AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

August 2016

I-B03

 

Signalment (JPC #1113469):  Cat

 

HISTORY:  This cat presented with multiple skin nodules.

 

HISTOPATHOLOGIC DESCRIPTION:  Haired skin:  Expanding the dermis, subcutis, separating and surrounding skeletal myofibers of the panniculus carnosus, elevating the overlying mildly hyperplastic and focally ulcerated epidermis, and widely separating adnexa, are multifocal to coalescing, 5-15 mm diameter nodules of pyogranulomatous inflammation.  Inflammatory nodules are often centered on areas of coagulative (with loss of differential staining and retention of tissue architecture) and lytic (loss of normal architecture with replacement by eosinophilic cellular and karryorrhectic debris admixed with viable and degenerate neutrophils and hemorrhage) necrosis.  Necrotic foci are surrounded by numerous epithelioid macrophages, neutrophils, fewer multinucleate giant cells (Langhans and foreign body types), scattered lymphocytes, plasma cells, fibroblasts and fibrous connective tissue.  There are multiple, often perivascular aggregates of lymphocytes and plasma cells at the periphery of the pyogranulomatous nodules.  Entrapped lymphatics are moderately ectatic.  Multifocally, inflammatory cells separate and surround skeletal myocytes of the panniculus carnosus; affected myofibers are occasionally swollen, with pale, vacuolated sarcoplasm (degeneration).  The overlying epidermis is focally extensively ulcerated and replaced by a serocellular crust composed of abundant degenerate neutrophils admixed with eosinophilic cellular and karyorrhectic debris, erythrocytes and eosinophilic, fibrillar, beaded material (fibrin).  The epidermis adjacent to the ulcer is mildly acanthotic and spongiotic, with minimal orthokeratotic hyperkeratosis.

 

Slide B:  Haired skin (acid fast):  There are moderate numbers of 3-5 um acid-fast bacilli, often arranged in parallel bundles present within the cytoplasm of epithelioid macrophages and multinucleate giant cells.

 

MORPHOLOGIC DIAGNOSIS:  Haired skin and subcutis:  Dermatitis and panniculitis, pyogranulomatous and ulcerative, multifocal to coalescing, marked, with intrahistiocytic acid-fast bacilli, breed unspecified, feline.

 

ETIOLOGIC DIAGNOSIS:  Cutaneous mycobacteriosis

 

CAUSE:  Mycobacterium lepraemurium

 

CONDITION:  Feline leprosy syndrome

 

GENERAL DISCUSSION:

·         A group of rare granulomatous mycobacterial skin diseases caused by various acid-fast bacteria (AFB) that are not culturable using standard mycobacteriological methods

·         Most prevalent in temperate maritime climates of New Zealand, Australia, North America (e.g. northwest US), and Europe

·         Feline cutaneous mycobacteriosis is now known to be caused by several different species of Mycobacterium often with overlapping clinical and histological features precluding development of a simple classification scheme; however, three manifestations are classically described:

1.    Feline leprosy syndrome:  Two distinct forms have been described, thought to be associated with the host’s immune response and species of infection:

§  Tuberculoid form (usually M. lepraemurium):  Associated with a strong cell mediated response and paucibacillary histopathology; usually occurs in younger cats <5 years old; and is a localized nodular disease with occasional widespread cutaneous and subcutaneous lesions

§  Lepromatous form (a novel mycobacterium related to M. leprae, M. haemophilum, and M. malmoense):  Associated with a poor cell mediated immune response and multibacillary histopathology; usually occurs in older cats >9 years old; and is a multifocal, slowly progressive, nodular, and infiltrative skin disease

§  Feline multisystemic granulomatous mycobacteriosis is a distinct form of lepromatous leprosy caused by a slow-growing taxa (provisionally called M. visibilis) and characterized by diffuse cutaneous disease with widespread dissemination to internal organisms

2.    Atypical mycobacteriosis (opportunistic mycobacterial granulomas):  Chronic or recurrent fistulous tracts, ulcers, fasciitis, and ulcerative nodules most frequently on ventral abdomen; most cases caused by rapidly growing species (e.g. M. fortuitum, M. phlei, M. smegmatis, M. chelonae) or rarely, slowly growing species (M. avium, M. chitae, M. xenopi, M. ulcerans); ease of culture differentiates atypical mycobacteriosis from feline leprosy

3.    Cutaneous tuberculosis: Multiple ulcers, plaques, nodules, and abscesses that discharge a thick exudate composed of pyogranulomatous inflammation with caseous necrosis; caused by M. bovis, M. tuberculosis, or rarely, M. avium or M. microti

 

PATHOGENESIS:

·         Cat or rat bite (suspected mode of transmission) > enters macrophages > blocks fusion of phagosome and lysosome > intracellular replication > persistence of antigen in tissue > tissue destruction via cell mediated inflammatory response

·         Immunosuppression has been proposed to contribute to infection, particularly in lepromatous leprosy caused by a novel mycobacterial species in older cats; however, no association concurrent infection (e.g. FIV, FeLV) has been proven

