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==Overview==
==Overview==
[[Prolactinoma]] is the most common type of [[Pituitary adenoma|Pituitary adenomas]]. [[Prolactinoma]] may occur in approximately 30% of [[Multiple endocrine neoplasia type 1]].It may also occur with [[Carney complex]] or [[McCune-Albright syndrome]]. There are a few reports of [[familial]] cases of [[prolactinoma]] unrelated to [[Multiple endocrine neoplasia type 1|MEN 1 syndrome]].<ref name="pmid16411062">{{cite journal| author=Ciccarelli A, Daly AF, Beckers A| title=The epidemiology of prolactinomas. | journal=Pituitary | year= 2005 | volume= 8 | issue= 1 | pages= 3-6 | pmid=16411062 | doi=10.1007/s11102-005-5079-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16411062  }} </ref>
[[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]]. There are a few reports of [[familial]] cases of [[prolactinoma]] unrelated to [[Multiple endocrine neoplasia type 1|MEN 1 syndrome]].<ref name="pmid16411062">{{cite journal| author=Ciccarelli A, Daly AF, Beckers A| title=The epidemiology of prolactinomas. | journal=Pituitary | year= 2005 | volume= 8 | issue= 1 | pages= 3-6 | pmid=16411062 | doi=10.1007/s11102-005-5079-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16411062  }} </ref>
 
[[Prolactinoma]] is also associated with various [[familial]] syndromes.<ref name="pmid17613551">{{cite journal| author=Karhu A, Aaltonen LA| title=Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update. | journal=Hum Mol Genet | year= 2007 | volume= 16 Spec No 1 | issue=  | pages= R73-9 | pmid=17613551 | doi=10.1093/hmg/ddm036 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17613551  }} </ref> On gross pathology, [[prolactinoma]] is divided on the basis of size into microprolactinoma and macroprolactinoma. On microscopic histological analysis, [[prolactinoma]] has two types: sparsely granulated and densely granulated.


