Article By

R. Mashelkar
Manjula R.
A. Dias
R. G. W. Pinto

Abstract
We report a case of plasma cell leukemia, occurring de novo, in a 46-year-old male. The clinical presentation, laboratory and histopathology features are discussed.

Keywords
Plasma cell leukemia, multiple myeloma

Introduction:
Plasma cell leukemia (PCL) is a rare and aggressive disorder, characterised by a malignant proliferation of plasma cells in the bone marrow and a concomitant peripheral blood involvement; accounting for 2% to 4% of all plasma cell dyscrasias. It is classified as a primary plasma cell leukemia, when it occurs de novo with no prior history of multiple myeloma and secondary plasma cell leukemia, occurring in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinico-pathological entity, with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration, with unsatisfactory response to therapy.[1]

Case report:

The patient is a 46-year-old male who had been regularly following up in the Medicine outpatient department with complaints of generalized weakness. He was being treated for dimorphic anemia with iron, folic acid, and Vitamin B complex tablets. He then suddenly presented to the Emergency department with a history of intermittent chest pain for 15 days which had worsened the same day and was now present even at rest. The chest pain was retrosternal, not associated with nausea, vomiting or sweating. He also complained of breathlessness while doing routine activities and a dry cough for the past 15 days. There was no history of breathlessness at rest, orthopnoea and paroxysmal nocturnal dyspnoea. He was admitted for further investigation of chest pain.

Electrocardiogram (ECG) did not show any significant abnormality. Echocardiography (ECHO) showed mild tricuspid regurgitation and mild pulmonary arterial hypertension. All routine investigations were done while the patient was admitted. A complete hemogram done showed haemoglobin of 7.8 mg/dl, total white blood cell count of 12,100/ml and a platelet count of 1,60,000/ml. Peripheral smear showed 52% of plasma cells with an eccentric nucleus and mild to moderate amount of cytoplasm; some showed prominent nucleoli (Figure 1); rouleaux formation was also seen (Figure 2). A diagnosis of plasma cell leukemia was made.

TC-July2017-007 - Peripheral smear showing plasma cells - Wright stain 40 x view

TC-July2017-008 - Peripheral smear showing rouleaux forrmation; Wright stain 10 x view

Patient was investigated further. The striking findings were serum calcium levels of 14.5 mg/dl, erythrocyte sedimentation rate (ESR) of 60 mm/hr, deranged renal function tests with blood urea levels of 317 mg/dl and serum creatinine levels of 7.0 mg/dl, serum phosphate levels of 7.3 mg/dl and serum uric acid levels of 10.1 mg/dl. Skeletal survey however, did not show any lytic lesions in the bones. Urine was also negative for Bence Jones Proteins. Creactive protein was normal. Serum electrophoresis was done which showed M band. A bone marrow aspiration was then done and sent to pathology department. Microscopic examination of the marrow smears revealed replacement of the marrow by a monotonous population of cells with eccentric nucleus and greyish blue cytoplasm, with a few binucleate cells and occasional plasma blasts (Figure 3).

TC-July2017-009 - Bone marrow aspiration smear showing replacement of marrow by a monotonous population of plasma cells

Normal bone marrow cells were suppressed. The findings were consistent with Multiple Myeloma. A final diagnosis of primary plasma cell leukemia was made. Two days later the patient developed a pneumonia and expired 5 days later.

LABORATORY EVALUATION:

Diagnosis of plasma cell leukemia requires a comprehensive history, physical examination, laboratory and radiological investigations.

  • Increased frequency of Bence Jones proteinuria, as an isolated proteinuria has been reported
  • Decreased levels of serum albumin
  • Increased serum lactate dehydrogenase levels
  • Increased beta-2 micro globulin (>6 mg/l)
  • Increased serum calcium and creatinine levels.

