An Interesting Hematopathology Case: Christopher Julien PGY2

An Interesting
Hematopathology Case
Christopher Julien PGY2
Initial Presentation
• The patient (60 y.o. M) initially presented in 2009
with mild lymphocytosis
• In March 2011, the patient had an elevated WBC of

22 k/mL
• August 2011, a repeat CBC showed a WBC of 23

k/mL
• August 2011: Flow cytometry revealed a CD5+
CD23+ cell population consistent with CLL
• Starting in December of 2014, treatment was initiated
• In December of 2015, restaging bone marrow biopsy

and chest CT were performed
Jan. 2016
CT chest
January 2016 BMBx
5x 10x
50x 40x
Jan 2016 Bone Marrow Bx
CD23 CD5
CD20 CD79a
Jan. 2016
•
Flow Cytometry
Flow Cytometry demonstrated a population of
Kappa-restricted CD5(dim)+ CD10- CD19+
CD20- B cells.
• These findings are diagnostic of a mature B-cell
neoplasm, and favor Chronic Lymphocytic
Leukemia
Cytogenetics
• Positive FISH studies for a deletion of TP53 and gain
of ATM
• Abnormal male karyotype:

•
• 45,XY,-17,add(19)(q13.1)[13]/46,XY[13]
Next Generation Sequencing
• October 2016 - June 2019: Ibrutinib mono therapy
420 mg qd
• February 2017: PET/CT demonstrates partial

metabolic response
• September 2018: Continues on Ibrutinib. Notices a

lump in the right groin that waxes and wanes
• June 2019: Notices spleen enlargement. Has missed

several doses of Ibrutinib earlier in the month
Initial Presentation
• 59 y/o M with PMH of CLL/SLL presents for
excisional biopsy of a right inguinal lymph node
• Read as ‘suspicious for transformed lymphoma’ by

radiology
2019 Excisional Lymph
Node Biopsy
August
2019
Excisional
Biopsy
5x
August 2019 Excisional Biopsy
August 2019 Excisional Biopsy
PAX5
CD10
August 2019
Excisional
Biopsy
Summary of IHC Findings
Result + + + (weak) + + (var) + + + (weak, + + in a

(partial) focal) minor
subset
Result - - - - - - - - -
Flow Cytometry
• Flow Cytometry demonstrated a population of CD19- CD20+
CD56+ CD10+ CD200- CD22- CD38+ cells. The cells are
kappa-restricted by cytoplasmic light chain analysis.
•
• Interpretation:
Kappa-restricted neoplasm with plasma cell differentiation.
No evidence of chronic lymphocytic leukemia

Ddx
• Plasmablastic lymphoma
• Plasmablastic Plasma Cell Neoplasm

Plasmablastic Lymphoma
• A very aggressive lymphoma with diffuse proliferation of
large neoplastic cells
• Often associated with immunodeficiency, including HIV;

tumor cells are EBV-infected in most patients
• LBCLs with plasmablastic features may occur as

transformation of small B-cell lymphoid neoplasms .
Plasmablastic lymphoma
• Morphology: Immunoblasts and/or cells with more
obvious plasmacytoid differentiation
• Diffuse growth pattern
• Frequent mitotic figures

Plasmablastic lymphoma
• Immunophenotype:
•
• CD138, CD38, IRF4 / MUM1, CD79a (40%) positive

• Cytoplasmic IgG & Kappa or Lambda chain is commonly expressed
• Genetic profile:
•
• Clonal IGH rearrangement is demonstrable, even with immunoglobulin expression is

not detectable
• Frequent complex karyotypes
• MYC translocation has been identified in as many as 50% of cases
• May be impossible to distinguish from plasmablastic plasma cell myeloma (on IHC, H&E
& cytogenetics)
Plasma Cell Myeloma
• PCM is a bone marrow-based, multifocal neoplastic
proliferation of plasma cells
• Monocloncal plasma cells may be scattered

interstitially, in small clusters, in focal nodules, or in
diffuse sheets.
• In almost 10% of cases, there is plasmablastic

morphology
Plasma Cell Myeloma
• Immunophenotype
•
• CD38, CD138 positive; CD45, CD19 negative
• Monotypic cytoplasmic Ig
• Usually lack surface Ig
• Cytogenetics
•
• Karyotype abnormalities are common
• Translocations involving IGH on 14q32 are present in 55-70% of PCMs
• The remaining cases are mostly hyperdiploid and only infrequently have one of the common
IGH translocations
• Monosomy or partial deletion of chromosome 13 is found in nearly 50% of PCMs
• MYC rearrangements are found in nearly 50%

