Neural transformation in a pituitary corticotroph adenoma.

A pituitary mass was removed by the transsphenoidal approach from a 63-year-old man with the clinical history and laboratory findings characteristic of Cushing's disease with partial hypopituitarism. Histological, immunohistochemical, ultrastructural and immunoelectron microscopic investigation demonstrated a periodic acid-Schiff-positive, adrenocorticotropic hormone (ACTH)-immunoreactive, pituitary corticotroph adenoma with the formation of neural tissue resembling neuropil within the tumor. The neural elements showed immunopositivity for neurofilament protein and ACTH, but were immunonegative for other adenohypophysial hormones and for corticotropin-releasing hormone. Although the molecular mechanism accounting for neural transformation in this corticotroph adenoma remained obscure, based on the clinical, histological and morphological findings it appears that formation of neural tissue most likely indicate a favorable prognosis.

Pituitary adenoma with neuronal choristoma (PANCH): composite lesion or lineage infidelity?

Fifteen cases of the rare association of pituitary adenoma and neuronal choristoma (PANCH) were investigated by histology, immunohistochemistry, and electron microscopy. Acromegaly was apparent clinically in 11 patients and was equivocal in 1, and 3 lesions appeared to be nonfunctioning. Histology revealed various proportions of chromophobic PA and nervous tissue consisting of neuronlike cells and neuropil. Immunohistochemistry documented growth hormone (GH) in every PA, including those unassociated with clinical acromegaly. In contrast, the NCH component showed no consistent immunohistochemical profile. Most frequent reactivities were for the pituitary hormone alpha subunit, thyroid-stimulating hormone, and GH, whereas only a few cases displayed scattered positivity for GH-releasing hormone. Low-molecular weight keratin tested positive in PAs and in a few cells and processes of an NCH. A few fibrous bodies were immunoreactive for neurofilament protein. Electron microscopy revealed sparsely granulated GH cell adenoma, neurons, and neuropil. Cells intermediate between PA and neurons were numerous in 1 lesion. The present morphologic findings as well as lack of GH cell hyperplasia and the consistent association of NCH with but one type of PA do not support the causative role of NCH in the initiation of PA, as proposed previously. It appears that NCH is the result of neuronal differentiation within sparsely granulated GH cell adenomas.

[Is it useful to isolate a chromophobe cell variant among carcinomas of the kidney?]. / Est-il utile d'isoler parmi les carcinomes du rein, une variante à cellules chromophobes?

Chromophobe cell carcinoma is a little known variety of renal cell carcinoma representing 7 to 9% of all renal tumors. This tumor is confused with either clear cell carcinoma (clear subvariety) or oncocytoma (eosinophilic subvariety). Until ultrastructural and prospective studies of the prognosis of this tumor become available, it already seems important to perform colloidal iron staining to establish the differential diagnosis between oncocytoma and chromophobe cell carcinoma.

[Pathological study of 23 cases of nonfunctional pituitary adenoma].

23 cases of nonfunctional pituitary adenoma were studied with light and electron microscopy as well as with immunohistochemical stains PAP technique. Under routine light microscopy, 17 cases were chromophobic adenomas; anyhow, electron microscopy showed that there were 6 cases of oncocytoma; 7 cases of undifferentiated cell adenoma; 4 cases of gonadotropic adenoma; 4 cases of mixed adenomas 1 cases of sparsely granulated GH cell adenoma and 1 case of sparsely granulated PRL cell adenoma. Immunohistochemical stain showed: null cell adenomas 7 cases, FSH cell adenoma 3 cases, LH cell adenoma 1 case, GH cell adenoma 2 cases and other mixed adenoma 10 cases. Therefore, the nonfunctional pituitary adenoma is actually a mixture, and the null cell adenoma was only about 1/3 in this series. Among them, most of the hormones gave no function expression themselves.

Fluorescence histochemistry of RNA in human pituitary adenomas.

