Indian Journal of Dermatology
  Publication of IADVL, WB
  Official organ of AADV
Indexed with Science Citation Index (E) , Web of Science and PubMed
 
Users online: 372  
Home About  Editorial Board  Current Issue Archives Online Early Coming Soon Guidelines Subscriptions  e-Alerts    Login  
    Small font sizeDefault font sizeIncrease font size Print this page Email this page


 
Table of Contents 
RESIDENTS PAGE
Year : 2013  |  Volume : 58  |  Issue : 4  |  Page : 327
Civatte bodies: A diagnostic clue


Department of Immunopathology, PGIMER, Chandigarh, India

Date of Web Publication25-Jun-2013

Correspondence Address:
Chhabra Seema
Department of Immunopathology, PGIMER, Sector-12, Chandigarh
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.113974

Rights and Permissions



How to cite this article:
Pranay T, Kumar AS, Seema C. Civatte bodies: A diagnostic clue. Indian J Dermatol 2013;58:327

How to cite this URL:
Pranay T, Kumar AS, Seema C. Civatte bodies: A diagnostic clue. Indian J Dermatol [serial online] 2013 [cited 2019 Jul 22];58:327. Available from: http://www.e-ijd.org/text.asp?2013/58/4/327/113974



   Introduction Top


The presence of numerous civatte bodies (CBs) in biopsies is a characteristic finding in skin lesions of patients with various dermatoses, particularly lichen planus (LP) and discoid lupus erythematosus (DLE). In the absence of a clear diagnosis, their presence is suggestive of disorders characterized by interface dermatitis. These bodies are generated by damaged basal keratinocytes through apoptotic cell death, consist largely of keratin intermediate filaments, and are almost invariably covered with immunoglobulins, mainly IgM. Although CBs can be found in whole lot of conditions as described in [Table 1], yet they are an important diagnostic finding in conditions like LP and DLE.
Table 1: Diseases which can reveal civatte body deposits


Click here to view



   History Top


CBs have been variously termed cytoid, hyaline, colloid, or keratin bodies. Their formation and transport were initially explained by Sabouraudin (1910). [1] One of the groups in 1970s studied the origin of CBs and proved its derivation from degenerated epidermal keratinocytes. [2],[3] Some investigators have also described that CBs may be derived from melanocytes. [4]

  • Apoptosis and CBs: Apoptosis or physiologic cell death is a process of genetically programmed cell death by which senescent and diseased cells are eliminated from the body. [5] The cell undergoing apoptosis is represented by a cytoplasmic remnant existing as small shrunken cell or hyaline residue. [6] Earlier studies have described the CBs to be typical of apoptotic cells. [6]



   Pathogenesis Top


There are two proposed causative mechanisms, one of which describes apoptosis of keratinocytes in which they are found locally both in the epidermis and papillary dermis. [7] The second source is the destruction of the thickened basement membrane of cells by any physiologic/pathologic mechanism which limits them in the papillary dermis region. [8] Most common theory behind generation of CBs is apoptosis of keratinocytes that may occur in any interface dermatitis in which damage to the basal cells occurs. Such dead cells may be either eliminated from the epidermis transepidermally toward the stratum corneum or expelled toward dermis if apoptotic cells was in basal layer. [2] These dropped-off filamentous cells or masses may subsequently be phagocytosed by macrophages or provide a matrix for the deposition of complement fragments, immunoglobulins, and fibrin suggesting the activation of complement as well as fibrinogen cascade.These products in turn act as chemoattractants for leukocytes leading to augmentation of inflammatory response, which perpetuates the basal cell damage. Hence, positive immunofluorescence findings represent possible secondary immunological process rather than a primary one. Further elucidation of the facts is needed to validate whether these events are a cause or effect of pathological processes in interface dermatitis. [9]


