Hong Kong J. Dermatol. Venereol. (2012) 20, 77-81

Case Report

Lepromatous leprosy: a case simulating verrucouscarcinoma

MM Chang and PCL Choi

A 59-year-old immigrant from China presented with a rapidly-enlarging exophytic growth on hisleft heel for 4 months. He was also found to have peripheral neuropathy, Charcot's joint, diffuseerythematous papules and acquired ichthyosis. Classical histologic features of leprosy were noted,together with atypical verrucoid proliferation. The diagnosis of lepromatous leprosy was madeafter clinical-pathological correlation and confirmation by polymerase chain reaction.

Keywords:Keywords:Keywords:Keywords:Keywords: Digitate papules, lepromatous leprosy, leprosy, multibacillary leprosy, verrucouscarcinoma

Division of Dermatology, Department of Medicine andDivision of Dermatology, Department of Medicine andDivision of Dermatology, Department of Medicine andDivision of Dermatology, Department of Medicine andDivision of Dermatology, Department of Medicine andTherapeutics, Prince of WTherapeutics, Prince of WTherapeutics, Prince of WTherapeutics, Prince of WTherapeutics, Prince of Wales Hospital, Hong Kongales Hospital, Hong Kongales Hospital, Hong Kongales Hospital, Hong Kongales Hospital, Hong Kong

MM Chang, MBChB, MRCP

Department of Anatomical and Cellular PDepartment of Anatomical and Cellular PDepartment of Anatomical and Cellular PDepartment of Anatomical and Cellular PDepartment of Anatomical and Cellular Pathologyathologyathologyathologyathology,,,,,Prince of WPrince of WPrince of WPrince of WPrince of Wales Hospital, Hong Kongales Hospital, Hong Kongales Hospital, Hong Kongales Hospital, Hong Kongales Hospital, Hong Kong

PCL Choi, MBChB, FRCPA

Correspondence to: Dr. MM Chang

Department of Medicine and Therapeutics, 9/F ClinicalSciences Building, Prince of Wales Hospital, 30-32 NganShing Street, Shatin, New Territories

IntroductionIntroductionIntroductionIntroductionIntroduction

The cutaneous manifestations of leprosy are vast.We report a case of lepromatous leprosy with

classical clinical and histological features, but alsoco-existing with verrucoid growth, which is seldomencountered.

Case reportCase reportCase reportCase reportCase report

A 59-year-old man was referred to the OrthopaedicTumour Clinic for a fungating growth on his leftheel for four months. It was asymptomatic butgrowing rapidly. There was no history of traumaor contact with fish. He had a history of closedfracture on the same ankle that was treatedconservatively in childhood, and carcinoma ofrectum, now in remission, following surgery andchemo-radiation therapy 12 years ago.

MM Chang and PCL Choi78

Clinically, the mass was 45 cm, with verrucoussurface and irregular border (Figure 1). There wasno satellite lesion or regional lymphadenopathy.The provisional diagnosis by the orthopaedic teamwas squamous cell carcinoma. MRI excluded deepfascial invasion. Wide local excision followed bystaged skin graft was performed.

The patient was referred to the dermatology teamwhen the histology suggested otherwise. Onfurther enquiry, he complained of insidious onsetof dry skin, sensation loss of the extremities causingfrequent scald injuries after handling hot waterand progressive painless deformity of left anklefrom which he reported difficulty findingappropriate shoes. Social history revealed that he

was born and immigrated from a village inGuangdong 40 years ago, but he did not recallany history of similar condition among his closefamily members. On examination, he had slightsaddle-nose deformity, Charcot's joint on the leftankle (Figure 2), acquired ichthyosis on the limbs,multiple non-descript ill-defined erythematouspapules on the back (Figures 3 & 4) and enlargedulnar nerves on palpation. Peripheral neuropathywas confirmed on nerve conduction study.

Histologically, there was verrucoid epidermalhyperplasia without invasion, atypia or increasedmitotic activities (Figure 5). There were patchymixed inflammatory lymphohistiocytic infiltratesand some plasma cells. Globi formation wasnoted with foamy histiocytes (Figures 6 & 7). Ziehl-Neelsen stain and Wade-Fite stains showedabundant acid-fast bacilli (Figure 8), while PAS,Grocott, Warthin-Starry and Gram stains were allnegative. Polymerase chain reaction (PCR) analysisof paraffin tissue was positive for Mycobacteriumleprae DNA but not M. tuberculosis. A second skin

Figure 1.Figure 1.Figure 1.Figure 1.Figure 1. Verrucous growth on heel.

