Thyroid nodule pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
Line 16: Line 16:
The pathophysiology of [disease name] depends on the histological subtype.
The pathophysiology of [disease name] depends on the histological subtype.
==Pathogenesis==
==Pathogenesis==
=== Common causes ===
<ref name="pmid3755697">{{cite journal |vauthors=Aozasa K, Inoue A, Katagiri S, Matsuzuka F, Katayama S, Yonezawa T |title=Plasmacytoma and follicular lymphoma in a case of Hashimoto's thyroiditis |journal=Histopathology |volume=10 |issue=7 |pages=735–40 |year=1986 |pmid=3755697 |doi= |url=}}</ref><ref name="pmid862558">{{cite journal |vauthors=Bastomsky CH |title=Enhanced thyroxine metabolism and high uptake goiters in rats after a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin |journal=Endocrinology |volume=101 |issue=1 |pages=292–6 |year=1977 |pmid=862558 |doi=10.1210/endo-101-1-292 |url=}}</ref><ref name="pmid8612537">{{cite journal |vauthors=Brix K, Lemansky P, Herzog V |title=Evidence for extracellularly acting cathepsins mediating thyroid hormone liberation in thyroid epithelial cells |journal=Endocrinology |volume=137 |issue=5 |pages=1963–74 |year=1996 |pmid=8612537 |doi=10.1210/endo.137.5.8612537 |url=}}</ref><ref name="pmid8608777">{{cite journal |vauthors=Burch HB |title=Evaluation and management of the solid thyroid nodule |journal=Endocrinol. Metab. Clin. North Am. |volume=24 |issue=4 |pages=663–710 |year=1995 |pmid=8608777 |doi= |url=}}</ref><ref name="pmid2627756">{{cite journal |vauthors=Coclet J, Foureau F, Ketelbant P, Galand P, Dumont JE |title=Cell population kinetics in dog and human adult thyroid |journal=Clin. Endocrinol. (Oxf) |volume=31 |issue=6 |pages=655–65 |year=1989 |pmid=2627756 |doi= |url=}}</ref><ref name="pmid2196027">{{cite journal |vauthors=de los Santos ET, Keyhani-Rofagha S, Cunningham JJ, Mazzaferri EL |title=Cystic thyroid nodules. The dilemma of malignant lesions |journal=Arch. Intern. Med. |volume=150 |issue=7 |pages=1422–7 |year=1990 |pmid=2196027 |doi= |url=}}</ref><ref name="pmid2164546">{{cite journal |vauthors=Di Carlo A, Mariano A, Pisano G, Parmeggiani U, Beguinot L, Macchia V |title=Epidermal growth factor receptor and thyrotropin response in human thyroid tissues |journal=J. Endocrinol. Invest. |volume=13 |issue=4 |pages=293–9 |year=1990 |pmid=2164546 |doi=10.1007/BF03349565 |url=}}</ref><ref name="pmid1661579">{{cite journal |vauthors=Dumont JE, Maenhaut C, Pirson I, Baptist M, Roger PP |title=Growth factors controlling the thyroid gland |journal=Baillieres Clin. Endocrinol. Metab. |volume=5 |issue=4 |pages=727–54 |year=1991 |pmid=1661579 |doi= |url=}}</ref><ref name="pmid7920658">{{cite journal |vauthors=Duprez L, Parma J, Van Sande J, Allgeier A, Leclère J, Schvartz C, Delisle MJ, Decoulx M, Orgiazzi J, Dumont J |title=Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism |journal=Nat. Genet. |volume=7 |issue=3 |pages=396–401 |year=1994 |pmid=7920658 |doi=10.1038/ng0794-396 |url=}}</ref><ref name="pmid1995765">{{cite journal |vauthors=Ericsson UB, Lindgärde F |title=Effects of cigarette smoking on thyroid function and the prevalence of goitre, thyrotoxicosis and autoimmune thyroiditis |journal=J. Intern. Med. |volume=229 |issue=1 |pages=67–71 |year=1991 |pmid=1995765 |doi= |url=}}</ref><ref name="pmid8026388">{{cite journal |vauthors=Farid NR, Shi Y, Zou M |title=Molecular basis of thyroid cancer |journal=Endocr. Rev. |volume=15 |issue=2 |pages=202–32 |year=1994 |pmid=8026388 |doi=10.1210/edrv-15-2-202 |url=}}</ref><ref name="pmid11172729">{{cite journal |vauthors=Liekens S, De Clercq E, Neyts J |title=Angiogenesis: regulators and clinical applications |journal=Biochem. Pharmacol. |volume=61 |issue=3 |pages=253–70 |year=2001 |pmid=11172729 |doi= |url=}}</ref><ref name="pmid7714083">{{cite journal |vauthors=Gaitan E, Cooksey RC, Legan J, Lindsay RH |title=Antithyroid effects in vivo and in vitro of vitexin: a C-glucosylflavone in millet |journal=J. Clin. Endocrinol. Metab. |volume=80 |issue=4 |pages=1144–7 |year=1995 |pmid=7714083 |doi=10.1210/jcem.80.4.7714083 |url=}}</ref><ref name="pmid1356609">{{cite journal |vauthors=Gaskin D, Parai SK, Parai MR |title=Hashimoto's thyroiditis with medullary carcinoma |journal=Can J Surg |volume=35 |issue=5 |pages=528–30 |year=1992 |pmid=1356609 |doi= |url=}}</ref><ref name="pmid7988459">{{cite journal |vauthors=Gerber H, Huber G, Peter HJ, Kämpf J, Lemarchand-Beraud T, Fragu P, Stocker R |title=Transformation of normal thyroids into colloid goiters in rats and mice by diphenylthiohydantoin |journal=Endocrinology |volume=135 |issue=6 |pages=2688–99 |year=1994 |pmid=7988459 |doi=10.1210/endo.135.6.7988459 |url=}}</ref><ref name="pmid21190442">{{cite journal |vauthors=Wang CC, Friedman L, Kennedy GC, Wang H, Kebebew E, Steward DL, Zeiger MA, Westra WH, Wang Y, Khanafshar E, Fellegara G, Rosai J, Livolsi V, Lanman RB |title=A large multicenter correlation study of thyroid nodule cytopathology and histopathology |journal=Thyroid |volume=21 |issue=3 |pages=243–51 |year=2011 |pmid=21190442 |pmc=3698689 |doi=10.1089/thy.2010.0243 |url=}}</ref><ref name="pmid9429860">{{cite journal |vauthors=Gharib H |title=Changing concepts in the diagnosis and management of thyroid nodules |journal=Endocrinol. Metab. Clin. North Am. |volume=26 |issue=4 |pages=777–800 |year=1997 |pmid=9429860 |doi= |url=}}</ref><ref name="pmid9020075">{{cite journal |vauthors=Giordano C, Stassi G, De Maria R, Todaro M, Richiusa P, Papoff G, Ruberti G, Bagnasco M, Testi R, Galluzzo A |title=Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis |journal=Science |volume=275 |issue=5302 |pages=960–3 |year=1997 |pmid=9020075 |doi= |url=}}</ref><ref name="pmid2196027">{{cite journal |vauthors=de los Santos ET, Keyhani-Rofagha S, Cunningham JJ, Mazzaferri EL |title=Cystic thyroid nodules. The dilemma of malignant lesions |journal=Arch. Intern. Med. |volume=150 |issue=7 |pages=1422–7 |year=1990 |pmid=2196027 |doi= |url=}}</ref><ref name="pmid1987443">{{cite journal |vauthors=Greenspan FS |title=The problem of the nodular goiter |journal=Med. Clin. North Am. |volume=75 |issue=1 |pages=195–209 |year=1991 |pmid=1987443 |doi= |url=}}</ref><ref name="pmid1632470">{{cite journal |vauthors=Isaacson PG, Androulakis-Papachristou A, Diss TC, Pan L, Wright DH |title=Follicular colonization in thyroid lymphoma |journal=Am. J. Pathol. |volume=141 |issue=1 |pages=43–52 |year=1992 |pmid=1632470 |pmc=1886561 |doi= |url=}}</ref><ref name="pmid1726932">{{cite journal |vauthors=Ledent C, Parmentier M, Maenhaut C, Taton M, Pirson I, Lamy F, Roger P, Dumont JE |title=The TSH cyclic AMP cascade in the control of thyroid cell proliferation: the story of a concept |journal=Thyroidology |volume=3 |issue=3 |pages=97–101 |year=1991 |pmid=1726932 |doi= |url=}}</ref><ref name="pmid1371462">{{cite journal |vauthors=Ledent C, Dumont JE, Vassart G, Parmentier M |title=Thyroid expression of an A2 adenosine receptor transgene induces thyroid hyperplasia and hyperthyroidism |journal=EMBO J. |volume=11 |issue=2 |pages=537–42 |year=1992 |pmid=1371462 |pmc=556484 |doi= |url=}}</ref><ref name="pmid7036066">{{cite journal |vauthors=Livolsi VA, Merino MJ |title=Histopathologic differential diagnosis of the thyroid |journal=Pathol Annu |volume=16 |issue=Pt 2 |pages=357–406 |year=1981 |pmid=7036066 |doi= |url=}}</ref><ref name="pmid9274519">{{cite journal |vauthors=Ludgate M, Jasani B |title=Apoptosis in autoimmune and non-autoimmune thyroid disease |journal=J. Pathol. |volume=182 |issue=2 |pages=123–4 |year=1997 |pmid=9274519 |doi=10.1002/(SICI)1096-9896(199706)182:2<123::AID-PATH832>3.0.CO;2-F |url=}}</ref><ref name="pmid3484533">{{cite journal |vauthors=Maceri DR, Sullivan MJ, McClatchney KD |title=Autoimmune thyroiditis: pathophysiology and relationship to thyroid cancer |journal=Laryngoscope |volume=96 |issue=1 |pages=82–6 |year=1986 |pmid=3484533 |doi= |url=}}</ref><ref name="pmid1570743">{{cite journal |vauthors=Moriuchi A, Yokoyama S, Kashima K, Andoh T, Nakayama I, Noguchi S |title=Localized primary amyloid tumor of the thyroid developing in the course of Hashimoto's thyroiditis |journal=Acta Pathol. Jpn. |volume=42 |issue=3 |pages=210–6 |year=1992 |pmid=1570743 |doi= |url=}}</ref><ref name="pmid8242306">{{cite journal |vauthors=McKee RF, Krukowski ZH, Matheson NA |title=Thyroid neoplasia coexistent with chronic lymphocytic thyroiditis |journal=Br J Surg |volume=80 |issue=10 |pages=1303–4 |year=1993 |pmid=8242306 |doi= |url=}}</ref><ref name="pmid3605864">{{cite journal |vauthors=Ott RA, McCall AR, McHenry C, Jarosz H, Armin A, Lawrence AM, Paloyan E |title=The incidence of thyroid carcinoma in Hashimoto's thyroiditis |journal=Am Surg |volume=53 |issue=8 |pages=442–5 |year=1987 |pmid=3605864 |doi= |url=}}</ref><ref name="pmid3285378">{{cite journal |vauthors=Paynter OE, Burin GJ, Jaeger RB, Gregorio CA |title=Goitrogens and thyroid follicular cell neoplasia: evidence for a threshold process |journal=Regul. Toxicol. Pharmacol. |volume=8 |issue=1 |pages=102–19 |year=1988 |pmid=3285378 |doi= |url=}}</ref><ref name="pmid8626858">{{cite journal |vauthors=Berndorfer U, Wilms H, Herzog V |title=Multimerization of thyroglobulin (TG) during extracellular storage: isolation of highly cross-linked TG from human thyroids |journal=J. Clin. Endocrinol. Metab. |volume=81 |issue=5 |pages=1918–26 |year=1996 |pmid=8626858 |doi=10.1210/jcem.81.5.8626858 |url=}}</ref><ref name="pmid1036742">{{cite journal |vauthors=Bialas P, Marks S, Dekker A, Field JB |title=Hashimoto's thyroiditis presenting as a solitary functioning thyroid nodule |journal=J. Clin. Endocrinol. Metab. |volume=43 |issue=6 |pages=1365–9 |year=1976 |pmid=1036742 |doi=10.1210/jcem-43-6-1365 |url=}}</ref>
