NHS North West Genomics
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Use Case: Cytogenetics and Haemato-Oncology Diagnostic Pathway (Shire to HODS)

This is currently being elaborated and subject to change. </div>

References

  1. Inter Laboratory Workflow (ILW) - Sub-orders LAB-35 and LAB-36
  2. Cheshire and Merseyside Pathology - the related pathology-LIMS (CFT Shire) reflex scenario without HODS orchestration
  3. Cancer Background Information for Use Cases - NHS North West Children Cancer Example
  4. HL7 FHIR Genomics Reporting Implementation Guide - see Future Process and Data Models below
  5. Sample Shire LAB-36 cytogenetics messages: Shire-1, Shire-2 - raw HL7 v2, today's actual format
  6. The same two messages, illustrating a future structured FHIR equivalent: Shire-1-structured, Shire-2-structured - published in this IG as Examples below

Clinical Pathway Overview

What is being tested

A single referral for suspected haematological malignancy (blood cancer) triggers a cytogenetic assessment - karyotyping and/or FISH, performed by the pathology laboratory (Shire LIMS) and returned as a Cytogenetic Genomic Report - and, where indicated, further molecular genomic testing by a separate genomics laboratory, without the referring clinician needing to place two separate orders. Together these identify the specific chromosomal/molecular abnormalities that confirm a haematological malignancy subtype and guide treatment choice.

The end-to-end clinical journey

  1. Patient presents - a clinician sees a patient with findings suggestive of a blood cancer (e.g. an abnormal blood count) and places a single haemato-oncology referral.
  2. Sample taken - a blood or bone marrow sample is collected.
  3. Cytogenetic assessment - the referral is orchestrated to the pathology laboratory (Shire LIMS) first, which returns a Cytogenetic Genomic Report (karyotype/FISH). (A LAB-35 reflex order.)
  4. Molecular genomic reflex, if indicated - based on the cytogenetic findings and local protocol, a further reflex order is placed with the genomics laboratory. (Another LAB-35 reflex order.)
  5. Combined report - the cytogenetic and molecular genomic results are brought together into a single report back to the referring clinician. (LAB-3.)
  6. Clinical decision - the haematology MDT confirms the diagnosis and subtype, and plans treatment accordingly.
flowchart LR
    A[Suspected blood cancer -<br/>single referral placed] --> B[Sample taken]
    B --> C["Cytogenetic assessment<br/>(Shire LIMS) -<br/>Cytogenetic Genomic Report"]
    C -->|If indicated| D[Molecular genomic<br/>reflex testing]
    C --> E[Combined report to<br/>referring clinician]
    D --> E
    E --> F[Haematology MDT -<br/>diagnosis and<br/>treatment plan]

Why this matters for developers

  • One referral becomes two separate sub-orders (cytogenetics, then molecular genomics) orchestrated by HODS - not a single combined order - see the Transactions table below.
  • The Shire → HODS report (LAB-36) is a Cytogenetic Genomic Report (karyotype/FISH), not a general pathology/morphology result - see Data Models below for what this content actually contains and how it could be modelled.
  • The molecular genomic reflex order is conditional, triggered by the cytogenetic result/local protocol, not by the original referring clinician - this reflex decision logic sits inside HODS/pathology and isn't modelled by this IG.
  • The report the referring clinician ultimately receives is a single combined LAB-3 report, not two separate cytogenetic and molecular genomic reports.
  • The cytogenetics reflex order goes to Shire LIMS, but this order is not believed to be electronic today - see Current Process.
  • The combined LAB-3 report back to the referring clinician is also not believed to be sent as HL7 ORU_R01/LAB-3 today - more likely a secure email alert with a link to the report, matching the same pattern already confirmed for the equivalent LAB-3 leg in NE&Y Management Information (ctDNA). Of the transactions in this pathway, only the Shire → HODS Cytogenetic Genomic Report (LAB-36) is confirmed electronic - see Current Process.

Actors

IHE Actor Role
Order Placer Referring clinician / EPR
Order Filler (receiving LAB-1) / Requestor (ILW, sending LAB-35) HODS - haemato-oncology order comms system, orchestrates cytogenetics and molecular genomics reflex testing for a single referral
Subcontractor (ILW) Pathology laboratory (cytogenetics) - Shire LIMS, MFT's cellular pathology LIMS. Returns a Cytogenetic Genomic Report (LAB-36). The LAB-35 order to Shire is not believed to be electronic today - see Current Process
Subcontractor (ILW) Genomics laboratory (molecular)

Transactions

Transaction Description Direction
LAB-1 Laboratory Order Order Placer → Order Filler (HODS)
LAB-35 (not believed to be electronic) Cytogenetics Reflex Order Order Filler (HODS) → Order Filler (Pathology - Shire LIMS)
LAB-36 Cytogenetic Genomic Report Order Filler (Pathology - Shire LIMS) → Order Filler (HODS)
LAB-35 Molecular Genomic Reflex Order Order Filler (HODS) → Order Filler (Genomics)
LAB-36 Molecular Genomic Report Order Filler (Genomics) → Order Filler (HODS)
LAB-3 (believed to be a secure email alert with a report link, not electronic HL7 v2) Laboratory Report (combined) Order Filler (HODS) → Order Placer

Only the Shire → HODS Cytogenetic Genomic Report (LAB-36) above is confirmed as an electronic transaction today; the electronic status of the molecular genomic reflex order/report (LAB-35/LAB-36 to/from the genomics laboratory) has not been separately confirmed for this pathway.

