Immunohistochemical characterisation and TNF-α expression of the granulomatous infiltration of the brainstem in a case of sudden death due to neurosarcoidosis

Forensic Sci Int. 2011 May 20;208(1-3):e1-5. doi: 10.1016/j.forsciint.2011.01.021. Epub 2011 Feb 24.


Neurosarcoidosis carries a mortality of 10%, over twice that of sarcoidosis overall, although it has been rarely reported as a cause of sudden death. The current evidence suggests that sarcoidosis results from an enhanced immune reaction to a variety of antigens, non-self or self which causes CD4 (helper-inducer) T-cell accumulation with a ratio of helper-inducer T cells to suppressor-cytotoxic T cells usually high in affected organs, activation and release of inflammatory cytokines, and formation of granulomatous lesions. Numerous cytokines and other mediators are produced by both activated macrophages and T lymphocytes bearing the CD4-helper phenotype during the granuloma responses. A number of data suggest that interferon-gamma (IFN-gamma) and cytokines such as TNF-α, IL-2, and IL-18 play a critical role in the formation of granulomas. In this article, we describe the clinical and pathological characteristics of a patient who suddenly died due to acute respiratory failure. Neurosarcoidosis with massive and extensive involvement of the brainstem was established as the cause of death. Western blot analysis in the patient demonstrated the TNF-α presence as a 51-kDa protein in the brain tissue. The immunohistochemical analysis showed a poor positiveness for CD4 in all samples around the granulomas, as well as moderate positiveness for CD8, CD15, and CD20; CD45 and CD68 showed a strong positiveness in all the brain samples. Histological findings, immunohistochemical analysis, and proteomic studies addressed the diagnosis of neurosarcoidosis with involvement of the nucleus of the solitary tract in the brainstem and central hypoventilation as the cause of death.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Brain / metabolism
  • Brain / pathology
  • Brain Diseases / diagnosis*
  • Brain Stem / metabolism*
  • Brain Stem / pathology
  • Death, Sudden / etiology
  • Death, Sudden / pathology
  • Forensic Pathology
  • Granuloma, Foreign-Body / metabolism*
  • Granuloma, Foreign-Body / pathology
  • Granuloma, Giant Cell / metabolism*
  • Granuloma, Giant Cell / pathology
  • Humans
  • Immunohistochemistry
  • Lung / pathology
  • Male
  • Microscopy, Confocal
  • Respiratory Insufficiency / etiology
  • Sarcoidosis / diagnosis*
  • Tumor Necrosis Factor-alpha / metabolism*


  • Antigens, CD
  • Tumor Necrosis Factor-alpha