Osteosclerotic Myeloma

Definition

• Plasmacytoma with osteosclerosis accompanied by clinical POEMS syndrome and lymph node changes resembling plasma cell variant of Castleman disease

Alternate/Historical Names

• POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes)
• Multicentric Castleman disease
• Crowe-Fukase syndrome

Diagnostic Criteria

• Osteosclerotic plasmacytoma
  • Plasma cells entrapped in fibrosis
  • Thickened trabecular bone
  • Usually lambda light chain restricted
  • Usually does not meet criteria for classical myeloma
    • Bone marrow plasmacytosis usually <5-10%, if present
    • Serum M protein usually <3.5 g/dL, if present
    • Bence Jones protein usually <1 g/24hr, if present
• Lymph nodes may show changes of multicentric plasma cell type Castleman disease
  • Reactive follicular hyperplasia
  • Interfollicular plasmacytosis
  • Some follicles with hyaline vascular changes
• Clinical findings of POEMS syndrome present
  • Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes
• Serum VEGF often markedly elevated
  • (Under consideration as a diagnostic criterion)

Dita Gratzinger MD PhD

Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Initial posting/updates : 9/1/07, 4/15/10

Supplemental studies

• Clonal plasma cells can be demonstrated by flow, immunohistology or in situ hybridization
  • Usually lambda light chain
  • Bone marrow plasmacytosis usually <5-10%, if present

Useful Laboratory Tests

• Serum or urine protein electrophoresis, immunofixation, light chain quantification
  • Serum M protein usually <3.5 g/dL, if present
  • Bence Jones protein usually <1 g/24hr, if present
• Quantitation and typing of monoclonal immunoglobulin / light chain
  • Usually IgA or IgG lambda
• Serum free light chain analysis may be required to demonstrate clonal light chains
• These studies may be used to
  • Establish presence of a monoclonal plasma cell population
  • Quantitation helps subtype the plasma cell dyscrasia (i.e. >3g/dL serum monoclonal protein is a major criterion for myeloma)
  • Track disease burden over time
• Serum VEGF often markedly elevated

Differential Diagnosis

Osteosclerotic Myeloma	Myeloma	Plasmacytoma
Osteosclerotic lesion	Osteolytic lesions	Osteolytic lesion
<5% plasma cells	usually >> 5% plasma cells	< 5% plasma cells
POEMS syndrome present	No POEMS syndrome	No POEMS syndrome
Castleman like node changes may be present	No Castleman changes	No Castleman changes

Hematolymphoid Disorders with Marrow Fibrosis (overview)

Disorder	Distinguishing Feature(s)
Polycythemia Vera, Fibrotic Phase	History of PV / JAK2+
Essential Thrombocythemia, Fibrotic Phase (rare)	History of ET / may be JAK2+
CML, Fibrotic Phase	History of CML / BCR-ABL1+
MDS with Fibrosis	Dysplastic features in marrow
Acute Megakaryoblastic Leukemia	Blasts, acute onset
Osteosclerotic Myeloma	Plasma cells. light chain restricted
Acute Pan-myelosis with Myelofibrosis	Bone pain, acute onset
Primary Myelofibrosis	Clustered atypical megakaryocytic hyperplasia
Hairy cell leukemia	Clonal B cells

MDS with Fibrosis = descriptive term that includes primary MDS (often RAEB2) with fibrosis and therapy related myeloid neoplasms with fibrosis

Clinical

• Rare, apparently more prevalent in Japan
• Median age 50 years
• May be associated with HHV8 in setting of multicentric Castleman disease
• Signs and symptoms of POEMS syndrome
  • Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes
  • Occasional findings
    • Edema/effusions/ascites, papilledema, clubbing
    • Thrombocytosis, polycythemia
    • Bone pain, fatigue
• Better prognosis than usual myeloma
  • Median survival >14 years

Grading / Staging / Report

• Grading is not applicable

Durie-Salmon Staging System

• Stage I
  • Hemoglobin >10 g/dL
  • Serum IgG <5 g/dL
  • Serum IgA <3 g/dL
  • Normal serum calcium
  • Urine monoclonal protein excretion <4 g/day
  • No generalized lytic bone lesions
• Stage II
  • Intermediate between stage I and III
• Stage III
  • Hemoglobin <8.5 g/dL
  • Serum IgG >7 g/dL
  • Serum IgA >5 g/dL
  • Serum calcium >12 g/dL
  • Urine monoclonal protein excretion >12 g/day
  • Advanced lytic bone lesions

The pathology report should contain the following information:

• Diagnosis in the World Health Organization (WHO) classification
  • Equivalent diagnosis in other classifications used by relevant clinicians
• Results of supplementary studies if performed
• Relationship to other specimens from the same patient
• Information relevant to staging if available

Lists

Plasma cell neoplasms / Immunosecretory disorders (WHO 2008)

• Monoclonal gammopathy of undetermined significance (MGUS)
• Plasma cell myeloma
  • Variants:
    • Non-secretory
    • Smoldering
    • Plasma cell leukemia
• Plasmacytoma
  • Solitary plasmacytoma of bone
  • Extraosseus (extramedullary) plasmacytoma
• Monoclonal immunoglobulin deposition diseases
  • Primary amyloidosis
  • Systemic light chain and heavy chain deposition diseases
• Osteosclerotic myeloma (POEMS syndrome)
• Heavy chain diseases (variants of lymphoma rather than plasma cell neoplasms)
  • Gamma heavy chain disease (see lymphoplasmacytic lymphoma)
  • Mu heavy chain disease (see chronic lymphocytic leukemia)
  • Alpha heavy chain disease / immunoproliferative small intestinal disease (variant of extranodal marginal zone lymphoma)

Bibliography

• Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW . WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, International Agency for Research on Cancer, Lyon, 2008
• Warnke RA, Weiss LM, Chan JKC, Cleary ML, Dorfman RF . Tumors of the Lymph Nodes and Spleen, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 14, 1995
• Dispenzieri A.POEMS syndrome. Blood Rev. 2007 Nov;21(6):285-99.