64:
95:
209:
285:
is now the preferred method of establishing a diagnosis for MEN 2B, and is thought to be almost 100% sensitive and specific. Gordon et al. reported cases of a difference disease—the "multiple mucosal neuroma syndrome"—having the physical phenotype of MEN2B, but without variations in the RET gene and
216:
Unlike Marfan syndrome, the cardiovascular system and the lens of the eye are unaffected. Mucosal neuromas are the most consistent and distinctive feature, appearing in 100% of patients. Usually there are numerous yellowish-white, sessile, painless nodules on the lips or tongue, with deeper lesions
256:
cause MEN2B. In recent decades no case of MEN2B has been reported that lacks such a variation. The M918T variant alone is responsible for approximately 95% of cases. All DNA variants that cause MEN2B are thought to enhance signaling through the RET protein, which is a receptor molecule found on
333:
Without treatment, persons with MEN2B die prematurely. Details are lacking, owing to the absence of formal studies, but it is generally assumed that death in the 30s is typical unless prophylactic thyroidectomy and surveillance for pheochromocytoma are performed (see below). The range is quite
293:
was the most important laboratory test for MEN2B. Calcitonin is produced by the "C" cells of the thyroid, which, because they are always hyperplastic or malignant in MEN2B, produce more calcitonin than normal. Calcitonin levels remain a valuable marker to detect recurrence of medullary thyroid
119:
in 1922, and was first recognized as a syndrome in 1965–1966 by E.D. Williams and D.J. Pollock. It is caused by the pathogenic variant p.Met918Thr in the RET gene. This variant can cause medullary thyroid cancer and
Pheochromocytoma. Presentation can include a Marfanoid body, enlarged lips, and
362:
Because prophylactic thyroidectomy improves survival, blood relatives of a person with MEN2B should be evaluated for MEN2B, even if lacking the typical signs and symptoms of the disorder.The mucosal neuromas of this syndrome are asymptomatic and self-limiting, and present no problem requiring
325:, but the streaming fascicles of mucosal neuroma are usually more uniform and the intertwining nerves of the traumatic neuroma lack the thick perineurium of the mucosal neuroma. Inflammatory cells are not seen in the stroma and dysplasia is not present in the neural tissues.
304:
of some fibers, and lesional cells react immunohistochemically for S-100 protein, collagen type IV, vimentin, NSE, and neural filaments. More mature lesions will react also for EMA, indicating a certain amount of perineurial differentiation. Early lesions, rich in acid
334:
variable, however: death early in childhood can occur, and a few untreated persons have been diagnosed in their 50s. Recently, a larger experience with the disease "suggests that the prognosis in an individual patient may be better than previously considered."
146:
have been proposed for MEN 2B, such as
Williams-Pollock syndrome, Gorlin-Vickers syndrome, and Wagenmann-Froboese syndrome. However, none ever gained sufficient traction to merit continued use, and they are no longer used in the medical literature.
408:, and probably his mother. The "mole" on Lincoln's right cheek, the asymmetry of his face, his large jaw, his drooping eyelid, and "pseudo-depression" are also suggested as manifestations of MEN2B. Lincoln's longevity (dying at 56 of a
268:
trait. The other half appear to be spontaneous mutations, usually arising in the paternal allele, particularly from older fathers. The sex ratio in de novo cases is also uneven: sons are twice as likely to develop MEN 2B as daughters.
340:
is the mainstay of treatment, and should be performed without delay as soon as a diagnosis of MEN2B is made, even if no malignancy is detectable in the thyroid. Without thyroidectomy, almost all patients with MEN2B develop
1305:
690:
Schimke RN, Hartmann WH, Prout TE, Rimoin DL (1968). "Syndrome of bilateral pheochromocytoma, medullary thyroid carcinoma and multiple neuromas. A possible regulatory defect in the differentiation of chromaffin tissue".
150:
The prevalence of MEN2B is not well established, but has been derived from other epidemiological considerations as 1 in 600,000 to 1 in 4,000,000. The annual incidence has been estimated at 4 per 100 million per year.
289:
MEN2B should be entertained as a diagnosis whenever a person is found to have either medullary thyroid carcinoma or pheochromocytoma. Before DNA testing became available, measurement of serum
1298:
823:
Pujol RM, Matias-Guiu X, Miralles J, Colomer A, de
Moragas JM (August 1997). "Multiple idiopathic mucosal neuromas: a minor form of multiple endocrine neoplasia type 2B or a new entity?".
