Oncology

Understanding the 4 Subtypes: Location and Behavior

At a Glance

Anaplastic Large Cell Lymphoma (ALCL) is divided into four main subtypes: ALK-positive, ALK-negative, breast implant-associated (BIA-ALCL), and primary cutaneous ALCL. Each type behaves differently, requiring specific staging and treatment approaches based on genetic markers and location.

While all types of Anaplastic Large Cell Lymphoma (ALCL) share a common marker called CD30, they are not the same disease ^[1]. Where the lymphoma starts and which genetic “switches” are flipped determine how it behaves and how it is staged. Doctors divide ALCL into four main subtypes, each with its own personality and outlook.

1. ALK-Positive Systemic ALCL

This is the most common subtype in children and young adults ^[2]. It is defined by a genetic change that causes the cells to produce a protein called ALK (Anaplastic Lymphoma Kinase) ^[3].

Behavior: It is an aggressive, fast-growing lymphoma that often involves the lymph nodes, bone, or skin ^[3].
Staging: It uses the Ann Arbor system (Stages I–IV), which looks at how many lymph node groups are affected and if they are on both sides of the diaphragm ^[4].
Prognosis: Despite being aggressive, it is highly treatable. Long-term survival rates are generally high, often between 60% and 90% depending on the specific case ^[5]^[6].

2. ALK-Negative Systemic ALCL

This subtype is more common in older adults (usually over age 40 to 60) ^[7]. It looks similar to the ALK-positive version under a microscope but lacks the ALK protein ^[3].

Behavior: Also aggressive and systemic, but its behavior can vary based on other genetic markers like DUSP22 (generally a better outlook) or TP63 (generally a more challenging outlook) ^[8]^[7].
Staging: Also uses the Ann Arbor system ^[4].
Prognosis: Historically, this had a lower survival rate than the ALK-positive version, but new targeted therapies (like brentuximab vedotin) are significantly improving these numbers ^[9]^[7].

3. Breast Implant-Associated ALCL (BIA-ALCL)

This is a rare version that develops in the scar tissue (capsule) around a textured breast implant ^[10]. It is almost always ALK-negative ^[11].

Behavior: Most cases are “indolent” (slow-moving) and stay confined to the fluid or the capsule around the implant ^[12]^[13].
Staging: Because it behaves more like a solid tumor than a typical blood cancer, doctors use a specialized TNM system (Tumor, Node, Metastasis) ^[14]^[15].
Prognosis: The prognosis is excellent. When the cancer is caught early and the implant and capsule are fully removed, the 2-year survival rate is approximately 98% ^[16]^[11].

4. Primary Cutaneous ALCL (pcALCL)

This version is limited strictly to the skin at the time of diagnosis ^[17]. It is also ALK-negative.

Behavior: It often appears as one or more red nodules or sores on the skin ^[18]. It grows slowly and rarely spreads to the rest of the body ^[17].
Staging: It uses a specific staging system for skin lymphomas that focuses on the number of lesions and their location on the body ^[19].
Prognosis: The outlook is very good, with a 5-year survival rate typically exceeding 90% ^[17].

Comparison of ALCL Subtypes

Subtype	Most Common Age	ALK Status	Staging System	Growth Pattern
ALK-Positive	Kids / Young Adults	Positive	Ann Arbor	Fast / Aggressive
ALK-Negative	Older Adults	Negative	Ann Arbor	Fast / Aggressive
BIA-ALCL	Adults (with implants)	Negative	TNM	Slow / Localized
Primary Cutaneous	Older Adults	Negative	Skin TNM	Slow / Skin-only

Note: While these categories help doctors choose the right therapy, every patient’s situation is unique. Your care team will use your specific stage and markers to tailor your treatment ^[20].

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Common questions in this guide

What is the difference between ALK-positive and ALK-negative ALCL?

ALK-positive ALCL has a genetic change that produces the ALK protein, while ALK-negative ALCL lacks this protein. Both are fast-growing, but ALK-positive is more common in younger people and has high survival rates, whereas ALK-negative usually affects older adults.

Is breast implant-associated ALCL (BIA-ALCL) an aggressive cancer?

Most cases of BIA-ALCL are slow-growing and stay confined to the scar tissue or fluid around a textured breast implant. When it is caught early and treated by completely removing the implant and capsule, the prognosis is excellent.

Does primary cutaneous ALCL spread to the rest of the body?

Primary cutaneous ALCL usually remains limited strictly to the skin at the time of diagnosis. It tends to grow slowly and rarely spreads to other organs or lymph nodes, resulting in a very good long-term outlook.

What does it mean if my ALCL is systemic?

Systemic ALCL means the lymphoma can affect lymph nodes and other organs throughout the body, like bone or skin. Both ALK-positive and ALK-negative systemic ALCL are typically fast-growing and are staged using the Ann Arbor system.

Curated prompts to bring to your next appointment.

1.Is my ALCL considered 'systemic' or 'localized'?
2.Which staging system was used for my diagnosis—Ann Arbor or TNM?
3.If I have ALK-negative ALCL, was my tissue tested for the DUSP22 or TP63 genetic markers?
4.For BIA-ALCL, was the cancer found only in the fluid, or had it grown into the surrounding tissue or lymph nodes?
5.What is my IPI (International Prognostic Index) score, and how does that affect our treatment plan?

