INDIAN JOURNAL OF MEDICAL SPECIALITIES 2012; 3(2)

Cutaneous tuberculosis- a clinico-pathological study

Ranjan Agrawal, Mukta Kumar, Parbodh Kumar
Original Article
Department of Pathology, Rohilkhand Medical College Hospital, Bareilly, UP, India.
Corresponding Author: Dr. Ranjan Agrawal, Associate Professor, Department of Pathology, Rohilkhand Medical College Hospital, Pilibhit Byepass
Road, Bareilly, UP, India.
E-mail: [email protected]
Received: 25-06-2012 | Accepted: 03-08-2012 | Published Online: 06-08-2012
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (creativecommons.org/licenses/by/3.0)
Confict of interest: None declared Source of funding: Nil
Abstract
Objectives: Clinico-morphological study of different cutaneous tuberculosis lesions and determine their
relative frequencies.
Materials and Methods: A total of 1054 skin biopsies were reviewed, of which 64 cases of cutaneous
tuberculosis were diagnosed.
Results: Of the 64 cases of cutaneous tuberculosis, 26 (40.63%) were lupus vulgaris, 19 (29.69%) tuberculosis
cutis, 12 (18.75%) tuberculosis verrucosa cutis, 3 (4.69%) scrofuloderma and 2 (3.1%) each of papular
tuberculid and lichen scrofulosorum. Acid-fast bacilli (AFB) were demonstrated in total 11 cases (17.19%).
Conclusion: Cutaneous tuberculosis formed 6.1% of all biopsied lesions of skin, mainly affecting the males.
The most common subtype was lupus vulgaris followed by tuberculosis cutis and tuberculosis verrucosa
cutis which together constituted approximately 90% of all cutaneous forms of tuberculosis. AFB positivity
was more common in caseating granulomas.
Key words: Lupus vulgaris; skin tuberculosis; scrofuloderma; granuloma.
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Introduction
Granulomatous reactions of skin are classifed as
infectious or non-infectious, based on the presence
or absence of an infectious pathogen serving as
the inciting antigen. They frequently present
a diagnostic challenge. An identical histologic
pattern may be produced by several causes, and
conversely, a single cause may produce several
histologic patterns. Many conditions classifed as
granulomatous lesions may show only non-specifc
changes in the early phase and in late or resolving
stage show fbrosis and non-specifc changes
without granulomas. The frequency and types of
different granulomatous lesions vary according to
geographical locations [1-3]. Certain lesions viz.
cutaneous tuberculosis, fungal and related lesions,
leprosy, sarcoidosis, foreign-body granulomas,
juvenile xanthogranuloma, cutaneous leishmaniasis
etc. may simulate each other and pose diffculty to
the dermatologist in differentiating them clinically.
The onus then lies on the histopathologist to provide
the verdict of fnal diagnosis [4].
Tuberculosis can involve any organ or tissue of
the body including skin. World-wide incidence of
tuberculosis varies from 0.1 to 1% of all cutaneous
disorders [1,5]. The present study was undertaken
with the aim of studying the histological features of
different tubercular lesions of skin and to correlate
them with those of clinical observations.
Methods
A total of 1054 skin biopsies were included in the
present study. Of these, 64 cases of cutaneous
INDIAN JOURNAL OF MEDICAL SPECIALITIES 2012; 3(2)
tuberculosis were reported.
A thorough clinical history and examination was
carried out in these patients followed by punch
biopsy of the representative lesions. These biopsies
were fxed in 10% formalin for histopathological
examination after routine processing. The slides
were stained with Haematoxylin and Eosin (H&E) and
Modifed Ziehl-Neelsen (for AFB using 20% Sulphuric
Acid for decolourising) as and when required.
Biopsy was taken from a fully developed primary
lesion including subcutaneous fat. In patients who
had several types of lesions; biopsy was taken from
more than one lesion.
Studentst test, Chi-square test (with or without
Yates correction) and kappa test were applied to
calculate the signifcance of the observed values;
p value of 0.05 was taken as the critical level of
signifcance.
