Difference between revisions of "Langerhans cell histiocytosis"

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'''Langerhans cell histiocytosis''', abbreviated '''LCH''', is a rare genetic disorder of tissue macrophages. It broadly fits into the category of ''[[histiocytoses]]''.
[[Image:Langerhans cell histiocytosis - very high mag.jpg|thumb|right|Langerhans cell histiocytosis. [[H&E stain]]. (WC/Nephron)]]
'''Langerhans cell histiocytosis''', abbreviated '''LCH''', is a rare disorder of tissue macrophages. It broadly fits into the category of ''[[histiocytoses]]''.  It used to known as ''eosinophilic granuloma''. 
 
It has been referred to by several eponyms - '''Hand-Schüller-Christian disease''', '''Abt-Letterer-Siwe disease''' or '''Letterer-Siwe disease''', and '''histiocytosis X'''.
 
This article deals with LCH in general. A separate article exists for ''[[pulmonary Langerhans cell histiocytosis]]''.


==General==
==General==
*Looks like eosinophilic granuloma of the lung - see ''[[Medical_lung_diseases#Pulmonary_Langerhans_cell_histiocytosis|medical lung diseases]]''.
===Overview===
LCH is really four (or three) diseases (depending on how one classifies it) - that happen to share the same histology:<ref name=Ref_PCPBoD8_338-9>{{Ref PCPBoD8|338-9}}</ref><ref name=pmid16295427>{{Cite journal  | last1 = Chhabra | first1 = UD. | last2 = Desai | first2 = SS. | last3 = Jambhekar | first3 = NA. | title = Langerhans' cell histiocytosis: a clinicopathological study of 50 cases. | journal = Indian J Pathol Microbiol | volume = 47 | issue = 3 | pages = 370-6 | month = Jul | year = 2004 | doi =  | PMID = 16295427 }}</ref>
{| class="wikitable sortable"
! Disease
! Other name(s)
! Prognosis
! Demographic
! Location
! Risks/cause
|-
| [[Pulmonary Langerhans cell histiocytosis]]
| Eosinophilic granuloma
| good with smoking cessation
| adults - smokers
| lung only; typically upper lung field
| due to smoking
|-
| Multifocal multisystem Langerhans cell histiocytosis
| multisystem LCH, Letterer-Siwe disease
| outcome dependent on organ involved,<ref name=pmid21351807>{{Cite journal  | last1 = Minkov | first1 = M. | title = Multisystem Langerhans cell histiocytosis in children: current treatment and future directions. | journal = Paediatr Drugs | volume = 13 | issue = 2 | pages = 75-86 | month = Apr | year = 2011 | doi = 10.2165/11538540-000000000-00000 | PMID = 21351807 }}</ref> natural history 2 year survival, 50% five year survival with treatment
| usu. children < 2 years old, rarely adults<ref name=pmid22470214>{{Cite journal  | last1 = Garg | first1 = A. | last2 = Kumar | first2 = P. | title = Multisystem Langerhans cell histiocytosis in adult. | journal = Indian J Dermatol | volume = 57 | issue = 1 | pages = 58-60 | month = Jan | year = 2012 | doi = 10.4103/0019-5154.92683 | PMID = 22470214 }}</ref>
| multiple systems (skin, spleen, liver, lung, bone marrow)
| possibly genetic ‡
|-
| Unifocal Langerhans cell histiocytosis †
| Eosinophilic granuloma
| may spontaneously regress, may cure with surgery
| children (?)
| bone only
| possibly genetic ‡
|-
| Multifocal unisystem Langerhans cell histiocytosis †
| multifocal LCH, eosinophilic granuloma, Hand-Schuller-Christian syndrome = bone defect, diabetes insipidus & exopthalmos
| may spontaneously regress, may cure with surgery (?)
| children (?)
| usu. bone; may be in: skin, lungs, stomach
| possibly genetic ‡
|}
 