[[Prolactinoma]] is also associated with various familial syndromes.<ref name="pmid17613551">{{cite journal| author=Karhu A, Aaltonen LA| title=Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update. | journal=Hum Mol Genet | year= 2007 | volume= 16 Spec No 1 | issue=  | pages= R73-9 | pmid=17613551 | doi=10.1093/hmg/ddm036 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17613551  }} </ref> On gross pathology, [[prolactinoma]] is divided on the basis of size: microprolactinoma and macroprolactinoma. On microscopic histological analysis, [[prolactinoma]] has two types: sparsely granulated variant and densely granulated variant.
==Pathophysiology==
==Pathophysiology==
*[[Prolactinoma]] are [[monoclonal]] in nature. This suggests that [[somatic]] [[Cell (biology)|cell]] [[mutation]] occurs before clonal expansion of [[Lactotroph|lactotrophs]].<ref name="pmid1977759">{{cite journal| author=Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S| title=Clonal origin of pituitary adenomas. | journal=J Clin Endocrinol Metab | year= 1990 | volume= 71 | issue= 6 | pages= 1427-33 | pmid=1977759 | doi=10.1210/jcem-71-6-1427 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1977759  }} </ref>
*[[Prolactinoma]] are [[monoclonal]] in nature. This suggests that [[somatic]] [[Cell (biology)|cell]] [[mutation]] occurs before clonal expansion of [[Lactotroph|lactotrophs]].<ref name="pmid1977759">{{cite journal| author=Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S| title=Clonal origin of pituitary adenomas. | journal=J Clin Endocrinol Metab | year= 1990 | volume= 71 | issue= 6 | pages= 1427-33 | pmid=1977759 | doi=10.1210/jcem-71-6-1427 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1977759  }} </ref>
*Gene involved in the pathogenesis of [[prolactinoma]] include Pituitary tumor transforming gene-1(PTTG-1).<ref name="pmid17325339">{{cite journal| author=Vlotides G, Eigler T, Melmed S| title=Pituitary tumor-transforming gene: physiology and implications for tumorigenesis. | journal=Endocr Rev | year= 2007 | volume= 28 | issue= 2 | pages= 165-86 | pmid=17325339 | doi=10.1210/er.2006-0042 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17325339  }} </ref><ref name="pmid10022450">{{cite journal| author=Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD et al.| title=Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. | journal=J Clin Endocrinol Metab | year= 1999 | volume= 84 | issue= 2 | pages= 761-7 | pmid=10022450 | doi=10.1210/jcem.84.2.5432 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10022450  }} </ref>
*One [[gene]] involved in the pathogenesis of [[prolactinoma]] is the [[PTTG1|pituitary tumor transforming gene-1]] ([[PTTG1|PTTG-1]]).<ref name="pmid17325339">{{cite journal| author=Vlotides G, Eigler T, Melmed S| title=Pituitary tumor-transforming gene: physiology and implications for tumorigenesis. | journal=Endocr Rev | year= 2007 | volume= 28 | issue= 2 | pages= 165-86 | pmid=17325339 | doi=10.1210/er.2006-0042 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17325339  }} </ref><ref name="pmid10022450">{{cite journal| author=Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD et al.| title=Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. | journal=J Clin Endocrinol Metab | year= 1999 | volume= 84 | issue= 2 | pages= 761-7 | pmid=10022450 | doi=10.1210/jcem.84.2.5432 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10022450  }} </ref>
**PTTG-1 gene is related to various endocrine and non-endocrine tumors such as:
**The [[PTTG1|PTTG-1 gene]] is related to various endocrine and non-endocrine tumors such as:
***Endocrine related tumors: [[pituitary]], [[thyroid]], [[breast]], [[ovarian]], and [[uterine]] tumors.
***Endocrine related tumors: [[pituitary]], [[thyroid]], [[breast]], [[ovarian]], and [[uterine]] tumors.
***Non-endocrine related tumor: Tumors involving the central nervous, [[pulmonary]], and [[gastrointestinal]] systems.
***Non-endocrine related tumors: [[central nervous system]], [[pulmonary]], and [[gastrointestinal]] tumors.
**[[Prolactinoma]] with higher expression of PTTG-1 gene tend to be more [[invasive]].
**[[Prolactinomas]] with a higher expression of the [[PTTG1|PTTG-1 gene]] tend to be more [[invasive]].
*Many [[prolactinoma]] are related to [[multiple endocrine neoplasia type 1]].<ref name="pmid15153434">{{cite journal| author=Agarwal SK, Lee Burns A, Sukhodolets KE, Kennedy PA, Obungu VH, Hickman AB et al.| title=Molecular pathology of the MEN1 gene. | journal=Ann N Y Acad Sci | year= 2004 | volume= 1014 | issue=  | pages= 189-98 | pmid=15153434 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15153434  }} </ref>
*Many [[prolactinomas]] are related to [[multiple endocrine neoplasia type 1]].<ref name="pmid15153434">{{cite journal| author=Agarwal SK, Lee Burns A, Sukhodolets KE, Kennedy PA, Obungu VH, Hickman AB et al.| title=Molecular pathology of the MEN1 gene. | journal=Ann N Y Acad Sci | year= 2004 | volume= 1014 | issue=  | pages= 189-98 | pmid=15153434 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15153434  }} </ref>
