Neurofibroma pathophysiology: Difference between revisions

Jump to navigation Jump to search
Line 3: Line 3:
{{CMG}}; {{AE}}{{S.M.}}{{SC}}
{{CMG}}; {{AE}}{{S.M.}}{{SC}}
==Overview==
==Overview==
Neurofibromas arise from the nonmyelinating-type [[Schwann cells]]. Gene involved in the pathogenesis of [[plexiform neurofibroma]] is ''[[Neurofibromatosis type I|NF1]]'' which codes for neurofibromin that leads to loss of ''[[RAS]]'' [[control]] causing increased [[Activity (chemistry)|activity]] of [[Downstream (molecular biology)|downstream]] [[RAS]] pathways involved in increased [[Cell (biology)|cell]] [[growth]] and [[Survival rate|survival]]. [[Neurofibroma|Neurofibromas]] can occur anywhere in [[body]]. On gross pathology, a nonencapsulated superficial [[mass]] is the characteristic finding of localised or diffuse neurofibroma; whereas the "bag of worms" appearance is the characteristic finding of [[plexiform neurofibroma]]. On microscopic histopathological analysis, nerve fibers, schwann cells, [[spindle cell]]s with wavy [[nuclei]] without pleomorphism, shredded carrot [[collagen]], moderate increase of cellularity vis-a-vis normal [[dermis]], blood vessels, [[mast cells]], pseudomeissnerian [[Body|bodies]], and varying [[Degree (angle)|degrees]] of myxoid [[degeneration]] are characteristic findings of neurofibroma. Electron microscopy of neurofibromas shows [[Schwann cells]] enclosing [[axons]] in plasmalemmal [[Invagination|invaginations]] (mesaxons).
Neurofibromas arise from the nonmyelinating-type [[Schwann cells]]. Gene involved in the pathogenesis of [[plexiform neurofibroma]] is ''[[Neurofibromatosis type I|NF1]]'' which codes for neurofibromin that leads to loss of ''[[RAS]]'' [[control]] causing increased [[Activity (chemistry)|activity]] of [[Downstream (molecular biology)|downstream]] [[RAS]] pathways involved in increased [[Cell (biology)|cell]] [[growth]] and [[Survival rate|survival]]. [[Neurofibroma|Neurofibromas]] can occur anywhere in [[body]]. On gross pathology, a nonencapsulated superficial [[mass]] is the characteristic finding of localised or diffuse neurofibroma; whereas the "bag of worms" appearance is the characteristic finding of [[plexiform neurofibroma]]. On microscopic histopathological analysis, nerve fibers, schwann cells, [[spindle cell]]s with wavy [[nuclei]] without pleomorphism, shredded carrot [[collagen]], moderate increase of cellularity vis-a-vis normal [[dermis]], blood vessels, [[mast cells]], pseudomeissnerian [[Body|bodies]], and varying [[Degree (angle)|degrees]] of myxoid [[degeneration]] are characteristic findings of neurofibroma. However, plexiform neurofibroma shows a characteristic target sign on [[Histopathology|histopathology,]] representing a [[central]] [[Core (anatomy)|core]] of [[collagenous]] and [[Fibril|fibrillary]] [[Tissue (biology)|tissue]] with peripheral less [[Dense|densely]] [[cellular]] myxoid [[Tissue (biology)|tissue]]. Electron microscopy of neurofibromas shows [[Schwann cells]] enclosing [[axons]] in plasmalemmal [[Invagination|invaginations]] (mesaxons).


==Pathogenesis==
==Pathogenesis==

Revision as of 17:48, 30 April 2019

Neurofibroma Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Neurofibroma from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

Staging

History and Symptoms

Physical Examination

Laboratory Findings

X Ray

CT

MRI

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

Neurofibroma pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Neurofibroma pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Neurofibroma pathophysiology

CDC on Neurofibroma pathophysiology

Neurofibroma pathophysiology in the news

Blogs on Neurofibroma pathophysiology

Directions to Hospitals Treating Neurofibroma

Risk calculators and risk factors for Neurofibroma pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[3]Shanshan Cen, M.D. [4]

