Utility of Pit-1 Immunostaining in Distinguishing Pituitary Adenomas of Primitive Differentiation from Null Cell Adenomas

2017 ◽  
Vol 28 (4) ◽  
pp. 287-292 ◽  
Author(s):  
Julieann C. Lee ◽  
Melike Pekmezci ◽  
Jonathan L. Lavezo ◽  
Hannes Vogel ◽  
Laurence Katznelson ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Null Cell ◽  
Null Cell Adenomas

The immunohistochemical and radiological features of nonfunctioning pituitary adenomas

2015 ◽  
Vol 61 (6) ◽  
pp. 4-9 ◽  
Author(s):  
Anna Konstantinovna Lipatenkova ◽  
Larisa Konstantinovna Dzeranova ◽  
Ekaterina Aleksandrovna Pigarova ◽  
Nadezhda Sergeevna Dalantaeva ◽  
Ljudmila Igorevna Astaf'eva ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Area Under The Curve ◽  
Pituitary Hormones ◽  
Serum Markers ◽  
Invasive Growth ◽  
Null Cell ◽  
Ki 67 ◽  
Nonfunctioning Pituitary Adenomas ◽  
Radiological Features ◽  
Null Cell Adenomas

Pituitary adenomas without clinically active hypersecretion are summarized under the term nonfunctioning pituitary adenomas (NFPAs). Since there are no specific serum markers, the differential diagnosis and treatment imply special difficulties.Aim.To investigate the immunohistochemical and radiological features of NFPAs and assess the granins — chromogranin A (CgA), secretogranin II (SgII), secretoneurin (Sn) as immunohistochemical markers of NFPAs.Matherial and methods.50 pituitary adenomas excised surgically were immunostained to reveal pituitary hormones, ki-67, CgА. SgII, Sn. All patients underwent MRI, invasive growth was estimated due to J.Hardy classification (1973).Results.24 (51,1%) were gonadotropic tumors, 12 (25,5%) — null cell adenomas. Immunopositivity for ACTH was determined in 6 cases (12,7%), for GH in 5 (10,6%) cases, for PRL in 4 (8,5%). The median level of ki-67 was 2% (min. — 0.5%, max. — 7%). The CgA, SgII, Sn immunopositivity was found in 83, 93,6, 85,1% respectively, being more expressed in gonadotropinomas and null cell adenomas. Invasive growth was detected in 28 (44%) cases, among the invasive adenomas 22 tumors were giant. CgA expression is adverse prognostic factor, area under the curve (AUC) with 0,705. We did not find any correlation between ACTH-, STH-, CgII- and Sn- immunopositivity, ki-67 and invasive growth.Conclusions.Our work shows that a majority of NFPAs are truly secreting adenomas with significant numbers comprising potentially hazardous cortico- and somatotropinomas. CgA, SgII and Sn have a high expression in most of the NFPAs.

Morphological study of clinically nonsecreting pituitary adenomas in patients under 40 years of age

1991 ◽  
Vol 75 (6) ◽  
pp. 902-905 ◽  
Author(s):  
Shozo Yamada ◽  
Kalman Kovacs ◽  
Eva Horvath ◽  
Tadashi Aiba
Keyword(s):  
Microscopic Examination ◽  
Pituitary Adenomas ◽  
Electron Microscopic Examination ◽  
Electron Microscopic ◽  
Null Cell ◽  
Younger Patients ◽  
Content Type ◽  
Morphological Studies ◽  
Null Cell Adenomas ◽  
Fine Print