** [[MEN1]] [[gene]] is located on 11q13.
** The [[MEN1]] [[gene]] is located on 11q13.
** [[MEN1]] [[gene]] is a [[tumor suppressor gene]] which follows the [[Tumor suppressor gene|'two-hit hypothesis']], which implies that both [[Allele|alleles]] that code for a particular [[gene]] must be affected before an effect is manifested.
** The [[MEN1]] [[gene]] is a [[tumor suppressor gene]] that follows the '[[Tumor suppressor gene|two-hit hypothesis]],' which implies that both [[Allele|alleles]] that code for a particular [[gene]] must be affected before an effect manifests.
**This is due to the fact that if only one [[allele]] for the [[gene]] is damaged, the second can still produce the correct [[protein]].
**This is due to the fact that if only one [[allele]] for the [[gene]] is damaged, the second can still produce the correct [[protein]].
**Affected individuals carries one altered copy of [[MEN1]] [[gene]] and the other copy is lost due to [[somatic]] [[mutation]].
**Affected individuals carry one altered copy of the [[MEN1]] [[gene]] and the other copy is lost due to [[somatic]] [[mutation]].
==Associated Diseases==
==Associated Diseases==
[[Prolactinoma]] may be associated with:<ref name="pmid16411062">{{cite journal| author=Ciccarelli A, Daly AF, Beckers A| title=The epidemiology of prolactinomas. | journal=Pituitary | year= 2005 | volume= 8 | issue= 1 | pages= 3-6 | pmid=16411062 | doi=10.1007/s11102-005-5079-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16411062  }} </ref>
[[Prolactinoma]] may be associated with:<ref name="pmid16411062">{{cite journal| author=Ciccarelli A, Daly AF, Beckers A| title=The epidemiology of prolactinomas. | journal=Pituitary | year= 2005 | volume= 8 | issue= 1 | pages= 3-6 | pmid=16411062 | doi=10.1007/s11102-005-5079-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16411062  }} </ref>
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==Genetics==
==Genetics==
====Familial [[Pituitary adenoma|pituitary adenomas]]====
====Familial Pituitary adenoma|pituitary adenomas====
*A pituitary adenoma may be part of a familial syndrome:<ref name="pmid17613551">{{cite journal| author=Karhu A, Aaltonen LA| title=Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update. | journal=Hum Mol Genet | year= 2007 | volume= 16 Spec No 1 | issue=  | pages= R73-9 | pmid=17613551 | doi=10.1093/hmg/ddm036 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17613551  }} </ref>
*A [[pituitary adenoma]] may be part of a familial syndrome:<ref name="pmid17613551">{{cite journal| author=Karhu A, Aaltonen LA| title=Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update. | journal=Hum Mol Genet | year= 2007 | volume= 16 Spec No 1 | issue=  | pages= R73-9 | pmid=17613551 | doi=10.1093/hmg/ddm036 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17613551  }} </ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Syndrome
! Syndrome
Line 36: Line 37:
|-
|-
| [[Multiple endocrine neoplasia type 1|Multiple endocrine neoplasia I]]
| [[Multiple endocrine neoplasia type 1|Multiple endocrine neoplasia I]]
| MEN1
| [[MEN1]]
| 11q13
| 11q13
| Characterized by the 3 Ps: [[Pituitary adenoma|'''p'''ituitary adenoma]], [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[Pancreatic neuroendocrine tumor|'''p'''ancreatic neuroendocrine tumor]]
| Characterized by the 3 Ps: [[Pituitary adenoma|'''p'''ituitary adenoma]], [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[Pancreatic neuroendocrine tumor|'''p'''ancreatic neuroendocrine tumor]]
Line 43: Line 44:
| CDKN1B
| CDKN1B
| 12q13
| 12q13
| Associated with pituitary adenoma, parathyroid adenoma, neuroendocrine tumor
| Associated with [[pituitary adenoma]], [[parathyroid adenoma]], [[neuroendocrine tumor]]
|-
|-
| [[Carney complex]]
| [[Carney complex]]
| PRKAR1A
| [[PRKAR1A]]
| 17q24
| 17q24
| Other findings (mnemonic ''NAME''): [[Nevus|nevi]], [[atrial myxoma]], myxoid [[neurofibroma]], ephelides ([[freckles]])
| Other findings (mnemonic ''NAME''): [[Nevus|nevi]], [[atrial myxoma]], myxoid [[neurofibroma]], ephelides ([[freckles]])
Line 54: Line 55:
| 11q13
| 11q13
|
|
*Classically growth hormone-producing adenoma - leads to [[acromegaly]]
*Classically [[growth hormone]]-producing [[adenoma]], leads to [[acromegaly]]
*May also be associated with prolactinomas.<ref name="pmid22612670">{{cite journal| author=Korbonits M, Storr H, Kumar AV| title=Familial pituitary adenomas - who should be tested for AIP mutations? | journal=Clin Endocrinol (Oxf) | year= 2012 | volume= 77 | issue= 3 | pages= 351-6 | pmid=22612670 | doi=10.1111/j.1365-2265.2012.04445.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22612670  }} </ref>
*May also be associated with prolactinomas<ref name="pmid22612670">{{cite journal| author=Korbonits M, Storr H, Kumar AV| title=Familial pituitary adenomas - who should be tested for AIP mutations? | journal=Clin Endocrinol (Oxf) | year= 2012 | volume= 77 | issue= 3 | pages= 351-6 | pmid=22612670 | doi=10.1111/j.1365-2265.2012.04445.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22612670  }} </ref>
|}
|}


