Diagnoses Discussed In This Chapter
Cancers Not Staged Using This Staging System
| These histopathologic types of cancer… | Are staged according to the classification for… | and can be found in chapter… |
|---|---|---|
| Plasma cell myeloma | Plasma cell myeloma | 82.1 |
Summary of Changes
| Change | Details of Change | Level of Evidence |
|---|---|---|
| Updated definition of solitary plasmacytoma | Divides this heterogeneous entity into two clinically distinct groups with markedly different risks of progression | I |
ICD-O-3 Topography Codes
| Code | Description |
|---|---|
| C31.0 | Maxillary sinus |
| C31.1 | Ethmoid sinus |
| C31.2 | Frontal sinus |
| C31.3 | Sphenoid sinus |
| C31.8 | Overlapping lesion of accessory sinuses |
| C31.9 | Accessory sinus, NOS |
| C40.0 | Long bones of upper limb, scapula and associated joints |
| C40.1 | Short bones of upper limb and associated joints |
| C40.2 | Long bones of lower limb and associated joints |
| C40.3 | Short bones of lower limb and associated joints |
| C40.8 | Overlapping lesion of bones, joints and articular cartilage of limbs |
| C40.9 | Bone of limb, NOS |
| C41.0 | Bones of skull and face and associated joints |
| C41.1 | Mandible |
| C41.2 | Vertebral column |
| C41.3 | Rib, sternum, clavicle and associated joints |
| C41.4 | Pelvic bones, sacrum, coccyx and associated joints |
| C41.8 | Overlapping lesion of bones, joints and articular cartilage |
| C41.9 | Bone, NOS |
| C42.1 | Bone marrow |
| C44.0 | Skin of lip, NOS |
| C44.2 | External ear |
| C44.3 | Skin of other and unspecified parts of face |
| C44.4 | Skin of scalp and neck |
| C44.5 | Skin of trunk |
| C44.6 | Skin of upper limb and shoulder |
| C44.7 | Skin of lower limb and hip |
| C44.8 | Overlapping lesion of skin |
| C44.9 | Skin, NOS |
| C51.0 | Labium majus |
| C51.1 | Labium minus |
| C51.2 | Clitoris |
| C51.8 | Overlapping lesion of vulva |
| C51.9 | Vulva, NOS |
| C60.0 | Prepuce |
| C60.1 | Glans penis |
| C60.2 | Body of penis |
| C60.8 | Overlapping lesion of penis |
| C60.9 | Penis, NOS |
| C63.2 | Scrotum, NOS |
WHO Classification of Tumors
This list includes histology codes and preferred terms from the WHO Classification of Tumors and the International Classification of Diseases for Oncology (ICD-O). Most of the terms in this list represent malignant behavior. For cancer reporting purposes, behavior codes /3 (denoting malignant neoplasms), /2 (denoting in situ neoplasms), and in some cases /1 (denoting neoplasms with uncertain and unknown behavior) may be appended to the 4-digit histology codes to create a complete morphology code.
| Code | Description |
|---|---|
| 9671 | Malignant lymphoma, lymphoplasmacytic |
| 9731 | Solitary plasmacytoma of bone |
| 9734 | Extraosseous plasmacytoma |
| 9761 | Waldenström macroglobulinemia |
International Agency for Research on Cancer, World Health Organization. International Classification of Diseases for Oncology. ICD-O-3-Online.http://codes.iarc.fr/home. Accessed August 16, 2017. Used with permission.
Multiple myeloma (MM) is a neoplastic disorder characterized by the proliferation of a single clone of plasma cells derived from B cells. This clone of plasma cells grows in the bone marrow and frequently invades the adjacent bone, producing skeletal destruction that results in bone pain and fractures. Other common clinical findings include anemia, hypercalcemia, and renal insufficiency. Recurrent bacterial infections and bleeding may occur, but the hyperviscosity syndrome is rare. The clone of plasma cells produces monoclonal (M) protein of IgG or IgA (rarely IgD, IgE, or IgM) or free monoclonal light chains (kappa or lambda; Bence Jones protein).
Clinical Classification
The criteria for the diagnosis of multiple myeloma and related plasma cell proliferative disorders are provided in Table 111.1. The diagnosis requires >=10% clonal plasma cells in the bone marrow or presence of a biopsy-proven plasmacytoma plus any one or more myeloma-defining events (MDEs). Metastatic carcinoma, lymphoma, leukemia, and connective tissue disorders must be excluded. In addition, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and solitary plasmacytoma must be excluded.
| Disorder | Disease definition |
|---|---|
| Multiple myeloma | Both of the following criteria must be met:
|
| Non-IgM MGUS | All three of the following criteria must be met:
|
| IgM MGUS | All three of the following criteria must be met:
|
| Light chain MGUS | All of the following criteria must be met:
|
| SMM | Both of the following criteria must be met:
|
| Solitary plasmacytoma | All four of the following criteria must be met:
|
| Solitary plasmacytoma with minimal marrow involvement** | All four of the following criteria must be met:
|
*A bone marrow biopsy may be deferred in patients with low-risk MGUS (IgG type, M protein <15 g/L, normal FLC ratio) in whom there are no clinical features concerning for myeloma.
