Author: PathologyMCQ Editorial Team
Category: Skin Pathology / Infectious Pathology
Last Updated: October 2026
Read Time: 20 minutes
Difficulty: Moderate (MD/DNB, FRCPath, NEET-SS)

At a glance

• What it is: the multibacillary pole of Hansen disease, caused by Mycobacterium leprae (and rarely M. lepromatosis) in patients with weak cell-mediated immunity.
• Histology triad: Grenz zone + sheets of foamy (Virchow) macrophages + Fite-positive bacilli and globi.
• Numbers that matter: bacteriological index usually 4+ to 6+; WHO multi-drug therapy for 12 months.
• In this post: 3 zoomable virtual slides (2 H&E and a Fite stain), an annotated slide, and 10 interactive MCQs including 4 slide-based questions.

What is lepromatous leprosy?

Lepromatous leprosy (LL) is the multibacillary pole of Hansen disease caused by Mycobacterium leprae, an obligate intracellular, slow-growing acid-fast bacillus with a tropism for macrophages and Schwann cells. Patients have weak, Th2-biased cell-mediated immunity, so bacilli multiply unchecked: the dermis fills with laden macrophages, nerves are widely infiltrated, and skin smears show huge numbers of bacilli. Clinically there are numerous symmetrical macules, papules, nodules and diffuse infiltration (leonine facies, madarosis), with glove-and-stocking anaesthesia. The lepromin (Mitsuda) test is negative.

Core histopathology

• Epidermis: thinned and flattened, with loss of rete ridges.
• Grenz zone: a clear band of uninvolved papillary dermis beneath the epidermis.
• Dermis: diffuse sheets of foamy macrophages (Virchow or lepra cells) around vessels, nerves and adnexa, with few lymphocytes and no compact epithelioid granulomas.
• Nerves: infiltrated by macrophages and bacilli, with an onion-skin perineurium, but architecture is preserved for a long time.
• Fite stain: enormous numbers of acid-fast bacilli, singly, in bundles and as globi.

Grenz zone and diffuse dermal infiltration

• The Grenz zone shows that lepra macrophages do not invade the epidermis.
• It separates lepromatous from tuberculoid leprosy, where granulomas reach the epidermis.
• It goes with widespread, symmetrical, diffusely infiltrated lesions.

Cutaneous nerve involvement

• Bacilli invade Schwann cells, producing glove-and-stocking anaesthesia.
• Nerves show macrophages and bacilli with an onion-skin perineurium; destruction is slower than in tuberculoid leprosy.
• Long-standing involvement leads to muscle wasting and trophic ulcers.

Fite stain and bacillary load

• Fite-Faraco uses peanut oil–xylene and gentle decolourisation to preserve the weakly acid-fast lipid wall of M. leprae.
• Solid-staining rods are viable; fragmented or granular rods are dead.
• Bacillary load reflects infectivity and is used to monitor treatment.

Globi

• Globi are clumps of bacilli held in a lipid-rich gloeal matrix inside macrophages.
• They are seen at the lepromatous end of the spectrum (LL and BL).
• They indicate massive replication and a high relapse risk if treatment is incomplete.

Hair follicle, sebaceous and sweat gland involvement

• Hair follicles: infiltration causes madarosis (loss of eyebrows) and alopecia.
• Sebaceous glands: loss of sebum causes dry, fissured skin and secondary infection.
• Sweat glands: destruction causes anhidrosis and contributes to trophic ulcers.

Ridley–Jopling spectrum and WHO classification

Type	Histology	Bacilli (BI)	Lepromin
TT tuberculoid	Compact epithelioid granulomas with Langhans cells and dense lymphocytes, reaching the epidermis; nerves destroyed	Rare or none (0–1+)	Strongly positive
BT borderline tuberculoid	Epithelioid granulomas along nerves, narrow Grenz zone may appear, fewer lymphocytes	0–2+	Positive
BB mid-borderline	Diffuse epithelioid cells without giant cells, clear Grenz zone, sparse lymphocytes	2–3+	Weak
BL borderline lepromatous	Macrophages with some foamy change, many lymphocytes, onion-skin perineurium	4–5+	Negative
LL lepromatous	Sheets of foamy Virchow cells, Grenz zone, few lymphocytes, globi	5–6+	Negative
Indeterminate	Sparse perineural and periadnexal lymphohistiocytic infiltrate	Rare	Variable

WHO operational classification (2018): multibacillary leprosy = more than 5 skin lesions, or nerve involvement, or bacilli on slit-skin smear at any site. Paucibacillary = 1 to 5 skin lesions without bacilli on smear. All LL and BL cases are multibacillary.

