Pediatric Patient With Neurological And Leukemic Peripheral Blood Involvement By Small Cell Variant Of ALK- Positive Anaplastic Large Cell Lymphoma (ALCL): Case Study

Abstract

Abstract Casestudy Anaplastic large cell lymphoma (ALCL), is a T-cell lymphoma typically consisting of large lymphoid cells including characteristic horseshoe- shaped hallmark cells. The rare small cell morphological variant of ALCL may pose a challenge in diagnosis, especially when the initial presentation is unusual. Results Our patient, a 7-year-old girl presented with a headache. A complete blood count showed leukocytosis and anemia. The smear was reported to have segmented neutrophils, reactive lymphocytes, and monocytes. A spinal tap was performed and flow analysis identified a minute aberrant T cell population (0.3% of total), positive for CD3, CD4, bright CD7; negative CD5, CD8 in the CSF sample. The peripheral blood sample was reviewed again; some small- medium atypical lymphocytes, with irregular nuclear contours and cytoplasmic azurophilic granules were noted. Flow immunophenotyping displayed an aberrant T cell population positive for CD45, CD2, CD3, bright CD7, CD4, CD13; negative CD30, TdT CD5, CD8, CD117, CD34; consistent with T cell lymphoma/leukemia. A cell block prepared from peripheral blood sample showed blood with numerous atypical cells with irregular nuclei positive for ALK, CD30, CD3, CD4, CD7; negative CD5 and CD8. A diagnosis of leukemic ALK(+) ALCL was rendered, though classic hallmark cells were difficult to see. A marrow biopsy showed interstitial and sinusoidal pattern of mainly small to medium-sized cells with irregular nuclei. Molecular study revealed ALK gene alteration showing characteristic NPM1-ALK fusion. The patient underwent a bone bone marrow transplantation but recently relapsed with a submandibular lymph hode biopsy showing the presence of many larger ALCL cells. Conclusion Correct clinical diagnosis of the small-cell variant of ALCL is often challenging as the scarce “hallmark cells” are scattered and difficult to recognize. While leukemic peripheral blood involvement is rare in ALCL, an association has been reported with small-cell variants, which may be a potential explanation for the poor prognosis and aggressive nature of small-cell variant ALCL. A meticulous examination of peripheral blood smears, comprehensive immunophenotypic studies, and early bone marrow and lymph node/tissue biopsy are needed to facilitate diagnosis.