Difference between revisions of "Lisch nodule"

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*[[NF1]] is due to [[mutations]] in the [[NF1]] [[gene]], located at [[chromosome]] 17q11.2.
 
*[[NF1]] is due to [[mutations]] in the [[NF1]] [[gene]], located at [[chromosome]] 17q11.2.
 
*[[Neurofibromin]], the [[protein]] product encoded by the [[gene]], is expressed in many [[tissues]], including [[brain]], [[kidney]], [[spleen]], and [[thymus]].
 
*[[Neurofibromin]], the [[protein]] product encoded by the [[gene]], is expressed in many [[tissues]], including [[brain]], [[kidney]], [[spleen]], and [[thymus]].
*[[Mutations]] in the [[NF1]] [[gene]] result in loss of production or reduced [[Function (biology)|function]] of [[protein]]; this causes a wide spectrum of clinical findings, including NF1-associated tumors.<ref name="LubsBauer1991">{{cite journal|last1=Lubs|first1=Marie-Louise E.|last2=Bauer|first2=Mislen S.|last3=Formas|first3=Maria E.|last4=Djokic|first4=Borivoje|title=Lisch Nodules in Neurofibromatosis Type 1|journal=New England Journal of Medicine|volume=324|issue=18|year=1991|pages=1264–1266|issn=0028-4793|doi=10.1056/NEJM199105023241807}}</ref>
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*[[Mutations]] in the [[NF1]] [[gene]] result in loss of production or reduced [[Function (biology)|function]] of [[protein]]; this causes a wide spectrum of clinical findings, including [[NF1]]-associated [[Tumor|tumors]].<ref name="LubsBauer1991">{{cite journal|last1=Lubs|first1=Marie-Louise E.|last2=Bauer|first2=Mislen S.|last3=Formas|first3=Maria E.|last4=Djokic|first4=Borivoje|title=Lisch Nodules in Neurofibromatosis Type 1|journal=New England Journal of Medicine|volume=324|issue=18|year=1991|pages=1264–1266|issn=0028-4793|doi=10.1056/NEJM199105023241807}}</ref>
*[[Histopathology|Histopathologically]], Lisch nodules are composed of [[melanocytes]] and [[spindle cells]], usually concentrated on the superficial layers of the [[iris]] stroma.
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*[[Histopathology|Histopathologically]], Lisch nodules are composed of [[melanocytes]] and [[spindle cells]], usually concentrated on the superficial layers of the [[iris]] [[stroma]].
*The [[spindle cells]] are larger than the normal iris [[melanocytes]].
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*The [[spindle cells]] are larger than the normal [[Iris (anatomy)|iris]] [[melanocytes]].
 
*[[Immunohistochemical]] studies show positive reaction against the following
 
*[[Immunohistochemical]] studies show positive reaction against the following
 
**[[Vimentin]]
 
**[[Vimentin]]
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== Risk Factors ==
 
== Risk Factors ==
  
*The biggest risk factor for Lisch nodules associated with neurofibromatosis is a family history of the disorder
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*The biggest [[risk factor]] for Lisch nodules associated with [[neurofibromatosis]] is a family history of the disorder.
**NF1 and NF2 are both autosomal dominant disorders, which means that any child of a parent with the disorder has a 50 percent chance of inheriting the genetic mutation.
 
**About half of people with NF1 and NF2 inherited the disease from the affected parent.
 
*People with NF1 and NF2 that don't have affected relatives likely have a new gene mutation.
 
*Neurofibromatosis is caused by genetic defects (mutations) that either are passed on by a parent or occur spontaneously at conception.
 
**The NF1 gene is located on chromosome 17. This gene produces a protein called neurofibromin that helps regulate cell growth.  The mutated gene causes a loss of neurofibromin, which allows cells to grow uncontrolled.
 
**The NF2 gene is located on chromosome 22, and produces a protein called merlin (also called schwannomin), which suppresses tumors.  The mutated gene causes a loss of merlin, leading to uncontrolled cell growth.
 
**Two genes are known to cause schwannomatosis. Mutations of the genes SMARCB1 and LZTR1, which suppress tumors, are associated with this type of neurofibromatosis.
 
