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Indian Journal Pathology and Microbiology


Year : 2008 | Volume : 51 | Issue : 4 | Page : 543-545

Multiple myeloma presenting with coexisting severe marrow hypoplasia

K Medhi, Dipti Kalita, Anita Chopra, Mona Anand, Vinod Raina, Rajive Kumar
Laboratory Oncology Unit, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110 029, India

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A 68-year-old man was referred to us with clinical and bone marrow (BM) features compatible with aplastic anemia. The correct
diagnosis, hypoplasia of the BM coexisting with multiple myeloma, became apparent after noting rouleaux in the peripheral blood
(PB) and approximately 50% plasma cells in the touch imprint of one of the two BM biopsies done. As standard therapy was
precluded, the patient was put on dexamethasone but died within 4 days. This first case of the coexistence of untreated myeloma
with aplastic BM shows that even apparently straightforward hypoplasia seen on the BM biopsy should be interpreted in conjunction
with the PB smear and the BM touch imprint findings. Among other things, the BM biopsy and imprint should be repeated if the PB
has findings such as rouleaux that do not fit with straightforward aplastic anemia. The combination of myeloma and BM aplasia
precludes standard therapy and is rapidly fatal.

Keywords: Hypoplastic bone marrow, multiple myeloma

How to cite this article:

Medhi K, Kalita D, Chopra A, Anand M, Raina V, Kumar R. Multiple myeloma presenting with coexisting severe marrow
hypoplasia. Indian J Pathol Microbiol 2008;51:543-5

How to cite this URL:

Medhi K, Kalita D, Chopra A, Anand M, Raina V, Kumar R. Multiple myeloma presenting with coexisting severe marrow
hypoplasia. Indian J Pathol Microbiol [serial online] 2008 [cited 2017 May 12];51:543-5. Available


Multiple myeloma is one of the causes of bone marrow (BM) failure. Failure of hematopoiesis in myeloma may result from the
replacement of normal hematopoietic tissue by plasma cells, it may be cytokine mediated, it may be due to fas ligand mediated
apoptosis, or it may be the result of renal-failure-induced erythropoietin deficiency. [1],[2],[3] Bone marrow failure due to marrow
hypoplasia, to the best of our knowledge, has not been described in untreated myeloma. In this article, we report the diagnostic and
therapeutic issues pertaining to multiple myeloma presenting with coexisting severe marrow hypoplasia.

Case Report

A 68-year-old man presented with progressive weakness and decreased appetite for 6 months and constipation for 1 month. There
was no history of fever or bleeding from any site. There was no lymphadenopathy or organomegaly. In an earlier evaluation at
another hospital, the patient had been diagnosed with aplastic anemia based on pancytopenia and a severely hypocellular BM (<5%
cellularity). A BM touch imprint had been reported as showing megaloblastic erythroid hyperplasia. He had been given 20 units of
packed red cell transfusions. A bone marrow biopsy and touch imprint slides were made available for review.

The patient's hemoglobin level was 52 g/L, his total leukocyte count was 1.2 x 10 9 / L and his platelet count was 29 x 10 9 / L. The
differential leukocyte count revealed neutrophils 30%, lymphocytes 68%, and monocytes 2%. A peripheral blood (PB) smear
showed rouleaux formation and platelets were reduced. Blood chemistry revealed a random blood sugar of 134 mg/dl, uric acid of
6.1 mg/dl, total protein of 13.3g/dl, albumin of 2.1 g/dl, globulin of 11.2 g/dl, blood urea of 31 mg/dl, serum creatinine of 1.4 mg/dl,
calcium of 8.7 mg/dl, phosphate of 1.4 mg/dl, sodium of 126 m Eq/L, potassium of 3.9 mEq/L, SGOT 17 U/L, SGPT 17/L, alkaline
phosphatase 183 U/L, and LDH 212 U/L. The BM touch imprint was reviewed and found to be a cellular preparation of poor quality
but showed increased plasma cells, approximately 50%, including several abnormal forms, compatible with multiple myeloma. Bone
marrow biopsy, both the slides submitted by the referring hospital and another repeated in our hospital showed severely
hypocellular marrow (cellularity <5%) [Figure 1]. The rare cellular areas were constituted largely by lymphoid cells and plasma cells
including a few, discernible because of help provided by the touch imprint findings, as abnormal forms. Normal hematopoietic cells
were virtually absent [Figure 2]. The touch imprint corresponding to this biopsy was essentially acellular.

A high-resolution electrophoresis of serum showed a dense, sharp, and wide 'M' band in the gamma globulin region,
densitometrically 5.2 g/dl. Normal background polyclonal gamma globulin was reduced. Immunofixation on serum showed the 'M'
band to be IgG lambda. Urine electrophoresis showed an IgG lambda M band. Serum beta-2 microglobulin was 12,375 g/L, IgG
was 2670.0 mg/dl, IgA 21.0 was mg/dl, and IgM was 17.0 mg/dl. A skeletal survey showed no osteolytic lesions. The patient was
diagnosed with multiple myeloma, Stage IIIA with severe bone marrow hypoplasia.

