August 2016




Signalment (JPC #1662297):  6-year-old male chimpanzee (Pan troglodytes).


HISTOPATHOLOGIC DESCRIPTION:  SLIDE A:  Haired skin:  Diffusely expanding the dermis, elevating the epidermis, widely separating collagen bundles, and extending to surgical margins are numerous histiocytes and fewer lymphocytes, plasma cells, and reactive fibroblasts arranged in variably sized nodular aggregates and multifocally infiltrating peripheral nerves.  Histiocytes either have abundant microvacuolated eosinophilic cytoplasm or a variably sized, clear cytoplasmic vacuole (up to 50um in diameter) with clumped aggregates of amphophilic to lightly basophilic fibrillar material (lepra cells).  Dermal collagen is often fragmented and hypereosinophilic (collagenolysis).  Multifocally, small vessels within the nodules are lined by reactive endothelium.  Multifocally, the epidermis is mildly hyperplastic with acanthosis, and diffuse mild to moderate orthokeratotic hyperkeratosis.


Peripheral nerve:  Diffusely expanding and infiltrating into the nerve fasicles, expanding and elevating the perineurium and epineurium are large numbers of previously described histiocytes.  Cytoplasmic vacuoles within lepra cells are up to 100um.  There are multifocal areas of mild perineural fibrosis admixed with numerous lymphocytes and fewer plasma cells.


Liver:  Multifocally and randomly there are variably sized nodular aggregates of the previously described histiocytes that contain large, clear vacuoles.  Frequently these nodules also contain small to moderate numbers of viable and degenerate neutrophils.  Hepatocytes are diffusely degenerate with multiple intracytoplasmic clear vacuoles.


Slide B:  Acid-fast stain:  Haired skin, liver, and peripheral nerve:  Within the vacuoles of the histiocytes, there are numerous acid-fast, 2-3 um x 1 um bacilli occurring singly and in long, beaded chains up to 8-10 um long.


MORPHOLOGIC DIAGNOSIS:  1.  Haired skin:  Dermatitis, granulomatous, diffuse, severe, with granulomatous neuritis, orthokeratotic hyperkeratosis, and intrahistiocytic acid-fast bacilli, chimpanzee (Pan troglodytes), nonhuman primate.

2.  Peripheral nerve:  Neuritis, granulomatous, diffuse, severe, with mild perineural fibrosis, and intrahistiocytic acid-fast bacilli.

3.  Liver:  Hepatitis, histiocytic and neutrophilic, random, mild, with intrahistiocytic acid-fast bacilli.


ETIOLOGIC DIAGNOSIS:  Mycobacterial dermatitis, neuritis, and hepatitis.


CAUSE:  Mycobacterium leprae


CONDITION: Lepromatous leprosy


SYNONYMS:  Leprosy, Hansen's disease



·         Mycobacterium leprae is an acid-fast obligate intracellular organism, and the etiologic agent of leprosy in humans and nonhuman primates; causes a chronic granulomatous disease that primarily affects the cooler areas of skin (upper respiratory tract mucosa, digits, hands, nose, ears, tail, and scrotum) and peripheral nerves

·         Principally encountered in tropical climates

·         Zoonotic; armadillos are a natural reservoir and are likely a source of M. leprae infection for humans



·         Organisms transmitted via inhalation > taken up by alveolar macrophages > disseminated through blood > cooler areas of body (i.e. skin and extremities)

·         May present as benign disease (tuberculoid leprosy) or as malignant disease (lepromatous leprosy) with a spectrum of intermediate stages between the two, depending on the host immune response

·         T-helper lymphocyte response determines if the patient develops lepromatous or tuberculoid leprosy

·         Lepromatous, (a.k.a. anergic, diffuse) leprosy (malignant disease)

  • Numerous foamy epithelioid macrophages filled with many mycobacteria (multibacillary)
  • Develops in those with a dominant CD4+, TH2 response or a defective CD4+, TH1 response where CD4+ TH2 cells release IL-4, IL-5, IL-10 which suppresses macrophage activation
  • IL-4 inhibits the TH1 response allowing the TH2 response to dominate; IL-4 also induces antibody production by B cells that is not protective and may lead to antigen-antibody complexes resulting in vasculitis and glomerulonephritis
  • More neurotropic; nerve involvement usually symmetrical/generalized

·         Tuberculoid leprosy (benign disease)

  • Granuloma formation with few mycobacteria (paucibacillary)
  • Mediated by CD4+, TH1 cell response and production of IL-2 and IFN-gamma; gamma/delta receptor T-cell lymphocytes are also present and also produce IFN-gamma; macrophages produce IL-12 that is critical for the TH1 response
  • Nerve involvement is generally more asymmetric/localized



·         Macular, nodular and papular lesions in the cooler areas (e.g. face, ears, distal extremities, scrotum, upper airways, anterior chamber of eye)

·         Skin lesions hypoasthetic or anesthetic; loss of sensation and nerve damage lead to trophic changes and paralytic deformities in extremities



·         Erythematous macules, papules or nodules; frequently ulcerated; usually on the skin of the subperiorbital area, lips, chin, ears, and scrotum

