Thymic Carcinoid Research Articles

Multiple Endocrine Neoplastic-Associated Thymic Carcinoid Tumour in Close Relatives: Octreotide Scan as a New Diagnostic and Follow-up Modality: Two Case Reports

Thymic carcinoid tumours constitute less than 1% of all carcinoids, and differ markedly from true thymomas in natural history, morphology, prognosis and therapeutic options. New clinical and diagnostic modalities are described in two brothers with thymic carcinoid associated with multiple endocrine neoplasia syndrome. Octreotide scintigraphy proved useful for diagnosis and follow-up, and somatostatin receptor positivity may provide new prospects for treatment of non-resectable or recurrent tumour.

Fine-needle aspiration of the mediastinum: a clinical, radiologic, cytologic, and histologic study of 42 cases.

Forty-two fine-needle aspirates (FNA) of the mediastinum were reviewed from 1984-1995. The clinical, radiologic, pathologic, and cytologic material was studied. Twenty-five males and 17 females had an age range from 10-72 yr and a mean of 41 yr. Common complaints were chest pain, dyspnea, and cough. Thirty-eight tumors were in the anterior/superior mediastinum. Fifty-seven percent were primary neoplasms (Hodgkin's lymphoma, 7; non-Hodgkin's lymphoma, 6; thymoma, 3; germ-cell tumor, 3; thymic carcinoid and angiosarcoma, 1 each; and malignant not otherwise specified, 3). Twenty-four percent were metastatic tumors (carcinoma, 9; and sarcoma, 1). Twelve percent were benign conditions (granulomatous disease, 2; multinodular goiter, 1; extramedullary hematopoesis, 1; and one thymic cyst). Seven percent were inconclusive. FNA yielded adequate tissue for diagnosis in 83% and a correct diagnosis in 86%. There was one false-negative and no false-positive diagnosis. FNA is a useful tool for accurate tissue diagnosis of mediastinal masses.

Fine‐needle aspiration of the mediastinum: A clinical, radiologic, cytologic, and histologic study of 42 cases

Forty-two fine-needle aspirates (FNA) of the mediastinum were reviewed from 1984–1995. The clinical, radiologic, pathologic, and cytologic material was studied. Twenty-five males and 17 females had an age range from 10–72 yr and a mean of 41 yr. Common complaints were chest pain, dyspnea, and cough. Thirty-eight tumors were in the anterior/superior mediastinum. Fifty-seven percent were primary neoplasms (Hodgkin's lymphoma, 7; non-Hodgkin's lymphoma, 6; thymoma, 3; germ-cell tumor, 3; thymic carcinoid and angiosarcoma, 1 each; and malignant not otherwise specified, 3). Twenty-four percent were metastatic tumors (carcinoma, 9; and sarcoma, 1). Twelve percent were benign conditions (granulomatous disease, 2; multinodular goiter, 1; extramedullary hematopoesis, 1; and one thymic cyst). Seven percent were inconclusive. FNA yielded adequate tissue for diagnosis in 83% and a correct diagnosis in 86%. There was one false-negative and no false-positive diagnosis. FNA is a useful tool for accurate tissue diagnosis of mediastinal masses. Diagn. Cytopathol. 1998;19:428–436. © 1998 Wiley-Liss, Inc.

The variable penetrance and spectrum of manifestations of multiple endocrine neoplasia type 1

