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Transformation of Small B-Cell Lymphoma Into Large Cell [CD30.sup.+], [CD4.sup.+], Epstein-Barr Virus-Negative Lymphoma.

Strong CD30 positivity is an immunohistochemical finding typically associated with anaplastic large cell lymphoma (ALCL), classical Hodgkin lymphoma, cutaneous T-cell lymphoproliferative diseases, and large B-cell lymphomas, including those associated with Epstein-Barr virus (EBV) infection. (1) Aside from this well-known group, CD30 expression may be noted sporadically in other B- and T-cell lymphomas, including recently described cases of transformation into histiocytic/dendritic cell sarcomas. (2,3) In these sporadic cases, CD30 expression is typically variable and is seen alongside normal lineage-specific markers. (4,5)

In this article, we present 2 separate but similar cases of [CD30.sup.+] B-cell lymphomas that do not fit into any of the categories described above. Both patients presented with a morphologically high-grade lymphoma whose immuno phenotype ([CD30.sup.+], [CD4.sup.+], EBV-, B-cell lineage markers with negative or focal and weak staining) led to an initial suspicion of ALCL in both cases. However, both patients had a history of prior low-grade follicular lymphoma, and molecular studies demonstrated the same clonal pattern of immunoglobulin heavy chain gene (IGH@) rearrangements in both the transformed lymphomas and their corresponding original low-grade B-cell lymphomas. To our knowledge, these cases are the first to be reported that demonstrate this particular combination of morphology (anaplastic large cells) and immunophenotype (CD30 strongly positive; negative for other markers including Epstein-Barr virus-encoded small RNA [EBER], histiocytic/ dendritic cell markers, anaplastic lymphoma kinase [ALK], and CD138; and B-cell markers negative or weak and focal) in a malignancy that can be incontrovertibly shown on molecular grounds to be a transformed follicular lymphoma. These cases are relevant not only as a further example of the plasticity of tumors of B-cell origin, but also as a way to highlight a potential diagnostic pitfall, since both were nearly given the formal diagnosis of ALCL before knowledge of the patients' antecedent low-grade lymphomas prompted further immunohistochemical and molecular studies.

PATIENT HISTORIES

Patient 1 is a 50-year-old man who presented in August 2008 with inguinal lymphadenopathy, proven by biopsy of an inguinal lymph node to be low-grade follicular lymphoma. He was subsequently treated with multiagent chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]), followed by 2 cycles of rituximab and bendamustine. A computed tomography scan performed subsequent to this therapy demonstrated continuing generalized lymphadenopathy, without evidence of interval decrease, compared to initial images. Repeated biopsy was performed 18 months later, demonstrating the presence of a large cell lymphoma. All original biopsies were performed at an outside institution, and all material, including paraffin-embedded tissue blocks, were received for review at Vanderbilt University Medical Center (VUMC) in Nashville, Tennessee, as part of the patient's plan of care for treatment of large cell lymphoma.

Patient 2 is a 50-year-old man who presented with left inguinal and pelvic lymphadenopathy, proven by biopsy to be low-grade follicular lymphoma with bony lesions. The patient underwent palliative radiotherapy, with subsequent progression of disease to nodes (right pectoral and supraclavicular) outside of the radiation field. Excisional biopsy of a right cervical node was performed 2 years after initial diagnosis, documenting the presence of a large cell lymphoma. All biopsies were performed at Cooper University Hospital (CUH) in Camden, New Jersey.

Follow-up clinical data were unavailable for both patients after pathology review.

MATERIALS AND METHODS

Morphologic Studies, Immunohistochemistry, and In Situ Hybridization

The 2 patients were seen independently at separate institutions: patient 1 at VUMC and patient 2 at CUH, with substantially overlapping but independent workups performed. Hematoxylin-eosin (H&E)-stained slides were cut from paraffin-embedded tissue blocks (from an outside institution for patient 1, with studies performed on 5-im sections; in-house blocks for patient 2, with studies performed on 4-im sections). Immunohistochemical stains and in situ hybridization (ISH) studies were performed at each institution separately, as summarized in Table 1.

