Atypical presentation of cutaneous T-cell lymphosarcoma in a 19-month-old Holstein heifer

Abstract

A 19-month-old Holstein heifer was presented with bilateral auricular masses. Multiple cutaneous masses and prefemoral lymphadenopathy were also found. On post-mortem, masses affecting internal viscera were observed. The heifer was seronegative for Bovine leukemia virus (BLV). The cutaneous form of sporadic juvenile lymphosarcoma was diagnosed and determined to be of T-cell origin.

A 19-month old Holstein heifer was presented for examination of bilateral auricular masses during a routine herd health examination. The owner had first observed the masses 2 wk previously and had administered a single treatment with short-acting penicillin subcutaneously.

On physical examination, the heifer was bright, alert, and in good body condition. The respiratory rate was 20 breaths/min, rectal temperature was 39.0°C, and heart rate was 68 beats/min. Findings were normal on transrectal examination. The heifer was 3 mo in calf. An irregularly shaped ulcerated mass, approximately 20 cm in diameter, was found in the right ear and appeared to be associated with the ear tag. In the left ear, a friable, ulcerated cauliflower-like mass, approximately 15 cm in diameter, with areas of necrosis completely obstructing the ear canal was unassociated with the ear tag. On further examination, additional 10–12 round, firm subcutaneous masses were found distributed over the thorax and neck. A firm round mass, approximately 12 cm in diameter, was found between the right fore and hind quarters of the udder, and bilateral enlargement of prefemoral lymph nodes was identified. All other lymph nodes were normal in size. Several small warts, 2–3 cm in diameter, were present around the tailhead and escutcheon. Neoplasia was the primary differential diagnosis; however, an atypical presentation of bovine papillomatosis was also considered.

The heifer was sedated with 0.1 mg/kg bodyweight (BW) of xylazine hydrochloride (Xylamax; Bimeda-MTC, Cambridge, Ontario) and 0.5 mg/kg BW of butorphanol (Torbugesic; Wyeth Canada, St. Laurent, Quebec) administered, IV, and a regional auricular nerve block was performed bilaterally by using 10 mL of 2% lidocaine hydrochloride (Xylocaine; Astra Pharma, Mississauga, Ontario) for each ear. Both auricular masses were surgically debrided (Figure 1) and a sample was sent for histopathologic examination. Blood was submitted for a complete blood (cell) count (CBC), biochemical analysis, and serological testing for antibodies against Bovine leukemia virus (BLV). Fine needle aspirates of the prefemoral lymph nodes, the udder mass, and a cervical mass were sent for cytological examination.

Figure 1.

Left ear 2 days following surgical debridement of the auricular mass.

Numerical results of the CBC were unremarkable. On microscopic examination of blood smears, a few abnormal lymphocytes with cleaved nuclei and densely stained clumps of chromatin were observed. Results from the biochemical analysis showed mild elevations in creatinine, total bilirubin, creatine kinase, and nonesterified fatty acids, along with a very mild decrease in total protein and cholesterol. Serological test results for antibodies to BLV were negative. These results and the age of the heifer ruled out enzootic bovine leukosis (EBL).

Histopathological examination of the samples from the auricular masses showed sheets of densely packed round cells completely obliterating normal tissue architecture. The neoplastic cells had occasional indented euchromatic nuclei containing up to 3 nucleoli and scant amphophilic cytoplasm. The mitotic index was high, and ulcerated areas of the masses were infiltrated with variable numbers of degenerate neutrophils, fibrin, macrophages, and occasional bacteria. The superficial aspect of the tumor showed infiltrates of scattered neutrophils and eosinophils.

Cytological analysis of the fine needle aspirates showed a monomorphic population of medium-sized lymphocytes with high nuclear to cytoplasmic ratios, scant dark basophilic cytoplasm, multiple distinct nucleoli, and a finely stippled chromatin pattern in each sample (Figure 2). A diagnosis of sporadic bovine leukosis (SBL) was made.

Figure 2.

Fine needle aspirate from a prefemoral lymph node showing a monomorphic population of abnormal lymphocytes. Bar = 10 μm

Two days following the initial examination, the heifer became progressively weaker and, eventually, was found recumbent with mild hemorrhage from the left nostril; she was euthanized.

At necropsy, generalized multifocal masses, 1–15 cm in diameter, were found in the peritoneum, throughout the mesentery, and in the spleen. All mesenteric lymph nodes were markedly enlarged. Moderate diffuse hepatomegaly was present. The surface of the liver was homogenous, but on cut section, sinusoidal dilation was evident. A membranous sac-like structure, nearly 25 cm in diameter, containing moderate amounts of serosanguineous fluid, multiple fatty aggregates, and large blood clots was present in the retroperitoneal space. A cluster of 3 small, 1–2 cm in diameter, cream-colored masses were found near the right ovary, attached to the ovarian ligament, but not associated directly with ovarian tissue. No other abnormal findings were noted. The head was not opened and examined. Samples of mesenteric lymph node, a subcutaneous mass, spleen, liver, kidney, lung, and heart were fixed in 10% buffered formalin and submitted for histopathologic examination and immunohistochemical staining.

