ligneous inflammation of the female genital tract
DESCRIPTION
Ligneous inflammation (LI) is characterized by pseudomembranes andinflammation. A possible autoimmune etiology similar to lichen sclerosus is proposed. There have been no series of LI involving the female genital tract (FGT). In this study, we aimed to characterize the morphology, genotype and immunophenotype of LI of the FGT.TRANSCRIPT
G Caponetti1; C Otis1; I Mert2; S Marconi1; V Schuster3; M Ziegler3; K Tefs3; J Hecht4; M Tug2 and L Pantanowitz1 1Baystate Medical Center/Tufts University, Springfield, MA; 2Zekai Tahir Burak Hospital, Ankara, Turkey;
3University of Leipzig, Leipzig, Germany and 4Beth Israel Deaconess Medical Center, Boston, MA.
ABSTRACT
Background: Ligneous inflammation (LI) is characterized by pseudomembranes and
inflammation. A possible autoimmune etiology similar to lichen sclerosus is proposed. There
have been no series of LI involving the female genital tract (FGT). We aimed to characterize
the morphology, genotype and immunophenotype of LI of the FGT.
Design: Tissue from 4 patients with LI (12 specimens), 10 of chronic cervicitis (CC), and 10 of
vulvar lichen sclerosus (LS) were studied. Sections were stained with H&E, PAS, PTAH,
Congo Red, CD3, CD4, CD8 and CD20. The distribution and proportion (graded 0-4) of T&B
cells was recorded. DNA from LI patients was studied for mutations in the plasminogen gene
(PLG) by PCR and direct sequencing.
Results: LI patients were of mean age 41 years, 2 with low plasminogen antigen and
functional activity (12% & 18% of normal). LI on biopsy showed abundant stromal deposits of
eosinophilic (Fig. 1), PAS+, PTAH+, Congo Red negative fibrin associated with chronic
inflammation. Table 1 shows the inflammatory infiltrate of LI resembles CC more than LS. In
LI cases with low plasminogen, there was a homozygous mutation in one patient and a
heterozygous mutation in another. No mutations were found in the other 2 women with LI.
Multiple PLG polymorphisms were detected in all four LI patients.
Conclusion: LI of the FGT is related to plasminogen deficiency secondary to PLG genetic
defects. Mutations in unidentified regulatory sequences of the PLG may explain the lack of
demonstrable genetic mutations in some cases. Failure of plasminogen to remove fibrin results
in tissue deposition. Given this molecular mechanism, and evidence that the inflammatory
infiltrate resembles a reactive process, a role for autoimmunity in LI appears unlikely.
The authors have no potential conflicts of interest to disclose.
BACKGROUND
Ligneous inflammation (LI) of the female genital tract is an uncommon but
distinctive condition, characterized by ligneous (“woody”) pseudomembranes
with subepithelial fibrin deposition and associated inflammation1.
The condition can be associated with infertility, and can involve extragenital
sites, most commonly the eyes (i.e. ligneous conjunctivitis), middle ear and oral
mucosa.
LI has been recently shown to be due to mutation(s) of the plasminogen gene
(PLG) and subsequent plasminogen deficiency, with failure to remove fibrin
upon deposition in injured mucosal tissue2.
A possible autoimmune etiology has been suggested3,4.
OBJECTIVE
The aim of this study is to characterize the morphological and genotypic
profile of LI of the female genital tract, and to define the immunophenotype
and nature of the associated inflammatory infiltrate through a comparative
case control study.
Ligneous Inflammation of the Female Genital Tract: Morphologic, Immunophenotypic, and Molecular Characterization
Medizinische Fakultät
RESULTS
The patients with LI (age range 20-82 year-old) presented with some of the
following complaints: primary infertility, dysmenorrhea, dyspareunia,
poscoital bleeding, pelvic pain, post-menopausal vaginal bleeding, vaginal
discharge, conjunctivitis and gingivitis.
Decreased plasminogen activity and antigen (12% 18% of normal) was
detected in two patients with LI.
Other laboratory values, including standard coagulation tests were within
normal values in all four LI cases.
H&E stains of the LI cases (n=12) revealed stromal deposits of amorphous
acellular eosinophilic material, consistent with fibrinous deposits, with diffuse
moderate chronic subepithelial and intraepithelial inflammatory infiltrates.
(Fig.1)
The cases of CC showed subepithelial and intraepithelial inflammatory
infiltrates, congestive vessels and mild edema in the connective tissue, along
with variable reactive epithelial changes. (Fig.1)
LS lesions were characterized by homogenous, acellular zones of subepithelial
sclerosis and band-like chronic inflammatory infiltrates. (Fig.1)
The proportion of CD3 and CD20 lymphocytes and their location was similar
in the LI and CC cases, and different from that of the LS cases. (Table 1)
Molecular genetic analysis of the PLG in the two LI patients with low
plasminogen yielded a type-1 homozygous K19E mutation in one patient and a
type-1 heterozygous K19E mutation in the other.
No mutations were identified in the PLG of the two patients with unknown
plasminogen levels.
Several PLG heterozygous and homozygous polymorphisms were detected in
all four patients.
CONCLUSION
LI of the FGT is related to plasminogen deficiency secondary to PLG genetic
defects.
Failure of plasminogen to remove fibrin results in tissue deposition.
Mutations in unidentified regulatory sequences of the PLG may explain the
lack of demonstrable genetic mutations in some cases.
Given this molecular mechanism, and evidence that the inflammatory
infiltrate resembles a reactive process, a role for autoimmunity in LI appears
unlikely.
REFERENCES
1. Karaer A, et al. Ligneous inflammation involving the female genital tract. J Obstet Gynaecol Res.
2007;33(4):581-4.
2. Tefs K, et al. Molecular and clinical spectrum of type I plasminogen deficiency: A series of 50
patients. Blood. 2006;108(9):3021-6.
3. Deen S, et al. Ligneous cervicitis; is it the emperor's new clothes? Case report and different analysis
of aetiology. Histopathology. 2006;49(2):198-9.
4. Scurry J, et al. Ligneous (pseudomembranous) inflammation of the female genital tract. A report of
two cases. J Reprod Med. 1993;38(5):407-12.
DESIGN
Tissue from 4 patients with LI (12 specimens), 10 of chronic cervicitis (CC),
and 10 of vulvar lichen sclerosus (LS) were studied.
Sections were stained with H&E, PAS, PTAH, Congo Red, CD3, CD4, CD8
and CD20.
The distribution and proportion (graded 0-4) of T and B lymphocytes was
recorded. (0=None, 1=Rare, 2=Few, 3=Several, 4=Many)
DNA from LI patients was studied for mutations in the plasminogen gene
(PLG) by PCR and direct sequencing.
Fig.1: Comparison of the histological appearance on H&E and the immunophenotypes of
Ligneous Inflammation (LI), Lichen Sclerosus (LS) and Chronic Cervicitis (CC).
LI
LS
CC
H&E CD3 CD20