Contributed by Sarika Jain, MD, Christopher Cogbill, MD and Fiona E. Craig, MD
A 66 year old female with excessive fatigue. On examination, patient was found to have splenomegaly measuring 7-8 cm below the costal margin. CT scan was negative for lymphadenopathy.
Laboratory work-up: WBC-277 x 109 / L, Hb-8.5 gm/dl, MCV-98 fl, MCH-34 pg, MCHC 34.7 gm/dl, RDW-22, platelets-28 x 109 / L, absolute lymphocyte count-251.6 x 109 / L, absolute neutrophil count-19.4 x 109 / L, absolute monocyte count-9.9 x 109 / L, LDH-3430 IU/L.
Peripheral blood: Lymphoid cells varied from small to intermediate size, with round to slightly irregular nuclei, prominent nucleoli and scant to moderate amount of blue cytoplasm with occasional cytoplasmic blebs (Fig. 1).
Bone marrow: Markedly hypercellular (80-90%) with decreased myelopoiesis and erythropoiesis. Sheets of small to intermediate cells with round to slightly irregular nuclei, prominent nucleoli and moderate amount of cytoplam were seen (Fig. 2).
Flow cytometric evaluation of the bone marrow:
Aberrant T-cell population: CD45 negative, surface CD3 negative, CD2 positive, CD 5 positive, CD7 positive, CD4 positive, CD16/57 possible partial positive, CD56 negative, CD34 negative, and CD52 positive.
Flow cytometric evaluation of the peripheral blood:
Immunohistochemistry of the abnormal lymphoid population:
Positive immunostains: CD2, CD3, CD5, Beta-F1
Negative immunostains: CD20, PD-1, CD56, CD57/Leu7, TIA1, Granzyme B, S100, EBV-ISH (EBER)
Fluorescent in-situ hybridization:
Fig. 3: Left: FISH shows one red (p53) and one green (ATM) signal which is consistent with the loss of one copy of both the genes. Right: Split signal FISH for TCL1 gene rearrangement is negative ( green and red signal are not separated).
FISH analysis: nuc ish( ATM,TP53)x1[215/254] and (TCL1x2)
FISH was positive for loss of both the ATM and TP53 tumor suppressor genes in 215 of the 254 interphase cells examined (84.6%) and negative for TCL1 gene rearrangement.