Current Process

A haemato-oncology order comms system (HODS) orchestrates cytogenetics and molecular genomics reflex testing for a single referral - see Inter Laboratory Workflow (ILW) for the generic sub-order/reflex pattern this follows (LAB-35/LAB-36), and Cheshire and Merseyside Pathology for the related pathology-LIMS (CFT Shire) reflex scenario without HODS orchestration.

The cytogenetics laboratory here is Shire LIMS (MFT's cellular pathology LIMS), the same LIMS as the Cheshire and Merseyside scenario. The Cytogenetics Reflex Order (LAB-35) from HODS to Shire is not believed to be an electronic transaction today, pending confirmation - shown in the sequence diagram below as such. The combined report (LAB-3) from HODS back to the referring clinician is similarly not believed to be sent electronically (as HL7 ORU_R01) today - more likely a secure email alert with a link to the report, following the same pattern already confirmed for the equivalent LAB-3 leg in NE&Y Management Information (ctDNA) (there, delivered as a PDF via NHS.net secure email). Of the transactions in this pathway, only the Shire → HODS Cytogenetic Genomic Report (LAB-36) is confirmed electronic.

Haematological Malignancy Diagnostic Services

sequenceDiagram


participant EPR as Order Placer
participant LIMS as Order Filler (HODS)
participant LIMSP as Order Filler (Pathology - Shire LIMS)
participant LIMSG as Order Filler (Genomics)


EPR ->> LIMS: Submit Laboratory Order O21 (LAB-1)

opt Order Filler (HODS) creates Cytogenetics Order


    LIMS -->> LIMSP: Cytogenetics Reflex Order (LAB-35) - not believed to be electronic today
    LIMS -->> LIMSP: Send Specimen (not a technical interaction)
    LIMSP -->> LIMSP : Performs Test
    LIMSP ->> LIMS: Send Cytogenetic Genomic Report R01 (LAB-36)
end

opt Order Filler (HODS) creates Molecular Genomic Order

   
    LIMS ->> LIMSG: Submit Molecular Genomic Reflex Order O21 (LAB-35)
    LIMSP -->> LIMSG: Send Specimen (unsure of workflow)
    LIMSG -->> LIMSG : Performs Test
    LIMSG ->> LIMS: Send Molecular Genomic Report R01 (LAB-36)
end
LIMS -->> LIMS: Write Report
LIMS -->> EPR: Send Laboratory Report (LAB-3) - believed to be a secure email alert with a report link, not electronic HL7 v2

This pathway can also apply to children's cancer referrals - see Cancer NOS for the NHS North West Children Cancer notification example.

Future Process

No distinct future-state changes are currently defined for the order/report orchestration in this pathway - this section will be populated as the HODS orchestration workflow above is formalised.

However, the genomic content of the Shire → HODS LAB-36 Cytogenetic Genomic Report is itself a candidate for future modelling. The sample messages for this pathway (Shire-1, Shire-2) carry cytogenetic/molecular findings for suspected MDS and AML - a karyotype (ISCN nomenclature) and, in Shire-2, a FISH result - but represent them entirely as narrative free text: every line of the report is a separate OBX|n|FT|CYTO||... segment, OBR-4 (Universal Service Identifier) is not populated with a coded test name, and there is no structured representation of the abnormal karyotype, the FISH probe/assay used, or the proportion of cells affected (e.g. "93 out of 100 interphase cells"). Report amendments are also represented only as an inline text marker (-Amendment 14/10/20 in Shire-2) rather than as a distinct report/observation status. This is genomic reporting in substance but does not currently align with the HL7 FHIR Genomics Reporting Implementation Guide.

A future state for this pathway should consider re-expressing these results as discrete, coded FHIR resources rather than a single narrative block, so that findings such as "7q deletion" or "trisomy 8" are computable rather than requiring text-mining of OBX-5. See Data Models below for a proposed direction, and Developer Guide 12 for a worked build of that conversion against these two messages, whose output is published as this page's Examples.

