An unusual case of ectopic corticotrophin-releasing hormone syndrome caused by an adrenal noncatecholamine-secreting pheochromocytoma: a case report.

BACKGROUND: Pheochromocytoma, especially for noncatecholamine-secreting pheochromocytoma, is an extremely rare cause of ectopic corticotrophin-releasing hormone (CRH) syndrome. CASE PRESENTATION: A 27-year-old Chinese woman was administered dexamethasone for a skin allergy, but her general condition rapidly deteriorated over a month. She was subsequently hospitalized for typical clinical features of Cushing's syndrome. Endocrinological investigation confirmed severe hypercortisolism along with elevated plasma adrenocorticotropin hormone (ACTH). However, magnetic resonance imaging (MRI) revealed no pituitary adenoma. Abdominal contrast-enhanced computed tomography (CT) revealed a 6.5 cm heterogeneous right adrenal mass with mildly contrast enhancement. The tumor was found during a routine physical check-up at a local hospital 16 months ago; however, the patient did not have any symptoms and did not seek further medical attention at that time. Laparoscopic resection of the right adrenal tumor led to a rapid remission of Cushing's syndrome. Based on pathological findings and the presence of normal catecholamine metabolites in her serum and urine, the patient was diagnosed with noncatecholamine-secreting pheochromocytoma. Immunohistochemical staining of the adrenal tumor revealed positive staining for CRH and negative staining for ACTH. CONCLUSIONS: This is an extremely rare case of ectopic CRH syndrome caused by an adrenal noncatecholamine-secreting pheochromocytoma. Both ectopic ACTH syndrome and ectopic CRH syndrome should be considered in patients presenting with ACTH-dependent Cushing's syndrome caused by extrapituitary diseases.

Contrast-enhanced MRI in preoperative assessment of myometrial and cervical invasion, and lymph node metastasis: diagnostic value and error analysis in endometrial carcinoma.

OBJECTIVE: To determine the ability of contrast-enhanced magnetic resonance imaging to predict myometrial invasion, cervical invasion, and pelvic lymph node metastasis in endometrial carcinoma and to analyze factors that lead to errors in this identification. DESIGN: A retrospective study. SETTING: University general hospital. POPULATION: A total of 167 women diagnosed with endometrial carcinoma. METHODS: All patients received a preoperative contrast-enhanced magnetic resonance imaging scan. Histopathological findings were used as the definitive diagnosis. MAIN OUTCOME MEASURES: The results were compared with histopathological findings, factors that make accurate assessment of myometrial invasion, cervical invasion, and pelvic lymph node metastasis difficult by contrast-enhanced magnetic resonance imaging were analyzed. RESULTS: The sensitivity, specificity, diagnostic accuracy, positive predictive values, and negative predictive values of contrast-enhanced magnetic resonance imaging were 90.9, 91.8, 91.6, 73.2 and 97.6%, respectively, for identifying deep myometrial invasion; 84.2, 96.0, 94.6, 72.7 and 97.9%, respectively, for identifying cervical invasion; and 45.0, 91.2, 85.6, 40.9 and 92.4%, respectively, for identifying pelvic lymph node metastasis. The main causes of error in contrast-enhanced magnetic resonance imaging were myomas, cornual lesions, deep myometrial invasion, large tumor size, non-endometrioid tumor type, and lower tumor grade. CONCLUSION: Contrast-enhanced magnetic resonance imaging has a high accuracy and a low tendency to produce false-negative predictive values. Gynecological oncologists should combine the imaging data and clinical information to make therapeutic decisions and avoid diagnostic errors.

[Pheochromocytomas in adrenal medulla or extra-adrenal and multiple endocrine neoplasms:a clinicopathologic analysis of 181 cases].

