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Correlation between Clinical and Histopathological Diagnosis and Classification

of Hansen's Disease -A Seven Year Retro- spective Study from Himachal
Pradesh, India

Article in Indian Journal of Leprosy · April 2024

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 Indian J Lepr 2024, 96 : 9-16 Kumari et al 9
http://www.ijl.org.in
© Hind Kusht Nivaran Sangh, New Delhi

Original Article

Correlation between Clinical and Histopathological Diagnosis

and Classification of Hansen’s Disease - A Seven Year Retro-
spective Study from Himachal Pradesh, India
K Kumari1, S Asotra2, A Gupta3, S Sharad4, A Sharma5, G Shah6, R Kumari7

Received: 27.04.2023 Revised: 13.11.2023 Accepted: 19.12.2023

Leprosy is a chronic granulomatous disease; its clinical presentation depends upon the immunologic responses
of the host towards the pathogen. While histopathology is considered important to confirm the diagnosis in
cases with vague clinical features, its correlation with clinical classification of disease has not always been
found to be straightforward. This study has been done to correlate the histological picture in biopsy proven
leprosy cases with the clinical findings in these cases to determine the usefulness of combining these two
approaches. In this study, a retrospective analysis of 104 histopathologically confirmed leprosy cases has been
done to correlate with the clinical diagnosis and classification of the leprosy cases who were attending the
Dermatology Department of Dr Rajendra Prasad Government Medical College, Tanda, Kangra. Data analysis
and histological review of all cases was done in the Department of Pathology in an anonymous manner.
Hematoxylin and Eosin staining of tissue slides of all cases was done and all details recorded. Fite Faraco
staining was also done for assessing the bacteriological index (BI) in the slides and recorded. These were
compared with the clinical notes recorded at the time of taking biopsy. Among these histologically confirmed
leprosy cases, Lepromatous Leprosy-LL (41.34%) was the most common leprosy type observed, followed by
Borderline Lepromatous-BL (25%) and Borderline Tuberculoid-BT (18.26%) disease. However, Borderline
Tuberculoid leprosy was the most common diagnosis in these 104 cases by clinical examination alone.
Maximum concordance with clinical classification was seen with Lepromatous Leprosy (88.57%) and the least
28.5% for Tuberculoid (TT). One of three clinically diagnosed TT cases and 14/19 BT cases were found to be
smear positive by Fite Faraco (FF) stain in their tissue slides. Furthermore, other clinically diagnosed MB cases
were also found to be positive for acid fast bacilli (AFB) using the Fite Faraco stain. As this is a retrospective
study the cases could not be followed up to know the outcome of treatment of cases who would have been
treated with paucibacillary regimen but were found to have high bacteriological index (BI). With a decrease in
the burden of cases, there is a need for closer follow-up of leprosy cases to see their response to treatment so
that scope for improving the therapy may be determined out especially in cases with histopathology pointing
to more extensive bacilliferous disease. Technical/Biological issues resulting in discordance even in polar

1
Dr. Kavita Kumari, MD, Senior Resident, Department of Pathology
2
Dr. Sarita Asotra, MD, Assistant Professor, Department of Pathology
3
Dr. Aruna Gupta, MD, Assistant Professor, Department of Pathology
4
Dr. Satyendra Sharad, MD, Senior Resident, Department of Pharmacology
5
Dr. Anuradha Sharma, MD, Senior Resident, Department of Pathology
6
Dr. Garima Shah, MD, Junior Resident, Department of Pathology
7
Dr. Rajneesh Kumari, MD, Senior Resident, Department of Pathology
Dr Rajendra Pradesh Govt Medical College, Tanda, Kangra, Himachal Pradesh-176001, India
Presently: 1Assistant Professor, Pathology, Dr RKGMCH Hamirpur, HP-177001, 2Associate Professor, IGMC Shimla, 3Associ-
ate Professor, Dr RPGMCH Tanda, 4Assistant Professor, Pharmacology, Dr RKGMCH Hamirpur, 5Assistant Professor, Pathology,
Dr RKGMCH Hamirpur, 6Senior Resident, Dr Dr RPGMCH, Tanda, 7Assistant Professor Pathology, Dr RKGMCH Hamirpur, Himachal
Pradesh, India
Corresponding Author: Dr Aruna Gupta, Email: [email protected]
10 Correlation between Clinical and Histopathological Diagnosis and Classification of Hansen’s Disease - A Seven Year...

cases like TT and also reactions like ENL also merit in-depth analysis. Thus, our study highlights the need for
using both ZN staining and Fite Faraco staining for AFB of biopsies wherever possible and analyze them with
treatment and follow-up.

