Pathology in Practice

Caitlyn R. Martinez 1Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Tracey D. Jensen 3Wellington Veterinary Hospital, Wellington, CO 80549

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Allison M. Bradley 2Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Andrea A. Bohn 1Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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History

A 2-year-old 3.7-kg (8.1-lb) spayed female domestic longhair cat was referred to a veterinary teaching hospital because of a 1-week history of hyporexia, weight loss (moderate to marked; body condition score, 3/9), and respiratory signs. The cat was primarily an outdoor cat and had never traveled outside of Colorado.

Clinical and Clinicopathologic Findings

Physical examination findings included tachypnea (70 breaths/min) and increased respiratory effort with harsh expiratory lung sounds. Results of a CBC and serum biochemical panel were unremarkable. The cat was negative for anti-FIV antibody and FeLV antigen; no additional evidence of immunosuppression was detected. Thoracic radiography and CT revealed multifocal regions of pulmonary alveolar infiltrates and consolidation. A large gas-attenuating region within the left caudal lung lobe was also observed. Fine-needle aspirate specimens of the infiltrated pulmonary parenchyma were examined cytologically (Figure 1). The specimens were cellular with moderate blood in the background. Many foamy macrophages were present along with low to moderate numbers of neutrophils. Some cells appeared to contain phagocytosed microorganisms.

Figure 1—
Figure 1—

Photomicrograph of a fine-needle aspirate specimen obtained from a pulmonary lesion in a cat with a 1-week history of hyporexia, weight loss (moderate to marked), and respiratory signs. Foamy macrophages and neutrophils are visible on a background of blood. Several microorganisms are observed within a macrophage. Wright-Giemsa stain; bar = 20 μm.

Citation: Journal of the American Veterinary Medical Association 256, 8; 10.2460/javma.256.8.883

Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→

Additional Cytologic and Microbiological Findings

On further examination of the fine-needle aspirate specimens, the organisms in the macrophages and neutrophils were round to oval (maximal dimension, 2 to 4 μm), with a basophilic internal structure and a thin, clear halo (Figure 2). Rarely, these organisms displayed narrow-based budding.

Figure 2—
Figure 2—

Additional photomicrographs of a fine-needle aspirate specimen obtained from a pulmonary lesion in the cat in Figure 1. A—Notice the phagocytosis by a foamy macrophage of several round to oval microorganisms that have a maximal dimension of 2 to 4 μm. Wright-Giemsa stain; bar = 20 μm. B—A neutrophil contains similar organisms, some of which have narrow-based budding. Wright-Giemsa stain; bar = 10 μm.

Citation: Journal of the American Veterinary Medical Association 256, 8; 10.2460/javma.256.8.883

A urine sample was collected via cystocentesis from the cat and submitted to a diagnostic laboratory.a An assay to detect Histoplasma antigenb was performed on the urine sample, and the result was positive (reading was greater than the assay's limit of quantification).

Fungal culture of a lung lesion specimen yielded growth of microorganisms, which were sent to another laboratoryc for DNA probing. The DNA probing results were negative for Histoplasma capsulatum and weakly positive for Blastomyces dermatitidis. The fungal isolate underwent DNA sequencing and had 100% identity with Emmonsia helica (since reclassified as Blastomyces helicus).

Cytologic Interpretation and Case Summary

Cytologic interpretation: pyogranulomatous inflammation of the pulmonary parenchyma with intracellular yeast.

Case summary: B helicus pneumonitis in a cat.

Comments

At the referral evaluation, the radiographic and CT findings for the cat of the present report led clinicians to obtain fine-needle aspirate specimens of the infiltrated pulmonary parenchyma for microscopic examination. The cytologic findings directed additional diagnostic testing, which provided a diagnosis of B helicus pneumonitis. The cat was treated with itraconazole (10 mg/kg [4.5 mg/lb], PO, q 24 h) for 10 months, at which time treatment was changed because of the owner's financial constraints to fluconazole (13.5 mg/kg [6.1 mg/lb], PO, q 12 h) for an additional 3 months. The total duration of antifungal administration was 13 months. Nine months after diagnosis, a Blastomyces antigen assayd was performed on a urine sample collected from the cat and the result was negative. A CT scan of the cat was performed 2 years after diagnosis, which revealed marked improvement of the alveolar infiltrates; however, there was evidence of mineralization, fibrosis, and loss of volume in the left lung lobes, all of which were supportive of secondary changes following a chronic inflammatory process. The cat underwent thoracic radiography 3 years after diagnosis, and the radiographic findings corroborated the follow-up CT findings.

The yeast organisms observed were originally suspected to be H capsulatum on the basis of morphology alone. As highlighted by the case described in the present report, B helicus should be considered an important differential diagnosis when yeast organisms with H capsulatum-like morphology are observed in examined specimens. Frequently, a urine antigen assayb is the only additional diagnostic test pursued to confirm a cytologic diagnosis of histoplasmosis. The sensitivity and specificity for the detection of H capsulatum antigen in feline urine by the Histoplasma antigen assayb are reported as 92% and 99%, respectively. The sensitivity and specificity of the Blastomyces antigen assayd for the detection of B dermatitidis antigen in urine samples from cats are reported as 90% and 99%, respectively. Specificity appears related to mycoses in general, and the cross-reactivity between these 2 tests for the detection of H capsulatum or B dermatitidis antigen is nearly 99%.1 As in the case described in the present report, it is apparent that the Histoplasma antigen assayb used can additionally cross-react with B helicus antigen, resulting in an erroneous diagnosis of histoplasmosis if specimens had not undergone fungal culture and PCR assay had not been pursued.

