Journal of Applied Hematology

Dear Editor,

Atypical lymphocytes are a group of cells with varied morphology. Although some of their features are classically documented in malignant hematological conditions, they can also be part of benign spectrum.[¹]

Downey and McKinlay first described the atypical lymphocytes seen in cases of infectious mononucleosis in 1923. They further categorized the atypical lymphocytes of different etiologies under three subtypes naming Type I, Type II, and Type III.[²] With the changing times, findings of atypical lymphocytes with the morphological description as was initially illustrated have been observed in various infectious, autoimmune disorders, and drug-induced changes.[^3,4]

We wished to re-emphasize the morphological heterogeneity of atypical lymphocytes in diagnosed seropositive dengue patients. We aimed to highlight numerous benign changes in lymphocytes, which otherwise are documented and given importance in monoclonal malignant plasma cell disorders.

A total of 30 patients with seropositive dengue infection were included in the study. The study was conducted after ethical approval from the institute ethics committee. Peripheral blood samples were collected at the time of hospital admission. Giemsa-stained peripheral blood smears were made for each case, and the smears were screened for atypical cells of lymphocytic lineage by two independent observers.

Among the 30 patients, 25 cases had florid reactive changes in the peripheral blood smear, while four smears had very less populations of reactive cells, and one smear had no change at all.

For the morphological classification of Downey cells, we applied the descriptions used by Downey and McKinlay.[²]

1. Type I as highly differentiated “leukocytoid lymphocyte,” round-to-lobulated nucleus, mature clumped chromatin with or without nucleoli and with varying degree of basophilia in the cytoplasm
2. Type II as larger cells with round-to-lobulated nucleus, chromatin resembling that of plasma cells, moderate amount of cytoplasm with mild basophilia. Cytoplasmic skirting/scalloping is a commonly described feature in some of them
3. Type III cells are large cells with a round to slightly indented nucleus, chromatin mostly immature with diffuse sieve-like arrangements and nucleoli.

All three types of Downey cells were observed along with some other variants which included larger cells with deeply convoluted nucleus, cells with crystalline rods and granules in the cytoplasm, flame cells, Mott cells, and some intermediate forms whose morphology has not been defined in the available literature.

We classified these variant lymphocytes into three categories:

1. Class A cells: These are cells having cytoplasmic immunoglobulin crystals, globules, or Russell body, and sometimes, they may transform into a Mott cell creating a suspicion of malignant plasma cell disorder.[⁵] [Figure 1abc and f] shows lymphocytes with crystalline cytoplasmic inclusions while [Figure 1d and e] shows Mott cells. These crystalline rod-like inclusions have been discussed as a morphological variant of inclusion bodies in multiple myeloma but, to the best of our knowledge, have never been reported in benign conditions[⁶]
2. Class B cells: These cells have long polar cytoplasmic extensions with azure granules, both of which are commonly mentioned as part of malignant lymphoid changes.[⁷] Some of the Class B cells showed purple red or magenta staining of cytoplasm characteristically described in flame cells. The magenta staining cytoplasm of flame cells has been theorized as that due to the presence of an anomaly in the carbohydrate moiety of the immunoglobulin component.[⁸] [Figure 1ghijkl] depicts these cells.
3. Class C cells: They have deeply grooved, convoluted, or even lobated nucleus. Deep nuclear grooving may create a morphological confusion with hematological neoplasms of monocytic lineage. Figure 2 shows these characteristic features of class C cells.

Our observation suggests that these cells in the peripheral blood do not necessarily indicate a neoplastic etiology, rather in endemic areas of an infectious agent-like dengue virus can induce such changes too.[⁹]

In our conclusion, we wish to state that benign lymphocyte morphology is diverse and can alter more in reactive situations. Identification of atypical lymphocytes of reactive origin is important to reduce further unnecessary investigations and streamline the flow of diagnostics toward infectious etiology.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Acknowledgment

We wish to express our sincere gratitude to Dr. Irshad, our head of department when the study was conducted, and to the technical staff at the Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi.

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