Background: Some experts maintain that (1) >90% of patients with multiple endocrine neoplasia type 1 (MEN1) are first seen with hyperparathyroidism (HPTH) so that routine screening for other features is unnecessary and (2) MEN1 has ≥94% penetrance by age 50 years. Methods: We constructed a regional registry of patients with or at risk for MEN1 and examined phenotypic profiles in 34 patients. MEN1 was defined as (1) endocrinopathy of 2 of the 3 principal related tissues (parathyroid, gastrointestinal endocrine, pituitary) or (2) 1 such feature plus a first-degree relative with MEN1. Results: The initial feature of MEN1 was HPTH in 50%, pituitary tumor in 18%, and gastrointestinal endocrine tumor in 32% of patients, with overall incidences of 82%, 65%, and 74%, respectively. HPTH developed by age 50 years in 73% of patients and by age 70 years in 83%. Penetrance of MEN1 at age 50 years was 82%. Associated features included renal (1) and rectal (1) cancer, malignant thymic carcinoid (1), and malignant pheochromocytoma (1). Conclusions: Expression of MEN1 can vary considerably from established patterns. In our geographic region HPTH does not routinely precede other features of MEN1 and cannot be used to distinguish affected patients among those at risk. MEN1 can be inapparent until late in life and may be significantly underdiagnosed. (Surgery 1998;124:1106-14.)

Anti-neuronal nuclear autoantibodies, types 1 and 2: their utility in the study of tumors of the nervous system.

This is a comprehensive immunohistochemical study of selected archival tumors of the nervous system applying human anti-neuronal nuclear autoantibodies of types 1 and 2 (ANNA-1 and -2), serum markers of paraneoplastic syndromes associated primarily with small cell lung cancer (SCLC). Neither ANNA-1 nor ANNA-2 bound to glial tumors regardless of histological grade and subtype; instead they labeled neurons in overrun normal parenchyma. Central neurocytomas and the neuronal components of mixed glioneuronal tumors were also immunoreactive for both. In addition, varying proportions of tumor cells were stained in dysembryoplastic neuroepithelial tumor, subependymal giant cell astrocytoma (SEGA), tuber and neuroblastoma. All other tumors were nonreactive, namely choroid plexus papilloma, pituitary adenoma, pineocytoma, pheochromocytoma, thymic and pulmonary carcinoid, chordoma, meningioma, schwannoma and metastatic melanoma. SCLC was immunonegative for ANNA-1 and ANNA-2 in paraffin preparations, but displayed strong immunoreactivity for both in frozen sections: this discrepancy was not observed in other tumors studied. In conclusion, the human IgG autoantibodies ANNA-1 and ANNA-2 provide novel tools for studying the cytogenesis of tumors of the nervous system in that they permit the identification of both normal and neoplastic, poorly differentiated and small neuronal cells that may escape detection using commercially available anti-neuronal antibodies.

Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors.

Synthetic GH secretagogues (GHSs; GH-releasing peptides and their nonpeptide mimetics) stimulate GH release, activate the hypothalamo-pituitary-adrenal axis, and release PRL in vivo. Patients with acromegaly show an exuberant GH response to GHSs, whereas patients with pituitary-dependent ACTH-secreting tumors show an exaggerated rise in ACTH and cortisol. We, therefore, studied the presence of GHS receptor (GHS-R) messenger ribonucleic acid (RNA) in 38 human pituitary tumors of different cell types, 3 ectopic ACTH-secreting tumors, a pancreatic gastrinoma, 3 insulinomas, and a non-secreting thymic carcinoid as well as in 7 normal pituitary glands. Certain pituitary tumors were also studied by in vitro cell culture with measurement of secreted GH, ACTH, PRL, FSH, LH, alpha-subunit, and TSH. RNA was extracted from tissue samples and, after RT, a duplex PCR reaction with primers for the GHS-R gene and for the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase was performed, allowing semiquantitation of GHS-R expression. All the somatotroph adenomas (n = 8) showed a 2-10 times higher expression of the GHS-R gene compared to normal pituitaries. Higher than normal expression was shown in 5 of 18 tumors from patients with ACTH-secreting pituitary adenomas and in 1 of 3 ectopic ACTH-secreting carcinoid tumors. Two of the pituitary ACTH-secreting adenoma samples showed completely absent expression of the GHS-R, 8 showed expression similar to that of normal pituitary tissue, and 3 of the corticotroph adenoma tissue samples and 2 ectopic ACTH-secreting tumors showed a very low level of expression. One of 4 prolactinoma samples showed a high level of expression, 1 showed expression similar to that of normal pituitary, and 2 samples showed a very low level of expression. Nonfunctioning pituitary adenoma samples showed either absent or very low level expression of the GHS-R. The pancreatic gastrinoma sample showed expression similar to that of normal pituitary tissue, whereas 3 insulinomas showed low level expression of the GHS-R gene; a nonsecreting thymic carcinoid tumor showed no detectable expression. In summary, although GHS-R messenger RNA is abundant in human somatotroph adenomas, it is also present in other pituitary adenomas, particularly ACTH-secreting tumors. These findings may explain the in vivo responses to GHSs in patients harboring such tumors. It also appears from our study that GHS-R may be expressed in other neuroendocrine tumors.

