Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases.

Thompson LD.
Am J Surg Pathol. 2002 May;26(5):551-66.
No comprehensive series has evaluated the histologic features of pheochromocytoma to separate benign from malignant pheochromocytoma by histomorphologic parameters only. Fifty histologically malignant and 50 histologically benign pheochromocytomas of the adrenal gland were retrieved from the files of the Armed Forces Institute of Pathology. The patients included 43 females and 57 males, with an age range of 3-81 years (mean 46.7 years). Patients usually experienced hypertension (n = 79 patients). The mean tumor size was 7.2 cm (weight was 222 g). Histologically, the cases of malignant pheochromocytomas of the adrenal gland more frequently demonstrated invasion (vascular [score = 1], capsular [score = 1], periadrenal adipose tissue [score = 2]), large nests or diffuse growth (score = 2), focal or confluent necrosis (score = 2), high cellularity (score = 2), tumor cell spindling (score = 2), cellular monotony (score = 2), increased mitotic figures (>3/10 high power fields; score = 2), atypical mitotic figures (score = 2), profound nuclear pleomorphism (score = 1), and hyperchromasia (score = 1) than the benign tumors. A Pheochromocytoma of the Adrenal gland Scaled Score (PASS) weighted for these specific histologic features can be used to separate tumors with a potential for a biologically aggressive behavior (PASS > or =4) from tumors that behave in a benign fashion (PASS <4). The pathologic features that are incorporated into the PASS correctly identified tumors with a more aggressive biologic behavior. Application of these criteria to a large cohort of cases will help to elucidate the accuracy of this grading system in clinical practice.
PubMed ID: 11979086
Article Size: 3 MB

Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients.

Wieneke JA, Thompson LD, Heffess CS.
Am J Surg Pathol. 2003 Jul;27(7):867-81.
Adrenal cortical neoplasms in pediatric patients (<20 years) are rare. The clinical manifestations and biologic behavior of these lesions can be quite distinct from their histologically similar counterparts in the adult population, making pathologic criteria for distinguishing benign from malignant tumors equivocal. We undertook a study of 83 adrenal cortical neoplasms to determine if adult clinical and histologic features can be applied to pediatric patients in an outcome-based analysis. Most of the patients (50 girls and 33 boys) presented with hormone-related symptoms present for a mean of 6.8 months. The tumors ranged in size from 2 to 20 cm (mean 8.8 cm). Histologic parameters examined included capsular and/or vascular invasion, extraadrenal soft tissue extension, growth pattern, cellularity, necrosis, cytoplasmic eosinophilia, nuclear pleomorphism, nuclear-to-cytoplasmic ratio, prominent nucleoli, mitotic figures, atypical mitotic figures, bands of fibrosis, and calcifications. Immunophenotypically, there was reactivity with inhibin, vimentin, CK5, and focally with p53 and Ki-67. All patients underwent adrenalectomy, and 20 patients received adjuvant therapy. All patients with tumors classified as adenomas (n = 9) were alive, without evidence of disease (mean 14.7 years), whereas 21 patients with carcinomas had died with disease (mean 2.4 years). Only 31% of histologically malignant tumors behaved in a clinically malignant fashion. Features associated with an increased probability of a malignant clinical behavior included tumor weight (>400 g), tumor size (>10.5 cm), vena cava invasion, capsular and/or vascular invasion, extension into periadrenal soft tissue, confluent necrosis, severe nuclear atypia, >15 mitotic figures/20 high power fields, and the presence of atypical mitotic figures. Vena cava invasion, necrosis, and increased mitotic activity (>15 mitotic figures/20 high power fields) independently suggest malignant clinical behavior in multivariate analysis.
PubMed ID: 12826878
Article Size: 2 MB

Corticomedullary mixed tumor of the adrenal gland.

Wieneke JA, Thompson LD, Heffess CS.
Ann Diagn Pathol. 2001 Oct;5(5):304-8.
Corticomedullary mixed tumors of the adrenal gland are quite rare, with only five well-documented cases reported in the literature.(1-4) Herein, we report the light microscopic and immunohistochemical features of two cases of this rare tumor. Patient 1 is a 34-year-old woman who presented with hypertension, hair loss, and amenorrhea of 1-year duration. Patient 2 is a 52-year-old woman who presented with flank pain and what appeared to be a renal mass on arteriogram with no history of hypertension, Cushing’s syndrome, or other endocrine abnormalities. At surgery, the tumor was noted to arise from the adrenal gland rather than the kidney and adrenalectomy was performed. In both cases, the surgically resected specimens consisted of a well-circumscribed, single adrenal mass surrounded by a rim of uninvolved adrenal cortical tissue. The tumors were composed of adrenal cortical cells intimately admixed with pheochromocytes. Immunohistochemical studies highlighted these two cellular components. The pheochromocytes were strongly reactive with chromogranin and the sustentacular cells with S-100 protein, whereas the adrenal cortical cells reacted specifically with inhibin. Thus, we report two additional cases of mixed corticomedullary tumor of the adrenal gland. Ann Diagn Pathol 5:304-308, 2001. This is a US government work. There are no restrictions on its use.
PubMed ID: 11598859
Article Size: <1 MB


Thompson LDR.
Pathol Case Rev 2005;10 (5): 243-25.
Pheochromocytomas are tumors arising from the chromaffin cells of the adrenal medulla. They are equivalent to paragangliomas in other anatomic sites. They are uncommon neoplasms and most are sporadic, although 10% are described in syndromes, another 10% are bilateral (usually syndrome associated), and about 10% are malignant. They develop in both genders and peak in the fourth to fifth decades, although familial tumors occur at a younger age. Patients present clinically with the pharmacologic effects of excess catecholamines, manifested by episodic, postural, paroxysmal and/or labile hypertension, headaches, diaphoresis, palpitations, chest pain, and anxiety. Radiographic studies with nucleotide scans are often diagnostic. Malignant pheochromocytomas have historically required the presence of metastatic tumor to confirm the diagnosis of a malignant neoplasm. However, a series of histologic features, when used in conjunction with laboratory findings, radiographic findings, macroscopic features, and immunohistochemical results, can help to prospectively diagnose malignant heochromocytoma. These features include invasion, large nests or diffuse growth (loss of Zellballen architecture), focal or confluent necrosis, high cellularity, tumor cell spindling, cellular monotony, increased mitotic figures, atypical mitotic figures, profound nuclear pleomorphism, and hyperchromasia. Overall, the patient prognosis for benign pheochromocytoma is excellent, although that for malignant pheochromocytoma is intermediate, with surgery achieving the best clinical result of about 75% 5-year survival. Separation from benign pheochromocytoma and adrenal cortical neoplasms is important as the management is different.
PubMed ID: n/a
Article Size: 4 MB