Bicavitary involvement of feline eosinophilic sclerosing fibroplasia with intralesional methicillin-resistant Staphylococcus aureus

Abstract

Case summary

A 4-year-old spayed female domestic shorthair cat was presented for evaluation of multiple abdominal masses and hyperglobulinemia. Thoracic radiographs and abdominal ultrasonography revealed a cranial abdominal mass with extension through the aortic hiatus of the diaphragm and into the caudodorsal mediastinum. A diagnosis of feline eosinophilic sclerosing fibroplasia (FESF) with intralesional methicillin-resistant Staphylococcus aureus (MRSA) was obtained based on necropsy results.

Relevance and novel information

To the authors’ knowledge, this case report is the first to describe extension of a primary FESF lesion through the diaphragm and is the first confirmed case of intralesional MRSA in an FESF lesion. In addition, this case is one of a growing number of reports of FESF lesions that do not involve the gastrointestinal tract. This case further contributes to the growing evidence that FESF should be considered as a differential diagnosis, in addition to neoplasia, feline infectious peritonitis or abscessation, in cats with masses, especially when there is concurrent hyperglobulinemia, a low albumin:globulin ratio and/or eosinophilia. This case also highlights the importance of considering this differential for masses outside the abdominal cavity, those involving both the chest and the abdomen, and those that do not involve the gastrointestinal tract.

Case description

A 4-year-old spayed female domestic shorthair cat was referred to the UW Veterinary Care Small Animal Internal Medicine Service for evaluation of multiple abdominal masses. The cat had an unremarkable physical examination 4 months prior and the owners had noted abdominal distension approximately 1 month before presentation of the cat to UW Veterinary Care. Bloodwork performed 8 days prior showed hyperglobulinemia (9.8 g/dl, reference interval [RI] 2.8–5.1), hypoalbuminemia (2.1 g/dl, RI 2.2–4.0), an albumin:globulin (AG) ratio of 0.2, elevated symmetric dimethylarginine (16 µg/dl, RI 0–14), non-regenerative anemia (hematocrit 24%, RI 30.3–52.3), eosinophilia (2.1 K/µl, RI 0.17–1.57) and monocytosis (0.73 K/µl, RI 0.05–0.67). The cat had maintained a normal appetite, energy, urination and defecation, and the only changes noted by the owners were tachypnea and left-sided abdominal distension. The cat had been started on injectable GS-441524 treatment at an unknown dose before referral owing to clinical concern for feline infectious peritonitis (FIP).

Upon presentation to UW Veterinary Care, the cat weighed 3.84 kg and had a body condition score of 5/9. The patient was tachypneic with a respiratory rate of 50 breaths/min and normal respiratory effort. The cat was normothermic. Physical examination revealed a grade II/VI parasternal systolic heart murmur with a gallop rhythm, a large and firm left-sided abdominal mass, and several smaller masses palpated in the right abdomen.

Thoracic radiographs (Figure 1) revealed a caudodorsal mediastinal mass effect with aortic hiatal herniation and extension into the visible cranial abdomen and bicavitary effusion (pleural and peritoneal). Abdominal ultrasonography revealed a large mass (Figure 2) in the region of the left pancreas caudal to the stomach with intrathoracic extension into the caudodorsal mediastinum through the aortic hiatus. Power Doppler revealed minimal blood flow within the mass. Peritoneal lymphadenopathy and scant bicavitary effusion were also identified. Three fine-needle aspirates (FNAs) of the mass were obtained. Cytology of these aspirates did not contain any tissue cells for analysis, but did show peripheral blood leukocytes and erythrocytes on a proteinaceous background. Additional diagnostics, including repeat FNAs, fluid analysis and surgical biopsy of the mass, were declined by the owner.

Figure 1

(a) Right lateral, (b) left lateral and (c) ventrodorsal radiographic projections of the thorax. A large, opaque soft tissue mass is superimposed on the lung lobes within the caudodorsal thorax, extending cranially to the level of T8. Scant pleural effusion is evidenced by retraction of the lung lobes from the body wall and widened pleural fissure lines. In addition, the patient has a mild diffuse bronchial pulmonary pattern and enlarged cardiac silhouette, occupying >2.5 intercostal spaces and >65% of the thoracic width

Figure 2

Ultrasonographic images of a large, heterogeneous mass (indicated by *) in the region of the left pancreas extending from the level of the stomach to the urinary bladder and displacing the spleen to the right side of the abdomen. The mass extended cranially through the aortic hiatus, passing cranial to the caudate lobe of the liver. Scale is in centimeters

The cat was discharged on continued GS-441524 treatment (unknown dose); no other medications were prescribed as the cat was eating well and assessed to be non-painful on examination. The cat was presented to the UW Veterinary Care Small Animal Emergency Service 2 days later for worsening tachypnea and abdominal pain, and was subsequently euthanized. A necropsy was performed. In the mesentery between the pancreas and the stomach were four white to tan to red, multilobular, irregularly shaped masses with a diameter in the range of 5–11 cm (Figure 3a). Collectively, the masses weighed 445.57 g (11% of the patient’s body weight). Multiple fibrous adhesions extended between the masses and the stomach, pancreas and right body wall. On cut section, the masses did not bulge and had multiple variably sized cavitations containing brown to tan to yellow fluid, exudate and friable necrotic tissue (Figure 3b). The most cranial mass extended into the thoracic cavity at the level of the aortic hiatus. The peritoneal cavity contained 39 ml of light brown opaque fluid. The thoracic cavity contained 12.5 ml of opaque, dark red, non-clotting fluid.