✓ Clinically nonsecreting pituitary adenomas removed at surgery from 69 patients under 40 years of age were studied by histological, immunocytochemical, and transmission electron microscopic examination. By morphological analysis. 19 tumors were found to be null-cell adenomas. 17 silent gonadotroph adenomas, 14 silent subtype 3 adenomas of unknown cellular origin, 13 silent subtype 1 or subtype 2 corticotroph adenomas, three oncocytomas, and three silent thyrotroph adenomas. These results indicate that the incidence of null-cell adenomas and oncocytomas, which are known to be the most common types of nonsecreting pituitary adenomas in patients over 40 years of age, is relatively low in younger patients. This trend is even more obvious in patients younger than 30 years of age. It can be concluded that clinically nonsecreting pituitary adenomas represent a heterogeneous group morphologically, and that the incidence of the different tumor types varies depending on the patient's age. These findings underline the importance of careful morphological studies. It is proposed that, in order for the correct morphological diagnosis to be made, tumors removed surgically from patients with clinically nonsecreting pituitary adenomas (especially younger patients) should be investigated not only by histological means but also by immunocytochemical and electron microscopic examination. The information obtained from such analysis may be useful in assessing prognosis and deciding on the appropriate treatment.

scholarly journals Reduced expression levels of the cell-cycle inhibitor p27Kip1 in human pituitary adenomas

1999 ◽  
pp. 250-255 ◽  
Author(s):  
CM Bamberger ◽  
M Fehn ◽  
AM Bamberger ◽  
DK Ludecke ◽  
FU Beil ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenomas ◽  
Anterior Pituitary ◽  
Cellular Proliferation ◽  
Cell Types ◽  
Null Cell ◽  
Human Pituitary ◽  
Expression Levels ◽  
Cell Cycle Inhibitor ◽  
Null Cell Adenomas

The molecular mechanisms leading to increased cellular proliferation rates and, thus, tumor formation in the anterior pituitary gland are poorly understood. The cyclin-dependent kinase inhibitor p27Kip1 is a key molecule regulating the G1 phase of the cell cycle in many cell types. Furthermore, it was shown that p27 knock-out mice develop pro-opiomelanocortin-positive pituitary tumors. In an effort to clarify the role of p27 in the normal and tumorous human pituitary, we studied the expression of p27 by immunohistochemistry, using a highly specific mouse monoclonal anti-human p27 antibody. Normal pituitaries and 54 pituitary adenomas (twelve somatotrope adenomas, nine prolactinomas, twelve corticotrope adenomas, three TSH-producing tumors, six gonadotrope adenomas, six null cell adenomas, and six oncocytomas) were analyzed. p27 expression was determined semiquantitatively with regard to both the percentage of positive cells and the intensity of the staining. Normal human pituitaries showed strong expression of p27 in most nuclei. In contrast, the levels of p27 were reduced in the majority of the tumors analyzed. Twenty-two tumors (six somatotrope adenomas, five prolactinomas, four corticotrope adenomas, two TSH-producing tumors, two gonadotrope adenomas, and three null cell adenomas) were completely p27-negative. In 18 tumors, p27 expression was found in < or = 10% of the cells. In the other ten tumors, 11-80% of the cells were p27-positive. In summary, we were able to demonstrate reduced expression levels of the cell-cycle inhibitor p27 in tumors derived from all pituitary cell types. Our data indicate that p27 may be an important regulator of cellular proliferation in the anterior pituitary, the underexpression of which could play a role in pituitary tumorigenesis.

scholarly journals Clinically Non-Functioning Human Pituitary Adenomas

1992 ◽  
Vol 19 (2) ◽  
pp. 228-235 ◽  
Author(s):  
Sylvia L. Asa ◽  
Kalman Kovacs
Keyword(s):  
Pituitary Adenomas ◽  
Cell Types ◽  
Null Cell ◽  
Human Pituitary ◽  
Endocrine Activity ◽  
Hormone Synthesis ◽  
A Subunit ◽  
Null Cell Adenomas