Keywords : Hansen’s Disease, Fite-Faraco Staining, Tuberculoid Leprosy, Histoid Leprosy, Bacteriological Index

Introduction These two types have /were included in the five-

Gerhard Armauer Hansen identified the bacillus group classification given by Indian Association of
Mycobacterium leprae as the causative organism Leprologists (IAL 1982) which is followed in our
of leprosy in 1873. Since then, Leprosy or country. Earlier, World Health Organization (1982)
Hansen’s disease has become a well-known used the bacillary index (BI) for the operational
chronic granulomatous disease, predominantly classification of leprosy for treatment purposes,
affecting the skin and peripheral nerves. Less as multibacillary (MB) and paucibacillary (PB).
commonly affected parts are the eye, testis, In Paucibacillary leprosy, the BI index was <2 (on
bones, lymph nodes etc. The involvement of the Ridley Scale) and in Multibacillary leprosy,
internal organs is rarely manifested clinically the BI index is >2 at any skin site. Broadly
and reported in leprosy. This may be due to a speaking, Indeterminate (Ind), Tuberculoid
high core temperature not allowing the growth (TT), and Borderline Tuberculoid (BT) cases of
of Mycobacterium Leprae (Lastória & Abreu leprosy were classified as paucibacillary, whereas
2014). In endemic settings where almost the Mid-Borderline (BB), Borderline Lepromatous
entire population is exposed to the agent, more (BL), Lepromatous leprosy (LL) and Polyneuritc
than 90% of population does not develop the leprosy were classified as multibacillary (MB).
disease. Some of the cases who do develop the This classification is also used for deciding the
disease selfheal and do not have any clinical treatment protocol (WHO 1982). However,
manifestations of the disease. In a very small smear examination had several drawbacks, and
percentage of exposed persons, develop the flaws and could not be undertaken in all places/
disease, The manifestations are mainly in the laboratories; There was a lot of inter observer
skin and nerves, varied and depends on the
differences in reading of the stained smears and it
immunological host response to the bacterium.
was time consuming. Therefore, for the universal
Histological classification for leprosy was implementation of Leprosy control programs and
proposed by Ridley and Jopling in the year 1966 operational feasibility for providing treatment an
(Ridley & Jopling 1966) which is based primarily operational classification system was proposed
on immunological, clinical and histopathological by WHO. This was based on clinical findings of the
assessment. According to this classification number of skin lesions and nerves involved (WHO
system, leprosy is classified as Tuberculoid (TT), 1994). According to this operational classification
Borderline Tuberculoid (BT), Mid-Borderline (BB), for treatment purposes, patient with more than
Borderline Lepromatous (BL), and Lepromatous 5 skin lesions and nerve involvement/thickening
leprosy (LL) (Arif et al 2018). The drawback of was classified as multibacillary (MB) Leprosy and
this classification is that Indeterminate leprosy given treatment with 3 drugs for 1 year; and
(Ind) and pure Neuritic (N) have not adequately those with less than five lesions (which included
considered due to lack of such cases in their skin and nerve involvement) was considered as
series and ill-defined distinguishing features. paucibacillary Leprosy and treated with 2 drugs
 Kumari et al 11

