2013, Cilt 29, Sayı 1, Sayfa(lar) 041-045
Histopathologic Analysis of Female Genital Tuberculosis: A Fifteen-Year Retrospective Study of 110 Cases in Eastern India
Santosh Kumar Mondal
Department of Pathology, Medical College, KOLKATA, INDIA
Anahtar Kelimeler: Tüberküloz, Kadın genital, Histopatoloji, HIV
Tüberküloz evrensel bir sağlık sorunudur ve önemli mortalite
ve morbidite nedenidir. Batı dünyasında nadir olmakla birlikte kadın
genital sistemi tüberkülozu Hindistan gibi gelişmekte olan ülkelerde
gündemdedir. Bu çalışmada, kadın genital sistemi tüberkülozunun
histolojik özellikleri ve diğer bulgular ile ilişkisi araştırılmaktadır.
Gereç ve Yöntem: Onbeş yıllık dönemde tanı konan toplam 92 olguda
110 kadın genital sistemi tüberkülozu çalışmaya alınmıştır. Olguların
yaşları 17-45 arasında değişmekteydi ve ortalama yaş 26,3 olarak
gözlendi. Tanıda küretaj biyopsi, histerektomi, histolojik inceleme,
kültür, Mycobacterium tuberculosis - Polimeraz Zincir Reaksiyonu,
laparoskopi, histerosalpingografi ve ultrasonografi kullanılmıştı.
Bulgular: Kadın genital sistemi tüberkülozu olguları infertilite (%65-
70), pelvik/ abdominal ağrı (%50-55) ve menstrual yakınmalarla
(%20-25) başvurmuşlardı. Kadın genital sistemi tüberkülozu vulva
(2), vajina (1), serviks (5), endometrium (66), tuba (24) ve ovaryumları
(12) tutmuştu. Olguların 66'sında endometrium tüberkülozu
yanısıra proliferatif, sekretuvar ve atrofik endometrium gözlendi (sırasıyla
53, 9, 4 olgu). Sadece 5 olguda HIV ko-enfeksiyonu gözlendi.
Olguların 7'sinde doku kesitlerinde asit fast basil saptandı.
Sonuç: Kadın genital sistemi tüberkülozu gelişmekte olan ülkelerde
nadir değildir ve infertilitenin önemli bir nedenidir. Çoğu çalışmada
tubular en sık tutulan organ olmasına karşılık, çalışmamızda
endometrium en sık tutulan organ olarak dikkati çekmektedir.
Morgagni first described genital tuberculosis in the
mid eighteenth century and the tuberculous bacillus
was discovered in 1882 by Koch1
. Tuberculosis is the second most common cause of death worldwide amongst
communicable diseases. It kills nearly 2 million people
each year and developing countries are mostly affected2
. Genital tuberculosis in females occurs secondary to primary disease in the lung, lymph nodes, urinary tract,
bones, joints, and bowel. The spread is usually by the
hematogenous or lymphatic route. Sexual transmission of
female genital tuberculosis (FGTB) has been reported but
direct spread from other intraperitoneal foci is very rare.
The exact incidence of FGTB cannot be determined
with certainty as some cases are asymptomatic and
detected incidentally during investigation of infertility. In
developing countries, FGTB accounts for ≥3% of patients
A retrospective study on FGTB was done over a period
of 15 years in our institute from April, 1997 to March,
2012. Detailed clinical information, radiologic and other
relevant investigations were recorded from case sheets.
The clinical information included age of the patients,
signs and symptoms, socio-economic background,
presence of tuberculosis (lung/non-genital) and HIV in
the patient and family. Radiologic investigations included
chest X-ray, ultrasonography (USG) of abdomen/pelvis,
hysterosalpingography (HSG) and computed tomography
scan. Information regarding other relevant investigations
like Mantoux test/Purified Protein Derivative (PPD) skin
tests, erythrocyte sedimentation rate etc. were also recorded.
Histologic examination of tissue biopsies was done in the
pathology department and reports were collected. Slides
were stained by Hematoxylin and Eosin and Ziehl-Neelsen
(ZN) routinely. Periodic Acid Schiff and other special stains
like Gomori's methanamine silver stain were done whenever necessary to exclude fungal etiology. Microbiological culture
was done in all cases and Mycobacterium Tuberculosis
Polymerase Chain Reaction (MTB-PCR) was done in 72
A total of 110 cases of FGTB were retrieved during this
15 years period from 92 patients. The age range of the
patients was 17-45 years; with a median age of 26.3 years.
Most common specimens in this study were endometrial
curettage and biopsy (61 cases) for evaluation of infertility,
followed by tubo-ovarian mass and hysterectomy. In 8 cases,
specimens of total hysterectomy with bilateral salpingoophorectomy
were submitted with lesions involving
Diagnosis of FGTB was established by epithelioid
granulomas in histopathologic examination (which
was a must) and positivity by PCR, culture, PPD, HSG,
laparoscopy, USG, etc. and clinical features. Rather than
depending on a single diagnostic test, we preferred to
combine all diagnostic tests together along with clinical
corroboration and presence of epithelioid granulomas for
making a diagnosis of FGTB. Mycobacterial culture was
done on Lowenstein Jensen medium/BACTEC culture and
for MTB-PCR; we looked for positive band of 123 bp DNA
fragment of IS 6110 gene of M. Tuberculosis.
