Feline Mesenteric form of Multinodal Lymphoma: A Case Report

Introduction: Feline lymphoma is one of the most important forms of tumor which is not completely understood. Complications and pathogenesis of tumor growth and development is quite difficult to diagnose due to varied etiology and pathogenesis. Mesenteric form of lymphoma is quite rare (8-18%) in felines and tumor regression and palliation are quite challenging in these patients. Case Presentation: An 8 year old, desi, short-hair breed feline was reported to the hospital with the consistent respiratory distress and abnormally swollen neck for the past two weeks. The feline was a recently adopted stray pet and the preventive strategies like vaccination, birth control etc., were not undertaken as per the history collected. The animal was diagnosed as stage IV high Case Study Chandrasekar et al.; ARRB, 9(1): 1-6, 2016; Article no.ARRB.22436 2 grade, anaplastic large cell lymphoma after employing various diagnostic strategies. The animal was treated with University of Wisconsin-Madison Modified Chemotherapy Protocol which led to the successive regression of the condition. Conclusion: Lymphoma is one of the common hematological malignancies of felines whose management still remains challenging. There are various forms of lymphoma depending on the site of occurrence and metastasis. Chemotherapy and surgical options are the best available strategies in management of lymphoma. Multi-nodal lymphoma is occur in10-20% of the felines. Chemotherapy protocol as standardized by the University of Wisconsin-Madison is still efficient in management of lymphoma in felines irrespective of the stage and clinical grade of presentation.


INTRODUCTION
Hematopoietic tumors like lymphoma (LA), acute myeloid leukemia (AML) are quite common in felines [1]. The occurrence has been reported relatively higher in non-vaccinated and poorly vaccinated animals [1,2]. Though vaccination plays an important role in the prevention of the occurrence, the exact reasons for reduced occurrence is still under study. One possible reason could be due to the vaccination against Feline Leukemia virus (FeLV).
In general, it is considered that cats are at a greater risk for a broad range of anatomical and histological forms of lymphoma than any other species. There are various forms of lymphoma that may occur in felines. These include nasal LA, cranial mediastinal LA, multicentric LA, renal LA, central nervous system (CNS) LA, and alimentary LA and also malignant forms in various lymphatic drainage regions. In comparison with canine lymphoma, feline lymphoma is more acute and much more complicated and, response to therapy is also exaggerated in felines than in canines.
The alimentary form of lymphoma is more common in felines than in human beings and canines [2]. An increased occurrence of the alimentary form of lymphoma is reported to up to 72% in all vaccinated felines [3]. This could be due to various other etiology like environmental tobacco smoke [4], helicobacter infection [5], etc. The multi-nodal/ multicentric form of lymphoma with lymph node involvement along with metastasis to liver or the spleen is quite rare (10-20%) in felines [2]. The major lymph nodes involved include the mediastinal, mesenteric, iliac, inguinal, submandibular lymph nodes.
The commonly employed diagnostic strategies include PCR for identification of FIV antigen to rule out viral causes for malignancy and enzyme linked Immuno-Sorbent assay [6,7]. Under a clinical setup, ultrasonography guided biopsy of the enlarged lymph nodes can be obtained for assessment of the tumor. The flow cytometry is considered to be the best diagnostic strategy [8] for a clinical diagnosis of lymphoma which can be employed if necessary. Bone marrow biopsy is very essential to stage the form of tumor and as well as to assess invasion into the marrow [9,10]. Based on cells involved and anaplastic changes, lymphoma can be classified based on various systems like the Kiel system, Rappaport system, Luke & Collins System, Working formulation system [7].

PRESENTAION OF CASE
An 8 year old of the desi short-hair breed Tomcat was admitted to the Critical Care Unit, Madras Veterinary College, Chennai, with the history of respiratory distress and never been vaccinated before. Further history suggested that respiratory distress occurred in a slowly progressing phase. The initial clinical assessment suggested that masses in the submandibular region ( Fig. 1) and pleural effusion. The patient was carefully placed on sternal recumbence and the effusate fluid in the pleural space was gradually aspirated out and sent in for laboratory assessment. Subsequently, under local anesthesia, Fine Needle Aspiration Biopsy (FNAB) of the swollen mass in the submandibular region was carried out. For further assessment of the patient, abdominal ultrasonography and radiography of the thorax was done. The ultrasonographic assessment revealed that mesenteric lymph nodes (Fig. 2) were enlarged and were compressing the intestinal walls. Under general anesthesia, the patient was carefully positioned and ultrasound guided biopsy of the enlarged mesenteric lymph node was obtained. The radiography revealed mediastinal lymph node enlargement. For further staging, as per standard operating procedure, core biopsy of the bone marrow was obtained. The hematology and serum biochemical panel analysis was also carried out.

LABORATORY EXAMINATION AND INTERPRETATION
The hematological examination revealed that the animal was anemic with marked leukopenia. Serological examination revealed characteristic paraneoplastic syndrome associated with T-cell lymphoma and hypercalcemia. The effusate fluid from pleural space smeared on clean glass slides and stained by the May-Grunwald-Giemsa staining technique. It revealed reactive lymphocytes. The FNAB of the submandibular masses revealed multinuclear giant cells with anaplastic changes. The lympho-granuloma bodies (LGB) were also associated with the giant cells (Fig. 3). Similarly, biopsy from the mesenteric lymph node also revealed large, multinucleated giant cells with major anaplastic changes and diminished cellular inhibition suggestive of 'Anaplastic Large Cell Lymphoma' (Fig. 3). Based on NCI-Working Formulation System of Classification, this patient was characterized to be ailing from High-grade Lymphoma.