Note:
* † Robbins lumps these groups together.
* ‡ Incompletely understood. Somatic BRAF mutations identified in approximately half of the individuals.<ref name=pmid20519626>{{Cite journal  | last1 = Badalian-Very | first1 = G. | last2 = Vergilio | first2 = JA. | last3 = Degar | first3 = BA. | last4 = MacConaill | first4 = LE. | last5 = Brandner | first5 = B. | last6 = Calicchio | first6 = ML. | last7 = Kuo | first7 = FC. | last8 = Ligon | first8 = AH. | last9 = Stevenson | first9 = KE. | title = Recurrent BRAF mutations in Langerhans cell histiocytosis. | journal = Blood | volume = 116 | issue = 11 | pages = 1919-23 | month = Sep | year = 2010 | doi = 10.1182/blood-2010-04-279083 | PMID = 20519626 }}</ref><ref name=pmid22017623>{{Cite journal  | last1 = Badalian-Very | first1 = G. | last2 = Vergilio | first2 = JA. | last3 = Degar | first3 = BA. | last4 = Rodriguez-Galindo | first4 = C. | last5 = Rollins | first5 = BJ. | title = Recent advances in the understanding of Langerhans cell histiocytosis. | journal = Br J Haematol | volume = 156 | issue = 2 | pages = 163-72 | month = Jan | year = 2012 | doi = 10.1111/j.1365-2141.2011.08915.x | PMID = 22017623 }}</ref>
 
===Clinical presentation===
Features - dependent on subtype:<ref name=Ref_PCPBoD8_338-9>{{Ref PCPBoD8|338-9}}</ref>
*May present with fever, anemia, bone pain, bone fracture, diabetes insipidus, exophthalmos.
*Can be an incidental finding.


==Microscopic==
==Microscopic==
Features:
Features:<ref name=pmid16295427/>
*Langerhans cells histiocytes - '''key feature'''.
*Langerhans cells histiocytes - '''key feature'''.
**Clusters of cells (histiocytes) with a reniform (kidney-shaped) nucleus and abundant foamy cytoplasm.
**Clusters of cells (histiocytes) with a reniform (kidney-shaped) nucleus and abundant foamy cytoplasm.
***Nucleus may look like a "coffee bean", i.e. have nuclear grooves (similar to those in [[papillary thyroid carcinoma]]) -- appearance dependent on the rotation of the nucleus.<ref>BN. 15 March 2011.</ref>
***Nucleus may look like a "[[coffee bean nucleus|coffee bean]]", i.e. have nuclear grooves (similar to those in [[papillary thyroid carcinoma]]) -- appearance dependent on the rotation of the nucleus.<ref>BN. 15 March 2011.</ref> May be called "buttock cells".
***Chromatin pattern: fine granular, light gray.
***Chromatin pattern: fine granular, light gray.
*+/-Eosinophils - often prominent.
*+/-Eosinophils - often prominent.
 
*+/-Fibrosis - common.
Images:
*+/-Other inflammatory cells - neutrophils, plasma cells (uncommon).
*[http://commons.wikimedia.org/wiki/File:Langerhans_cell_histiocytosis_-_very_high_mag.jpg LCH - lymph node - very high mag. (WC)].
*+/-Multinucleated giant cells - uncommon.
*[http://commons.wikimedia.org/wiki/File:Langerhans_cell_histiocytosis_-_high_mag.jpg LCH - lymph node - high mag. (WC)].


DDx:
DDx:
*[[Kimura disease]] - eosinophilia.
*[[Kimura disease]] - eosinophilia.
*See ''[[lymph node pathology]]''.
*See ''[[lymph node pathology]]''.
*See ''[[Long_power_list#Many_eosinophils|lesions with many eosinophils]]''.
===Images===
<gallery>
Image:Langerhans cell histiocytosis - very low mag.jpg| LCH - very low mag. (WC/Nephron)
Image:Langerhans cell histiocytosis - low mag.jpg| LCH - low mag. (WC/Nephron)
Image:Langerhans cell histiocytosis - intermed mag.jpg| LCH - intermed. mag. (WC/Nephron)
Image:Langerhans cell histiocytosis - very high mag.jpg| LCH - very high mag. (WC/Nephron)
</gallery>
====www====
*[http://path.upmc.edu/cases/case533.html LCH - several images (upmc.edu)].