Figure 2.Figure 2.Figure 2.Figure 2.Figure 2. Charcot's joint.Figure 3.Figure 3.Figure 3.Figure 3.Figure 3. A close-up of digitate-like ill-definedpapules on back.

Lepromatous leprosy in a Chinese male 79

Figure 4.Figure 4.Figure 4.Figure 4.Figure 4. Multiple erythematous papules on back.

Figure 5.Figure 5.Figure 5.Figure 5.Figure 5. Low magnification showed verruoidepidermal hyperplasia with underlying fibrous stroma(H&E, Original magnification 20).

Figure 6.Figure 6.Figure 6.Figure 6.Figure 6. Biopsy from the back showed intradermalcollections of lymphocytes and histiocytes. Note thepresence of globi (H&E, Original magnification 20).

Figure 7.Figure 7.Figure 7.Figure 7.Figure 7. Medium magnification showed the presenceof globi admixed with lymphocytes and histiocytes(H&E, Original magnification 200).

biopsy on a papule on the back also showedidentical histology (Figure 6).

The diagnosis of lepromatous leprosy was madeand the patient was started on rifampicin, dapsoneand minocycline in hospital. There was noobservable reaction on treatment and the graftwas taking well. Screening for HIV and diabeteswas negative. On discharge, he was referred tothe Leprosy Skin Clinic for continuation of multi-drug therapy and contact tracing.

MM Chang and PCL Choi80

DiscussionDiscussionDiscussionDiscussionDiscussion

Leprosy is a chronic granulomatous infection ofthe skin and peripheral nerves. It is transmittedby Mycobacteria leprae (M. leprae), an obligateintracellular Gram-positive bacillus with acid-fastproperty and affinity for macrophages andSchwann cells. It is a global disease affecting allraces, highly endemic in Africa and SouthAmerica, and prevalent in developing countriesin South-East Asia and parts of China. With theintroduction of WHO multi-drug therapy (MDT),the disease is now controlled with decreasingprevalence. In fact, Hong Kong is declared byWHO to be eliminated from leprosy1 with itsincidence of 0.088/10000 population. In the1950s and 60s, the majority of leprosy patientsin Hong Kong (90%) were born in China,2 whilein recent years, imported leprosy from South EastAsian countries accounted for the majority.

The infection caused by M. leprae carries a longincubation period, from months to 20 years,averaging three to five years. The majority ofexposed individuals do not develop disease.Host genetic and environmental factors influenceindividual susceptibil i ty to infection anddisease progression. In lepromatous leprosy, a

Figure 8.Figure 8.Figure 8.Figure 8.Figure 8. Wade-Fite stain demonstrated manyintracellular acid fast bacilli (red in stain) (WF, Originalmagnification 40).

predominant-Th2 response suppressesmacrophage activity and cell mediated immunitywhile a heightened Th1 response is found intuberculoid leprosy. Several leprosy susceptibilityloci on chromosome 6 and 10 are found; andthe presence of HLA allele DQ1 gears towardslepromatous expression. In a genome-wideassociation study in Han Chinese, novelassociation with NOD2, TNFSF15, RIPK2 arefound, indicating heterogeneity of geneticsusceptibility between ethnic groups.3 Transmissionresults from early childhood close contact with asource with high infectivity (lepromatous leprosy),and spreading by droplets of nasal or oralsecretions. The household risk of acquiring diseasein an endemic area is 10%. There are a few reportsof infections acquired through open wound andfomites, and, recently, armadillos as a zoonotictransmission.4 Moreover, another species,Mycobacterium lepromatosis, has been found tocause diffuse form of lepromatous leprosy inMexico and the Caribbean.5

Our patient had classical clinical and histologicfeatures of lepromatous leprosy, whichrepresented the more severe spectrum of diseasewith multi-bacillary involvement and poor hostimmunity. What was atypical would be the lateage of onset, very long incubation and verrucoidpresentation. Most literature reported specialforms of leprosy as histoid, dermatofibroma-likepapules, digitate or shagreen-like patches.Verrucoid presentations are rare in leprosyand were found in few anecdotal reportsof lepromatous leprosy wi th coexis tentchromoblastomycosis,6 or in HIV-positiveindividuals.7 A more logical association would besquamous cell carcinoma arising from chronicunhealed leg ulcers, and even with that, verrucouscarcinoma arising from such lesion was rarelyreported.8 The underlying reason that ourimmunocompetent patient developed verrucoidgrowth was obscure. Without other supportingcutaneous suggestions of leprosy, the differentialdiagnosis would have been malignant tumours(squamous cell carcinoma, verrucous carcinoma,

Lepromatous leprosy in a Chinese male 81

cutaneous metastasis, amelanotic melanoma), orinfection (giant condyloma, deep fungal infection,atypical mycobacterial infection or tuberculosisverrucosa cutis). A biopsy for histology and culturewould be helpful to establish the diagnosis.