Molecular Studies

For both patients, DNA isolation was performed from paraffin-embedded tissue blocks by using commercially available kits as summarized in Table 1. For patient 1, IGH@ VDJ rearrangements were tested by polymerase chain reaction (PCR), using primers specific for consensus sequences in the VHFRIII region of IGH@ and appropriate controls, (6) followed by separation on a 10% polyacrylamide gel and visualization with ethidium bromide. For analysis of TRG@ VJ rearrangements, PCR amplification of multiple sites in the T-cell receptor region was performed with previously reported primers and modified reaction conditions. (7) Amplicons were radioactively labeled, separated by using a 6% denaturing polyacrylamide gel, and visualized by using autoradiography. BCL2 gene rearrangement studies were performed with primers specific for the [J.sub.H] region of IGH@ and for the major breakpoint region (MBR) and minor cluster region (mcr) of the BCL2 locus. (8) Polymerase chain reaction products were separated on a 0.7% agarose gel, analyzed by Southern blot, and hybridized to BCL2specific [sup.32]P-labeled specific probes. (8) For patient 2, IGH@ and TRG@ rearrangement studies were performed with commercially available kits, as summarized in Table 1. BCL2 gene rearrangement studies were performed by using quantitative real-time PCR assays on an ABI7300 thermocycler (Applied Biosystems, Foster City, California) with specific primers for the BCL2 MBR-[J.sub.H] and the BCL2 mcr-[J.sub.H] rearrangement regions, according to the BIOMED-2 Concerted Action protocol. (9)

RESULTS

Morphologic Studies

Review at VUMC of the H&E-stained slides for the original low-grade lymphoma of patient 1 revealed a lymph node entirely effaced by a population of small lymphocytes in a predominantly diffuse pattern, with focal organization into round follicles with absent zonation, markedly attenuated mantle zones, and lack of tingible body macrophages. The lymphocytic infiltrate was composed predominantly of a monotonous population of small centrocytes with occasional intermediate-sized cells with small nucleoli (Figure, A). Slides of recurrent lymphoma for patient 1 demonstrated complete effacement by sheets of large, abnormal cells with large oval to irregular nuclei, vesicular chromatin, single central nucleoli, and abundant eosinophilic cytoplasm (Figure, B). Focal areas of sclerosis and coagulative necrosis were noted.

Review at CUH of H&E-stained slides from the low-grade lymphoma of patient 2 revealed a lymph node replaced by a population of small- to medium-sized centrocytes in a vaguely nodular pattern (Figure, C) without a significant population of large, irregular centroblasts or anaplastic cells. Slides of transformed lymphoma from the patient demonstrated a node partially replaced by a diffuse infiltrate of large cells with irregular nuclei, large oval to slightly irregular nuclei, vesicular chromatin, occasional prominent nucleoli, and abundant amounts of eosinophilic cytoplasm (Figure, D). Focal confluent necrosis was present.

In the transformed samples from both patients, there were no classic Reed-Sternberg or hallmark cells, and no morphologic evidence of persistent low-grade lymphoma.

Immunohistochemical Studies and In Situ Hybridization

The results of immunohistochemical staining, as well as in situ hybridization and molecular studies, on all 4 samples are summarized in Table 2. To summarize the most relevant findings, the initial lymphoma of patient 1 had a typical follicular lymphoma immunophenotype, expressing CD10, CD20, BCL2, and BCL6, and was negative for CD30 and EBER. The transformed lymphoma of patient 1 was diffusely and strongly positive for CD4 and CD30, negative for CD10 and BCL2, weakly and focally positive for CD79a, BCL6, and PAX5, and negative for CD20 (with a history of rituximab treatment). Additional markers, including EBER, CD138, ALK, and many T-cell and histiocytic/dendritic cell markers, all showed negativity (listed fully in Table 2).

The initial lymphoma of patient 2 expressed CD10, CD20, BCL6, and PAX5, and was negative for CD30, BCL2, and EBER. The transformed lymphoma of patient 2 was diffusely and strongly positive for CD4 and CD30, was focally positive for CD79a and PAX5, and was negative for CD10, CD20, CD22, BCL2, and BCL6. Additional markers, including EBER, ALK, and many T-cell and histiocytic/dendritic cell markers all showed negativity (listed fully in Table 2).

