Pathology & Genetics: Decoding Your Report
At a Glance
Anaplastic Large Cell Lymphoma (ALCL) pathology reports rely on key markers to guide treatment. A confirmed ALCL diagnosis requires a positive CD30 marker, while testing for ALK status and other genetic changes like DUSP22 helps doctors determine your specific prognosis and treatment plan.
Your pathology report is the “blueprint” for your treatment plan. While it may look like a collection of complex codes, it contains the specific genetic and cellular clues that tell your doctors exactly which type of Anaplastic Large Cell Lymphoma (ALCL) you have [1]. Understanding a few key terms can help you ensure your report is complete and your diagnosis is accurate.
The Cellular Clue: “Hallmark Cells”
Pathologists look for a specific type of cell to identify ALCL, famously known as a hallmark cell [1]. These are large, unusual-looking white blood cells that often have a horseshoe-shaped or kidney-shaped nucleus [2]. Seeing these cells is often the first step in differentiating ALCL from other types of cancer or infections [1].
The Mandatory Marker: CD30
For a diagnosis of ALCL, the presence of a protein called CD30 is mandatory [3][4]. Think of CD30 as a specific “ID badge” worn by the cancer cells.
- Why it matters: On your report, you should see CD30 listed as “positive,” “strong,” or “diffuse” [5]. This is critical because modern treatments, such as brentuximab vedotin, are specifically designed to find and attack cells wearing this CD30 badge [6][7].
The Great Divide: ALK Status
The most important word on your pathology report is ALK (Anaplastic Lymphoma Kinase) [8]. This protein determines how the cancer behaves and which treatments will work best.
ALK-Positive (ALK+)
In these cases, a genetic “glitch” called the NPM-ALK fusion (or translocation) occurs [9][10]. This fusion acts like a broken light switch that is stuck in the “ON” position, telling the cells to grow uncontrollably [9].
- Prognosis: ALK+ systemic ALCL generally has a very favorable outlook, with 5-year survival rates between 70% and 90% [11][12].
ALK-Negative (ALK-)
If the ALK protein is absent, the lymphoma is ALK-negative [8]. Because this group is more diverse, doctors must look for other genetic markers to understand the prognosis:
- DUSP22: A rearrangement here often signals a more favorable outlook, similar to the ALK+ version [13][14].
- TP63: A rearrangement here is much rarer and typically signals a more aggressive course that may require more intensive treatment [14][15].
- Triple-Negative: Many ALK-negative patients do not have DUSP22 or TP63 rearrangements. This “triple-negative” group generally has an intermediate prognosis, and its absence on your report does not mean the report is incomplete [14].
Pathology Report Completeness Checklist
When reviewing your report, look for these specific data points. If they are missing, it is worth asking your doctor if more testing is needed.
- [ ] Morphology: Mention of “hallmark cells” or “anaplastic features” [1].
- [ ] CD30 Status: Must be listed as positive (usually “strong and diffuse”) [5].
- [ ] ALK Status: Must be explicitly stated as positive or negative [8].
- [ ] T-Cell Markers: Testing for CD2, CD3, CD4, CD5, CD7, or CD8 (ALCL cells often “lose” these markers) [16].
- [ ] EMA: (Epithelial Membrane Antigen) often positive in systemic ALCL [17].
- [ ] Molecular Testing (for ALK- cases): FISH testing for DUSP22 and TP63 rearrangements [14][15].
If your report is unclear, you have the right to request a second opinion from a hematopathologist—a doctor who specializes specifically in blood and lymph node cancers [18].
Common questions in this guide
What does CD30 positive mean on my pathology report?
What is the difference between ALK-positive and ALK-negative ALCL?
Do I need more genetic testing if my ALCL is ALK-negative?
What are hallmark cells in an ALCL diagnosis?
Why does my report mention a loss of T-cell markers?
Questions to Ask Your Doctor
Curated prompts to bring to your next appointment.
- 1.Can we review the 'Immunohistochemistry' section of my report together?
- 2.Does my report confirm 'strong and diffuse' CD30 expression?
- 3.Since I am ALK-negative, was a FISH test performed for DUSP22 and TP63?
- 4.What does the 'loss of T-cell markers' in my report mean for my diagnosis?
- 5.Are there any 'ancillary tests' like GATA3 or PD-L1 that could provide more detail about my subtype?
Questions For You
Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.
References
References (18)
- 1
Systemic and primary cutaneous anaplastic large cell lymphoma: Clinical features, morphological spectrum, and immunohistochemical profile.
Kwatra KS, Paul PAM, Calton N, et al.
South Asian journal of cancer 2017; (6(3)):129-131 doi:10.4103/2278-330X.214575.
PMID: 28975123 - 2
Systemic, primary cutaneous, and breast implant-associated ALK-negative anaplastic large-cell lymphomas present similar biologic features despite distinct clinical behavior.
Gerbe A, Alame M, Dereure O, et al.
Virchows Archiv : an international journal of pathology 2019; (475(2)):163-174 doi:10.1007/s00428-019-02570-4.
PMID: 30953147 - 3
ALK-negative anaplastic large-cell lymphoma.
Gaulard P, de Leval L
Blood 2016; (127(2)):175-7 doi:10.1182/blood-2015-11-676916.
