NEUROTROPIC T-CELL LYMPHOMA AND NEUROLYMPHOMATOSIS IN A CAT

A 5 years old Domestic Short Hair spayed female cat living in a shelter was referred to the Veterinary Teaching Hospital of the Bologna University for a history of sudden onset of monoplegia of the left forelimb associated to jaw paralysis, not responsive to antibiotics and corticosteroid treatment. On physical examination, performed four days after the onset of the signs, the cat showed poor body condition score, dull hair and scales, inspiratory stridor, hypothermia and moderate dehydration state. On neurological examination, the cat showed a severely depressed mental status, ambulatory tetraparesis with monoplegia of the left forelimb and plantigrade stance of the pelvic limbs. Other findings included decreased conscious proprioception in pelvic limbs and severely decreased withdrawal reflex in all four limbs. Multiple cranial nerves deficits included bilateral absence of palpebral reflex and menace response, decreased reaction to cotton ball test, reduction of facial sensation and of the gag reflex, paresis of the tongue and jaw paralysis. Horizontal nystagmus with a left fast phase and left partial Horner syndrome were also present. Neuroanatomical localization was consistent with a multifocal syndrome. Ante-mortem clinicopathologic evaluation included CBC, serum biochemistry panel, FIV/FeLV serology and cerebrospinal fluid (CSF) analysis. CBC was normal. Biochemical panel showed a severe increase in CK (10256 U/L, reference interval 91 – 326 U/L) and a slight increase in transaminase and bile acids. Serologic test for FeLV was positive. CSF examination, despite corticosteroids ongoing treatment, was markedly abnormal, showing severe mononuclear pleocytosis (526 cells/μl, reference interval 0 – 5 cell/μl) and elevated protein concentration (97,5 mg/dl, reference interval 0 - 30 mg/dl). On cytology the CSF specimens were highly cellular and almost exclusively composed by large (36 – 40 μm) monomorphic lymphocytes with high N:C ratio, diffuse chromatin pattern and prominent nucleoli; mitoses were also readily evident (one to two mitotic figures per high power field). Due to poor prognosis, the cat was euthanized for human reasons. At necropsy, whitish soft 3-5 mm multilobulated masses were evident at the skull base, surrounding oculomotor nerves and semilunar ganglia, and around ganglia and roots of thoracic spinal nerves. No other changes were grossly apparent. Histology revealed the monotonous proliferation of medium-to-large lymphocytes, with scarce cytoplasm, round to oval nuclei and prominent central nucleoli. The lymphomatous tissue aggressively infiltrated and extended to the nervous tissue, with multifocal leptomeningeal involvement, occasional perivascular cuffings, focal neuropilar infiltration of the brain stem and spinal cord, and massive endoneurium infiltration. As a direct effect of the lymphoid infiltration, there were marked degeneration and atrophy of ganglionic perikaria, which showed severe pyknosis, chromatolysis and reactive satellite cells hyperplasia, and of axons, which showed distinct formation of digestion chambers. The lymphomatous infiltration extended also to cervical muscles; no lymphoid infiltrates were evident in other histologically examined tissues (lymph nodes, liver, kidney, spleen, lungs, heart, stomach, gut). Immunohistochemistry revealed strong and diffuse CD3 immunopositivity and CD79a negativity, thereby demonstrating T-cell phenotype (peripheral T-cell lymphoma). Fragment analysis (GeneScanning) of feline TCR gene rearrangements evidenced an oligoclonal pattern with few peaks of similar height. Integrated Feline Leukemia provirus was detected by PCR in isolated snap-frozen samples. Tumors of the peripheral nervous system (PNS) are very rare in cats, and lymphomas extending to PNS have been reported occasionally. Primary lymphomas of the nervous system are also rare and have been associated in human, feline and avian species wi...