<ref name="pmid3755697">{{cite journal |vauthors=Aozasa K, Inoue A, Katagiri S, Matsuzuka F, Katayama S, Yonezawa T |title=Plasmacytoma and follicular lymphoma in a case of Hashimoto's thyroiditis |journal=Histopathology |volume=10 |issue=7 |pages=735–40 |year=1986 |pmid=3755697 |doi= |url=}}</ref><ref name="pmid862558">{{cite journal |vauthors=Bastomsky CH |title=Enhanced thyroxine metabolism and high uptake goiters in rats after a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin |journal=Endocrinology |volume=101 |issue=1 |pages=292–6 |year=1977 |pmid=862558 |doi=10.1210/endo-101-1-292 |url=}}</ref><ref name="pmid8612537">{{cite journal |vauthors=Brix K, Lemansky P, Herzog V |title=Evidence for extracellularly acting cathepsins mediating thyroid hormone liberation in thyroid epithelial cells |journal=Endocrinology |volume=137 |issue=5 |pages=1963–74 |year=1996 |pmid=8612537 |doi=10.1210/endo.137.5.8612537 |url=}}</ref><ref name="pmid8608777">{{cite journal |vauthors=Burch HB |title=Evaluation and management of the solid thyroid nodule |journal=Endocrinol. Metab. Clin. North Am. |volume=24 |issue=4 |pages=663–710 |year=1995 |pmid=8608777 |doi= |url=}}</ref><ref name="pmid2627756">{{cite journal |vauthors=Coclet J, Foureau F, Ketelbant P, Galand P, Dumont JE |title=Cell population kinetics in dog and human adult thyroid |journal=Clin. Endocrinol. (Oxf) |volume=31 |issue=6 |pages=655–65 |year=1989 |pmid=2627756 |doi= |url=}}</ref><ref name="pmid2196027">{{cite journal |vauthors=de los Santos ET, Keyhani-Rofagha S, Cunningham JJ, Mazzaferri EL |title=Cystic thyroid nodules. The dilemma of malignant lesions |journal=Arch. Intern. Med. |volume=150 |issue=7 |pages=1422–7 |year=1990 |pmid=2196027 |doi= |url=}}</ref><ref name="pmid2164546">{{cite journal |vauthors=Di Carlo A, Mariano A, Pisano G, Parmeggiani U, Beguinot L, Macchia V |title=Epidermal growth factor receptor and thyrotropin response in human thyroid tissues |journal=J. Endocrinol. Invest. |volume=13 |issue=4 |pages=293–9 |year=1990 |pmid=2164546 |doi=10.1007/BF03349565 |url=}}</ref><ref name="pmid1661579">{{cite journal |vauthors=Dumont JE, Maenhaut C, Pirson I, Baptist M, Roger PP |title=Growth factors controlling the thyroid gland |journal=Baillieres Clin. Endocrinol. Metab. |volume=5 |issue=4 |pages=727–54 |year=1991 |pmid=1661579 |doi= |url=}}</ref><ref name="pmid7920658">{{cite journal |vauthors=Duprez L, Parma J, Van Sande J, Allgeier A, Leclère J, Schvartz C, Delisle MJ, Decoulx M, Orgiazzi J, Dumont J |title=Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism |journal=Nat. Genet. |volume=7 |issue=3 |pages=396–401 |year=1994 |pmid=7920658 |doi=10.1038/ng0794-396 |url=}}</ref><ref name="pmid1995765">{{cite journal |vauthors=Ericsson UB, Lindgärde F |title=Effects of cigarette smoking on thyroid function and the prevalence of goitre, thyrotoxicosis and autoimmune thyroiditis |journal=J. Intern. Med. |volume=229 |issue=1 |pages=67–71 |year=1991 |pmid=1995765 |doi= |url=}}</ref><ref name="pmid8026388">{{cite journal |vauthors=Farid NR, Shi Y, Zou M |title=Molecular basis of thyroid cancer |journal=Endocr. Rev. |volume=15 |issue=2 |pages=202–32 |year=1994 |pmid=8026388 |doi=10.1210/edrv-15-2-202 |url=}}</ref><ref name="pmid11172729">{{cite journal |vauthors=Liekens S, De Clercq E, Neyts J |title=Angiogenesis: regulators and clinical applications |journal=Biochem. Pharmacol. |volume=61 |issue=3 |pages=253–70 |year=2001 |pmid=11172729 |doi= |url=}}</ref><ref name="pmid7714083">{{cite journal |vauthors=Gaitan E, Cooksey RC, Legan J, Lindsay RH |title=Antithyroid effects in vivo and in vitro of vitexin: a C-glucosylflavone in millet |journal=J. Clin. Endocrinol. Metab. |volume=80 |issue=4 |pages=1144–7 |year=1995 |pmid=7714083 |doi=10.1210/jcem.80.4.7714083 |url=}}</ref><ref name="pmid1356609">{{cite journal |vauthors=Gaskin D, Parai SK, Parai MR |title=Hashimoto's thyroiditis with medullary carcinoma |journal=Can J Surg |volume=35 |issue=5 |pages=528–30 |year=1992 |pmid=1356609 |doi= |url=}}</ref><ref name="pmid7988459">{{cite journal |vauthors=Gerber H, Huber G, Peter HJ, Kämpf J, Lemarchand-Beraud T, Fragu P, Stocker R |title=Transformation of normal thyroids into colloid goiters in rats and mice by diphenylthiohydantoin |journal=Endocrinology |volume=135 |issue=6 |pages=2688–99 |year=1994 |pmid=7988459 |doi=10.1210/endo.135.6.7988459 |url=}}</ref><ref name="pmid21190442">{{cite journal |vauthors=Wang CC, Friedman L, Kennedy GC, Wang H, Kebebew E, Steward DL, Zeiger MA, Westra WH, Wang Y, Khanafshar E, Fellegara G, Rosai J, Livolsi V, Lanman RB |title=A large multicenter correlation study of thyroid nodule cytopathology and histopathology |journal=Thyroid |volume=21 |issue=3 |pages=243–51 |year=2011 |pmid=21190442 |pmc=3698689 |doi=10.1089/thy.2010.0243 |url=}}</ref><ref name="pmid9429860">{{cite journal |vauthors=Gharib H |title=Changing concepts in the diagnosis and management of thyroid nodules |journal=Endocrinol. Metab. Clin. North Am. |volume=26 |issue=4 |pages=777–800 |year=1997 |pmid=9429860 |doi= |url=}}</ref><ref name="pmid9020075">{{cite journal |vauthors=Giordano C, Stassi G, De Maria R, Todaro M, Richiusa P, Papoff G, Ruberti G, Bagnasco M, Testi R, Galluzzo A |title=Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis |journal=Science |volume=275 |issue=5302 |pages=960–3 |year=1997 |pmid=9020075 |doi= |url=}}</ref><ref name="pmid2196027">{{cite journal |vauthors=de los Santos ET, Keyhani-Rofagha S, Cunningham JJ, Mazzaferri EL |title=Cystic thyroid nodules. The dilemma of malignant lesions |journal=Arch. Intern. Med. |volume=150 |issue=7 |pages=1422–7 |year=1990 |pmid=2196027 |doi= |url=}}</ref><ref name="pmid1987443">{{cite journal |vauthors=Greenspan FS |title=The problem of the nodular goiter |journal=Med. Clin. North Am. |volume=75 |issue=1 |pages=195–209 |year=1991 |pmid=1987443 |doi= |url=}}</ref><ref name="pmid1632470">{{cite journal |vauthors=Isaacson PG, Androulakis-Papachristou A, Diss TC, Pan L, Wright DH |title=Follicular colonization in thyroid lymphoma |journal=Am. J. Pathol. |volume=141 |issue=1 |pages=43–52 |year=1992 |pmid=1632470 |pmc=1886561 |doi= |url=}}</ref><ref name="pmid1726932">{{cite journal |vauthors=Ledent C, Parmentier M, Maenhaut C, Taton M, Pirson I, Lamy F, Roger P, Dumont JE |title=The TSH cyclic AMP cascade in the control of thyroid cell proliferation: the story of a concept |journal=Thyroidology |volume=3 |issue=3 |pages=97–101 |year=1991 |pmid=1726932 |doi= |url=}}</ref><ref name="pmid1371462">{{cite journal |vauthors=Ledent C, Dumont JE, Vassart G, Parmentier M |title=Thyroid expression of an A2 adenosine receptor transgene induces thyroid hyperplasia and hyperthyroidism |journal=EMBO J. |volume=11 |issue=2 |pages=537–42 |year=1992 |pmid=1371462 |pmc=556484 |doi= |url=}}</ref><ref name="pmid7036066">{{cite journal |vauthors=Livolsi VA, Merino MJ |title=Histopathologic differential diagnosis of the thyroid |journal=Pathol Annu |volume=16 |issue=Pt 2 |pages=357–406 |year=1981 |pmid=7036066 |doi= |url=}}</ref><ref name="pmid9274519">{{cite journal |vauthors=Ludgate M, Jasani B |title=Apoptosis in autoimmune and non-autoimmune thyroid disease |journal=J. Pathol. |volume=182 |issue=2 |pages=123–4 |year=1997 |pmid=9274519 |doi=10.1002/(SICI)1096-9896(199706)182:2<123::AID-PATH832>3.0.CO;2-F |url=}}</ref><ref name="pmid3484533">{{cite journal |vauthors=Maceri DR, Sullivan MJ, McClatchney KD |title=Autoimmune thyroiditis: pathophysiology and relationship to thyroid cancer |journal=Laryngoscope |volume=96 |issue=1 |pages=82–6 |year=1986 |pmid=3484533 |doi= |url=}}</ref><ref name="pmid1570743">{{cite journal |vauthors=Moriuchi A, Yokoyama S, Kashima K, Andoh T, Nakayama I, Noguchi S |title=Localized primary amyloid tumor of the thyroid developing in the course of Hashimoto's thyroiditis |journal=Acta Pathol. Jpn. |volume=42 |issue=3 |pages=210–6 |year=1992 |pmid=1570743 |doi= |url=}}</ref><ref name="pmid8242306">{{cite journal |vauthors=McKee RF, Krukowski ZH, Matheson NA |title=Thyroid neoplasia coexistent with chronic lymphocytic thyroiditis |journal=Br J Surg |volume=80 |issue=10 |pages=1303–4 |year=1993 |pmid=8242306 |doi= |url=}}</ref><ref name="pmid3605864">{{cite journal |vauthors=Ott RA, McCall AR, McHenry C, Jarosz H, Armin A, Lawrence AM, Paloyan E |title=The incidence of thyroid carcinoma in Hashimoto's thyroiditis |journal=Am Surg |volume=53 |issue=8 |pages=442–5 |year=1987 |pmid=3605864 |doi= |url=}}</ref><ref name="pmid3285378">{{cite journal |vauthors=Paynter OE, Burin GJ, Jaeger RB, Gregorio CA |title=Goitrogens and thyroid follicular cell neoplasia: evidence for a threshold process |journal=Regul. Toxicol. Pharmacol. |volume=8 |issue=1 |pages=102–19 |year=1988 |pmid=3285378 |doi= |url=}}</ref><ref name="pmid8626858">{{cite journal |vauthors=Berndorfer U, Wilms H, Herzog V |title=Multimerization of thyroglobulin (TG) during extracellular storage: isolation of highly cross-linked TG from human thyroids |journal=J. Clin. Endocrinol. Metab. |volume=81 |issue=5 |pages=1918–26 |year=1996 |pmid=8626858 |doi=10.1210/jcem.81.5.8626858 |url=}}</ref><ref name="pmid1036742">{{cite journal |vauthors=Bialas P, Marks S, Dekker A, Field JB |title=Hashimoto's thyroiditis presenting as a solitary functioning thyroid nodule |journal=J. Clin. Endocrinol. Metab. |volume=43 |issue=6 |pages=1365–9 |year=1976 |pmid=1036742 |doi=10.1210/jcem-43-6-1365 |url=}}</ref>


