INTRODUCTION
Lymphoma is the most common malignancy among felines, and the gastrointestinal (GI) tract is the most common site of this disease[1]. Alimentary lymphoma can affect the upper or lower GI tract, liver, or pancreas and is characterized by infiltration of neoplastic lymphocytes. There are different grades of gastrointestinal lymphoma, often referred to as low grade (lymphocytic or small cell), high grade (lymphoblastic, immunoblastic or large cell), and moderate. Gastrointestinal lymphoma is usually a disease of older cats. Clinical signs commonly include vomiting, diarrhea, anorexia, and weight loss. It is widely accepted that serum concentrations of cobalamin and folate reflect poor enteric absorption and are common in cats with small intestinal lymphoma[2]. Because ultrasonography provides information about the specific site of involvement of the lesion and other abdominal organs, it aids in staging the regional extent of the disease and screening for concomitant disorders. The main diagnosis is made by histopathological examination of the lymph node in the affected area. The median disease-free intervals and survival times of cats with low-grade lymphoma are significantly longer than cats with high-grade lymphoma treated with chemotherapy. Low-grade gastrointestinal lymphoma has a more favorable outcome than previously reported for high-grade lymphoma and supports treatment with chemotherapeutic agents. In this study, we aimed to present the treatment of our case diagnosed with diffuse diffuse alimentary lymphoma with CHOP protocol chemotherapy.
Lymphoma is the most common malignancy among felines, and the gastrointestinal (GI) tract is the most common site of this disease[1]. Alimentary lymphoma can affect the upper or lower GI tract, liver, or pancreas and is characterized by infiltration of neoplastic lymphocytes. There are different grades of gastrointestinal lymphoma, often referred to as low grade (lymphocytic or small cell), high grade (lymphoblastic, immunoblastic or large cell), and moderate. Gastrointestinal lymphoma is usually a disease of older cats. Clinical signs commonly include vomiting, diarrhea, anorexia, and weight loss. It is widely accepted that serum concentrations of cobalamin and folate reflect poor enteric absorption and are common in cats with small intestinal lymphoma[2]. Because ultrasonography provides information about the specific site of involvement of the lesion and other abdominal organs, it aids in staging the regional extent of the disease and screening for concomitant disorders. The main diagnosis is made by histopathological examination of the lymph node in the affected area. The median disease-free intervals and survival times of cats with low-grade lymphoma are significantly longer than cats with high-grade lymphoma treated with chemotherapy. Low-grade gastrointestinal lymphoma has a more favorable outcome than previously reported for high-grade lymphoma and supports treatment with chemotherapeutic agents. In this study, we aimed to present the treatment of our case diagnosed with diffuse diffuse alimentary lymphoma with CHOP protocol chemotherapy.
MATERIAL-METHOD
The case is an 11-year-old male tabby cat brought to the clinic with complaints of loss of appetite and chronic vomiting. On clinical examination, abdominal pain, constipation and lethargy were detected. Hematological examination revealed lymphopenia and anemia (IDEXX Catalyst Dx® Biochemical Analyzer, IDEXX ProCyte® Hematology Analyzer). Direct and indirect x-ray with positive contrast was performed with the suspicion of obstruction in the gastrointestinal tract and no obstruction was detected. A protocol was created for the treatment of anemia, lymphopenia and clinical symptoms of the case. On the 5th day of the treatment, a mass was detected in the ileocecal region in the ultrasonographic examination performed after he vomited again in the first meal after the administration of Maropitant (Cerenia®) was discontinued. In the preoperative period, the patient’s general condition and hematological findings improved with treatment, and a diagnostic laparotomy operation was performed. A biopsy sample was taken from the hyperplastic cranial mesenteric lymph node for histopathological diagnosis. The biopsy specimen was fixed in 10% formalin solution for 24 hours. Then, the tissue sample was embedded in paraffin blocks after routine tissue follow-up procedures. Sections of 3-4 μm thickness were taken from paraffin blocks and stained with Hematoxylin-Eosin.
The case is an 11-year-old male tabby cat brought to the clinic with complaints of loss of appetite and chronic vomiting. On clinical examination, abdominal pain, constipation and lethargy were detected. Hematological examination revealed lymphopenia and anemia (IDEXX Catalyst Dx® Biochemical Analyzer, IDEXX ProCyte® Hematology Analyzer). Direct and indirect x-ray with positive contrast was performed with the suspicion of obstruction in the gastrointestinal tract and no obstruction was detected. A protocol was created for the treatment of anemia, lymphopenia and clinical symptoms of the case. On the 5th day of the treatment, a mass was detected in the ileocecal region in the ultrasonographic examination performed after he vomited again in the first meal after the administration of Maropitant (Cerenia®) was discontinued. In the preoperative period, the patient’s general condition and hematological findings improved with treatment, and a diagnostic laparotomy operation was performed. A biopsy sample was taken from the hyperplastic cranial mesenteric lymph node for histopathological diagnosis. The biopsy specimen was fixed in 10% formalin solution for 24 hours. Then, the tissue sample was embedded in paraffin blocks after routine tissue follow-up procedures. Sections of 3-4 μm thickness were taken from paraffin blocks and stained with Hematoxylin-Eosin.