==IHC==
==IHC==
*CD1a +ve.
*CD1a +ve.
*S100 +ve.
*S100 +ve.
*CD207 ([[AKA]] Langerin) +ve.<ref name=omim604862>{{OMIM|604862}}</ref>
==Molecular==
*Commonly have BRAF mutations ~ 40-70% of cases.<ref name=pmid26980021>{{Cite journal  | last1 = Alayed | first1 = K. | last2 = Medeiros | first2 = LJ. | last3 = Patel | first3 = KP. | last4 = Zuo | first4 = Z. | last5 = Li | first5 = S. | last6 = Verma | first6 = S. | last7 = Galbincea | first7 = J. | last8 = Cason | first8 = RC. | last9 = Luthra | first9 = R. | title = BRAF and MAP2K1 mutations in Langerhans cell histiocytosis: a study of 50 cases. | journal = Hum Pathol | volume =  | issue =  | pages =  | month = Feb | year = 2016 | doi = 10.1016/j.humpath.2015.12.029 | PMID = 26980021 }}</ref>
**The ''[[BRAF V600E mutation|V600E mutation]]'' is the most common BRAF mutation.<ref name=pmid27094161>{{Cite journal  | last1 = Tatsuno | first1 = M. | last2 = Shioda | first2 = Y. | last3 = Iwafuchi | first3 = H. | last4 = Yamazaki | first4 = S. | last5 = Iijima | first5 = K. | last6 = Takahashi | first6 = C. | last7 = Ono | first7 = H. | last8 = Uchida | first8 = K. | last9 = Okamura | first9 = O. | title = BRAF V600 mutations in Langerhans cell histiocytosis with a simple and unique assay. | journal = Diagn Pathol | volume = 11 | issue = 1 | pages = 39 | month =  | year = 2016 | doi = 10.1186/s13000-016-0489-z | PMID = 27094161 }}</ref>
**MAP2K1 mutations are often found in the cases without BRAF mutations.<ref name=pmid26980021/><ref>{{Cite journal  | last1 = Chakraborty | first1 = R. | last2 = Hampton | first2 = OA. | last3 = Shen | first3 = X. | last4 = Simko | first4 = SJ. | last5 = Shih | first5 = A. | last6 = Abhyankar | first6 = H. | last7 = Lim | first7 = KP. | last8 = Covington | first8 = KR. | last9 = Trevino | first9 = L. | title = Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. | journal = Blood | volume = 124 | issue = 19 | pages = 3007-15 | month = Nov | year = 2014 | doi = 10.1182/blood-2014-05-577825 | PMID = 25202140 }}</ref>


==Electron microscopy==
==Electron microscopy==
*[[Birbeck granules]].
*[[Birbeck granules]].
Etiology:
*Cell membrane invagination.<ref>URL: [http://path.upmc.edu/cases/case147/micro.html http://path.upmc.edu/cases/case147/micro.html]. Accessed on: 7 January 2012.</ref>
Appearance:
*Electron dense, cytoplasmic tennis racket-like body.
Images:
*[http://path.upmc.edu/cases/case147/micro.html LCH (upmc.edu)].
*[http://path.upmc.edu/cases/case298/images/fig09.jpg Birbeck granule - perfect 'tennis racket' (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case298.html http://path.upmc.edu/cases/case298.html]. Accessed on: 14 January 2012.</ref>


==See also==
==See also==
Line 35: Line 112:


[[Category:Haematopathology]]
[[Category:Haematopathology]]
[[Category:Diagnosis]]

Latest revision as of 03:32, 25 April 2016

Langerhans cell histiocytosis. H&E stain. (WC/Nephron)

Langerhans cell histiocytosis, abbreviated LCH, is a rare disorder of tissue macrophages. It broadly fits into the category of histiocytoses. It used to known as eosinophilic granuloma.

It has been referred to by several eponyms - Hand-Schüller-Christian disease, Abt-Letterer-Siwe disease or Letterer-Siwe disease, and histiocytosis X.

This article deals with LCH in general. A separate article exists for pulmonary Langerhans cell histiocytosis.

General

Overview

LCH is really four (or three) diseases (depending on how one classifies it) - that happen to share the same histology:[1][2]

Disease Other name(s) Prognosis Demographic Location Risks/cause
Pulmonary Langerhans cell histiocytosis Eosinophilic granuloma good with smoking cessation adults - smokers lung only; typically upper lung field due to smoking
Multifocal multisystem Langerhans cell histiocytosis multisystem LCH, Letterer-Siwe disease outcome dependent on organ involved,[3] natural history 2 year survival, 50% five year survival with treatment usu. children < 2 years old, rarely adults[4] multiple systems (skin, spleen, liver, lung, bone marrow) possibly genetic ‡
Unifocal Langerhans cell histiocytosis † Eosinophilic granuloma may spontaneously regress, may cure with surgery children (?) bone only possibly genetic ‡
Multifocal unisystem Langerhans cell histiocytosis † multifocal LCH, eosinophilic granuloma, Hand-Schuller-Christian syndrome = bone defect, diabetes insipidus & exopthalmos may spontaneously regress, may cure with surgery (?) children (?) usu. bone; may be in: skin, lungs, stomach possibly genetic ‡

Note:

  • † Robbins lumps these groups together.
  • ‡ Incompletely understood. Somatic BRAF mutations identified in approximately half of the individuals.[5][6]

Clinical presentation

Features - dependent on subtype:[1]

  • May present with fever, anemia, bone pain, bone fracture, diabetes insipidus, exophthalmos.
  • Can be an incidental finding.