The diagnosis of leprosy is suggested by (1) thepresence of skin lesions with definite sensory loss(except borderline lepromatous or lepromatousleprosy), (2) thickened peripheral nerves, or (3)the presence of acid-fast bacilli on skin smears ortissue biopsy.9 The sensitivity and positivepredictive values based on the above diagnosticfeatures are more than 95% in endemic countries.10

M. leprae cannot be cultured in artificial media.Newer techniques like serology for M. lepraeantibody, phenolic glycolipid-1 (PGL-1), or PCRfor M. leprae DNA detection are useful inmultibacillary disease with high bacterial load. Thesensitivity for serology ranges from 40%(paucibacillary) to 90% (multibacillary) and it canbe used to monitor the effectiveness of treatmentas its level declines with MDT. The sensitivity ofPCR using M. leprae specific repetitive sequencein multibacillary disease is 80% and can beperformed on skin or nasal biopsy specimen andextracts of slit skin smear.11 These tests are usedmore as identification tools rather than detectiontools for leprosy, as the sensitivity for paucibacillarydisease is low overall.

Standard multi-drug therapy with monthlysupervised rifampicin 600 mg and clofazimine300 mg, and daily self-administered dapsone100 mg and clofazimine 100 mg was prescribedto our patient. He tolerated treatment well withcounseling, psychological support and regularfollow-up. Podiatry assessment and footwearadjustment was made. The relapse rate after twoyears of WHO-MDT is quoted to be 0.77%globally1 to 3% locally.12 In our locality, a moreconservative approach is adopted with prolongedMDT until all skin lesions are inactive, followedby dapsone monotherapy for 10 years after theslit skin smear is negative.

In conclusion, although leprosy is a fading disease,clinicians should remain vigilant in the screeningand diagnosis of leprosy in Hong Kong. Earlyspecialist referral is recommended in view ofits protean manifestations and infectiousimplications.

AcknowledgementsAcknowledgementsAcknowledgementsAcknowledgementsAcknowledgements

The author would like to thank Dr Lo Kuen Kongand Dr Luk Nai Ming, for their supervision, andDr Tse Lung Fung, for supplying the surgicalphoto.

RRRRReferenceseferenceseferenceseferenceseferences

1. World health organization leprosy fact sheet.2. Ho CK. Leprosy - a review. Hong Kong J Dermatol

Venereol 1999;7:65-70.3. Zhang FR, Huang W, Chen SM, Sun LD, Liu H, Li Y, et

al. Genome wide association study of leprosy. N Engl JMed 2009; 361: 2609-18.

4. Truman RW, Singh P, Sharma R, Busso P, Rougemont J,Paniz-Mondolfi A, et al. Probable zoonotic leprosy inthe Southern United States. N Engl J Med 2011;364:1626-33.

5. Han XY, Sizer KC, Thompson EJ, Kabanja J, Li J, Hu P,et al. Comparative sequence analysis of Mycobacteriumleprae and the new leprosy-causing Mycobacteriumlepromatosis. J Bacteriol 2009;191:6067-74.

6. Silva Cde M, Silva AC, Marques SC, Saldanha AC,Nascimento JD, Branco MR, et al. Chromoblastosisassociated with leprosy: report of 2 cases. Rev Soc BrasMed Trop 1994;27:241-4.

7. Manjare AK, Tambe SA, Phiske MM, Jerajani HR. Atypicalpresentation of leprosy in HIV. Indian J Lepr. 2010;82:85-9.

8. Karthikeyan K, Thappa DM. Squamous cell carcinomain plantar ulcers in leprosy: a study of 11 cases. IndianJ Lepr 2003;75:219-24.

9. Walker SL, Lockwood DN. Leprosy. Clin Dermatol 2007;25:165-72.

10. Britton WJ, Lockwood DN. Leprosy. Lancet 2004;363:1209-19.

11. Kang TJ, Kim SK, Lee SB, Chae GT, Kim JP. Comparisonof 2 different amplification products in the diagnosis ofMycobacterium leprae. Clin Exp Dermatol 2003;28:420-4.

12. Ho CK, Lo KK. Epidemiology of leprosy and responseto treatment in Hong Kong. Hong Kong Med J 2006;12:174-9.