Line 79: Line 77:


=== Neoplastoc nodules ===
=== Neoplastoc nodules ===
Neoplastic nodules development may involve the activation of oncogenes, as the underlying event leading to uncontrolled cell growth. Proto-oncogens activation are associated with thyroid adenoma, hyperplasia, and malignancies. Thyroid gland is made of different follicles, and each follicle is composed of different clones of cells (polyclonal). During nodule formation, cells replicate in a coordinated way simultanously, so each follicle of the nodule share the same heterogenity with other cells. Also during neoplasm formation in the nodule, the neoplastic follicle mostly shows a monoclonal pattern. These findings may indicate that neoplasia arises from a single cell genetic mutation.  The most important oncogens related to thyroid neoplasia development are mentioned in the table below.<ref name="pmid19209125">{{cite journal |vauthors=Taccaliti A, Boscaro M |title=Genetic mutations in thyroid carcinoma |journal=Minerva Endocrinol. |volume=34 |issue=1 |pages=11–28 |year=2009 |pmid=19209125 |doi= |url=}}</ref><ref name="pmid10834397">{{cite journal |vauthors=Vecchio G, Santoro M |title=Oncogenes and thyroid cancer |journal=Clin. Chem. Lab. Med. |volume=38 |issue=2 |pages=113–6 |year=2000 |pmid=10834397 |doi=10.1515/CCLM.2000.017 |url=}}</ref><ref name="pmid7629379">{{cite journal |vauthors=Fusco A, Santoro M, Grieco M, Carlomagno F, Dathan N, Fabien N, Berlingieri MT, Li Z, De Franciscis V, Salvatore D |title=RET/PTC activation in human thyroid carcinomas |journal=J. Endocrinol. Invest. |volume=18 |issue=2 |pages=127–9 |year=1995 |pmid=7629379 |doi=10.1007/BF03349720 |url=}}</ref><ref name="pmid8806699">{{cite journal |vauthors=Fugazzola L, Pierotti MA, Vigano E, Pacini F, Vorontsova TV, Bongarzone I |title=Molecular and biochemical analysis of RET/PTC4, a novel oncogenic rearrangement between RET and ELE1 genes, in a post-Chernobyl papillary thyroid cancer |journal=Oncogene |volume=13 |issue=5 |pages=1093–7 |year=1996 |pmid=8806699 |doi= |url=}}</ref><ref name="pmid8918855">{{cite journal |vauthors=Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, van Amstel HK, Lips CJ, Nishisho I, Takai SI, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xue F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjöld M, Komminoth P, Hendy GN, Mulligan LM |title=The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis |journal=JAMA |volume=276 |issue=19 |pages=1575–9 |year=1996 |pmid=8918855 |doi= |url=}}</ref><ref name="pmid1468509">{{cite journal |vauthors=Goretzki PE, Simon D, Röher HD |title=G-protein mutations in thyroid tumors |journal=Exp. Clin. Endocrinol. |volume=100 |issue=1-2 |pages=14–6 |year=1992 |pmid=1468509 |doi=10.1055/s-0029-1211167 |url=}}</ref>
Neoplastic nodules development may involve the activation of proto-oncogenes as the underlying event leading to uncontrolled cell growth. Proto-oncogens activation are associated with thyroid adenoma, hyperplasia, and malignancies. Thyroid gland is made of different follicles, and each follicle is composed of different clones of cells (polyclonal). During nodule formation, cells replicate in a coordinated way simultanously, so each follicle of the nodule share the same heterogenity with other cells. Hyperplastic thyroid nodules are considered as risk factor for neoplasia development, as these cells may express neoplasia during their rapid proliferation phase. During neoplasm formation in the nodule, the neoplastic follicle mostly shows a monoclonal pattern. These findings may indicate that neoplasia arises from a single cell genetic mutation.  The most important oncogens related to thyroid neoplasia development are mentioned in the genetic table below.<ref name="pmid19209125">{{cite journal |vauthors=Taccaliti A, Boscaro M |title=Genetic mutations in thyroid carcinoma |journal=Minerva Endocrinol. |volume=34 |issue=1 |pages=11–28 |year=2009 |pmid=19209125 |doi= |url=}}</ref><ref name="pmid10834397">{{cite journal |vauthors=Vecchio G, Santoro M |title=Oncogenes and thyroid cancer |journal=Clin. Chem. Lab. Med. |volume=38 |issue=2 |pages=113–6 |year=2000 |pmid=10834397 |doi=10.1515/CCLM.2000.017 |url=}}</ref><ref name="pmid7629379">{{cite journal |vauthors=Fusco A, Santoro M, Grieco M, Carlomagno F, Dathan N, Fabien N, Berlingieri MT, Li Z, De Franciscis V, Salvatore D |title=RET/PTC activation in human thyroid carcinomas |journal=J. Endocrinol. Invest. |volume=18 |issue=2 |pages=127–9 |year=1995 |pmid=7629379 |doi=10.1007/BF03349720 |url=}}</ref><ref name="pmid8806699">{{cite journal |vauthors=Fugazzola L, Pierotti MA, Vigano E, Pacini F, Vorontsova TV, Bongarzone I |title=Molecular and biochemical analysis of RET/PTC4, a novel oncogenic rearrangement between RET and ELE1 genes, in a post-Chernobyl papillary thyroid cancer |journal=Oncogene |volume=13 |issue=5 |pages=1093–7 |year=1996 |pmid=8806699 |doi= |url=}}</ref><ref name="pmid8918855">{{cite journal |vauthors=Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, van Amstel HK, Lips CJ, Nishisho I, Takai SI, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xue F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjöld M, Komminoth P, Hendy GN, Mulligan LM |title=The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis |journal=JAMA |volume=276 |issue=19 |pages=1575–9 |year=1996 |pmid=8918855 |doi= |url=}}</ref><ref name="pmid1468509">{{cite journal |vauthors=Goretzki PE, Simon D, Röher HD |title=G-protein mutations in thyroid tumors |journal=Exp. Clin. Endocrinol. |volume=100 |issue=1-2 |pages=14–6 |year=1992 |pmid=1468509 |doi=10.1055/s-0029-1211167 |url=}}</ref>