Bacteriological and morphological index

BI (Ridley)	Bacilli per oil-immersion field
0	None in 100 fields
1+	1–10 in 100 fields
2+	1–10 in 10 fields
3+	1–10 per field
4+	10–100 per field
5+	100–1000 per field
6+	More than 1000 per field, many globi

The bacteriological index falls slowly, by about 0.6–1 log a year on treatment. The morphological index (MI) is the percentage of solidly staining (viable) bacilli; it falls within months of effective therapy and a rising MI suggests relapse or drug resistance. The granuloma fraction is the proportion of the dermis occupied by the infiltrate.

Lepra reactions and variants

Entity	Who gets it	Histopathology
Type 1 (reversal) reaction	Borderline (BT, BB, BL)	Dermal oedema, increased lymphocytes and epithelioid cells, giant cells, upgrading towards tuberculoid
Type 2 reaction: erythema nodosum leprosum (ENL)	LL and BL, often during treatment	Neutrophils superimposed on foamy macrophages, leukocytoclastic vasculitis, lobular panniculitis; immune complex mediated
Lucio phenomenon	Diffuse non-nodular LL (Lucio leprosy), Mexico and Central America; linked to M. lepromatosis	Necrotising vasculitis of small vessels with bacilli in endothelial cells, thrombosis and haemorrhagic infarcts
Histoid leprosy	LL, relapse or dapsone resistance	Circumscribed nodules of spindle histiocytes in a storiform pattern, Grenz zone, enormous numbers of long solid bacilli

Differential diagnosis: foamy macrophages in the dermis

Mimic	Clue	Deciding test
Xanthoma	Lipid-laden foam cells, Touton giant cells, cholesterol clefts	Fite negative; lipid profile
Rhinoscleroma	Nasal site, Mikulicz cells, Russell bodies, plasma cells	Warthin-Starry or PAS; Klebsiella rhinoscleromatis culture
Atypical mycobacteria (e.g. MAI in HIV)	Foamy histiocytes stuffed with bacilli, immunosuppressed patient	ZN strongly positive; culture or PCR
Leishmaniasis	Parasitised macrophages, plasma cells	Giemsa shows amastigotes with kinetoplast; Fite negative
Histoplasmosis, cryptococcosis	Yeasts within histiocytes	GMS and PAS positive; mucicarmine for Cryptococcus
Histoid leprosy vs dermatofibroma	Storiform spindle cells	Fite shows abundant bacilli in histoid leprosy

What’s new: WHO 2018 treatment, prophylaxis and diagnostics

• Uniform three-drug MDT: rifampicin, dapsone and clofazimine for all patients; 6 months for paucibacillary and 12 months for multibacillary leprosy.
• Single-dose rifampicin post-exposure prophylaxis (SDR-PEP) for household and close contacts once active disease is excluded.
• Drug resistance: rifampicin-resistant leprosy is treated with second-line drugs (ofloxacin or minocycline plus clofazimine); molecular testing targets rpoB, folP1 and gyrA.
• PCR: M. leprae DNA (for example the RLEP repeat) helps in paucibacillary or atypical cases where bacilli are scanty.
• M. lepromatosis (described in 2008) causes diffuse lepromatous leprosy and Lucio phenomenon and cannot be told apart from M. leprae by histology.

More practice: leprosy quiz

Exam pearl and key takeaway

Exam pearl: Grenz zone + sheets of foamy Virchow cells + Fite-positive bacilli in globi = lepromatous leprosy. Compact granulomas touching the epidermis with destroyed nerves and few bacilli = tuberculoid leprosy.

Key takeaway: lepromatous leprosy replaces the dermis with bacilli-laden macrophages, infiltrates nerves and adnexa, and carries a BI of 4+ to 6+. Always order a Fite stain, place the biopsy on the Ridley–Jopling spectrum, and look for reactions such as ENL.

Watch the slide discussion video