Results
Six subtypes of cutaneous tuberculosis were
observed in the present study (Table 1). Lupus
vulgaris was the commonest subtype- 26 cases
(40.63%), followed by Tuberculosis cutis in 19
(29.69%), Tuberculosis verrucosa cutis 12 (18.75%),
Scrofuloderma 3 (4.69%), Papular tuberculid 2
(3.13%) and Lichen scrofulosorum 2 (3.13%) cases.
The mean age of patients was 28.91 14.76 years
(age range 3-70 years) and male to female ratio was
1.3:1. The predominant sites affected were face and
neck in 25 (39.06%) followed by upper extremities
in 17 (26.56%), lower extremities in 12 (18.75%) and
trunk and back in 7 (10.94%) cases. Multiple sites
were affected in 3 (4.69%) cases.
Twenty six cases of lupus vulgaris were studied.
The mean age of the patients was 30.22 15.21
years, which is signifcantly higher than the mean
age of patients with scrofuloderma (t=1.745;
p<0.05) but insignifcantly different from other
subtypes. Face was the commonest site to be
affected, in 15 cases (57.69%). Flat reddish brown
plaques with yellowishbrown peripheral nodules
were the presenting features in 20 (76.92%) cases.
Superfcial ulcers were seen in 23 (88.46%) cases. In
seven cases (26.92%), nodules were the presenting
features. Hyperkeratosis and focal acanthosis of
the epidermis was observed in nine (34.61%) cases.
Dermis showed diffuse cellular infltrate in all the
cases with presence of epithelioid cells, Langhans
giant cells, lymphocytes and few plasma cells
(Figure 1). Histiocytes and polymorphs were present
in seven (26.92%) cases. Minimal caseation was
evident in 14 (53.85%) cases. AFB was demonstrated
in four (15.38%) cases.
Tuberculosis cutis was the second commonest form
of tubercular lesion. The mean age of the patients
was 30.93 16.68 years which is signifcantly higher
than the mean age observed in scrofuloderma
(t=1.765; p<0.05) but insignifcantly different
from those of other subtypes. All the patients had
granulation tissue at the site of lesion. Multiple
sites were involved in three cases (15.79%).
Histologically, there was diffuse granulomatous
reaction, flling most of the dermis with areas of
Subtypes n M F Mean age Face & Upper Lower Trunk & Multiple AFB
(years) Neck extremities extremities Back Sites Positivity

Lupus vulgaris 26 (40.63%) 11 15 30.2215.21 15 6 3 2 - 4 (15.38%)
Tuberculosis cutis 19 (29.69%) 11 8 30.93 16.68 2 5 6 3 3 3 (15.79%)
Tuberculosis 12 (18.75%) 8 4 26.00 11.48 3 5 3 1 - 2 (16.67%)
verrucosa cutis
Scrofuloderma 3 (4.69%) 2 1 12.51 13.44 2 - - 1 - 1 (33.3%)
Papular tuberculid 2 (3.13%) 2 - 35 1 1 - - - Nil
Lichen 2 (3.13%) 2 - 28 2 - - - - 1 (50%)
scrofulosorum
Total 64 36 28 25 17 12 7 3 11 (17.19%)
Table 1- Distribution of various subtypes of Cutaneous Tuberculosis and their AFB Positivity
INDIAN JOURNAL OF MEDICAL SPECIALITIES 2012; 3(2)
necrosis, epithelioid cells and few Langhans giant
cells (Figure 2). AFB positivity was demonstrable in
three cases (15.79%).
The study included twelve (18.75%) cases of
Tuberculosis verrucosa cutis with the mean age
26 11.48 years. All the patients presented with
vegetative, warty growths. Central depigmentation
was observed in four cases (33.33%) and atrophy
in three (25%). Past history of injury or abrasion
of the affected site was present in four cases
(33.33%). In all these cases, lesions were solitary.