1291:
123:
MEN 2B typically manifests before a child is 10 years old. Affected individuals tend to be tall and lanky, with an elongated face and protruding, blubbery lips. Benign tumors (
1425:
813:
This reference quotes a prevalence of 1 in 40,000, but this figure is inconsistent with the same reference's calculated incidence of 4 per 100 million per year for MEN2B.
1028:
627:
1790:
1196:
1528:
240:, intertwined with one another in a plexiform pattern. This tortuous pattern of nerves is seen within a background of loose endoneurium-like fibrous
1336:
1331:
412:
and without any apparent suggestion of ill health otherwise) is the principal challenge to the MEN2B theory, which could be proven by DNA testing.
1418:
1085:
Sizemore GW, Carney JA, Gharib H, Capen CC (1992). "Multiple endocrine neoplasia type 2B: eighteen-year follow-up of a four-generation family".
592:
Williams, E. D., Pollock, D. J. (1966). "Multiple mucosal neuromata with endocrine tumours: a syndrome allied to von
Recklinghausen's disease".
1795:
1156:
917:
858:
Dyck, PJ (October 1979). "Multiple endocrine neoplasia, type 2b: phenotype recognition; neurological features and their pathological basis".
799:
460:
1363:
431:
236:
and myelinated fibers overlay the posterior columns of the spinal cord. Mucosal neuromas are made up of nerve cells, often with thickened
1754:
1749:
1358:
1353:
1244:
426:
115:, differentiated by the presence of benign oral and submucosal tumors in addition to endocrine malignancies. It was first described by
1411:
1129:
181:
1175:
The
Physical Lincoln: Finding the Genetic Cause of Abraham Lincoln's Height, Homeliness, Pseudo-Depression, and Imminent Cancer Death
1043:
1326:
409:
359:- is also present in 50% of cases. Affected individuals are encouraged to get yearly screenings for thyroid and adrenal cancer.
1608:
1455:
258:
1392:
1044:"The ultrastructure of oral neuromas in multiple mucosal neuromas, pheochromocytoma, medullary thyroid carcinoma syndrome"
1785:
1741:
1348:
421:
363:
treatment. They may, however, be surgically removed for aesthetic purposes or if they are being constantly traumatized.
112:
63:
1780:
221:
in the body of the lips to produce enlargement and a "blubbery lip" appearance. Similar nodules may be seen on the
1598:
1575:
345:, in a more aggressive form than MEN 2A. The ideal age for surgery is 4 years old or younger, since cancer may
1651:
1591:
1570:
1434:
1255:
342:
314:
132:
1561:
401:
1646:
241:
1703:
1022:
621:
1693:
1523:
397:
17:
1698:
1586:
94:
135:
almost always occurs, sometimes in infancy. It is often aggressive. Cancer of the adrenal glands (
1506:
1343:
883:
772:
306:
265:
253:
1283:
1071:
1685:
1533:
1514:
1450:
1266:
1152:
1146:
1125:
1121:
1113:
1094:
1063:
1010:
969:
940:"Multiple endocrine neoplasia type 2B (mucosal neuroma syndrome, Wagenmann-Froboese syndrome)"
913:
907:
875:
840:
795:
764:
708:
672:
609:
574:
506:
456:
322:
83:
726:
Marx, Stephen J (2011). "Chapter 41: Multiple endocrine neoplasia". In Melmed, Shlomo (ed.).
228:
Histologically, neuromata contain a characteristic adventitious plaque of tissue composed of
1663:
1603:
1548:
1055:
1000:
987:
Gordon CM, Majzoub JA, Marsh DJ, Mulliken JB, Ponder BA, Robinson BG, Eng C (January 1998).
959:
951:
867:
832:
754:
700:
662:
654:
601:
564:
556:
496:
352:
194:
188:
136:
116:
1726:
1658:
1616:
1482:
1375:
1315:
381:
377:
297:
165:
108:
1641:
1556:
1059:
964:
939:
667:
642:
501:
484:
282:
836:
569:
544:
212:
A patient with
Multiple endocrine neoplasia type 2B, presenting with mucosal neuromas.
1774:
1675:
1668:
1633:
1621:
380:
had MEN2B. This theory suggests
Lincoln had all the major features of the disease: a
356:
337:
88:
887:
776:
1713:
1579:
1518:
1179:
989:"Four cases of mucosal neuroma syndrome: multiple endocrine neoplasm 2B or not 2B?"
