Silent subtype 3 pituitary adenoma: A clinicopathologic analysis of the Mayo Clinic experience

D. Erickson, B. Scheithauer, J. Atkinson, E. Horvath, K. Kovacs, R. V. Lloyd, William Francis Young

Research output: Contribution to journalArticle

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Abstract

Background Macroadenomas represent 50% of pituitary tumours and are often (30%) nonfunctioning. Their immunophenotype suggests differentiation toward a specific pituitary cell line. A substantial proportion of tumours with particularly aggressive behaviour are so called 'silent subtype 3 adenoma'. Its diagnosis requires ultrastructural confirmation. Although once included among silent corticotroph adenomas, this aggressive, morphologically distinctive tumour is now recognized as a major form of plurihormonal adenoma and, in fact, some patients might present with clinical hormonal excess. The cytogenesis and pathobiology of silent subtype 3 adenomas is unsettled. Objective We undertook a systematic clinicopathologic examination of the Mayo Clinic experience with this poorly understood tumour. Design This retrospective, single institution study found 27 confirmed examples of silent subtype 3 adenoma, a frequency of 0·9% of adenomas. Despite histologic and immunophenotypic variation, their ultrastructural features were diagnostic and the sole basis for case inclusion. Results The study group was comprised of 16 men (59%) and 11 women (41%); two patients (7%) had definitive diagnosis of multiple endocrine neoplasia type 1 (MEN1). Three tumours (11%) were discovered incidentally. Nine patients each (38%) presented with headaches or visual field loss. Endocrine hyperfunction was noted in eight cases (30%), including GH excess in five (19%) and clinically significant PRL elevation in three (11%). Hypogonadism was noted in 17 cases (63%) and growth arrest in one (4%). All tumours were macroadenomas; 16 (60%) showed radiographic evidence of invasion. Most tumours were plurihormonal, featuring immunoreactivity for PRL (17), GH (15), TSH (16) or ACTH (3); only one lesion was immunonegative. Although a gross total resection was achieved in 19 cases (70%), re-operation for recurrence(s) was required in seven of these (37%). Follow-up (mean, 69 months) showed a high (59%) rate of persistent or recurrent of tumour. Overall, 14 patients (54%) underwent radiotherapy after surgical treatment: three patients (12%) for substantial residual tumour, eight (31%) as adjuvant therapy and three (12%) for tumour regrowth. Conclusion Silent subtype 3 adenoma, a plurihormonal tumour, is rare and aggressive in nature. This adenoma must be considered in the differential of often clinically nonfunctioning but plurihormonal adenomas featuring variable cytologic atypia. Electron microscopy is required for confirmation of the diagnosis. The cytogenesis of silent subtype 3 adenoma remains unsettled.

Original languageEnglish (US)
Pages (from-to)92-99
Number of pages8
JournalClinical Endocrinology
Volume71
Issue number1
DOIs
StatePublished - Jul 2009

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Pituitary Neoplasms
Adenoma
Neoplasms
ACTH-Secreting Pituitary Adenoma
Multiple Endocrine Neoplasia Type 1
Hypogonadism
Residual Neoplasm
Visual Fields
Adrenocorticotropic Hormone
Headache
Electron Microscopy
Radiotherapy
Recurrence
Cell Line
Therapeutics
Growth

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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Silent subtype 3 pituitary adenoma : A clinicopathologic analysis of the Mayo Clinic experience. / Erickson, D.; Scheithauer, B.; Atkinson, J.; Horvath, E.; Kovacs, K.; Lloyd, R. V.; Young, William Francis.

In: Clinical Endocrinology, Vol. 71, No. 1, 07.2009, p. 92-99.