On microscopy, nine (75.00%) revealed marked
verrucous, hyperkeratosis, parakeratosis and
irregular acanthosis (Figure 3). Typical tubercles
were present in fve (41.66%), while caseation was
evident in four (33.33%) cases. Fibrosis of varying
degree was present in all the biopsies. AFB was
positive in two (16.67%) cases.
Figure 3- Tuberculosis verrucosa cutis. Papillomatosis,
acaanthosis with granuloma of epithelioid cells,
Langhans giant cells and lymphocytes (H & E X40).
Figure 1- Lupus vulgaris (a) A plaque on the dorsum
of hand with peripheral spreading and central healing
alongwith oedema of little fnger () (b) Tubercles
of epithelioid cells, Langhans giants cells and
lymphocytes in the dermis. (H & E X40).
Figure 2- Tuberculosis cutis. (a) Two verrucous
lesions over the lateral aspect of foot. (b)Tubercles of
epithelioid cells, Langhans giants cells, lymphocytes
and caseation. (H & E X40).
The mean age of patients with scrofuloderma was
signifcantly lower than that observed in lupus
vulgaris and tuberculosis cutis (t=1.745 and 1.765;
p<0.05 respectively) but insignifcantly different
from other subtypes. The presenting complaints
were of long standing swelling in the neck area
which later ulcerated; along with discharge of thick
pus. Histopathology of the curetted material along
the ulcer margin revealed tubercular granuloma
with epithelioid cells, lymphocytes and occasional
Langhans giant cells.
Two cases each of papular tuberculid and lichen
scrofulosorum were observed. Papular tuberculid
presented mainly with multiple erythematous
lesions over the face and upper limbs. Few lesions
showed central plugging. Histology revealed a
central area of necrosis, with epithelioid cells and
Langhans giant cells at the periphery. Lymphocytes
were abundant. Histology of Lichen scrofulosorum
showed epithelioid cell collection, occasional giant
cells and scanty lymphocytes. Both the sections
were AFB negative.
Discussion
The pattern of cutaneous tuberculosis is well known
in temperate and tropical climates; however, its
frequency is greater in the former. The incidence
has been declining in developing countries and is
rare in developed countries with the exception
of immigrants, in whom an increase of the non-
INDIAN JOURNAL OF MEDICAL SPECIALITIES 2012; 3(2)
pulmonary forms has been reported [1,5]. With
emergence of anti-tuberculosis drug-resistant strains
and AIDS epidemic, there has been a worldwide rise
of tuberculosis in the recent years. More so ever,
in poverty-struck areas of the world due to poor
nutrition, poverty, non-availability of diagnostic
aids and treatment, overcrowding, ignorance about
the disease, ease of migration of people across the
globe, rise in immunosuppressive therapy, decline
in tuberculosis control efforts and the emergence
of resistant strains of mycobacterium [5,6].
Histopathology combined with the clinical features
is helpful in differentiating skin tuberculosis from
other granulomatous disorders.
Almost one-fourth of the granulomatous lesions
are cutaneous tuberculosis. The overall prevalence
of cutaneous tuberculosis in our study was a little
different than that found in other Indian studies
[5-7]. Average age of the patients and the male to
female ratio reported in the present study were
similar to that observed by some workers [4,5].
Lupus vulgaris was the commonest subtype (40.6%)
observed in our study and as reported by other
authors [3-5]. Distinction between lupus vulgaris
and sarcoidosis can be diffcult. Sarcoidosis has
epithelioid cell granuloma with a thin mantle of
lymphocytes (naked granuloma). Distinction from
nodular tertiary syphilis can be made on the basis
of the greater degree of vascular proliferation,
endarteritis obliterans and greater number of plasma
cells. The other differential diagnoses include
other types of cutaneous tuberculosis, foreign
body reactions and deep mycoses. Lupus vulgaris
lesions occur in normal skin after direct extension
from underlying tubercular focus, by lymphatic or
haematogenous spread, after primary inoculation,
after BCG vaccination or in old scrofuloderma scars
[5-7].