==Gross Pathology==
==Gross Pathology==
Gross pathology of [[prolactinoma]] is as follows:<ref>{{cite book | last = Bigner | first = D. D. | title = Russell and Rubinstein's pathology of tumors of the nervous system | publisher = Hodder Arnold Distributed in the United States of America by Oxford University Press | location = London New York, NY | year = 2006 | isbn = 978-0340810071 }}</ref>
Gross pathology of [[prolactinoma]] is as follows:<ref>{{cite book | last = Bigner | first = D. D. | title = Russell and Rubinstein's pathology of tumors of the nervous system | publisher = Hodder Arnold Distributed in the United States of America by Oxford University Press | location = London New York, NY | year = 2006 | isbn = 978-0340810071 }}</ref>
*Microprolactinoma (<10mm size) are usually found in the [[lateral]] wing of [[pituitary gland]]. They are most often surrounded by well defined pseudocapsule composed of [[reticulin]].
*Microprolactinomas (<10mm size) are usually found in the [[lateral]] wing of [[pituitary gland]]. They are most often surrounded by well defined pseudocapsules composed of [[reticulin]].
*Macroprolactinoma (>10mm size) differ substantially in size and behavior. Some causes [[Sella turcica|sellar]] expansion while others invade the [[skull]] base.
*Macroprolactinomas (>10mm size) differ substantially in size and behavior. Some cause [[Sella turcica|sellar]] expansion while others invade the [[skull]] base.
*About 50% of all [[prolactinoma]] grossly invade surrounding structure.
*About 50% of all [[prolactinoma]] grossly invade surrounding structures.


==Microscopic Pathology==
==Microscopic Pathology==
*[[Prolactinoma]] are of two types based on microscopy:
*[[Prolactinoma]] are divded into two types based on microscopy:
# Sparsely granulated variant
# Sparsely granulated variant
# Densely granulated variant
# Densely granulated variant

Revision as of 18:44, 8 August 2017

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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. There are a few reports of familial cases of prolactinoma unrelated to MEN 1 syndrome.[1]

Prolactinoma is also associated with various familial syndromes.[2] On gross pathology, prolactinoma is divided on the basis of size into microprolactinoma and macroprolactinoma. On microscopic histological analysis, prolactinoma has two types: sparsely granulated and densely granulated.

Pathophysiology

Associated Diseases

Prolactinoma may be associated with:[1]

Genetics

Familial Pituitary adenoma|pituitary adenomas

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

Gross pathology of prolactinoma is as follows:[8]

  • Microprolactinomas (<10mm size) are usually found in the lateral wing of 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

  1. Sparsely granulated variant
  2. Densely granulated variant


References

  1. 1.0 1.1 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.
  2. 2.0 2.1 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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. 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.

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