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Anaplastic Large Cell Lymphoma

Anaplastic Large Cell Lymphoma Curation Notes

OpenAI MONDO:0020325 Model: gpt-5

Anaplastic Large Cell Lymphoma Curation Notes

Modeling Decision

This curation follows the cancer modeling guidance from dismech issue #1198 and the Wilms tumor pattern:

  • The dismech page is the disease-level mechanism graph for ALCL, not a one-page-per-ontology-subclass expansion.
  • disease_term stays MONDO-first at MONDO:0020325 (anaplastic large cell lymphoma).
  • Major ALCL entities are represented as flat subtype facets under one page:
  • Systemic ALK-positive
  • Systemic ALK-negative
  • Primary cutaneous
  • Breast implant-associated
  • Genetic subgroups such as DUSP22-rearranged and TP63-rearranged ALK-negative ALCL are modeled as mechanism/genetic facts inside the unified disease page, not as separate dismech pages.
  • Current schema only provides Subtype.subtype_term as a MONDO-grounded slot and does not expose a disease-level ncit_mappings slot. Because of that, NCIT grounding was carried through histopathology findings, biomarkers, and treatment regimens/agents rather than by inventing non-schema subtype mapping structures.

Ontology Anchors

Disease

  • MONDO disease anchor: MONDO:0020325 anaplastic large cell lymphoma
  • NCIT companion cancer concept: NCIT:C3720 Anaplastic Large Cell Lymphoma

MONDO subtype anchors used in YAML

  • MONDO:0017602 ALK-positive anaplastic large cell lymphoma
  • MONDO:0017603 ALK-negative anaplastic large cell lymphoma
  • MONDO:0017598 primary cutaneous anaplastic large cell lymphoma
  • MONDO:0850112 breast implant-associated anaplastic large cell lymphoma

NCIT companion subtype concepts used in interpretation

  • NCIT:C37195 Systemic Anaplastic Large Cell Lymphoma, ALK-Positive
  • NCIT:C37196 Systemic Anaplastic Large Cell Lymphoma, ALK-Negative
  • NCIT:C6860 Primary Cutaneous Anaplastic Large Cell Lymphoma
  • NCIT:C139012 Breast Implant-Associated Anaplastic Large Cell Lymphoma

Histopathology / biomarker / treatment grounding

  • NCIT:C39679 Hallmark Cell
  • NCIT:C193484 CD30 Antigen [Presence] in Tissue by Immune Stain
  • NCIT:C38906 Tumor Necrosis Factor Receptor Superfamily Member 8
  • NCIT:C81946 ALK Fusion Protein Expression
  • NCIT:C66944 Brentuximab Vedotin
  • NCIT:C159558 CHP-Brentuximab Vedotin Regimen
  • NCIT:C160013 Crizotinib Regimen

PMID-Backed Evidence Used

Disease framing and subtype axes

  • PMID:40565334
  • Quote: Anaplastic Large Cell Lymphoma (ALCL) represents a diverse group of mature T-Cell Lymphomas unified by strong CD30 expression but with different molecular and clinical subtypes.
  • Use: disease-level definition and justification for one unified ALCL page.
  • PMID:40565334
  • Quote: ALCL comprises four major entities: systemic ALK-positive ALCL, systemic ALK-negative ALCL, Breast Implant-Associated ALCL (BIA-ALCL), and primary cutaneous ALCL.
  • Use: flat subtype facet structure.
  • PMID:24894770
  • Quote: Thus, ALK-negative ALCL is a genetically heterogeneous disease with widely disparate outcomes following standard therapy.
  • Use: ALK-negative modeled as one subtype with internal genetic heterogeneity, not split into multiple pages.

Histopathology and diagnosis

  • PMID:28975123
  • Quote: Histologically, all the subtypes showed pleomorphic and "hallmark" cells with strong CD30 expression and variable loss of T-cell antigens.
  • Use: hallmark-cell histopathology and diffuse CD30-positive tissue phenotype.
  • PMID:28975123
  • Quote: Diagnosis of ALCL is based on recognizing the key morphological features, especially the presence of "hallmark" cells.
  • Use: diagnostic emphasis on morphology.
  • PMID:28975123
  • Quote: The inclusion of CD30 in the initial IHC panel will help identify LCA negative cases and avoid misdiagnosis.
  • Use: diagnostic workflow and IHC panel design.
  • PMID:35941721
  • Quote: Together with previous data, these findings support a 4-marker immunohistochemistry algorithm using ALK, LEF1, TIA1, and p63 for genetic subtyping of ALCL.
  • Use: ancillary subtype-specific diagnostic testing.

