Distinct clonal composition of primary and metastatic adrencorticotrophic hormone‐producing pituitary carcinoma
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Bibliographic record
Abstract
The pathogenetic mechanisms underlying pituitary tumorigenesis are largely unknown. Previous reports have suggested that aggressive pituitary adenomas and/or carcinomas may be associated with genetic alterations that are distinct from those responsible for the more common and less aggressive pituitary adenomas. Here, we describe the clonal composition of a pituitary carcinoma, its recurrence and its metastasis. The samples studied were from a 48-year-old woman who presented with recurrent Cushing's syndrome. During the 8-year course of her disease, she had an ACTH-producing pituitary carcinoma requiring two transsphenoidal procedures and resection of a metastatic cervical lymph node. Her disease remained active despite surgical resection, external beam irradiation and medical treatment with ketoconazole. Ultimately, bilateral adrenalectomy was performed to control the hypercortisolism. Morphological and immunohistochemical studies revealed that the primary and recurrent pituitary tumours and the metastatic lesion were an endocrine tumour with ACTH and growth hormone immunoreactivity. Primary, recurrent and metastatic tumour DNAs were analysed for X-chromosome inactivation and loss of heterozygosity (LOH) at several microsatellite loci on chromosomes 9,10, 11, 13 and 22. All three lesions were monoclonal in composition as suggested by the pattern of X chromosome inactivation of the PGK-1 allele. Moreover, the primary, recurrent and metastatic lesions demonstrated LOH at the microsatellite allelic markers PYGM and D10S217. In contrast, however, the metastatic lesion showed a loss-to-retention pattern at two distinct loci (IFNA and D22S156) compared to the primary and recurrent pituitary tumours. These findings, while consistent with a clonal composition of the primary and metastatic pituitary lesions, show each clone to be distinct. This is the first description of a metastatic pituitary carcinoma with a distinct clonal composition from its primary source.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it