During the fifteen-year study period, we received 110
cases of FGTB, of which tuberculosis of the endometrium
made up 66 cases, fallopian tube 24 cases, ovary 12 cases,
cervix 5 cases, vulva 2 cases, and vagina 1 case (Table I
Most of these patients affected by FGTB were poor with
low education (78 patients). Twelve patients were from
the middle income group, whereas only two patients came
from affluent families. Most of the endometrial tuberculosis
cases were in the proliferative phase (53/66), followed by
the secretory phase (9/66) and atrophic endometrium
(4/66). Bilateral involvement was seen in 18 out of 24 cases
of fallopian tube tuberculosis and in 7 out of 12 cases of
ovarian tuberculosis. HIV co-infection was seen in 5 cases
and caseation was found in 16 cases. Acid-fast bacilli (AFB)
in tissue section were detected in 7 cases.
All the five patients with HIV co-infection presented
with weight loss and fever. Three of them had generalised
lymphadenopathy and one had pulmonary fungal infection
(candidiasis). Among the 110 cases of FGTB, positivity for
PCR, culture and PPD test were present in 41 cases (37.3%),
9 cases (8.2%) and 45 cases (40.9%), respectively.
The main histologic finding in endometrial tuberculosis
was the presence of epithelioid cell granulomas in different
stages. Most of these granulomas were small to medium
sized, isolated and scattered through the functionalis layer
(Figure 1). Confluent granulomas were not detected in
endometrial tuberculosis. Multinucleated giant cells of both
Langhans and foreign body type were present in some cases
(11/66), and disruption of endometrial glands was seen in 3
cases. Plasma cells were found in 5 cases, where secondary
infection was also present. Caseation was rarely found in
endometrial tuberculosis (2/66), and both of these patients
were post-menopausal. AFB were also rarely detected
(2/66) (Figure 2).
Click Here to Zoom
|Figure 1: Photomicrograph showing epithelioid granulomas of
tuberculosis in the proliferative endometrium. Both Langhans
and foreign body type of giant cells are also present (H&E, x10).
Click Here to Zoom
|Figure 2: Zeihl-Neelsen stain showing bacilli of tuberculous
mycobacterium in the same endometrium (x100).
Fallopian tubes involved by tuberculosis appeared to be
enlarged and slightly oedematous grossly (23/24). The
external surface was irregular due to adhesions (17/24). In
five cases, the fimbria were everted with a patent orifice,
imparting a characteristic ”tobacco pouch” appearance.
On cut surface, serosanguinous fluid was found in 9 cases,
blood in 2 cases, caseous material in five cases, clear fluid /
hydrosalpinx in 5 cases and pus in 3 cases. Diffuse or focal
mucosal ulceration were noted in most of the cases (21/24).
Microscopically, the features were of chronic salpingitis
with occasional non-caseating granulomas in early stage
(7/24). Plical adhesion with follicular salpingitis was seen in
the early stage (Figure 3). In the late advanced stage (17/24),
single and/or multiple confluent epitheloid granulomas
were present in the lamina propria. Involvement of the
muscularis layer (4/24) and serosa (2/24) were seen
occasionally. Caseation (9/24) and AFB in tissue sections
(4/24) were found in a fair number of cases.
Click Here to Zoom
|Figure 3: Photomicrograph showing tuberculous granulomas in
the mucosal layer of fallopian tube and fused plica (H&E, x10).
Ovarian tuberculosis presented as tubo-ovarian mass and
usually a sequel of tuberculous salpingitis (Figure 4). The
granulomas were seen in the cortical area in the majority
of cases (3/12). Caseation was seen in three cases, of which
one showed AFB in tissue sections.
Click Here to Zoom
|Figure 4: Gross photograph showing tubo-ovarian mass which
was the presenting feature in a case of ovarian tuberculosis.
Cervical tuberculosis grossly appeared as red, enlarged,
ulcerated and friable with clinical misdiagnosis of cervical
cancer in three cases. The commonest site of involvement
was the mucosa of the endocervical canal. As in other
sites, epithelioid granulomas were present but caseation
was absent in all five cases. The vulva (2 cases) and vagina
(1 case) were rarely involved and caseation and AFB were
absent as in cervical tuberculosis.
A clinical suspicion of FGTB was present in 85 cases. The
diagnosis was established only by MTB-PCR in 5 cases
(where other tests were negative) and in the remaining 105
cases by multiple ancillary tests.