Ddx
Plasma Cell + + - or dim + in 75-80% - + in 10-20% -

Myeloma
Plasmablastic + + - or dim + in 25% + - or dim(+) +

Lymphoma
FISH
Myeloma FISH
• Deletion 1q32 (CDKN2C)- Within normal limits in 100 cells
• Gain 1q21 (CKS1B)- Within normal limits in 100 cells
• FGFR3-IGH [t(4:14)] rearrangement- Within normal limits however 62/100 cells showed loss of
FGFR3 signal
• CCND1-IGH [t(11;14)] rearrangement- Within normal limits in 100 cells
• IGH-MAF [t(14;16)] rearrangement- Within normal limits however 57/100 cells showed loss of MAF
• TP53 deletion- Positive in 39/100
• Monosomy 17- Positive in 52/100
DHL FISH
• MYC rearrangement: Positive in 78/100 cells
• BCL6 rearrangement: Within normal limits in 100 cells
Richter Transformation
• First described in 1928 by Maurice Richter as the
development of an aggressive large-cell lymphoma in
the setting of an underlying CLL/SLL
• Although DLBCL is the most common histology seen

in patients with RT, other lymphomas have been
reported
• Richter transformation to plasmablastic lymphoma is

extremely rare
Rx Plays a Role
• Treatment may predispose patients to Richter
Transformation
• Our patient was treated with: chlorambucil,

obinutuzumab, rituximab, bendamustine, idelalisib,
ibrutinib
Rx for Plasmablastic Lymphoma
• Regarding treatment, there is no standard of care for

patients with plasmablastic lymphoma
References
1) Robak T, et al. Plasmablastic lymphoma in a patient with chronic lymphocytic leukemia heavily pretreated
with cladribine (2-CdA): an unusual variant of Richter's syndrome. Eur J Haematol. 2001 Nov-Dec;67(5-6):322-7.
2) Ronchi A, et al. Richter Syndrome With Plasmablastic Lymphoma at Primary Diagnosis: A Case Report With
a Review of the Literature. Appl Immunohistochem Mol Morphol. 2017 Jul;25(6):e40-e45.
3) Holderness BM, Malhotra S, Levy NB, Danilov AV. Brentuximab vedotin demonstrates activity in a patient
with plasmablastic lymphoma arising from a background of chronic lymphocytic leukemia. J Clin Oncol. 2013 Apr
20;31(12):e197-9.
4) Hatzimichael et al. Plasmablastic Lymphoma with Coexistence of Chronic Lymphocytic Leukemia in an
Immunocompetent Patient: A Case Report and Mini-Review. Case Reports in Hematology. Volume 2017 (2017),
Article ID 2861596, 5 pages. https://doi.org/10.1155/2017/2861596
5) Martinez D, et al. Plasmablastic transformation of low-grade B-cell lymphomas: report on 6 cases. Am J
Surg Pathol. 2013 Feb;37(2):272-81.8)
6) Pines A, et al. Transformation of chronic lymphocytic leukemia to plasmacytoma. Cancer. 1984 Nov
1;54(9):1904-7.
7) Yahata N, et al. Chronic lymphocytic leukemia complicated by plasmacytoma originating fromdifferent
clones. Leuk Lymphoma. 2000 Sep;39(1-2):203-7.
8) Belinchón I, et al. Primary cutaneous plasmocytoma in a patient with chronic lymphatic leukemia. J Am Acad
Dermatol. 1996 Nov;35(5 Pt 1):777-8.
9) Chantepie SP, et al. Unusual Extramedullary Plasmacytoma: A Rare but Possible Cause of
Lymphadenopathy in Chronic Lymphocytic Leukemia. Case Rep Med. 2015;2015:657049.
10) Pan Z, et al. Plasmablastic transformation of low-grade CD5+ B-cell lymphoproliferative disorder with MYC
gene rearrangements. Hum Pathol. 2013 Oct;44(10):2139-48.
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An Interesting

• In March 2011, the patient had an elevated WBC of

• August 2011, a repeat CBC showed a WBC of 23

• In December of 2015, restaging bone marrow biopsy

• Abnormal male karyotype:

• February 2017: PET/CT demonstrates partial

• September 2018: Continues on Ibrutinib. Notices a

• June 2019: Notices spleen enlargement. Has missed

• Read as ‘suspicious for transformed lymphoma’ by

Result + + + (weak) + + (var) + + + (weak, + + in a

No evidence of chronic lymphocytic leukemia

• Plasmablastic Plasma Cell Neoplasm

• Often associated with immunodeficiency, including HIV;

• LBCLs with plasmablastic features may occur as

• Diffuse growth pattern

• Frequent mitotic figures

• CD138, CD38, IRF4 / MUM1, CD79a (40%) positive

• Clonal IGH rearrangement is demonstrable, even with immunoglobulin expression is

• Monocloncal plasma cells may be scattered

• In almost 10% of cases, there is plasmablastic

• CD38, CD138 positive; CD45, CD19 negative

• Usually lack surface Ig

• Karyotype abnormalities are common

• Translocations involving IGH on 14q32 are present in 55-70% of PCMs

• Monosomy or partial deletion of chromosome 13 is found in nearly 50% of PCMs

• MYC rearrangements are found in nearly 50%

Plasma Cell + + - or dim + in 75-80% - + in 10-20% -

Plasmablastic + + - or dim + in 25% + - or dim(+) +

• Although DLBCL is the most common histology seen

• Richter transformation to plasmablastic lymphoma is

• Our patient was treated with: chlorambucil,

• Regarding treatment, there is no standard of care for

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