Atypical lymphocytes

Morphologically abnormal lymphocytes must be differentiated from normal lymphocytes. Atypical lymphocyte are either inflammatory reactive cells or malignant cells within the manifestation of lymphatic neoplasms of mature cells.

For a long time, there was no unified nomenclature for atypical lymphocytes. The term was used as well for inflammatory reactive lymphocytes as for generally conspicuous lymphocytes.

A German group of experts (Arbeitskreis Laboratorium der DGHO) proposed in 2011 a new unified nomenclature. In a first step, normal lymphocytes are differentiated from morphologically abnormal Lymphocytes. If cytologically possible, the abnormal cells should be differentiated in a second step into "atypical lymphocytes" of probably reactive nature and "atypical lymphocytes" of probably neoplastic nature.

Reactive atypical lymphocytes

Synonym:

Stimulated lymphocytes

Appearance:

Reactive atypical lymphocytes can vary widely in size, form and shape. They are larger than normal lymphocytes and have a large volume of light to dark basophilic cytoplasm that has a more intense color along the cell membrane. Vacuoles and azure granules may also be present. The nucleus is often kidney-shaped. The chromatin is finer than in small lymphocytes and often has one or more nucleoli. Atypical lymphocytes can not always be clearly identified and are often confused with leukemic blasts by those who are inexperienced. In contrast to blasts, the chromatin of atypical lymphocytes it not fine enough and their appearance is too polymorphic. Atypical lymphocytes can belong to the B-call line as well as to the T-cell line.

Occurrence/Presence:
- Viral infections such as infectious mononucleosis, cytomegalovirus and primary HIV infection
- Toxoplasmosis 

Possibly neoplastic atypical lymphocytes

Synonym:

Lymphoma cells

Definition:

All morphologically altered lymphocytes in the peripheral blood, that can not be clearly identified as large granular lymphocytes (LGL) or reactive atypical lymphocytes, are suspected to be mature cells of lymphatic neoplasms (= dissemination of lymphoma cells). The appearance of such cells can vary widely. They can not always be a assigned to specific diseases. Occasionally, possibly neoplastic atypical lymphocytes are found in an otherwise normal lymphatic population.

Appearance of mature neoplastic B- and T-cells in the peripheral blood:

• Splenic marginal zone lymphoma with villous lymphocytes (SMZL):
  High to medium nucleus-to-cytoplasm ratio; medium sized, round to oval nuclei with dense chromatin; basophilic cytoplasm with fine uni- or bipolar cytoplasmic extensions.
• Lymphoplasmacytic lymphoma (Waldenström's macroglobulinemia):
  Low nucleus-to-cytoplasm ratio; round to oval eccentrically located nuclei with medium fine chromatin; asymmetrically enlarged light basophilic cytoplasm.
• B-prolymphocytic leukemia (B-PLL):
  Medium nucleus-to-cytoplasm ratio; large round nucleus with medium fine chromatin and mostly with a large prominent nucleolus; light basophilic cytoplasm. Often with pronounced lymphocytosis.
• Hairy cell leukemia (HCL):
  Low nucleus-to-cytoplasm ratio; oval to kidney shaped nucleus with reticular chromatin; large grey-blue cytoplasm with plump circular cytoplasmic extensions.
• Follicular lymphoma (FL):
  Small cells with high nucleus-to-cytoplasm ratio; round, often incised or cleaved nucleus with dense chromatin; missing to very narrow cytoplasmic margin.
• Mantle cell lymphoma (MCL):
  Medium nucleus-to-cytoplasm ratio; medium size folded nucleus with fine chromatin; medium large basophilic cytoplasm.
• Diffuse large B-cell lymphoma (DLBCL):
  Variable nucleus-to-cytoplasm ratio; large, variably sized round to oval to very sinuate nuclei, mostly with visible nucleoli; medium large, dark basophilic cytoplasm.
• T-cell prolymphocytic leukemia (T-PLL):
  Medium nucleus-to-cytoplasm ratio; small to medium sized lymphocytes with round to distinct irregularly shaped nuclei and mostly one nucleolus; medium large, basophilic slightly asymmetric cytoplasm. Often pronounced lymphocytosis.
• Sézary disease:
  Medium nucleus-to-cytoplasm ratio; medium size, gyrated or folded nucleus; missing to very narrow cytoplasmic margin.