IP Archives of Cytology and Histopathology Research

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Get Permission Sheik, Krupal Variganji, Renuka Inuganti, Uppala, and Meghana Bolla: Clinico-hematological profile of multiple myeloma in a teaching hospital - A 2 year study


Introduction

Multiple myeloma is a clonal malignant neoplasm of plasma cells originating in the bone marrow along with the presence of monoclonal immunoglobulin in the blood and or urine associated with end-organ damage. It accounts for 1% of all malignant tumors, 10 -15% of all hematologic malignancies, and 20% of deaths from hematological malignancies.1 Multiple myeloma is a disease of the elderly, with a peak age of 60-70 years at presentation.2 It is more common in males when compared to females.3 The etiology of the disease remains poorly understood. Certain etiological risk factors like ionizing radiation, pesticides, benzene, arsenic, carbon monoxide have been mentioned in the literature.4 There is marked variability in the clinical features seen in patients with multiple myeloma from healthy patients to those presenting with generalized weakness, bone pains, fever, infections, anemia. In some patients, complications like renal failure, pathological fractures, and lytic bone lesions may lead to significant morbidity and mortality. The study aims to find out the incidence of multiple myeloma and to study the clinico-hematological profile along with radiological features.

Materials and Methods

The present study was done both retrospectively and prospectively in 26 patients of multiple myeloma diagnosed over a period of 2 years from June 2017 to June 2019 in our teaching hospital. All newly diagnosed patients of Multiple Myeloma with relevant data during the above mentioned period were collected from the records and included in the study. Patients under remission were excluded from the study. A detailed history was taken, and clinical examination was performed. Hematological investigations like Hemoglobin estimation (Hb), Total and differential counts, Erythrocyte sedimentation rate (ESR), platelet count, peripheral blood smear, and bone marrow examination were done. Serum protein electrophoresis was done, and urine was examined for Bence Jones Proteinuria. Radiological investigations included X-ray, imaging studies like magnetic resonance imaging, and data was noted. For evaluation of each case, Revised International Myeloma Working Group criteria were applied. As per the revised International Myeloma Working Group criteria, the diagnosis of multiple myeloma requires the presence of one or more myeloma defining events (MDE) in addition to evidence of 10% or more clonal plasma cells on bone marrow examination or biopsy-proven plasmacytoma. MDE consist of established CRAB features (hypercalcemia, renal failure, anemia, or lytic bone lesions) as well as three specific biomarkers clonal bone marrow plasma cells ≥ 60%, serum-free light chain ratio ≥ 100and more than one focal lesion on magnetic resonance imaging (MRI).5

Out of 26 patients,15 were males (57%), and 11 were females (43%) with male preponderance, as shown in Table 1. The sixth decade was the most common age group at presentation in both the genders. The mean age at presentation in our study population was 60 years with a range of 41-74 years as shown in Table 1 .

Table 1
Age group(years) Male (%) Female (%) Total (%)
<40 0 0 0
41-50 2(33%) 4(66%) 6(23%)
51-60 4(66%) 2(33%) 6(23%)
61-70 8(66%) 4(33%) 12(46%)
>70 1(50%) 1(50%) 2(8%)
Total 15(57%) 11(43%) 26

Age and Gender wise distribution of patients

Common clinical presentations were fever (50%), bone pains (42%), and generalized weakness (42%), as shown in Table 2.

Table 2
Clinico-hematological manifestation No. of patients Percentage
Anaemia 18 70%
Fever 13 50%
Bone pains 11 42%
Generalised weakness 11 42%
Renal impairment 9 35%
Pathological fracture 1 4%

Clinico-hematological manifestations

Other rare presentations include decreased urine output, fractures, backache, shortness of breath and motor weakness of lower limbs. Clinical examination revealed pallor, bony tenderness and swelling, hepatomegaly, splenomegaly, and pedal edema. Hematological features were anemia in 18 patients (70%) as shown in Table 2. The mean hemoglobin concentration was 7.8g/dl with a range of 4.7-13.9 g/dl. ESR was elevated in 19 patients (73%). Rouleaux formation was observed in 15 patients (57%) Figure 1.