385:
321:
are elevated in serum and urine. Under the microscope, tumors may closely resemble
233:
107:(MEN 2B) is a genetic disease that causes multiple tumors on the mouth, eyes, and
75:
1260:
811:
759:
742:
1731:
1538:
1464:
704:
405:
310:
237:
229:
1271:
1145:
Lester W. Burket; Martin S. Greenberg; Michaël Glick; Jonathan A. Ship (2008).
208:
171:
masses beneath mucosal surfaces in the mouth, lips, and eyes (discussed below);
1491:
1478:
1473:
1460:
1403:
346:
318:
290:
71:
1721:
1469:
1385:
1380:
605:
389:
128:
1005:
988:
768:
578:
1098:
1014:
973:
871:
844:
712:
676:
658:
613:
510:
1442:
1370:
1183:
1067:
955:
879:
560:
124:
1197:
Scientist Wants to Test
Abraham Lincoln's Bloodstained Pillow for Cancer
810:
by
Electron Kebebew, Jessica E. Gosnell and Emily Reiff. Pages 695-701.
545:"A review of 17 cases of carnicoma of the thyroid and phaeochromocytoma"
218:
1236:
1496:
1487:
393:
301:
222:
143:
483:
Carlson KM, Bracamontes J, Jackson CE, et al. (December 1994).
1173:
168:" body build, in which long bones are disproportionately elongated;
485:"Parent-of-origin effects in multiple endocrine neoplasia type 2B"
207:
524:
Wagenmann A. (1922). "Multiple neurome des Auges und der Zunge".
451:
Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007).
1249:
1407:
1287:
1120:(5th ed.). Philadelphia: Elsevier-Saunders. pp.
74:
of medullary thyroid carcinoma, as may be seen in MEN 2b.
912:(3 ed.). Elsevier Health Sciences. pp. 246–7.
1042:
R. L. Miller; N. J. Burzynski; B. L. Giammara (1977).
264:
About half of cases are inherited from a parent as an
177:
gastrointestinal complaints, especially constipation;
1226:
1740:
1712:
1684:
1632:
1547:
1505:
1441:
1230:
82:
39:
34:
1114:"Chapter 192: Multiple endocrine neoplasia type 2"
743:"Multiple endocrine neoplasia type 2: an overview"
131:of almost all organs in the first decade of life.
643:"Mucosal neuromata syndrome (MEN type IIb (III))"
792:Neurocutaneous Disorders : The Phakomatoses
396:and a family history of the disorder - his sons
376:In 2007, Dr. John Sotos proposed that President
159:The most common clinical features of MEN2B are:
257:cell membranes, whose ligands are part of the
217:having normal coloration. There may be enough
1419:
1299:
8:
1027:: CS1 maint: multiple names: authors list (
626:: CS1 maint: multiple names: authors list (
933:
931:
929:
901:
899:
897:
728:Williams Textbook of Endocrinology, 12th ed
1426:
1412:
1404:
1306:
1292:
1284:
1227:
93:
62:
31:
1004:
963:
758:
666:
568:
500:
478:
476:
474:
472:
174:low muscle mass, sometimes with myopathy;
1048:Journal of Oral Pathology & Medicine
938:Morrison PJ, Nevin NC (September 1996).
641:Fryns JP, Chrzanowska K (October 1988).
443:
384:-like body habitus, large, bumpy lips,
48:Mucosal neuromata with endocrine tumors
1791:Endocrine-related cutaneous conditions
1151:(11 ed.). PMPH-USA. p. 141.
1116:. In DeGroot, LJ; Jameson, JL (eds.).
1020:
619:
808:Multiple Endocrine Neoplasia Type 2B
7:
432:Multiple endocrine neoplasia type 2a
105:Multiple endocrine neoplasia type 2B
35:Multiple endocrine neoplasia type 2b
18:Multiple endocrine neoplasia type 2b
427:Multiple endocrine neoplasia type 1
355:- a hormone secreting tumor of the
52:Multiple endocrine neoplasia type 3
1060:10.1111/j.1600-0714.1977.tb01647.x
317:is present, levels of the hormone
182:medullary carcinoma of the thyroid
127:) develop in the mouth, eyes, and
25:
1327:Autoimmune polyendocrine syndrome
455:. St. Louis: Mosby. p. 858.