Molecular Genetic Studies

IGH@ rearrangement studies on samples from both patients revealed identical monoclonal bands for the original and transformed lymphomas in each case. TRG@ [gamma] rearrangement studies performed on both samples from each patient revealed no evidence of a monoclonal rearrangement. BCL2 rearrangement studies on patient 1 demonstrated an identical rearrangement involving MBR in both the original and transformed lymphomas. BCL2 rearrangement studies performed on both samples from patient 2 revealed no evidence of a t(14; 18) translocation in either the original or the transformed sample.

Clinical Diagnoses

The original lymphoma of patient 1 was diagnosed as a follicular lymphoma, World Health Organization (WHO) grade 1 to 2 of 3, with a predominantly diffuse pattern. The transformed lymphoma of this patient was diagnosed at VUMC as large cell lymphoma, arising from transformation of the original follicular lymphoma; this corrected the initial diagnosis of ALCL that had been rendered at an outside institution without the benefit of a full set of immunohistochemical or genetic studies.

The original lymphoma of patient 2 was diagnosed as follicular lymphoma, WHO grade 1 to 2 of 3, with a predominantly follicular pattern. The clinical report noted that BCL2 negativity by immunohistochemistry can be seen in up to 15% of low-grade follicular lymphomas. (10) The transformed lymphoma in patient 2 was initially diagnosed as ALCL, but on further consultation and review, and with benefit of a full immunohistochemical and molecular workup, the diagnosis was amended to [CD30.sup.+] large cell lymphoma of B-cell origin.

COMMENT

We present here 2 cases of small B-cell lymphoma that each transformed into a lymphoma with aggressive features, including anaplastic morphology, with loss of many B-cell lineage-specific antigens as well as loss of germinal center markers. At the same time, both cases acquired diffuse and strong expression of CD30 and CD4. The loss of CD20 expression in patient 1 may be ascribed to rituximab administration; however, the significant loss of many other markers, including CD79a and PAX5, as well as other markers present in the original lymphoma, including CD10, BCL2, and BCL6, cannot be explained by rituximab effect. Patient 2 was never treated with rituximab and lost expression of CD20 along with many other B-cell markers. In both cases, T-cell and histiocytic/dendritic cell markers showed negativity, as did ISH for EBER (see Table 2 for a summary of findings). In the absence of any concomitant morphologic or immunophenotypic evidence of persistent low-grade lymphoma to suggest transformation, only the presence of identical IGH@ (and BCL2 in the case of patient 1) rearrangements permitted the unequivocal identification of large cell lymphomas as transformed B-cell lymphomas, clonally related to the previous low-grade disease.

Although strong and uniform CD30 expression may be seen in a variety of B-cell lymphomas, no other case reports in the literature document a combination of morphology and immunophenotype similar to that described here. The most well-known CD30+ B-cell neoplasm is classical Hodgkin lymphoma, with its characteristic morphologic appearance and immunophenotype, including expression of PAX5 and a few other B-cell markers, with only rare expression of T-cell markers. (11) Among the non-Hodgkin B-cell lymphomas, those associated with EBV or other viral infection may frequently express CD30 variably, consistent with EBV's known ability to upregulate CD30 expression in B-cells during infection, often showing bizarre, large cell morphology. However, our case fits neither the morphologic nor the immunophenotypic profile of classical Hodgkin lymphoma nor is it EBV positive.

While CD30 expression is well described as an uncommon event associated with transformation of follicular lymphoma, in all reported cases, CD30 expression is seen alongside normal expression of standard markers of B-cell or follicular center differentiation, including CD20, CD79a, PAX5, and BCL6. (4,5) Transformed follicular lymphomas can lose some B-cell-specific markers, ranging from the loss of CD20 positivity classically seen after treatment with rituximab to, more uncommonly, a wide-ranging loss of multiple B-cell markers. Loss of CD20 and other B-cell marker expression has been associated with more aggressive clinical behavior and poor prognosis. (12,13) However, this loss of B-cell markers has not previously been described in association with the uniform strong CD30 expression that was seen in our case.

Transformation of B-cell lymphomas into histiocytic/ dendritic cell sarcomas has been described in multiple case reports and case series. (2,3) These transformed neoplasms often have bizarre, anaplastic cytomorphology, and a significant subset of cases express CD30. Staining with B-cell markers is negative or weak, and there is no association with EBV. However, malignant cells in these cases all are positive for significant expression of histiocytic/dendritic cell markers, including CD1a, CD23, CD68, CD163, and S100. Our cases were negative for a wide range of markers that characterize histiocytes or dendritic cells.