·         Tuberculoid leprosy is characterized by a TH1 response with production of IL-2 and IFN-gamma (which activates macrophages); IL-12 is important in the generation of a TH1 response, and lack of IL-12 may lead to lepromatous leprosy

·         Lepromatous leprosy is characterized by a defective TH1 response or a dominant TH2 response with production of IL-4, IL-5, and IL-10 that may suppress macrophage activation

 

TYPICAL CLINICAL FINDINGS:

·         Tuberculoid leprosy:  Affects younger adult cats (<5 years); rapidly progressive; lesions tend to spread, ulcerate, and recur following surgery

·         Lepromatous leprosy (novel mycobacterial infection): Affects older adult cats (>9 years); slowly progressive; may be initially localized and progress to widespread, or generalized from the outset

·         Lepromatous leprosy (feline multisystemic granulomatous mycobacteriosis): Diffuse (vs. nodular) disease with widespread dissemination to internal organs

·         Systemic illness is rare

·         Spontaneous remission has been reported

 

TYPICAL GROSS FINDINGS:

·         Tuberculoid leprosy:  Locally extensive; nonpainful nodules typically on the head, neck, and distal limbs (rarely tongue, lips, nasal planum) +/- regional lymphadenopathy; nodules often ulcerate

·         Lepromatous leprosy (novel mycobacterial infection):  More generalized (though may be localized initially) nodular skin lesions that tend not to ulcerate

·         Lepromatous leprosy (feline multisystemic granulomatous mycobacteriosis): Diffuse (vs. nodular) thickening, alopecia, edema, and ulceration primarily on the

·         Regional lymph nodes are often enlarged

·         Systemic dissemination is rare

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·         Tuberculoid leprosy:

·         Dermal to subcutaneous granulomas with central caseation, surrounded by pyogranulomatous inflammation with epithelioid macrophages and occasional multinucleated giant macroophages

·         Relatively few to moderate AFB, often confined to necrotic areas

·         Lepromatous leprosy:

·         Nodular to diffuse granulomatous dermatitis and panniculitis without necrosis

·         Sheets or nodules of large, foamy macrophages with sparse giant cells

·         Variable numbers of scattered lymphocytes, plasma cells, multinucleate giant macrophages, and neutrophils

·         Abundant intracellular AFB (multibacillary) arranged in dense parallel intrahistiocytic intracytoplasmic accumulations which displace the nucleus

·         Mineralization and encapsulation not typically observed

·         +/- Acanthosis and/or ulceration in overlying epidermis

 

ADDITIONAL DIAGNOSTIC TESTS:

·         Acid fast stains:  Ziehl-Neelsen (standard), Fite-Farraco (modified), Kinyoun’s (modified)

·         Extremely difficult to culture; requires an enriched egg yolk medium; may take weeks to months to grow

·         Presence of acid-fast bacilli with a negative mycobacterial culture supports the diagnosis of feline leprosy but is not definitive

·         PCR

·         Transmission of the disease to laboratory animals

 

DIFFERENTIAL DIAGNOSIS:

·         Grossly, nodules resemble neoplasms

·         Xanthoma: sterile granulomas composed of foamy macrophages; resemble lepromatous leprosy but lack the numerous AFB typically seen in lepromatous leprosy

·         Mycotic infections (e.g. sporotrichosis, cryptococcosis and other systemic mycoses): differentiate with fungal stains, culture

·         Atypical mycobacteriosis and cutaneous tuberculosis may resemble leprosy; differentiate with culture, PCR

·   Sterile granuloma and pyogranuloma syndrome

·         Foreign body granulomas/reactions

·         Chronic bacterial infection

·         Progressive dendritic cell histiocytosis

 

COMPARATIVE PATHOLOGY:

·         Canine leproid granuloma: Granulomatous disease of skin and subcutis caused by an as yet unnamed species related to M. tilburgii, M. simiae, and M. genavense; thought to enter via trauma or biting arthropods; often self-limiting in immunocompetent dogs; breed predilection for short-haired breeds (especially boxers); variable number of AFB seen

·         Bovine cutaneous tuberculosis (cutaneous opportunistic mycobacteriosis): nodular lesions in the dermis and subcutis primarily of lower legs (may spread proximally) without lymph node involvement; saprophytic mycobacterial implicated and thought to enter via abrasions (M. kansasii has been reported in some cases); may cause false positive reaction to bovine tuberculin skin tests

·         Mycobacterium lepraemurium causes rodent leprosy in rats

·         Mycobacterium leprae infects humans, chimpanzees, sooty mangabeys, and armadillos; in contrast to human leprosy, feline leprosy is not typified by peripheral nerve involvement

·         Mycobacterium microti: Vole tuberculosis; field vole is the maintenance host, the disease is of ecological interest due to adverse effects on field voles; increasing prevalence with age, skin lesions only occur in advanced stages of disease; generally a systemic disease; subcutaneous and skin lesions are almost exclusively in the cranial part of the body; tuberculosis lesions were noted in the liver and spleen in 90% and 80% of affected animals; never found tuberculosis lesions in lungs without systemic disease (involvement of liver and spleen)

 

REFERENCES:

1.     Appleyard GD, Clark EG. Histologic and genotypic characterization of a novel Mycobacterium species found in three cats. J Clin Microbiol. 2006;40:2425-2430.

