Search Database ICD-O-3 Code Lists

Name

Heavy chain diseases, NOS (HCD)

ICD-O-3 Morphology

9762/3: Heavy chain disease
Effective 2001 and later

Reportable

for cases diagnosed 1992 and later

Primary Site(s)

See Module 7
See abstractor notes for the most common sites of involvement for the different variants.

Coding Manual: Hematopoietic Coding Manual (PDF)

Abstractor Notes

For 2026+ diagnoses, Heavy chain deposition disease will be 9762/3. Prior to 2026, the disease is coded as 9769/1.

Heavy chain disease, NOS (HCD) is part of the Mature B-cell neoplasms lineage table in the WHO 5th edition of Hematolymphoid Tumors. (See Appendix B in the Hematopoietic Manual, Table B15)

Mu heavy chain disease: The rarest form of the heavy chain diseases. The spleen is frequently involved, with hepatic involvement in 3/4 of patients, nodal disease in 40% and bone marrow involvement in 20%.

Gamma heavy chain disease: Most patients have disseminated nodal disease, with or without splenomegaly or marrow involvement. Localized extranodal disease may be limited to the bone marrow or another site, most commonly the skin.

Alpha heavy chain disease: The duodenum is most often involved (63% of cases), followed by the jejunum (17%) and ileum (8%). Involvement of the stomach, colon, mesenteric lymph nodes, respiratory tract, thyroid, or more than one anatomical site has been reported in rare cases.

Diagnostic Confirmation

This histology can be determined by positive histology (including peripheral blood) with or without genetics and/or immunophenotyping. Review the Definitive Diagnostic Methods, Immunophenotyping and Genetics Data sections below, and the instructions in the Hematopoietic Manual for further guidance on assigning Diagnostic confirmation.

Module Rule

None

Alternate Names

Alpha heavy chain disease (AHCD)
Franklin disease
Gamma heavy chain disease (GHCD)
Immunoproliferative neoplasm (disease) (see 9760/3 prior to 2010)
Immunoproliferative small intestinal disease (IPSID) (see 9764/3 prior to 2010)
Mediterranean (abdominal) lymphoma (see 9764/3 prior to 2010)
Mu heavy chain disease (MHCD)

Definition

The heavy chain diseases (HCDs) are three rare B-cell neoplasms (alpha, gamma, and mu) each characterized by the production of a shortened monoclonal immunoglobulin heavy chain, with typically no light chain.

Mu heavy chain disease (HCD) is a systemic B-cell neoplasm with hepatosplenic, nodal, and bone involvement characterized by vacuolated plasma cells and secretion of defective serum mu heavy chains that lack associated light chains; free serum and/or urine kappa light chains may also be present. (WHO 5th edition).

Gamma heavy chain disease (HCD) is a B-cell lymphoplasmacytic neoplasm exhibiting variable morphology with nodal, bone marrow, and extranodal involvement. All cases secrete an M protein characterized as gamma heavy chain, without associated light chains. (WHO 5th edition)

Alpha heavy chain disease (HCD) is a variant of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL) that typically involves the gastrointestinal tract and secretes defective, truncated alpha heavy chains lacking light chains. (WHO 5th edition)

Definitive Diagnostic Methods

Cytogenetics
Genetic testing
Histologic confirmation
Immunohistochemistry
Immunophenotyping

Genetics Data

Deletions in Alpha, Gamma, or Mu heavy chain gene
Possible insertions of DNA of unknown origin

Immunophenotyping

CD5 and CD10- (no expression/negative) (AHCD)
CD20+ CD5-, CD10- on marginal zone cells (AHCD)
CD20-, DC138+ on plasma cells (AHCD)
CD79a and CD20 on lymphocytic component (AHCD)
Express B-cell antigens (AHCD)
Monoclonal cytoplasmic alpha chain without light chain on plasma cells and marginal zone cells (GHCD)
Monoclonal cytoplasmic gamma chain without light chains (GHCD)
Monoclonal cytoplasmic Mu heavy chain, with or without monotypic light chain (MHCD)

Treatments

Chemotherapy
Other therapy

Transformations to

Transformations from

None

Same Primaries

Corresponding ICD-10 Codes (Cause of Death codes only)

C88.1 Alpha heavy chain disease
C88.2 Gamma heavy chain disease

Corresponding ICD-10-CM Codes (U.S. only)

C88.2 Heavy chain disease (effective October 01, 2015 - September 30, 2024)
C88.20 Heavy chain disease (effective October 01, 2024)
C88.21 Heavy chain disease, in remission (effective October 01, 2024)

Signs and Symptoms

Abdominal pain (alpha)
Anorexia (gamma)
Diarrhea (alpha)
Fever (alpha & gamma)
Hypocalcemia (alpha)
Malabsorption (alpha)
Recurrent bacterial infections (gamma)
Vasculitis (gamma)
Wasting (alpha)
Weakness (gamma)
Weight loss (gamma)

Diagnostic Exams

Blood chemistry studies
Bone marrow aspiration and biopsy
CT (CAT) scan
Cytogenetic analysis
Immunophenotyping
Peripheral blood smear

Progression and Transformation

None

Epidemiology and Mortality

Incidence: rare (gamma, mu)
Sex: female predominance (gamma)
Age: Sixth or seventh decade (gamma, mu)
Survival: < 1 month to 20 years (gamma)
Sex: male predominance (alpha, mu)
Survival: < 1 month to decades (mu)
Age: young (alpha)
Incidence: higher in the Mediterranean, Middle East (alpha)

Sources

WHO Classification of Tumours Editorial Board. Haematolymphoid tumours. Lyon (France): International Agency for Research on Cancer; 2024. (WHO classification of tumours series, 5th ed.; vol. 11). https://publications.iarc.who.int/637.
Section: Plasma cell neoplasms and other diseases with paraproteins
Pages: Part B: 613-620

International Classification of Diseases for Oncology, 3rd edition (including revisions). Geneva: World Health Organization, 2001, 2011, 2020.
Section: ICD-O-3.2 (2020) Morphological Codes
Pages: http://www.iacr.com.fr/index.php?option=com_content&view=category&layout=blog&id=100&Itemid=577

PDQ® Adult Treatment Editorial Board. PDQ Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment. Bethesda, MD: National Cancer Institute. Updated <03/28/2025>. Available at: https://www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq. Accessed <03/30/2025>. [PMID: 26389362]
Section: Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Health Professional Version
Pages: Version https://www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq
Glossary