   Morphology Top


Light microscopy

CBs are seen as rounded, homogenous, eosinophilic masses on routine H and E staining lying in the deeper parts of epidermis/epithelium and more frequently in dermis/connective tissue. They are known as CBs (in epithelium/epidermis), colloid bodies, or hyaline bodies (in connective tissue). They are 10-25 μm in diameter and situated mostly within or above the inflammatory cell infiltrate. In LP, the number of necrotic keratinocytes may be so large that they are seen lying in clusters in the uppermost dermis [Figure 1]. These bodies show a positive periodic acid Schiff (PAS) reaction and are diastase resistant. [9]
Figure 1: Photomicrograph from a case of lichen planus (LP) showing rounded, homogenous, eosinophilic cytoid body at the dermoepidermal junction (H and E, ×400)

Click here to view


Electron microscopy

Ultrastructurally, CBs are made up of whorls or distinct filaments (60-80 Ε), which may be attached to desmosomes. [2] The nuclei in them are lost by condensation or diffuse disintegration and the cytoplasm may show vacuoles. [2] The adjoining dermal phagocytes show the evidence of filaments in their cytoplasm which were forming the CBs. [2] The CBs may contain chromosomes, centrioles, nuclear membrane particles, and spindle tubules. [2] The ultrastructural diversity in morphology of the nuclear material appearing within these bodies indicates a high probability of cells being converted to CBs at any stage during cell division. [2] The objective recognizable evidence of mitosis recedes with the advancement of degenerative changes. [2]

Direct immunofluorescence microscopy

On direct immunofluorescence (DIF) microscopy, CBs may be observed in about 10% of skin biopsies. They can be seen as scattered or grouped bodies in the epidermis, along or underneath the dermal-epidermal junction (DEJ), with or without other positive DIF findings [Figure 2]. There have been extensive studies in past which have demonstrated immunoreactant deposits at CBs in a wide variety of diseases. [10],[11] All types of immunoglobulin (Ig) subclasses like IgG, IgA, IgM, complement components (C3), and fibrinogen can be demonstrated on CBs, but IgM is the most common immunoreactant deposit in LP, [7],[8] bullous pemphigoid, and erythema multiforme. [10]
Figure 2: Direct immunofluorescence (DIF) photomicrograph showing IgM reactive large grouped globular (++) deposits (civatte body) in the papillary dermis (anti-IgM, ×400)

Click here to view


Presence of CBs alone or in combination with other immunoreactant deposits at DEJ can help in differentiating the diseases presenting sometimes with close overlapping features, for example, LP and DLE. In these clinically and histopathologically equivocal cases, there is a need to concentrate on CBs on DIF examination of skin biopsies. [11] It is always important to consider the number of CBs (few vs. numerous); their location (epidermis vs. papillary dermis); their arrangement (singly scattered vs. clustering); immunoreactant deposit (IgM or others), number (single vs. combination), and intensity (brighter vs. dim) of various positive immunoreactants at CBs. The presence of additional positive immunofluorescence findings along with CBs in the same biopsy further help in clinching a final diagnosis, for example, shaggy fibrin/granular Ig deposits at DEJ and superficial blood vessels (SBVs). So it is important to look at the DIF slide as a whole, while taking into consideration clinical and histopathological features.

The features that are more in favor of LP include the following: CBs alone without any other positive immunofluorescence finding, CBs numerous in number, CBs arranged in clusters of 10 or more in the papillary dermis, CBs showing a brighter intensity for IgM along with positivity for a combination of various types of immunoreactants (seen in 55% cases), sometimes involving more than 3 immunoreactants (22% cases), and a combination of fibrin deposition at the DEJ. There is generally an absence of granular Ig deposits at DEJ and SBVs. Here, the noteworthy point is that some cases of LP do not show any CBs, and this may be due to phagocytosis of these apoptotic bodies in older lesions. There is no statistically significant difference in the positive DIF yield between specimens derived from skin and from oral lesions.

