<b>OBJECTIVEb>To describe the morphologic features and immunohistochemistry of spindle cell carcinoma of breast with neuroendocrine differentiation.

<b>METHODSb>Retrospective review of 2500 cases of breast carcinoma showed 5 cases (0.2%) with a predominance (> 80%) of spindle cell component. Amongst the 5 cases studied, 2 represented intraductal spindle cell carcinoma and 3 represented invasive spindle cell carcinoma. The paraffin sections were stained with hematoxylin and eosin, alcian blue, periodic acid-Schiff and reticulin stain. Immunohistochemical studies for AE1/AE3, CEA, EMA, CK7, 34betaE12, NSE, synaptophysin, chromogranin A, Leu-7, vimentin, S-100, SMA, calponin, estrogen receptor, progesterone receptor, c-erbB2, E-cadherin, Ki-67 and p53 were also carried out. Follow-up information was available in 4 of the 5 cases.

<b>RESULTSb>The mean age of the patients was 68 years. Histologically, all tumors were predominantly composed of elongated spindle cells. Three of these cases also contained tumor cells with vacuolated cytoplasm, alcian blue-positive tumor cells were observed in 4 cases. Immunohistochemically, the spindle tumor cells in all cases expressed AE1/AE3, CEA, EMA, E-cadherin and synaptophysin. CK7 was positive in 4 cases, NSE in 3 cases, chromogranin A and Leu-7 in 2 cases. Estrogen receptor was expressed in 4 cases and progesterone receptor in 2 cases. Overexpression of c-erbB2 oncoprotein was detected in only 1 case. Vimentin was focally positive in 1 case. Two cases of intraductal spindle cell carcinoma and 1 of the 3 cases of invasive spindle cell carcinoma were classified as neuroendocrine carcinoma of spindle cell type, while the remaining 2 cases of invasive spindle cell carcinoma were considered as metaplastic carcinoma with neuroendocrine differentiation. Amongst the 4 patients with follow-up information available, 3 were still alive 24 to 58 months after the initial diagnosis. One patient died within 27 months of diagnosis.

<b>CONCLUSIONSb>The presence of spindle tumor cells and sometimes intracytoplasmic mucin are useful morphologic clues in diagnosing spindle cell carcinoma of the breast with neuroendocrine differentiation. Intraductal neuroendocrine spindle cell carcinoma needs to be distinguished from usual ductal hyperplasia and intraductal papilloma. On the other hand, invasive spindle cell carcinoma with neuroendocrine differentiation needs to be distinguished from spindle cell myoepithelioma, malignant melanoma and sometimes soft tissue neoplasm.

Aged ; Biomarkers, Tumor ; analysis ; Breast Neoplasms ; chemistry ; pathology ; Carcinoma ; chemistry ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; chemistry ; pathology ; Chromogranin A ; Chromogranins ; analysis ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neuroendocrine Tumors ; chemistry ; pathology ; Phosphopyruvate Hydratase ; analysis ; Retrospective Studies ; Synaptophysin ; analysis

<b>OBJECTIVEb>To study the impact of short-term neoadjuvant hormonal treatment on neuroendocrine (NE) differentiation and the relation of NE differentiation and tumor regression.

<b>METHODSb>The radical prostatectomy specimens and the biopsy specimens of the same 18 patients with prostate cancer were compared. The effect of hormonal treatment on NE-differentiation was evaluated by specific antibodies against chromogranin A (ChA) and serotonin (5-HT).

<b>RESULTSb>The ChA-positive cell count was 3.2 x 10(-5)/microm(2) [(0-5.7) x 10(-5)/microm(2)] before hormonal treatment and 2.3 x 10(-5) microm(2)[(0-6.6) x 10(-5)/microm(2)] afterward (P > 0.05). For the proportion of NE-positive tumor, it was 7.0% (0%-14.9%) and 4.5% (0%-13.1%) (P > 0.05). No correlation existed between NE-differentiation and the neoadjuvant hormonal treatment. The NE cell density did not differ significantly between 12 non-/slightly regressive tumor foci and 6 highly regressive ones (P > 0.05).

<b>CONCLUSIONb>Short-term neoadjuvant hormonal therapy does not induce clonal propagation of NE cells. The degree of tumor regression following short-term neoadjuvant hormonal therapy is not correlated with the NE differentiation.