Tuberculosis verrucosa cutis (TVC) is an exogenous
cutaneous infection in a host with moderate-to-
high tuberculin sensitivity and usually presents as
hyperkeratotic (verrucous) lesions on exposed sites,
mostly on the extremities and face. Variable reports
of incidences of TVC have been reported. TVC needs
to be histologically differentiated from atypical
mycobacterial infections, deep fungal infections
and tertiary syphilis. Scrofuloderma presented
as ulcerated lesions in the neck with discharging
cheesy material [6-9].
Scrofuloderma represents direct extension into
the skin from an underlying tubercular focus,
most commonly tubercular lymphadenitis or
skeletal tuberculosis. Cervical lymph nodes are
most commonly involved. Scrofuloderma presents
relatively early due to higher visibility, more
symptoms and the greater number of cases of
tubercular lymphadenopathy associated with it.
Additionally, consumption of unboiled/unpasteurised
milk leading to infection by Mycobacterium bovis,
in turn leading to cervical node infection via tonsils,
may be one factor in Uttar Pradesh (India) leading
to higher scrofuloderma prevalence rates [8,9].
The mean age group of presentation was lower as
compared to other age groups.
Tuberculids comprising of papular tuberculid and
lichen scrofulosorum was represented by 2 (3.13%)
cases each in the present study. The differential
diagnosis included papulofollicular lesions of
sarcoidosis and follicular secondary syphilis. The
absence of a perivascular plasma cell infltrate in
the adjacent dermis helped to rule out secondary
syphilis; whereas, based on histology alone,
sarcoidosis cannot be excluded [8-10].
The presence of granuloma should always
suggest looking for an infectious agent. It is also
recommended to perform special stains on multiple
sections. Despite exhaustive search, these stains can
fail to demonstrate the presence of microorganisms.
Looking for AFB in Ziehl-Neelsen staining is a time
consuming and laborious procedure. In cutaneous
tuberculosis, diagnosis is achieved by the correlation
of the various relative and absolute criterias. In our
study the overall AFB positivity was found in 11
cases (17.19%). AFB were more positive in caseating
granulomas than non-caseating granulomas in the
ratio of 8:3 which was statistically signifcant [9,11].
In order to apply the knowledge effectively when
examining biopsy sections, it is essential that
submitting physicians provide detailed clinical
information. This must include age and sex of the
patient, shade of skin colour essential for judging
pigmentary change, the exact site of the biopsied
lesion, and a concise history and description of the
dermatoses. Clinical diagnosis or a list of differential
diagnosis should always be provided.
INDIAN JOURNAL OF MEDICAL SPECIALITIES 2012; 3(2)
In all cases of true cutaneous tuberculosis, there
was a good response to anti-tubercular treatment,
this being a good sign since multidrug resistance is
being observed now. Unlike pulmonary tuberculosis,
there are no defnite guidelines for the treatment of
multidrug-resistant cutaneous tuberculosis.
Cutaneous tuberculosis continues to be one of
the most elusive and more diffcult diagnoses to
make for dermatologists practicing in developing
countries. Not only because they have to consider
a wider differential diagnosis (leishmaniasis,
leprosy, actinomycosis, deep fungal infections,
etc.) but also because of the diffculty in obtaining
a microbiological confrmation. Despite all the
advances in diagnostics, including sophisticated
techniques such as polymerase chain reaction,
the sensitivity of new methods are no better than
the gold standard. Even now, in the 21st century,
we rely on methods as old as the intradermal
reaction purifed protein derivative (PPD) test
and therapeutic trials, as diagnostic tools. In this
situation, it is important to recognise the myriad
clinical presentations of cutaneous tuberculosis to
prevent missed or delayed diagnoses.
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Key Points
Tuberculosis involving the skin can have
varied manifestations- commonest being
lupus vulgaris, followed by tuberculosis
cutis, tuberculosis verrucosa cutis and
scrofuloderma, in that order.
Clinical diagnosis can at times be
challenging, despite histopathological
correlation since granulomatous disorders
in the tropics are aplenty.
AFB positivity observed in 17.2% cases along
with a positive response to anti-tubercular
therapy, do aid in clinching the diagnosis.