**Solitary plasmacytoma with >=10% clonal plasma cells is considered multiple myeloma.
Monoclonal Gammopathy of Undetermined Significance
The prevalence of monoclonal gammopathy of undetermined significance (MGUS), including light chain MGUS, is 4% in persons 50 years or older, 9% in those over 80 years of age, and is higher in men than women; African-Americans have a 2-fold higher prevalence of MGUS than whites.2 The rate of progression is approximately 0.5% to 1% per year. [The level of monoclonal protein and the subtype (i.e., IgA and IgM are at greater risk) along with the serum free light chain (FLC) level are important prognostic features.] Patients must continue to be observed throughout their life because the risk of progression persists.3,4
Smoldering Multiple Myeloma (SMM)
SMM is characterized by the presence of M protein >=3 g/dL and/or 10-60% clonal plasma cells in the bone marrow but no myeloma-defining events. Based on retrospective registry data, the risk of progression to multiple myeloma or AL amyloidosis is 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and then 1% per year for the following 10 years.
Waldenström's Macroglobulinemia
Waldenström's macroglobulinemia (WM) is a clonal lymphoplasmacytic neoplasm associated with the secretion of an IgM monoclonal protein. The diagnostic criteria include IgM protein spike (of any size), >=10% bone marrow lymphoplasmacytic infiltration (usually intertrabecular) by small lymphocytes that exhibit plasmacytoid or plasma cell differentiation, and a typical immunophenotype (e.g., surface IgM+, CD5+/-, CD10-, CD19+, CD20+, CD23-) that satisfactorily excludes other lymphoproliferative disorders, including chronic lymphocytic leukemia and mantle cell lymphoma. Patients who meet criteria for WM who do not have anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder are considered to have smoldering WM. In contrast to multiple myeloma, no immunoglobulin heavy chain translocations are found. Most patients have a recurrent somatic mutation, L265P, involving the MYD88 gene. Median survival is approximately 6 years. (Gender; age; hemoglobin, neutrophil, and platelet levels; serum albumin; and β2-microglobulin are all prognostic features.)
Solitary Plasmacytoma (Solitary Myeloma) of Bone
The diagnosis of solitary plasmacytoma of bone depends on histologic proof of a solitary plasma cell tumor (Table 111.1). Solitary bone plasmacytoma (normal bone marrow) has a risk of progression of approximately 10% within 3 years. In contrast, solitary bone plasmacytoma with minimal marrow involvement (clonal bone marrow cells present but <10%) is associated with a risk of progression of approximately 60% within 3 years. The persistence of a serum monoclonal protein >=0.5 g/dL 1 to 2 years after diagnosis and an abnormal FLC ratio at the time of diagnosis indicate a high risk for disease progression.
Solitary Extramedullary Plasmacytoma
Solitary extramedullary plasmacytoma is a plasma cell tumor that arises outside the bone marrow. The upper respiratory tract is involved in approximately 80% of cases. As with solitary bone plasmacytoma, the risk of progression varies depending on whether the bone marrow is involved. Solitary extramedullary plasmacytoma (normal bone marrow) has a risk of progression of approximately 10% within 3 years. In contrast, solitary extramedullary plasmacytoma with minimal marrow involvement (clonal bone marrow cells present but <10%) is associated with a risk of progression of approximately 20% within 3 years.
Imaging
The imaging test relevant for diagnosis and assessment of treatment response in multiple myeloma is either MR imaging or low-dose whole-body CT or PET/CT, with the choice depending on availability and local expertise. In the past, planar X-rays were used for a skeletal survey to look for lytic lesions. Currently, this is regarded as an outdated approach and should be used only if the newer imaging modalities are not available.
MR imaging is most useful for evaluating marrow lesions.5 CT imaging usually is done without iodinated intravenous contrast. The imaging findings sought with CT are lytic bone lesions. CT is more sensitive than planar X-rays but less sensitive than MR imaging. Note that if a PET/CT scan is performed, there is no need to order a separate CT scan.
MR and CT imaging should include the skull, spine, sternum, clavicles, shoulders, proximal humeri, pelvis, and proximal femora. PET/CT imaging is done with fluorine-18 fluorodeoxyglucose (FDG) from the top of the head to mid-thigh. The PET/CT findings that indicate active lmultiple myeloma are focal areas of increased FDG uptake (hot spots) in marrow or in soft tissue masses. The hot spots may be difficult to detect in the presence of diffuse marrow involvement. PET/CT assessment of marrow involvement is less accurate than MR imaging, because normal marrow uptake may be heterogeneous and may be markedly elevated in patients treated with granulocyte colony-stimulating factor.5
There are no registry data collection variables for other plasma cell disorders at this time.
Prognostic Factors Required for Stage Grouping
There are no required, recommended or emerging prognostic factors for other plasma cell disorders at this time.
Risk Assesment Models
The AJCC recently established guidelines that will be used to evaluate published statistical prediction models for the purpose of granting endorsement for clinical use.7 Although this is a monumental step toward the goal of precision medicine, this work was published only very recently. Therefore, the existing models that have been published or may be in clinical use have not yet been evaluated for this cancer site by the Precision Medicine Core of the AJCC. In the future, the statistical prediction models for this cancer site will be evaluated, and those that meet all AJCC criteria will be endorsed.
There are no recommendations for clinical trial stratification for other plasma cell disorders at this time.