Atypical presentation of disseminated mycobacteriosis due to Mycobacterium avium in an aged cat

Abstract

In cats, mycobacteriosis tends to present in a syndromic manner, with cases either being due to tuberculosis (TB) (in countries where TB is endemic), one of the “leprosy‐like” diseases affecting the skin and subcutis, panniculitis caused by infection of subcutaneous tissues generally with rapidly growing Mycobacteria spp. or widely disseminated granulomatous disease, which is usually caused by members of the Mycobacterium avium‐intracellulare complex (MAC). Disseminated MAC disease is rare, but when it occurs, usually develops in immunocompromised hosts with defective cell‐mediated immunity. This report describes a case of widely disseminated mycobacteriosis in a 10‐year‐old American Shorthair cat with an atypical multi‐organ distribution including rarely documented thyroid gland involvement. The cat presented for a chronic history of inappetence and weight loss. Abdominal ultrasonography revealed a large mass on the left kidney, and an aspirate (FNA) from this mass showed abundant negative‐staining bacilli which were confirmed to be acid‐fast with Ziehl–Neelsen (ZN) staining. This was consistent with a mycobacterial aetiology. Necropsy revealed mycobacterial granulomas and/or granulomatous inflammation in the kidneys, thyroid gland, liver, spleen, lungs and left mandibular lymph node, with abundant intralesional acid‐fast bacilli in all these tissues. Polymerase chain reaction (PCR) and culture on samples of all affected tissues were positive for M. avium. Collectively, the findings are consistent with disseminated mycobacteriosis due to M. avium with atypical distribution of lesions. Very likely, the cat had underlying immunodeficiency of undetermined cause, exacerbated by the administration of depot corticosteroid.

Mycobacterial infections represent a major global health challenge for humans and animals alike due to their widespread environmental distribution and difficulty in treatment. ¹ , ² Treatment complexity is due to a combination of factors including the necessity for multidrug therapy, often with a long duration, presence of intrinsic and acquired resistance, associated financial challenges, difficulty medicating the cat for a long period and the potential toxicities of certain drugs. ³ , ⁴ Mycobacteria spp. have wide variations in host affinities and pathogenic potential, and their behaviour can range from obligate mammalian pathogens to environmental saprophytes. ¹ , ² , ⁴ , ⁵ , ⁶ , ⁷

Mycobacteria spp. are slow growing organisms and require special media for optimum growth. Hence, diagnosis is most commonly made through direct visualisation of the intralesional “acid‐fast” bacilli (AFB) via cytology and/or histology, negative‐staining bacilli in DiffQuik‐stained cytological preparations and molecular techniques such as polymerase chain reaction (PCR) of specific gene targets followed by sequence analysis of the resulting amplicons. ⁴ , ⁶ Ultimately, the difficulty of achieving a definitive diagnosis and speciation of Mycobacteria spp. infections contributes to the challenging nature of diagnosis and therapy. ³ This is especially the case given that drug susceptibilities can differ between mycobacterial species. ³

In cats, mycobacterial infections commonly cause skin infections and are typically classified into three main groups according to their biological behaviour – the tuberculosis (TB) complex group, the non‐tuberculous mycobacteria (NTM) group and the increasingly complicated “feline and canine leprosy group.” ² , ⁴ , ⁵ , ⁶ , ⁸ The TB complex group includes M. tuberculosis, M. bovis and M. microti. ⁴ , ⁶ , ⁹ M. tuberculosis is mainly a pathogen of humans and is the causative pathogen associated with the human disease tuberculosis. ¹ , ⁴ , ⁶ In cats, infection with M. tuberculosis is uncommon but can occur after the ingestion of infected game meat such as venison that is not subject to meat inspection. ¹⁰ Feline TB typically manifests as skin lesions and less commonly, systemic disease with either pulmonary or abdominal involvement. ⁴ , ⁶ M. bovis infects cattle, dogs, cats and reservoir hosts such as badgers (the United Kingdom) and brush tailed possums (New Zealand), as well as humans. Historically, it is spread to people and cats through the consumption of unpasteurised milk. ¹ , ⁶ , ¹¹ M. microti most commonly causes mandibular lymphadenopathy and/or cutaneous lesions in sites that are prone to animal bites such as the face, legs and tail base. ⁶ The NTM group comprises a large number of mycobacterial species, importantly the M. avium‐intracellulare complex (MAC) which is a group that includes M. avium subspecies (subspp.) avium, hominissus and paratuberculosis (the cause of Johne's disease in sheep and cattle). ⁴ , ⁵ , ⁶ , ⁸ MAC species are opportunistic pathogens which rarely cause granulomatous disease in felines, but when they do, they are either associated with localised infections of the skin and subcutis (e.g., after a cat scratch) in immunocompetent hosts, or disseminated disease in immunocompromised hosts, such as Abyssinian cats with an unknown genetic predisposition. ⁴ , ⁵ , ⁶ , ¹² In previous case reports of feline disseminated M. avium infections, the most commonly affected organs included lymph nodes, lungs, liver and spleen. ¹² Other uncommon to rarely reported organs included bone marrow, intestine, kidneys, omentum, brain, mesentery, peritoneum, vulva, pancreas; and one previous case report of thyroid involvement. ¹² , ¹³ Finally, the feline and canine leprosy group includes M. lepraemurium, M. visible, M. tarwinense, M. lepraefelis and the canine leproid granuloma organism. ⁴ , ⁶ Infection with M. ulcerans, the cause of Buruli ulcer in humans, has also been previously reported in a cat resulting in the formation of a subcutaneous granuloma. ¹⁴