Histopathologic examination of the samples collected at necropsy demonstrated a monomorphic population of moderately sized lymphocytes with hyperchromatic nuclei and scant pale basophilic cytoplasm with discrete cellular borders. In the lymph node, all normal architecture had been replaced by sheets of neoplastic cells. In the skin, the dermis and subcutis had also been replaced by sheets of neoplastic cells, and in the spleen, the neoplastic cells were present in nodular aggregates adjacent to the splenic capsule. The liver showed moderate expansion of portal tracts by neoplastic cells and diffuse capsular thickening with similar types of cells. There were no significant lesions in the kidney, heart, or lung.

Immunohistochemical labelling demonstrated variable staining of all cells with antibodies against the CD3+ molecule, characterizing the neoplastic lymphocytic cells as being of T-cell origin. A final diagnosis of the cutaneous form of sporadic bovine leukosis was made.

Discussion

Lymphoma is a term used to describe solid neoplasms of lymphocytes. In cattle, lymphosarcoma, or malignant lymphoma, has been used collectively to describe the entity of lymphoid neoplasia (1).

Two broad lymphosarcoma syndromes have been recognized in cattle: enzootic bovine leukosis (EBL) and sporadic bovine leukosis (SBL). The former, also known as the “adult form,” is directly related to infection with the Bovine leukemia virus (BLV) and is a disease of mature cattle. Sporadic lymphoma, on the other hand, is a disease of younger animals (< 3 y) and occurs independently of BLV infection. Three forms of sporadic lymphoma have been described: calf, thymic, and cutaneous (1). The cutaneous form has 2 subsets, nonepitheliotropic and epitheliotropic (2), according to the degree of epidermal involvement. A possible genetic etiology for SBL has been suggested (3), but the etiology and epidemiology remain largely unknown, despite worldwide occurrence of the condition. Enzootic bovine leukosis is a neoplasm of B-lymphocytes, while SBL may originate from the malignant transformation of either B- or T-lymphocytes (4–6).

Sporadic bovine leukosis has remained a clinical and pathologic curiosity despite recent efforts to further characterize the disorder. It occurs much less frequently than enzootic bovine leukosis, and of its 3 recognized forms, the cutaneous form, as in this case, has been most commonly reported, while the thymic form has been least commonly reported (8).

The cutaneous form of SBL primarily affects young adults 1–3 y old (1). Cutaneous lesions are described to be discrete, alopecic intradermal plaques or nodules of varying sizes that often become ulcerated and bleed, particularly in the advanced stages of disease (5,8,9). Reportedly, the lesions can regress over a period of time (1), but it is thought that recurrences occur with subsequent systemic involvement (7). Involvement of peripheral lymph nodes and internal viscera, including the heart, kidneys, liver, and spleen, has been reported to occur in 50% of cases (10).

It has been postulated that nonepitheliotropic forms are of B-cell lineage, whereas the epitheliotropic forms, which are less common, are of T-cell origin (8). The gross appearance of the lesions is similar in both forms, though microscopically there are differences. Epitheliotropic lymphosarcomas demonstrate an affinity for Langerhans’ cells and follicular epithelium of hairs, with progressive accumulation of neoplastic lymphocytes developing within these sites. There tends to be more severe destruction of adnexal structures (8–10).

Disease progression in epitheliotropic and nonepitheliotropic lymphosarcoma also differs in that epitheliotropic forms appear to be confined primarily to the skin and superficial lymph nodes, whereas nonepitheliotropic forms develop visceral involvement late in the course of the disease (2). However, most descriptions of epitheliotropic cutaneous lymphosarcoma have originated from canine cases, where euthanasia may have prevented visceral involvement from developing (2). In cattle, the clinical presentation of epitheliotropic cutaneous lymphosarcoma has been poorly described.

Auricular tumors similar to those described in this case have not been reported previously. The gross appearance of the cutaneous lesions found over the trunk, neck, and udder in this case were atypical in that rather than being raised, alopecic, intradermal nodules, they were completely subcutaneous with no visible ulceration.

The histopathological characteristics of dermal destruction by neoplastic lymphocytes in the skin lesions and destruction of lymph node architecture and the CD3+ T-cell origin fit the description of the epitheliotropic form of cutaneous lymphosarcoma, despite the presence of atypical gross lesions. The visceral involvement may characterize late stage epitheliotropic cutaneous lymphosarcoma, which has not been described previously in cattle due to the rarity of cases.