Nuclear DNA content and morphological characteristics in the prognosis of adrenocortical carcinoma

Malignant primary adrenal tumors are rare forms of cancer with an estimated incidence of two to ten new cases per one million inhabitants per year. The 5-year survival rate for adrenocortical carcinoma is approximately 35%, whereas the 10-year survival rate of malignant pheochromocytoma reaches 40%. Clinical studies support repeated surgery as the mainstay of treatment, either with curative or palliative intention. For adrenocortical carcinoma, adjunctive treatment with oral mitotane leads to well-documented improvement of survival. Rare malignant pheochromocytomas with distant metastases are preferably treated by 131I-MIBG. Chemotherapy is reserved for unresectable tumors without sufficient response to mitotane or 131I-MIBG, respectively. Cisplatin and etoposide as single therapy, or in combination with doxorubicin or etoposide, appear to be effective in adrenocortical carcinoma. Malignant pheochromocytoma may be treated with vincristine, dacarbazine, and cyclophosphamide. Treatment with octreotide is currently being evaluated. Radiotherapy is indicated if unresectable tumor masses cause local symptoms. If symptoms of endocrine activity are not sufficiently controlled by measures aiming at tumor mass reduction, specific inhibitors of hormone synthesis or action are available. Ketoconazole is widely used for adrenocortical carcinoma, and phenoxybenzamine and metyrosine are available for malignant pheochromocytoma. This review provides guidelines for rational disease management based on still scanty clinical evidence.

show abstract

“…Metastases were present at the time of diagnosis in 30±40% of cases (Luton et al 1990;Haak et al 1993). …”

Section: Clinical Presentationmentioning

confidence: 99%

Clinical management of malignant adrenal tumors

Kopf

Goretzki

Lehnert

2001

Journal of Cancer Research and Clinical Oncology

View full text Add to dashboard Cite

show abstract

“…Nuclear DNA content by flow cytometry correlates poorly with histological and mitotic indices and cannot reliably differentiate between adrenocortical adenoma and carcinoma (8). P53 tumor suppressor gene alterations have been shown to have variable expression and little prognostic value for adrenocortical carcinoma (8 -10).…”

mentioning

confidence: 99%

Adrenocortical Adenoma and Carcinoma: Histopathological and Molecular Comparative Analysis

et al. 2003

View full text Add to dashboard Cite

We compared histomorphological features and molecular expression profiles of adrenocortical adenomas (ACAd) and carcinomas (ACCa). A critical histopathological review (mean, 11 slides per patient) was conducted of 37 ACAd and 67 ACCa. Paraffinembedded tissue cores of ACAd (n ‫؍‬ 33) and ACCa (n ‫؍‬ 38) were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, p27, and Ki-67 were investigated by immunohistochemistry and correlated with histopathology and patient outcome using standard statistical methodology. Median follow-up period was 5 years. Tumor necrosis, atypical mitoses, and >1 mitosis per 50 high-power fields were factors that were highly specific for ACCa (P < .001). Number (0 to 4) of unfavorable markers [Ki-67 (؉), p21 (؉), p27 (؉), mdm-2(؊)] expressed was significantly associated with mitotic activity and morphologic index (i.e., number of adverse morphologic features) and highly predictive of malignancy (P < .001). Ki-67 overexpression occurred in 0 ACAd and 36% ACCa (P < .001) and was significantly associated with mitotic rate and unfavorable morphologic index (P < .001). Tumor necrosis, atypical mitoses, >5 mitoses per 50 high-power fields, sinusoidal invasion, histologic index of >5, and presence of more than two unfavorable molecular markers were associated significantly with metastasis in ACCa. Wellestablished histopathologic criteria and Ki-67 can specifically distinguish ACCAd from ACCa. Tumor cell proliferation (Ki-67) correlates with mitotic activity and morphologic index. Tumor morphology is a better predictor of metastatic risk in ACCa than current immunohistochemistry-detected cell cycle regulatory and proliferation-associated proteins.KEY WORDS: Adenoma, Adrenal, Carcinoma, IHC, Tissue microarray. Mod Pathol 2003;16(8):742-751Adrenocortical carcinoma is a highly aggressive, rare endocrine malignancy. However, benign, clinically occult adrenal adenomas, adrenal "incidentalomas," are encountered frequently by abdominal imaging performed for unrelated indications. The unsuspected adrenal mass is detected in 2-4% of the general population and in Յ6% of abdominal computed tomography scans in patients aged 60 -70 years (1, 2). The size of the adrenal mass is considered to be the most reliable predictor of malignancy. As 8 -13.5% of resected adrenocortical carcinomas are Ͻ5 cm, size alone is an imperfect criterion for malignancy (3). In a study of metastasizing and nonmetastasizing adrenocortical tumors among 43 patients followed for a median of 11 years, Weiss (4) demonstrated the utility of nine histomorphologic criteria in predicting the biology of adrenocortical neoplasms. The histologic findings most predictive of malignancy were Ͼ5 mitoses per 50 high-power fields, atypical mitoses, and venous invasion. No single criterion could distinguish benign from malignant tumor biology; all but one of the benign adrenocortical tumors had two or fewer criteria. In a later study, Weiss et al. (5) modified the diagnostic criteria for benign and malig...

show abstract

“…1,4,5,7,25,31 Adrenocortical carcinomas may be diploid, and adenomas may be aneuploid. 7,13 Patients with diploid and aneuploid carcinomas have been clinically free of metastases. 5,7,25,31 However, in published series, most patients who developed metastases had aneuploid tumors.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 The value of DNA ploidy and proliferation index results in the assessment of malignancy is controversial as well. 4,5,7,13 With newer radiologic imaging techniques, smaller tumors are being de- More studies are needed to correlate p53 protein overexpression in adrenal cortical carcinoma with ploidy and proliferation marker assessment.tected, 18 and with the recent advent of fine needle aspiration biopsy (FNAB), a smaller amount of material is available for diagnosis. 18,35 Furthermore, a histologic scoring system may not be applicable or technically feasible for cytologic specimens, and other ways to establish the diagnosis should be considered.…”

mentioning

confidence: 99%