1524:ACTH-secreting pituitary adenoma
111:. It is the most severe type of
1456:Pancreatic neuroendocrine tumor
294:carcinoma after thyroidectomy.
259:transforming growth factor beta
1529:GH-secreting pituitary adenoma
1:
1314:Disorders involving multiple
837:10.1016/S0190-9622(97)70025-2
1796:Autosomal dominant disorders
1349:Multiple endocrine neoplasia
1112:Hoff, AO; Gagel, RF (2006).
760:10.1097/GIM.0b013e318216cc6d
422:Multiple endocrine neoplasia
392:, a history compatible with
113:multiple endocrine neoplasia
1435:Tumours of endocrine glands
1211:Lincoln's Shroud of Turin,
705:10.1056/NEJM196807042790101
56:Wagenmann–Froboese syndrome
1812:
1186:: Mt. Vernon Book Systems.
906:Sperling, Mark A. (2008).
372:Abraham Lincoln hypothesis
200:dry eyes or lack of tears;
139:) occurs in 50% of cases.
1393:Woodhouse–Sakati syndrome
1322:
790:Martino Ruggieri (2005).
453:Dermatology: 2-Volume Set
70:
61:
1652:Adrenocortical carcinoma
741:Moline J, Eng C (2011).
526:Ber Dtsch Ophthalmol Ges
343:medullary thyroid cancer
315:medullary thyroid cancer
309:, stain positively with
133:Medullary thyroid cancer
1609:Squamous-cell carcinoma
993:J Clin Endocrinol Metab
909:Pediatric Endocrinology
606:10.1002/path.1700910109
232:, interlacing bands of
1647:Adrenocortical adenoma
1148:Burket's oral medicine
1006:10.1210/jcem.83.1.4504
278:Differential diagnosis
213:
187:symptoms derived from
180:symptoms derived from
1213:Philadelphia Inquirer
1087:Henry Ford Hosp Med J
872:10.1002/ana.410060404
825:J. Am. Acad. Dermatol
730:. pp. 1728–1767.
659:10.1136/jmg.25.10.703
211:
1694:Parathyroid neoplasm
956:10.1136/jmg.33.9.779
794:. Berlin: Springer.
747:Genetics in Medicine
594:J. Pathol. Bacteriol
561:10.1136/jcp.18.3.288
543:Williams ED (1965).
300:staining identifies
286:without malignancy.
1786:Endocrine neoplasia
1587:Parafollicular cell
1074:on 13 October 2012.
860:Annals of Neurology
367:Society and culture
307:mucopolysaccharides
252:Variations in the
1781:Hereditary cancers
1344:Carcinoid syndrome
1172:Sotos, JG (2008).
831:(2 Pt 2): 349–52.
266:autosomal dominant
261:signaling system.
254:RET proto-oncogene
214:
155:Signs and symptoms
120:ganglionueuromas.
1768:
1767:
1534:Craniopharyngioma
1515:Pituitary adenoma
1451:Pancreatic cancer
1401:
1400:
1281:
1280:
1200:Discover Magazine
1158:978-1-55009-345-2
919:978-1-4160-4090-3
801:978-3-211-21396-4
489:Am. J. Hum. Genet
462:978-1-4160-2999-1
323:traumatic neuroma
102:
101:
29:Medical condition
16:(Redirected from
1803:
1664:Pheochromocytoma
1428:
1421:
1414:
1405:
1316:endocrine glands
1308:
1301:
1294:
1285:
1228:
1216:
1209:
1203:
1194:
1188:
1187:
1169:
1163:
1162:
1142:
1136:
1135:
1109:
1103:
1102:
1093:(3–4): 236–244.
1082:
1076:
1075:
1070:. Archived from
1039:
1033:
1032:
1026:
1018:
1008:
984:
978:
977:
967:
935:
924:
923:
903:
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891:
855:
849:
848:
820:
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805:
787:
781:
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762:
738:
732:
731:
723:
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687:
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670:
638:
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589:
583:
582:
572:
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534:
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521:
515:
514:
504:
480:
467:
466:
448:
353:Pheochromocytoma
302:myelin sheathing
203:delayed puberty.
