Baylor University Medical Center Proceedings April 2014, Volume 27, Number 2 | Page 51

Triple-hit lymphoma
Naresh Pemmaraju, MD, Javed Gill, MD, Saurabh Gupta, PhD, and John R. Krause, MD

We report a case of a triple-hit lymphoma in a 72-year-old man. This
lymphoma was diagnosed using morphology, flow cytometry, immunochemistry, and cytogenetics. Since many triple-hit lymphomas have not
been documented in the literature, it is important to bring attention to
this entity, as this lymphoma has different prognostic and therapeutic
implications than other diffuse large B-cell lymphomas, thus making a
correct and early diagnosis important.

hromosomal translocations are biologic and diagnostic
hallmarks of disease in many B-cell lymphomas. There is
a unique subset, the so-called “double-hit lymphomas,”
that are defined by a chromosomal breakpoint affecting
the MYC/8q24 locus in combination with another recurrent breakpoint, usually at (14;18)(q32;q21) involving BCL-2. This led to a
new category of lymphomas in the 2008 World Health Organization (WHO) classification: “B-cell lymphoma unclassifiable with
features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL).” Double-hit lymphomas are
associated with a poor prognosis. An even more uncommon entity
is the “triple-hit lymphoma.” The exact incidence is unknown, and
the WHO has not, as of yet, classified it specifically. Triple-hit lymphomas also have morphologic, phenotypic, and genetic features
intermediate between DLBCL and BL. However, the characteristic
cytogenetic abnormalities involve chromosomal rearrangements of
c-MYC, BCL-2, and BCL-6 genes. The clinical implication of correctly diagnosing this entity is significant, as triple-hit lymphomas
also have a much worse prognosis than either DLBCL or BL alone,
and therapeutic options are different. We report a case of a patient
presenting with fever, fatigue, night sweats, and an inguinal mass
that was biopsied to reveal a DLBCL of germinal center origin on
first impression. Because of a high proliferative index, cytogenetics were obtained, which showed chromosomal rearrangements
consistent with a diagnosis of triple-hit lymphoma.

C

CASE REPORT
A 72-year-old African American man with previous chronic
gout and hypertension was admitted to Baylor University Medical Center at Dallas due to weight loss of 25 pounds, fatigue,
and failure to thrive. He was found to have an enlarging inguinal mass on the left side measuring 7 cm, which had been
Proc (Bayl Univ Med Cent) 2014;27(2):125–127

Figure 1. Large cell lymphoma (hematoxylin and eosin, ×500).

present for 2 months. His lactate dehydrogenase was 882 U/L
(reference range, 100–190); beta-2-microglobulin, 5.56 ng/mL
(reference range, 0.60–2.29); ferritin, 926 ng/mL (reference
range, 22–322); hemoglobin, 8.5 g/dL; and hematocrit, 24.9%.
Radiographic imaging disclosed bilateral kidney masses, as well
as a mass in the left lobe of the liver. His hospital course was
complicated by acute renal failure and urinary tract infection
treated with antibiotics and intravenous fluids.
The inguinal mass was biopsied. Sections showed a diffuse
infiltrate consisting of sheets of discohesive medium and large
cells with large nuclei, irregular nuclear membranes, and prominent nucleoli with no architectural pattern (Figures 1 and 2).
Flow cytometry showed a 62% population of large clonal B
cells expressing CD10, CD19, CD20, CD45, and Kappa, but
not CD5. Immunochemistry showed CD45, BCL-2, BCL6, CD10, CD20, and CD79a positivity and CD30, MUM1,
EBER, and CD34 negativity. Ki-67 (proliferation index