This report describes a rare case of feline disseminated mycobacteriosis due to M. avium with unusual and atypical distribution of lesions, including uncommonly documented involvement of the thyroid gland. ⁵ , ¹² , ¹³ This represents the second reported case of thyroid infection in a cat due to disseminated M. avium. ¹³

Case report

History and clinical presentation

A 10‐year‐old, indoor‐only, spayed female American Shorthair cat (3.1 kg) presented to Clayfield Veterinary Clinic, Queensland on 7 December 2023 for a chronic history of inappetence and weight loss (last recorded weight was 4.4 kg on 28 August 2023). Her diet consisted of commercial dry kibble, and she had never been fed raw meat or unpasteurised milk. The cat had been previously treated with methylprednisolone (16 mg) on two occasions, 23 May 2023 and 13 July 2023, for pyogranulomatous inflammation of the nasal planum with eventual resolution of this lesion. No infectious agents were identified in biopsies taken at the time including with Ziehl–Neelsen (ZN) staining and Grocott's methenamine silver stains to highlight acid‐fast organisms and fungi, respectively. The lesion was interpreted to be most likely due to a focal antigenic or allergic reaction to an unknown external stimulus. On physical examination, the cat was dull, had increased respiratory excursions, a moderate “skin tent” and low‐grade pyrexia (rectal temperature 39.4°C). An underlying systemic infection or neoplastic process was suspected. The cat was given mirtazapine (2 mg, to stimulate appetite) and subcutaneous Hartmann's solution to correct dehydration. Haematology and biochemistry revealed hypoalbuminemia (24 g/L; reference interval [RI] 25–38), hypocholesterolaemia (1.8 mmol/L; RI 2.2–5.5), low serum creatinine concentration (0.07 mmol/L; RI 0.08–0.20) and a lymphopenia (0.5 × 10⁹/L; RI 0.9–7.0 × 10⁹/L).

The cat re‐presented to the clinic on the 16 January 2024. On physical examination, further weight loss (cat now weighed 2.89 kg), severe lethargy, a low‐grade pyrexia (rectal temperature 39.4°C) and a large mass in the left submandibular area were noted. This was suspected to be left mandibular lymphadenomegaly, although a fine needle aspirate (FNA) of this mass was inconclusive. The cat was treated with 50 mg amoxicillin/clavulanic acid BID and 0.5 mg of meloxicam. An abdominal ultrasound was performed, and a large mass was found associated with the left kidney. An FNA of this mass was taken and sent to QML Vetnostics, Queensland for interpretation. Cytology revealed a population of macrophages containing numerous intracytoplasmic negatively staining bacilli. A ZN stain confirmed that the bacteria were acid‐fast (Figure 1A,B). Based on the poor prognosis and marked continual clinical deterioration of the cat, she was subsequently euthanased on 19 January 2024 and submitted for a necropsy.

Figure 1.

