reached due to the clinical situation. The serum levels of these patients were low (6.3 +/- 4.2 micrograms/ml). Mean survival time was significantly longer for those patients who reached serum levels above 14 micrograms/ml in comparison to those who failed to reach such high levels (41.3 +/- 16.2 vs 6.3 +/- 3.6 months, p < 0.01). The dose which was necessary to reach high levels was individually different. All patients developed adrenocortical insufficiency. Other side effects were fatigue (seven patients), gastrointestinal problems and elevated liver enzymes (six patients each), changes in blood count (five patients) and central nervous disorder (four patients). All patients developing intolerable side effects had very high serum levels of o,p'-DDD (> 20 micrograms/ml). CONCLUSIONS: Our data confirm that the efficacy of a therapy with o,p'-DDD as well as the risk to develop intolerable side effects depend on the serum levels of o,p'-DDD. Monitoring of o,p'-DDD therapy by measuring serum levels of o,p'-DDD helps to adapt this therapy individually, avoiding serious side effects as well as to realize antitherapeutical resistance. Determination of o,p'-DDD serum levels helps to decide over intensification or cessation of therapy.