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Silent subtype 3 carcinoma of the pituitary: a case report

Pituitary carcinomas are rare lesion defined as adenohypophyseal tumours that metastasize throughout the craniospinal axis or to systemic sites, usually bone, liver or lymph nodes. Most are endocrinologically functional and only a minority present as nonfunctioning lesions including silent corticotroph, gonadotroph [1] and presumed null cell carcinomas [2–13]. Pituitary adenomas of silent subtype 3 (SS3) are very uncommon tumours that typically present as invasive, clinically nonfunctioning macroadenomas. They often exhibit prolactin (PRL), growth hormone (GH) and/or thyroid-stimulating hormone (TSH) immunoreactivity and, although they are typically described as endocrinologically nonfunctioning, SS3 may uncommonly present with acromegaly or galactorrhoea. To date, no examples of SS3 carcinoma have been documented [14,15]. We report a male patient who presented in 1980 at the age of 43 years with a nonfunctioning pituitary macroadenoma. Symptoms at onset included fatigue, weight loss, epistaxis and visual field loss. The patient underwent a transfrontal, subtotal adenomectomy. Post-operative anterior pituitary insufficiency prompted Synthroid, Cortef and testosterone therapy, but visual field testing did show improvement. That same year, external radiation therapy (45 Gy in 25 fractions) was administered for residual disease. In 1989, a large, invasive recurrence was noted on computerized tomographic scan. New symptoms of visual loss and dizziness had developed, and persistent anterior hypopituitarism was documented. The patient underwent trans-sphenoidal debulking. The surgeon commented upon the fibrous texture of the tumour as well as upon a firm, fibrous capsule, which was partly left in place given significant intraoperative haemorrhage. On post-operative magnetic resonance imaging scan, a large component of the lesion remained within the right cavernous and sphenoid sinuses. Contiguous tumour destroyed the inferior petrous apex and clivus. In addition, the lesion extended posteriorly into the prepontine cistern. Due to significant residual disease, Octreotide treatment was instituted but failed to halt growth of the lesion. In 1991, considerable extension towards the nasopharynx was noted. In early 1992, he developed proptosis, third and seventh cranial nerve palsies, as well as right-sided hearing loss due to massive sphenoid sinus, parasellar and petrous apex involvement. The patient then underwent an extended bifrontal craniotomy with a right lateral approach to the optic foramen. The nasopharyngeal component was completely removed and a subtotal resection of the intradural component was achieved. Five months thereafter, a magnetic resonance imaging scan demonstrated no change in tumour size when compared with immediate post-operative imaging. Nonetheless, during the following years, tumour progression was noted as were metastases to calvarium, ribs and spine. Biopsy of a rib lesion revealed metastatic pituitary carcinoma. Additional external radiation therapy to the parasellar region and to spinal metastases was undertaken. Additional follow-up indicated tumour progression. The patient died of tumour in 1996; no post mortem examination was performed. Histological analysis of the primary tumour, its recurrences and a rib metastasis showed similar features. Tumour fragments consisted of trabecula, cords and nests of chromophobic, periodic acid Schiff-negative cells with moderate nuclear pleomorphism and some nuclear enlargement (Figure 1A). Only occasional mitoses were noted. Approximately 10% of tumour cells were immunoreactive for PRL (Dako Cytomaton, Carpinteria, CA, USA; 1:2000, monoclonal) (Figure 1B) and about 20% for alpha-subunit (Launch Diagnostics, Longfield, UK; 1:200; monoclonal) (Figure 2C); immunostains for GH (Novocastra, Burlingame, CA, USA; 1:500, polyclonal), adrenocorticotrophic hormone (Laboratory Vision, Fremont, CA, USA; 1:200, polyclonal), luteinizing hormone (Zymed, San Francisco, CA, USA; 1:600, ZSL11), folliclestimulating hormone-beta subunit (Novocastra, 1:2500, INNHSH60), TSH-beta subunit (Novocastra, 1:200, monoclonal) were negative. The Ki67 (Dako Cytomaton; 1:300, MIB-1) labelling index was estimated to be about 1%; intense p53 (Dako Cytomaton, 1:2000, DO7) staining was present in 30% of tumour cells (Figure 2D). The