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Year : 2020  |  Volume : 63  |  Issue : 4  |  Page : 600-603
Histopathology of morphea: Sensitivity of various named signs, a retrospective study


1 Department of Dermatology, Venereology, and Leprosy, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Dehradun, Uttarakhand, India
2 Department of Pathology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Dehradun, Uttarakhand, India

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Date of Submission21-Jan-2020
Date of Decision16-Mar-2020
Date of Acceptance18-Mar-2020
Date of Web Publication28-Oct-2020
 

   Abstract 


Background: Morphea or localized scleroderma is characterized histopathologically by sclerosis, fibrosis, and atrophy of the skin and subcutaneous tissue. Various authors have named the characteristic findings seen in histopathology of morphea and have labeled them as specific signs, including line sign, cookie-cutter sign, and square biopsy sign. Besides, other findings mentioned include high eccrine glands and the presence of interstitial mucin. The present study was undertaken to assess the sensitivity of these tests in the histopathological diagnosis of morphea. Methods: All cases clinically diagnosed and histopathologically reported as morphea in the last 3 years (September 2016 to August 2019) were included. The slides were reviewed by two independent investigators for the presence of line sign, cookie-cutter sign, square biopsy sign, high eccrine glands, and mucin. The sensitivity of these signs in accurately diagnosing morphea was assessed. Besides, specificity, positive predictive value, and negative predictive value of these signs were assessed using 40 random histopathology slides as controls. Results: The highest sensitivity was of high eccrine glands (82.5%) followed by the presence of mucin in the dermis (77.5%). Cookie-cutter sign and square biopsy signs were seen in 70% and 62.5% patients, respectively. Line sign was least sensitive of all, seen in 45% of biopsy specimens, but was most specific (82.5%). Conclusion: A fair number of biopsies of morphea displays the presence of high eccrine glands, mucin, cookie-cutter sign, square biopsy sign, and line sign. These signs thus can be of immense help to the dermatopathology trainees.

Keywords: Cookie cutter sign, high eccrine gland, line sign, morphea, mucin, square biopsy sign

How to cite this article:
Jindal R, Shirazi N, Chauhan P. Histopathology of morphea: Sensitivity of various named signs, a retrospective study. Indian J Pathol Microbiol 2020;63:600-3

How to cite this URL:
Jindal R, Shirazi N, Chauhan P. Histopathology of morphea: Sensitivity of various named signs, a retrospective study. Indian J Pathol Microbiol [serial online] 2020 [cited 2020 Nov 25];63:600-3. Available from: https://www.ijpmonline.org/text.asp?2020/63/4/600/299320





   Introduction Top


Morphea or localized scleroderma is characterized histopathologically by sclerosis, fibrosis, and atrophy of the skin and subcutaneous tissue. Its incidence varies between 4–27 per million per year.[1] Various authors have named the characteristic findings seen in histopathology of morphea and have labeled them as specific signs, including line sign (LS), cookie-cutter sign (CCS), and square biopsy sign (SBS).[2] Besides, other findings mentioned include high eccrine glands (HEG) and the presence of interstitial mucin.[3] The advantages of these signs presumably are the quicker diagnosis of morphea. However, these have not been well-studied or validated. The present study is being undertaken to assess the sensitivity, specificity, positive predictive value, and negative predictive value of these tests in the diagnosis of morphea. For those found to be highly sensitive, specific needs must be given due consideration while reporting histopathology of morphea.


   Objectives Top


To assess the sensitivity, specificity, positive predictive value, and negative predictive value of LS, CCS, SBS, HEG, and presence of interstitial mucin in the histopathological diagnosis of morphea.