for 6 months (Parkash 2009). correlation was investigated. The new Indian
Government of India in the year 1954-55 launched Association of Leprologists (IAL) classification
National Leprosy Control Program which was which has been shown to correlate well with the
later in 1983 renamed as National Leprosy Ridley Jopling Classification has been used in the
Eradication program. In the year 2005 India has study (IAL 1982). The clinical classification was
achieved the National target of prevalence of made in the Dermatology Department, which
leprosy less than 1 case per 10,000 population as was based on the number of lesions, type of
per WHO criteria for elimination of leprosy as a lesion, symmetry of the lesions. degree of loss
public health problem. However, this could not of sensation, number and consistency of nerves
be achieved at sub-national level. Some pockets involved. These characteristics are described in
still remain, and new cases continue to occur and detail by Kumar et al (2017).
are being treated. A targeted action is required Hematoxylin & Eosin (H & E) stained slides were
to achieve zero leprosy goal of National Leprosy examined. Fite-Faraco’s staining was done after
Eradication Program. One of the approaches deparaffinizing each section with a mixture of
could be using histopathology for diagnosis of xylene-peanut oil. The section is then stained
new cases with the help of special stains like, into a carbol fuchsin solution for twenty minutes.
suitably adapted Ziehl-Neelsen staining (ZN Followed by counter staining with methylene blue
staining) / Fite-Faraco staining (FF staining) (Fite (Fite et al 1947). The stained slides were viewed,
et al 1947) especially in tertiary care centers, so and histopathological diagnosis was reached
the patients are optimally treated and there is a and recorded. The histological classification and
break in the transmission of the disease. Among diagnosis was made based on presence/absence
these 2-staining methods sensitivity, positive of epidermal atrophy, presence of Grenz zone,
predictive value and negative predictive value is presence/absence of granulomas, distribution of
maximum with Fite-Faraco stain (Reja et al 2013). lymphocytes, histiocytes & foam cells, giant cell
This analysis focuses on usefulness of Fite-Faraco and their presence in the dermis, in and around
nerves, blood vessels and adnexa and presence of
staining of histopathological sections from
acid fast bacilli (AFB).The Bacteriological index was
leprosy cases for assessing the bacterial load in
assessed from the sections and histopathological
these cases.
classification of the type of leprosy was recorded
Material and Methods based on the above findings.
A seven-year retrospective data analysis
Results
and histopathology slide review of all skin
Out of 104 skin histopathological proven leprosy
biopsies with suspected leprosy submitted for
cases studied, 67 were male and 37 females. The
histopathological evaluation in the Department
male/female ratio was 1.8:1 (Table 1). Youngest
of Pathology during 2013 to 2019 was carried out.
as well as the oldest patient were males, of 15
One hundred and eleven untreated cases were
years and 84 years of age respectively. The
submitted with a clinical diagnosis of leprosy of
youngest female patient was 16 years, and the
different types. Out of these, 104 cases were
eldest female patient was 70 years old.
histopathologically confirmed as that of leprosy.
All these cases were taken into consideration The maximum number of cases (25 out of 104)
for the study purpose. Data about age, sex, and was in the 5th decade (41-50 years age group) of
clinical presentation was analyzed, from the life. This was closely followed by the 31 to 40 year
clinical details submitted, and a clinic-pathological and 21 – 30 years age groups. Sixty-five percent
12 Correlation between Clinical and Histopathological Diagnosis and Classification of Hansen’s Disease - A Seven Year...

of cases were seen in the 21 to 50 years of age Histoid leprosy 3, (2.88%); Neuritic 2, (1.92%);
group. A small proportion (3.8%) of cases were and Erythema nodosum leprosum 2, (1.92%);
seen in the 8th decade of life. There was no case in the series. The Histo pathological diagnosis
seen under 10 years of age (Table 1). of indeterminate leprosy was made in 4 cases.
The histopathological spectrum of the leprosy In all these cases, there was mild lymphocytic
was Indeterminate 4, (3.84%); Tuberculoid 3, infiltration around adnexal tissue with no
(2.88%); Borderline Tuberculoid 19, (18.26%)’ Mid epidermal atrophy, no granuloma was observed,
Borderline 2, (1.92%); Borderline Lepromatous and none of them had a Grenz zone, no AFB was
26, (25%); Lepromatous leprosy 43, (41.34%); seen using Fite Faraco stain. However, none of

Fig. 2 : Skin biopsy showing histopathological

Fig. 1 : Skin biopsy showing histopathological features of Pure neuritic leprosy - lymphohis-
features of Histoid leprosy. Spindled histiocytes tiocytic infiltrates around the nerve,
in storiform pattern, 10X (H and E stain). 40X (H and E stain).

