Stanford School of Medicine

Surgical Pathology Criteria

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  • Clonal plasma cell proliferation that is immunophenotypically and cytologically identical to plasma cell myeloma, but manifests as localized disease

Diagnostic Criteria

  • Osseous plasmacytoma/solitary plasmacytoma of bone
    • Solitary lytic bone lesion consisting of clonal plasma cells
    • No evidence of plasmacytosis in other bone marrow sites or clinical features of plasma cell myeloma (renal insufficiency/ anemia/ hypercalcemia/ additional lesions on skeletal survey)
  • Extraosseous plasmacytoma
    • Extraosseous/extramedullary mass of neoplastic plasma cells
    • No evidence of plasmacytosis in other bone marrow sites or clinical features of plasma cell myeloma (renal insufficiency/ anemia/ hypercalcemia/ additional lesions on skeletal survey)

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

  • Flow cytometry or immunohistochemical studies to establish plasma cell differentiation and light chain monoclonality, as for plasma cell myeloma
    • Hematolymphoid markers
      • CD45 absent or dim in >99%
    • B cell and plasma cell markers
      • CD138 >99%
      • CD38 >99%
      • CD79a, most
      • CD20 variable, often absent
      • CD19 variable, often absent
      • CD56 up to 80% -- aberrant antigen
      • Cytoplasmic kappa or lambda light chain by flow cytometry, in situ hybridization, or immunohistochemistry
  • Useful Laboratory Tests
    • Serum or urine protein electrophoresis, immunofixation, light chain quantification
    • Quantitation and typing of monoclonal immunoglobulin / light chain
    • 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

Differential Diagnosis

Plasmacytoma Myeloma
Single osseous or extraosseus lesion Lytic bony lesions
No increase away from lesion Usually increased plasma cells on random bone marrow biopsy
No end-organ damage May have end-organ damage

Plasmacytoma / Myeloma Reactive Plasmacytosis
Light chain restriction by flow cytometry, immunohistochemistry or in situ hybridization No light chain restriction

Plasmablastic Lymphoma Anaplastic (Plasmablastic) Plasmacytoma/Myeloma
Plasmablastic morphology Subset plasmablastic
Often HIV+ or otherwise immunosuppressed Usually not immunosuppressed
Often in oral cavity or mucosal areas of head Extraosseous sites overlap
~60% EBV+ usually EBV negative
Plasmacytoma and plasmablastic lymphoma have the same immunophenotype, other than EBV and are generally separated based on clinical grounds

Plasmacytoma / Myeloma Lymphoplasmacytic Lymphoma and Nodal, Extranodal and Splenic Marginal Zone Lymphomas
Plasma cells may be pleomorphic or plasmablastic Plasma cell component usually not markedly atypical
Uniform plasma cell morphology Plasma cells mixed with small lymphocytes
IgG or IgA M component most common IgM or IgG M component most common
CD20 often negative CD20 80%
Uniformly CD138 positive Scattered CD138 positive cells
Often CD56+, CD19-, CD45- CD56-, CD19+, CD45+

ALK Positive Large B Cell Lymphoma Plasmacytoma
ALK positive ALK negative
Often involves nodes in sinusoidal pattern No sinusoidal node involvement
Usually presents with adenopathy without lytic bone lesions Usually presents with lytic bone lesions without adenopathy
No M component May have M component
May show ALK-clathrin translocation t(2;17)(p23;q23) Lacks this translocation
Both may have basophilic cytoplasm with a perinuclear hof

Primary Effusion Lymphoma Plasmacytoma
HHV8 positive HHV8 negative
EBV in situ positive EBV in situ infrequently positive
Most patients HIV positive No significant HIV predilection
Usually presents as malignant effusion Usually presents as lytic bone lesion
PEL may rarely occur outside of body cavities; both may have plasmablastic appearance


  • About 5% of plasma cell neoplasms each are osseous and extraosseous plasmacytomas
  • Younger age at onset than overt myeloma
  • Lack anemia, hypercalcemia, and renal impairment
  • Osseous sites variable
    • 50% involve spine as a single lesion
  • Extraosseous sites variable
    • Most in oropharynx / nasoopharynx
    • Minority may involve draining nodes
  • Myeloma develops in 2/3 of osseous plasmacytoma patients
  • Myeloma develops in 15% of extraosseous plasmacytoma patients

Grading / Staging / Report

  • Grading is not applicable
  • Staging is not applicable

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



Plasma cell neoplasms / Immunosecretory disorders (WHO 2008)


  • 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
  • Chang ST, Liao YL, Lu CL, Chuang SS, Li CY. Plasmablastic cytomorphologic features in plasma cell neoplasms in immunocompetent patients are significantly associated with EBV. Am J Clin Pathol. 2007 Aug;128(2):339-44.
  • Greipp PR, Leong T, Bennett JM, Gaillard JP, Klein B, Stewart JA, Oken MM, Kay NE, Van Ness B, Kyle RA. Plasmablastic morphology--an independent prognostic factor with clinical and laboratory correlates: Eastern Cooperative Oncology Group (ECOG) myeloma trial E9486 report by the ECOG Myeloma Laboratory Group. Blood. 1998 Apr 1;91(7):2501-7
  • Martin W, Abraham R, Shanafelt T, Clark RJ, Bone N, Geyer SM, Katzmann JA, Bradwell A, Kay NE, Witzig TE. Serum-free light chain-a new biomarker for patients with B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia. Transl Res. 2007 Apr;149(4):231-5.
  • Raja KR, Kovarova L, Hajek R.Review of phenotypic markers used in flow cytometric analysis of MGUS and MM, and applicability of flow cytometry in other plasma cell disorders. Br J Haematol. 2010 Mar 1. [Epub ahead of print]
  • Van Camp B, Durie BG, Spier C, De Waele M, Van Riet I, Vela E, Frutiger Y, Richter L, Grogan TM. Plasma cells in multiple myeloma express a natural killer cell-associated antigen: CD56. Blood. 1990 Jul 15;76(2):377-82.
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