In one case report, Ozdemirli et al (14) described the transformation of chronic lymphocytic leukemia to a large cell lymphoma with CD30 and CD4 expression and anaplastic morphology. This large cell lymphoma shares many clinical similarities with ours, including expression of CD30 and CD4 with loss of B-cell markers, but was strongly EBER positive, and occurred in the context of an EBV infection.

Both cases reported here were diffusely positive for CD4 in addition to their CD30 expression. Aberrant CD4 expression has been documented in a variety of B-cell lymphomas, including ALK-positive large B-cell lymphoma, diffuse large B-cell lymphoma, and classical Hodgkin lymphoma, in all cases in the context of an otherwise normal immunophenotype for that category of disease. (15) In the 2 cases reported here the CD4 positivity is remarkable less as an unusual occurrence in its own right, but more for the danger that coexpression of CD4 alongside CD30 might lead to misdiagnosis as an ALCL.

The 2 cases presented in this report demonstrate the novel finding of transformation of low-grade B-cell lymphoma to a [CD30.sup.+], [CD4.sup.+] large cell lymphoma with profound loss of B-cell lineage-specific markers, negativity of T-cell and histiocytic/dendritic cell lineage markers, and without any evidence of EBV infection. Although many cases have been described that match some elements of this presentation, we are unable to find any reports in the literature of cases with this particular combination of morphology and immuno-phenotype. More than just an unusual combination of markers, the particular phenotype seen in these cases represents an instructive danger to the practicing pathologist; both cases were temporarily misclassified as ALCL before each was reevaluated with full immunohistochemical and molecular genetic studies. In these cases, ancillary molecular genetic testing provides a vital key for rendering a definitive diagnosis.

Please Note: Illustration(s) are not available due to copyright restrictions.

References

(1.) Hu S, Xu-Monette ZY, Balasubramanyam A, et al. CD30 expression defines a novel subset of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from The International DLBCL Rituximab-CHOP Consortium Program Study. Blood. 2013; 121(14):2715-2724.

(2.) Shao H, Xi L, Raffeld M, Feldman A. Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a study of seven cases. Mod Pathol. 2011; 24(11):1421-1432.

(3.) Feldman AL, Arber D, Pittaluga S, et al. Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone. Blood. 2008; 111(12):5433-5439.

(4.) Alsabeh R, Medeiros LJ, Glackin C, Weiss LM. Transformation of follicular lymphoma into CD30-large cell lymphoma with anaplastic cytologic features. Am J Surg Pathol. 1997; 21(5):528-536.

(5.) Gardner LJ, Polski JM, Evans HL, Perkins SL, Dunphy CH. CD30 expression in follicular lymphoma. Arch Pathol Lab Med. 2001; 125(8):1036-1041.

(6.) Sukpanichnant S, Vnencak-Jones CL, McCurley TL. Detection of clonal immunoglobulin heavy chain gene rearrangements by polymerase chain reaction in scrapings from archival hematoxylin and eosin-stained histologic sections: implications for molecular genetic studies of focal pathologic lesions. Diagn Mol Pathol. 1993; 2(3):168-176.

(7.) Greiner TC, Raffeld M, Lutz C, Dick F, Jaffe ES. Analysis of T cell receptor-gamma gene rearrangements by denaturing gradient gel electrophoresis of GC-clamped polymerase chain reaction products: correlation with tumor-specific sequences. Am J Pathol. 1995; 146(1):46-55.

(8.) LeBrun DP, Ngan BY, Weiss LM, Huie P, Warnke RA, Cleary ML. The bcl-2 oncogene in Hodgkin's disease arising in the setting of follicular non-Hodgkin's lymphoma. Blood. 1994; 83(1):223-230.

(9.) Van Dongen JJM, Langerak AW, Bruggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immuno-globulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003; 17(12):2257-2317.

(10.) Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press; 2008. World Health Organization Classification of Tumours; vol 2.

(11.) Tzankov A, Bourgau C, Kaiser A, et al. Rare expression of T-cell markers in classical Hodgkin's lymphoma. Mod Pathol. 2005; 18(12):1542-1549.

(12.) HiragaJ, Tomita A, Sugimoto T, et al. Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance. Blood. 2009; 113(20): 4885-4893.

