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Abstract

Malignant pituitary tumours are rare and their pathogenesis is not fully understood. We have performed genetic analyses on tissues arising from a pituitary carcinoma that initially presented as a silent corticotroph adenoma but which failed to respond to repeated, aggressive surgical and medical therapy. Loss of heterozygosity (LOH) of known or putative tumour suppressor genes (TSG) was assessed by microsatellite analysis of microdissected tumour and matched patient blood DNA. Clonality of the pituitary tumour samples was analysed by two PCR-based techniques; one employing the highly polymorphic short tandem repeat (STR) within the human androgen receptor allele (HUMARA), another based on a restriction fragment length polymorphism of the X chromosome phosphoglycerokinase (PGK-1) gene. Screening with 9 microsatellite markers demonstrated allelic loss at 3 sites (D1S190, D3S1283 and D10S297) in all tumour samples except the presenting pituitary tumour. X chromosome inactivation analysis demonstrated polyclonality in the original presenting tumour and a metastatic deposit but monoclonality in tissue samples from a second and third transsphenoidal resection. In these cases of tumour recurrence both LOH and X chromosome inactivation suggest that monoclonality arose from preferential clonal growth from the original polyclonal tumour. Polyclonality of the metastatic deposit suggests that this was derived from the presenting tumour, although the LOH pattern indicates that a single clone dominates. The data are consistent with increasing allelic loss associated with tumour dedifferentiation and malignant transformation.

Recent Clinical and Pathophysiological Advances in Non-Functioning Pituitary Adenomas

“…The silent corticotroph adenoma subgroup members (subtypes 1 and 2) seem to have a more aggressive clinical course and higher recurrence rate than null cell adenomas and oncocytomas [13,14,15]. Corticotroph carcinoma presenting as a silent corticotroph adenoma has also been described [16]. While it is well established that patients with functioning corticotroph adenomas have a high female preponderance, there is controversy regarding the male:female ratio of silent adenomas, as summarized in table 2.…”

A Case of Corticotroph Carcinoma that Caused Multiple Cranial Nerve Palsies, Destructive Petrosal Bone Invasion, and Liver Metastasis

“…Of the 53 reported patients, including 34 women and 19 men, only 32 subjects were diagnosed as having Cushing' syndrome or disease at initial presentation [5–9, 12–18, 20–22, 27–32, 34, 35, 38, 39, 43]. The remaining 21 cases were endocrinologically asymptomatic, except for one case of galactorrhea–amenorrhea syndrome [25], and presented with the pituitary mass compressing the adjacent tissues [10, 11, 19, 23, 24, 26, 27, 33, 36, 37, 40–42, 44, 45]: visual disturbance in 13 cases, headache in one case, and visual impairment plus headache in five cases (symptoms not described in one case [39]). These 21 hormonally asymptomatic tumors, which were initially diagnosed as non-functioning adenomas, can be divided into two subgroups on the basis of the subsequent clinical course.…”

“…These 21 hormonally asymptomatic tumors, which were initially diagnosed as non-functioning adenomas, can be divided into two subgroups on the basis of the subsequent clinical course. One subgroup consisted of 15 adenomas that developed characteristic features of Cushing's disease 73 ± 12 months (range, 6–144 months) after initial diagnosis [10, 11, 19, 23–26, 33, 36, 37, 39, 40, 42, 44, 45]. Of these 15 adenomas, only five tumors underwent initial immunohistochemical examination, and all were positive for ACTH, indicating that these 5 adenomas were silent corticotroph adenomas at the initial presentation.…”

“…The most common is corticotroph carcinoma, representing 42% of pituitary carcinomas [1–4], and 53 cases of corticotroph carcinoma have been described in the English literature so far [5–45]. At the time of diagnosis, 32 (60%) of the 53 cases presented with symptoms and signs of chronic hypercortisolemia characteristic of Cushing's disease [5–9, 12–18, 20–22, 27–32, 34, 35, 38, 39, 43], while 15 (28%) of the 53 cases developed these features 6 months to 12 years after an initial presentation as a pituitary mass compressing the surrounding tissues [10, 11, 19, 23–26, 33, 36, 37, 39, 40, 42, 44, 45]. Although very rarely, silent corticotroph carcinoma has also been recognized by the presence of metastatic lesions in the absence of clinical features associated with chronic hypercortisolemia [27, 41].…”

Orbital metastasis of pituitary growth hormone secreting carcinoma causing lateral gaze palsy

“…[58131719253951] Because of the close proximity of the cavernous sinuses and critical neurovascular structures, subtotal resection with follow up radiation therapy is a fairly common clinical scenario. [11213203158] Conventional radiotherapy is extensively utilized and yields excellent local rates of control. [30545557] Increasingly, radiosurgery has begun to gain favor as a modality producing similar control rates with possibly earlier secretory control, especially for GH-secreting adenomas.…”