   Methodology Top


This was a retrospective observational study. All cases clinically diagnosed and histopathologically reported as late-stage morphea in the last 3 years (September 2016 to August 2019) were included. The histopathology slides were reviewed by two independent investigators. Discordance was resolved by reaching a consensus after discussion. Hematoxylin and eosin-stained sections were assessed for the presence of the following features:

  1. Line sign (LS): Defined as a straight/linear interface between subcutis and sclerotic collagen of the reticular dermis as seen at scanning magnification.[3]
  2. Cookie-cutter sign (CCS): Defined as straight/parallel lateral edges of biopsy section as seen at scanning magnification.[3]
  3. Square biopsy sign (SBS): Defined as approximate 90 angles between the four corners of the biopsy section seen at scanning magnification.[3]
  4. High eccrine glands (HEG): Presence of eccrine glands in upper 2/3rd of the dermis as seen on scanning magnification.[3]
  5. Presence or absence of interstitial mucin as assessed at 40 × magnification.


The sensitivity of these tests in accurately diagnosing morphea was assessed. Simultaneously, 40 random slides taken as controls of different diagnoses [Table 1] were assessed for the presence of these signs to find the specificity, positive predictive value, and negative predictive valve. Statistical analysis was done using statistical package for social sciences (SPSS) version 22. Frequency along with percentage was calculated for qualitative variables.
Table 1: Diagnoses of control slides (n=40)

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   Results Top


A total of 40 cases were identified; 28 females and 12 males (female to male ratio of 2.3:1). The age of patients ranged from 3 to–48 years. Twenty-nine patients had limited plaque morphea, six had linear morphea, three disseminated plaque morphea, and one each had morphea en coup de sabre and pan-sclerotic morphea. Numbers of cases of morphea as well as controls showing positive signs have been depicted in [Figure 1]. High eccrine glands were seen in 33 [Figure 2], cookie-cutter sign in 28 [Figure 3]a and b], square biopsy sign in 25 [Figure 3]c and d], and line sign in 18 [Figure 4]a and [Figure 4]b slides of morphea. Mucin was present in 31 slides [Figure 5]a and [Figure 5]b of morphea. Sensitivity was highest for the presence of high eccrine glands (82.5%) [Figure 6]. Line sign had the lowest sensitivity (45%) but the highest specificity (85%). The presence of high eccrine glands had the highest positive (80%) and negative predictive value (82.5%) [Table 2]. [Figure 7] shows control slides showing positive LS, CCS, SBS, and HEG.
Figure 1: Number of cases of morphea and controls showing positive sign (n = 40)

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Figure 2: Presence of high eccrine glands (circle) in morphea (H and E, 4×)

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Figure 3: (a and b) Showing cookie-cutter sign (parallel lines), (c and d) Showing square biopsy sign (purple squares) in morphea (H and E, 4×)

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Figure 4: (a and b) Showing line sign (black arrows) in morphea (H and E, 4×)

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Figure 5: (a) Showing presence of dermal mucin in morphea (H and E, 40×), (b) Showing positive Alcian blue staining for mucin (40×)

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Figure 6: Sensitivity of line sign, cookie-cutter sign, square biopsy sign, high eccrine glands, and presence of interstitial mucin

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Table 2: Sensitivity, specificity, positive predictive value, and negative predictive value of LS, CCS, SBS, and HEG

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Figure 7: (a) Shows line sign (black arrow) in psoriasis vulgaris, (b) Shows high eccrine glands (blue circle) in prurigo nodularis, (c) Shows cookie-cutter sign (orange lines) in pityriasis rosea, and (d) Shows square biopsy sign (purple square) in lichen planus. (H and E, 4×)

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   Discussion Top


Morphea clinically presents as single or multiple indurated plaques with an active lilac border during the initial stages. Confirmation of the diagnosis is done on histopathology. Depending on the stage of the disease the histopathology characteristics vary.[4] The early inflammatory stage is characterized by the presence of lymphoplasmacytic infiltrate among thickened collagen bundles in the reticular dermis. With advancing lesion the infiltrate decreases and more collagen bundles are deposited which are closely packed and hypocellular. Furthermore, the eccrine glands become atrophic and the adipocytes surrounding them are replaced by collagen.[5] They appear to lie higher in the dermis due to excessive collagen deposition beneath them. At times a secondary cutaneous mucinosis is also noted between collagen bundles.[6]