195:craniosynostosis
189:pheochromocytoma
137:pheochromocytoma
109:endocrine glands
98:
97:
66:
32:
21:
1811:
1810:
1806:
1805:
1804:
1802:
1801:
1800:
1771:
1770:
1769:
1764:
1736:
1727:Pinealoblastoma
1708:
1680:
1628:
1617:Thyroid adenoma
1562:epithelial-cell
1543:
1501:
1483:Somatostatinoma
1437:
1432:
1402:
1397:
1376:Werner syndrome
1318:
1312:
1282:
1277:
1276:
1239:
1225:
1220:
1219:
1215:, 13 April 2009
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693:N. Engl. J. Med
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378:Abraham Lincoln
374:
369:
349:before age 10.
331:
298:Luxol fast blue
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250:
206:
164:a tall, thin, "
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30:
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22:
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1557:Thyroid cancer
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1231:Classification
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1223:External links
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1137:
1131:978-0721603766
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1559:(malignant):
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1202:20 April 2009
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1118:Endocrinology
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1054:(5): 253–63.
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1002:
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950:(9): 779–82.
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653:(10): 703–6.
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410:gunshot wound
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338:Thyroidectomy
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234:Schwann cells
231:
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225:and eyelids.
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142:A variety of
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89:Endocrinology
87:
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76:H&E stain
73:
69:
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60:
57:
53:
49:
45:
42:
38:
33:
27:
19:
1759:
1714:Pineal gland
1580:Hurthle cell
1565:
1560:
1519:Prolactinoma
1265:
1254:
1243:
1212:
1207:
1199:
1192:
1180:Mount Vernon
1174:
1167:
1147:
1140:
1117:
1107:
1090:
1086:
1080:
1072:the original
1051:
1047:
1037:
1023:cite journal
999:(1): 17–20.
996:
992:
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908:
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828:
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818:
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727:
721:
696:
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622:cite journal
600:(1): 71–80.
597:
593:
587:
552:
548:
538:
529:
525:
519:
492:
488:
452:
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386:constipation
375:
361:
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230:hyperplastic
227:
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122:
104:
103:
55:
51:
47:
43:
26:
1732:Pineocytoma
1686:Parathyroid
1539:Pituicytoma
1465:Glucagonoma
806:- Chapter:
388:, muscular
347:metastasize
311:alcian blue
283:DNA testing
238:perineurium
40:Other names
1775:Categories
1599:Anaplastic
1576:Follicular
1492:Gastrinoma
1474:Insulinoma
1267:DiseasesDB
699:(1): 1–7.
438:References
319:calcitonin
291:calcitonin
72:Micrograph
1722:Pinealoma
1704:Carcinoma
1592:Medullary
1571:Papillary
1566:carcinoma
1507:Pituitary
1386:Metageria
1381:Acrogeria
1122:3533–3550
390:hypotonia
329:Treatment
273:Diagnosis
166:marfanoid
129:submucosa
125:neoplasms
117:Wagenmann
84:Specialty
1604:Lymphoma
1443:Pancreas
1371:Progeria
888:24328061
777:22402472
769:21552134
579:14304238
532:: 282–5.
416:See also
219:neuromas
1699:Adenoma
1659:Medulla
1613:Benign
1549:Thyroid
1261:D018814
1099:1362413
1015:9435410
974:8880581
965:1050735
845:9270546
713:4968712
677:2906373
668:1051565
614:4957444
511:7977365
502:1918453
313:. When
144:eponyms
1642:Cortex
1497:VIPoma
1250:162300
1155:
1128:
1097:
1068:409817
1066:
1013:
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880:554522
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612:
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570:472926
567:
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499:
459:
404:, and
402:Willie
394:cancer
382:marfan
248:Causes
242:stroma
223:sclera
91:
44:MEN 2B
1272:22784
884:S2CID
773:S2CID
398:Eddie
1337:APS2
1332:APS1
1256:MeSH
1245:OMIM
1153:ISBN
1126:ISBN
1095:PMID
1064:PMID
1029:link
1011:PMID
970:PMID
914:ISBN
876:PMID
841:PMID
796:ISBN
765:PMID
709:PMID
673:PMID
628:link
610:PMID
575:PMID
507:PMID
457:ISBN
1742:MEN
1056:doi
1001:doi
960:PMC
952:doi
868:doi
833:doi
755:doi
701:doi
697:279
663:PMC
655:doi
602:doi
565:PMC
557:doi
497:PMC
406:Tad
1777::
1760:2B
1755:2A
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1364:2B
1359:2A
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