Thymic Carcinoids in Multiple Endocrine Neoplasia Type 1

To study the clinical, pathologic, and genetic features of thymic carcinoids in the setting of multiple endocrine neoplasia type 1 (MEN1) and to study means for detection and prevention of this tumor in patients with MEN1. Thymic carcinoid is a rare malignancy, with approximately 150 cases reported to date. It may be associated with MEN1 and carries a poor prognosis, with no effective treatment. Its underlying etiology is unknown. Ten patients with MEN1 from eight families with anterior mediastinal tumors were included in a case series study at tertiary referring hospitals. Clinicopathologic studies were done on these patients, with a review of the literature. Mutation analysis was performed on the MEN1 gene in families with clusterings of the tumor to look for genotype-phenotype correlation. Loss of heterozygosity was studied in seven cases to look for genetic abnormalities. Histologic studies of all tumors were consistent with the diagnosis of thymic carcinoid. Clustering of this tumor was found in some of the families-three pairs of brothers and three families with first- or second-degree relatives who had thymic carcinoid. All patients described here were men, with a mean age at detection of 44 years (range 31 to 66). Most of the patients had chest pain or were asymptomatic; none had Cushing's or carcinoid syndrome. All tumors were detected by computed tomography (CT) or magnetic resonance imaging (MRI) of the chest. The results of octreoscans performed in three patients were all positive. Histopathologic studies were consistent with the diagnosis of thymic carcinoid and did not stain for ACTH. Mutation analysis of the families with clustering revealed mutations in different exons/introns of the MEN1 gene. Loss of heterozygosity (LOH) studies of seven tumors did not show LOH in the MEN1 region, but two tumors showed LOH in the 1p region. MEN1-related thymic carcinoids constitute approximately 25% of all cases of thymic carcinoids. In patients with MEN1, this is an insidious tumor not associated with Cushing's or carcinoid syndrome. Local invasion, recurrence, and distant metastasis are common, with no known effective treatment. We propose that CT or MRI of the chest, as well as octreoscanning, should be considered as part of clinical screening in patients with MEN1. We also propose performing prophylactic thymectomy during subtotal or total parathyroidectomy on patients with MEN1 to reduce the risks of thymic carcinoid and recurrence of hyperparathyroidism. Its male predominance, the absence of LOH in the MEN1 region, clustering in close relatives, and the presence of different MEN1 mutations in these families suggest the involvement of modifying genes in addition to the MEN1 gene. A putative tumor suppressor gene in 1p may be involved.

Thymic carcinoids in multiple endocrine neoplasia type 1.

Thymic carcinoid is a rare malignancy with about 150 cases reported to date. It is associated with multiple endocrine neoplasia type 1 (MEN-1), but compared with other MEN-1-related neoplasia little is known about it. We have recently described and studied 20 MEN-1-related cases and found that up to 25% of all reported thymic carcinoids are MEN-1 related. It is an insidious tumour not associated with Cushing's syndrome or carcinoid syndrome. Local invasion, recurrence and distant metastasis are common with no known effective treatment. Its male predominance, the absence of loss of heterozygosity (LOH) in the MEN1 region, clustering in some MEN-1 families and the findings of different MEN1 mutations in these clustered families suggest the involvement of additional aetiological factors. We propose that computed tomography (CT) or magnetic resonance imaging (MRI) of the chest should be included as part of the clinical workup for all MEN-1 patients. Prophylactic thymectomy should be considered during subtotal or total parathyroidectomy on MEN-1 patients to reduce the risk of this malignancy.