Table 1 : Age wise distribution of cases studied.

Age group in years Total No. of patients (n=104) Percentage Male: Female ratio
11-20 5 4.80 4:1
21-30 19 18.26 1.1:1
31-40 24 23.07 2:1
41-50 25 24.03 1.3:1
51-60 14 13.36 1.8:1
61-70 12 11.53 3:1
71-80 4 3.84 4:0
81-90 1 0.96 1:0
 Kumari et al 13

them were clinically diagnosed as Indeterminate neurovascular lymphocytic infiltration around

leprosy. There was 100 percent discordance the pilosebaceous unit in the sections. There was
between clinical and histopathological diagnosis no epidermal atrophy, and no Granz zone. The
in this group (Table 2). The mean age of Bacillary Index was found 1+ on the Fite Faraco
presentation of Indeterminate leprosy was 40 stain (Table 3).
years. The youngest patient was 28 years old Among the 19 clinically diagnosed BT cases,
female patient with having single lesion on 13 cases were histologically confirmed as BT.
her lips. The duration of symptoms was only 3 In the discordant cases 2 were histologically
months, whereas in other cases it ranged from 2 Indeterminate, 1 BB and 3 BL. None of the cases
to 6 years. Of the 7 TT cases diagnosed by clinical in the series were mid borderline both clinically
criteria 2 were confirmed histologically, whereas and histologically. Of the 31 clinically diagnosed
the other 5 had a different diagnosis as shown BL cases 21 were confirmed as BL histologically,
in Table 2. One case was histopathologically while the rest were classified differently
diagnosed as Lepromatous leprosy (Table 2). histologically (1- Indeterminate; 2 – BT; 1- BB
His lesion had ill-defined granuloma, and dense and 6 LL cases). Thirty-one cases out of 35

Table 2 : Clinico-Histopathological Correlation.

Clinical Histopathological diagnosis
diagnosis IL TT BT BB BL LL Histoid Neuritic ENL Concor- Discor-
4/104 3/104 19/104 2/104 26/104 3/104 26/104 2/104 2/104 dance dance
3.8 % 2.88% 18.26% 1.92% 25% 2.88% 25% 1.92% 1.92%
IL - - - - - - - - - 0% 100%
(0/104)
TT 1 2 3 - - 1 - - - 28.57% 71.42%
(7/104)
BT 2 - 13 1 3 - - - - 68.42% 31.57%
(19/104)
BB - - - - - - - - - 0% 100%
(0/104)
BL 1 - 2 1 21 6 - - - 67.74% 32.25%
(31/104)
LL - 1 1 - - 31 2 - - 88.57% 11.42%
(35/104)
Histoid - - - - - 1 1 - - 50% 50%
(2/104)
Primary - - - - 1 - - 2 - 66.66% 33.33%
Neuritic
(3/104)
Leprosy - - - - 1 4 - - 2 28.57% 71.42%
reaction
(7/104)
14 Correlation between Clinical and Histopathological Diagnosis and Classification of Hansen’s Disease - A Seven Year...

Table 3 : Bacteriological index (BI) in histopathology slides by Fite- Faraco staining.

Histopathological Bacteriological index (BI)
diagnosis 0 1+ 2+ 3+ 4+ 5+ 6+
IL = 4/104 4 0 0 0 0 0 0
TT= 3 /104 2 1 0 0 0 0 0
BT=19/104 5 5 9 0 0 0 0
BB= 2/104 1 0 0 1 0 0 0
BL=26/104 4 0 10 6 6 0 0
LL=43/104 0 0 1 1 16 14 11
Histoid=3/104 0 0 0 0 1 1 1
Neuritic = 2/104 1 0 0 0 0 0 1
ENL=2/104 1 0 1 0 0 0 0
Total 17.30% 5.8% 20.19% 7.69% 22.11% 14.42% 12.5%

