Prolactinoma pathophysiology
|
Prolactinoma Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Prolactinoma pathophysiology On the Web |
|
American Roentgen Ray Society Images of Prolactinoma pathophysiology |
|
Risk calculators and risk factors for Prolactinoma pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2], Faizan Sheraz, M.D. [3]
Overview
Prolactinoma is the most common type of pituitary adenoma. Prolactinoma may occur in approximately 30% of multiple endocrine neoplasia type 1 patients. It may also occur with Carney complex or McCune-Albright syndrome. Prolactinoma is also associated with various familial syndromes for example MEN1 syndrome. There have been familial cases of prolactinoma unrelated to MEN 1 syndrome as well. On gross pathology, prolactinoma is divided on the basis of size into microprolactinoma and macroprolactinoma. On histological analysis, prolactinoma may be divided into sparsely granulated and densely granulated.
Pathophysiology
- Prolactinoma are monoclonal in nature. This suggests that the somatic cell mutation responsible for the development of prolactionoma, occurs before clonal expansion of lactotrophs.[1]
PTTG-1 gene
- One gene involved in the pathogenesis of prolactinoma is the pituitary tumor transforming gene-1 (PTTG-1).[2][3]
- The PTTG-1 gene is related to various endocrine and non-endocrine tumors such as:
- Prolactinomas with a higher expression of the PTTG-1 gene tend to be more invasive.
MEN1 syndrome
- Many prolactinomas are related to multiple endocrine neoplasia type 1.[4]
- The MEN1 gene is located on 11q13.
- The MEN1 gene is a tumor suppressor gene that follows the concept of 'two-hit hypothesis,' which implies that both alleles that code for a particular gene must be affected before an effect manifests.
- The consequence of this mode of tumor development is that if one allele for the gene is damaged, the second can still produce the correct form of normal protein.
- Affected individuals carry one altered copy of the MEN1 gene and the other copy is lost due to somatic mutation.
Associated Diseases
Prolactinoma may be associated with:[5]
Genetics
Familial pituitary adenomas
- A pituitary adenoma may be part of a familial syndrome:[6]
| Syndrome | Gene | Gene locus | Notes |
|---|---|---|---|
| Multiple endocrine neoplasia I | MEN1 | 11q13 | Characterized by the 3 Ps: pituitary adenoma, parathyroid adenoma, pancreatic neuroendocrine tumor |
| MEN1-like syndrome | CDKN1B | 12q13 | Associated with pituitary adenoma, parathyroid adenoma, neuroendocrine tumor |
| Carney complex | PRKAR1A | 17q24 | Other findings (mnemonic NAME): nevi, atrial myxoma, myxoid neurofibroma, ephelides (freckles) |
| Familial isolated pituitary adenoma | AIP | 11q13 |
|
Gross Pathology
The gross pathology of prolactinoma is as follows:[8]
- Microprolactinomas (<10mm size) are usually found in the lateral wing of the pituitary gland. They are most often surrounded by well defined pseudocapsules composed of reticulin.
- Macroprolactinomas (>10mm size) differ substantially in size and behavior. Some cause sellar expansion while others invade the skull base.
- About 50% of all prolactinoma grossly invade surrounding structures.
Microscopic Pathology
- Prolactinoma are divded into two types based on microscopy:[8]
- Sparsely granulated variant
- This is common type of variant.
- This contains chromophobic cells.
- Densely granulated variant
- This is a rare varaint.
- This contains acidophilic cells.
- Note: There is no clinical, biological and prognostic difference between the tow variants.
References
- ↑ Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S (1990). "Clonal origin of pituitary adenomas". J Clin Endocrinol Metab. 71 (6): 1427–33. doi:10.1210/jcem-71-6-1427. PMID 1977759.
- ↑ Vlotides G, Eigler T, Melmed S (2007). "Pituitary tumor-transforming gene: physiology and implications for tumorigenesis". Endocr Rev. 28 (2): 165–86. doi:10.1210/er.2006-0042. PMID 17325339.
- ↑ Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD; et al. (1999). "Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas". J Clin Endocrinol Metab. 84 (2): 761–7. doi:10.1210/jcem.84.2.5432. PMID 10022450.
- ↑ Agarwal SK, Lee Burns A, Sukhodolets KE, Kennedy PA, Obungu VH, Hickman AB; et al. (2004). "Molecular pathology of the MEN1 gene". Ann N Y Acad Sci. 1014: 189–98. PMID 15153434.
- ↑ Ciccarelli A, Daly AF, Beckers A (2005). "The epidemiology of prolactinomas". Pituitary. 8 (1): 3–6. doi:10.1007/s11102-005-5079-0. PMID 16411062.
- ↑ Karhu A, Aaltonen LA (2007). "Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update". Hum Mol Genet. 16 Spec No 1: R73–9. doi:10.1093/hmg/ddm036. PMID 17613551.
- ↑ Korbonits M, Storr H, Kumar AV (2012). "Familial pituitary adenomas - who should be tested for AIP mutations?". Clin Endocrinol (Oxf). 77 (3): 351–6. doi:10.1111/j.1365-2265.2012.04445.x. PMID 22612670.
- ↑ 8.0 8.1 Bigner, D. D. (2006). Russell and Rubinstein's pathology of tumors of the nervous system. London New York, NY: Hodder Arnold Distributed in the United States of America by Oxford University Press. ISBN 978-0340810071.