Environmental factors can play an important role in triggering the oncogen mutation. The most important carcinogens involved in the pathogenesis of neoplastic thyroid nodules are:
* Thionamid compounds: thiourea, methimazole, ethylenethiourea (ETU), thiouracil, propylthiouracil
* Aminotriazole: herbicide
* Acetylaminofluorene (AAF). Use: insecticide
* Oxydianiline (ODA). Use: Azo-Dye
* Methylene benzenamine. Use: Dye intermediate
* Nitrosamines
* Nitrosoureas (NMU), (NBU), (ENU). Use: derivatives (BCNU, CCNU, MeCCNU) are drugs against tumors. Streptozocin (naturally occurring nitrosourea) is used in the treatment of islet-cell carcinoma of the pancreas)
=== Colloid nodules ===
=== Colloid nodules ===
The colloid nodules consist of colloid droplets and thyroglobulin vesicles. These nodules are produced as a defect of intraluminal thyroglobulin reabsorption. 
The colloid nodules consist of colloid droplets and thyroglobulin vesicles. Thyroid gland keeps a balance between colloid and thyroglobulin production by interacting between secretion of thyroglobulin into colloid and reabsorption of colloid into thyroid follicular cells. The mentioned interaction is processed by macro-pinocytosis (pseudopods) and micro-pinocytosis (microvilli). Any imbalance between secretion and reabsorption of thyroglobulin equilibrium produces a colloid appeared thyroid nodule. These nodules may also be produced as a defect of intraluminal thyroglobulin reabsorption. 
 
By the process of macro (pseudopods) and micro-pinocytosis (microvilli), Colloid is reabsorbed into the follicular cells, forming colloid droplets, whereas newly synthesized thyroglobulin is compacted into exocytotic vesicles and secreted into the colloid. The mentioned interaction is processed by macro-pinocytosis (pseudopods) and micro-pinocytosis (microvilli). Any imbalance between secretion and reabsorption of thyroglobulin equilibrium produces a colloid appeared thyroid nodule.