Figure 1

P.S showing rouleaux formation, Leishman stain, 400x

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White blood cell count was less than 5000 cells/mm3 in 9 patients (35%), platelet count was less than 1 lakh/mm3 in 7 patients(27%) and more than 4 lakh/mm3 in 1 patient(4%). Serum creatinine of more than 2 mg/dl was seen in 9 patients (35%) at presentation and hypercalcemia was observed 32% of patients. All patients had the presence of M band in the gamma region on serum electrophoresis. 27% of patients had urinary Bence Jones protein -positive as shown in Table 3.

Table 3
Investigations Result Percentage
E.S.R elevated 73%
Peripheral smear Rouleaux formation 57%
Serum Creatinine >2 mg/ dl 35%
Serum Calcium >12 mg/dl 32%
Serum electrophoresis M band in gamma region 100%
Urine Bence Jones Protein Positive 27%

Investigations

Result

Among skeletal involvement, 19 patients had osteolytic lesions (73%) on radiological investigations, and one patient had a pathological fracture (4%). Spine was the most frequent site of involvement (63%) Figure 2 followed by ribs and pelvis(27%) and skull(10%), as shown in Table 4.

Figure 2

CT Chest showing lytic lesions in the vertebral body

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Table 4
Osteolytic lesions No. of patients Percentage
Spine 12 63%
Ribs and pelvis 5 27%
Skull 2 10%
Total 19 73%

Radiological survey

On bone marrow examination, more than 70% of plasma cells in 6 patients (23%), 1 patient (4%) had 50% of plasma cells, 10 patients (38%) had plasma cells in the range of 30-50%, 9 patients (35%) had plasma cells in the range of 10-30% as shown in Table 5.

Table 5
% of plasma cells No.of patients % of patients
10-30 9 35%
30-50 10 38%
50-70 1 4%
>70 6 23%

Bone Marrow Examination (% of plasma cells)

Bone marrow aspiration smear characteristically showed a high percentage of plasma cells with binucleation, Russell bodies and Mott cells Figure 3,Figure 4,Figure 5.

Figure 3

B.M.A showing plasma cells, Leishman stain, 400x

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Figure 4

B.M.A showing plasma cells and mott cell, Leishman stain, Oil immersion

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Figure 5

B.M.A showing binucleated plasma cell, Leishman stain, oil immersion

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Bone marrow biopsy showed sheets of plasma cells also with binucleation and multinucleation Figure 6.

Figure 6

B.M.B showing sheets of plasma cells, H & E stain, 400x

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Discussion

Multiple myeloma is a bone marrow based, multifocal neoplastic proliferation of plasma cells, usually associated with an M protein in serum and urine or either one and evidence of organ damage related to the plasma cell neoplasm. Multiple myeloma is mainly seen in people over the age of 60 years. The age group included in our study ranged from 41-74 years, with a mean age of 60 years. The commonest age group at presentation was the 6th decade, which is similar to studies done by Diwan et al.2 and Mohanty et al.6

The majority of the patients in our study were males with a Male to Female ratio of 1.3:1. Similarly, Sagale et al.3 Sultan et al.7 and Odunukwe et al.8 found that multiple myeloma is more common in males. This finding is in discordance with a study done by Vahini et al., which showed female preponderance.9

The most common clinical manifestation at the time of presentation was fever (50%), followed by bone pains (42%) and generalized weakness (42%) in our study. This finding is in discordance with other studies where bone pains are the most common clinical manifestation.2,3,9

The majority of the patients were anemic (73%). This finding is comparable to other studies.2,3,9,10 In our study, nine patients (35%) had hemoglobin below 7g/dl, which is similar to the study done by Mohanty et al.6 and Kyle et al.11 The proposed mechanism of anemia in most is inadequate red blood cell production due to either erythropoietin deficiency from the accompanying renal failure or replacement of the marrow by myeloma cells.