Primary plasma cell leukaemia involves more extensive bone marrow infiltration often with plasma blastic cytomorphology. Patients with secondary plasma cell leukemia have laboratory abnormalities that are similar to those of primary plasma cell leukemia except that renal impairment is more in patients with primary plasma cell leukemia.[2]

Considerable overlap of immunophenotypic markers exists between multiple myeloma and plasma cell leukemia. However significant differences in antigen expression have been identified which help to differentiate the two variants.

TC-July2017-010 - Table 1 - Typical antigen expression as follows

CD 28 is more frequently expressed on malignant plasma cells in secondary than in primary ; which is consistent with an observation made in myeloma i.e. that acquisition of the CD 28 antigen on plasma cells appear to correlate with an increased proliferative rate and disease progression. By comparative genomic hybridization and by FISH techniques, losses of 13q and monosomy 13 are seen in >80% cases of plasma cell leukemia.

Over expression of Cyclin D1 plays an important role in controlling the cell cycle in plasma cell leukemia.

TREATMENT AND PROGNOSIS

The overall prognosis is extremely poor with significantly worse outcome for patients with secondary disease. Although primary plasma cell leukemia may respond to treatment, they have a median survival of 8 months. On the other hand, secondary plasma cell leukemia is a resistant, rapidly progressive and fatal disease with median survival rate of 2 months.

Alkalyting agents in higher doses and steroids have also been used for the treatment. Allogenic stem cell transplantation is an option in many patients.[3] 

Discussion:

Plasma cell leukemia is a rare disorder, accounting for 2-4% plasma cell dyscrasias. By definition there should be >/=20% plasma cells in the peripheral blood or an absolute plasma cell count >/=2×109 /L (Kyle’s criteria).

The presentation may be primary, occurring de novo (60%-70%) or secondary evolving from an existing case of multiple myeloma as a part of the terminal phase of the disease.[4]

Plasma cell leukemia occurs in patients with multiple myeloma and is seen more frequently in light chain only, IgE, IgD myeloma and less frequently in IgG and IgA myeloma. The median age of patients is 50-60 years with an equal incidence in males and females. Clinical presentation of Plasma cell leukemia is more aggressive than that of multiple myeloma with a higher presenting tumour burden and higher frequencies of extra medullary involvement, anaemia, thrombocytopenia, hypercalcemia, renal impairment, increased levels of serum lactate dehydrogenase, beta-2 microglobulin and plasma cell proliferative activity. The incidence of lytic lesions is slightly lower than that usually observed in multiple myeloma.[5]

Though the clinical and laboratory features of primary and secondary plasma cell leukemia are similar, the response to therapy and overall survival in primary plasma cell leukemia goes from poor to worse.

Priyanka Raghuvir Mashelkar, M.B.B.S Post-graduate student Email: priyankamashelkar1703@gmail.com Manjula R., M.B.B.S Post-graduate student Email: manjular98@yahoo.com Avril Dias, M.B.B.S.,M.D. Associate Professor Email: avrildias@gmail.com R. G. W. Pinto, M.B.B.S, M.D., D.N.B, MNAMS, MIAC Professor and Head Department of Pathology Goa Medical College Bambolim Goa Email: wisemanpinto@yahoo.com

References:

1.  Fernandez de Larrea C, de Larrea; Kyle RA, Durie BG, et al. Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations, by the International Myeloma Working Group (IMWG). Leukemia 2013;27(4):780-91.

2.  Blade J, Kyle RA. Non-secretory myeloma, immunoglobulin D myeloma and plasma cell leukemia. Haematol Oncol Clin North Am.1999;13:1259-127.

3.  Garcia Sanz R, Orfao A, Gonzales M, et al. Primary plasma cell leukemia: clinical, immunophenotypic DNA ploidy and cytogenetic characteristics. Blood. 1999;93;1032-1037.

4.  Hageman SR, Fonseca R. Plasma cell leukemia. Current treatment options in oncology 2001;1;205-216.

5.  Greer JP, Foerster J, et al. Wintrobes clinical haematology; Volume 2. 12th Edition.2008. Wolters Kluwer/Lippincott Williams & Wilkins. p 241.