PMID: 26769771 - 4
Breast Implant-Associated Anaplastic Large Cell Lymphoma: Two Distinct Clinical Presentations.
Miranda P, Moita F, Vargas Moniz J, Rodrigues Dos Santos C
Acta medica portuguesa 2022; (35(11)):835-839 doi:10.20344/amp.16578.
PMID: 35584637 - 5
Best Practices in CD30 Immunohistochemistry Testing, Interpretation, and Reporting: An Expert Panel Consensus.
Gru AA, Lim MS, Dogan A, et al.
Archives of pathology & laboratory medicine 2023; (147(1)):79-86 doi:10.5858/arpa.2021-0270-OA.
PMID: 35472771 - 6
Anaplastic large cell lymphoma: pathology, genetics, and clinical aspects.
Tsuyama N, Sakamoto K, Sakata S, et al.
Journal of clinical and experimental hematopathology : JCEH 2017; (57(3)):120-142 doi:10.3960/jslrt.17023.
PMID: 29279550 - 7
Precision therapy with anaplastic lymphoma kinase inhibitor ceritinib in ALK-rearranged anaplastic large cell lymphoma.
Subbiah V, Kuravi S, Ganguly S, et al.
ESMO open 2021; (6(4)):100172 doi:10.1016/j.esmoop.2021.100172.
PMID: 34242968 - 8
Whole exome sequencing reveals activating JAK1 and STAT3 mutations in breast implant-associated anaplastic large cell lymphoma anaplastic large cell lymphoma.
Blombery P, Thompson ER, Jones K, et al.
Haematologica 2016; (101(9)):e387-90 doi:10.3324/haematol.2016.146118.
PMID: 27198716 - 9
Recombinant expression, characterization, and quantification in human cancer cell lines of the Anaplastic Large-Cell Lymphoma-characteristic NPM-ALK fusion protein.
Kourentzi K, Crum M, Patil U, et al.
Scientific reports 2020; (10(1)):5078 doi:10.1038/s41598-020-61936-w.
PMID: 32193476 - 10
Preclinical Evaluation of Gilteritinib on NPM1-ALK-Driven Anaplastic Large Cell Lymphoma Cells.
Kuravi S, Cheng J, Fangman G, et al.
Molecular cancer research : MCR 2021; (19(5)):913-920 doi:10.1158/1541-7786.MCR-20-0738.
PMID: 33514657 - 11
The biology and management of systemic anaplastic large cell lymphoma.
Hapgood G, Savage KJ
Blood 2015; (126(1)):17-25 doi:10.1182/blood-2014-10-567461.
PMID: 25869285 - 12
Advances in the treatment and prognosis of anaplastic lymphoma kinase negative anaplastic large cell lymphoma.
Wang X, Wu J, Zhang M
Hematology (Amsterdam, Netherlands) 2019; (24(1)):440-445 doi:10.1080/16078454.2019.1613290.
PMID: 31072226 - 13
Systemic ALK-negative anaplastic large cell lymphoma: Insights into morphologic, immunophenotypic, genetic and molecular characteristics.
Xie W, Medeiros LJ, Fan G, et al.
Human pathology 2025; (156()):105671 doi:10.1016/j.humpath.2024.105671.
PMID: 39424106 - 14
ALK-Negative Anaplastic Large Cell Lymphoma (ALCL): Prognostic Implications of Molecular Subtyping and JAK-STAT Pathway.
Parkhi M, Bal A, Das A, et al.
Applied immunohistochemistry & molecular morphology : AIMM 2021; (29(9)):648-656 doi:10.1097/PAI.0000000000000936.
PMID: 33901030 - 15
Gene expression profiling reveals 2 overarching types of ALCL with distinct targetable biology: an LLMPP study.
Feldman AL, Dasari S, Rimsza LM, et al.
Blood 2026; (147(11)):1199-1214 doi:10.1182/blood.2024027700.
PMID: 41329859 - 16
Differential diagnosis and identification of prognostic markers for peripheral T-cell lymphoma subtypes based on flow cytometry immunophenotype profiles.
Pu Q, Qiao J, Liu Y, et al.
Frontiers in immunology 2022; (13()):1008695 doi:10.3389/fimmu.2022.1008695.
PMID: 36466894 - 17
JAK/STAT3 Signaling Activation Related to Distinct Clinicopathologic Features in Systemic ALK - Anaplastic Large Cell Lymphomas : New Insights into Their Heterogeneity.
Wang JC, Zhong LH, Lin WQ, et al.
The American journal of surgical pathology 2023; (47(1)):55-64 doi:10.1097/PAS.0000000000001995.
PMID: 36315833 - 18
Comparative analysis on efficacy of lymph node sampling through whole node excision versus core needle biopsy: focusing on diagnostic yield for interpretation.
Singh N, Mishra S, Balasubramanian P, et al.
Journal of hematopathology 2025; (18(1)):46 doi:10.1007/s12308-025-00662-6.
PMID: 41087604
This page explains ALCL pathology terminology for educational purposes only. Your hematopathologist and oncologist are the best sources for interpreting your specific pathology report and making treatment decisions.
Get notified when new evidence is published on Anaplastic large cell lymphoma.
We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.