(13.) Johnson NA, Boyle M, Bashashati A, et al. Diffuse large B-cell lymphoma: reduced CD20 expression is associated with an inferior survival. Blood. 2009; 113(16):3773-3780.

(14.) Ozdemirli M, Cheson B, Jaffe ES. What is anaplastic large cell lymphoma? [author reply in Am J Surg Pathol. 2004; 28(12):1665-1667]. Am J Surg Pathol. 2004; 28(12):1664-1665.

(15.) Kaleem Z, White G, Zutter MM. Aberrant expression of T-cell-associated antigens on B-cell non-Hodgkin lymphomas. Am J Clin Pathol. 2001; 115(3):396-403.

Aaron C. Shaver, MD, PhD; Ly Ma, MD; Cindy Vnencak-Jones, PhD; Roland S. Schwarting, MD; Kristina J. Fasig, MD; Annette S. Kim, MD, PhD

Accepted for publication August 8, 2013.

From the Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, Tennessee (Drs Shaver, Vnencak-Jones, Fasig, and Kim); and the Department of Pathology, Cooper University Hospital, Camden, New Jersey (Drs Ma and Schwarting).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Annette S. Kim, MD, PhD, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, 1301 Medical Center Dr, 4603A TVC, Nashville, TN 37232-5310 (e-mail: annette.s.kim@vanderbilt.edu).

Caption: Morphologic appearance of original and transformed lymphomas. Hematoxylin-eosin-stained slides from patient 1 (A and B) and patient 2 (C and D). Both original lymphomas (A and C) consisted of small, irregular lymphocytes with scant cytoplasm. The transformed lymphomas (B and D) were composed of large, anaplastic cells, with open chromatin, single central nucleoli, and abundant amounts of eosinophilic cytoplasm. No significant residual population of small abnormal lymphocytes was present in this specimen for either patient (original magnifications X400 [A through D]).
Table 1. Suppliers and Platforms for Materials and Methods

Immunohistochemistry and                Antibody Supplier
In Situ Hybridization

Patient 1:
  CD1a, CD3, CD20, CD79a,      Ventana (Tucson, Arizona)
    CD138, ALK, EMA
  CD4, CD5, CD8, CD10,         Leica-Microsystems
    CD23, CD30, CD68,          (Bannockburn, Illinois)
    BCL2, BCL6, PAX5, S100
  CD7, lysozyme                Dako (Carpinteria, California)
  TIA1                         Immunotech (Prague, Czech Republic)
  EBER                         Leica-Microsystems

Patient 2:

  CD3, CD20, CD30, BCL2        Ventana
  CD4, BCL6                    Cell Marque (Rocklin, California)
  PAX5                         BioCare (Concord, California)
  CD10                         Leica-Microsystems
  CD163                        Novocastra (Bannockburn, Illinois)
  EBER                         Ventana

Molecular Studies                         Kit/Apparatus

Patient 1:
  DNA isolation                QIAquick PCR Purification Kit

Patient 2:
  DNA isolation                QIAamp DNA Mini Kit

  IGH gene amplification       Biomed-2 IGH primer set
                               (Cat No. 1-101-0021)

  TCR gene amplification       TCR gamma primer set
                               (Cat No. 1-207-0011)

  Quantitative real-time PCR   ABI7300 thermocycler

  Capillary electrophoresis    ABI310 and ABI Prism GeneScan

Immunohistochemistry and                  Stainer
In Situ Hybridization

Patient 1:
  CD1a, CD3, CD20, CD79a,      Ventana BenchMark Ultra
    CD138, ALK, EMA
  CD4, CD5, CD8, CD10,         Leica BondmaX
    CD23, CD30, CD68,
    BCL2, BCL6, PAX5, S100
  CD7, lysozyme                Dako Autostainer Plus
  TIA1                         Dako Autostainer Plus
  EBER                         Leica BondmaX

Patient 2:

  CD3, CD20, CD30, BCL2        BenchMark XT
  CD4, BCL6                    BenchMark XT
  PAX5                         BenchMark XT
  CD10                         BenchMark XT
  CD163                        BenchMark XT
  EBER                         BenchMark XT

Molecular Studies                        Supplier

Patient 1:
  DNA isolation                Qiagen (Valencia, California)

Patient 2:
  DNA isolation                Qiagen

  IGH gene amplification       InVivoScribe Technologies
                               (San Diego, California)

  TCR gene amplification       InVivoScribe Technologies

  Quantitative real-time PCR   Applied Biosystems
                               (Foster City, California)

  Capillary electrophoresis    Applied Biosystems

Abbreviations: ALK, anaplastic lymphoma
kinase; EBER, Epstein-Barr virus-encoded
small RNA; EMA, epithelial membrane
antigen; IGH, immunoglobulin heavy chain;
PCR, polymerase chain reaction; TCR, T cell
receptor.

