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CASE REPORT Table of Contents   
Year : 2008  |  Volume : 51  |  Issue : 4  |  Page : 543-545
Multiple myeloma presenting with coexisting severe marrow hypoplasia

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 2022 Aug 16];51:543-5. Available from: https://www.ijpmonline.org/text.asp?2008/51/4/543/43756

   Introduction Top

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 Top

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.

   Discussion Top

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 presents.

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.

   References Top

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.  Back to cited text no. 1    
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.  Back to cited text no. 2  [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.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Selby PJ, McElwain TJ, Selby PJ, Nandi AC, Selby PJ, Perren TJ, et al.   Back to cited text no. 4    
5.McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet 1983;2:822-4.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
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.  Back to cited text no. 6    

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

DOI: 10.4103/0377-4929.43756

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