ABSTRACT:Clinically non-functioning pituitary adenomas are morphologically classified into two groups, those which have hormone immunoreactivity and ultrastructural features of known adenohypophysial cell types but are clinically silent, and those composed of cells that do not resemble nontumorous adenohypophysial cell types. Among the fomer are the silent somatotroph adenomas, silent corticotroph adenomas and silent gonadotroph adenomas; the latter include the silent type III adenomas, null cell adenomas and oncocytomas. We review their histological, immunohistochemical and ultrastructural features, the results of in situ hybridization to determine hormone synthesis by these tumors and data obtained from tissue culture characterizing their hormone release in vitro. Non-functioning adenomas represent a heterogeneous group. The discrepancies between morphology, immunoreactivity and lack of endocrine activity of silent adenomas are not clear. Oncocytomas are variants of null cell adenomas. We suggest that null cell adenomas and oncocytomas originate in uncommitted pluripotent precursor cells capable of undergoing multidirectional differentiation. The progenitor cells differentiate most frequently toward FSH / a-subunit producing cells; the mechanism of preferential differentiation is obscure.

Immunonegative "Null Cell" Adenomas and Gonadotropin (Gn) Subunit (SUs) Immunopositive Adenomas Share Frequent Expression of Multiple Transcription Factors

2006 ◽  
Vol 17 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Yudo Ishii ◽  
Masanori Suzuki ◽  
Susumu Takekoshi ◽  
Noboru Egashira ◽  
Michio Yamazaki ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Null Cell ◽  
Null Cell Adenomas

Multiple pituitary adenomas in Cushing's disease

2000 ◽  
Vol 93 (5) ◽  
pp. 753-761 ◽  
Author(s):  
John K. Ratliff ◽  
Edward H. Oldfield
Keyword(s):  
Cushing’S Disease ◽  
Medical Records ◽  
Pituitary Adenomas ◽  
Cushing's Disease ◽  
Clinical Database ◽  
Null Cell ◽  
Content Type ◽  
Initial Surgery ◽  
Repeated Surgery ◽  
Fine Print

Object. Clinically evident multiple pituitary adenomas rarely occur. The authors assess the incidence and clinical relevance of multiple adenomas in Cushing's disease.Methods. A prospective clinical database of 660 pituitary surgeries was analyzed to assess the incidence of multiple pituitary adenomas in Cushing's disease. Relevant radiographic scans, medical records, and histopathological reports were reviewed.Thirteen patients with at least two separate histopathologically confirmed pituitary adenomas were identified. Prolactinomas (nine patients) were the most common incidental tumors. Other incidental tumors included secretors of growth hormone ([GH], one patient) and GH and prolactin (two patients), and a null-cell tumor (one patient). In two patients, early repeated surgery was performed because the initial operation failed to correct hypercortisolism, in one instance because the tumor excised at the initial surgery was a prolactinoma, not an adrenocorticotropic hormone—secreting tumor. One patient had three distinct tumors.Conclusions. Multiple pituitary adenomas are rare, but may complicate management of patients with pituitary disease.

Pathology of invasive pituitary tumors with special reference to functional classification

1986 ◽  
Vol 65 (6) ◽  
pp. 733-744 ◽  
Author(s):  
Bernd W. Scheithauer ◽  
Kalman T. Kovacs ◽  
Edward R. Laws ◽  
Raymond V. Randall
Keyword(s):  
Pituitary Adenomas ◽  
Prognostic Significance ◽  
Pituitary Tumors ◽  
Thyroid Stimulating Hormone ◽  
Biological Behavior ◽  
Null Cell ◽  
Content Type ◽  
Acth Cell ◽  
Ultrastructural Characteristics ◽  
Fine Print