Table 2. Morphologic, Immunophenotypic, and Genetic Features

                                         Patient 1

                               Initial                Transformed

Morphologic pattern    Predominantly diffuse     Diffuse
Cytomorphology         Small, low grade          Anaplastic
IHC, B-cell markers
  CD20                            +                     (-) (a)
  CD22                           ND                       ND
  CD79a                          ND              Weak, focal
  PAX5                            +              Weak, focal
IHC, T-cell markers
  CD3                             -                        -
  CD4                             -                        +
  CD5                          (-) (b)                     -
  CD7                            ND                        -
  CD8                            ND                        -
  TIA1                           ND                        -
IHC, histiocytic/dendritic cell markers
  CD1a                           ND                        -
  CD23                            -                        -
  CD68                           ND                        -
  CD163                          ND                       ND
  Lysozyme                       ND                        -
  S100                           ND                        -
IHC, additional markers
  CD10                            +                        -
  CD30                            -                        +
  CD43                         (-) (b)                  (-) (b)
  CD138                          ND                        -
  ALK                            ND                        -
  BCL2                            +                        -
  BCL6                            +                   Weak, focal
  EMA                            ND                        -
  MPO                            ND                       ND
  ISH for EBER                    -                        -
Genetic studies
  ICH rearrangement    Monoclonal band           Monoclonal band,
                                                 identical to original
  TCR rearrangement    No monoclonal             No monoclonal
  BCL2 rearrangement   Positive, involving MBR   Positive, involving
                                                 MBR

                                     Patient 2

                           Initial               Transformed

Morphologic pattern    Follicular         Diffuse
Cytomorphology         Small, low grade   Anaplastic
IHC, B-cell markers
  CD20                        +                       -
  CD22                        ND                      -
  CD79a                       ND          Weak, focal
  PAX5                        +           Moderate, subset
IHC, T-cell markers
  CD3                         -                       -
  CD4                         -                       +
  CD5                         -                       -
  CD7                         ND                      ND
  CD8                         -                       -
  TIA1                        ND                      ND
IHC, histiocytic/dendritic cell markers
  CD1a                        ND                      ND
  CD23                        -                       -
  CD68                        ND                      ND
  CD163                       ND                      -
  Lysozyme                    ND                      ND
  S100                        ND                      ND
IHC, additional markers
  CD10                        +                       -
  CD30                        -                       +
  CD43                        ND                    Subset
  CD138                       ND                      ND
  ALK                         ND                      -
  BCL2                        -                       -
  BCL6                        +                       -
  EMA                         ND                      ND
  MPO                         ND                      -
  ISH for EBER                -                       -
Genetic studies
  ICH rearrangement    Monoclonal band    Monoclonal band, identical
                                          to original
  TCR rearrangement    No monoclonal      No monoclonal
  BCL2 rearrangement   Negative           Negative

Abbreviations: ALK, anaplastic lymphoma kinase; EBER, Epstein-Barr
virus-encoded small RNA; EMA, epithelial membrane antigen; IGH,
immunoglobulin heavy chain; IHC, immunohistochemistry; ISH, in situ
hybridization; MBR, major breakpoint region; MPO, myeloperoxidase; ND,
test not performed on that specimen; TCR, T cell receptor; +, positive
expression for that marker; -, absent expression for that marker.

(a) Indicates prior treatment with rituximab.

(b) Indicates a test performed by report at original referring
institution, and not replicated.
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Author:Shaver, Aaron C.; Ma, Ly; Vnencak-Jones, Cindy; Schwarting, Roland S.; Fasig, Kristina J.; Kim, Anne
Publication:Archives of Pathology & Laboratory Medicine
Date:Aug 1, 2014
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