Thymic carcinoid with mucinous stroma: a case report

Thymic carcinoid with mucinous stroma: a case report

Diagnostic and therapeutic criteria in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1.

About 25% of patients with ZES have MEN-1. Except for diarrhoea, less frequent in patients with ZES MEN-1 than in sporadic ZES, and specific MEN-1-related signs, clinical characteristics are similar in both ZES types. Acid output and gastrin level are also similar whether in the basal state or after secretin. Primary hyperparathyroidism (pHPT) exists in the majority of ZES MEN-1 patients, 30% have pituitary adenoma (prolactinomas for half), 30% adrenal involvement, 25-30% have ECLomas: bronchial and thymic carcinoids have probably been underevaluated. Gastrinomas are multiple predominantly located in the duodenal wall, but also in the pancreas in association with clinically silent endocrine tumours. The spread of the disease metastases to the liver (LM), mediastinum, bones, is evaluated best by Octreoscan. Associated endoscopic ultrasonography evaluates the number, size and anatomical characteristics of gastrinomas. Patients without LM have an excellent prognosis. Surgery never cures ZES, but is necessary in cases of associated life-threatening conditions such as insulinoma. Although the size of the tumour, when located in the pancreas >3 cm, favours metachronous LM occurrence, surgery in our experience has not been able to prevent LM development.

Expression of the MEN-1 gene in a large kindred with multiple endocrine neoplasia type 1.

In 1983 a large family with MEN-1 (designated Tasman 1) was identified in Tasmania. Kindred screening and case follow-up over the subsequent 15 years has yielded data on over 160 MEN-1-affected patients. Hyperparathyroidism is present in over 60% of gene carriers by age 20 years and 95% by age 30 years. Hyperplasia is the characteristic pathological finding. Kaplan-Meier analysis indicates hyperparathyroidism recurs in the majority of patients despite near-total parathyroidectomy. Gastrinoma, 'nonfunctioning' pancreatic adenoma and insulinoma occur in up to 60, 50 and 10% of patients, respectively. Metastatic gastroenteropancreatic (GEP) tumours develop in up to 35% of family members, being frequent in some branches of Tasman 1, whilst rare in others. Pituitary disease developed in 19% of patients. Prolactinoma and 'nonfunctioning' adenoma account for 76 and 24%, respectively, of pituitary abnormalities. Prolactinomas exhibit clustering within branches of the Tasman 1 kindred. Adrenal adenomas occur in 36% of patients. The majority of adrenal lesions are benign and nonsecretory and develop in association with pancreatic neoplasia. Carcinoid tumours are uncommon but important malignancies. Malignant thymic carcinoid occurs in male patients, whereas bronchial carcinoid occurs predominantly in women. Prior to recognition of MEN-1 in Tasman 1, complications of hyperparathyroidism and malignancy accounted for the majority of patient mortality. Since commencement of prospective screening, malignant GEP tumours and cardiovascular disease have become the most prevalent causes of death amongst MEN-1-affected patients.

Neuroendocrine differentiation in thymic epithelial tumors with special reference to thymic carcinoma and atypical thymoma