Data Models

Future genomic data model (proposed)

Shire's LAB-36 Cytogenetic Genomic Report (and any genomic content folded into the combined LAB-3 report) is a candidate for restructuring in place of the current free-text OBX|FT|CYTO pattern seen in the sample Shire messages - note this is the pathology laboratory's (Shire's) report, not the separate molecular genomics laboratory's LAB-36. Two complementary sources were reviewed for this:

HL7 FHIR Genomics Reporting IG. As of this IG's current build, the HL7 FHIR Genomics Reporting Implementation Guide's own Cytogenomic Reporting section states that the Clinical Genomics work group is still reviewing this use case and has not yet prioritised it - there is currently no finalised, balloted profile for karyotype/FISH results. An earlier (2018, work-in-progress, never balloted) draft of the IG sketched four candidate observation shapes - Chromosome analysis G-banding panel, Chromosome analysis FISH panel, Copy Number Change (a structural-variant finding), and Chromosome Analysis Overall Interpretation - but marked them incomplete ("TODO - detailed explanation of these observations") and they were not carried forward. Building against this IG's cytogenomics content today would mean building against an acknowledged gap, not a stable target.

LOINC cytogenetics panels. LOINC already publishes a mature, granular panel structure for exactly this content, which maps more directly onto today's OBX segments than waiting on the FHIR IG to mature:

LOINC code Panel/result
62389-2 Chromosome analysis master panel
62386-8 Chromosome analysis summary panel
77314-3 Chromosome analysis basic associated observations panel - Blood or Tissue by Cytogenetics
62356-1 Chromosome analysis result in ISCN expression
62349-6 Chromosome analysis panel - Blood [from Fetus] by G-banded (a non-fetal, blood/bone-marrow equivalent should be selected for this pathway)
62367-8 Chromosome analysis panel by FISH
50684-0 Chromosome analysis.interphase [Interpretation] in Blood by FISH Narrative
62343-9 Chromosome analysis copy number change panel by Microarray
82255-1 Marker and derivative chromosome analysis in Blood or Tissue Document by Cytogenetics

(Codes sourced from loinc.org search; the exact panel members and the correct non-fetal specimen variant should be confirmed against the full LOINC hierarchy and with the genomics laboratory before adoption.)

Candidate direction, to be confirmed with the genomics and pathology laboratories:

  • DiagnosticReport as the container for the Cytogenetic Genomic Report, distinct from any other, general cellular pathology DiagnosticReport Shire may also issue, with DiagnosticReport.conclusion carrying the free-text interpretive summary (e.g. "Complex abnormal hyperdiploid karyotype … consistent with AML") and DiagnosticReport.conclusionCode carrying a coded diagnosis/impression (e.g. SNOMED CT MDS/AML) where the laboratory is willing to commit to one.
  • Specimen identifying blood vs. bone marrow, referenced by the report, rather than left as an uncoded OBR field.
  • Discrete Observation resources per finding, coded to the LOINC panel members above, one per karyotype/FISH result rather than one per line of prose, for example:
    • an Observation coded 62356-1 (ISCN expression) carrying the karyotype string (e.g. 46,XY,del(20)(q*q*)[]) as a structured value, with the plain-language description as Observation.note rather than the sole representation of the finding;
    • a separate Observation per FISH probe/locus tested, coded under the 62367-8 FISH panel (e.g. a 7q36.1 deletion probe), with Observation.method for the assay/probe set used (e.g. Cytocell MyProbe [Del(7q) Plus]), and a component for the count/percentage of cells positive (e.g. "93/100 interphase cells") as a quantity rather than embedded in a sentence;
    • individual cytogenetic findings (e.g. monosomy 7, trisomy 8, 12p loss) as their own coded Observations grouped via Observation.hasMember under the 62389-2 master panel (or DiagnosticReport.result), so each can be queried independently rather than only as part of one long karyotype string.
  • DiagnosticReport.status = corrected, with a linked Provenance history for amendments, replacing the current inline -Amendment <date> text markers seen in Shire-2.
  • SNOMED CT codes for the coded diagnosis/impression, and confirmation of the exact LOINC panel members to use, are not yet selected and should be agreed with the genomics laboratory as this model is developed - this section records a proposed resource shape and starting-point codes, not a final specification.

This is additive to, not a replacement for, the existing ServiceRequest/DiagnosticReport models already listed above for the order/report envelope.

Developer Guide 12 builds this conversion by hand against Shire-1.txt/Shire-2.txt, and its output is published below as this page's Examples - a first illustrative pass, using LOINC 62356-1 (ISCN expression), 62389-2 (master panel) and 62367-8 (FISH panel) from the table above, rather than a laboratory-agreed final shape.

Examples

Illustrative future structured FHIR equivalents of the raw HL7 v2 LAB-36 messages in References above - not today's actual format (see Current Process), and not yet agreed with the genomics laboratory (see Future genomic data model above):

Example Source message Content
Bundle/Shire1StructuredR01 Shire-1.txt A single karyotype finding (20q deletion, MDS) as a coded 62356-1 Observation under a 62389-2 master panel, with a 33893-9 DiagnosticReport
Bundle/Shire2StructuredR01 Shire-2.txt As above, plus a 62367-8 FISH panel result (complex hyperdiploid AML karyotype)

Security Considerations

Includes:

Developer Guides

Developer Guide 12 - Haemato-Oncology Cytogenetics: From Free-Text HL7 v2 to Structured Observations builds the conversion above by hand against the two sample messages, and is the source of the Examples published on this page.