Figure 3

(a) The removed proximal gastrointestinal tract, highlighting the orientation of the multilobular masses (white asterisks) between the stomach and proximal small intestine. The masses had multiple adhesions to the stomach, pancreas and body wall, but did not infiltrate the stomach (black asterisk), pancreas (black arrows) or intestine (white arrowheads). (b) Representative cut sections of the masses, which were often tan to white and firm (black asterisk), with multifocal green to yellow-brown areas. In some areas, the masses had cavitations filled with white to yellow to tan, opaque, viscous exudate and tan-brown fluid (white asterisk)

Histologically, the abdominal masses were composed of anastomosing bands and trabeculae of dense collagenous tissue with low numbers of fibroblasts interspersed with moderate to large numbers of mixed inflammatory cells (Figure 4a). Eosinophils predominated and were highlighted with Congo red stain (Figure 4b). Variable numbers of macrophages, plasma cells, lymphocytes and mast cells were admixed (Figure 4c). Both toluidine blue and Giemsa stains confirmed the presence of low numbers of scattered mast cells. Centrally within the masses were multiple areas of necrosis, often associated with aggregates of Gram-positive cocci (Figure 5). These necrotic areas contained numerous degenerated neutrophils and/or degranulated eosinophils. Peripherally, the masses were variably lined with fibrovascular connective tissue with moderate numbers of plasma cells. No normal remnant tissue was present for histologic context, and no tissue compatible with gastric or pancreaticoduodenal lymph node was identified. No fungal structures were found on routine hematoxylin and eosin-stained slides or with a periodic acid-Schiff reaction. Aerobic culture of frozen tissue from the mass isolated a heavy growth of methicillin-resistant Staphylococcus aureus (MRSA). Examined lymph nodes from other areas of the abdomen exhibited moderate lymphoid hyperplasia and sinuses drained variable numbers of macrophages and plasma cells, and occasional eosinophils.

Figure 4

(a) Anastomosing bands of dense collagen with fibroblasts interspersed with a mixed inflammatory cell population. Viewed at 10×, hematoxylin and eosin staining. (b) Cytoplasmic granules of eosinophils stained red with Congo red stain, highlighting numerous eosinophils within the inflammatory population. Viewed at 40×. (c) Giemsa stain highlighting mast cells, which have purple, metachromatic cytoplasmic granules. Viewed at 40×

Figure 5

Representative images of multiple large aggregates of Gram-positive cocci within the mass, viewed at 60×

Discussion

This case report is the first to describe a cat presenting with extension of a feline eosinophilic sclerosing fibroplasia (FESF) lesion through the diaphragm and is the first case of FESF associated with confirmed intralesional MRSA.

FESF has become increasingly recognized in recent years. FESF lesions have been identified throughout the gastrointestinal tract,^1–4 including the colon and rectum.^5,6 In several case reports, FESF lesions have been found involving extragastrointestinal tissues, including the nasal cavity, ⁷ subcutis, ⁸ cervical lymph nodes, ⁸ retropharyngeal lymph nodes, ⁷ mesentery,^2,9,10 cranial mediastinum, ¹¹ pancreas,^10,12 liver^13–15 and retroperitoneum. ¹⁶ To the authors’ knowledge, this is the first report of bicavitary involvement via extension of a primary mesenteric lesion through the diaphragm.

The clinical signs, duration of signs and physical examination findings can vary significantly. Gastrointestinal signs such as vomiting, dysrexia, stool changes and weight loss are commonly reported with gastrointestinal FESF.^1–3,13 A palpable abdominal mass is common on physical examination and patients may experience abdominal discomfort.^1–3,13 Patients without gastrointestinal involvement show clinical signs that correlate to the affected site,^7,11,16 and some patients do not show any clinical signs in the days before presentation.^3,17 In this case of mesenteric involvement, abdominal distension was the only clinical sign reported on initial presentation to the primary veterinarian.