==== Iodine related nodules pthogenesis: ====
Iodine excess can lead to colloid nodules in thyroid gland, leading to a colloid goitre. The mechanism is due to several idoine effects on thyroid cells:
Iodine excess can lead to colloid nodules in thyroid gland, leading to a colloid goitre. The mechanism is due to several idoine effects on thyroid cells:
* Endocytosis inhibition: High dosage of iodine may lead to inhibition of the protease activity of thyroid lysosomes, and thereby inhibiting endocytosis  
* Endocytosis inhibition: High dosage of iodine may lead to inhibition of the protease activity of thyroid lysosomes, and thereby inhibiting endocytosis  
Line 93: Line 98:


=== Cystic nodules ===
=== Cystic nodules ===
# True cysts
Cystic thyroid nodules can be classified into the following types:
# Pseudo cysts
* Necrotic cystic nodules:
hyperplasia of thyroid nodules proceed towards necrosis, colliquation and ultimately to pseudocyst formation
** May be due to a relative insufficiency of blood supply
 
*** Inadequate blood supply for a neoplastic cells growth
necrosis is due to a relative insufficiency of blood supply, which is inadequate for the growth of the replicating neoplasia or is due to an imbalance between angiogenesis and cell growth where replicating cells do not outgrow but gradually compress neovascularization, leading to cell damage, necrosis and colliquation
*** Imbalance between angiogenesis and cell growth
 
*** Compression of new vessels due to lack of cellular outgrow, leading to cell damage, necrosis and colliquation
autoimmunity might participate in the formation of the serum-like cyst
** Hyperplastic thyroid nodules may proceed towards necrosis, colliquation, and pseudocyst formation
 
* Serum-like cystic nodules:
An increased concentration of VEGF/VPF has been found in the fluid of thyroid cysts, particularly in the fluid of rapidly enlarging or recurrent cysts. This finding suggests that VEGF/VPF stimulates vascular permeability and promotes accumulation of fluid. 
** May be related to autoimmunity
 
* Apoptotic cystic nodules:
Cysts may also be considered as the end result of apoptosis 
** Cysts that may be related to normal cellular apoptosis or neoplastic/infected cellular apoptosis
* Vascular growth factor related cystic nodules:
** Cyst formation may be the result of an increased concentration of VEGF/VPF inside the cystic area
** VEGF/VPF lead to stimulation of vascular permeability and promoting the accumulation of fluids in the cysts
** VEGF/VPF are particularly found in the cystic fluid of rapidly enlarging or recurrent cysts


=== Thyroiditic nodule ===
=== Thyroiditic nodule ===
Nodular lymphocytic thyroiditis includes two different entities: lymphocyte thyroiditis growing as a nodule in a hyperplastic or normal gland; and lymphocytic thyroiditis associated with other nodular thyroid diseases.
Nodular lymphocytic thyroiditis almost always present in combination with other thyroiditic diseases. They can also present as a part of infection. It has been sown that the ability of super antigens (SAgs) to activate the immune system may play a role in the course of autoimmune disorders. In most of these thyroiditis diseases, the mechanism of nodular lesion is the same as the mechanism of the main disease, meaning that the thyroid nodule is a part of normal disease pattern. Many of these nodules are not identifiable based on physical exam, and are detected during thryoid scintigraphy. The most important thyroiditic diseases that may present as lymphocytic nodular thyroid are:
* Local infections:
** Piogenic infection
**Tuberculosis
**Parasites
* Subacute de Quervain’s thyroiditis
* Fibrosing (Riedel’s) thyroiditis
* Plasmacell granuloma
* Plasmacytoma
* Primary amyloid tumor and amyloidosis
* Thymoma
* Primary thyroid lymphoma
** Thyroiditic nodule due to diffuse B-cell infiltration into lymphoma presented areas
* Histocytosis X
* Medullary carcinoma
* Papillary carcinoma
** Thyroiditic nodule may be due to an immune response to some abnormal thyroid antigen expressed in the tumor


In Hashimoto thyroiditis, by scintigraphy solitary or dominant cold nodules are common
by cytology and ultrasonography thyroiditic nodules are easily diagnosed
**
* Carcinogenics:
** Thionamid compounds: thiourea, methimazole, ethylenethiourea (ETU), thiouracil, propylthiouracil
** Aminotriazole: herbicide
** Acetylaminofluorene (AAF). Use: insecticide
** Oxydianiline (ODA). Use: Azo-Dye
** Methylene benzenamine. Use: Dye intermediate
** Nitrosamines
** Nitrosoureas (NMU), (NBU), (ENU). Use: derivatives (BCNU, CCNU, MeCCNU) are drugs against tumors. Streptozocin (naturally occurring nitrosourea) is used in the treatment of islet-cell carcinoma of the pancreas).
=== Less common causes ===
*Piogenic infection
*Tuberculosis
*de Quervain’s thyroiditis
*Fibrosing (Riedel’s) thyroiditis,
*Parasites
*Dyshormonogenesis
*Amyloidosis
*Plasma cell granuloma
*Histiocytosis X
==Genetics==
==Genetics==
*Some diseases are genetic, and have particular inheritance patterns, and express different phenotypes
Genetic mutation is considered as one of the most important mechanisms of developing thyroid nodules, especially neoplastic thyroid nodules. Most of these mutations occur as somatic mutations, while some may occur in a familial order. The most important category of familial thyroid cancers are due to genetic mutation in genes called FNMTC
*The effect that genetics may have on the pathophysiology of a disease can be described in this section
 
* familial nonmedullary thyroid cancer (FNMTC):
* familial nonmedullary thyroid cancer (FNMTC):
** rare  
** rare  

Revision as of 16:13, 7 August 2017


Thyroid nodule Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Thyroid nodule from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic study of choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Thyroid nodule pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Thyroid nodule pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Thyroid nodule pathophysiology

CDC on Thyroid nodule pathophysiology

Thyroid nodule pathophysiology in the news

Blogs on Thyroid nodule pathophysiology

Directions to Hospitals Treating Thyroid nodule

Risk calculators and risk factors for Thyroid nodule pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

[Pathogen name] is usually transmitted via the [transmission route] route to the human host. Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell. On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name]. On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name]. [Disease name] is transmitted in [mode of genetic transmission] pattern. [Disease/malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells]. Development of [disease name] is the result from multiple genetic mutations. Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3]. The progression to [disease name] usually involves the [molecular pathway]. The pathophysiology of [disease name] depends on the histological subtype.

Pathogenesis

[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][6][19][20][21][22][23][24][25][26][27][28][29][30][31]

Hyperplastic nodules

Hyperplastic nodule pathogenesis seems to start with an increase in thyroid proliferation, which lead to thyroid hyperplasia. Rapid thyroid prolifertion mainly occur in response to certain stimulants. Stimulants mainly act through TSH mediated activity and production. Following the hyperplasia development phase, a new phase may begin, leading to a neoplasia.

TSH role in thyroid nodule formation

Growth signals in thyroid tissue start their pathways by an stimulant, that attaches to the thyroid receptors. The following signals can be transmitted through 3 distinct pathways:

  • Adenylate cyclase/protein kinase A system
  • Phospholipase C pathways
  • Phospholipase A2 system (intracellular metabolism of prostaglandins)

The most important and effective pathway for thyroid growth is the activation of adenylate cyclase/protein kinase A system. Activation of phosholipase C and phospholipase A2 have only a minor or absent effect on thyroid growth.

TSH acts as an stimulant by binding to the receptor and activating both the adenylate cyclase and phospholipase C pathways. As mentioned, the phospholipase C pathways has minor effects, and most of the TSH effect on cell growth is generated by adenylate cyclase pathway. The signal generated by the adenylate cyclase cAMP-dependent pathways is then transduced into the nucleus where transcription factors–upon phosphorylation–induce the expression of cAMP-inducible genes. It has been definitely established that TSH has a main mitogenic role, through cAMP, Gs proteins (G-protein heterotrimeric α-, β- and γ-subunits coded by the gsp gene which, binding to GTP, relays the TSH signal from its receptor to adenyl cyclase) and protein kinase A, which activates the metabolic cascade leading to the stimulation of growth

However, to produce hyperplasia overproduction of cAMP must be continuous, as it occurs in mutations constitutive of the genes which regulate cAMP production. Constitutive cAMP overproduction has been demonstrated to be due to point mutation of the TSH receptor [70] or Gs protein

Constitutive cAMP overproduction not only stimulates growth but also function.

