Corticotroph carcinoma of the pituitary: a clinicopathological study

Abstract

To understand the relationship between pituitary adenoma and carcinoma, four adrenocorticotropic hormone-producing pituitary adenomas and corresponding metastatic carcinomas were studied. All were functional macroadenomas (three cases of Nelson syndrome and one of Cushing disease) that initially invaded the sella turcica and occurred in women ranging in age from 17 to 66 years (mean 45 years). Metastases (two craniospinal and two systemic) occurred after latency periods of 6 to 13 years. Histological specimens were immunostained for pituitary hormones, Ki-67 antigen (MIB-1), p53 and p27 proteins, D-type cyclins, and glucocorticoid receptor messenger (m)RNA. The DNA content of the specimens was assessed using Feulgen stain. Reactivities were quantified by digital image analysis. Primary/recurrent lesions and metastatic tumors differed according to their respective mean mitotic indices (1.2/10 hpf compared with 4.3/10 hpf), MIB-1 labeling (1.7% compared with 8%), p53 staining (37.3% compared with 49.9%), and p27 labeling (48% compared with 25%). Cyclin D, immunoreactivity provided no prognostically significant information. Glucocorticoid receptor mRNA was detected in all cases. Results of a ploidy analysis were variable and nonprognostic. In keeping with the 2000 World Health Organization classification of endocrine neoplasms, our findings support the concept that primary tumors that exhibit mitotic activity, an increased (> 3%) MIB-1 labeling index, and/or p53 immunoreactivity should be termed "atypical adenomas" to denote their aggressive potential and the possibility of future malignant transformation.

Malignant pituitary corticotroph adenomas: report of two cases and a comprehensive review of the literature

“…In 8 cases including one of our cases, metastases were found solely in bone, of which 4 patients were still alive at time of report in the literature [21,26,42]. Those patients had been treated with surgery (our case, [15]), with radiotherapy [21,26], and with combined chemotherapy and radiotherapy [26].…”

“…In our second case, Cushing's disease recurred two times for which the patient was treated by transsphenoidal surgery, bilateral adrenalectomy, and radiotherapy. Recurrences of Cushing's disease were reported frequently in the other case reports of malignant Cushing's disease; one recurrence was reported in 15 patients [8, 11, 12, 17, 18, 20-22, 30, 34, 35, 40, 45, 47, 48], two recurrences in 7 patients [13,14,21,24,26,44] and three or more recurrences in 10 patients [15,19,21,23,28,29,32,37,39,41]. Nelson's syndrome, defined as pituitary tumor progression after bilateral adrenalectomy, developed in one of our patients.…”

“…A few metastases were asymptomatic and only found during routine follow-up screening for (recurrent) Cushing's disease [12,13,23,46]. Most of the metastases, however, caused problems such as pain or local compression due to local growth in liver [12,21,25,27,32,39,45], bones [8,11,14,18,26,35], and the central nervous system [15,17,21,22,24,[29][30][31]. In nine cases metastases were found only by postmortem analysis in the liver, intracranial, meninges, and spinal cord [16,19,20,28,34,36,38,43,47].…”

“…Within the central nervous system, metastatic sites were intracranial in 43%, and extracranial in 24%. Extramedullary metastases (62% of the cases) were mostly reported in the liver [3,11,12,14,16,20,21,25,27,32,35,36,39,[41][42][43][44][45], lymph nodes [3,12,31,40,48], and bone [3, 11, 14, 18, 21, 22, 25-27, 39, 40, 42].…”

“…Those patients had been treated with surgery (our case, [15]), with radiotherapy [21,26], and with combined chemotherapy and radiotherapy [26]. Time interval to death in the other four cases ranged from 0.4 to 2.7 years [3,15,22,40].…”