To determine the neuroendocrine (NE) features of thymic epithelial tumor, immunohistochemistry and electron microscopy studies were performed on eight NE tumors (thymic carcinoids) and 26 non-NE tumors (nine thymic carcinomas, five atypical thymomas, and 12 thymomas other than lymphocytic thymoma). Immunohistochemical studies were performed with antibodies against general markers for NE cells (synaptophysin, a subunit of a guanine nucleotidebinding protein, Go, and small-cell lung carcinoma cluster 1 antigen), and a broad panel of antibodies for hormonal substances. Thymic carcinoid showed synchronous diffuse immunoreactivity for the three NE markers and contained cells that were positive for a variety of hormonal products: human chorionic gonadotropin (hCG) a-subunit (eight of eight), hCG β-subunit (three of eight), adrenocorticotropic hormone (ACTH) (three of eight), calcitonin (two of eight), calcitonin gene-related peptide (two of eight), and serotonin (one of eight). Conversely, although positivity for NE markers was neither synchronous nor diffuse in non-NE tumors, seven of nine thymic carcinomas, three of five atypical thymomas (focal or dispersed distribution), and none of the five thymomas were positive for at least two of these NE markers. A small number of neoplastic cells were positive for hCGa-subunit or ACTH in three thymic carcinomas and one atypical thymoma. Ultrastructurally, dense core granules (DCG) were much more frequent in thymic carcinoid, but several DCG-like granules were identified in 12 of 13 non-NE tumors with or without immunoexpression of NE markers. The presence of focal or dispersed NE cells in thymic carcinoma and atypical thymoma may reflect multidirectional differentiation within the tumor, which, like cytological atypia, epithelial CD5 expression, and lack of immature T cell infiltration, may be another feature of this group at thymic tumors.

ACTH precursors: biological significance and clinical relevance.

ACTH is synthesized as part of the precursor proopiomelanocortin or POMC (Fig. 1). In the human pituitary POMC is enzymatically processed to pro-ACTH, which is then cleaved to give ACTH. Processing of POMC in the pituitary takes place within the regulated secretory pathway and is accomplished by the protease PC1 located within mature dense core granules (Benjannet et al., 1991; Smeekens et al., 1991). The presence of ACTH precursors in plasma was first demonstrated in normal subjects after stimulation with metyrapone (Yalow & Berson, 1971) and was later observed after insulin-induced hypoglycaemia (Hale et al., 1986). However, complex chromatographic techniques were required to separate ACTH precursors from ACTH. Clearly, this approach could not be used for large numbers of patient samples and would not provide a quantitative assessment of the concentrations of the ACTH precursors in plasma. We have subsequently quantified the concentrations of ACTH precursors in the human circulation under basal conditions. Direct measurement of these peptides was made possible by the development of a two-site immunoradiometric assay for the ACTH precursors, POMC and pro-ACTH (Crosby et al., 1988). The assay is based on a labelled monoclonal antibody which binds within the ACTH region of POMC and a solid phase antibody which recognizes N-terminal POMC (N-POC, Fig. 1). As binding of both antibodies is required to generate a signal, the assay does not detect ACTH. Using this assay, the concentrations of ACTH precursors in normal subjects were found to be 5-40 pmol/l which is equivalent to or greater than those of ACTH, N-POC, b-lipotrophin (b-LPH) and b-endorphin (Gibson et al., 1994). The levels of ACTH precursors and ACTH in the circulation at any given time are dependent on regulatory mechanisms influencing expression of the POMC gene. However, the relative concentrations of ACTH precursors and ACTH will depend on precursor processing and mechanisms of secretion from the corticotroph cells. Evidence from studies with the mouse corticotroph adenoma cell line, AtT20, suggests that in the absence of stimulation, corticotroph cells ‘leak’ newly synthesized POMC (Kelly, 1985). Furthermore, results we have obtained in normal subjects and from clinical studies indicate that acute regulation of secretion of ACTH and ACTH precursors differs (see below).

Mutation and expression analysis of the p27/kip1 gene in corticotrophin-secreting tumours.

