Signalment:  

3-year-old, female spayed greyhound dog (Canis familiaris).The dog developed two cutaneous nodules on the right and left dorsal ear pinnae two months prior to presentation.

Gross Description:  

The nodules on the right and left dorsal pinnae were alopecic, firm, focally ulcerated and measured 1 cm and 2 mm in diameter, respectively.

Histopathologic Description:

Each sample has a well-demarcated, dense, nodular proliferation of inflammatory cells that expands the deep dermis and subcutis and elevates the overlying epidermis. Inflammatory cells consist predominantly of epithelioid macrophages with rare multinucleated giant cells admixed with lymphocytes, plasma cells and scattered aggregates of neutrophils. Discrete granuloma formation is not present. Between aggregates of inflammatory cells, there is a moderate collagenous stroma and blood vessels are lined by hypertrophied endothelial cells. Within the inflammatory lesion, there are few foci of acute hemorrhage and there are scattered melanophages. In the larger nodule, from the right pinna, there is a focal ulcer (present in some sections) covered by a fibrinocellular exudate.
In the adjacent dermis, there is clumping of melanin within hair follicles with multiple melanophages in the surrounding dermis and mild periadnexal infiltrates of lymphocytes and plasma cells.
Ziehl-Neelson acid fast stain: Low numbers of acid-fast-positive bacilli, measuring 1-2 um in length, are within the cytoplasm of epithelioid macrophages.

Morphologic Diagnosis:  

1. Haired skin (dorsal pinna): regional nodular granulomatous and lymphoplasmacytic dermatitis with focal ulcer and rare intrahistiocytic acid-fast bacilli (canine leproid granuloma syndrome).
2. Haired skin (dorsal pinna): follicular melanin clumping with dermal melanophages (possible color dilution alopecia).

Condition:  

Canine leproid granuloma

Contributor Comment:  

Canine leproid granuloma syndrome is a mycobacterial skin disease characterized by single or multiple, well-circumscribed, firm, variably-sized (2 mm to 5 cm diameter) nodules within the skin or subcutis, predominantly affecting the ear pinna, head and occasionally the distal extremities.(2,6) Short-coated dog breeds, particularly boxer dogs and boxer crosses, are most commonly affected.(2,6) The nodules are thought to be non-pruritic and painless, and occasionally, particularly in the larger nodules, the overlying epidermis is ulcerated or alopecic.(2,6) The nodules have been reported to spontaneously regress without treatment and in some cases surgical excision is considered curative.(2,6) Other cases with a more persistent infection may require antimicrobial therapy.(7) The lesions are confined to the skin with no involvement of lymph nodes or internal organs.(2,6)

On cytologic evaluation of fine-needle aspirates of the nodules, there are spindle-shaped macrophages with variable numbers of lymphocytes and plasma cells with fewer neutrophils and there are few to moderate numbers of negative-staining bacilli extracellularly or within macrophages.(1) On histopathology, there is dermal and/or subcutaneous granulomatous inflammation, with or without pyogranulomatous foci, and the inflammatory lesion consists mainly of epithelioid macrophages and neutrophils with lymphocytes, plasma cells, and rare multinucleated giant cells.(1,2,6) In Ziehl-Neelson acid-fast-stained specimens, there are very low to low numbers of intracellular bacilli in the majority of cases.(1,2,6)

The cause is a saprophytic, as yet unnamed and uncultivated, species of Mycobacterium.(1,2,4,6) Culture is unsuccessful, but with 16s rRNA PCR-based gene analysis on fresh and formalin-fixed, paraffin-embedded tissue, a proposed novel mycobacterial sequence has been identified.(4) The closest relatives of this agent are Mycobacterium tilburgii, M. simiae, and M. genavense.(4) There are significant molecular similarities between the organisms identified in the United States and those in Australia and New Zealand.(2) The suggested mode of transmission of the etiologic agent in canine leproid granuloma syndrome is thought to be percutaneous inoculation via wounds or biting insects.(2,6)

In the present case, the follicular melanin clumping with dermal melanophages is suggestive of concurrent color dilution in this dog. Color dilution alopecia is a hereditary skin disease in dogs with blue or fawn color-diluted coats and has been reported in the greyhound.(3) This disease is typically characterized by atrophy, distortion and abnormal melanin pigmentation of hair follicles with variable alopecia. Large amounts of clumped melanin pigment are within the hair follicle and within melanophages in the dermis around the base of hair follicles.(3) Some of the features of color dilution alopecia, such as the melanin clumping, may be seen in color-dilute dogs without alopecia and are not of pathologic significance.(3) Without enough supporting clinical history in this case, the contributors cannot determine whether this dog was color-diluted or fits the criteria for color dilution alopecia.