(A) Smears made from a fine needle aspirate (FNA) of the renal mass in a cat with disseminated M. avium infection stained with Modified Wrights stain. Black arrow shows a macrophage containing abundant intracytoplasmic clear staining bacilli. A few neutrophils are also present. (B) A replicate smear of the same FNA stained with a Ziehl–Neelsen (ZN) stain to highlight acid‐fast organisms. Image shows abundant positively stained intrahistiocytic acid‐fast bacilli.

Gross findings

A necropsy was performed at the Veterinary Pathology Diagnostic Services (VPDS), Sydney School of Veterinary Science, The University of Sydney. The cat weighed 2.9 kg. No skin lesions were observed on the body. The left mandibular lymph node was markedly enlarged (2.3 × 2.2 × 1.5 cm), firm, pale tan and variably gritty (Figure 2A,B). The left and right lobes of the thyroid gland each had a moderately demarcated, slightly firm, pale‐yellow nodule (left: 0.3 × 0.2 × 0.1 cm; right: 0.8 × 0.6 × 0.3 cm) (Figure 2C). Firmly adhered to the cranial pole of the left kidney and its overlying capsule, and extending into the underlying parenchyma, was a large (3.9 × 3.8 × 2.1 cm) moderately demarcated, firm, pale yellow‐green, gritty, slightly cavitated mass which extended into and effaced the underlying renal cortex and medulla (Figure 2D,E). Scattered throughout the mass were many small pinpoint off‐white, gritty foci.

Figure 2.

(A) The mandibular lymph node in a cat with disseminated M. avium infection. Black arrow shows the markedly enlarged left mandibular lymph node. (B) The cut surface of the markedly enlarged left mandibular lymph node in a cat with disseminated mycobacteriosis. Black arrow indicates the cut surface. (C) Left and right lobes of the thyroid gland in a cat with disseminated mycobacteriosis. Each thyroid lobe has a moderately demarcated, slightly firm, pale‐yellow nodule (indicated by the black arrows). (D) Abdominal organs in situ in a cat with disseminated mycobacteriosis. Black arrow indicates the left kidney with a large mass. (E). Kidneys after removal at necropsy in a cat with disseminated mycobacteriosis. Black arrow indicates the cut surface of the large mass associated with the left kidney. This mass extends into and effaces the underlying cortex and medulla. (F) High power photomicrograph of the left renal granuloma stained with a ZN stain to highlight acid‐fast bacilli in a cat with disseminated mycobacteriosis. Image shows abundant positively stained intrahistiocytic acid‐fast bacilli in the lesion.

A standard set of tissues, including the brain, lungs, liver, spleen, kidneys (including the left renal mass), adrenal glands, heart, thyroid gland, oesophagus, trachea, urinary bladder, skeletal muscle, sciatic nerve, pancreas, small and large intestine and mandibular lymph nodes, were collected and fixed in 10% neutral buffered formalin and processed routinely for histological examination. Samples of the liver, lung, left kidney and mass, spleen, right thyroid lobe and the left mandibular lymph node were stored in a frozen state for microbiology.

Microscopic findings

The masses associated with the left mandibular lymph node, left kidney and thyroid gland were consistent with pyogranulomas containing large numbers of macrophages variably intermixed with lymphocytes, plasma cells and polymorphonuclear leukocytes. Additional sites of granulomatous inflammation were identified in the lungs, spleen and liver. In all tissues with inflammation, ZN staining demonstrated the presence of intrahistiocytic short acid‐fast bacilli (AFB; 2–3 μm) which were most abundant in the left renal and mandibular lymph node tissues (Figure 2F). Intravascular (large veins) extracellular AFBs were also observed in the left and right kidneys (Figure 3A,B).

Figure 3.

(A) Low power photomicrograph of a renal blood vessel stained with a ZN stain to highlight acid‐fast organisms in a cat with disseminated mycobacteriosis. Black arrow shows a cluster of acid‐fast bacilli within the vascular lumen. (B) Higher power photomicrograph of the same section. Black arrow shows a cluster of acid‐fast bacilli within the vascular lumen.

