Cytology of the lymphoid organs (Proceedings)
As the primary cell type present in lymphoid organs is lymphocytes, the first part of this handout will describe the morphologic features of lymphocytes and then briefly describe other methods to assess lymphocytes. The second part of the handout will describe the interpretation of various lymphoid organs.
Small lymphocytes are smaller in size than a neutrophil and have a round nuclei that takes up the majority of the cell. The nuclei contain densely aggregated chromatin forming large chromocenters (condensed chromatin). Nucleoli are not seen. The cytoplasm is scant (sometimes only a very thin rim is visible) and lightly basophilic in color. These are typically called 'mature lymphocytes'. However, early lymphoid progenitor cells, hematopoietic stem cells, certain stages and types of dendritic cells, and other immature precursor cells may have a very similar morphology to 'mature, well-differentiated, small, resting lymphocytes'.Intermediate to large lymphocytes range in size from slightly larger than small lymphocytes to the size of neutrophils. The nuclei still takes up the majority of the cell, however more abundant cytoplasm is visible in these cells. Often, the nuclei is placed eccentrically within the cytoplasm. The nuclear chromatin is finely clumped to granular. Typically, nucleoli are not seen although strands of loosely clumped nuclear chromatin may be mistaken for nucleoli. The cytoplasm is lightly basophilic in color. Occasionally these cells contain azurophilic granules suggestive of a natural killer (NK) phenotype.
Lymphoblasts are as large as a neutrophil or larger. Size alone does not indicate neoplasia. Very large lymphoblasts (2-4x the size of neutrophils) may be seen in reactive and hyperplastic processes. Lymphoblasts contain round to oval nuclei with fine or stippled chromatin (loosely aggregated chromatin). One or more nucleoli may be visible. The cytoplasm is moderately to deeply basophilic. Occasionally (seen more in cats than dogs) the cytoplasm may contain punctate vacuoles.
Reactive lymphocytes are similar in morphology to small lymphocytes but are slightly larger and have more abundant, more basophilic cytoplasm.
Plasma cells are intermediate sized cells that contain small, round, eccentrically placed nuclei with condensed chromatin. Cytoplasm is abundant, deeply basophilic, and often contains a prominent, eccentric, perinuclear, clear zone that corresponds to the Golgi.
Morphologic features and typical findings used to characterize atypical lymphocytes
Lymphoglandular bodies are round, homogeneous, basophilic structures comprised of cytoplasmic fragments. The presence of lymphoglandular bodies is seen in cytologic preparations of lymphoid tissue that contains increased numbers of lymphoblasts. This can be due to neoplasia (lymphoma) or hyperplasia.
The presence of an eccentric, perinuclear clearing zone is often suggested as a feature of B-cells and plasma cells. The clearing zone is the Golgi and it is a prominent feature in plasma cells. However, the Golgi apparatus is an organelle found in most cells, including T-cells and myeloid cells.
In humans, Sezary cells are described as medium to large lymphocytes with ceribriform nuclei. These neoplastic T-cells are characteristic features of Sezary syndrome which encompasses mycosis fungoides, an epitheliotropic variant of cutaneous lymphoma. A similar syndrome occurs in dogs but has been rarely reported in cats. In dogs, epitheliotropic T-cell lymphoma is also seen in the gastrointestinal tract. T-cells predominate in both the cutaneous and GI variants. Interestingly, expression of protein gene product 9.5 (PGP 9.5), a marker previously considered specific for neural and neuroendocrine tissues, was recently detected in over 8/14 cases of canine cutaneous mycosis fungoides suggesting that there may be other biologic differences between the human and canine variants.
In humans, the presence of flower cells or cloverleaf cells is most often associated with T-cell disease and is particularly a feature of infection with human T-lymphotrophic virus-1 (HTLV-1). In dogs and cats, similar morphology has been seen in both B-cell and T-cell lymphoproliferative disease as well as myeloproliferative disease.
In humans, CLL is considered a disease of B-cells. In contrast, CLL of dogs and cats is primarily a T-cell disease. In dogs, CD8+ (cytotoxic) CLL predominate while in cats, CD4+ (T-helper) CLL is more common. However, there is variation in the disease in both dogs and cats and B-cell, CD4+ T-cell, and CD8+ T-cell CLL have all been diagnosed in small animals.
Chronic lymphocytosis: In dogs, a chronic lymphocytosis comprised of intermediate sized lymphocytes with small azurophilic granules has been reported in association with Ehrlichiosis.