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References (20)

1
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
2
Small cell/lymphohistiocytic morphology is associated with peripheral blood involvement, CD8 positivity and retained T-cell antigens, but not outcome in adults with ALK+ anaplastic large cell lymphoma.
Khanlari M, Li S, Miranda RN, et al.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2022; (35(3)):412-418 doi:10.1038/s41379-021-00944-1.
PMID: 34628481
3
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
4
Anaplastic Large Cell Lymphoma: Molecular Pathogenesis and Treatment.
Zhang XR, Chien PN, Nam SY, Heo CY
Cancers 2022; (14(7)) doi:10.3390/cancers14071650.
PMID: 35406421
5
Crizotinib induces apoptosis and gene expression changes in ALK+ anaplastic large cell lymphoma cell lines; brentuximab synergizes and doxorubicin antagonizes.
Hudson S, Wang D, Middleton F, et al.
Pediatric blood & cancer 2018; (65(8)):e27094 doi:10.1002/pbc.27094.
PMID: 29697184
6
Anaplastic lymphoma kinase-negative primary systemic anaplastic large cell lymphoma mimicking a ruptured epidermal cyst of the scalp: a case report and literature review.
Ahn IY, Bae TH, Kang SH, et al.
Archives of craniofacial surgery 2024; (25(6)):298-302 doi:10.7181/acfs.2024.00262.
PMID: 39551572
7
[Current standard in diagnostic and therapy of peripheral T-cell lymphoma].
Hopfinger G, Staber P
Deutsche medizinische Wochenschrift (1946) 2019; (144(20)):1400-1404 doi:10.1055/a-0597-7606.
PMID: 31594013
8
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
9
Frontline Management of Nodal Peripheral T-Cell Lymphomas.
Ngu HS, Savage KJ
American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting 2023; (43()):e390334 doi:10.1200/EDBK_390334.
PMID: 37262395
10
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
11
Cell of Origin and Immunologic Events in the Pathogenesis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma.
Turner SD, Inghirami G, Miranda RN, Kadin ME
The American journal of pathology 2020; (190(1)):2-10 doi:10.1016/j.ajpath.2019.09.005.
PMID: 31610171
12
Breast implant-associated anaplastic large cell lymphoma: a review.
Quesada AE, Medeiros LJ, Clemens MW, et al.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2019; (32(2)):166-188 doi:10.1038/s41379-018-0134-3.
PMID: 30206414
13
Breast Implant-Associated Anaplastic Large-Cell Lymphoma: Current Understanding and Recommendations for Management.
St Cyr TL, Pockaj BA, Northfelt DW, et al.
Plastic surgery (Oakville, Ont.) 2020; (28(2)):117-126 doi:10.1177/2292550320925906.
PMID: 32596187
14
Breast Implant-Associated Anaplastic Large Cell Lymphoma.
Rastogi P, Deva AK, Prince HM
Current hematologic malignancy reports 2018; (13(6)):516-524 doi:10.1007/s11899-018-0478-2.
PMID: 30345474
15
An Unusual Case of Breast Implant-Associated Anaplastic Large Cell Lymphoma.
Premji S, Barbieri A, Roth C, et al.
Case reports in hematology 2022; (2022()):4700787 doi:10.1155/2022/4700787.
PMID: 35721802
16
Treatment and outcome of breast implant-associated anaplastic large cell lymphoma: a population-based cohort study in the Netherlands.
Meeuwes FO, Brink M, van der Poel MWM, et al.
Leukemia & lymphoma 2025; (66(11)):2064-2070 doi:10.1080/10428194.2025.2530167.
PMID: 40629917
17
No TP63 rearrangements in a selected group of primary cutaneous CD30+ lymphoproliferative disorders with aggressive clinical course.
Schrader AM, Chung YY, Jansen PM, et al.
Blood 2016; (128(1)):141-3 doi:10.1182/blood-2016-02-694455.
PMID: 27146432
18
Primary Cutaneous Anaplastic Large Cell Lymphoma with Locoregional Lymph Node Involvement: Challenges in Diagnosis and Clinical Management.
Garcia-Garcia M, Tardin Cardoso AL, Val IS, et al.
The American Journal of dermatopathology 2025; (47(11)):866-870 doi:10.1097/DAD.0000000000003103.
PMID: 40810669
19
ALK-Negative Anaplastic Large Cell Lymphoma: Current Concepts and Molecular Pathogenesis of a Heterogeneous Group of Large T-Cell Lymphomas.
Pina-Oviedo S, Ortiz-Hidalgo C, Carballo-Zarate AA, Zarate-Osorno A
Cancers 2021; (13(18)) doi:10.3390/cancers13184667.
PMID: 34572893
20
STAT3 and TP53 mutations associate with poor prognosis in anaplastic large cell lymphoma.
Lobello C, Tichy B, Bystry V, et al.
Leukemia 2021; (35(5)):1500-1505 doi:10.1038/s41375-020-01093-1.
PMID: 33247178

This page explains ALCL subtypes and their general behaviors for educational purposes. Always consult your oncologist to understand your specific lymphoma type, stage, and personalized treatment plan.

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