Lymph node cytology (Proceedings)

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You should consider three major processes when evaluating cells from an enlarged lymph node: 1) Reactive lymph node 2) Lymphadenitis 3) Neoplasia- lymphoma or metastatic.

Lymph node cytology

You should consider three major processes when evaluating cells from an enlarged lymph node: 1) Reactive lymph node 2) Lymphadenitis 3) Neoplasia- lymphoma or metastatic.

Enlarged lymph nodes tend to exfoliate well and often yield very thick aspirates. It is important to examine the thinner, more peripheral portions of the smear, as the thick, central regions often do not stain well. Regardless of aspiration or smear technique, lymphocytes tend to be fragile and many will rupture on the slide. These cells will appear as large, pale pink nuclei without any surrounding cytoplasm and should be disregarded. Numerous small, round basophilic structures about the size of platelets (lymphoglandular bodies) can be seen in most lymph node aspirates and represent cytoplasmic fragments.

Reactive lymph nodes

Reactive lymph nodes are nodes that are responding to antigenic stimulation and/or inflammation in the region which they drain.

The majority of the lymphocytes in a reactive node should be small lymphocytes (smaller than a neutrophil or eosinophil) with smaller numbers of intermediate sized lymphocytes (about the size of a neutrophil) and even fewer numbers of lymphoblasts (large cells with prominent nucleoli). Plasma cell numbers are increased in reactive nodes and will vary from 5-25% of the total cell numbers in some areas of the slide. Increased plasma cell numbers are considered to be one of the hallmarks of reactive lymph nodes and are responding to antigenic stimulation. Plasma cells are characterized by a small, round, often eccentrically located nucleus that has a very coarse chromatin pattern and moderate amounts of basophilic cytoplasm. A perinuclear clear zone in the cytoplasm can often be seen. Inflammatory cells are often present in small to moderate numbers and may be neutrophils, eosinophils, mast cells or macrophages. Lymph nodes draining regions of cutaneous inflammation will often contain increased numbers of eosinophils and mast cells. Mast cell numbers should generally be less than three percent of the total cells in a reactive lymph node. A significant increase above those numbers warrants a search for a primary mast cell tumor.

Lymphadenitis

Lymphadenitis implies that there is inflammation within the lymph node and the type of inflammation can be classified as suppurative, pyogranulomatous or granulomatous based on the predominant cell types.

Reactive lymph nodes are also frequently somewhat inflamed. Some authors have characterized lymphadenitis as consisting of greater than 5% neutrophils or 3% eosinophils; lymph nodes that have increased numbers of plasma cells and have been classified as reactive commonly contain this many inflammatory cells. For practical purposes, the term lymphadenitis is generally used in cases in which lymph nodes contain large numbers of inflammatory cells often as a result of an infectious process. Pyogranulomatous inflammation can be seen with sytemic fungal disease such as coccidiomycosis, histoplasmosis, blastomycosis and cryptococcosis. Granulomatus lymphadenitis can be seen in mycobacterial infections. Suppurative responses are generally seen with bacterial infections.

Neoplastic lymph nodes

Metastatic neoplasia

Many primary tumors metastasize via the lymphatics and any suspected tumor with regional lymphadenopathy warrants lymph node aspiration. The presence of cells not normally found in a lymph node, especially when they can be compared to the cells found in the suspected primary mass, provides information about tumor behavior and potential prognosis. In addition, neoplasia should be suspected when there are increased numbers of cells that are normally found in small numbers in lymph nodes. Mast cells should generally not be found in numbers greater than 3% of the total population and significant increases should be a concern for metastatic mast cell tumor. Lymph nodes with metastatic tumors will often have features of reactive lymph nodes (increased numbers of plasma cells and inflammatory cells) so a thorough examination of the slide for neoplastic cells is always indicated.

Lymphoma

Lymphocytes can undergo clonal, neoplastic proliferation at any stage of development. Because of this, lymphomas can be comprised of lymphoblasts, intermediate-sized lymphocytes or small lymphocytes. The important distinction between neoplastic lymphocytes and other neoplastic cells is that uniformity of cells is the hallmark of lymphomas. In normal or reactive lymph nodes, small lymphocytes predominate but there are also a mix of intermediate-sized lymphocytes and lymphoblasts giving the overall appearance of cellular heterogeneity. Lymphoma, on the other hand, will usually consist of a monomorphic population of lymphocytic cells. Lymphoblastic lymphomas can be pretty straight-forward especially when the lymphoblast concentration is greater than 50%. Earlier stages of lymphoblastic lymphoma may have notably increased numbers of lymphoblasts yet not numbers high enough to be confident of lymphoma. Lymphomas comprised of smaller, non-blastic cells can also be more difficult to interpret. Sending these cytologic specimens to a clinical pathologist is recommended, as is excisional biopsy. When possible, lymph node biopsies should involve removing the entire node as this will allow the pathologist to examine lymph node architecture and be much more definitive in their diagnosis.

Note: In general, when sending slides out for cytologic interpretation, try to include one or two unfixed, unstained smears and never send unstained slides in the same container as a jar containing formalin.

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