Signalment:  

6-month-old, female, Cavia porcellus, Hartley guinea pigExperimental animal, infected via aerozolization with Mycobacterium tuberculosis. This animal was euthanized after being infected for 90 days.

Gross Description:  

The left mammary gland is markedly enlarged and exudes necrosuppurative material upon mild palpation. This affected region may incorporate and efface normal inguinal lymphoid architecture as this node is neither palpable nor observed. Approximately 30-40% of pulmonary parenchyma is replaced by primary tuberculoid lesions with the remaining lung parenchyma affected by secondary lesions. The primary lesions are depressed centrally and are surrounded by a dense fibrotic parenchyma. The mediastinal lymph nodes are diffusely enlarged with loss of lymphoid architecture and are further expanded by fibrinous adhesions which connect with the ventral aspect of the thoracic pleura. Multifocally, the spleen and the liver contain multifocal to coalescing granulomas and are markedly enlarged. The spleen is approximately 10x larger than normal.

Histopathologic Description:

Haired skin, subcutis, and mammary glandular tissue. The deep subcutaneous tissue is effaced by large coalescing nodules of epithelioid macrophages, admixed with heterophils, rare lymphocytes and multinucleated giant cells (Fig. 4-1). Multifocally, these nodules contain central areas of necrosis characterized by degenerate heterophils, hypereosinophilic debris (necrosis), and karyorrhectic debris. In some sections, large areas of cavitation of these necrotic regions are observed. Admixed within this extensive inflammatory response are rare entrapped adipocytes and remnant mammary glands. There are no remaining ductules. Within the superficial subcutis, subjacent to the deep dermis, there are small granulomas comprised of macrophages and lymphocytes. There is superficial expansion of the epidermis by a moderate amount of orthokeratotic hyperkeratosis. An acid-fast stain revealed few positive bacilli within the necrotic centers.

Morphologic Diagnosis:  

Mammary gland: Mastitis, necrosuppurative, granulomatous, regionally extensive, with acid- fast bacilli

Lab Results:  

Lung, viable cell count; approximately 9.8 X 106

Condition:  

Mycobacterium tuberculosis

Contributor Comment:  

The guinea pig is used extensively as an animal model of human tuberculosis. (5) The primary lesion complex in both humans and guinea pigs are similar and comprises multifocal granulomatous inflammatory lesions within the lung and draining lymph nodes. Similar to humans, guinea pigs develop small foci of mixed inflammation which subsequently develops into the characteristic granuloma which is comprised predominantly of macrophages and occasionally granulocytes.(8) As seen in this case, these large granulomas develop a central zone of necrosis, which is where the highest concentrations of bacterium can be observed in both humans and in guinea pigs.(1)

The guinea pig in this case was experimentally infected via aerosolization with Mycobacterium tuberculosis to evaluate pulmonary tuberculosis. Diagnosis of tuberculosis in the mammary gland was an incidental finding. To the contributors knowledge, tuberculosis mastitis has never been reported in an experimentally infected guinea pig. In human patients, involvement of the mammary gland is a rare manifestation of the disease.(2) Clinically, tuberculoid granulomas of the mammary gland are unilateral and may mimic breast cancer and/or breast abscesses which are all managed differently making accurate diagnosis crucial.(3,9) The reliable diagnostic tests include bacteriologic culture, histopathology, and guinea pig inoculation.(6)

Tuberculosis mastitis (TM) in humans can occur as primary or secondary disease. Secondary involvement of the mammary gland is more common than primary infection of the mammary gland.(6) Common routes of infection include the lymphatic route, hematogenous route or from direct spread from local organs. The direct form of spread in humans may occur from an infected rib, cartilage, or joint.(6)

In humans, there are three forms of mammary tuberculosis: nodular, diffuse, and sclerosing. The nodular form is the most common presentation in women and is typically slow growing and often develops a caseating center.(7) The sclerosing form develops excess fibrous connective tissue and is often the most difficult to differentiate from mammary gland carcinoma.(7)

JPC Diagnosis:  

Mammary gland: Mastitis, pyogranulomatous, focally extensive, severe with acid-fast bacilli

Conference Comment:  

Mycobacteria are non-motile, non-spore forming organisms with a lipid-rich cell wall that stains poorly with gram-stain. Acid-fast stains are commonly used to identify mycobacteria in tissue sections. The term tuberculosis is now conventionally used to describe only infections caused by Mycobacterium bovis and Mycobacterium tuberculosis, whereas diseases caused by other mycobacterial species are referred to as mycobacteriosis or atypical mycobacteriosis.(4)

Susceptibility to tuberculosis and organ system affected varies greatly among domesticated animal species. The hallmark lesion of tuberculosis is the granuloma. These granulomas may be in different organs with slightly different histologic appearances based on the route of entry and species affected. Below is a brief list of animal species, susceptibility, and organ systems affected by tuberculosis.

Species	Susceptibility	Organ System Affected
Cat	More susceptible to M. bovis	Gastrointestinal disease ingestion of contaminated wildlife or milk
Dog	Susceptible to M. bovis and M. tuberculosis	Respiratory form
Cattle	More susceptible to M. bovis	Respiratory and gastrointestinal forms calcification can also occur
Pigs	Susceptible to both M. bovis and M. tuberculosis	Systemic infection
Small ruminants	Rare cases	Similar to cattle when infected
Horses	Rare; usually M. bovis	Gastrointestinal; also see lesions in retropharyngeal and mesenteric lymph nodes
Non-Human Primates	Very susceptible to M. tuberculosis	Infected humans transmit respiratory form to NHPs
Birds (Psittacines)	Only birds to get tuberculosis; get both M. tuberculosis and M. bovis	Respiratory form - transmitted from humans

(4)

References:

1. Basaraba RJ, Bielefeldt-Ohmann H, Eschelback EK, Reisenauer C, Tolnay AE, Taraba LC, Shanley CA, Smith EA, Bedwell CL, Chlipala EA, Orme IM: Increased expression of host iron-binding proteins precedes iron accumulation and calcification of primary lung lesions in experimental tuberculosis in the guinea pig. Tuberculosis 88:69-79, 2008
2. Bani- Hani KE, Yaghan RJ, Matalka II, Mazahreh TS: Tuberculous mastitis: a disease not to be forgotten. International Journal of Tuberculosis Lung Disease 9(8):920-925, 2005
3. Bedi US, Bedi RS: Bilateral breast tuberculosis. The Indian Journal of Tuberculosis 215-217, 2001
4. Caswell JK, Williams KJ: Respiratory system. In: Jubb, Kennedy and Palmers Pathology of Domestic Animals, ed. Maxie MG, 5th ed., pp. 606-610. Elsevier Limited, Philadelphia, PA, 2007
5. Gupta UD, Katoch VM: Animal models of tuberculosis. Tuberculosis 85:277-293, 2005
6. Hale JA, Peters GN, Cheek JH: Tuberculosis of the breast: rare but still extant. The American Journal of Surgery 150:620-624
7. Hamit HF, Ragsdale TH: Mammary tuberculosis. Journal of the Royal Society of Medicine 75:764-765, 1982
8. McMurray DN: Guinea pig model of tuberculosis. In: Tuberculosis: Pathogenesis, Prevention, and Control, ed. Broom BR, pp. 135-147. ASM Press. Washington, DC, 1994
9. Mufide AN, Saglam L, Polat P, Erdogan F, Albayrak Y, Povoski SP: Mammary tuberculosis- importance of recognition and differentiation from that of a breast malignancy: report of three cases and review of the literature. World Journal of Surgical Oncology 5:67-73, 2007

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4-1. Mammary gland, guinea pig

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