The infectious yeast in the case described in the present report was identified as E helica and then recently reclassified as B helicus.2 Some of the fungi of the genus Emmonsia were reclassified into the genus Blastomyces (including E helica [reclassified as B helicus] and Emmonsia parva [reclassified as Blastomyces parvus]). Others, such as Emmonsia crescens, remained in the genus Emmonsia. Prior to speciation and reclassification, the yeast isolated in this case was identified only as Emmonsia spp. Fungal infections currently classified as Emmonsia infections and those recently reclassified as Blastomyces infections can present in 2 distinct manners, as localized adiaspiromycosis or systemic dimorphic yeast. The type of infection may be dependent on the specific species of fungus involved. When first discovered, fungi identified as Emmonsia spp were often not further speciated; consequently, reports of Emmonsia spp infections could include both the current Emmonsia genus and the newly reclassified fungi that fall into the Blastomyces genus. These fungi were noted not to replicate during infection but to grow as spherical adiaspores that range from 2 to 4 μm to 40 to 500 μm in diameter and elicit a foreign body reaction.3

Adiaspiromycosis appears to most often develop following inhalation of soil conidia.3,4 It is most commonly observed in small rodents and other small mammals worldwide and is typically identified as infection with E crescens or B parvus (formerly E parva).3,5 Reports of infection in nonhuman mammals are rare and include reports of adiaspiromycosis in 2 dogs, a goat, a deer, and a horse.6–10 These affected animals were not apparently immunocompromised, and the disease was an incidental finding at necropsy in most cases. In the horse, the yeast was identified as E crescens; in one of the dogs, the yeast was identified as B parvus.6,10 The infective organisms in the other 3 nonhuman animal cases were identified by morphology only as Emmonsia spp.7–9 Adiaspiromycosis in both immunocompetent and immunocompromised humans has been reported,3,11 although the disease tends to be more severe in immunocompromised individuals.

More recently, disseminated Emmonsia-related disease often involving lungs and skin has been described predominantly for immunocompromised humans.3 In those reported cases,3 the fungus was dimorphic, replicated in yeast form, and appeared to be an opportunistic infection. The cat of the present report was assessed as immunocompetent. In addition to the present case, isolates of B helicus have been associated with pulmonary infections involving 1 other cat and 2 dogs in the western United States.2 In the cat and one of those dogs, yeast organisms observed in histologic or cytologic specimens were initially mistaken for H capsulatum.2 The immunologic state of the animals in these other B helicus cases was unknown.2 The route of transmission that results in Emmonsia-related disease also appears to be inhalation of soil conidia.2,3 However, definitive determination of the route of transmission in the case described in the present report could not be determined because of the chronicity of the cat's disease. There are no reports of transmission of Emmonsia spp or B helicus from animal to animal, human to animal, or animal to human. Thus, adiaspiromycosis and disseminated Emmonsia-related disease are not suspected to be of zoonotic concern, although both nonhuman animals and humans can be infected by both disease forms.

Emmonsia spp and B helicus are most closely related to B dermatitidis and H capsulatum.3 This relationship was likely the reason that the Histoplasma antigen assay yielded a positive result and the DNA probing for Blastomyces yielded a weakly positive result for the cat of the present report. Morphologically, Emmonsia yeast forms have been mistaken for both B dermatitidis and H capsulatum on histologic examination and culture of specimens.3 In the case described in the present report, it should be noted that the cytologic appearance of B helicus was very different from that of B dermatitidis but similar to that of H capsulatum. In other instances, the histologic appearance of large Emmonsia adiaspores has been confused with that of Coccidioides spp.12

Emmonsia adiaspores do not grow well in culture, and diagnosis is often dependent on morphological features or PCR assay results. However, yeast forms of Emmonsia generally grow well in culture and can subsequently be identified with a PCR assay.3 The nomenclature of Emmonsia fungi has varied, with genus names including Haplosporangium and Chrysosporium in addition to Emmonsia and Blastomyces.11 No obvious misclassifications of Emmonsia-related adiaspiromycosis or disseminated disease in domestic veterinary species associated with either of the previous genera (Haplosporangium and Chrysosporium) were discovered upon the authors' review of published literature. The reclassification of E helica and E parva as B helicus and B parvus, respectively, should be noted for future investigation of veterinary cases involving fungal infections of this description.

Differentiation of B helicus infections from H capsulatum infections may be important to help elucidate the true prevalence of B helicus infection. It is possible that the infrequent reports of B helicus infection are attributable to the organisms' similarity to other more well-known fungi, such as H capsulatum, rather than to a low prevalence of infection. Moreover, understanding differences between infections with these 2 fungal organisms in regard to prognosis, response to treatment, and risk factors for infection (including geographic distribution and animal species affected) would be valuable.

Acknowledgments

Presented as a Mystery Slide Case at the American College of Veterinary Pathologists and American Society for Veterinary Clinical Pathologists Concurrent Annual Meeting, New Orleans, December 2016.

The authors thank Dr. Tim Kloer, Colorado State University, for assistance with CT images and radiographic interpretations.

Footnotes

a.

MiraVista Diagnostics, Indianapolis, Ind.

b.

MiraVista Histoplasma antigen assay, MiraVista Diagnostics, Indianapolis, Ind.

c.

Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio, San Antonio, Tex.

d.

MiraVista Blastomyces antigen assay, MiraVista Diagnostics, Indianapolis, Ind.

References

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