Mechanism notes kept atomic in YAML

  • PMID:29617304
  • Quote: ALK is rearranged in approximately 80% of systemic ALCL cases with one of its partner genes, most commonly NPM1
  • Use: discrete ALK Fusion Oncogene Formation node.
  • PMID:11850821
  • Quote: We show here that expression of activated ALK induces the constitutive phosphorylation of Stat3 in transfected cells as well as in primary human ALCLs.
  • Use: separate ALK-Driven STAT3 Activation node.
  • PMID:11850821
  • Quote: These studies support a pathogenic mechanism whereby stimulation of anti-apoptotic signals through activation of Stat3 contributes to the successful outgrowth of ALK positive tumor cells.
  • Use: separate BCL2L1-Mediated Apoptosis Resistance node.
  • PMID:19088198
  • Quote: NPM/ALK induces CD274 expression by activating its key signal transmitter, transcription factor STAT3.
  • Use: separate PD-L1-Mediated Immune Evasion node.
  • PMID:34572893
  • Quote: Additionally, systemic ALK- ALCL-apart from DUSP22-rearranged cases-harbors JAK1 and/or STAT3 mutations that result in the activation of the JAK/STAT signaling pathway.
  • Use: subtype-scoped JAK/STAT3 Pathway Alteration in ALK-Negative ALCL.
  • PMID:34382383
  • Quote: Consistent with the genomic data, transcriptome analysis uncovered upregulation of signal transduction routes associated with the PI-3-K, MAPK and G-protein pathways (e.g., ERK, phospholipase C, AKT).
  • Use: distinct primary-cutaneous signaling node rather than collapsing all non-ALK biology together.

Phenotypes and treatment

  • PMID:37655119
  • Quote: This lymphoma has a median age of 34 years, is more common in males, and is in advanced stage at the time of diagnosis in most patients.
  • Use: advanced-stage presentation phenotype for systemic ALK-positive disease.
  • PMID:24346900
  • Quote: Primary cutaneous anaplastic large-cell lymphoma is part of the spectrum of CD30+ lymphoproliferative cutaneous processes, characterized by single or multifocal nodules that ulcerate, are autoregressive and recurrent.
  • Use: skin-nodule phenotype for primary cutaneous ALCL.
  • PMID:38102324
  • Quote: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a subtype of ALCL that arises as a seroma or a mass in the capsule surrounding textured breast implants.
  • Use: seroma and capsule-mass phenotypes for BIA-ALCL.
  • PMID:30914464
  • Quote: In November 2018, the U.S. Food and Drug Administration (FDA) approved brentuximab vedotin (BV) for the treatment of adult patients with previously untreated systemic anaplastic large cell lymphoma
  • Use: frontline brentuximab vedotin plus CHP.
  • PMID:28974506
  • Quote: These final results, which demonstrated ... durable remissions in a subset of patients with relapsed or refractory systemic ALCL, provide evidence that single-agent brentuximab vedotin may be a potentially curative treatment option.
  • Use: relapsed/refractory brentuximab vedotin.
  • PMID:37549532
  • Quote: CONCLUSION: Crizotinib shows efficacy and an acceptable safety profile in ALK+ ALCL relapsed/refractory patients.
  • Use: targeted ALK inhibition.
  • PMID:26628470
  • Quote: Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014)
  • Use: surgery-first management for BIA-ALCL.

Why Separate Pages Were Not Created

Separate disease files were not created for ALK-positive ALCL, ALK-negative ALCL, primary cutaneous ALCL, or BIA-ALCL because:

  • the user explicitly requested application of the #1198 cancer-guideline pattern;
  • ALCL is represented in current disease ontology usage as one disease family with major subtype entities;
  • the important modeling burden here is subtype-scoped mechanism and treatment separation inside one page, not proliferating disease pages; and
  • only some branches, especially ALK-positive systemic disease and cutaneous/BIA disease, show clearly different mechanistic programs, which are captured by atomic nodes and subtype-scoped evidence inside the single page.

Cached References Added for This Slice

  • PMID:40565334
  • PMID:29617304
  • PMID:37655119
  • PMID:24894770
  • PMID:35941721
  • PMID:34382383
  • PMID:34572893
  • PMID:24404580
  • PMID:19088198
  • PMID:11850821
  • PMID:30914464
  • PMID:28974506
  • PMID:37549532
  • PMID:24346900
  • PMID:26628470
  • PMID:38102324