FINDINGS CLINICAL AND RADIOGRAPHIC FINDINGS In the clinical examination of the patient with a history of chronic vomiting, abdominal pain and lethargy were detected. Complete blood count and serum biochemistry panel were evaluated in the hematological examination. As a result, lymphopenia and regenerative anemia were observed. Subsequently, direct and indirect positive contrast X-Ray examination was performed to detect the presence of obstruction in the gastrointestinal tract. It was determined that there was no occlusion in the repeated recordings (0. min, 15. min, 30. min, 60. min, 24 hours) performed after contrast agent administration (FIGURE 1 and FIGURE 2).
In X-Rays, it was observed that the transit time of the contrast agent from the duodenal region was prolonged, but segmentation and contrast agent residues were not observed in the stomach and intestines. In the light of these findings, the abdominal organs were observed in the ultrasonographic examination, which was examined after the symptom of vomiting again in the meal after the experimental discontinuation of the antiemetic drug from the prescription of the patient whose treatment was initiated. In our case with gastric and intestinal wall thickening, generalized hyperplasic mesenteric lymph nodes, especially in the ileocecal region, were observed. Diagnostic laparotomy operation of the case whose general condition and hematological findings were improved with treatment was performed under general anesthesia. During the operation, diffuse inflammation in the intestines and mesenterium, vasodilation, and hyperplasia of the mesenteric lymph nodes were macroscopically observed (FIGURE 3).
It was observed that the mass existing in the ileocecal region decreased peristalsis and narrowed the lumen (FIGURE 4).
A biopsy sample taken from the cranial mesenteric lymph node (FIGURE 5) was sent to the pathology laboratory for diagnosis.
MICROSCOPIC FINDINGS
The histological structure of the examined lymph node was completely deteriorated, and atypical lymphoid cells were seen in each area, with prominent atypical nuclei in different sizes, and follicular- looking foci of different sizes (FIGURE 6). At low magnification, these atypical cells also showed a starry sky appearance due to the limited lysis of lymphoid cells in different areas (FIGURE 7). At high magnification, 2-4 mitotic structures were detected in different areas in atypical lymphoid cells (2-4 x 40 HPF). Most of the lymphoid cells were immunoblastic and lymphocyte type, and atypical lymphoid cells of different sizes with multiple nuclei were detected in some cells with prominent nuclear atypia (FIGURE 8). In the determined picture, it was found to be compatible with mixed cell follicular type alimentary lymphoma with diffuse spread.
The histological structure of the examined lymph node was completely deteriorated, and atypical lymphoid cells were seen in each area, with prominent atypical nuclei in different sizes, and follicular- looking foci of different sizes (FIGURE 6). At low magnification, these atypical cells also showed a starry sky appearance due to the limited lysis of lymphoid cells in different areas (FIGURE 7). At high magnification, 2-4 mitotic structures were detected in different areas in atypical lymphoid cells (2-4 x 40 HPF). Most of the lymphoid cells were immunoblastic and lymphocyte type, and atypical lymphoid cells of different sizes with multiple nuclei were detected in some cells with prominent nuclear atypia (FIGURE 8). In the determined picture, it was found to be compatible with mixed cell follicular type alimentary lymphoma with diffuse spread.
TREATMENT
Systemic antibiotic Enrofloxacin 5 mg/kg/day (Baytril®), Hydroxycobalamin 40 mcg/kg/week (Dodeks®), Maropitant 1 mg/kg/day (Cerenia®), Prednisolone 1 mg/kg/day in the clinical treatment approach of our case in the preoperative period. 12 hours (Deltakortil®) and Ranitidine 1 mg/kg/day (Ulcuran®) were administered. The patient’s general condition and hematological values improved, and a diagnostic laparotomy operation was performed under general anesthesia (induction with propofol, maintenance with isoflurane). There were no complications in the post-operative period. Following the diagnosis of high- grade alimentary lymphoma, the CHOP chemotherapy protocol was established[3] (FIGURE 9), based on the reference literature source. The chemotherapy protocol was applied in the form of weekly administration and in a 25-week period. Complete blood count and serum biochemistry panel were checked before each chemotherapy treatment. According to the protocol, chemotherapy was postponed for 5-7 days in case of findings of neutropenia (Neutrophil count <1500 cells/μl) in the complete blood count. Before each chemotherapy, ondansetron 0.1 mg/kg IV slow infusion, prednisolone 1 mg/kg/12 hours PO (Deltakortil®), ranitidine 1 mg/kg/day SC (Ulcuran®) and diphenhydramine 1 mg/kg SC were administered. In our case, whose general condition and clinical controls were followed up regularly, no relapse occurred after the end of chemotherapy from the date of diagnosis and including the date of case report.