The molecular mechanisms leading to Cushing's disease are unclear. Inhibitors of cyclin-cyclin dependent kinase (CDK) complexes are regulators of the cell cycle and may function as tumour suppressor genes, many of which have been involved in the pathogenesis of several human malignancies. A member of this family, the p27/kip1 gene, maps to chromosome 12p13 and encodes an inhibitor of several cyclin-CDK complexes; these control the progression of the cell cycle from G1 to S-phase. Complete lack of p27/kip1 function, as occurs in the p27/kip1 'knockout' mouse, produces a complex phenotype associated with the development of pituitary tumours, specifically those of the intermediate lobe corticotrophs. We therefore investigated whether structural and functional abnormalities of the p27/kip1 gene and loss at the chromosome 12p13 region were present in human corticotrophin (ACTH)-secreting pituitary tumours. We studied 21 pituitary tumours, of which 20 were ACTH-secreting (two of these had biochemical and histological features of 'intermediate-lobe' tumours and one was malignant) while the remaining tumour was a prolactinoma; three ectopic secretors of ACTH (two bronchial and one thymic carcinoid); and a non-secretory thymic carcinoid. The whole coding region of the p27/ kip1 gene was screened for mutations by PCR-SSCP analysis and/or direct sequencing, while tumour mRNA expression was analysed by means of a semi-quantitative duplex PCR. Three polymorphic microsatellite markers of the 12p13 region were used to assess loss of heterozygosity (LOH) in 12 samples. Finally, tumour p27/kip1 protein expression was assessed by immunohistochemistry using a monoclonal antibody in 12 samples suitable for analysis. No sequence abnormalities were found in any of the samples other than a previously-described polymorphism. No LOH was observed in the tumours analysed. p27/kip1 mRNA expression was similar in tumour samples in comparison with normal pituitaries. Seven of the eight corticotroph tumours analysed by immunohistochemistry stained positive for p27/kip1, including the intermediate lobe. The only malignant pituitary tumour in the original series showed an absence of staining for p27/kip1. In addition, the three carcinoid tumours studied were negative on immunohistochemistry. Of a further three malignant pituitary tumours assessed, two (including a prolactinoma) were essentially negative, while the third was moderately positive. We conclude that mutations of the p27/kip1 gene, deletions of the 12p13 area or changes in expression, are not a general feature of corticotroph tumours, even those with intermediate lobe characteristics. However, other mechanisms of p27/kip1 inactivation, such as an abnormality at the post-translational level, may be related to more aggressive histological subtypes of ACTH-secreting and possibly other pituitary tumours.

胸腺カルチノイド例

Thymic carcinoid is a rare tumor. The case of an 86-year-old male with a thymic carcinoid is presented. The patient was discovered to have an abnormal mass, as an incidental finding, at the thoracic inlet during a routine examination. He had slight dysphagia for 6 months. The tumor had displaced the trachea to the right, and compressed the esophagus. A CT scan demonstrated that the tumor was located in the superior mediastinum, and extended to the aortic arch. The preoperative diagnosis was a mediastinal goiter. The tumor was resected completely through a general collar incision, without a median sternotomy. The tumor measured 6.5×5.5×4.5cm in size, was grossly well-encapsulated and was diagnosed histologically as a carcinoid tumor. Mitoticfigures were not seen. The tumor cells had a few argyrophillic granules, and showed positive immunoreactivity for chromogranin A. Electronmicroscopy disclosed small granules with diameters of about 160nm. There were no clinical manifestations suggestive of a specific syndrome, such as a carcinoid syndrome. The patient recieved no postoperative radiation or chemotherapy, and is now quite well at 2 years after the operation.

A large multiple endocrine neoplasia type 1 family with clinical expression suggestive of anticipation.

We describe a large multigenerational multiple endocrine neoplasia Type 1 (MEN1) family with clinical expression suggestive of anticipation. In the second and third generations, two deceased obligate gene carriers died at the ages of 85 and 76 without the history of MEN1, whereas two other living gene carriers above the age of 65 have had no clinical evidence of MEN1 to date. In the fourth generation, eight members were affected, with four having severe MEN1-related and atypical malignancies: a case of metastatic endocrine pancreatic tumor, two cases of metastatic thymic carcinoids, and a case of spinal ependymoma. In the fifth generation, all five patients were below the age of 22 when the disease was detected. MEN1 was confirmed in the family by linkage analysis using MEN1-linked microsatellite markers and by identification of a nonsense mutation in the MEN1/menin gene. Alleotyping showed loss of heterozygosity (LOH) involving the wild-type alleles in seven tumors in the family including the ependymoma, which is the first MEN1-related case that shows genetic abnormality in chromosome 11q13, suggesting that MEN1 gene might be involved in the tumorigenesis of a subset of ependymomas. In relation to clinical anticipation, repeated expansion studies were carried out but failed to detect any expansion. We conclude that this is a unique MEN1 family and that an unknown genetic mechanism might be contributing to the anticipation phenomenon. We demonstrate in this family that all gene carriers, including the very young members, will need close and careful follow-up.