clinically diagnosed LL cases were confirmed as tissue sections and ,5 showed 1+ in the series
LL cases while 4 cases were classified differently (Table 3). Similarly, One out of 2 BB patient and
histologically (1 as TT; 1 as BT and 2 as Histoid 4/26 BL patients; one of the two Neuritic and one
leprosy). One of the 2 cases of clinically diagnosed out of 2 ENL patients were also AFB negative in
Histoid leprosy was confirmed histologically their tissue sections (Table 3).
(Fig. 1) while the other showed only LL features
Discussion
histologically. Two of the three Neuritic leprosy
Male predominance has been observed in many
cases were confirmed as Neuritic leprosy (Fig. 2)
studies as in the present study where the M: F
while the remaining third case had BL features
is 1.8:1. Atram et al (2020) study had a similar
histologically. Although 7 cases were diagnosed
finding with a M: F of 1.5:1. Semwal et al (2018)
clinically as ENL cases, only 2 could be confirmed
had similar observations. This trend can be
as having histological features of ENL while, 1 as
attributed to the higher chances of contracting
that of BL and 4 of LL type. It may be noted that
infection due to higher outdoor activity of males
ENL reactions occur in borderline and LL cases
and frequent meetings with several persons.
only and maybe the biopsy specimen was taken
Another reason could be fewer numbers of
from the non-inflammatory skin tissue and not
females are brought to tertiary care centers for
from the ENL nodules.
treatment.
Using the Fite-Faraco staining of tissue sections
Most of patients in our study were in their 4th
for detecting Acid fast bacilli (AFB) the details of
and 5th decades of life accounting for 47.11%
BI are shown in Table 3. None of the histologically
which is similar to that reported by Kaur et al
proven Indeterminate cases showed presence of
(2003) and Suri et al (2014) in their respective
AFB, while 1 case of TT leprosy and 5 cases of
studies. As the studies have been conducted in
BT leprosy were also 1+ BI positive in the tissue
Tertiary care center and Medical College it is not
sections. Nine cases of clinically diagnosed BT
surprising. Lesser cases have been reported in
leprosy showed 2+ positivity for AFB in their
 Kumari et al 15

the younger age group as well as those over 80 Neurtic cases were between 4 to 6+ AFB positive
years of age. as observed by Fite Faraco staining. These cases
The most common type of leprosy observed need to be followed up and treated carefully,
in the present study was lepromatous leprosy preferably till AFB negativity or as determined
which accounted for 41.34% of total cases. This by proper trials is attained to prevent relapses,
observation was similar to studies conducted at disabilities and reduce the transmission risk in
Himachal Pradesh by Tegta et al (2019), Rattan the community.
et al (2017) and Jindal et al (2009). However, in Conclusions and future perspective
a study reported by Sharma et al (2008) from Our study shows major discordance among
Jammu; Bhanusree et al (2016) from Puducherry; clinical and histopathological diagnosis in
study from Rajasthan by Kumar et al (2014), several cases whose biopsies were sent to
reported BT as the commonest form of leprosy Pathology. Reasons for several well-defined
in their series. This observation of Lepromatous clinical types being identified as Indeterminate
leprosy being the commonest type at Himachal by histopathology, TT diagnosed as BT and their
Pradesh may be due to the late reporting of cases implications on prognosis should be investigated.
in this hilly region. In the present study, clinical- BT cases with high BI by Fite-Faraco staining may
histopathological concordance was highest in LL also have therapeutic relevance which should
(88.57%) similar to the result seen by Banushree be studied prospectively in relation to outcomes
et al (2016) and the least concordance was and comparative usefulness of other techniques
in Indeterminate leprosy (0%). While taking including molecular assays (Reza et al 2013).
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How to cite this article : Kumari K, Asotra S, Gupta A et al (2024). Correlation between Clinical and
Histopathological Diagnosis and Classification of Hansen’s Disease - A Seven Year Retrospective Study
from Himachal Pradesh, India . Indian J Lepr. 96: 9-16.

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