Research output: Contribution to journalArticle

Erickson, D. ; Scheithauer, B. ; Atkinson, J. ; Horvath, E. ; Kovacs, K. ; Lloyd, R. V. ; Young, William Francis. / Silent subtype 3 pituitary adenoma : A clinicopathologic analysis of the Mayo Clinic experience. In: Clinical Endocrinology. 2009 ; Vol. 71, No. 1. pp. 92-99.
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abstract = "Background Macroadenomas represent 50{\%} of pituitary tumours and are often (30{\%}) nonfunctioning. Their immunophenotype suggests differentiation toward a specific pituitary cell line. A substantial proportion of tumours with particularly aggressive behaviour are so called 'silent subtype 3 adenoma'. Its diagnosis requires ultrastructural confirmation. Although once included among silent corticotroph adenomas, this aggressive, morphologically distinctive tumour is now recognized as a major form of plurihormonal adenoma and, in fact, some patients might present with clinical hormonal excess. The cytogenesis and pathobiology of silent subtype 3 adenomas is unsettled. Objective We undertook a systematic clinicopathologic examination of the Mayo Clinic experience with this poorly understood tumour. Design This retrospective, single institution study found 27 confirmed examples of silent subtype 3 adenoma, a frequency of 0·9{\%} of adenomas. Despite histologic and immunophenotypic variation, their ultrastructural features were diagnostic and the sole basis for case inclusion. Results The study group was comprised of 16 men (59{\%}) and 11 women (41{\%}); two patients (7{\%}) had definitive diagnosis of multiple endocrine neoplasia type 1 (MEN1). Three tumours (11{\%}) were discovered incidentally. Nine patients each (38{\%}) presented with headaches or visual field loss. Endocrine hyperfunction was noted in eight cases (30{\%}), including GH excess in five (19{\%}) and clinically significant PRL elevation in three (11{\%}). Hypogonadism was noted in 17 cases (63{\%}) and growth arrest in one (4{\%}). All tumours were macroadenomas; 16 (60{\%}) showed radiographic evidence of invasion. Most tumours were plurihormonal, featuring immunoreactivity for PRL (17), GH (15), TSH (16) or ACTH (3); only one lesion was immunonegative. Although a gross total resection was achieved in 19 cases (70{\%}), re-operation for recurrence(s) was required in seven of these (37{\%}). Follow-up (mean, 69 months) showed a high (59{\%}) rate of persistent or recurrent of tumour. Overall, 14 patients (54{\%}) underwent radiotherapy after surgical treatment: three patients (12{\%}) for substantial residual tumour, eight (31{\%}) as adjuvant therapy and three (12{\%}) for tumour regrowth. Conclusion Silent subtype 3 adenoma, a plurihormonal tumour, is rare and aggressive in nature. This adenoma must be considered in the differential of often clinically nonfunctioning but plurihormonal adenomas featuring variable cytologic atypia. Electron microscopy is required for confirmation of the diagnosis. The cytogenesis of silent subtype 3 adenoma remains unsettled.",
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T2 - A clinicopathologic analysis of the Mayo Clinic experience

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AU - Kovacs, K.

AU - Lloyd, R. V.

