Comparison of time since onset of disease and cell groups

Comparison of the time since onset of the disease in the cats placed in cell group 1 with the time since onset in the cell group 2 cats by a Mann-Whitney test showed no significant difference (p=0.12). The mean time since onset in months ± SD for group 1 (n=10) was 9.800 ± 7.193 and for group 2 (n=11) was 20.18 ± 21.85 (Table 6.4, Figure 6.5)

Chapter 6 Histopathological changes in tissue biopsies of cats with FCGS 129 Figure 6.2: Photomicrographs of biopsies of the palatoglossal folds

A: Severe lymphoplasmacytic infiltrate of the lamina propria B: Severe plasmacytic infiltrate of the lamina propria with Mott cells and neutrophils marginating the vessels.

A

B

Chapter 6 Histopathological changes in tissue biopsies of cats with FCGS 130 Figure 6.3: Percentage of cats in the different severity of inflammation groups according to predominant cell group

Group 1: lymphoplasmacytic infiltrate, group 2: plasmacytic infiltrate. Inflammation severity: 1:

mild, 1-2: mild-moderate, 2: moderate, 2-3: moderate-severe, 3: severe.

Figure 6.4: Age distribution of the two cell groups

Each ● represents one biopsy, the line represents the mean.

1 1-2 2

2-3 3

0 20 40 60 80 100

Group 1 Group 2

Severity grade

Percentage of total cats

Gro up 1

Gro up 2 0

50 100 150 200 250

Age

Chapter 6 Histopathological changes in tissue biopsies of cats with FCGS 131 Figure 6.5: Duration since onset of disease in the two cell groups

Each ● represents one biopsy, line represents the mean.

Gro up 1

Gro up 2 0

20 40 60 80 100

Duration in months

Chapter 6 Histopathological changes in tissue biopsies of cats with FCGS 132

6.4 Discussion

Several studies have investigated the histopathology of FCGS. Standard findings within the epithelium of FCGS lesions include hyperplasia, ulceration, dysplasia and suppuration (Johnessee and Hurvitz, 1983; Hennet, 1997; Baird, 2005). In the current study, many of the FCGS biopsies showed hyperplasia of the palatoglossal folds. This was also evident in the healthy biopsies where it was considered ‘normal’. Ulceration, dysplasia and suppuration are pathological. A large proportion of the FCGS biopsies showed ulceration and erosion with 69% showing at least one of the two lesions.

Dysplasia was much less common (13.7%).

Pathological findings in the mucosa and submucosa are described as being lymphoplasmacytic (Hennet, 1997), lymphoplasmacytic and eosinophilic (Baird, 2005), sheets of plasma cells (Frost and Williams, 1986), predominantly plasma cells with binucleated cells and cells containing Russell bodies (Mott cells) and variable numbers of neutrophils, lymphocytes and histiocytes (Johnessee and Hurvitz, 1983). Other studies have described two different patterns, one being diffuse primarily plasmacytic and lymphocytic and the other having primarily plasma cells (White et al., 1992; Lyon, 2005; Wiggs, 2007). An acute reaction in the oral mucosa is normally associated with neutrophil infiltration while chronic reactions show lymphocytes, plasma cells, monocytes and macrophages. Suppurative inflammation is characterised by neutrophils as the predominant cell type (Pedersen, 1992; Nanci, 2008).

A number of samples in the current study had an infiltrate with a majority of plasma cells and low numbers of lymphocytes. This infiltrate, often seen in combination with Mott cells and binucleate plasma cells, can normally be seen in diseases with a suggested immune-mediated background such as rheumatoid arthritis and feline plasma cell pododermatitis (Perry et al., 1997; Dias Pereira and Faustino, 2003). Binucleate plasma cells were commonly found in multiple samples in the current study. Plasma cells are considered to be a fully differentiated state of the B-lymphocyte and therefore do not normally divide further. Binucleate and multinucleate plasma cells have been located in human rheumatoid arthritis (Perry et al., 1997) and several human oral diseases (Jinnfei and Ellabban, 1986), and have also been described in feline plasma cell pododermatitis (Dias Pereira and Faustino, 2003). The origin of binucleate plasma cells is controversial. One study suggested that they form through cell fusion (Jinnfei and Ellabban, 1986) but a later study reported that the morphology was more consistent with plasma cells that had undergone division (Perry et al., 1997). A rare disease in humans with a similar histopathological appearance is plasma cell mucositis

Chapter 6 Histopathological changes in tissue biopsies of cats with FCGS 133

(Puvanendran et al., 2012). Histopathology shows an acanthotic epidermis and rete ridges as seen in histopathology of FCGS. A dense infiltrate of plasma cells is seen as well as Russell-bodies. The aetiopathogenesis of plasma-cell mucositis is not known but often a history of immunological dysfunction is described in the patients. Treatment is unreliable but most often corticosteroids are used in patients suffering from the disease.

The cats in this study were all considered to have a similar clinical appearance, and to be suffering FCGS. The biopsies could, however, be divided into two groups according to the histopathological appearance as described by Barker et al. (1992). Group 1:

lymphocytic plasmacytic stomatitis with a chronic inflammation, characterised predominantly by plasma cells and lymphocytes (present in 45% of cases) and group 2:

feline plasma cell gingivitis, with predominantly plasma cells in the lamina propria and showing fewer lymphocytes, neutrophils and macrophages (present in 55% of cases). The two types of cell infiltrate were compared to the severity of the infiltrate. A significant correlation could be seen, with the most severely inflamed samples being part of the plasmacytic group (group 2) and the less severely inflamed samples being categorised into the lymphoplasmacytic group (group 1). White et al. (1992) showed that 70% of cats with FCGS had a predominantly plasma-lymphocytic infiltrate and 30% had a predominantly plasmacytic infiltrate. Russell bodies, neutrophils and eosinophils could be found in some sections. Another study reported that lymphocytes or plasma cells were predominant in 25% of cases and neutrophils were predominant in 50% of cases (Harvey, 1991). The study also showed that there was no significant correlation between gingival index and the type of cells seen; however, the severity of inflammation and gingival index were significantly correlated. A much higher proportion of cats in our study represented the plasmacytic group when compared to previous studies. Taking into account that the more severe cases were predominantly plasmacytic in nature, it is possible that a higher number of severe cases were seen in this study due to the origin of the samples. Samples were collected at a referral veterinary dentist where one could expect a higher number of severe cases being presented.

Barker et al. (1992) reported that the lymphoplasmacytic type of infiltrate is more common in older cats. This was not verified by the current study. No difference in age was seen between the two cell-type groups. For 21 cats, an estimated start date of the disease was recorded but no difference could be seen in the time since disease onset between the two cell-type groups. The lymphoplasmacytic infiltrate has previously been described to be more common in cats having lesions of the tongue, palate and gingiva (Barker et al., 1992). In the current study, four cats possessed lesions of the tongue and

Chapter 6 Histopathological changes in tissue biopsies of cats with FCGS 134

five had lesions of the oropharynx. Neither of the two cell-type groups was overrepresented in these cats. The clinical appearance was not always a good predictor of the histopathological features.

The current study showed that there are two different cell-type groups seen within the FCGS biopsies: group 1, showing a predominant lymphoplasmacytic infiltrate and group 2 showing a predominant plasmacytic infiltrate. There is a possible correlation between severity of inflammation and the cell-type groups seen.