Null cell adenoma of the human pituitary

Summary Among 343 surgically-removed pituitary adenomas, 56 tumors were unassociated clinically or biochemically with increased hormone secretion and contained no adenohypophysial hormones by the immunoperoxidase technique, except for 10 cases in which a few scattered cells showed positive immunostaining for -TSH or -FSH, -EH, prolactin and/or -subunit. These tumors were chromophobic adenomas with no PAS, lead hematoxylin or carmoisine positivity and electron microscopy failed to reveal their morphogenesis. The term null cell adenoma of the pituitary is proposed to designate this tumor type. This term recognizes the most obvious features of these tumors: the absence of markers which would permit the disclosure of their cellular origin. Null cells are also found in the nontumorous adeno-hypophysis, suggesting that null cell adenomas derive from preexisting nonneoplastic null cells. The question of whether pituitary null cells are hormonally inactive committed precursors, uncommitted stem cells or dedifferentiated cells remains to be elucidated.This work was supported in part by Grant MA-6349 of the Medical Research Council of Canada and Grant 1 R01 CA 21905-01 awarded by the National Cancer Institute, DHEW     

人垂体腺瘤诱导胚胎干细胞源性表皮样干细胞分化

目的探讨ES细胞源性表皮样干细胞在人垂体腺瘤诱导下的分化潜能。方法 129小鼠E14胚胎干细胞与人羊膜共培养,定向诱导其分化为表皮样干细胞克隆,取新鲜人垂体瘤组织,用生长有表皮样干细胞克隆的人羊膜将其包裹,无菌手术下移植入裸鼠双侧背部皮下,术后4周取材,对移植后细胞的分化情况进行形态学观察。结果移植物在裸鼠皮下生长4周后体积明显增大,HE染色表明,人羊膜表面有垂体瘤样细胞形成。结论ES细胞源性表皮样干细胞在适当的条件下有分化为垂体腺瘤样细胞的潜能。     

Sphenoidal pituitary adenoma.

A 62 year old female died of a chromophobe pituitary adenoma of the sphenoid bone. A normal pituitary gland was present within the sella turcica. She also had a chief cell parathyroid adenoma, a papillary thyroid carcinoma, and an ovarian thecoma (multiple endocrine neoplasia syndrome).     

Silent mixed growth hormone cell-prolactin cell pituitary adenoma

The case of a 51 -year-old man with recurrent nonfunctioning pituitary adenoma is presented. Despite clinically and endocrinologically normal pituitary function in regard to growth hormone and prolactin, many growth hormone- and prolactin-positive cells were immunohis-tochemically detected in adenoma tissue. Furthermore, a quite rare tumor of silent mixed growth hormone cell-prolactin cell pituitary adenoma was confirmed by the double-labeling immunoelectron-microscopical study.     

Prolactin-producing pituitary adenoma associated with prolactin cell hyperplasia

A 24-yr-old woman with amenorrhea, galactorrhea, hyperprolactinemia, and sellar mass underwent transsphenoidal surgery. Histologic, immunohistochemical, and electron microscopic investigation revealed a well-differentiated, sparsely granulated prolactin (PRL) cell adenoma of the pituitary showing conclusive PRL immunoreactivity. In the nontumorous adenohypophysis PRL cell hyperplasia was noted. Marked differences were evident between the neoplastic and hyperplastic areas. The tumor consisted of sparsely granulated PRL cells immunoreactive only for PRL. As demonstrated by immunoelectron microscopy, the hyperplastic are a comprised monohormonal sparsely granulated PRL cells as well as bihormonal mammosomatotrophs immunoreactive for both PRL and growth hormone. The MIB-1 index was higher whereas microvessel density was lower in the adenoma as compared with the hyperplastic area. In addition, the nontumorous area showed lymphocytic infiltration whereas inflammatory reaction was not seen in the adenoma. This case represents a rare association of a PRL cell adenoma and PRL cell hyperplasia. The fact that these two lesions were contiguous in the surgically removed material raises the possibility that hyperplasia can precede and transform into adenoma.     

TFF3 knockout in human pituitary adenoma cell HP75 facilitates cell apoptosis via mitochondrial pathway

Trefoil factor 3 (TFF3), a regulatory protein composed of 59 amino acids, has been suggested to be involved in pathogenesis, proliferation, differentiation, invasion, migration and apoptosis in multiple malignant tumors. This study thus investigated the effect of TFF3 knockout in human pituitary adenoma cell line HP75 on cell apoptosis and related pathways. RNA interference approach was used to knock down the expression of TFF3 protein. The gene silencing was validated by RNA denaturing gel electrophoresis and Western blotting. The effect of TFF3 knockout on cell apoptosis was analyzed by Western blotting and flow cytometry. TFF3 protein level in pituitary adenoma was about 3.61 ± 0.48 folds of that in normal tissues (P < 0.01). After transfecting with small interference RNA (siRNA) against TFF3, the apoptotic ration was significantly elevated (P < 0.01). Apoptosis related protein Bcl-2 and caspase-3 levels were remarkably depressed after siRNA transfection, while Bax and cleaved caspase-3 levels were elevated. TFF3 protein knockout can facilitate apoptosis of human pituitary adenoma HP75 cells via mitochondrial pathway.     

Crystalline structures in human pancreatic beta cell adenoma.

