14.4 Hematopoietic & Lymphoid Neoplasms: Heme Manual, Heme DB, Multiple Primary & Primary Site Rules
Key Takeaways
Histologies 9590–9993 with behavior /3 are reportable; /1 heme histologies such as in situ follicular or mantle cell neoplasia are not reportable in the U.S., and for heme reportability "consistent with" counts as a definitive diagnosis.
Heme rule M2: a single histology is always a single primary, whatever the timing or site, and bilateral involvement is one primary; the exception is nodal plus extranodal MALT lymphoma (9699/3), which is two primaries.
A chronic and an acute neoplasm diagnosed in the initial clinical workup with one biopsy are a single primary coded to the acute neoplasm (M8), but two biopsies make them multiple primaries (M11).
A chronic neoplasm followed by an acute transformation after the initial workup is multiple primaries (M10); acute followed by chronic is a single primary without treatment (M12) and multiple primaries after treatment (M13).
Leukemias, MDS, MPNs and other marrow diseases are always coded to bone marrow C421; lymphoma in several lymph node regions is coded C778; the Heme DB Multiple Primaries Calculator is used only when rules M1–M14 do not apply (M15).
The tools
| Tool | Use |
|---|---|
| Hematopoietic and Lymphoid Neoplasm Case Reportability and Coding Manual | Reportability, multiple primary (M) rules, primary site and histology (PH) rules, and grade and staging notes |
| Hematopoietic Database (Heme DB) | One page per histology: reportability status, ICD-O code and valid years, synonyms, definitive diagnostic methods, immunophenotype and genetics, transformations to and from, treatment, grade, primary site notes, and the Multiple Primaries Calculator |
The Heme DB is built from the WHO classification of haematolymphoid tumours (5th edition). It now also lists the corresponding ICD-O-4 codes for learning purposes. Registries still code with ICD-O-3.2 and the Heme DB.
Reportability
- Search the Heme DB "Reportable" field. It covers every term in the current WHO book, including non-reportable terms and terms without an ICD-O code.
- Report morphology 9590–9993 with behavior /3.
- /1 heme histologies are not reportable in the U.S. This includes in situ lymphomas such as in situ follicular neoplasia (9695/1) and in situ mantle cell neoplasia (9673/1), for any year. Myeloid precursor lesions such as clonal hematopoiesis are not reportable.
- Exception: a /1 heme neoplasm that a physician calls malignant is reported with behavior changed to /3 under the matrix rule.
- "Consistent with" is definitive for heme reportability and casefinding. It was removed from the ambiguous-terms list because pathologists commonly use it for heme diagnoses.
- The ambiguous terms apparently, appears, comparable with, compatible with, favor(s), malignant appearing, most likely, presumed, probable, suspect(ed), suspicious (for) and typical (of) also make a heme case reportable. Ambiguous cytology alone is not reportable.
- Follow-back to the physician is recommended, because heme cases are often diagnosed outside the hospital and are otherwise underreported.
Multiple primary rules (M1–M15)
| Rule | Outcome | Situation |
|---|---|---|
| M1 | Single | Minimal information (DCO, pathology report only) |
| M2 | Single | Single histology. Recurrence of the same histology is always the same primary, timing and site do not matter, and bilateral involvement is one primary. Exception: nodal MALT (C77x, 9699/3) before or after extranodal MALT is two primaries. Follicular lymphomas (9690, 9691, 9695, 9698) are always the same primary; update the histology to the higher grade. Therapy-related myeloid neoplasm is one primary coded 9920/3 |
| M3 | Single | Myeloid sarcoma with or after AML, or mast cell sarcoma with or after mast cell leukemia (a manifestation of the leukemia). Does not apply to CML |
| M4 | Single | Two or more B-cell non-Hodgkin lymphomas in the same specimen (not cutaneous lymphomas) |
| M5 | Single | Hodgkin and B-cell non-Hodgkin lymphoma in the same location at the same time, during the initial workup |
| M6 | Multiple | Hodgkin in one location and non-Hodgkin lymphoma in a different location |
| M7 | Single | A more specific histology after an NOS, when the Multiple Primaries Calculator confirms they are the same primary. Update the original histology if the code was valid in that diagnosis year |
| M8 | Single (code the acute) | Chronic and acute neoplasm diagnosed during the initial clinical workup with one positive biopsy |
| M9 | Single (acute) | Chronic and acute in the initial workup, no biopsy documentation (rarely used) |
| M10 | Multiple | Chronic neoplasm first, then an acute neoplasm diagnosed after the initial workup is completed |
| M11 | Multiple | Chronic and acute in the initial workup with two biopsies, one confirming each |
| M12 | Single | Acute first, then reverts to a related chronic neoplasm after the workup, with no treatment (or treatment unknown) |
| M13 | Multiple | Acute first, then a chronic neoplasm after treatment of the acute one, even if treatment was not finished |
| M14 | Single | PTLD diagnosed in the same report with a B-cell, T-cell or Hodgkin lymphoma or plasmacytoma/myeloma. Code the accompanying lymphoma |
| M15 | Calculator | None of M1–M14 applies: use the Heme DB Multiple Primaries Calculator |
The chronic/acute rules (M8–M13)
- They apply only when the Heme DB lists the two diseases as "transformations to" or "transformations from" each other. Otherwise go to M14 and M15.
