Biclonal gammopathy extramedullary disease multiple myeloma case presentation

1. Dr. / Marwa Mahmoud Khalifa
Internal Medicine & Hematology Specialist
Damanhour Oncology Centre
Biclonal Gammopathy :
Lymphoma Vs Myeloma

2.  50-year-old female patient, housewife
married with 3 offspring from Damanhour,
with no past history of any chronic disease
(diabetes, hypertension, cardiac, hepatic or
renal).
 She reported menorrhagia 6m ago that was
relieved after removal of the IUD at that time
her HB was 6 gm/dl and received 2 packed
RBCs, then was shifted to parenteral iron
supplementation , but she developed allergic
reaction in the form of skin rash.

3. • 3 months later she started to complain from
multiple swellings in her neck , both axillae and
groin rapidly increasing in size and unintentional
weight loss.
• The patient denied B-symptoms (i.e fevers, chills
or night sweats).
• Diffuse bone pains especially over her Rt. hip
joint.
• Tingling sensation and burning pain over her
upper and lower limbs.

4. Physical Examination
• She was pale, morbidly obese (140 kg )
• Macular eruption over both lower limbs
• Chest examination: decreased air entry
bilaterally
• Hepatosplenomegaly with no ascites
• Generalized lymphadenopathy (cervical,
axillary, inguinal) firm , non tender

5. Lab Investigations
• CBC: microcytic, hypochromic anemia Hb 9.7gm/dl
, normal platelet count, leucocytosis 26.6*106/L
mainly neutrophils 18 *106/L
• Urea 37mg/dl, creatinine 0.9 mg/dl
• Uric acid 8.4 mg/dl
• Total calcium 8.8mg/dl
• Ferritin 124.4 ng/ml, transferrin saturation 21.4%
• ALT, AST, Bilirubin : within normal range
• HBs Ag, HCV Ab : negative

6. RBCs show rouleux formation at peripheral blood smear

7. CT scan of neck , chest, abdomen
and pelvis with IV contrast

9. • Excisional lymph node biopsy was done,
showed atypical lymphoid proliferation ?? For
immunohistochemistry which is pending

10. BMA & biopsy
• Diluted bone marrow aspiration

11.  Hypercellular BM with adequate megakaryopoiesis,
depressed erythropoeisis and graulopoiesis
 Infilteration with medium to large size mononuclear
cells

13. IHC for CD20
Negative CD20

14. IHC for CD38
Positive CD38

15. IHC for CD138
Positive CD138

16. SPEP
Decreased albumin , increase in gammaglobulin region with 2
monoclonal bands (biclonal gammopathy)

17. Serum Immunofixation
2 monoclonal bands:IgG Kappa type, IgG Lambda type

18. • β2 microglobulin : 15.3 mg/l
• Skeletal survey is pending

19. The Diagnosis

21. • MM represents 13% of all haematologic
malignancies affecting mainly the elderly,
median age at diagnosis is 65 .
• Better imaging techniques increased the
incidence of extramedullary disease (EMD) in
MM, an aggressive, mostly resistant entity
with poor prognosis for patients.
Todorovic, Z., Jovanovic, M., Todorovic, D., Ivosevic, A., Marković, M., Radovanovic, D., Djurdjevic, P. (2017).
Extramedullary Involvement of Lymph Nodes in Multiple Myeloma. Serbian Journal of Experimental and Clinical
Research, 18, 257-261.

22. • EMD can be present at initial MM diagnosis
with an estimated incidence of 3–5% or it can
occur in relapsed/refractory patients with an
incidence of 6 to 20%.
• Among patients with EMD, male sex and
younger age is more common.
Jagosky, M. H., & Usmani, S. Z. (2020). Extramedullary Disease in Multiple Myeloma. Current Hematologic
Malignancy Reports, 15(2), 62-71.

23. • EMD develops because of ‘BM escape’ of a
subclone of PC. This subclone migrates out of
the BM infiltrating soft tissues losing
dependence on the BM microenvironment .
• Secondary changes in the escaping subclone,
such as more frequent TP53 mutations,
t(4;14) and del(13).
Sevcikova, S., Minarik, J., Stork, M., Jelinek, T., Pour, L., & Hajek, R. (2019). Extramedullary disease in multiple
myeloma – controversies and future directions. Blood Reviews, 36, 32-39.

24. Classification
• Bone-related plasmacytomas affecting the
axial skeleton (ribs, vertebrae, skull, sternum,
and pelvis), which originate from the
underlying BM through disruption of the
cortical bone. (EMD-B)
• EMD secondary to hematogenous spread to
soft-tissue with PC infiltration of an
anatomical site distant from the BM (mostly
liver, skin, CNS, pleural effusion, kidneys,
lymph nodes, and pancreas) (EMD-S)
Cyrille Touzeau, P. M. (2016). How I treat extramedullary myeloma. Blood, 127, 971-976.