An electron microscopic observation on a pancreatic tumor removed from a 34-year-old woman revealed the fine structural morphology of a functional beta cell adenoma. Characteristic PAS positive crystalline structures were frequently observed in the cytoplasm of the tumor cells. They were not bounded by a membrane and had a rectangular or irregular hexagonal shape. Highly regular patterns were seen as such as lattice or honeycomb and parallel ripple structures. They are similar to the Reinke's crystal or crystalline structures reported in human hepatocytes suffering from several different diseases and considered as a protein-carbohydrate complex. Occasionally, small paracrystalline structures appeared to indicate an immature type of these structures in the opaque fine fibrillar mass. Crystalline or paracrystalline structures were not detected in the normal pancreatic tissue removed with the tumor from the patient.     

Metastasis to pituitary adenoma

Neoplasm to neoplasm metastasis is a medical curiosity. We report two cases of adenocarcinoma metastatic to pituitary adenoma. In both, abrupt progression of symptoms referable to the sellar region was noted and followed by the death of the patient.     

Metastatic prolactin-secreting pituitary adenoma

A 62-year-old man had a malignant prolactin-secreting pituitary adenoma. The tumor was initially resected through a transfrontal approach. Recurrence six years later was manifested by an occipital metastasis, which was excised. Progressive clinical deterioration ensued despite irradiation and chemotherapy of the intrasellar and occipital recurrence, and the patient died. Pathologic examination of tumor tissue obtained from the occipital metastasis showed increased cellular pleomorphism and mitotic rate in comparison with the original surgical specimen. The only true indication of malignant transformation, however, was the invasion of tumor capsule by adenoma cells, observed in the autopsy specimen. These findings support the contention that the diagnosis of a malignant pituitary adenoma rests ultimately on the demonstration of local invasive growth and/or distant metastasis. Since prolactinomas are usually non-aggressive, malignant degeneration of adenomas is decidedly rare. Its occurrence underlines the need for aggressive follow-up and treatment.     

Null cell adenoma of the pituitary with features of plurihormonality and plurimorphous differentiation

The case of a 35-year-old man with pituitary macroadenoma who was complaining of reduced sexual activity is presented. Histologic examination showed a chromophobic adenoma corresponding mainly to a null cell adenoma at the ultrastructural level. Focal plurihormonality and plurimorphous differentiation of adenoma cells were demonstrated by immunohistochemical and electron-microscopic studies. It is suggested that adenomatous null cells represent pluripotent progenitor cells capable of transforming to different hormone-producing cell types. The factors accounting for differentiating to various cell populations have yet to be elucidated.     

RSUME促进小鼠垂体腺瘤细胞AtT-20凋亡

目的探讨小泛素化修饰增强子(RSUME)、核转录因子-κB抑制因子-α(IκB-α)及核转录因子-κB 1(NF-κB1)在小鼠垂体腺瘤中表达及其细胞凋亡的影响。方法用RSUME小干扰RNA(siRNA)转染At T-20细胞后,用蛋白印迹及实时荧光定量PCR检测RSUME、NF-κB1和IκB-α蛋白的表达及mRNA的表达,流式细胞计量术检测细胞凋亡。结果在蛋白水平,RSUME-siRNA转染后RSUME及IκB-α表达下调(P0.05),NF-κB1则上调(P0.05);在mRNA水平,转染后RSUME mRNA表达水平明显低于转染前(P0.05),而IκB-α及NF-κB1 mRNA水平无明显变化;转染后细胞凋亡率明显升高。结论 RSUME可以通过NF-κB1促进小鼠At T-20垂体腺瘤细胞的凋亡。     

Clinical diagnosis of pituitary adenoma

Clinical symptoms, signs, endocrine examinations, image diagnosis of GH cell adenoma, prolactin cell adenoma, TSH cell adenoma and nonsecreting pituitary adenoma are discussed.     

青蒿琥酯诱导垂体泌乳素瘤细胞凋亡并下调泌乳素蛋白表达

目的 初步研究青蒿琥酯( artesunate,ART)对泌乳素瘤细胞及其泌乳素(prolactin,PRL)蛋白表达的作用效果.方法 MTT观察青蒿琥酯作用细胞后,细胞增殖情况,并计算药物的半数抑制浓度(IC50),Hoechst33342染色观察细胞凋亡小体,TUNEL计算细胞凋亡率,Western blot和RT...     

A composite somatotroph-corticotroph pituitary adenoma

A 76-year-old woman presented with enlargement and weakness of her hands and feet coarsening of facial features, proximal muscle weakness, and worsening of her noninsulindependent diabetes mellitus. Serum growth hormone, somatomedin-C, and prolactin levels were elevated. Thyroid function test results and serum cortisol and adrenocorticotropic hormone levels were within normal limits. Luteinizing and follicle-stimulating hormone levels were both low, suggesting possible partial hypopituitarism. Magnetic resonance imaging of the sella demonstrated a pituitary lesion that measured 2.2 x 1 x 0.5 cm; it partially obliterated the suprasellar cistern and it distorted the optic chiasm. Light microscopic and ultrastructural examination of the trans-sphenoidally resected tissues identified characteristic features of 2 discrete pituitary adenomas that were in close apposition, but they were sharply demarcated. The 2 components were a corticotroph adenoma and a sparsely granulated somatotroph adenoma. Multiple adenomas of the pituitary are not rare; however, the majority are endocrinologically “nonfunctional.” We report a patient with clinical features of acromegaly whose tumor was a composite lesion: one area exhibited morphological characteristics of a corticotroph adenoma and another distinct area exhibited features of a somatotroph adenoma. The possible histogenesis is discussed.