Microscopic

Features:[2]

  • Langerhans cells histiocytes - key feature.
    • Clusters of cells (histiocytes) with a reniform (kidney-shaped) nucleus and abundant foamy cytoplasm.
      • Nucleus may look like a "coffee bean", i.e. have nuclear grooves (similar to those in papillary thyroid carcinoma) -- appearance dependent on the rotation of the nucleus.[7] May be called "buttock cells".
      • Chromatin pattern: fine granular, light gray.
  • +/-Eosinophils - often prominent.
  • +/-Fibrosis - common.
  • +/-Other inflammatory cells - neutrophils, plasma cells (uncommon).
  • +/-Multinucleated giant cells - uncommon.

DDx:

Images

  • LCH - very low mag. (WC/Nephron)

  • LCH - low mag. (WC/Nephron)

  • LCH - intermed. mag. (WC/Nephron)

  • LCH - very high mag. (WC/Nephron)

www

IHC

  • CD1a +ve.
  • S100 +ve.
  • CD207 (AKA Langerin) +ve.[8]

Molecular

  • Commonly have BRAF mutations ~ 40-70% of cases.[9]
    • The V600E mutation is the most common BRAF mutation.[10]
    • MAP2K1 mutations are often found in the cases without BRAF mutations.[9][11]

Electron microscopy

Etiology:

  • Cell membrane invagination.[12]

Appearance:

  • Electron dense, cytoplasmic tennis racket-like body.

Images:

See also

References

  1. ↑ 1.0 1.1 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 338-9. ISBN 978-1416054542.
  2. ↑ 2.0 2.1 Chhabra, UD.; Desai, SS.; Jambhekar, NA. (Jul 2004). "Langerhans' cell histiocytosis: a clinicopathological study of 50 cases.". Indian J Pathol Microbiol 47 (3): 370-6. PMID 16295427.
  3. ↑ Minkov, M. (Apr 2011). "Multisystem Langerhans cell histiocytosis in children: current treatment and future directions.". Paediatr Drugs 13 (2): 75-86. doi:10.2165/11538540-000000000-00000. PMID 21351807.
  4. ↑ Garg, A.; Kumar, P. (Jan 2012). "Multisystem Langerhans cell histiocytosis in adult.". Indian J Dermatol 57 (1): 58-60. doi:10.4103/0019-5154.92683. PMID 22470214.
  5. ↑ Badalian-Very, G.; Vergilio, JA.; Degar, BA.; MacConaill, LE.; Brandner, B.; Calicchio, ML.; Kuo, FC.; Ligon, AH. et al. (Sep 2010). "Recurrent BRAF mutations in Langerhans cell histiocytosis.". Blood 116 (11): 1919-23. doi:10.1182/blood-2010-04-279083. PMID 20519626.
  6. ↑ Badalian-Very, G.; Vergilio, JA.; Degar, BA.; Rodriguez-Galindo, C.; Rollins, BJ. (Jan 2012). "Recent advances in the understanding of Langerhans cell histiocytosis.". Br J Haematol 156 (2): 163-72. doi:10.1111/j.1365-2141.2011.08915.x. PMID 22017623.
  7. ↑ BN. 15 March 2011.
  8. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 604862
  9. ↑ 9.0 9.1 Alayed, K.; Medeiros, LJ.; Patel, KP.; Zuo, Z.; Li, S.; Verma, S.; Galbincea, J.; Cason, RC. et al. (Feb 2016). "BRAF and MAP2K1 mutations in Langerhans cell histiocytosis: a study of 50 cases.". Hum Pathol. doi:10.1016/j.humpath.2015.12.029. PMID 26980021.
  10. ↑ Tatsuno, M.; Shioda, Y.; Iwafuchi, H.; Yamazaki, S.; Iijima, K.; Takahashi, C.; Ono, H.; Uchida, K. et al. (2016). "BRAF V600 mutations in Langerhans cell histiocytosis with a simple and unique assay.". Diagn Pathol 11 (1): 39. doi:10.1186/s13000-016-0489-z. PMID 27094161.
  11. ↑ Chakraborty, R.; Hampton, OA.; Shen, X.; Simko, SJ.; Shih, A.; Abhyankar, H.; Lim, KP.; Covington, KR. et al. (Nov 2014). "Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis.". Blood 124 (19): 3007-15. doi:10.1182/blood-2014-05-577825. PMID 25202140.
  12. ↑ URL: http://path.upmc.edu/cases/case147/micro.html. Accessed on: 7 January 2012.
  13. ↑ URL: http://path.upmc.edu/cases/case298.html. Accessed on: 14 January 2012.
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