Non myelosuppressive therapy was started with only dexamethasone pulses in the first cycle. It was planned to add thalidomide
later once his general condition improved. Unfortunately, the patient developed severe sepsis with disseminated intravascular
coagulation and multi-organ failure and died on day 4 of therapy before any response could be evaluated.


To the best of our knowledge, severely hypoplastic BM as a presenting feature of multiple myeloma has not been reported before
and is the reason for this article. This rare combination was of interest because of the diagnostic and therapeutic challenges it

The clinical presentation of severe pallor, absence of organomegaly, pancytopenia, and severely hypoplastic BM was compatible
with a diagnosis of aplastic anemia. This is what had been diagnosed at the referring hospital. After the case was reviewed at our
hospital, a repeat peripheral blood smear and BM examination showed the reason for the erroneous diagnosis and put us on the
right track. There was rouleaux formation in the peripheral blood smear, a reflection of the patient's raised serum gamma globulin
and total protein. This finding, not quite in keeping with aplastic anemia alone, should have aroused suspicion of the presence of
complicating factors. Additionally, in the first BM touch imprint, which was cellular, there were increased plasma cells that had been
misinterpreted as megaloblastic erythroid precursors. This made us look closely at the BM biopsy, which with its < 5% cellularity was
otherwise compatible with hypoplastic marrow. Had it not been for the lead provided by the peripheral blood and by the first touch
imprint, it would have been difficult to interpret the biopsy as anything other than straightforward hypoplastic marrow.
Our case reinforces the teaching that BM biopsies should preferably not be interpreted without taking into consideration touch
imprint and overall hematological parameters, especially the peripheral blood smear findings. Particularly in a case such as ours,
where the touch imprint is likely to be poorly cellular and non contributory, as indeed the imprint of the second BM biopsy was, the
peripheral blood smear changes can prove to be crucial.

Treatment-induced marrow failure in multiple myeloma is uncommon with the currently used chemotherapy. High-dose melphalan
without stem cell salvage is reported to be associated with prolonged severe thrombocytopenia and neutropenia. [4],[5] These
considerations, however, did not apply to our case and the reason for the co-existence of untreated myeloma and marrow aplasia
remained unclear. Such an association has, to the best of our knowledge, not been described before. Destruction of platelets due to
autoimmune phenomena is known in myeloma. [6] It is possible that in this case the monoclonal protein had a suppressive effect on
hematopoietic stem cells.

As with the diagnosis, management of our patient was difficult and needed considerations not relevant to most other patients of
myeloma. There were problems with both the short- and long-term treatment plans owing to severe hypoplasia of the marrow. Use
of alkylating agents in the first phase of treatment and high-dose chemotherapy with bone marrow autologous stem cell
transplantation in the second were both precluded. Even the starting therapy with the standard simultaneous administration of
thalidomide and dexamethasone had to be modified to begin with only dexamethasone with a plan to add thalidomide when the
general condition improved. Unfortunately, since the patient died within 4 days of the start of treatment, response to therapy in such
an uncommon setting could not be studied.

Our case shows that even an apparently straightforward hypoplastic BM should preferably be interpreted in conjunction with
peripheral blood and touch imprint findings. Presence of unexplained features such as rouleaux on the peripheral blood smear
should prompt a repeat BM biopsy and investigation for an underlying co-existing complicating factor. Also, the combination of BM
aplasia and myeloma precludes standard therapy and would invariably be rapidly fatal.


1. Bartl R, Frisch B, Burkhardt R, Fateh-Moghadam A, Mahl G, Gierster P et al. Bone marrow histology in myeloma: Its
importance in diagnosis, prognosis, classification and staging. Br J Haematol 1982;51:361-75.
2. Musto P, Falcone A, D'Arena G, Scalzulli PR, Matera R, Minervini MM, et al. Clinical results of recombinant erythropoietin in
transfusion-dependent patients with refractory multiple myeloma: Role of cytokines and monitoring of erythropoiesis. Eur J
Haematol 1997;58:314-9. [PUBMED]
3. Silvestris F, Cafforio P, Tucci M, Dammacco F. Negative regulation of erythroblast maturation by Fas-L (+)/TRAIL(+) highly
malignant plasma cells: A major pathogenetic mechanism of anemia in multiple myeloma. 2002;99:1305-13.
4. Selby PJ, McElwain TJ, Selby PJ, Nandi AC, Selby PJ, Perren TJ, et al.
5. McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet 1983;2:822-
6. Barlogie B, Shaughnessy, Epstein J, Sanderson R, Anaissie E, Walker R, et al. Plasma cell myeloma. In: Litchman MA,
Beutler E, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT, editors. Williams hematology. 7 th ed. New York: McGraw-Hill
Medical; 2006. p. 1508.

Correspondence Address:
Mona Anand
Laboratory Oncology, Institute Rotary Cancer Hospital, AIIMS, Ansari Nagar, New Delhi 110 029
Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.43756