Most cases of tuberculosis (95%) occur in developing
countries. However, the prevalence of tuberculosis in
developed countries has recently increased due to HIV
infection, immigration and the development of drugresistant
stains of Mycobacterium tuberculosis3
suffering from latent tuberculosis are more prone to have
active tuberculosis if co-infected with HIV (20 times more
risk than HIV-negative patients). HIV infection also causes
recent tuberculous infection as well4
. In our study, 5
cases of HIV co-infection were present amongst 110 cases
of FGTB (4.5%). According to a current report, nearly 5.1
million people in India are HIV-positive and 60% of these
patients also have tuberculosis5
FGTB patients are usually in the reproductive age group.
The most common presentation findings reported were infertility
(44%), pelvic pain (25%), vaginal bleeding (18%),
amenorrhoea (5%), vaginal discharge (4%), and postmenopausal
bleeding (2%)6,7. Less common presentations
were ascites, abdominal mass, tubo-ovarian abscess and
vague abdominal distention7. In our study, three common
presentations were infertility (65-70%), pelvic abdominal
pain (50-55%), and menstrual disturbances (20-25%).
In most of the studies, the fallopian tubes were affected in
100% of the cases followed by the endometrium (50%), ovaries
(20%), cervix (5%), and vulva and vagina (<1%)4,8.
However, the endometrium was the most common site in
our study (60%), followed by the fallopian tube (21.82%),
ovaries (10.9%), cervix (4.54%), vulva (1.81%), and vagina
The higher incidence of endometrial tuberculosis in
our study might be explained by the fact that most of
the specimens we received were endometrial curettage
specimens during work-up of infertile women. When
tuberculosis affects the female genital tract, the fallopian
tube is involved in almost all cases and endometrial
involvement is usually secondary to tubal disease. However,
the number of endometrial tuberculosis cases (66) is higher
than fallopian tube disease cases (24) in the present study.
This might be due to sample bias, as most specimens we
received were endometrial biopsies for diagnostic work-up
in infertile women.
During the reproductive period, caseation is rare in tuberculous
endometritis9. However in postmenopausal
women, tuberculous granulomas have enough time to develop
caseation as there is no periodic loss of endometrium
to menstruation. In our study also both the patients with
tuberculous endometritis with caseation were postmenopausal.
In the reproductive age, tuberculous granulomas
have to regenerate from the basal layer after menstrual
shedding of the functionalis layer. The granulomas become
well developed and numerous as the menstrual cycle progresses.
Biopsy is therefore recommended just before menstruation
or the late secretory phase, as the granulomas get
the longest possible time to develop and there is a greater
chance of providing an accurate diagnosis. In most of the
studies, endometrial tuberculosis occurs mainly in women
of the reproductive age group, but Falk V et al. found most
cases in the postmenopausal group10. Genital tuberculosis
is rare in postmenopausal women and comprises 1% of
postmenopausal bleeding cases11. The exact cause of the
low incidence of the disease in this age group is not known.
Most authors believe that an atrophic endometrium is a poor milieu for the growth of Mycobacterium tuberculosis
Pelvic tuberculosis may mimic ovarian malignancy and
CA-125 may be falsely elevated13,14. After successful
treatment of tuberculosis, CA-125 returned to normal
levels. FGTB usually occurs as a result of seeding of bacilli
immediately after puberty as blood supply to the pelvic organ
increases. As a result, more bacilli can reach these organs
and infect them15. Primary infection may also occur
if the male partner has active genito-urinary tuberculosis
and transmission may occur through sexual intercourse.
Infection of vulva, vagina and cervix may result from direct
inoculation and ascending infection to other genital organs15,16. In most of the series of FGTB, the vulva and vagina
are uncommon sites of infection17. In our study also, the
incidence of vulvar and vaginal tuberculosis was 1.81% and
The diagnosis of FGTB is challenging as it is rarely
pinpointed by clinical symptoms because of their low
specificity. Elaborate examination (pelvic ultrasound, chest
x-rays, bacteriological culture, ZN stain, PCR analysis,
histopathologic examination) should be carried out for
accurate diagnosis. Microscopic examination of AFB on
ZN stain requires the presence of at least 104 organisms/ml
in the sample whereas culture is more sensitive, requiring as
little as 102 organisms/ml18. Recently, PCR has emerged
as a rapid, sensitive and specific molecular method to
diagnose female genital TB with a turnaround time of 1-2
There are scant prospective data regarding optimal
management of FGTB. In our patients, anti-TB drugs
which included isoniazid, rifampicin, pyrazinamide and
ethambutol were given for a two-month period and the first
two agents for an additional four months20.
Surgical therapy usually consists of total abdominal
hysterectomy and salpingo-oophorectomy. Persistence
of pelvic mass and recurrence of pain or bleeding after 9
months of medical treatment are indications for surgical
intervention. Surgery should be attempted at least 6 weeks
after initiation of anti-tuberculosis regimen, as antimicrobial
treatment facilitates the surgical procedure and reduces the
risk of perioperative complications21.
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