Primary Mediastinal Tumors. Part 1*: Tumors of the Anterior Mediastinum

Primary anterior mediastinal neoplasms comprise a diverse group of tumors and account for 50% of all mediastinal masses. Thymomas are most common and can be locally invasive and associated with parathymic syndromes. Thymic carcinomas and thymic carcinoids are rare malignancies with a propensity for local invasion and distant metastases. Thymolipomas are benign thymic tumors. The mediastinal germ cell tumors are a heterogeneous group of benign and malignant neoplasms. Mediastinal lymphangiomas are rare tumors and predominantly occur in young children. In contrast, mediastinal goiters are relatively common in adults. Mediastinal parathyroid adenomas are an uncommon cause of persistent hyperparathyroidism and rarely cause a discernible mass. The clinical, radiologic, and therapeutic aspects of the most common masses are reviewed.

Human achaete-scute homolog-1 is highly expressed in a subset of neuroendocrine tumors

Human achaete-scute homolog-1 (hASH1) is critical for establishing the neuroendocrine (NE) phenotype of small cell lung cancer. To define its role in other neoplasms, we analyzed 33 tumors for hASH1 by Northern blotting. Significant levels of hASH1 mRNA were detected in 4 pheochromocytomas, 2 medullary thyroid cancers, and 1 thymic carcinoid. hASH1 transcripts were undetectable in 8 parathyroid lesions, 6 gastrinomas, 4 insulinomas, and 7 thyroid neoplasms, as well as in normal thyroid, adrenal, or pancreas tissue. Therefore, hASH1 mRNA is highly abundant in a subset of human tumors and may play a role in dictating their NE phenotype.

Diagnostic difficulties in periodic Cushing's syndrome.

A 22-year-old black woman presented with symptoms suggestive of Cushing's syndrome three years after chemotherapy for a presumed teratoma with cervical lymphadenopathy. Initially, the absence of clinical signs and the...

Plasma Chromogranin a in Prostatic Carcinoma and Neuroendocrine Tumors

Chromogranin A is a good tumor marker for neuroendocrine cells. Whether plasma chromogranin A could be a useful marker for neuroendocrine differentiation of prostatic carcinoma and neuroendocrine tumors was investigated using an enzyme-linked immunosorbent assay. Plasma levels of chromogranin A were measured by enzyme-linked immunosorbent assay in 33 patients with prostatic carcinoma, 10 with benign prostatic hyperplasia (BPH) and 13 with neuroendocrine tumors (2 medullary thyroid carcinomas, 1 thymic carcinoid, 1 gastrin producing duodenal carcinoid, 3 nonfunctioning pancreatic endocrine tumors, 2 neuroblastomas, 3 pheochromocytomas and 1 carotid body tumor). The normal level of chromogranin A from 40 healthy volunteers was 30 +/- 11 units per 1. (mean plus or minus standard deviation). Mean plasma chromogranin A in patients with BPH and prostatic carcinoma was 52.4 +/- 12.9 and 67.5 +/- 22.9 units per 1., respectively. All patients with neuroendocrine tumors, except 1 with a nonfunctioning pancreatic endocrine tumor, had elevated chromogranin A (mean 401 +/- 409 units per 1.). There were significant differences in plasma chromogranin A level between patients with BPH and neuroendocrine tumors (p < 0.01), prostatic carcinoma and neuroendocrine tumors (p < 0.01), and BPH and prostatic carcinoma (p < 0.05). Of the 33 patients with prostatic carcinoma 5 had elevated chromogranin A, only 1 of whom had elevated prostate specific antigen. Chromogranin A is an excellent marker for neuroendocrine tumors, particularly nonfunctioning tumors, and measurement of chromogranin A is also useful to detect prostatic carcinoma in patients whose prostate specific antigen is not elevated.