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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Oncology

Decoding Your Pathology Report

At a Glance

Your DLBCL pathology report provides the biological details needed to guide your treatment. Key factors include CD20 status, the cell of origin (GCB or ABC), and FISH testing results, which determine if you have a double-hit lymphoma requiring more intensive chemotherapy.

Your pathology report is the most important document in your medical file. It is the definitive “ID card” for your cancer, providing the biological details your oncologist needs to choose the right treatment. While some parts of the report are ready quickly, the most critical genetic tests can take a week or more to complete [1][2].

The Pathology Checklist

When you look at your report, ensure these three key pieces of information are present. If they aren’t, they may still be “pending” in the lab.

  • [ ] CD20 Status: Is the lymphoma “CD20 positive”? [3]
  • [ ] Cell of Origin (COO): Is it GCB or ABC (non-GCB)? [4]
  • [ ] FISH Results: Are there rearrangements in MYC, BCL2, or BCL6? [5]

CD20: The Treatment Target

Most DLBCL is CD20 positive, meaning the cancer cells have a specific protein called CD20 on their surface [3]. This is excellent news for treatment because it means your doctors can use Rituximab, a targeted antibody that acts like a homing missile, finding and attaching to those CD20 proteins to help destroy the cancer cells [3][6].

GCB vs. ABC: The Cell of Origin

DLBCL is not just one disease; it is divided into two main subtypes based on which stage of development the B-cell was in when it became cancerous [4][7].

  • Germinal Center B-cell (GCB): This subtype generally has a slightly better outlook with standard treatment [4].
  • Activated B-cell (ABC or non-GCB): This subtype often involves different biological pathways that may eventually be targeted with specific supplemental drugs [8][9].

FISH Testing: The “Hit” Status

FISH (Fluorescence In Situ Hybridization) is a specialized lab technique that looks deep inside the DNA of the cancer cells [10]. It checks for “rearrangements”—places where pieces of DNA have broken off and reattached in the wrong spots [5].

Term What it Means Impact on Treatment
Double-Hit Rearrangements in both MYC and either BCL2 or BCL6 [5]. Often requires more intensive chemotherapy, such as DA-EPOCH-R, rather than the standard R-CHOP [11][12].
Triple-Hit Rearrangements in all three: MYC, BCL2, and BCL6 [5]. Similar to Double-Hit, this is considered a high-grade lymphoma that needs aggressive treatment [13][12].
Double-Expressor The cells show high levels of MYC and BCL2 proteins (found via IHC) but don’t have the DNA rearrangements [14]. This is different from “Double-Hit” and typically doesn’t require the same high-intensity chemotherapy [15][16].

Safe Treatment While Waiting

It is completely normal to feel anxious if you are waiting for FISH results while knowing you have an “aggressive” cancer. However, if your tumor is causing severe symptoms, your doctor will likely start you on standard R-CHOP immediately for your first cycle. You can then safely switch to DA-EPOCH-R for your second cycle if the FISH test comes back as Double-Hit [17][18]. This is a standard, safe practice that ensures you get immediate treatment without losing the benefit of a tailored approach.

For details on these regimens, please refer to Your First-Line Treatment Options.