It is said that even at scanning magnification diagnosis of morphea can be accurately established due to certain peculiar features. Most striking of them is the square shape of the biopsy while others include a CCS, HEG, and a straight interface between subcutis and dermis. Another important finding assessed at higher magnification is the presence of interstitial mucin. Though these findings are often taught to dermatopathology trainees, their usefulness in being diagnostic needs to be elucidated.[7],[8],[9]

Yang et al. reviewed the histopathology of 73 cases of morphea and found that HEG was the most sensitive feature seen in 86% of patients. The sensitivity of LS was 82% while SBS and CCS were seen in relatively fewer biopsies (13% and 20%, respectively). They also compared the histopathology of morphea with those of other sclerosing disorders and found that the presence of mucin was highly specific (95%) for morphea.[3] In the present study, we found LS to be highly specific (85%) for morphea though its sensitivity (45%) was least. The low sensitivity could be due to the inability to assess in six of the slides reviewed as they lacked the subcutaneous tissue. The presence of HEG in our study had the highest sensitivity, positive predictive value as well as negative predictive value. Drazin et al. have reported sensitivity of LS to be 81% and CCS to be 41%.[2] The main disadvantage of these named signs is their subjective assessment as there is the scope of wide interobserver variability.

The presence of mucin is usually not considered a feature of morphea but Rongioletti et al. have reported it to be a constant feature of morphea and scleroderma.[10] We were also able to see the presence of mucin in 77.5% of our cases though we did not confirm by special stains.

Thus, knowledge of these signs will help in the quick diagnosis of morphea and should be taught to dermatologists as well as pathologists.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Peterson LS, Nelson AM, Su WP, Mason T, O'Fallon WM, Gabriel SE. The epidemiology of morphea (localized scleroderma) in Olmsted County 1960-1993. J Rheumatol 1997;24:73-80.  Back to cited text no. 1
    
2.
Draznin M, Fung M. The line sign. J Cutan Pathol. 2006;33:80-1.  Back to cited text no. 2
    
3.
Yang S, Draznin M, Fung M. The “line sign” a rapid and efficient diagnostic test for morphea: Clinicopathological study of 73 cases. Am J Dermatopathol 2018;40:873-8.  Back to cited text no. 3
    
4.
Mertens JS, Seyger MMB, Turling RM, Radstake TRDJ, deJong EMGJ. Morphea and eosinophilic fasciitis: An update. Am J Clin dermatol 2017;18:491-512.  Back to cited text no. 4
    
5.
Orteu CH. Morphoea and allied scarring and sclerosing inflammatory dermatoses. In: Griffiths C, Barker J, Blelker T, Chalmers R, Creamer D, editors. Rook's Textbook of Dermatology. 9th ed. West Sussex: Wiley Blackwell; 2016. p. 57.1-29.  Back to cited text no. 5
    
6.
Weedon D. Weedon's Skin Pathology. 3rd ed. China: Churchill Livingstone Elsevier; 2010. p. 304-29.  Back to cited text no. 6
    
7.
Fung MA. Inflammatory diseases of the dermis and epidermis. In: Busam KJ, editor. Dermatopathology. 2nd ed. Philadelphia: Elsevier Saudners; 2015. p. 71-2.  Back to cited text no. 7
    
8.
Winfield H, Jaworsky C. Connective tissue diseases. In: Elder DE, editor. Lever's Histopathology of the Skin. 11th ed. Alphen aan den Rijn: Wolters Kluwer; 2015. p. 348-9.  Back to cited text no. 8
    
9.
Ferringer T. Alterations in collagen and elastin. In: Elston DM, Ferringer T, editors. Dermatopathology. 2nd ed. Philadelphia: Elsevier Saunders; 2014. p. 214-5.  Back to cited text no. 9
    
10.
Rongioletti F, Gambini C, Micalizzi C, Pastorino A, Rebora A. Mucin deposits in morphea and scleroderma. Dermatology 1994;189:157-8.  Back to cited text no. 10
    

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Correspondence Address:
Payal Chauhan
Department of Dermatology, Venereology, and Leprosy, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Doiwala - 248 140, Dehradun, Uttarakhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_67_20

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1], [Table 2]



 

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