Microbiology

Frozen samples of the liver, lung, left kidney and mass, spleen, right thyroid lobe and the left mandibular lymph node were sent for mycobacterial culture and PCR testing at the Centre for Infectious Diseases and Microbiology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, New South Wales. PCR testing was performed on all tissue samples, following DNA extraction with Roche High Pure PCR Template Preparation Kit (Roche Diagnostics). In‐house PCR for M. avium complex was performed, ¹⁵ and all samples were positive for MAC. Mycobacterial culture was performed on tissue samples after digestion and decontamination with N‐acetyl‐cysteine‐sodium hydroxide (NALC‐NaOH). Concentrated digested samples were inoculated into two BD Bactec Mycobacterial Growth Indicator Tubes (MGIT), and incubated at 37 and 30°C. In‐house prepared Lowenstein–Jensen slopes were also inoculated, and incubated at 37°C. All samples were direct smear positive by auramine stain. The 37°C MGIT tubes were positive for acid‐fast bacilli at 7 days (lymph node and kidney), 9 days (lung, liver and thyroid gland) and 20 days (spleen). All six tissues returned positive results with an in‐house designed M. avium complex PCR, based in the internal transcribed spacer (ITS) region.

Discussion

This report describes an atypical case of feline disseminated mycobacteriosis due to M. avium. The lesion distribution was most unusual. The following discussion focuses on several key questions pertinent to this case – (i) What was the pathogenesis of M. avium in this instance? (ii) What was the primary portal of entry? (iii) What was the pathway(s) and mechanism for widespread dissemination? (iv) What predisposing factors may have increased this patient's susceptibility to infection? and (v) What are the similarities and differences with other species affected by disseminated M. avium?

Nontuberculous mycobacteria and specifically members of the MACcomplex are ubiquitous environmental organisms with a wide distribution including in soil, and both natural and engineered water systems including farm dams, stagnant pools, drinking water and tap aerosols. ⁷ , ⁸ , ¹² , ¹⁶ , ¹⁷ Indeed, humans are continuously exposed to low levels of environmental Mycobacteria spp. at approximately 50 to 500 bacilli per day. ⁷ Owing to their ubiquitous environmental distribution, NTMs are often opportunistic pathogens in humans and animals, causing infection in immunocompromised hosts or after penetrating injury, most notably in human patients with acquired immunodeficiency syndrome (AIDS) but also in patients with leukaemia, lymphoproliferative disorders, cancer, autoimmune disease and those undertaking immunosuppressive drug therapy. ¹ , ⁵ , ⁷ , ⁸ , ¹⁶ , ¹⁸ Prior to the development of highly effective antiretroviral therapy for human immunodeficiency virus (HIV), between 20% and 50% of severely immunocompromised AIDS patients developed disseminated MACinfections. ⁸

In cats, NTM infections are commonly cutaneous, usually due to contamination of a wound with dirt or soil following trauma or surgery. ⁴ , ¹² Disseminated disease due to NTM species are rare with the exception of the MAC. ⁴ , ¹² The exact pathogenesis of disseminated MAC infections in cats is not yet fully understood in all instances, though haematogenous dissemination is usually the proposed mode of spread from a primary respiratory or alimentary portal of entry. ⁵ Primary infection likely arises due to either ingestion of contaminated soil or water or through the inhalation of contaminated airborne dust in immunocompromised hosts. ⁵ Mycobacteria spp. are phagocytised by macrophages, but their ability to survive and even multiply intracellularly induces a granulomatous to pyogranulomatous inflammatory response in affected organs. ⁴

Within the MAC, M. avium is the most likely organism to cause disseminated disease in the cat. ¹⁸ Multi‐organ involvement is a feature of disseminated MAC infections, and diffuse interstitial lung involvement can be characteristic, at least in the Abyssinian breed. ¹² Whilst lymph nodes, lungs, liver and spleen have been previously reported as commonly affected sites in disseminated M. avium infections, this case features rarely documented prominent thyroid gland involvement ⁵ , ¹² , ¹³ and a large conspicuous granuloma adjacent to a kidney containing enormous numbers of AFBs, that is, multibacillary (or lepromatous) disease. Indeed, this report represents the second documented case of thyroid infection, ¹³ and the sixth report of renal involvement, amongst other reported cases of feline disseminated M. avium disease. ¹²