  
 
==Screening==
 
==Screening==
*Lisch Nodules are not regularly screened, they’re usually detected when other signs and symptoms of neurofibromatosis appear.<ref name="LubsBauer19913">{{cite journal|last1=Lubs|first1=Marie-Louise E.|last2=Bauer|first2=Mislen S.|last3=Formas|first3=Maria E.|last4=Djokic|first4=Borivoje|title=Lisch Nodules in Neurofibromatosis Type 1|journal=New England Journal of Medicine|volume=324|issue=18|year=1991|pages=1264–1266|issn=0028-4793|doi=10.1056/NEJM199105023241807}}</ref>
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*Lisch Nodules are not regularly screened, they’re usually detected when other signs and symptoms of [[neurofibromatosis]] appear.<ref name="LubsBauer19913">{{cite journal|last1=Lubs|first1=Marie-Louise E.|last2=Bauer|first2=Mislen S.|last3=Formas|first3=Maria E.|last4=Djokic|first4=Borivoje|title=Lisch Nodules in Neurofibromatosis Type 1|journal=New England Journal of Medicine|volume=324|issue=18|year=1991|pages=1264–1266|issn=0028-4793|doi=10.1056/NEJM199105023241807}}</ref>
*However, Lisch nodules are seen in 95% of children with NF1 by age 20
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*However, Lisch nodules are seen in 95% of children with [[NF1]] by age 20
*They can often be seen with no magnification, especially in adults, who usually have multiple, bilateral nodules
 
*A slit-lamp examination, however, is required to distinguish them from nevi on the iris, which are flat or minimally elevated, densely pigmented lesions with blurred margins.
 
  
 +
== Natural History, Complications and Prognosis ==
  
==[[Lisch nodule natural history|Natural History, Complications and Prognosis]]==
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=== Natural History ===
  
*The prognosis is excellent for eyes that contain iris Lisch nodules, unless associated with other ocular lesions including optic nerve gliomas and epiretinal membranes.
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=== Complications ===
*NF1 and NF2 vary based on location of chromosome mutation, tumor type and location, non-tumor manifestations and management techniques; however, clinical presentations of both subtypes may overlap, making diagnosis difficult
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*Both NF1 and NF2 are acquired through an inherited autosomal dominant transmission or sporadic mutation, with presentation of NF1 more common than NF2.
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=== Prognosis ===
*Therefore, members of the same family with NF may have different disease presentations from each other, as they do not always carry the same gene mutations.
 
*Lisch nodules rarely cause ocular complications and patients are typically asymptomatic
 
*NF patients may also present with plexiform neurofibroma, retinal tumors and optic nerve pathway gliomas as optical lesions
 
  
 
==Diagnosis==
 
==Diagnosis==

Revision as of 21:52, 20 September 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Swathi Venkatesan, M.B.B.S.[2]

Synonyms and Keywords: Sakurai-lisch nodule

Overview

Lisch nodules are well defined melanocytic hamartomas of the iris. Lisch nodules generally appear as dome-shaped gelatinous masses. Lisch nodules masses are more commonly develop on the surface of the iris, also known as iris hamartomas. Lisch nodules are gold-tan to brown in color, they may grow up to 2 mm in diameter and can be of different sizes on the same iris. Lisch nodules arise from mast cells, pigmented cells and fibroblast-like cells. The presence of Lisch nodules is the most common clinical sign of Neurofibromatosis 1; ninety-three percent of cases are bilaterally affected and an average of 25 nodules can be counted on each iris. Once iris hamartomas have developed, they remain stable throughout life. In 80% of eyes, Lisch nodules may be found in the inferior quadrants of the iris and this may be related to greater sun exposure, one of the postulated factors in the development of these benign tumefactions.

Historical Perspective

Lisch nodule classification

  • There is no established system for the classification of Lisch nodules.

Pathophysiology

Lisch nodule causes

Lisch nodule differential diagnosis

Epidemiology and Demographics

Incidence

Prevalence

  • The prevalence of Lisch nodules is approximately 1 in 3500 individuals worldwide.

Age

  • Lisch nodules are predominantly visible in children usually after the age of six years.
  • Lisch Nodule incidence in NF1 increases with age and their prevalence raises by about 10% per year of life, up to age 9.
  • Lisch nodules are found in 93% of adults with NF-1 but have not been described in NF-2.
  • Lisch Nodules may be found in a very limited number of individuals without NF.
  • The de novo mutations occur primarily in paternally derived chromosomes, and the likelihood of de novo NF1 increases with advanced paternal age.