Hyperplastic thyroid nodule pathogenesis can be devided into 2 phases:

1. Thyroid overgrowth stimulants:

Thyroid normally has a low proliferative activity, although it can start proliferation rapidly in response to certain stimulants. Stimulants mainly act through TSH mediated activity and production. The following stimulants look like to have the most important role in pathogenesis of hyperplastic nodules:[32][33]

  • Iodine deficiency:
    • Effects directly or indirectly 
    • The most important potent stimulator of the replicative potential of the gland 
    • Mechanism of action:
      • Acting as an initiator for TSH rise
      • May enhance the effect of other chemicals that induce a rise in TSH by inducing the promotor overactivity
      • The most important reason of high prevalence of thyroid hyperplasia and nodules in iodine-deficient areas
  • Industrial chemicals:
    • DDT
    • Polychlorinated byphenyls
    • Pesticides
  • Goitrogens:
    • Complex anions and inorganic atoms (iodine, lithium, CLO4–, TcO4–, BF4–)
    • Thiocyanate (SCN–)
    • Goitrin, isolated in plants of the genus brassica
    • Aniline derivatives (sulfonamides, tolbutamide, sulfaguanidine, sulfamethoxazole, etc.)
    • Phenol derivatives and polyhydroxyphenols
    • Flavonoids:
      • TPO inhibitors
      • Also act on thyroid metabolism by interacting with the nuclear receptor for thyroid hormones
  • Antithyroid drugs:
    • Thionamides that are used in the treatment of hyperthyroidism
  • Tobacco:
    • May be the reason of high prevalence of thyroid hyperplasia and nodules in iodine-sufficient areas 

Thyroid stromal cells interact with thyroid follicular cells by cytokines. Inappropriate cytokine activities also seem to be related to TSH overproduction and thyroid hyperplastic nodule formation. The most important cytokines that can exert an action of differentiation or inhibition of thyroid growth are:

  • TGFβ
  • IFNγ
  • IL-6
  • Somatostatin
2. Hyperplasia development phase:

Thyroid cells produce the angiogenic vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) sensitive to TSH stimulation. The vascular growth factor induces neovascularization by binding to specific receptors on endothelial cells and stimulating new vessel production. In response, endothelial cells produce growth factors that increase thyropid proliferaion and lead to thyroid hyperplasia. Neovascularization in thyroid matrix is accompanied by the production of proteolytic enzymes, which facilitate the expansion of thyroid tissue into the extracellular matrix.

Neoplasia development phase:

each follicle is composed of different clones of cells (polyclonal) but during nodule formation they replicate in a simultaneous and coordinated manner, so each follicle of the nodule reproduces the same heterogeneity of the mother follicle. When a neoplasm arises in the nodule, then the neoplastic follicle shows a monoclonal pattern, suggesting that cancer arises from a single cell. 

activated oncogenes are considered the underlying event leading to uncontrolled cell growth.

Neoplastoc nodules

Neoplastic nodules development may involve the activation of proto-oncogenes as the underlying event leading to uncontrolled cell growth. Proto-oncogens activation are associated with thyroid adenoma, hyperplasia, and malignancies. Thyroid gland is made of different follicles, and each follicle is composed of different clones of cells (polyclonal). During nodule formation, cells replicate in a coordinated way simultanously, so each follicle of the nodule share the same heterogenity with other cells. Hyperplastic thyroid nodules are considered as risk factor for neoplasia development, as these cells may express neoplasia during their rapid proliferation phase. During neoplasm formation in the nodule, the neoplastic follicle mostly shows a monoclonal pattern. These findings may indicate that neoplasia arises from a single cell genetic mutation. The most important oncogens related to thyroid neoplasia development are mentioned in the genetic table below.[34][35][36][37][38][39]

Environmental factors can play an important role in triggering the oncogen mutation. The most important carcinogens involved in the pathogenesis of neoplastic thyroid nodules are:

  • Thionamid compounds: thiourea, methimazole, ethylenethiourea (ETU), thiouracil, propylthiouracil
  • Aminotriazole: herbicide
  • Acetylaminofluorene (AAF). Use: insecticide
  • Oxydianiline (ODA). Use: Azo-Dye
  • Methylene benzenamine. Use: Dye intermediate
  • Nitrosamines
  • Nitrosoureas (NMU), (NBU), (ENU). Use: derivatives (BCNU, CCNU, MeCCNU) are drugs against tumors. Streptozocin (naturally occurring nitrosourea) is used in the treatment of islet-cell carcinoma of the pancreas)

Colloid nodules

The colloid nodules consist of colloid droplets and thyroglobulin vesicles. Thyroid gland keeps a balance between colloid and thyroglobulin production by interacting between secretion of thyroglobulin into colloid and reabsorption of colloid into thyroid follicular cells. The mentioned interaction is processed by macro-pinocytosis (pseudopods) and micro-pinocytosis (microvilli). Any imbalance between secretion and reabsorption of thyroglobulin equilibrium produces a colloid appeared thyroid nodule. These nodules may also be produced as a defect of intraluminal thyroglobulin reabsorption. 

Iodine related nodules pthogenesis:

Iodine excess can lead to colloid nodules in thyroid gland, leading to a colloid goitre. The mechanism is due to several idoine effects on thyroid cells:

  • Endocytosis inhibition: High dosage of iodine may lead to inhibition of the protease activity of thyroid lysosomes, and thereby inhibiting endocytosis
  • Exocytosis inhibition: Iodine reduces the expression of the TSH receptor on the surface of thyroid cells, and thereby inhibiting and decreasing colloid reabsorption
  • Iodine excess in combination with TSH over activity may lead to colloid goitre

Another mechanism that may lead to colloid goitre formation is due to loss of thyroglobulin packaging ability, that may lead to an enormous enlargement of the follicles and flattening of the epithelium. Therefore a colloid nodular goitre can be made.

Cystic nodules

Cystic thyroid nodules can be classified into the following types:

  • Necrotic cystic nodules:
    • May be due to a relative insufficiency of blood supply
      • Inadequate blood supply for a neoplastic cells growth
      • Imbalance between angiogenesis and cell growth
      • Compression of new vessels due to lack of cellular outgrow, leading to cell damage, necrosis and colliquation
    • Hyperplastic thyroid nodules may proceed towards necrosis, colliquation, and pseudocyst formation
  • Serum-like cystic nodules:
    • May be related to autoimmunity
  • Apoptotic cystic nodules:
    • Cysts that may be related to normal cellular apoptosis or neoplastic/infected cellular apoptosis
  • Vascular growth factor related cystic nodules:
    • Cyst formation may be the result of an increased concentration of VEGF/VPF inside the cystic area
    • VEGF/VPF lead to stimulation of vascular permeability and promoting the accumulation of fluids in the cysts
    • VEGF/VPF are particularly found in the cystic fluid of rapidly enlarging or recurrent cysts

Thyroiditic nodule

Nodular lymphocytic thyroiditis almost always present in combination with other thyroiditic diseases. They can also present as a part of infection. It has been sown that the ability of super antigens (SAgs) to activate the immune system may play a role in the course of autoimmune disorders. In most of these thyroiditis diseases, the mechanism of nodular lesion is the same as the mechanism of the main disease, meaning that the thyroid nodule is a part of normal disease pattern. Many of these nodules are not identifiable based on physical exam, and are detected during thryoid scintigraphy. The most important thyroiditic diseases that may present as lymphocytic nodular thyroid are:

  • Local infections:
    • Piogenic infection
    • Tuberculosis
    • Parasites
  • Subacute de Quervain’s thyroiditis
  • Fibrosing (Riedel’s) thyroiditis
  • Plasmacell granuloma
  • Plasmacytoma
  • Primary amyloid tumor and amyloidosis
  • Thymoma
  • Primary thyroid lymphoma
    • Thyroiditic nodule due to diffuse B-cell infiltration into lymphoma presented areas
  • Histocytosis X
  • Medullary carcinoma
  • Papillary carcinoma
    • Thyroiditic nodule may be due to an immune response to some abnormal thyroid antigen expressed in the tumor

Genetics

Genetic mutation is considered as one of the most important mechanisms of developing thyroid nodules, especially neoplastic thyroid nodules. Most of these mutations occur as somatic mutations, while some may occur in a familial order. The most important category of familial thyroid cancers are due to genetic mutation in genes called FNMTC

  • familial nonmedullary thyroid cancer (FNMTC):
    • rare
    • related to non-medullary tumors
    • Inheritance: autosomal dominant with incomplete penetrance and variable expressivity
    • earlier age of thyroid cancer onset
    • more benign thyroid nodules
    • Associated with multifocal disease
    • Associated with a higher rate of locoregional recurrence
Principal oncogenes and growth factors involved in thyroid carcinogenesis Gene mechanism Mutation effect Neoplasia
N&H ras ras-constitutively bound to GAP (GTPase-activating protein) Activation of adenylate cyclase and calcium channels
  • Adenoma
  • Ca. papillary
  • Follicular
  • Anaplastic
RET (Receptor for glial-derived neurotrophic GF)
  • Fusion proteins with constitutive TK activities
  • Dimerization of RET TKR
  • Mitogenic through constitutive activation of TKR
  • Increased auto-phosphorylation and alteration of substrate specificity
  • Ca. papillary
  • MEN 2A
  • FMTC
  • MEN 2B
gsp Ribosylated GS-α at arginine 201 Impairing of GTPase activity Hot adenomas
c-MET (α and β subunit) Increased receptors for HGF/SF Enhancement of receptor kinase activity Ca. papillary (aggressive)
TRK Receptor for NGF Mitogen activated TK cascade Ca. papillary
EGF / EGF-R Lack of activation of p21/Waf l gene expression Loss of regulation at the critical G1 to S phase Ca. anaplastic
p53 Lack of activation of p21/Waf l gene expression Loss of regulation at the critical G1 to S phase Ca. anaplastic