Ultrasonographically, FESF often appears as a mass effect, although gastrointestinal FESF can appear as focal thickening and loss or alteration of wall layering without an overt mass effect.^{2,4,13,18–23} Lesions appearing as a single mass on imaging can be composed of multiple small masses, as described in this report and others.^10,16,24 Abdominal lymphadenopathy is commonly reported and can be mistaken for metastatic neoplasia.^{1,3,6,8,10,16,19–21,25–28} A recent retrospective study found enlarged abdominal lymph nodes in 90% of patients that had abdominal ultrasonography performed. ² As in this report, FNA of masses is often inconclusive, and biopsy is most reliable for proper identification.^{1,6,11,13,16,21,26,29,30}

Histologically, FESF exhibits a distinct network of dense collagenous connective tissue trabeculae interspersed with populations of fibroblasts, spindle cells and inflammatory cells, with a predominance of eosinophils and mast cells.^1–4 This characteristic trabecular pattern can resemble an osteoid ¹ and some cases can resemble an extraskeletal osteosarcoma. The presence of mast cells in many cases can lead to the misdiagnosis of sclerosing mast cell tumor. Other differential diagnoses include lymphoma, fibrosarcoma, granuloma or a variety of diseases associated with eosinophilic inflammation. ³

The exact cause of FESF remains unclear, but evidence suggests that the pathophysiology involves a dysregulated eosinophilic inflammatory response.^1,3,31 Activated eosinophils produce fibrogenic mediators transforming growth factor-β and interleukin (IL)-1β, which induce fibroblast growth and lead to extracellular matrix deposition.^32–34 IL-33, which is found in the nucleus of epithelial and endothelial cells, induces cutaneous fibrosis and requires IL-13 secreted by eosinophils for activation.^32–34 It is possible that some cats, such as Ragdolls, possess a genetic predisposition towards eosinophil dysregulation.^1–3

The initial cause for antigenic stimulation often remains unidentified. Proposed mechanisms include the presence of foreign material or antigenic stimuli from dietary, environmental or infectious sources. Although intralesional bacteria have been identified in a number of cases,^{1–3,5,6,11,13,16,24,27–29,35,36} their absence in many lesions and lack of clinical response to antibiotics implies a more complex pathophysiology. A previous study identified intralesional methicillin-resistant, coagulase-positive cocci but was unable to differentiate between MRSA and methicillin-resistant Staphylococcus pseudintermedius. ⁸ To the authors’ knowledge, this is the first case of FESF associated with confirmed MRSA infection. In our case, histopathology of the masses revealed necrotic areas containing Gram-positive cocci. The location of the bacteria, correlation between culture and histologic morphology, isolation of a pure culture and association with a local tissue reaction all suggest the presence of a true infection rather than contamination. The source of the infection remains unclear, as no gastrointestinal defects, foreign material or draining tracts were found at necropsy. Given MRSA’s usual skin colonization, a healed wound or penetrating foreign body is possible, as is hematogenous spread from the genitourinary or respiratory tracts. ³⁷ However, the cat had no reported wounds or clinical signs before the development of a visible abdominal mass. Therefore, the origin of the MRSA and its role in the development of this cat’s disease process remain unclear.

Pertinent clinicopathologic findings for this patient included significant eosinophilia, mild monocytosis, moderate non-regenerative anemia, severe hyperglobulinemia and moderate hypoalbuminemia with an AG ratio of 0.2. These findings are commonly reported, although cats with FESF can also have normal bloodwork and clinicopathologic abnormalities may vary throughout the disease course.^{1–3,5,13,19,21,29,30,38} It is important to note that patients may have an AG ratio of less than 0.4, a common finding in FIP, which also may present as an abdominal mass.^3,13,19,30 Improvement in bloodwork abnormalities can be seen with treatment.^11,19

The prognosis is variable, but there are recent reports of survival times greater than 16 months and up to 10 years when FESF is properly diagnosed and treated.^{2,3,5,7,13,16,20,24,35,38,39} In this case, the cat’s owners declined further diagnostics, including surgical biopsy of the mass, which would have been necessary for definitive diagnosis and initiation of treatment. Although treatment with immunosuppressive doses of corticosteroids has shown to be beneficial in improving or resolving clinical signs and lesion size,^{2,5,9,16,17,19,24,38,39} the clinicians involved in this case were reluctant to initiate immunosuppressive therapy without a definitive diagnosis or excluding infectious causes. Despite the prevalence of bacterial involvement, treatment with antibiotics does not appear to influence the outcome,^2,3 and antibiotics were not prescribed in this case. Good outcomes can occur with medical management alone,^2,7,20,39 although surgical intervention may be beneficial in patients in which medical management has failed.^35,36 Unfortunately, the cat in this case declined rapidly and was euthanized; given the advanced nature of the cat’s disease, it is unknown whether this patient would have responded to medical management, even if a definitive diagnosis had been achieved.

Conclusions

This is the first report to describe the bicavitary involvement of FESF in a cat via transdiaphragmatic extension and is the first report of confirmed intralesional MRSA. This report further supports FESF as a differential diagnosis for cats with abdominal masses and a low AG ratio. FESF should be considered as a differential diagnosis for mass-like lesions within the abdomen as well as lesions within the thorax or other parts of the body, especially when FNA is inconclusive.