However, in lesions of LE, presence of CBs along with deposits at DEJ and SBVs is more common. LE lesions are likely to contain deposits of Ig and C3 at the DEJ. If IgM is present, there is a high probability that the patient has LE. Although C3 deposition occurs more frequently in LE than in LP, its presence has a low diagnostic value. The pattern of staining seen in the DEJ in LE is more likely to be a granular, broad, discontinuous band, but it may be smooth and continuous. Fibrinogen deposits may also be present, and CBs staining with Igs, C3, and/or fibrinogen may or may not be seen.


   Other Associated Diseases Top


CBs are also associated with actinic cheilitis, [12] acute generalized exanthematous pustulosis, [12] drug reaction with eosinophilia and systemic symptoms, [12] granulomatous rosacea, [12] lichen striatus, [12] prurigo pigmentosa, [12] pyoderma gangrenosum, [12] dermatitis herpetiformis, [7] porphyria cutanea tarda, [7] keratosis follicularis, Darier's disease, [7] familial benign chronic pemphigus, [7] and even normal skin. [3]

 
   References Top

1.Sabouraud R. Sur quelques points de l'anatomiepathologique du lichen plan de Wilson. Annl Derm Syph 1910;1:491-505. Quoted in: Griffin CJ, Jolly M, Smythe JD. The fine structure of epithelial cells in normal and pathological buccal mucosa. II. Colloid body formation. Aust Dent J 1980;25:12-9.  Back to cited text no. 1
    
2.Hashimoto K. Apoptosis in lichen planus and several other dermatoses. Intra-epidermal cell death with filamentous degeneration. Acta Derm Venereol 1976;56:187-210.  Back to cited text no. 2
    
3.Blenkinsopp WK, Clayton RJ, Haffenden GP. Immunoglobulin and complement in normal skin. J Clin Pathol 1978;31:1143-6.  Back to cited text no. 3
    
4.Ishibashi Y, Tsuru N, Kukita A. The "colloid body": Its nature and pathogenesis. J Dermatol 1978;5:199-208.  Back to cited text no. 4
    
5.Kerr JF, Wyllie AH, Currie AR. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972;26:239-57.  Back to cited text no. 5
    
6.Weedon D. Letter: Civatte bodies and apoptosis. Br J Dermatol 1974;91:357.  Back to cited text no. 6
    
7.Ueki H. Hyaline bodies in subepidermal papillae. Immunohistochemical studies in several dermatoses. Arch Dermatol 1969;100:610-7.  Back to cited text no. 7
    
8.Bursch W, Kleine L, Tenniswood M. The biochemistry of cell death by apoptosis. Biochem Cell Biol 1990;68:1071-4.  Back to cited text no. 8
    
9.Abell E, Presbury DG, Marks R, Ramnarain D. The diagnostic significance of immunoglobulin and fibrin deposition in lichen planus. Br J Dermatol 1975;93:17-24.  Back to cited text no. 9
    
10.Wu YH, Lin YC. Cytoid bodies in cutaneous direct immunofluorescence examination. J Cutan Pathol 2007;34:481-6.  Back to cited text no. 10
    
11.Chularojanamontri L, Tuchinda P, Triwongwaranat D, Pinkaew S, Kulthanan K. Diagnostic significance of colloid body deposition in direct immunofluorescence. Indian J Dermatol Venereol Leprol 2010;76:373-7.  Back to cited text no. 11
[PUBMED]  Medknow Journal  
12.Finan MC, Schroeter AL. Cutaneous immunofluorescence study of erythema multiforme: Correlation with light microscopic patterns and etiologic agents. J Am Acad Dermatol 1984;10:497-506.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]



 

Top
Print this article  Email this article
 
 
  Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Article in PDF (938 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


   Introduction
   History
   Pathogenesis
   Morphology
    Other Associated...
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed3535    
    Printed42    
    Emailed0    
    PDF Downloaded436    
    Comments [Add]    

Recommend this journal