Systemic antibiotic Enrofloxacin 5 mg/kg/day (Baytril®), Hydroxycobalamin 40 mcg/kg/week (Dodeks®), Maropitant 1 mg/kg/day (Cerenia®), Prednisolone 1 mg/kg/day in the clinical treatment approach of our case in the preoperative period. 12 hours (Deltakortil®) and Ranitidine 1 mg/kg/day (Ulcuran®) were administered. The patient’s general condition and hematological values improved, and a diagnostic laparotomy operation was performed under general anesthesia (induction with propofol, maintenance with isoflurane). There were no complications in the post-operative period. Following the diagnosis of high- grade alimentary lymphoma, the CHOP chemotherapy protocol was established[3] (FIGURE 9), based on the reference literature source. The chemotherapy protocol was applied in the form of weekly administration and in a 25-week period. Complete blood count and serum biochemistry panel were checked before each chemotherapy treatment. According to the protocol, chemotherapy was postponed for 5-7 days in case of findings of neutropenia (Neutrophil count <1500 cells/μl) in the complete blood count. Before each chemotherapy, ondansetron 0.1 mg/kg IV slow infusion, prednisolone 1 mg/kg/12 hours PO (Deltakortil®), ranitidine 1 mg/kg/day SC (Ulcuran®) and diphenhydramine 1 mg/kg SC were administered. In our case, whose general condition and clinical controls were followed up regularly, no relapse occurred after the end of chemotherapy from the date of diagnosis and including the date of case report.
CONCLUSION- DISCUSSION
High-grade alimental lymphoma in cats usually presents with rapidly progressive clinical signs with an aggressive course. Chemotherapy is the treatment of choice for alimentary lymphomas. Veterinary oncologists generally prefer the CHOP protocol because chemotherapy is thought to be well tolerated by cats. Although chemotherapy is a widely used treatment method, no known superior agent or protocol has yet been determined for selected chemotherapeutic drugs. The CHOP protocol, which is particularly successful in low-grade alimentary lymphoma cases, is also used in high-grade alimentary lymphoma cases, although it carries a high risk of metastasis and has a poor prognosis. In our case, the CHOP protocol, which is the frequently preferred chemotherapy method in alimentary lymphomas and recommended by veterinary oncologists in previous studies, was applied. In accordance with the literature, the process was managed without relapse in our patient on the 225th day after the application of this protocol in our case with a high grade diagnosis. In conclusion, it was predicted that CHOP chemotherapy treatment gave a positive response in our case with high-grade alimentary lymphoma and would contribute to the literature on veterinary oncology in clinical and oncological diagnosis and treatment approach. REFERENCE [1] Gieger T. (2011). Alimentary Lymphoma in Cats and Dogs. Vet Clin Small Anim 41. 419–432 [2] Richter K. P. (2003). Feline Gastrointestinal Lymphoma. Vet Clin Small Anim 33. 1083-1098 [3] Cartagena Albertus J. C., Engel Manchado J., Romairone Duarte A., Moise A., Moya Garcia S., Jones D., Mpntoya-Alonsı J. A. (2018). Use of a depot steroid formulation with CHOP-based protocol in the treatment of mediastinal lymphoma in cats. IJVR, Vol. 19, No. 2, Ser. No. 63, Pages 137-143
High-grade alimental lymphoma in cats usually presents with rapidly progressive clinical signs with an aggressive course. Chemotherapy is the treatment of choice for alimentary lymphomas. Veterinary oncologists generally prefer the CHOP protocol because chemotherapy is thought to be well tolerated by cats. Although chemotherapy is a widely used treatment method, no known superior agent or protocol has yet been determined for selected chemotherapeutic drugs. The CHOP protocol, which is particularly successful in low-grade alimentary lymphoma cases, is also used in high-grade alimentary lymphoma cases, although it carries a high risk of metastasis and has a poor prognosis. In our case, the CHOP protocol, which is the frequently preferred chemotherapy method in alimentary lymphomas and recommended by veterinary oncologists in previous studies, was applied. In accordance with the literature, the process was managed without relapse in our patient on the 225th day after the application of this protocol in our case with a high grade diagnosis. In conclusion, it was predicted that CHOP chemotherapy treatment gave a positive response in our case with high-grade alimentary lymphoma and would contribute to the literature on veterinary oncology in clinical and oncological diagnosis and treatment approach. REFERENCE [1] Gieger T. (2011). Alimentary Lymphoma in Cats and Dogs. Vet Clin Small Anim 41. 419–432 [2] Richter K. P. (2003). Feline Gastrointestinal Lymphoma. Vet Clin Small Anim 33. 1083-1098 [3] Cartagena Albertus J. C., Engel Manchado J., Romairone Duarte A., Moise A., Moya Garcia S., Jones D., Mpntoya-Alonsı J. A. (2018). Use of a depot steroid formulation with CHOP-based protocol in the treatment of mediastinal lymphoma in cats. IJVR, Vol. 19, No. 2, Ser. No. 63, Pages 137-143