Papillary

Follicular

Associated Conditions

  • Preoperative serum TSH is an independent risk factor for predicting malignancy in a thyroid nodule, and is associated with: 18160464 23731273
    • Higher differentiated thyroid cancer stage
    • Gross extrathyroidal extension
    • Neck node metastases

Gross Pathology

  • Gross pathology refers to macroscopic or larger scale manifestations of disease in organs, tissues and body cavities. The term is commonly used by pathologist to refer to diagnostically useful findings made during the gross examination portion of surgical specimen processing or an autopsy.
  • This section is a good place to include pictures. Search for copyleft images on The Pathology Wiki [1] and Ask Dr. Wiki [2].

Microscopic pathology

4071393

19888858

27078145

19888858

Cytology classification Referred to FNA Surgical biopsy May be seen in: FNA cytology
Follicular lesions  Benign (macrofollicular)
  • Adenomatoid adenoma
  • Hyperplastic adenoma
  • Colloid adenoma
 +
  • Normal thyroid tissue
  • Sporadic nodular goiter
  • Monoclonal macrofollicular tumors
  • Hyperplastic nodules
  • Colloid adenomas (most common)
  • May have areas of cystic degeneration with cellular debris and hemosiderin-laden macrophages
  • Cellular characteristics:
    • Small and flat
    • Uniform in size
    • Non-crowded
    • Smeared colloid is seen in the background
    • Follicle size may vary, with a few microfollicles interspersed among the macrofollicles, especially if the sample was obtained from an area close to the capsule of the lesion
  • Colloid:
    • May smear across the slide or occasionally aggregated into droplets due to disruption of follicles during FNA
    • Stains blue on a Papanicolaou stain
    • May be abundant in the background of macrofollicular lesions
Follicular neoplasm/microfollicular 
  • Cellular adenoma
  • Indeterminate adenoma
  • Trabecular adenoma
 +
  • Follicular adenomas
  • Follicular carcinomas
  • Follicular variant of papillary cancer
  • Occasionally from autonomously functioning thyroid nodules
  • Well-developed microfollicles
  • Crowding of cells
    • May form clusters and clumps
  • Scant colloid
  • Varying nuclear atypia
  • Varying cellular pleomorphism
  • Follicular carcinoma:
    • Focal microscopic invasion
  • Cellular or trabecular adenomas:
    • Lesions with less definite or no follicle formation
    • May show vascular or capsule invasion
Follicular lesion of undetermined significance (FLUS) + common, especially in nodular goiters.
  • FLUS:
    • the lesion has approximately equal number of macrofollicular fragments and microfollicles
  • AUS:
    • cells with mild nuclear atypia
  • Mostly due to compromised speciemens:
    • Poor fixation or obscuring blood (FLUS)
Atypia of undetermined significance (AUS)
Hürthle cells 
  • Oncocytes
  • Askanazy cells
  • Oxyphil cells
 +
  • Focal Hürthle-cell change:
    • Degenerating macrofollicular lesions
    • Hashimoto's thyroiditis
  • Large polyclonal cells
  • Oxyphil cytoplasm
  • Considered benign if there is no evidence of vascular or capsular invasion
  • Considered malignant if invasion is present
    • Hürthle-cell cancer
    • Follicular cancer
    • Oxyphil cell type cancer
Papillary cancer
  • The follicular variant of papillary cancer
 + Epithelioid giant cells
  • Papillary cancer
  • Degenerating areas of macrofollicular nodules
  • Subacute granulomatous thyroiditis

Psammoma bodies

  • Papillary carcinoma
  • Benign thyroid lesions
  • Large cells and nuclei 
  • Ground glass appearance of cytoplasm 
  • Nuclei appearance:
    • Clefts 
    • Grooves 
    • Holes 
    • Intranuclear cytoplasmic inclusions = Orphan Annie eyes 
    • Small nucleoli 
  • Psammoma bodies
    • Small laminated calcifications
  • Sticky colloid
    • Colloid "stick" to debris and cell clusters, instead of smearing across the slide
  • Epithelioid giant cells
    • Can also be seen in:
      • Degenerating areas of macrofollicular nodules
      • Subacute granulomatous thyroiditis
Medullary cancer  + Medullary cancer
  • Spindle-shaped cells
  • Frequently pleomorphic cells without follicle development
  • Supporting stroma may frequently stains for amyloid
  • Red cytoplasmic granules
  • Eccentrically placed nuclei
  • Slightly granular Cytoplasm that may be configured as a tear drop or cytoplasmic tail
Anaplastic thyroid cancer +

Large needle biopsy if needed

Anaplastic thyroid cancer
  • Spindle cells
  • Pleomorphic giant cell
  • Squamoid
  • Mitosis
    • Numerous mitotic figures
    • Atypical mitoses
  • Extensive necrosis.

Microscopic Pathology

  • Microscopic pathology is the disease process as it occurs at the microscopic level.
  • This section is a good place to include pictures. Search for copyleft images on The Pathology Wiki [3] and Ask Dr. Wiki [4].
  • Both polyclonal and monoclonal nodules appear similar on fine needle aspiration (FNA) (macrofollicular) and are benign 8426623
  • Thus, the diagnosis of follicular cancer in situ does not exist, because vascular or capsular invasion is required to make the diagnosis of follicular cancer. 8420446