JPC Diagnosis:  

1. Haired skin and subcutis: Dermatitis, pyogranulomatous, focally extensive, severe, with rare intrahistiocytic acid-fast bacilli.
2. Haired skin and subcutis: Follicular melanin clumping, multifocal, mild, with perifollicular pigmentary incontinence.

Conference Comment:  

The contributor provides an excellent review of canine leproid granuloma. Conference participants considered histocytoma, plasmacytoma, fungal dermatitis, atypical mycobacteriosis, and sterile granuloma and pyogranuloma syndrome in the differential diagnosis. This case lacks the typical histological features of histiocytoma, including epithelial hyperplasia, superficial dermal edema, occasional reniform nuclei and a moderate mitotic rate.(3) Plasmacytomas typically have few large nuclei and binucleated cells with differential staining of the chromatin pattern, vague packeting, and more differentiated plasma cells at the tumor periphery (3); additionally, small clusters of neutrophilic inflammation and scattered giant cells would be unusual histologic features for tumors of plasma cell origin. Opportunistic fungal infections could cause similar histologic lesions; however, fungal organisms are not observed. Atypical mycobacteriosis more commonly affects cats, and the histopathologic features consist of nodular pyogranulomatous dermatitis and panniculitis with draining tracts and rare acid-fast bacilli found within clear spaces in areas of inflammation.(2) Sterile granuloma and pygranuloma syndrome is an inflammatory condition of unknown cause that is responsive to glucocorticoid therapy; unlike leproid granuloma, lesions are more often multifocal and track hair follicles, and special stains do not reveal an etiological agent.(3) Due to the presence of epithelioid macrophages, giant cells and fibrosis, mycobacterial lesions can resemble sarcoma, and are therefore sometimes described as sarcomatoid.(5)

References:

1. Charles J, Martin P, Wigney DI, Malik R, Love DN: Cytology and histopathology of canine leproid granuloma syndrome. Aust Vet J 77:799-803, 1999
2. Foley JE, Borjesson D, Gross TL, Rand C, Needham M, Poland A: Clinical, microscopic, and molecular aspects of canine leproid granuloma in the United States. Vet Pathol 39:234-239, 2002
3. Gross TL, Ihrke PJ, Walder EJ, Affolter VK: Skin Diseases of the Dog and Cat: Clinical and Histopathologic Diagnosis, 2nd ed., pp. 281-283, 518-522, 840-845, 866-872. Blackwell Publishing, Ames, IA, 2005
4. Hughes MS, James G, Ball N, Scally M, Malik R, Wigney DI, Martin P, Chen S, Mitchell D, Love DN: Identification by 16S rRNA gene analyses of a potential novel mycobacterial species as an etiologic agent of canine leproid granuloma syndrome. J Clin Microbiol 38:953-959, 2000
5. Lopez A: Respiratory system. In: Pathologic Basis of Veterinary Disease, eds. McGavin MD, Zachary JF, 4th ed., p. 520. Mosby Elsevier, St. Louis, MO, 2007
6. Malik R, Love DN, Wigney DI, Martin P: Mycobacterial nodular granulomas affecting the subcutis and skin of dogs (canine leproid granuloma syndrome). Aust Vet J 76:403-407, 1998
7. Malik R, Martin P, Wigney D, Swan D, Sattler PS, Cibilic D, Allen J, Mithcell DH, Chen SCA, Hughes MS, Love DN: Treatment of canine leproid granuloma syndrome: preliminary findings in seven dogs. Aust Vet J 79:30-36, 2001

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3-1. Skin

3-2. Skin

3-3. Skin

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