·         Peripheral nerves, especially the ulnar and peroneal are affected often resulting in loss of sensation in the hands and feet which leads to injury/ulceration



·         Diffuse granulomatous dermatitis localized around neurovascular channels, with epidermal thinning, a sub-epidermal clear zone and abundant intra-histiocytic acid-fast bacilli

·         Perineurium fibrosis with granulomatous inflammation surrounding and entering peripheral neurons

·         Lepromatous form: lack distinct granulomas; coalescing nodules of histiocytes in dermis, nerves, and blood vessel walls

·         Presence of lepra cells- encapsulated amphophilic masses of bacilli found within macrophages

·         Tubercular form: Granulomas with central caseous core rimmed by multinucleated giant cells, epithelioid macrophages, lymphocytes, and plasma cells, sometimes with a rim of fibroblasts/connective tissue



·         Histiocytes with extensively interdigitating plasma membranes, multiple electron-lucent cytoplasmic vacuoles of variable size with dense round structures considered to be the acid-fast organisms



·         Does not grow in culture although has been grown in experimental animals, including the armadillo, non-human primates, and rodents

·         Slower growth than other mycobacteria; grows best at low temperatures (32 to 34 degrees Celsius)

·         Stains more consistently with the Fite-­Faraco acid fast method than with the Ziehl-Nielsen method; +/- silver stains

·         Evokes a delayed hypersensitivity reaction - detectable by skin testing with lepromin (10 kD heat shock protein of M. leprae) but negative tuberculin skin test

·         PCR



·         Other causes of granulomatous dermatitis: fungal, protozoal

·         Nerve involvement is a unique feature of M. leprae



·         Mycobacteria- leprosy group (obligate pathogens):

·         Occurs spontaneously in the nine-banded armadillo (Dasypus novemcinctus) because of their low normal core temperature (important animal model)

·         Reported in sooty mangabey (Cercocebus torquatus), chimpanzee, Cynomolgus macaque (Macaca fascicularis), white handed gibbon (Hylobates lar), rhesus macaque (Macaca mulatta), and African green monkeys (Cercopithecus aethiops)

·         Rats and mice - murine leprosy: Leprosy-like disease caused by M. lepraemurium; primarily viscera and skin (rarely peripheral nerves)

·         Cats: Develop cutaneous granulomas or (less commonly) disseminated disease from M. lepraemurium, M. visibile, MAC, M. microti, rarely M. bovis, and possibly other, atypical mycobacteria

·         Canine leprosy- granulomas/pyogranulomas, low numbers of bacilli

·         Bovine cutaneous opportunistic mycobacteriosis: Causative species unknown, likely secondary to cutaneous abrasions

·         Tuberculosis group (obligate pathogens):

·         M. tuberculosis, M. bovis- often pulmonary

·         Slow-growing opportunistic mycobacteria:

·         M. avium-intracellulare complex (MAIC):

·         M. avium avium (important in poultry), M. avium hominissuis (swine), M. avium silvaticum (rarely in birds) and M. avium paratuberculosis (Johne’s disease in ruminants)

·         M. kansasii, M. ulcerans

·         Rapidly-growing opportunistic (atypical) mycobacteria:

·         M. fortuitum, M. smagmatis, M. chelonae, M. abcessus, M. thermoresistible

·         Atypical mycobaceriosis in cats- recurrent draining nodules



1.     Ackermann MR. Inflammation and healing.  In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed., St. Louis, MO: Elsevier; 2017:111.

2.     Baskin GB. Leprosy. In: Jones TC, Mohr U, Hunt RD, eds. Nonhuman Primates II. Berlin, Germany: Springer-Verlag; 1993: 8-14.

3.     Bernacky BJ, Gibson SV, Keeling ME, Abee CR. Nonhuman primates. In: Fox JG, Anderson LC, Loew FM, Quimby FW, eds. Laboratory Animal Medicine. 2nd ed., San Diego, CA: Academic Press; 2002:741.

4.     Mauldin EA, Peters-Kennedy J.  Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016: 640-641.

5.     Hargis AM, Myers S. The integument.  In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed., St. Louis, MO: Elsevier; 2017:1032-1033, 1143.

6.     Malik R, Smits B, Reppas G, et al. Ulcerated and nonulcerated nontuberculous cutaneous mycobacterial granulomas in cats and dogs. Vet Dermatol. 2013;24(1):146-153.

7.     McAdam AJ, Milner DA, Sharpe AH. Infectious diseases. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philedelphia, PA: Elsevier Saunders; 2015:377-378.

8.     Simmons J, Gibson S. Bacterial and Mycotic Diseases of Nonhuman Primates. In: Abee CR, Mansfield K, Tardif S, Morris T, eds. Nonhuman Primates in Biomedical Research: Diseases. Vol 2. 2nd ed. London, UK: Academic Press; 2012:117-118.

9.     Truman RW, Singh P, Sharma R, et al. Probable Zoonotic Leprosy in the Southern United States. N Engl J Med. 2011;364(17):1626-1633.



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