Polymorphous lymphocytes are a common finding in blood and tissue samples, representing a diverse population of immune cells that have changed their appearance from their usual resting state. The term “polymorphous” means having many shapes, referring to the varied sizes and forms these lymphocytes take when viewed under a microscope. Their presence signals immune system activity, but determining if this activity is a simple, temporary reaction or a sign of a more serious disorder requires careful interpretation by pathologists.
The Distinctive Morphology of Polymorphous Lymphocytes
The typical, inactive lymphocyte is a small, uniform cell with a dense, round nucleus that occupies most of the cell, leaving only a thin rim of cytoplasm. Polymorphous lymphocytes, often called “atypical” or “reactive” lymphocytes, deviate noticeably from this standard appearance, reflecting their activated state. These cells can be significantly larger, sometimes exceeding 30 micrometers in diameter, compared to the 7 to 10 micrometers of a resting lymphocyte.
Their nuclei are a major source of the “polymorphous” description, as they can be round, elliptic, indented, or even folded and clefted. The nuclear chromatin may appear less condensed or more sieve-like than the tightly clumped chromatin of a normal lymphocyte. The cytoplasm also changes dramatically, becoming more abundant and sometimes deeply colored, or basophilic, due to an increase in internal cellular machinery. This abundant cytoplasm may also have a pale area where it meets the nucleus or appear to “skirt” around nearby red blood cells, a classic feature of these activated cells.
Reactive Polymorphous Lymphocytes and Benign Conditions
In most instances, the presence of polymorphous lymphocytes is a benign finding, signaling a healthy and robust immune response known as reactive lymphocytosis. This reaction is the immune system’s way of rapidly activating and proliferating its cells to fight off a perceived threat, such as a virus or bacteria. This type of change is considered “polyclonal,” meaning the varied lymphocytes are a mixed population arising from many different parent cells, all reacting to the same stimulus.
One classic example is infectious mononucleosis, commonly caused by the Epstein-Barr virus (EBV), where these atypical lymphocytes were first described. In this condition, the virus stimulates a massive proliferation of cytotoxic T-lymphocytes, which are the immune cells responsible for killing infected cells. The resulting polymorphous lymphocytes are often categorized into types based on their specific morphology, with the Downey type II cell being the most common variant seen in viral infections.
Reactive polymorphous cells can be seen in response to a variety of other triggers, including parasitic infections, certain drug reactions, and chronic inflammatory states. In these benign conditions, a pathologist reviewing a blood smear or tissue biopsy will observe a broad spectrum of lymphocyte morphologies, with small, medium, and large activated cells mixed with normal-looking cells. This heterogeneity supports a diagnosis of a temporary, reactive condition rather than a disease driven by uncontrolled, single-cell type proliferation.
The Significance of Polymorphous Lymphocytes in Malignancy
While often a sign of a benign reaction, polymorphous lymphocytes can also be a feature of certain types of cancer, particularly lymphomas, which are malignancies of the lymphatic system. When the cells are neoplastic, their varied appearance reflects an inherent instability and uncontrolled growth, rather than an organized immune response. The context of the finding is paramount, as the same general term describes different underlying processes in benign and malignant settings.
In lymphomas such as peripheral T-cell lymphoma, the malignant cells themselves can exhibit a high degree of pleomorphism, meaning they are inherently varied in size and shape. In conditions like Hodgkin lymphoma, the malignant Reed-Sternberg cells are often surrounded by a dense, polymorphous inflammatory background that includes small lymphocytes, plasma cells, and eosinophils. This complex mixture of cells can sometimes be misleading, making the distinction from a purely reactive process challenging.
Pathologists rely on sophisticated laboratory techniques to differentiate between a benign, reactive polymorphous population and a malignant, neoplastic one. Flow cytometry is often employed to determine clonality, which is the most definitive distinction. A reactive process is polyclonal, involving many different immune cell lines, whereas a malignant process is monoclonal, arising from the unchecked division of a single abnormal cell. In malignancy, the polymorphous cells often efface, or destroy, the normal architecture of the lymph node, a feature not seen in benign reactive hyperplasia. The overall uniformity of the atypical cells, even if they appear strange, can suggest malignancy, as all the cells are derived from the same cancerous clone.