Overall, descriptions of feline disseminated mycobacteriosis due to M. avium are rare and sporadic, as cats appear to be naturally resistant to these organisms, ¹⁸ except for certain breeds such as Siamese, Somali and Abyssinians which are over‐represented. ⁵ , ⁶ , ¹⁷ , ¹⁸ An underlying familial immune defect has been postulated similar to humans and dogs where such familial defects are well characterised, and mostly relate to a dysfunctional interferon‐gamma (IFNγ)‐mediated immunity or a specific defect in the CARD9 gene. ⁵ , ¹⁹ , ²⁰ Apart from cats, descriptions of disseminated MAC infection have also been described in humans, dogs, primates, swine, cattle, sheep, marsupials and horses. ¹⁷ , ¹⁸ , ²¹ , ²² Indeed, M. avium subspp. paratuberculosis is the causative agent of Johne's disease in ruminants, and possibly some cases of Crohn's disease in humans. ²¹ , ²³ Similar to cats, canine MAC infections tend to present with multisystemic disease, often with involvement of the lymph nodes, spleen, liver, lungs, omentum, intestinal wall and occasionally the kidneys. ¹⁷ , ²⁴ , ²⁵ In dogs, certain breeds such as Basset Hounds and Miniature Schnauzers are predisposed to M. avium infection. ¹⁷ , ²⁴ Non‐regenerative anaemia, neutrophilia, lymphopenia, hypoalbuminaemia, hypo‐ or hyperglobulinaemia with variable hypercalcaemia, hyperbilirubinaemia and elevated liver enzymes have been reported in dogs and cats with NTM infections, although it should also be noted that patients can present with an absence of haematologic and biochemical abnormalities. ¹⁷ In the case described, the patient did present with lymphopenia and hypoalbuminaemia with routine haematology and biochemistry. The low serum creatinine was probably related to the loss of muscle mass due to chronic hyporexia.

Immunocompromise is considered a risk factor for the development of systemic mycobacteriosis due to MAC, generally reflecting defective cell‐mediated immunity. ⁵ , ¹² , ¹⁸ However, it is also important to recognise that unlike in humans where retroviral (HIV) infections are a well‐established risk factor for MAC‐associated systemic mycobacteriosis, no significant association has been found to date between infection with either feline leukaemia virus (FeLV) and/or feline immunodeficiency virus (FIV) and mycobacterial infections. ¹² , ¹⁸ In this case, the cat was not tested for FIV or FeLV making it difficult to draw associations with retroviral status.

Some case reports have described systemic mycobacteriosis due to MAC/M. avium in cats that were on long term or post‐transplant immunosuppressive therapy, such as cyclosporine and prednisolone. ⁵ , ¹² , ²⁶ In the case described, the cat did receive injectable methylprednisolone, a potent long‐acting ‘depot’ corticosteroid, on two occasions (the last dose was administered 147 days prior to clinical presentation for systemic illness), for the treatment of a pyogranulomatous inflammatory lesion on the nasal planum which eventually resolved. As described earlier, biopsies of this lesion at the time allegedly did not reveal the presence of infectious agents, including with a ZN and Grocott's methenamine silver stain to highlight acid‐fast organisms and fungi, respectively. Although unproven in this case, it remains possible that the initial portal of entry for the M. avium infection may have been the nasal planum lesion. The corticosteroid therapy may have impaired the patient's cell‐mediated immunity, creating permissive conditions for dissemination. ⁵ Haematogenous dissemination was presumed in this case, especially given the histologic observation of intravascular AFBs, supporting the proposed mode of systemic spread suggested by the literature (Figure 3A,B). ⁵ A genetic immune defect cannot be fully excluded, although the American Shorthair breed is not considered to be a breed predisposed to mycobacterial infections and most genetically programmed immune defects occur in young animals. ⁵

Conclusion

This report describes a rare case of feline disseminated mycobacteriosis due to M. avium with an atypical distribution of lesions. This case also features uncommonly documented thyroid involvement and a large peri‐renal AFB‐rich granuloma in a cat with disseminated M. avium infection, supporting the atypical distribution. ⁵ , ¹² , ¹³ Systemic mycobacteriosis should therefore be a consideration in patients with intra‐abdominal masses and/or lymphadenomegaly, especially if there is a history of cutaneous lesions or immunosuppressive therapy.

Conflicts of interest and sources of funding

The authors declare no conflicts of interest or sources of funding for the work presented here.

Teh, A. , Robertson, J. , Donahoe, SL. , Crighton, T. , Boyd, S. and Malik, R. , Atypical presentation of disseminated mycobacteriosis due to Mycobacterium avium in an aged cat. Aust Vet J. 2025;103:121–126. 10.1111/avj.13410

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.