Beschreibung
This study aimed at re-evaluating the data of feline patients with meningioma in order to regrade the tumors histologically by means of the human medicine WHO classification from 2016 (Louis et al., 2016) to characterize the immunhistochemical expression pattern of feline meningioma, and to establish a primary cell culture from a feline meningioma.
The clinical re-evaluation revealed a good therapeutic success by surgical removal of the tumor in feline patients. All owners except one reported a good regeneration of their cats post operatively and said that they would choose to perform the surgery in another pet again. The median survival time was 32 months with a maximum survival time of 9 years in one patient. Only in one case of a spinal meningioma with two recurrences the meningioma was the cause of death by euthanasia. The recurrence rate was 37%. One cat didn’t show any symptoms due to the relapse and another one was reoperated, which prolonged his survival for five more years. The data showed that a reoperation can be a promising approach. Despite a good prognosis of survival and regeneration when the patient survived the postoperative period, a craniotomy is a high-risk intervention. 26% of the cats died perioperatively.
The comparison with the data of the study by Johanna Will (2020) showed that the median survival time of cats after surgical intervention was far longer than the one of the examined dogs. The median survival time of dogs was 43 weeks (9,8 months) after surgery. Moreover, at the end, the meningioma was the cause of death in half of the canine cases after successful surgery.
The histological regrading showed that all feline meningiomas were fibrous, transitional, meningothelial or psammomatous. These subtypes are graded as Grade I meningiomas. The dogs investigated by Will (2020) additionally showed the granular cell, papillary, microcystic and clear cell subtypes. Psammomatous meningeomas were more common in cats (24%) than in dogs (4%). The fibromatous subtype was more common in cats (15%) than in dogs (4%) as well. The meningothelial subtype was more frequent in dogs (41%) than in cats (15%).
94% of the feline meningiomas were Grade I tumours, 6% the more malignant Grade II, and none of the tumours was Grade III. One of the Grade II tumours was characterized as more malignant by its proliferation activity and the other one by brain invasion. The first one showed two quick recurrences of the tumour after surgery, the second one was taken out of a dissected animal that hadn’t shown any neurological symptoms prior to his death. This is why it was not possible to find a reliable correlation of the histological grading and the biological behaviour of the tumours, especially as other grade I meningeomas in this study had relapses as well.
In the group of canine meningiomas, there were 16% grade I, 54 % grade II and 29% grade III (Will 2020). Therefore, the canine meningiomas had a much more malignant histological appearance than the feline meningiomas. Canine patients showed a worse outcome than the feline patients as well. This shows that the histological WHO-grading in human neoplasias (2016) seems to have a prognostic relevance in veterinary medicine as well. Among cats, it was not possible to estimate the prognosis of the individual animal by the histological grade, because almost all of the meningiomas were graded as grade I and still had different clinical outcomes.
In addition to the histological regrading, this study investigated the immunhistochemical expression pattern of the feline meningiomas with the already established markers vimentin, S100, GFAP and cytokeratine. Another focus was the establishment of new diagnostic and in the best case prognostic immunhistochemical markers. The establishment of the diagnostic marker desmoplakin and PHH3 as possible prognostic marker succeeded. The use of an antibody against EMA and SSTR2A wasn’t successful although multiple adjustments of the protocols were tried. At the moment, EMA and SSTR2A are the most important immunhistochemical markers for meningeoma in human medicine. Feline meningiomas did show an expression of SSTR2A, but the positive controls showed a nonspecific staining of multiple tissues as well, so that the staining of the meningeomas was rated as not evaluable. Nevertheless, there should be more studies about the establishment of other antibodies against SSTR2A on feline meningeome tissues under different circumstances. The somatostatin receptor 2A is a target for medical treatment with somatostatin analoga and the possibility that feline meningiomas can express SSTR2A with the data from this study can not be ruled out.
The immunhistochemical investigations showed that the feline meningeoms almost all followed the same expression patterns with a positive staining for vimentin (strong, diffusely), S100 (mild, focally) and desmoplakin (strong, diffusely) and a negative staining for GFAP and cytoceratine. Individual tumours showed little divergences such as a mild expression of GFAP or cytoceratin or no expression of S100. The data of this study suggest that the expression of cytokeratin might be associated with a worse prognosis in feline meningioma. Every tumour showed a different amount of positive PHH3 staining, depending on its proliferation activity. Only one case of the feline meningiomas showed more than 4 mitoses per 10 HPF (grade II) and in no case there were more than 20 mitoses per 10 HPF (grade III).
It was shown that feline and canine meningeomas differ in their histological appearance and their clinical characterics as well as in the success of the surgical therapy. In contrast, the immunhistochemical examination showed similar expressions of the antigens in meningeomas of both species. There was only a difference in the proliferation activity which led to a stronger expression of PHH3 in most of the canine meningiomas. The fact that meningiomas of dogs and cats have such a different outcome and prognosis and still have almost the same immunhistochemical expression patterns shows, that the markers vimentin, S100, cytoceratin, GFAP and desmoplakin in these species seem to have a good diagnostic, but no significant prognostic value.
The results of this study show that especially in feline meningiomas, which almost exclusively are histologically graded as grade I, this grading often fails to correlate with the outcome of the individual patient. This corresponds with the data from human medicine, where especially grade I meningiomas sometimes show a more malignant biological behaviour than the histological grade predicted. This is the reason why molecular pathological examinations gain more significance these days with regard to estimating the prognosis of individual patients. This is reflected in the new version of WHO classification from 2021. In veterinary medicine, at the moment there are no scientific studies about this subject, but it seems to be an important and interesting topic for further examination. The results show how obsolete the actual veterinary WHO classification is (Koestner et al., 1999). Another focus of this thesis was the establishment of a primary cell culture out of feline meningioma cells as a basis for further studies about immortalization and in vitro testings of chemotherapeutics. Especially in canine meningiomas, as previously mentioned, the surgery is rather characterized by a middle-term therapy success. Thus, alternative therapy options such as chemotherapy could gain in importance.
The establishment of a primary cell culture out of two different feline meningioma tissues was successful. One of the tumours was psammomatous and the other one meningothelial. The characterization of the cells with immunfluorescence and immunhistochemistry was possible as well and showed that the expression corresponded with the one of the original tumour. Subculturing was possible for several times without changes in growth behaviour of the cells. This is a promising basis for future scientific studies.
