Abbey Veterinary Services

DIAGNOSTIC HISTOPATHOLOGY AND CYTOLOGY

CASE OF INTEREST

A case of T-Zone lymphoma in a crossbred dog.

By Richard Fox, Veterinary Pathologist

Case donated by Judith Hargreaves, Veterinary Pathologist.

A nine year old crossbred dog presented with moderately enlarged submandibular and minimally enlarged popliteal lymph nodes. Initially, four months previously, only the submandibular lymph nodes were enlarged. The dog was otherwise clinically well.

Fine needle aspiration (FNA) was performed on both submandibular lymph nodes and the left popliteal lymph node. Cytopathological examination was performed. The preparations had a good cell harvest and good cellular preservation. Preparations were composed mostly of medium sized monomorphic lymphocytes with only a minimal population of small well differentiated lymphocytes and large lymphocytes/lymphoblasts. Cells had a small amount of basophilic, granular cytoplasm. Nuclei were round and monomorphic with a size of one and a half times the diameter of an erythrocyte (10um). Nuclei were non-cleaved and lacked distinct nucleoli (Figure 1). Findings represented a relatively pure population of cells which suggested the presence of lymphoma and given the cell size and lack of mitoses, suggested a low or intermediate lymphoma. Surgical biopsy was then advised to confirm the cytopathologic interpretation.

Figure 1. Cytological preparation identifying a monomorphic population of medium sized lymphocytes and rare small lymphocytes. Cells have moderate amounts of basophilic cytoplasm (x40 obj.). Rapid Romanowsky Stain.

Surgical excision of the left popliteal lymph node was performed and submitted for histopathological examination. Histologically the normal lymph node architecture was disrupted but largely preserved. The subcapsular and medullary sinuses were markedly dilated. The medullary parenchyma was markedly reduced. In the cortex, occasional residual follicles were present with fading germinal centres. Many of these were peripheralised and layed directly beneath the capsule. The paracortex was expanded by a monomorphic population of lymphocytes. These were medium sized (approximately 13um in diameter) and had round or indented nuclei (approximately 10um in diameter) with single or multiple small chromocentres. They had moderate amounts of basophilic, granular cytoplasm. The mitotic index was 1. A diagnosis of indolent lymphoma was made and the morphology was consistent with T-Cell Zone lymphoma.

Figure 2. Histological section of lymph node, under low magnification, identifying dilated medullary lymphatic sinuses and peripheralised atrophic (subcapsular) lymphoid follicles with the cortex replaced by sheets of monomorphic lymphocytes (x5 obj.). HE Stain.

Figure 3. Histological section of the monomorphic lymphoid population. (x10 obj.). HE Stain.

Immunohistochemistry was performed on surgical biopsy material with antibodies specific for T-cell (CD3) and B-cell markers (CD79a and PAX-5). Results indicated that the monomorphic lymphocyte population expanding the paracortex were negatively stained for CD79a and PAX-5 and displayed strong peripheral (membranous and peripheral cytoplasmic) staining for CD3. A diagnosis of T-Zone lymphoma was made.

Figure 3. Histological section of lymph node stained immunohistochemically for the T-cell marker CD1. Note the negatively stained pre-existing lymphoid follicle (B-cells) (counter stained with Papanicolaou's) (x10 obj.).

Indolent lymphomas arise on a background of follicular lymphoid hyperplasia, and include follicular, mantle cell, and marginal zone lymphomas (MZL) of B-cell type, and T-zone lymphoma of T-cell type (TZL). The indolent lymphomas of B- and T-cell types share a low mitotic rate and slow rate of clinical progression. Indolent lymphomas in advanced stages retain the same cytomorphologic features, but lose the follicle-related architecture, without which their indolent nature may not be apparent on histologic examination. These lymphomas usually arise after a long period of benign hyperplasia and tend to contain capsular and medullary sclerosis.

T-Zone lymphoma (TZL) is characterized by cellular proliferation between fading follicles, rather than surrounding them, as in MZL Cytologically, TZL is composed of homogeneous population of CD3+ small lymphocytes that have sharp, shallow nuclear indentations, inapparent nucleoli, and a moderate volume of pale cytoplasm. In contrast, T-Zone hyperplasia consists of a heterogeneous population of small lymphocytes, macrophages, and dendritic cells, which imparts a moth-eaten appearance at low magnification.

The small number of reported cases have generally involved peripheral lymph nodes but one involved a mesenteric node. It is a type of lymphoma that is relatively common in the dog but rare in other species. Usually one or two lymph nodes are initially involved and found incidentally on examination. The dog is invariably in good health with normal appetite and activity. No tissues, apart form lymph nodes are known to be involved. Generalized lymph node involvement ensues but greatly enlarged nodes often retain their zonal architecture. Conservative therapy is recommended as owners perceive the dog to do as well without chemotherapy. Apparent long survival times have been noted but little prognostic data is available.

References:

1. Valli VE, Vernau W, de Lorimier LP, Graham PS, Moore PF. Canine indolent nodular lymphoma. Vet Pathol. 2006 May;43(3):241-56.

2. Mature (Peripheral) Nodal T-Cell (T-Zone) Lymphoma. in Veterinary Comparative Hematopathology, 1st edition (2007), Victor E. Valli pp. 295-302.