Nonneoplastic signet-ring cells in the gallbladder and uterine cervix. A potential source of overdiagnosis.

We describe 3 cases of nonneoplastic signet-ring cell change in ulcerated mucosa, 2 of them in the gallbladder and 1 in an endocervical polyp. In the gallbladder cases, there were focal collections of signet-ring cells both on the mucosal surface and within the lumen of tubules, whereas in the endocervical polyp, the signet-ring cell aggregates were entirely confined to the mucosal surface. In all 3 cases, the signet-ring cells were positive for Mayer's mucicarmine and immunoreactive for keratin AE1/AE3. The lack of nuclear atypicality, the arrangement in superficial and intraluminal nests, and the admixture with histiocytes and other inflammatory cells are in keeping with the interpretation that the signet-ring cells are disrupted mucosal goblet cells exhibiting hyperplastic and degenerative changes. A review of the literature disclosed only other 2 previously reported cases of benign signet-ring cell changes in the gallbladder and none--to the best of our knowledge--in an endocervical polyp. Awareness of this phenomenon is of importance to avoid a potential overdiagnosis of signet-ring cell adenocarcinoma.

Expression of p16(INK4A) gene in human pituitary tumours.

Pituitary adenomas comprise 10-15% of primary intracranial tumours but the mechanisms leading to tumour development are yet to be clearly established. The retinoblastoma pathway, which regulates the progression through the cell cycle, is often deregulated in different types of tumours. We studied the cyclin-dependent kinase inhibitor p16(INK4A) gene expression at mRNA level in human pituitary adenomas. Forty-six tumour specimens of different subtypes, 21 clinically non-functioning, 12 growth hormone-secreting, 6 prolactin-secreting, 6 adrenocorticotropin-secreting, and 1 thyrotropin-secreting tumours were studied. All clinically non-functioning and most of the hormone-secreting tumours were macroadenomas (38/46). The RT-PCR assay and electrophoresis of the PCR-products showed that p16(INK4A) mRNA was undetectable in: 62% of non-functioning, 8% of growth hormone-secreting, 17% of prolactin-secreting and 17% of adrenocorticotropin-secreting adenomas. Forty percent of all macroadenomas and 25% of microadenomas had negative p16(INK4A) mRNA, the latter results suggest that the absence of p16(INK4A) product might be an early event in tumours with no expression of this suppressor gene. Within the non-functioning adenomas 63% were "null cell" and 37% were positive for some hormone, both subgroups showed similar percentage of cases with absence of p16(INK4A) mRNA. Our results show that clinically non-functioning macroadenomas have impaired p16(INK4A) expression in a clearly higher proportion than any other pituitary tumour subtype investigated. Other regulatory pathways may be implicated in the development of tumours with positive p16(INK4A) expression.