Common questions in this guide

What does it mean if my DLBCL is CD20 positive?
Being CD20 positive means the cancer cells have a specific protein on their surface. This is excellent news because it allows doctors to use Rituximab, a targeted therapy that acts like a homing missile to find and destroy the lymphoma cells.
What is the difference between GCB and ABC in my pathology report?
GCB and ABC refer to the cell of origin, which is the stage of development the B-cell was in when it became cancerous. The GCB subtype generally has a slightly better outlook with standard treatment, while the ABC subtype may be targeted with different supplemental drugs.
What is double-hit lymphoma?
Double-hit lymphoma occurs when a FISH test reveals DNA rearrangements in both the MYC gene and either the BCL2 or BCL6 gene. This is considered a high-grade lymphoma that typically requires more intensive chemotherapy, such as DA-EPOCH-R.
What is the difference between double-hit and double-expressor lymphoma?
Double-hit lymphoma involves actual structural breaks and rearrangements in the DNA of specific genes. Double-expressor lymphoma means the cells show high levels of the proteins but lack the underlying DNA rearrangements. Double-expressor typically does not require the same high-intensity chemotherapy.
Is it safe to start chemotherapy before my FISH results come back?
Yes, it is a standard and safe practice to start standard R-CHOP chemotherapy immediately if you have severe symptoms. If your FISH results later show you have double-hit lymphoma, your doctor can safely switch you to a more intensive regimen for your second cycle.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is my Cell-of-Origin (GCB or ABC/non-GCB), and how does that affect my outlook?
  2. 2.Are the FISH results back for MYC, BCL2, and BCL6? Can I have a copy of that specific report?
  3. 3.Based on my FISH results, am I considered to have 'Double-Hit' or 'Triple-Hit' lymphoma?
  4. 4.Since my lymphoma is CD20 positive, will Rituximab be part of my treatment?
  5. 5.What was my Ki-67 percentage, and what does it tell us about how fast these cells are dividing?

Questions For You

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References

References (18)
  1. 1

    A Practical Approach to Diagnosis of B-Cell Lymphomas With Diffuse Large Cell Morphology.

    King JF, Lam JT

    Archives of pathology & laboratory medicine 2020; (144(2)):160-167 doi:10.5858/arpa.2019-0182-RA.

    PMID: 31990228
  2. 2

    The double-hit signature identifies double-hit diffuse large B-cell lymphoma with genetic events cryptic to FISH.

    Hilton LK, Tang J, Ben-Neriah S, et al.

    Blood 2019; (134(18)):1528-1532 doi:10.1182/blood.2019002600.

    PMID: 31527075
  3. 3

    Anti-CD20 Directed Therapy of B Cell Lymphomas: Are New Agents Really Better?

    Freeman CL, Sehn L

    Current oncology reports 2018; (20(12)):103 doi:10.1007/s11912-018-0748-0.

    PMID: 30483893
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    Diffuse large B-cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment.

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    Identification of BLNK and BTK as mediators of rituximab-induced programmed cell death by CRISPR screens in GCB-subtype diffuse large B-cell lymphoma.

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    The Immunology of DLBCL.

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    Cancers 2023; (15(3)) doi:10.3390/cancers15030835.

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    Gene regulation and suppression of type I interferon signaling by STAT3 in diffuse large B cell lymphoma.

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    MYD88L265P and CD79B double mutations type (MCD type) of diffuse large B-cell lymphoma: mechanism, clinical characteristics, and targeted therapy.

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    Therapeutic advances in hematology 2022; (13()):20406207211072839 doi:10.1177/20406207211072839.

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    Double-hit DLBCL: should we limit FISH testing?

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    PMID: 29724715
  11. 11

    DA-EPOCH-R therapy for high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements in a patient with renal dysfunction.

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    Comparison Between CHOP and DAEPOCH with or Without Rituximab in Adult High Grade B Cell Lymphoma, Not Otherwise Specified; A Retrospective Study From a Tertiary Cancer Hospital in South India.

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    Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 2022; (38(1)):15-23 doi:10.1007/s12288-021-01427-8.

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    Leukemic High Grade B Cell Lymphoma is Associated With MYC Translocation, Double Hit/Triple Hit Status, Transformation, and CNS Disease Risk: The Mayo Clinic Experience.

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    A case of primary cutaneous diffuse large B-cell lymphoma, leg type with MYC rearrangement and high BCL2 protein expression due to trisomy 18.

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This page explains DLBCL pathology terminology for educational purposes only. Your oncologist and pathologist are the best sources for interpreting your specific laboratory results and determining your treatment plan.

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