Hyperplasia in a lymph node can involve cortex (B cells), paracortex (T cells), medullary chords (plasma cells), and macrophages. Hyperplastic lesions of B cells are characterized by formation of lymphoid follicles with a prominent germinal center surrounded by mantle and marginal zones. The time to develop follicles in humans is closer to 2 weeks following antigenic exposure, whereas in dogs it is 10 days. Germinal centers are present predominantly in the cortex but may populate the paracortex with sustained antigenic stimulation. Germinal centers have a consistent architecture with the interior cells having a superficial or light pole and a deep or dark pole. Recognition of this polarity is important observation in distinguishing lymphoid hyperplasia from follicular lymphoma [2]. The cells within the superficial pole are small lymphocytes with a moderate amount of light-stained cytoplasm giving it a less dense appearance, whereas the cells of the deep pole are large lymphocytes with proportionally less cytoplasm that is deeply amphophilic, resulting in darker and compact appearance. Many tingible body macrophages are also scattered within the germinal centers and phagocytize lymphocytes whose antibody exhibits too high or too low avidity. Generally, well-developed germinal centers are not present at birth unless there has been intrauterine infection. The mantle cell zone is composed of relatively homogenous population of small lymphocytes that have round compact nuclei that lack nucleoli and have very little cytoplasm and give rise to pregerminal center B cells [2]. Marginal zone cells are not generally prominent in normal nodes but may become prominent in case of immune response [2]. The marginal zone cells have relatively abundant cytoplasm and round and larger nuclei with fine dispersed chromatin and a single nucleolus. These cells are believed to be memory cells [2]. Medullary cords are populated by plasma cells and macrophages. In the case of increased demand for erythropoiesis, cords can be populated by erythroid progenitors (extramedullary hematopoiesis). The immunohistochemical markers and their sources for macrophages and T and B cells are listed in Tables 9.1 and 9.2.

Tumors of lymphocyte origin ar e lymphosarcoma and leukemia. Lymphosarcoma is a solid tissue tumor arising in organs other than the bone marrow and are of B, T, and NK cell origin. However, in advanced stages, neoplastic cell can infiltrate the bone marrow. The term “lymphoma” implies benign tumor but almost all advanced lymphomas are malignant; therefore, “lymphosarcoma” is considered a better diagnosis. Histologically, lymphosarcoma can be diffuse or of nodular/follicular hierarchy origin, i.e., mantle zone, marginal zone, follicular, and T zone lymphomas. Leukemia is tumor of hematopoietic cells that originates in the bone marrow, e.g., RBC, neutrophils, eosinophils, megakaryocytes, lymphocytes, and monocytes. Neoplastic cells are present in the blood and/or bone marrow.

Lymphosarcoma in genetically intact mice often arises in the mesenteric lymph nodes, spleen, and intestinal Peyer’s patches. Involvement of lymph nodes can be primary or secondary [3]. In case of primary involvement, tumors originate in the lymph nodes, whereas they metastasize to regional lymph nodes in secondary involvement. The origin of metastases depends largely on the location of the primary neoplasm and subsequent spread to the regional lymph node, e.g., cervical and peritracheal lymph nodes are the most common metastatic sites for thyroid carcinomas. The mesenteric lymph nodes are common site of metastasis for small and large enteric carcinomas and enteric lymphoma. The mandibular lymph node is a common site for malignant Zymbal gland carcinoma metastasis.

The evaluation of a p otential treatment-related effect and subsequent alteration in the gross and histologic morphology depend on the physical and chemical properties of toxicologic agent or test compound, site of administration, and duration of the study. For example, oral administration of a paraffin compound resulted in granulomatous inflammation in the mesenteric lymph nodes with accumulation of macrophages in sinuses [4]. However, common toxicologic lesions include lymphocyte degeneration, necrosis, apoptosis, depletion, atrophy, and lymphoid and macrophage hyperplasia. A survey of nonneoplastic lesions in the mandibular and mesenteric lymph nodes in control B6C3F1 mice revealed lymphoid hyperplasia, plasma cell hyperplasia, lymphoid depletion, inflammation, sinus histiocytosis, angiectasis, hemorrhage, pigmentation, and extramedullary hematopoiesis [3].