AU - Young, William Francis

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N2 - Background Macroadenomas represent 50% of pituitary tumours and are often (30%) nonfunctioning. Their immunophenotype suggests differentiation toward a specific pituitary cell line. A substantial proportion of tumours with particularly aggressive behaviour are so called 'silent subtype 3 adenoma'. Its diagnosis requires ultrastructural confirmation. Although once included among silent corticotroph adenomas, this aggressive, morphologically distinctive tumour is now recognized as a major form of plurihormonal adenoma and, in fact, some patients might present with clinical hormonal excess. The cytogenesis and pathobiology of silent subtype 3 adenomas is unsettled. Objective We undertook a systematic clinicopathologic examination of the Mayo Clinic experience with this poorly understood tumour. Design This retrospective, single institution study found 27 confirmed examples of silent subtype 3 adenoma, a frequency of 0·9% of adenomas. Despite histologic and immunophenotypic variation, their ultrastructural features were diagnostic and the sole basis for case inclusion. Results The study group was comprised of 16 men (59%) and 11 women (41%); two patients (7%) had definitive diagnosis of multiple endocrine neoplasia type 1 (MEN1). Three tumours (11%) were discovered incidentally. Nine patients each (38%) presented with headaches or visual field loss. Endocrine hyperfunction was noted in eight cases (30%), including GH excess in five (19%) and clinically significant PRL elevation in three (11%). Hypogonadism was noted in 17 cases (63%) and growth arrest in one (4%). All tumours were macroadenomas; 16 (60%) showed radiographic evidence of invasion. Most tumours were plurihormonal, featuring immunoreactivity for PRL (17), GH (15), TSH (16) or ACTH (3); only one lesion was immunonegative. Although a gross total resection was achieved in 19 cases (70%), re-operation for recurrence(s) was required in seven of these (37%). Follow-up (mean, 69 months) showed a high (59%) rate of persistent or recurrent of tumour. Overall, 14 patients (54%) underwent radiotherapy after surgical treatment: three patients (12%) for substantial residual tumour, eight (31%) as adjuvant therapy and three (12%) for tumour regrowth. Conclusion Silent subtype 3 adenoma, a plurihormonal tumour, is rare and aggressive in nature. This adenoma must be considered in the differential of often clinically nonfunctioning but plurihormonal adenomas featuring variable cytologic atypia. Electron microscopy is required for confirmation of the diagnosis. The cytogenesis of silent subtype 3 adenoma remains unsettled.

AB - Background Macroadenomas represent 50% of pituitary tumours and are often (30%) nonfunctioning. Their immunophenotype suggests differentiation toward a specific pituitary cell line. A substantial proportion of tumours with particularly aggressive behaviour are so called 'silent subtype 3 adenoma'. Its diagnosis requires ultrastructural confirmation. Although once included among silent corticotroph adenomas, this aggressive, morphologically distinctive tumour is now recognized as a major form of plurihormonal adenoma and, in fact, some patients might present with clinical hormonal excess. The cytogenesis and pathobiology of silent subtype 3 adenomas is unsettled. Objective We undertook a systematic clinicopathologic examination of the Mayo Clinic experience with this poorly understood tumour. Design This retrospective, single institution study found 27 confirmed examples of silent subtype 3 adenoma, a frequency of 0·9% of adenomas. Despite histologic and immunophenotypic variation, their ultrastructural features were diagnostic and the sole basis for case inclusion. Results The study group was comprised of 16 men (59%) and 11 women (41%); two patients (7%) had definitive diagnosis of multiple endocrine neoplasia type 1 (MEN1). Three tumours (11%) were discovered incidentally. Nine patients each (38%) presented with headaches or visual field loss. Endocrine hyperfunction was noted in eight cases (30%), including GH excess in five (19%) and clinically significant PRL elevation in three (11%). Hypogonadism was noted in 17 cases (63%) and growth arrest in one (4%). All tumours were macroadenomas; 16 (60%) showed radiographic evidence of invasion. Most tumours were plurihormonal, featuring immunoreactivity for PRL (17), GH (15), TSH (16) or ACTH (3); only one lesion was immunonegative. Although a gross total resection was achieved in 19 cases (70%), re-operation for recurrence(s) was required in seven of these (37%). Follow-up (mean, 69 months) showed a high (59%) rate of persistent or recurrent of tumour. Overall, 14 patients (54%) underwent radiotherapy after surgical treatment: three patients (12%) for substantial residual tumour, eight (31%) as adjuvant therapy and three (12%) for tumour regrowth. Conclusion Silent subtype 3 adenoma, a plurihormonal tumour, is rare and aggressive in nature. This adenoma must be considered in the differential of often clinically nonfunctioning but plurihormonal adenomas featuring variable cytologic atypia. Electron microscopy is required for confirmation of the diagnosis. The cytogenesis of silent subtype 3 adenoma remains unsettled.

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