2.     Davies JL, Sibley JA, Myers S, Clark EG, Appleyard GD. Histological and genotypical characterization of feline cutaneous mycobacteriosis: a retrospective study of formalin-fixed paraffin-embedded tissues. Vet Dermatol. 2006;17:155-162.

3.     Gross TL, Ihrke PJ, Walder EJ, Affolter VK. In: Skin Diseases of the Dog and Cat. 2nd ed. Ames, IA: Blackwell Science; 2005:276-281.

4.     Hargis AM, Ginn PE. The integument. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO: Mosby Elsevier; 2012:1033-1034.

5.     Kipar A, Birthe SJ, Hetzel U, Abo Rokia M, Telfer S, Lambin X, Birtles RJ, Begon M, Bennett M.  Mycobacterium microti tuberculosis in Its maintenance host, the field vole: Characterization of the disease and possible routes of transmission.  Vet Pathol.  2014:51(5)903-914.

6.     Laprie C, Duboy J, Malik R, Fyfe J.  Feline cutaneous mycobacteriosis: a review of clinical, pathological and molecular characterization of one case of Mycobacterium microti skin infection and nine cases of feline leprosy syndrome from France and New Caledonia. Vet Dermatol. 2013;24:561-e134.

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

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

9.     Muller G, Scott D, Miller W, Griffin C. Veterinary Dermatology. 6th ed. W.B. Philadelphia, PA: Saunders; 2001:315-317.

 

 


 


 

Feline Cutaneous Mycobacteriosis Syndromes

Syndrome

Feline Leprosy – rare localized cutaneous infection caused by mycobacteria that cannot be cultured by standard mycobacteriologic standards

NO zoonotic potential

Atypical Mycobacteriosis (Opportunistic Mycobacterial Granulomas)

Cutaneous Tuberculosis

Subtype

Tuberculoid

Lepromatous

 

 

Subtype

 

Novel Mycobacterial Infection

Feline Multisystemic Granulomatous Mycobacteriosis

 

 

Etiology

M. lepraemurium non zoonotic

Novel species related to M. leprae, M. haemophilum, M. malmoense

M. visibilis (provisional)

Mostly rapidly growing species (M. fortuitum, M. phlei, M. smegmatis, M. chelonae) or rarely, slowly growing species (M. avium, M. chitae, M. xenopi, M. ulcerans)

M. bovis, M. tuberculosis, or rarely, M. avium or M. microti (causes cutaneous tuberculosis in cats)

Signalment

Young adults (<5 years), males possibly > females

Older adults (>9 years)

 

 Dz is seen in both healthy and immunocompromised individuals

 

Clinical Course

Rapidly progressive; tends to spread, ulcerate, and recur following surgery

Protracted, slowly progressive

 

Three syndromes: mycobacterial panniculitis involving chronic infection of the SQ and skin, pyogranulomatous lobar pneumonia and disseminated systemic disease in immunocompromised individuals

Most cases of M. microti involve submandibular lymphadenopathy and cutaneous lesions that affect the fight and bite sites

Clinical Findings

Locally extensive; granulomas concentrated on head and limbs (+/- tongue, lips, nasal planum)

Variable (i.e. localized with progression to widespread, or generalized disease from the outset)

Diffuse (vs. nodular) cutaneous disease with widespread dissemination to multiple internal organs

Chronic or recurrent fistulous tracts, ulcers, fasciitis, and ulcerative nodules most frequently on ventral abdomen

Multiple ulcers, plaques, nodules, and abscesses that discharge a thick exudate

Gross Findings

Multiple painless, raised, fleshy tumor-like lesions; may be invasive and drain to regional lymph nodes; may ulcerate

Generalized nodular skin lesions that do not ulcerate

Diffuse cutaneous disease

Lesions can occur anywhere on the cat but are most common in the caudal abdomen, inguinal region or lumbar region; causative organisms thrive in fatty tissues

Cutaneous lesions are single or multiple ulcers, plaques, nodules or abscesses that exude thick yellow to green fluid

Microscopic Findings

Paucibacillary; sparse to moderate numbers of AFB that do not stain with hematoxylin

Pyogranulomas with a necrotic core

Multibacillary; numerous AFB that do stain with hematoxylin

No areas of necrosis

Multibacillary; numerous AFB that do stain with hematoxylin ("visible")

Multinodular to diffuse pyogranulomatous inflammation with caseous necrosis; organisms are rare and difficult to find

Nodular to diffuse granulomatous to pyogranulomatous dermatitis and panniculitis with central caseous necrosis and few to many AFB

 

 


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