✓ Pituitary adenomas may remain intrasellar or infiltrate dura and bone. Invasive adenomas are not considered to be malignant; in biological behavior they are between non-infiltrative adenomas and pituitary carcinomas. The latter are defined as tumors with subarachnoid, brain, or systemic metastasis. Invasion may be defined radiologically, operatively, or histologically. On the basis of operatively assessed tumor size and gross invasion of dura and bone as well as immunocytochemical and ultrastructural analysis of 365 pituitary adenomas, the following data were obtained. There were 23 growth hormone (GH)-cell adenomas: 14% microadenomas and 86% macroadenomas; their overall frequency of invasion was 50%. There were 24 prolactin (PRL)-cell adenomas: 33% microadenomas and 67% macroadenomas, with an overall frequency of invasion of 52%. Mixed GH-cell and PRL-cell adenomas were found in 35 cases; 26% were microadenomas and 74% were macroadenomas, and the overall frequency of invasion was 31%. Sixty patients had adrenocorticotropic hormone (ACTH)-cell adenomas (Cushing's disease): 87% microadenomas and 13% macroadenomas; the overall frequency of invasion was 25% (in 8% of microadenomas and 62% of macroadenomas). Twenty patients had ACTH-cell adenomas (Nelson's syndrome): 30% microadenomas and 70% macroadenomas; the overall frequency of invasion in these cases was 50% (in 17% of microadenomas and 64% of macroadenomas). Silent ACTH-cell adenomas, 100% macroadenomas, were found in 11 patients, with an 82% frequency of invasion. There were 32 follicle-stimulating and luteinizing hormone adenomas, all macroadenomas, with a frequency of invasion of 21%. Four patients had thyroid-stimulating hormone adenomas, all macroadenomas, with a 75% frequency of invasion. Null-cell adenomas were found in 93 cases: 2% microadenomas and 98% macroadenomas, with a frequency of invasion of 42%. There were 63 plurihormonal adenomas (GH, PRL, glycoprotein): 25% microadenomas and 75% macroadenomas, with a 50% overall frequency of invasion. Based on this study, and on their usual frequency of occurrence, the estimated rate of gross invasion by pituitary adenomas of all types is approximately 35%. It is concluded that immunocytochemical and ultrastructural characteristics of pituitary adenomas reflect the tendency of these tumors to infiltrate and hence may be of prognostic significance.

Atypical pituitary adenomas: incidence, clinical characteristics, and implications

2011 ◽  
Vol 114 (2) ◽  
pp. 336-344 ◽  
Author(s):  
Gabriel Zada ◽  
Whitney W. Woodmansee ◽  
Shakti Ramkissoon ◽  
Jordan Amadio ◽  
Vania Nose ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Immunohistochemical Analysis ◽  
Null Cell ◽  
Cell Adenoma ◽  
Null Cell Adenoma ◽  
Tumor Subtypes ◽  
P53 Immunoreactivity ◽  
Mib 1

Object The 2004 WHO classification of pituitary adenomas now includes an “atypical” variant, defined as follows: MIB-1 proliferative index greater than 3%, excessive p53 immunoreactivity, and increased mitotic activity. The authors review the incidence of this atypical histopathological subtype and its correlation with tumor subtype, invasion, and surgical features. Methods The records of 121 consecutive patients who underwent transsphenoidal surgery for pituitary adenomas during an 18-month period were retrospectively reviewed for evidence of atypical adenomas. Results Eighteen adenomas (15%) met the criteria for atypical lesions; 17 (94%) of the 18 were macroadenomas. On imaging, 15 (83%) demonstrated imaging evidence of surrounding invasion, compared with 45% of typical adenomas (p = 0.004). Atypical tumors occurred in 12 female (67%) and 6 male (33%) patients. Patient age ranged from 16 to 70 years (mean 48 years). Nine patients (50%) had hormonally active tumors, and 9 had nonfunctional lesions. Four (22%) of the 18 patients presented to us with recurrent tumors. Immunohistochemical analysis demonstrated the following tumor subtypes: GH-secreting adenoma with plurihormonal staining (5 patients [28%]); null-cell adenoma (5 patients [28%]); silent ACTH tumor (3 patients [17%]), ACTH-staining tumor with Cushing's disease (2 patients [11%]), prolactinoma (2 patients [11%]), and silent FSH-staining tumor (1 patient [6%]). The MIB-1 labeling index ranged from 3% to 20% (mean 7%). Conclusions Atypical tumors were identified in 15% of resected pituitary adenomas, and they tended to be aggressive, invasive macroadenomas. More longitudinal follow-up is required to determine whether surgical outcomes, potential for recurrence, or metastasis of atypical adenomas vary significantly from their typical counterparts.

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