Acridine orange (AO)-RNA fluorescence was studied histochemically in 9 normal human pituitary glands, in 26 secretory and nonsecretory pituitary adenomas, and in a dysgerminoma. Six adenomas showing immunoreactivity for prolactin showed intense orange-red cytoplasmic fluorescence; 6 other tumours exhibiting immunoperoxidase activity of growth hormone showed less intense AO-RNA fluorescence, and 5 adrenocorticotropic hormone-containing adenomas showed still weaker orange fluorescence. Among the chromophobe adenomas without immunoreactivity for secretory products, 5 had uniformly very weak AO-RNA fluorescence, while in 4 other a few scattered cells with strong AO-RNA fluorescence were detected among the majority of weakly fluorescent cells. The pituitary dysgerminoma contained many cells with strong AO-RNA fluorescence. Electron microscopy of these cases showed good correlation of cytoplasmic concentration of ribosomes with AO-RNA fluorescence of the adenomas. AO is useful as an inexpensive, simple supplementary stain for frozen or paraffin sections of pituitary tumours to infer secretory activity as a correlate of RNA concentration and to demonstrate a secretory potential in some cells of hormonally inactive tumours.

Light and electron microscopical morphometry of pituitary adenomas in hyperprolactinemia.

Two highly differentiated acidophil prolactin-cell adenomas with hyperprolactinemia (group I), 8 large cell chromophobe adenomas with hyperprolactinemia (group II), and 2 small cell chromophobe adenomas (group III), one of which was combined with hyperprolactinemia, were studied immunohistologically. Morphometry was performed on the light- and electron microscopical level. The 11 active adenomas were immunohistologically positive for prolactin, the 12th adenoma with normal prolactin plasma level was negative for prolactin. Light microscopical morphometry displayed significantly more cells of smaller size in the "small cell chromophobe" adenomas, whereas the large cell chromophobe adenomas and the highly differentiated prolactin cell adenomas were not different. Ultrastructural morphometry demonstrated significant differences between highly differentiated prolactin cell adenomas (group I), and large cell chromophobe adenomas (group II). The latter contain smaller "relative volumes" of nucleoli and of secretory granules, whereas the rough endoplasmic reticulum, the Golgi fields and the nuclei were not different. Comparison of large cell chromophobe adenomas (group II), and small cell chromophobe adenomas (group III) revealed significantly larger relative volumes of nuclei and of mitochondria but smaller volumes of rough endoplasmic reticulum and of Golgi fields in the small cell chromophobe adenomas. Significant differences between the active and the inactive adenoma of small cell chromophobe type in the group III were not found. In spite of the low quantity of small cell chromophobe adenomas and of acidophil prolactin cell adenomas, our data demonstrate that there exist distinct and significant light microscopical and ultrastructural differences between the three adenoma types.(ABSTRACT TRUNCATED AT 250 WORDS)

Electron dense mitochondrial inclusions in a pituitary oncocytoma.

A 65-year-old man had a pituitary adenoma with a large expansion of the sella turcica; computerized tomography demonstrated suprasellar extension. The tumor, removed surgically, was diagnosed as nonsecretory partly chromophobic, partly acidophilic adenoma by light microscopy and immunocytology. Electron microscopic investigation revealed a pituitary oncocytoma with an unusual mitochondrial abnormality. Some mitochondria harbored single or multiple electron dense bodies which were also found in the cytoplasm as well as in the extracellular space. It appears that these bodies were originally formed in the mitochondria, then extruded into the cytoplasm and subsequently to the extracellular space.

[Immunohistological determination of beta-endorphin in chromophobe, clinically hormone-nonproducing hypophyseal adenomas]. / Immunhistologischer Nachweis von beta-Endorphin in chromophoben, klinisch hormonell inaktiven Hypophysenadenomen.