25. • EMD is associated with more with light
chain/non secretory subtypes, advanced stage,
greater monoclonal spike, higher LDH, worse
anemia, thrombocytopenia, and renal function.
• EMD is a hallmark for worse prognosis,
independent of other high-risk factors with a
median OS of patients who experience an
extramedullary relapse is <6 months.
Jagosky, M. H., & Usmani, S. Z. (2020). Extramedullary Disease in Multiple Myeloma. Current Hematologic
Malignancy Reports, 15(2), 62-71.

26. Biclonal gammopathies are a rare group
characterized by the production of two distinct
monoclonal proteins. Approximately 1.5% of
multiple myeloma cases present with biclonal
paraproteinemia.
Banerjee A, Pimpalgaonkar K, Christy AL. A Rare Case of Multiple Myeloma with Biclonal Gammopathy. J Clin Diagn
Res. 2016;10(12):BD03-BD04.

27. • IgG and IgA as the most common biclonal pair
seen in >50% of biclonal gammopathies.
• The occurrence of two IgG monoclonal
components corresponds to 10% or less amongst
all cases of biclonal gammopathy. (Kyle et al.
6/57)
Sharma, S., Gupta, P., Aggarwal, R., Malhotra, P., Minz, R., & Bansal, F. (2019). Review Demystifying Biclonal
Gammopathy: A Pathologist's Perspective.

28. • This finding can result from either a
proliferation of two clones of plasma cells with
each producing an unrelated monoclonal
spike or from the production of two
monoclonal spikes by a single clone of plasma
cells.
Kancharla, P., Patel, E., Hennrick, K., Ibrahim, S., & Goldfinger, M. (2019). A Rare Presentation of Biclonal
Gammopathy in Multiple Myeloma with Simultaneous Extramedullary Involvement: A Case Report. Case Reports in
Oncology, 12(2), 537-542.

29. • D’Angelo et al. hypothesized that a neoplastic
clone may undergo a subsequent neoplastic
change not closely related to the first and a
new subclone may evolve with possibility of
different light chain rearrangement.
Pradhan, D., Arora, P., Gami, A., & Kaur, N. (2015). Immunoglobulin G kappa biclonal gammopathy associated with
multiple myeloma, plasmacytoma and cast nephropathy. J Cancer Res Ther, 11, 660.

30. • Several cases of isotype switching have been
reported in myeloma patients with biclonal
spikes.
• A case exhibited a shift from primarily IgG
with a minor IgD component to a
predominant IgD immunoglobulin production
after chemotherapy with findings revealing
neoplastic origin from a single clone of B-cells
Kancharla, P., Patel, E., Hennrick, K., Ibrahim, S., & Goldfinger, M. (2019). A Rare Presentation of Biclonal
Gammopathy in Multiple Myeloma with Simultaneous Extramedullary Involvement: A Case Report. Case Reports
in Oncology, 12(2), 537-542.

31. • It is not uncommon to see biclonal bands with
isotype switching on serum immunofixation
of post stem cell transplant patients and
those receiving immunosuppressive therapy.
• Franck et al. reported another case with
shift from a single paraprotein IgG Kappa
to a biclonal paraprotein IgG kappa and IgD
kappa.
Kancharla, P., Patel, E., Hennrick, K., Ibrahim, S., & Goldfinger, M. (2019). A Rare Presentation of Biclonal
Gammopathy in Multiple Myeloma with Simultaneous Extramedullary Involvement: A Case Report. Case Reports
in Oncology, 12(2), 537-542.

32. Biclonal gammopathy of unknown significance
(BGUS) may progress to either MM, SMM, LA
or WM with the dominant clone being the
principal player through the course of the
disease.
Mullikin TC, Rajkumar SV, Dispenzieri A, et al. Clinical characteristics and outcomes in biclonal
gammopathies. Am J Hematol. 2016;91(5):473-475.

33. Kyle et al. reported no difference in prognosis
between biclonal and monoclonal
gammopathy. However, recognition of this
existence helps in assessing treatment response
during follow-up
Mullikin TC, Rajkumar SV, Dispenzieri A, et al. Clinical characteristics and outcomes in
biclonal gammopathies. Am J Hematol. 2016;91(5):473-475.

34. Conclusion
• Our case report highlights an extremely rare clinical
presentation of lymph node and bone marrow
involved by biclonal multiple myeloma.
• Better imaging increased the incidence of EMD
conferring poor prognosis
• Biclonal gammopathy can have its origin from either
a single clone or two clones of plasma cells.
• Identification of biclonality not only helps us to be
precise but also will be helpful in guiding treatment
and to follow up response of both clones to treatment

35. THANK YOU