- The phrase "initial clinical workup" replaced the old 21-day window.
- Examples:
- MDS diagnosed in 2019 and AML in 2024: M10 gives two primaries.
- CLL/SLL followed later by diffuse large B-cell lymphoma (Richter transformation), after the initial workup: M10 gives two primaries.
- A lymph node biopsy showing DLBCL and follicular lymphoma together is one specimen with two B-cell lymphomas. M4 gives one primary, and PH11 codes it as DLBCL.
- Never go straight to the calculator. Use it only when the rules send you there.
Primary site (PH rules)
| Situation | Primary site |
|---|---|
| Leukemias, MDS, MPNs and other bone marrow diseases | Always C421 (bone marrow) |
| Only a positive peripheral blood smear | C421 |
| Plasma cell myeloma | C421 |
| Plasmacytoma | The bone (PH3) or extraosseous site (PH2) involved |
| CLL/SLL with marrow or blood involvement | C421 (PH5), whatever the node or organ involvement |
| CLL/SLL without marrow or blood involvement, or unknown | The involved nodes, organ or tissue (PH6) |
| Lymphoma in one lymph node chain or region | That region (C770–C775) |
| Lymphoma in multiple lymph node regions | C778, unless a physician documents a specific region of origin (rare) |
| Lymphoma in an organ only, or an organ with its regional nodes | The organ, for example stomach C16x for gastric MALT lymphoma |
| AML with myeloid sarcoma | Follow the Module 5 rules (PH10) |
Bone marrow involvement by a lymphoma does not make C421 the primary site. For example, DLBCL in several node regions with a positive marrow is coded C778, and the marrow involvement is recorded in staging and the metastasis items.
Histology (PH rules) highlights
- PH11: DLBCL with any other non-Hodgkin lymphoma in the same site: code DLBCL (9680/3).
- PH14: B-cell non-Hodgkin and Hodgkin lymphoma together in the same node or node regions (the M5 situation): code 9596/3, composite Hodgkin and non-Hodgkin B-cell lymphoma.
- NOS versus specific (PH28–PH29): code the specific histology identified by the definitive diagnostic method in the Heme DB.
- PH31, the last resort: code the numerically higher ICD-O code.
Other heme coding points
- Grade: Grade Clinical and Grade Pathological are coded 8, and the post-therapy grades are blank (Section 13.4).
- Diagnostic Confirmation 3: positive histology plus immunophenotyping or genetic testing (Section 10.3).
- Staging: lymphomas use the AJCC Hodgkin and non-Hodgkin lymphoma chapters (Lugano) and Summary Stage rules. Leukemias are Summary Stage 7 (systemic).
A patient was treated for diffuse large B-cell lymphoma of the left renal pelvis in 2020. In 2026, a prostate biopsy shows diffuse large B-cell lymphoma. How many primaries are there?
Two, because the sites differ and more than five years have passed
One, because heme rule M2 says a single histology is always the same primary regardless of timing or site
Two, because the second lymphoma arose in an extranodal organ
Use the Multiple Primaries Calculator first
A patient diagnosed with myelodysplastic neoplasm in 2023 is diagnosed with acute myeloid leukemia in 2026, long after the initial workup. The Heme DB lists AML as a transformation of MDS. What is the result?
Two primaries, because a chronic neoplasm followed by an acute neoplasm after the initial clinical workup is multiple primaries (M10)
One primary, MDS, because the first diagnosis is kept
One primary, AML, because the acute neoplasm replaces the chronic one
Use the Multiple Primaries Calculator
A hematopathology report states "atypical lymphoid infiltrate, consistent with chronic lymphocytic leukemia." Under the Hematopoietic manual, is this reportable?
No, because "consistent with" is an ambiguous term that needs physician confirmation
Yes, because "consistent with" is treated as a definitive diagnosis for heme reportability and casefinding
Only if flow cytometry also confirms it
Only if the patient receives treatment
Sections you finish are checked off in the contents.