GRADING AND STAGING
Based on presence of metastatic lesions in the liver and the involvement of mediastinal lymph nodes and without any form of bone marrow infiltration, the condition was diagnosed as Stage IV High grade, Anaplastic large Cell Lymphoma as per the WHO system of classification.

THERAPEUTIC REGIME
The furosemide therapy at the rate of 3mg/kg body weight for the first four days was done to relieve pleural effusion. The chemotherapy protocol as prescribed by University of Wisconsin-Madison for feline lymphoma (Table 1) was subsequently initiated. The protocol was followed for the next 25 weeks at the prescribed periods. The hematological assessment regarding neutrophil levels were assessed before every therapeutic procedure (Fig. 4). The patient was maintained under critical care for a minimum of 3 hours following LG Bodies chemotherapy on all prescribed days. The size of the submandibular mass ( Fig. 1) was measured as 8 cm long and 2.7 cm wide on the day of first clinical presentation. The assessment of lymph nodes was carried out regularly on every visit to the hospital. A gradual reduction in the size of the lymph nodes was observed from the third dose of the chemotherapy. The final assessment 4 chemotherapy on all prescribed days. The size of 1) was measured as 8 cm long and 2.7 cm wide on the day of first clinical presentation. The assessment of lymph nodes was carried out regularly on every visit to the hospital. A gradual reduction in the size of lymph nodes was observed from the third dose of the chemotherapy. The final assessment was carried out in the 23 rd week and the lymph nodes have completely returned to the normal size and measured as 0.6 cm long and 0.25 cm wide.
The therapeutic regimen follow management of Anaplastic Large ce in this patient is as follows:

Neutrophil levels (1000 cells/µl) during the therapeutic regimen
; Article no. ARRB.22436 week and the lymph nodes have completely returned to the normal size and measured as 0.6 cm long and 0.25 cm n followed for the cell Lymphoma modified chemotherapy protocol mg/m2 IV400U/kg SC2 mg/kg

DISCUSSION
Lymphoma of felines is quite a common condition as it is a Feline Leukemia Virus (FeLV) induced lympho-proliferative disease. The condition is more common in unvaccinated pets rather than vaccinated pets. The prevalence of FeLV virus among feral and stray felines making it easily accessible to unvaccinated and poorly vaccinated pets. It is also suggested that 25% of felines with lymphoma do have FeLV Antigenemia [2]. The other etiologies for lymphoma include Helicobacter infection, diet and environmental tobacco smoke [4,5]. The occurrence of the disease is gradually reducing due to various control strategies like reduced exposure to stray and feral felines, vaccination etc. The alimentary lymphoma affects predominantly middle-to old-aged domestic crossbred cats (median age 10-13 years) [10].
The B cell lympho-types are commonly found in the mesenteric form but T cell Lymphoma do have mesenteric involvement when the tumor has progressed to multicentric phase [11]. The multicentric lymphoma usually results in reactive or hyperplastic lymph nodes. During this phase, there will be marked enlargement of nearly all lymph nodes in the body. The most common clinical feature during this phase is subsequent involvement of mediastinal lymph nodes leading to accumulation of effusate fluid in the pleural space [9]. This feature compromises respiration. The Fine Needle aspirate of the lymph node must be done compulsorily to rule out Hodgkin's Lymphoma. If possible, this can be confirmed by Flow-cytometric analysis [12,13] or immunehistochemistry (IHC) or an immunocytochemistry can be done for confirmation. Flowcytometry for assessment of Human CD79 acy can be done to identify between T cell and Human CD 3cy can be employed for B cell Lymphoma.
Radiation therapy and lymph node resection are the best therapeutic protocol against Multicentric Lymphoma. But due to cost constraints and various paraneoplastic syndromes, surgical options and radiation therapy were ruled out in this patient. The patient was switched onto chemotherapeutic strategy which did provide better results.

CONCLUSION
Multicentric form of lymphoma is a very rare form of lymphoma occurring in 10-20% of patients affected. Of this scale, one third of patients do have FeLV Antigenemia [2]. This form has multiple lymph node involvement, initially the subcutaneous lymph nodes followed by Liver and Splenic metastasis. Also a few patients are presented with subsequent Mesenteric form of Lymphoma. The Fine Needle Aspiration Biopsy of Mesenteric Lymph nodes and the Subcutaneous Lymph nodes followed by various imaging techniques like radiographic lymphangiography, ultrasonography assessment are the various procedures helpful in diagnosis. Flow cytometric assessment of blood and lymph node aspirate can be done for confirmation. The best therapeutic regimen is surgical excision of the lymph nodes if possible, radiation therapy and chemotherapy but chemotherapy is the only feasible protocol available. The University of Wisconsin-Madison modified chemotherapy strategy for lymphoma is the best protocol available as mentioned above. Chemotherapy strategy along with patient care in palliation and paraneoplastic syndrome management were essential for a successful recovery.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.