OBJECTIVE: To analyze the change in the incidence of pheochromocytomas in adrenal medulla or extra-adrenal and multiple endocrine neoplasm type 2 (MEN2), to summarize the clinical characteristics of benign, potentially malignant and malignant pheochromocytomas and to investigate the correlation between clinical manifestations and pathological changes. METHODS: Statistic analysis was performed to detect the incidence, constituent ratio, mean diagnostic age, sex proportion and correlation between clinical manifestions and pathologic changes in pheochromocytomas in adrenal medulla or extra-adrenal gland and MEN2 from 1993 to 2008 in the Department of Pathology, the General Hospital of Tianjin Medical University with Runs test, ANOVA, t test and chi-square test. RESULTS: The total number of biopsies within the 16 years was 167 702 cases (average 10 481 cases per year). The numbers (detectable rate) of total adrenal diseases, pheochromocytomas in adrenal medulla and extra-adrenal glands were 910 (0.54%), 139 (0.08%), and 42 (0.03%) cases, respectively. The numbers (constituent ratio) of benign, potentially malignant and malignant of pheochromocytomas in adrenal medulla were 102 cases (73.4%), 29 cases (20.9%) and 8 cases (5.7%), respectively; in the 102 cases of benign tumors, patients with MEN2 were 8 (7.8%); the three groups of the tumors in extra-adrenal sites were 18 (42.8%) cases, 12 (28.6%) cases and 12 (28.6%) cases. There were no changes in the detectable rate and constituent ratio of adrenal diseases, benign, potential malignant and malignant pheochromocytomas in adrenal medulla or extra-adrenal glands and patients with MEN2 during the past 16 years (P > 0.05), but there was a tendency that malignant transformation was gradually increased with age, which was more commonly found in male patients than females. The mean age at diagnosis of patients with benign and potentially malignant pheochromocytomas was 42.7 years (ranged from 10 - 74 years), and 40.1 years (13 - 66 years), respectively, which were younger than patients with malignant pheochromocytomas (51.6 years, P < 0.05); the mean age of patients with benign and potentially malignant pheochromocytomas in extra-adrenal sites was 43.1 years (ranged from 20 - 75 years) and 45.2 years (28 - 65 years) that were older than those with malignant (37.8 years, ranged from 14 - 58 years, P < 0.05). It was spectacular that patients with malignant pheochromocytoma in adrenal medulla (51.6 years) were older than that in extra-adrenal sites (37.8 years); all the patients with MEN2 were female benign pheochromocytoma in adrenal medulla, whose age (38.9 years) was younger than that of benign lesions (42.7 years, P < 0.05), in which thyroid medullary carcinoma appeared early than pheochromocytomas in adrenal medulla. The detectable rate of hypertension in patients with malignant pheochromocytomas in adrenal medulla and in extra-adrenal sites were less than that in benign and potentially malignant ones (P < 0.05). The bilateral lesions more commonly found in malignant pheochromocytoma (25.0%) than benign (15.7%) and potentially malignant pheochromocytomas (6.9%) only in adrenal medulla. Relapse rates in both adrenal and extra-adrenal tumors were rising from benign (11.8%, 0), potentially malignant (13.8%, 25.0%), to malignant (33.3%, 37.5%) groups; the average diameter of pheochromocytomas in both adrenal and extra-adrenal sites was increasing from benign (4.2 cm, 4.0 cm), potentially malignant (5.3 cm, 5.6 cm) to malignant (7.3 cm, 6.9 cm) groups (P < 0.05). CONCLUSIONS: The diagnostic criteria of benign, potentially malignant and malignant pheochromocytomas in adrenal medulla and in extra-adrenal sites are well established according to the WHO classification of endocrine tumors (2004). The closer relationship is found between clinical manifestations and pathologic changes. The definite type and nature of pheochromocytomas are mainly rested upon the pathologic examination.

[Pathologic study of expression and significance of matrix metalloproteinases-9, tissue inhibitor of metalloproteinase-1, vascular endothelial growth factor and transforming growth factor beta-1 in papillary carcinoma and follicular carcinoma of thyroid].

OBJECTIVE: To study the roles of matrix metalloproteinases-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF) and transforming growth factor ß-1 (TGFß-1) in differentiation, invasiveness and metastatic potential of papillary carcinoma and follicular carcinoma of thyroid. METHODS: Eighty-five cases of papillary thyroid carcinoma and 59 cases of follicular thyroid carcinoma were enrolled into the study. Immunohistochemistry using EnVision method was carried out for assessment of the expression of MMP-9, TIMP-1, VEGF and TGFß-1 in the tumor tissue. RESULTS: MMP-9, TIMP-1, VEGF and TGFß-1 were expressed in the cytoplasm of tumor cells. The positivity rates of MMP-9, TIMP-1, VEGF and TGFß-1 in papillary thyroid carcinoma (83.5%, 81.2%, 90.6% and 75.3%, respectively) were similar to or lower than those in follicular thyroid carcinoma (93.2%, 86.4%, 89.9% and 78.0%, respectively). The expression rates in papillary thyroid carcinoma with lymph node metastasis were also higher than those in tumors without lymph node metastasis. The expression rates of MMP-9, VEGF and TGFß-1 in poorly-differentiated follicular thyroid carcinoma were higher than those in well-differentiated follicular thyroid carcinoma. The expression of TIMP-1 however showed a negative correlation with the tumor cell differentiation. In general, the expression of VEGF and MMP-9 was higher than that of TIMP-1 and TGFß-1 in papillary thyroid carcinoma and follicular thyroid carcinoma. CONCLUSIONS: Immunohistochemical detection of MMP-9, TIMP-1, VEGF and TGFß-1 expression may carry clinical significance in evaluating the degree of differentiation, invasiveness, metastatic potential and prognosis of papillary thyroid carcinoma and follicular thyroid carcinoma.

Nonfunctional pancreatic endocrine tumor in the peripancreatic region in a Chinese patient with multiple endocrine neoplasia type 1.

Nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) in patients with multiple endocrine neoplasia type 1 (MEN1), which results from a mutation in the MEN1 gene, are commonly small, multiple tumors located in the pancreatic head and inside the pancreatic parenchyma. We herein describe a 35-year-old woman with bone pain and a 7-year history of a prolactinoma. She was clinically diagnosed with MEN1 based on the presence of the prolactinoma and parathyroid hyperplasia. Abdominal computed tomography revealed a 5-cm mass close to the splenic hilum. This soft tissue tumor, which was located outside the pancreatic parenchyma and the tissue origin of which could not be identified preoperatively, was found to be connected to the pancreatic tail. After resection, histological examination revealed a well-differentiated neuroendocrine tumor of pancreatic origin. Genetic testing revealed a heterozygous transition mutation of guanine to adenine at the coding nucleotide 133 in exon 2 (c.133G>A), resulting in an amino acid substitution of glutamic acid with lysine (E45K) in the MEN1 gene. This patient with MEN1 presented with a clinical condition involving a single non-metastatic NF-pNET located outside the pancreatic parenchyma with a missense mutation in the MEN1 gene, which could easily have been misdiagnosed as an accessory spleen.