A 65 years old female with insulin dependent diabetes mellitus  presented in 2015 with mild lymphocytosis (7.5 x 109/L) and by flow cytometry analysis was detected in her blood a lambda light chain restricted B lymphoid population with a non-Chronic lymphocytic leukemia immunophenotype(CLL) immunophenotype: CD20, CD22 bright, CD11c, CD79b and FMC7 positive, negative for CD5, CD23, CD10, CD25, CD103 and CD25 (absolute number 3.7 x 109/L).  CT examination at that time did not detect lymphadenopathy or splenomegaly. A limited cytogenetics study revealed a normal female karyotype 46,XX[13]. Approximately 25% of the lymphoid cells on the peripheral blood smear had nuclear abnormalities characterized by nuclear budding, with projections of variable amounts of nuclear material and formation of micronuclei. She was followed-up with CBCs and clinical visits every 6 months.  In 2019, the patient was hospitalized for a stroke, and her CBC was again remarkable for mild lymphocytosis with approximately 10% of the lymphoid cells exhibiting similar nuclear abnormalities. A CLL FISH panel was negative for trisomy 12, deletion 6q, ATM,13q and TP53.

A limited  number of publications mention nuclear budding, micronuclei and nucleocytoplasmic bridges in the lymphoid cells, with emphasis placed on chromosomal imbalance and chromosomal mal-segregation during anaphase1. In-vitro studies with cytokinesis block demonstrate similar findings of nuclear budding2 in folic acid deficient human lymphocytes.  In another study, the authors suggest that anomalies of the genes involved in cell cycle control  increase the number of abnormal chromosomes and, consequently, increase the nuclear budding3. Only one image report exists of a lymphoproliferative neoplasm, a case of chronic lymphocytic leukemia with a complex karyotype4 and TP53 deletion remarkable for nuclear budding of lymphoid cells.

Our case, best classified as a non-CLL type monoclonal B-cell lymphocytosis brings into consideration other causes of lymphoid cells chromosomal imbalance (? drugs), nuclear envelope proteins and nuclear pore complex abnormalities etc.

References:

1.        Fenech, M. et al. Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis 26, 125–132 (2011).

2.        Fenech, M. & Crott, J. W. Micronuclei, nucleoplasmic bridges and nuclear buds induced in folic acid deficient human lymphocytes-evidence for breakage-fusion-bridge cycles in the cytokinesis-block micronucleus assay. Mutat. Res. 504, 131–136 (2002).

3.        Shimizu, N., Itoh, N., Utiyama, H. & Wahl, G. M. Selective entrapment of extrachromosomally amplified DNA by nuclear budding and micronucleation during S phase. J. Cell Biol. 140, 1307–1320 (1998).

4.        Geyer, J. T. & Subramaniyam, S. Micronuclei and nuclear budding in chronic lymphocytic leukaemia. Br. J. Haematol. 167, 585 (2014).