Overview

Neurofibromas arise from the nonmyelinating-type Schwann cells. Gene involved in the pathogenesis of plexiform neurofibroma is NF1 which codes for neurofibromin that leads to loss of RAS control causing increased activity of downstream RAS pathways involved in increased cell growth and survival. Neurofibromas can occur anywhere in body. On gross pathology, a nonencapsulated superficial mass is the characteristic finding of localised or diffuse neurofibroma; whereas the "bag of worms" appearance is the characteristic finding of plexiform neurofibroma. On microscopic histopathological analysis, nerve fibers, schwann cells, spindle cells with wavy nuclei without pleomorphism, shredded carrot collagen, moderate increase of cellularity vis-a-vis normal dermis, blood vessels, mast cells, pseudomeissnerian bodies, and varying degrees of myxoid degeneration are characteristic findings of neurofibroma. However, plexiform neurofibroma shows a characteristic target sign on histopathology, representing a central core of collagenous and fibrillary tissue with peripheral less densely cellular myxoid tissue. Electron microscopy of neurofibromas shows Schwann cells enclosing axons in plasmalemmal invaginations (mesaxons).

Pathogenesis

Mast cells and the neurofibroma microenvironment. Potential cellular interactions in the plexiform neurofibroma microenvironment. NGF indicates nerve growth factor; and MMP, matrix metalloproteinase. Source: Staser Karl. et al

Genetics

Gross Pathology

Neurofibromas can occur anywhere in body. Following are the gross features of different types of neurofibromas:

Localised neurofibroma and Diffuse neurofibroma

Soft tissue neurofibroma

Plexiform neurofibroma

Large neurofibroma in a NF1 case (WC/jensflorian) [1]
Plexiform Neurofibroma of the Bladder. Horizontally oriented cross section of the tumor shows the bladder mucosa (M) surrounded by masses of nodules. Arrows = locations of the ureteric orifices. (Scale is in centimeters.)Source: Wilkinson LM. et al, From the Department of Medical Imaging, Hospital for Sick Children, Toronto, Ontario, Canada.
Gallbladder neurofibroma presenting as chronic epigastric pain - Case report and review of the literature. Intact gallbladder specimen following the operation. Neurofibroma extended along the inferior wall of the gallbladder from the cystic duct to the fundus, protruding extraluminally.Source: Sucandy I. et al, Department of Surgery, Abington Memorial Hospital, Abington, Pennsylvania, USA.
Gallbladder neurofibroma presenting as chronic epigastric pain - Case report and review of the literature. Opened gallbladder specimen showing mural nodules and normal mucosa. Gallbladder appeared to be normal without signs of inflammation. Silk sutures were used to ligate the cystic duct prior to division.Source: Sucandy I. et al, Department of Surgery, Abington Memorial Hospital, Abington, Pennsylvania, USA.
Plexiform neurofibroma of the submandibular gland in patient with von Recklinghausen's disease Photograph showed left ankle cutaneous neurofibroma (A), right forearm cutaneous neurofibroma (B), and Cafè -au-lait spots found on the body of the patient (C).Bisher HA. et al, Department of Surgery, Abington Memorial Hospital, Abington, Pennsylvania, USA.

Microscopic Pathology

Neurofibroma with Degenerative Atypia ("Ancient change")

Soft tissue neurofibromas

Plexiform neurofibromas

Plexiform Neurofibroma of the Bladder. Photomicrograph (original magnification, ×100; hematoxylin-eosin stain) shows that the oval plexiform neurofibroma (PNF) has a denser outer core with areas that have a looser configuration. It is surrounded by fibrous tissue and pushes aside elongated smooth muscle cells (SM). (b) Photomicrograph (original magnification, ×400; hematoxylin-eosin stain) shows that the plexiform neurofibroma (PNF) has variable architecture. On the right, the tumor cells have a wavy, parallel arrangement; on the left, the cells are arranged more loosely and haphazardly. There is no true capsule. The tumor pushes aside bundles of smooth muscle cells (SM).Source: Wilkinson LM. et al, From the Department of Medical Imaging, Hospital for Sick Children, Toronto, Ontario, Canada.
Plexiform Neurofibroma of the Bladder. Photomicrograph (original magnification, ×100; hematoxylin-eosin stain) shows that the oval plexiform neurofibroma (PNF) has a denser outer core with areas that have a looser configuration. It is surrounded by fibrous tissue and pushes aside elongated smooth muscle cells (SM). (b) Photomicrograph (original magnification, ×400; hematoxylin-eosin stain) shows that the plexiform neurofibroma (PNF) has variable architecture. On the right, the tumor cells have a wavy, parallel arrangement; on the left, the cells are arranged more loosely and haphazardly. There is no true capsule. The tumor pushes aside bundles of smooth muscle cells (SM).Source: Wilkinson LM. et al, From the Department of Medical Imaging, Hospital for Sick Children, Toronto, Ontario, Canada.
Gallbladder neurofibroma presenting as chronic epigastric pain - Case report and review of the literature. Histologic appearance of gallbladder neurofibroma. Photomicrograph shows diffuse neurofibroma cells with short fusiform and round shapes within fine fibrillary collagen matrix.Source: Sucandy I. et al, Department of Surgery, Abington Memorial Hospital, Abington, Pennsylvania, USA.
Photomicrograph of the plexiform neurofibroma, Histopathological image of the plexiform neurofibroma along with normal glandular tissue (Hematoxylin-Eosin stain) (A), Elongated, spindly cells with wavy nuclei (Hematoxylin-Eosin stain) (B), Immuno-positive staining for the S-100 protein (C).Source: Bisher HA. et al, Department of Surgery, Abington Memorial Hospital, Abington, Pennsylvania, USA.

