Epithelial and organ‐related marker expression in pituitary adenomas

Abstract

The histologic expression of epithelial and organ-related immunohistochemical markers in primary sellar region tumors has received little attention to date. This lack of empirical data may lead to mistaken assumptions in the evaluation of sellar region neoplasms. To address this issue, the frequency and specificity of epithelial (cytokeratin 7(CK7), CK20) and organ-related differentiation markers (gross cystic disease fluid protein-15 (GCDFP-15), thyroid transcription factor-1 (TTF-1), Napsin A, paired box 8 (PAX-8), hepatocyte paraffin 1 (HepPar1) and estrogen receptor (ER)) were studied in 40 patients with adenomas comprising five hormonal sub-types. Non-parametric statistical procedures were used to examine associations between marker expression and tumor sub-type. CK7 and CK20 immunoreactivity were seen in 48% and 8% of tumors, respectively, although never in a diffuse pattern. CK20 expression was nearly exclusive to corticotrophs, whereas CK7 frequently highlighted cells with dendritic-type morphology. The specificity of organ-related differentiation markers was 100% (monoclonal Napsin A, GCDFP-15 and TTF-1), 97% (HepPar1 and PAX-8), 90% (polyclonal Napsin A) and 72% (ER); no tumors demonstrated significant co-expression of these organ-related markers with either CK7 or CK20. The first major conclusion of this study is that CK7 staining in adenoma is more frequent than has been previously than has been previously described. CK7 immunoreactive cells often displayed a dendritic-type morphology, including within large macroadenomas, which raises the question as to whether these represent tumor cells with folliculo-stellate cell-type differentiation, as these also have dendritic cell-type morphology and express CK7 in non-neoplastic glands. The second major conclusion, which confirms earlier findings, is that CK20 staining is a very infrequent immunohistochemical finding in adenomas that is virtually limited to corticotrophs and thus is helpful in diagnostic confirmation of that sub-type. The final conclusion is in regard to those features that separate adenomas from sellar region metastases: adenomas do not demonstrate significant expression of TTF-1, monoclonal Napsin A, PAX-8, HepPar1 or GCDFP-15, nor do they exhibit diffuse expression of CK7 and CK20.

Pituitary Gangliocytoma Producing TSH and TRH: A Review of “Gangliocytomas of the Sellar Region”

“…However, some authors implied a participation of neural crest-derived cells ( 9 , 11 ). The immunohistochemical results of positivity for CAM5.2 and CK7 but negativity for CK20 were confirmed in a subpopulation of NENs as well as that of pituitary adenomas, which may indicate organ-related differentiation in neoplasms ( 38 , 74 ). While the European Pituitary Pathology Group has proposed the diagnostic algorithms for PitNETs, it is interesting to note that the pathological features of GCs/MGAs are more similar to those of NENs than to those of functional adenomas ( 67 , 75 ).…”

Posterior pituitary tumours: patient outcomes and determinants of disease recurrence or persistence

“…It is also expressed in the ventral forebrain and pituitary in rodents and in normal human pituicytes which originate from the ventral ectoderm ( 74 ). In a prior study, TTF-1 was found to be positively expressed in all subtypes of PPTs and was negative in normal or tumoral adenohypophyseal tissue ( 75 ). A recent study has reported a new entity PPETS, also expressing TTF-1 ( 15 ).…”

Tumor-to-tumor metastasis: lung adenocarcinoma into a clinically non-functioning gonadotroph pituitary adenoma: a rare case.

“…These cells contain cytoplasmic extensions resembling folliculostellate cells found in the anterior pituitary may look like a metastatic lesion. Therefore, the distribution pattern of CK7 positive cells is important since a diffuse pattern will most likely favor a metastatic neoplasm (13). No adenomas were ever found to have diffuse, strong CK7 immunoreactivity.…”