Aged ; Androgen Antagonists ; therapeutic use ; Antineoplastic Agents, Hormonal ; therapeutic use ; Chromogranin A ; Chromogranins ; analysis ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neurosecretory Systems ; pathology ; Prostatic Neoplasms ; drug therapy ; pathology ; Serotonin ; analysis

The changes on the regional distributions and frequencies of two types of chromogranin, chromogranin A (CGA) and bovine Sp-1 chromogranin (BCG)-immunoreactive (IR)cells in gastrointestinal (GI)tract of osteoporotic Sprague-Dawley rat induced by ovariectomy were studied by immunohistochemical methods. The experimental animals were divided into two groups, one is non-ovariectomized group (Sham)and the other is ovariectomized group (OVX). Samples were collected from each part of GI tract at 10th week after ovariectomy or sham operation. CGA-IR cells were restricted to the stomach regions with various frequencies regardless of ovariectomy except for the fundus of OVX in which no cells were detected. In addition, BCG-IR cells were also restricted to the pylorus and duodenum regardless of ovariectomy. A significantly decrease of CGA IR cells was detected in OVX compared to that of Sham in both fundus and pylorus, and BCG-IR cells were also significantly decreased in the duodenum(p<0. 05). However, in the pylorus, BCG-IR cells in OVX showed similar frequency compared to that of Sham. In conclusion, the abnormality in density of chromogranin, a generally used GI endocrine cell marker, detected in this study may contribute to the development of GI symptoms in osteoporosis such as impairments of calcium and some lipids, frequently encountered in patients with postmenopausal osteoporosis.
Animals ; Chromogranin A ; Chromogranins/*metabolism ; Female ; Gastric Mucosa/*metabolism/pathology ; Gene Expression Regulation/physiology ; Humans ; Immunoglobulins/*metabolism ; Immunohistochemistry ; Intestinal Mucosa/*metabolism/pathology ; Models, Animal ; Osteoporosis, Postmenopausal/*metabolism/pathology ; Ovariectomy ; Rats ; Rats, Sprague-Dawley

The regional distributions and relative frequencies of some gastrointestinal endocrine cells in the three portions (cecum, colon and rectum) of the large intestinal tract of C57BL/6 mice were examined with immunohistochemical method using 7 types of specific antisera against chromogranin A (CGA), serotonin, somatostatin, human pancreatic polypeptide (HPP), glucagon, gastrin and cholecyctokinin (CCK)-8. In this study, all 3 types of immunoreactive (IR) cells were identified. Most of these IR cells in the large intestinal portion were generally spherical or spindle in shape (open-typed cell) while cells with a round shape (close-typed cell) were found in the intestinal gland. Their relative frequencies varied according to each portion of the large intestinal tract. CGA-IR cells were found throughout the whole large intestinal tract but were most predominant in the colon. Serotonin-IR cells were detected throughout the whole large intestinal tract and showed highest frequency in the colon. Peculiarly, glucagon-IR cells were restricted to the colon with a low frequency. However, no somatostatin-, HPP-, gastrin- and CCK-8-IR cells were found in the large intestinal tract. In conclusion, some peculiar distributional patterns of large intestinal endocrine cells were identified in C57BL/6 mice.
Animals ; Chromogranin A ; Chromogranins/metabolism ; Enteroendocrine Cells/*metabolism/physiology ; Female ; Gastrins/metabolism ; Glucagon/metabolism ; Immunohistochemistry/veterinary ; Intestine, Large/*cytology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Pancreatic Polypeptide/metabolism ; Serotonin/metabolism ; Sincalide/metabolism ; Somatostatin/metabolism

No abstract available.
Adult ; Carcinoid Tumor/*diagnosis/pathology ; Chromogranins/metabolism ; Duodenal Neoplasms/*diagnosis/pathology ; Duodenoscopy ; Humans ; Male

Pseudohypoparayhyroidism (PHP) is a rare autosomal dominant or recessive genetic disorder characterized by low calcium, high phosphorus, and target organ resistance to parathyroid. The clinical characteristics and genetic features in 4 patients with Type Ib PHP in the Third Xiangya Hospital, Central South University, have been reviewed. All 4 patients had low calcium, high phosphorus, and parathyroid resistance. Among them, 2 patients had slightly elevated thyroid stimulating hormone and mild features of Albright's hereditary osteodystrophy, and one patient had hypokalemia. No guanine nucleotide-binding protein alpha-stimulating activity polypeptide 1 (GNAS) and gene variant associated with hypokalemia were identified using the whole exome sequencing. The results of the methylation-specific multiple ligation-dependent probe amplification showed that there were abnormal methylation of the upstream differentially methylated regions of GNAS in the 4 patients. There were phenotype overlap among the various subtypes of PHP. Detection of GNAS gene methylation in patients with clinical suspicion of Type Ib PHP is helpful for the diagnosis and treatment of PHP.
Humans ; Chromogranins/genetics* ; GTP-Binding Protein alpha Subunits, Gs/genetics* ; Hypokalemia ; Calcium ; Pseudohypoparathyroidism/genetics* ; Phosphorus

Large-cell neuroendocrine carcinoma of the colon is a rare entity with a prognosis that is usually poor due to the high likelihood of early metastasis. A 61-year-old man had surgery for colon cancer of the transverse colon and cecum. Microscopic examination of the tumor showed that the location was the proximal transverse colon, with small nests containing rosettes and palisading patterns of large tumor cells with faintly granular cytoplasm. The immunohistochemistry was positive for synaptophysin and chromogranins. The tumors were diagnosed as a large-cell neuroendocrine carcinoma of the colon. In addition, the tumor of the cecum showed microscopic findings consistent with a well-differentiated adenocarcinoma. The immunohistochemical panel showed that the tumor was negative for neuroendocrine markers. There were no clinical findings suggestive of hormone hypersecretion. Cancer metastasis was found in the peritoneum section of the small bowel. Postoperative chemotherapy was applied. The patient was alive with good performance after, and there was no sign of tumor progression. This is the first case of a synchronous large-cell neuroendocrine carcinoma and adenocarcinoma of the colon. The patient was treated successfully with debulking surgery and systemic chemotherapy.
Adenocarcinoma ; Carcinoma, Neuroendocrine ; Cecum ; Chromogranins ; Colon ; Colon, Transverse ; Colonic Neoplasms ; Cytoplasm ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Metastasis ; Neoplasms, Multiple Primary ; Peritoneum ; Prognosis ; Synaptophysin