Risk Factors

Screening

  • Lisch Nodules are not regularly screened, they’re usually detected when other signs and symptoms of neurofibromatosis appear.[10]
  • However, Lisch nodules are seen in 95% of children with NF1 by age 20

Natural History, Complications and Prognosis

Natural History

Complications

Prognosis

Diagnosis

Diagnostic Criteria for neurofibromatosis 1

(NIH consensus development conference 1988)

  • 6 or more café au lait macules (>0.5 cm in children or >1.5 cm in adults)
  • 2 or more cutaneous/subcutaneous neurofibromas or one plexiform neurofibroma
  • Axillary or groin freckling
  • Optic pathway glioma
  • 2 or more Lisch nodules (iris hamartomas seen on slit lamp examination)
  • Bony dysplasia (sphenoid wing dysplasia, bowing of long bone ± pseudarthrosis)
  • First degree relative with NF1

The diagnosis is based on clinical assessment and two or more of the features are required.

Physical Examination

  • Lisch nodules occur in 90% of adults with neurofibromatosis 1.
  • Eye-findings include orange-brown colored specks.
  • They are usually elevated and tan in appearance.
  • These are benign hamartomas that can be seen without magnification.
  • Also known as melanocytic hamartomas of the iris, often associated with neurofibromatosis (NF) I
  • Other associated ophthalmologic findings are optic gliomas
    • Optic gliomas can alter color vision and can produce progressive sight loss

Lisch nodule Diagnostic Studies

  • On slit-lamp examination, they have a smooth, dome-shaped appearance and are usually light brown, although some can be very pale.
  • Slit lamp examination can differentiate them from nevi on the iris by demonstrating elevated lesion instead of flat ones.
  • Lisch nodules develop during childhood, after the appearance of café-au-lait spots but before peripheral neurofibromas
  • This is useful in confirming the diagnosis of NF1 in children with no family history and only multiple café-au-lait spots

Treatment

Medical Therapy

  • There is no treatment for the underlying disease nor any necessity to treat these small benign lesions which do not interfere with visual function, but lifelong monitoring is necessary because of the widespread manifestations and serious threat of complications such as visual impairment, renal hypertension and ischemia of major organs.

References

  1. Antônio JR, Goloni-Bertollo EM, Trídico LA (2013). "Neurofibromatosis: chronological history and current issues". An Bras Dermatol. 88 (3): 329–43. doi:10.1590/abd1806-4841.20132125. PMC 3754363. PMID 23793209.
  2. Hosoi, Kiyoshi (1931). "MULTIPLE NEUROFIBROMATOSIS (von RECKLINGHAUSEN'S DISEASE)". Archives of Surgery. 22 (2): 258. doi:10.1001/archsurg.1931.01160020081004. ISSN 0272-5533.
  3. Gabhane SK, Kotwal MN, Bobhate SK (2010). "Segmental neurofibromatosis: a report of 3 cases". Indian J Dermatol. 55 (1): 105–8. doi:10.4103/0019-5154.60366. PMC 2856359. PMID 20418991.
  4. Boley S, Sloan JL, Pemov A, Stewart DR (2009). "A quantitative assessment of the burden and distribution of Lisch nodules in adults with neurofibromatosis type 1". Invest Ophthalmol Vis Sci. 50 (11): 5035–43. doi:10.1167/iovs.09-3650. PMC 2883270. PMID 19516012.
  5. Boyd KP, Korf BR, Theos A (2009). "Neurofibromatosis type 1". J Am Acad Dermatol. 61 (1): 1–14, quiz 15-6. doi:10.1016/j.jaad.2008.12.051. PMC 2716546. PMID 19539839.
  6. Lubs, Marie-Louise E.; Bauer, Mislen S.; Formas, Maria E.; Djokic, Borivoje (1991). "Lisch Nodules in Neurofibromatosis Type 1". New England Journal of Medicine. 324 (18): 1264–1266. doi:10.1056/NEJM199105023241807. ISSN 0028-4793.
  7. Radius RL, Herschler J (1980). "Histopathology in the iris-nevus (Cogan-Reese) syndrome". Am J Ophthalmol. 89 (6): 780–6. doi:10.1016/0002-9394(80)90165-8. PMID 6992584.
  8. Makley TA, Kapetansky FM (1988). "Iris nevus syndrome". Ann Ophthalmol. 20 (8): 311–5. PMID 3190109.
  9. Lubs, Marie-Louise E.; Bauer, Mislen S.; Formas, Maria E.; Djokic, Borivoje (1991). "Lisch Nodules in Neurofibromatosis Type 1". New England Journal of Medicine. 324 (18): 1264–1266. doi:10.1056/NEJM199105023241807. ISSN 0028-4793.
  10. Lubs, Marie-Louise E.; Bauer, Mislen S.; Formas, Maria E.; Djokic, Borivoje (1991). "Lisch Nodules in Neurofibromatosis Type 1". New England Journal of Medicine. 324 (18): 1264–1266. doi:10.1056/NEJM199105023241807. ISSN 0028-4793.

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