References

  1. ↑ Aozasa K, Inoue A, Katagiri S, Matsuzuka F, Katayama S, Yonezawa T (1986). "Plasmacytoma and follicular lymphoma in a case of Hashimoto's thyroiditis". Histopathology. 10 (7): 735–40. PMID 3755697.
  2. ↑ Bastomsky CH (1977). "Enhanced thyroxine metabolism and high uptake goiters in rats after a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin". Endocrinology. 101 (1): 292–6. doi:10.1210/endo-101-1-292. PMID 862558.
  3. ↑ Brix K, Lemansky P, Herzog V (1996). "Evidence for extracellularly acting cathepsins mediating thyroid hormone liberation in thyroid epithelial cells". Endocrinology. 137 (5): 1963–74. doi:10.1210/endo.137.5.8612537. PMID 8612537.
  4. ↑ Burch HB (1995). "Evaluation and management of the solid thyroid nodule". Endocrinol. Metab. Clin. North Am. 24 (4): 663–710. PMID 8608777.
  5. ↑ Coclet J, Foureau F, Ketelbant P, Galand P, Dumont JE (1989). "Cell population kinetics in dog and human adult thyroid". Clin. Endocrinol. (Oxf). 31 (6): 655–65. PMID 2627756.
  6. ↑ 6.0 6.1 de los Santos ET, Keyhani-Rofagha S, Cunningham JJ, Mazzaferri EL (1990). "Cystic thyroid nodules. The dilemma of malignant lesions". Arch. Intern. Med. 150 (7): 1422–7. PMID 2196027.
  7. ↑ Di Carlo A, Mariano A, Pisano G, Parmeggiani U, Beguinot L, Macchia V (1990). "Epidermal growth factor receptor and thyrotropin response in human thyroid tissues". J. Endocrinol. Invest. 13 (4): 293–9. doi:10.1007/BF03349565. PMID 2164546.
  8. ↑ Dumont JE, Maenhaut C, Pirson I, Baptist M, Roger PP (1991). "Growth factors controlling the thyroid gland". Baillieres Clin. Endocrinol. Metab. 5 (4): 727–54. PMID 1661579.
  9. ↑ Duprez L, Parma J, Van Sande J, Allgeier A, Leclère J, Schvartz C, Delisle MJ, Decoulx M, Orgiazzi J, Dumont J (1994). "Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism". Nat. Genet. 7 (3): 396–401. doi:10.1038/ng0794-396. PMID 7920658.
  10. ↑ Ericsson UB, Lindgärde F (1991). "Effects of cigarette smoking on thyroid function and the prevalence of goitre, thyrotoxicosis and autoimmune thyroiditis". J. Intern. Med. 229 (1): 67–71. PMID 1995765.
  11. ↑ Farid NR, Shi Y, Zou M (1994). "Molecular basis of thyroid cancer". Endocr. Rev. 15 (2): 202–32. doi:10.1210/edrv-15-2-202. PMID 8026388.
  12. ↑ Liekens S, De Clercq E, Neyts J (2001). "Angiogenesis: regulators and clinical applications". Biochem. Pharmacol. 61 (3): 253–70. PMID 11172729.
  13. ↑ Gaitan E, Cooksey RC, Legan J, Lindsay RH (1995). "Antithyroid effects in vivo and in vitro of vitexin: a C-glucosylflavone in millet". J. Clin. Endocrinol. Metab. 80 (4): 1144–7. doi:10.1210/jcem.80.4.7714083. PMID 7714083.
  14. ↑ Gaskin D, Parai SK, Parai MR (1992). "Hashimoto's thyroiditis with medullary carcinoma". Can J Surg. 35 (5): 528–30. PMID 1356609.
  15. ↑ Gerber H, Huber G, Peter HJ, Kämpf J, Lemarchand-Beraud T, Fragu P, Stocker R (1994). "Transformation of normal thyroids into colloid goiters in rats and mice by diphenylthiohydantoin". Endocrinology. 135 (6): 2688–99. doi:10.1210/endo.135.6.7988459. PMID 7988459.
  16. ↑ Wang CC, Friedman L, Kennedy GC, Wang H, Kebebew E, Steward DL, Zeiger MA, Westra WH, Wang Y, Khanafshar E, Fellegara G, Rosai J, Livolsi V, Lanman RB (2011). "A large multicenter correlation study of thyroid nodule cytopathology and histopathology". Thyroid. 21 (3): 243–51. doi:10.1089/thy.2010.0243. PMC 3698689. PMID 21190442.
  17. ↑ Gharib H (1997). "Changing concepts in the diagnosis and management of thyroid nodules". Endocrinol. Metab. Clin. North Am. 26 (4): 777–800. PMID 9429860.
  18. ↑ Giordano C, Stassi G, De Maria R, Todaro M, Richiusa P, Papoff G, Ruberti G, Bagnasco M, Testi R, Galluzzo A (1997). "Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis". Science. 275 (5302): 960–3. PMID 9020075.
  19. ↑ Greenspan FS (1991). "The problem of the nodular goiter". Med. Clin. North Am. 75 (1): 195–209. PMID 1987443.
  20. ↑ Isaacson PG, Androulakis-Papachristou A, Diss TC, Pan L, Wright DH (1992). "Follicular colonization in thyroid lymphoma". Am. J. Pathol. 141 (1): 43–52. PMC 1886561. PMID 1632470.
  21. ↑ Ledent C, Parmentier M, Maenhaut C, Taton M, Pirson I, Lamy F, Roger P, Dumont JE (1991). "The TSH cyclic AMP cascade in the control of thyroid cell proliferation: the story of a concept". Thyroidology. 3 (3): 97–101. PMID 1726932.
  22. ↑ Ledent C, Dumont JE, Vassart G, Parmentier M (1992). "Thyroid expression of an A2 adenosine receptor transgene induces thyroid hyperplasia and hyperthyroidism". EMBO J. 11 (2): 537–42. PMC 556484. PMID 1371462.
  23. ↑ Livolsi VA, Merino MJ (1981). "Histopathologic differential diagnosis of the thyroid". Pathol Annu. 16 (Pt 2): 357–406. PMID 7036066.
  24. ↑ Ludgate M, Jasani B (1997). "Apoptosis in autoimmune and non-autoimmune thyroid disease". J. Pathol. 182 (2): 123–4. doi:10.1002/(SICI)1096-9896(199706)182:2<123::AID-PATH832>3.0.CO;2-F. PMID 9274519.
  25. ↑ Maceri DR, Sullivan MJ, McClatchney KD (1986). "Autoimmune thyroiditis: pathophysiology and relationship to thyroid cancer". Laryngoscope. 96 (1): 82–6. PMID 3484533.
  26. ↑ Moriuchi A, Yokoyama S, Kashima K, Andoh T, Nakayama I, Noguchi S (1992). "Localized primary amyloid tumor of the thyroid developing in the course of Hashimoto's thyroiditis". Acta Pathol. Jpn. 42 (3): 210–6. PMID 1570743.
  27. ↑ McKee RF, Krukowski ZH, Matheson NA (1993). "Thyroid neoplasia coexistent with chronic lymphocytic thyroiditis". Br J Surg. 80 (10): 1303–4. PMID 8242306.
  28. ↑ Ott RA, McCall AR, McHenry C, Jarosz H, Armin A, Lawrence AM, Paloyan E (1987). "The incidence of thyroid carcinoma in Hashimoto's thyroiditis". Am Surg. 53 (8): 442–5. PMID 3605864.
  29. ↑ Paynter OE, Burin GJ, Jaeger RB, Gregorio CA (1988). "Goitrogens and thyroid follicular cell neoplasia: evidence for a threshold process". Regul. Toxicol. Pharmacol. 8 (1): 102–19. PMID 3285378.
  30. ↑ Berndorfer U, Wilms H, Herzog V (1996). "Multimerization of thyroglobulin (TG) during extracellular storage: isolation of highly cross-linked TG from human thyroids". J. Clin. Endocrinol. Metab. 81 (5): 1918–26. doi:10.1210/jcem.81.5.8626858. PMID 8626858.
  31. ↑ Bialas P, Marks S, Dekker A, Field JB (1976). "Hashimoto's thyroiditis presenting as a solitary functioning thyroid nodule". J. Clin. Endocrinol. Metab. 43 (6): 1365–9. doi:10.1210/jcem-43-6-1365. PMID 1036742.
  32. ↑ Gaitan E, Lindsay RH, Reichert RD, Ingbar SH, Cooksey RC, Legan J, Meydrech EF, Hill J, Kubota K (1989). "Antithyroid and goitrogenic effects of millet: role of C-glycosylflavones". J. Clin. Endocrinol. Metab. 68 (4): 707–14. doi:10.1210/jcem-68-4-707. PMID 2921306.
  33. ↑ Gaitan E (1990). "Goitrogens in food and water". Annu. Rev. Nutr. 10: 21–39. doi:10.1146/annurev.nu.10.070190.000321. PMID 1696490.
  34. ↑ Taccaliti A, Boscaro M (2009). "Genetic mutations in thyroid carcinoma". Minerva Endocrinol. 34 (1): 11–28. PMID 19209125.
  35. ↑ Vecchio G, Santoro M (2000). "Oncogenes and thyroid cancer". Clin. Chem. Lab. Med. 38 (2): 113–6. doi:10.1515/CCLM.2000.017. PMID 10834397.
  36. ↑ Fusco A, Santoro M, Grieco M, Carlomagno F, Dathan N, Fabien N, Berlingieri MT, Li Z, De Franciscis V, Salvatore D (1995). "RET/PTC activation in human thyroid carcinomas". J. Endocrinol. Invest. 18 (2): 127–9. doi:10.1007/BF03349720. PMID 7629379.
  37. ↑ Fugazzola L, Pierotti MA, Vigano E, Pacini F, Vorontsova TV, Bongarzone I (1996). "Molecular and biochemical analysis of RET/PTC4, a novel oncogenic rearrangement between RET and ELE1 genes, in a post-Chernobyl papillary thyroid cancer". Oncogene. 13 (5): 1093–7. PMID 8806699.
  38. ↑ Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, van Amstel HK, Lips CJ, Nishisho I, Takai SI, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xue F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjöld M, Komminoth P, Hendy GN, Mulligan LM (1996). "The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis". JAMA. 276 (19): 1575–9. PMID 8918855.
  39. ↑ Goretzki PE, Simon D, Röher HD (1992). "G-protein mutations in thyroid tumors". Exp. Clin. Endocrinol. 100 (1–2): 14–6. doi:10.1055/s-0029-1211167. PMID 1468509.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Thyroid_nodule_pathophysiology&oldid=1336395"