Pituitary adenomas are usually classified according to the nature of their proper hormonal production. Silent adenomas of the pituitary are tumors without clinical and biochemical evidence of overproduction of any known adenohypophyseal hormones. The proportion of such seemingly nonfunctioning tumors is 20 to 30%. Silent corticotropic adenomas are able to synthesize some normal or abnormal sequences of proopiomelanocortin precursor without any signs of hypercorticism. These tumors were divided into basophilic adenomas with strong periodic acid-Schiff (PAS) positivity and chromophobic adenomas with moderate or no PAS positivity. All of our cases were chromophobic adenomas. Two of the cases were positive for beta-endorphin by immunofluorescence. ACTH immunoreactivity was not present in the cells. Electron microscopic study of the adenoma cells showed small secretory granules with a halo. The diameter of these granules varied from 50 to 250 nm. Automated morphometric and densitometric investigations of silent corticotropic adenomas and adenomas from patients with Cushing's disease gave different karyometric results. The most important practical problem arising from the present investigation was the high frequency of recurrence of silent corticotropic tumors.

Pituitary adenomas producing growth hormone, prolactin, and one or more glycoprotein hormones: a histologic, immunohistochemical, and ultrastructural study of four surgically removed tumors.

The morphologic features of four pituitary adenomas, removed from 2 men and 2 women between 31 and 62 years of age, are reported. The tumors contained growth hormone (GH), prolactin (PRL), and one or more glycoprotein hormones--usually thyrotropin (TSH). Three tumors were associated with acromegaly and one with hyperprolactinemia. Hyperthyroidism was not evident in any of the patients. In the tumors of acromegalic subjects, GH-containing cells were the most numerous, whereas PRL cells were dominant in the adenoma accompanied by hyperprolactinemia. Electron microscopy revealed plurimorphous tumors comprised of various proportions of morphologically different cell types: densely granulated GH cells, TSH-like cells, and the less common mammosomatotrophs and PRL cells. It is suggested that pituitary adenomas producing GH, PRL, and glycoprotein hormones derive from the same precursor; their immunocytochemical profile, fine structural appearance, and endocrine function may depend on the degree and direction of the cellular differentiation.

Prolactinoma coexistent with granulomatous hypophysitis.

A 54-year-old man with a long-lasting left-sided headache and biochemical evidence of hyperprolactinemia was found to have a large chromophobe pituitary adenoma, which concurred with a granulomatous hypophysitis. The mechanism of the inflammatory reaction is discussed and the immunohistochemical and ultrastructural findings of this hitherto undescribed combination of lesions are presented.

Aggressive pituitary tumor growth.

Three cases with extrasellar extension from our material of 132 pituitary tumors are reported. One tumor secreted growth hormone, one secreted prolactin, and one secreted adrenocorticotropic hormone (ACTH). All three patients had a short case history. The tumors recurred rapidly after surgery. Light microscopy showed pleomorphic cells but no signs of morphologic malignancy. Ultrastructural analysis revealed intracellular filamentlike inclusions, with a cross-banded substructure in two cases. The DNA analysis of two of the cases showed aneuploidy. Our three cases of pituitary tumors are likely to represent a particularly aggressive type of tumor growth.

Immunohistochemical and immunoelectron-microscopic study of pituitary adenomas associated with Cushing's disease. A report of 13 cases.

Thirteen pituitary adenomas were removed from patients with Cushing's disease by the transphenoidal route. All cases demonstrated a typical histochemical and ultrastructural pattern. Immunocytochemical study by means of the immunoperoxidase technique and light or electron microscopy demonstrated 1-24/1-39 adrenocorticotropic hormone (ACTH) in all cases, lipotropin/melanotropin (beta-LPH/beta-MSH) in 10 cases, beta-endorphin in 8 cases, and an absence of calcitonin in all cases. In addition, in 2 cases tumor tissue contained a few antiprolactin immunoreactive cells. These ACTH, beta-LPH, and beta-endorphin immunoreactivities may reflect either the peptides themselves or their precursors or intermediate products. The authors also suggest a possible intermediate-lobe-like processing of beta-LPH leading to beta-endorphin production, which may act on PRL cells. In addition, no positive arguments for the existence of a common precursor for calcitonin and ACTH could be provided from this study.