The distributions and frequencies of some endocrine cells in the gastrointestinal (GI) tract of ddY mice were studied with immunohistochemical method using 7 types of antisera against bovine chromogranin (BCG), serotonin, gastrin, cholecystokinin (CCK)-8, somatostatin, glucagon and human pancreatic polypeptide (HPP). All of 7 types of immunoreactive (IR) cells were identified. Most of IR cells in the intestinal portion were generally spherical or spindle in shape (open typed cell) while cells showing round in shape (close typed cell) were found in the intestinal gland and stomach regions occasionally. Their relative frequencies were varied according to each portion of GI tract. BCG-IR cells were demonstrated throughout whole GI tract except for the cecum and they were most predominant in the fundus and pylorus. Serotonin-IR cells were detected throughout whole GI tract and they were most predominant cell types in this species of mice. Gastrin-IR cells were restricted to the pylorus and CCK-8-IR cells were demonstrated in the pylorus, duodenum and jejunum with numerous frequencies in the pylorus. Somatostatin-IR cells were detected throughout whole GI tract except for the cecum and rectum and they showed more numerous frequencies in the stomach regions. In addition, glucagon-IR cells were restricted to the fundus, duodenum and jejunum with rare frequencies, and HPP-IR cells were restricted to the rectum only with rare frequency. In conclusion, some strain-dependent unique distributional patterns of gastrointestinal endocrine cells were found in GI tract of ddY mice.
Animals ; Biological Markers/analysis ; Cholecystokinin/analysis ; Chromogranins/analysis ; Enteroendocrine Cells/*cytology/immunology ; Female ; Gastrins/analysis ; Glucagon/analysis ; Immunoenzyme Techniques ; Mice ; Pancreatic Polypeptide/analysis ; Protein Precursors/analysis ; Serotonin/analysis

Neuroblastomas are derived from the neural crest ectoderm, and are the most common solid abdominal masses of infancy. Congenital neuroblastoma, however, is rare. We report a rare case of congenital neuroblastoma with multiple metastases found at autopsy, performed at 2 days after birth. He was born by cesarian section and weighed 2,350 g. His respiration was weak and abdomen was distended. The patient died 2 days after birth. Postmortem examination revealed a relatively well demarcated ovoid mass, in the left adrenal, with necrosis and hemorrhage. Multiple small metastatic tumor nodules in the liver, lung, kidney, brain, rib, thyroid glands, and spleen, were noted. The histopathological pictures confirmed the diagnosis of neuroblastoma of the adrenal with multiple metastasis.
Adrenal Gland Neoplasms/congenital/*diagnosis/pathology ; Autopsy ; Chromogranins/biosynthesis ; Cytoplasm/metabolism ; Human ; Immunohistochemistry ; Infant, Newborn ; Male ; Necrosis ; Neoplasm Metastasis ; Neuroblastoma/congenital/*diagnosis/pathology ; Phosphopyruvate Hydratase/biosynthesis

OBJECTIVE: To preliminarily investigate the relationship between stimulatory G protein α subunit (GNAS) and thyroid hormone receptor α (THRA) gene mutations and clinical phenotypes in children with congenital hypothyroidism (CH). METHODS: A total of 70 children with CH diagnosed by neonatal screening were enrolled. Their peripheral blood samples were collected to extract genomic DNA. GNAS and THRA genes were screened for mutations using next-generation sequencing. Bioinformatics software was used to analyze the pathogenicity of gene mutations. RESULTS: Of the 70 children with CH, nine missense mutations (three known mutations and six novel mutations) in the GNAS gene were detected in three patients (4%), and one gene polymorphism, c.508A>G(p.I170V), in the THRA gene was detected in four patients. The analysis results of bioinformatics software and ACMG/AMP guidelines showed that the two GNAS gene mutations [c.301C>T(p.R101C) and c.334G>A(p.E112K)] were more likely to be pathogenic. Three children with GNAS gene mutations showed different degrees of hypothyroidism. CONCLUSIONS GNAS gene mutations are related to the development of CH, and children with CH have different clinical manifestations. THRA gene mutations may not be associated with CH.
Chromogranins ; genetics ; Congenital Hypothyroidism ; GTP-Binding Protein alpha Subunits, Gs ; genetics ; Genes, erbA ; Humans ; Infant, Newborn ; Mutation ; Phenotype ; Thyroid Hormone Receptors alpha ; genetics