Electron microscopy

References

  1. Muir D, Neubauer D, Lim IT, Yachnis AT, Wallace MR. (2003). "Tumorigenic properties of neurofibromin-deficient neurofibroma Schwann cells". American Journal of Pathology. 158 (2): 501–13. doi:10.1016/S0002-9440(10)63992-2. PMC 1850316. PMID 11159187.
  2. 2.0 2.1 Bernthal, NM.; Jones, KB.; Monument, MJ.; Liu, T.; Viskochil, D.; Randall, RL. (2013). "Lost in translation: ambiguity in nerve sheath tumor nomenclature and its resultant treatment effect". Cancers (Basel). 5 (2): 519–28. doi:10.3390/cancers5020519. PMID 24216989.
  3. 3.0 3.1 Staser, K.; Yang, FC.; Clapp, DW. (2010). "Mast cells and the neurofibroma microenvironment". Blood. 116 (2): 157–64. doi:10.1182/blood-2009-09-242875. PMID 20233971. Unknown parameter |month= ignored (help)
  4. Neurofibroma. Wikipedia 2015. https://en.wikipedia.org/wiki/Neurofibroma#cite_note-Yamashiroya2002-3 Accessed on November 17, 2015
  5. Mautner VF, Friedrich RE, von Deimling A, Hagel C, Korf B, Knöfel MT, Wenzel R, Fünsterer C. (2003). "Malignant peripheral nerve sheath tumours in neurofibromatosis type 1: MRI supports the diagnosis of malignant plexiform neurofibroma". American Journal of Pathology. 45 (9): 618–25. doi:10.1007/s00234-003-0964-6. PMID 12898075.
  6. http://www.bloodjournal.org/content/116/2/157?sso-checked=true
  7. 7.0 7.1 Neurofibroma. Dr Bruno Di Muzio and Dr Maxime St-Amant et al. Radiopaedia.org 2015. http://radiopaedia.org/articles/neurofibroma. Accessed on November 17, 2015
  8. MH Shen, PS Harper, M Upadhyaya. (1996). "Molecular genetics of neurofibromatosis type 1 (NF1)". Journal of Medical Genetics. 33 (1): 2–17. doi:10.1136/jmg.33.1.2. PMC 1051805. PMID 8825042.
  9. Rubin JB, Gutmann DH. (2005). "Neurofibromatosis type 1 - a model for nervous system tumour formation?". Nature Reviews Cancer. 5 (7): 557–64. doi:10.1038/nrc1653. PMID 16069817.
  10. Johnson MR, Look AT, DeClue JE, Valentine MB, Lowy DR. (1993). "Inactivation of the NF1 gene in human melanoma and neuroblastoma cell lines without impaired regulation of GTP.Ras". Proceedings of the National Academy of Sciences of the USA. 90 (12): 5539–43. doi:10.1073/pnas.90.12.5539. PMC 46756. PMID 8516298.
  11. Wilkinson LM, Manson D, Smith CR (2004). "Best cases from the AFIP: plexiform neurofibroma of the bladder". Radiographics : a Review Publication of the Radiological Society of North America, Inc. 24 Suppl 1: S237–42. doi:10.1148/rg.24si035170. PMID 15486243. Retrieved 2015-11-13.
  12. Neurofibroma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Neurofibroma#cite_note-pmid15486243-2 Accessed on November 17, 2015
  13. Neurofibroma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Neurofibroma#cite_note-pmid15486243-2 Accessed on November 17, 2015
  14. http://surgpathcriteria.stanford.edu/peripheral-nerve/neurofibroma/
  15. Neurofibroma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Neurofibroma#cite_note-pmid15486243-2 Accessed on November 17, 2015
  16. https://pubs.rsna.org/doi/10.1148/rg.24si035170#REF8


Template:WikiDoc Sources