[Immunomorphological and ultrastructural characteristics of hypophyseal adenomas in prolactinemia patients]. / Immunomorfologicheskaia i ul'trastrukturnaia kharakteristika adenom gipofiza u bol'nykh s prolaktinemiei.

It was shown by means of electron microscopy and immunohistochemical study that in 11 of 15 patients with high preoperative prolactinemia the tumor consisted mainly of prolactin-containing cells. Small groups of them occurred in the tumors of 2 patients, whereas in 2 other cases prolactin was not detected in the tumor cells by immunohistochemical method. Electron microscopy demonstrated hypophyseal oncocytomas in these 2 cases. Appreciable differences in the blood prolactin concentration, depending on the tumor ultrastructure, were not observed.

Adenoma of the human pituitary producing growth hormone and thyrotropin. A histologic, immunocytologic and fine-structural study.

A pituitary adenoma removed by surgery from a 22-year-old man was studied by histology, immunocytology, transmission electron microscopy and immunoelectron microscopy. Clinically, the patient had acromegaly and euthyroidism with elevated blood GH concentrations. Blood TSH and T4 levels were within the normal range. Histologically, the adenoma was chromophobic and exhibited no PAS, lead hematoxylin, aldehyde thionin or Grimelius silver positivity. By the immunoperoxidase technique GH, beta-TSH and alpha-subunit but no PRL, ACTH, alpha-endorphin, beta-FSH or beta-LH were demonstrated in the adenoma cells. Electron microscopy revealed adenoma cells which were similar to TSH cells and showed no resemblance to GH cells of nontumorous pituitaries or GH-secreting tumors. Immunoelectron microscopy demonstrated GH and beta-TSH in the secretory granules. It is concluded that pituitary adenomas composed of TSH-like cells may secret GH, resulting in acromegaly. Production of GH by adenomatous TSH cells cannot be explained on the basis of the one cell- one hormone theory. The question is raised whether bihormonal or multihormonal clones, capable of synthesizing more than one hormone, exist in the human pituitary. These cells are apparently dormant under normal conditions, but in the course of neoplastic transformation may undergo functional dedifferentiation and acquire the ability to produce two or more different hormones.

[Functional morphology of pituitary adenoma in acromegaly]. / Funktsional'naia morfologiia adenomy gipofiza pri akromegalii.

Twenty-one pituitary adenomas removed from patients with acromegaly were studied electron microscopically. In 9 cases the tumors underwent immunohistochemical analysis by Coons' indirect immunofluorescent technique. Before the operation, all the patients were found by radioimmunoassay to have concentrations of pituitary hormones in the blood serum. A clinico-morphological analysis performed showed that in all cases of acromegaly pituitary adenoma consisted of somatotropocytes differing by the degree of cell granulation. The concentration of the somatotropic hormone (STH) in the blood serum of the patients did not depend on the intensity of the ultrastructural signs of the secretory activity of the cells. In 4 adenomas, a positive immunohistochemical reaction to two hormones, STH and prolactine, was demonstrated.

Sparsely granulated prolactin cell adenomas of the pituitary gland. Correlation of ultrastructure with plasma hormone level.

The possible relationship between the preoperative plasma prolactin levels of patients having a sparsely granulated prolactin cell adenoma of the pituitary gland and the morphology of the tumors was studied by means of quantitative electron microscopy. To this end, a number of ultrastructural variables were chosen which are generally regarded to be indicative of cellular activity and which could be determined in a quantitative or semiquantitative way. These variables were determined in 19 adenomas from 17 patients and plotted against the corresponding prolactin levels. It appeared that marked endocrine activity was associated with a small number of granules per cell, a high frequency of exocytosis, and a marked development of the rough endoplasmic reticulum. Granule size and development of Golgi apparatus and lysosomes were not at all, or only poorly correlated with the plasma hormone levels. Finally, the number of mitochondria per cell showed a totally unexpected inverse correlation with endocrine activity. Due to the close mutual correlation existing between several of the variables investigated, combining them in a multivariate analysis did not significantly improve the correlation with the hormone level.