Persistent kidney dysfunction in multiple myeloma was most commonly caused by tubular nephropathy due to monoclonal immunoglobulin secreted by plasma cells.12 Renal impairment was present in 35% of cases in our study. The incidence of renal involvement is slightly higher in studies conducted by Dawson et al. and Kyle et al., who have found an incidence of 45% and 55%, respectively.13

Hypercalcemia was found in 32% of patients in our study, which is comparable to the study done by Vahini et al.9 and Todaro et al.14

In our study, 73% of patients had osteolytic lesions showing varied skeletal involvement in radiological investigations. Bone disease in multiple myeloma results in severe bone pain, pathological fractures, and hypercalcemia. Multiple myeloma bone lesions arise from altered bone remodeling due to both increased osteoclast activation and decreased osteoblast differentiation.15 Bone involvement in our study is in concurrence with the study conducted by Todaro et al,14 who found 74% of patients of multiple myeloma had osteolytic lesions.

In our study, all cases demonstrated M band on serum electrophoresis in the gamma region similar to the study done by Vahini et al.9

27% of patients in our study had urinary Bence Jones protein -positive, which is comparable to the study done by Diwan et al.2

Conclusion

Multiple myeloma is a disease with variable clinical presentation with the involvement of various organ systems. The clinico-hematological features are comparable to previously published data. It is most common in the 6th decade with slight male preponderance. The most frequent clinical presentation in our study is fever, followed by bone pains and generalized weakness with anemia as the most frequent hematological manifestation. Multiple myeloma should be considered as a differential diagnosis in an elderly patient presenting with various clinical presentations like infections, pathological fracture, generalized weakness, back ache, renal impairment, and unexplained anemia.

Conflict of interest

None

Source of funding

None

References

1 

R W Mckenna R A Kyle M A Kuehl N L Harris R W Coupland F Fend J Thiele S H Swerdlow E Campo N L Harris E S Jaffe S A Pileri H Stein Plasma cell neoplasmsWHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition)IARCLyon2017243248

2 

A G Diwan S A Gandhi K Krishna V P Shinde Clinical profile of the spectrum of multiple myeloma in a teaching hospitalMed J Dr. DY Patil Univ201472185188

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M S Sagale D P Dangmali S R Rane K K Kulkarni S C Puranik Clinico-hematological profile of multiple myeloma in tertiary care Hospital PuneIndian J Basic and Applied Med Res-Diagnostic res special issue2017622530

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C Gerecke S Fuhrmann S Strifler M Schmidt-Hieber H Einsele S Knop The diagnosis and treatment of multiple myelomaDtsch Arztebl Int2016113470476

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S V Rajkumar Multiple myeloma: 2016 update on diagnosis, risk-stratification, and managementAm J hematolo2016917719753

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P K Mohanty D K Patel R Nanda R S Panda Multiple myeloma: Review of 21 cases with special reference to associated illnesses in a referral center in Western OrissaIndian Pract200457285289

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S Sultan S M Irfan S Praveen H Ali M Basharat Multiple Myeloma: A retrospective analysis of 61 patients from a tertiary care centerAsian Pac J Cancer Prev201617418331835

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N N Odunukwe J A Madu O E Nnodu T S Akingbola I M Asuquo M T Balogun Multiple myeloma in Nigeria: a multi-center epidemiological and biomedical studyPan Afr Med J2015221

9 

Gudeli Vahini Renuka Inuganti Venkata Piddakala Premalatha Vaddanti Tejaswini Krishna R Clinicopathological spectrum of multifaceted myeloma with varied presentationsInt J Recent Trends in Sci Technol2015143709712

10 

N Sutandyo E Firna J Agustina N Prayogo L Widjaja Clinicopathology Profile and Bone Involvement of Multiple Myeloma Patients in Dharmais National Cancer HospitalIndonesia. Asian Pac J cancer prev2015161562616265APJCP

11 

R A Kyle M A Gertz T E Witzig J A Lust M Q Lacy A Dispenzieri Review of 1027 patients with newly diagnosed multiple myelomaMayo Clinic Proceedings2003782133Elsevier

12 

D Katagiri E Noiri F Hinoshita Multiple myeloma, and kidney diseaseThe Sci World J201319

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P Yadav M Cook P Cockwell Current trends of renal impairment in multiple myelomaKidney Diseases201514241257

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J Todaro J Bigonha D M Borducchi L L Matos D C Trufelli S M Sales Multiple myeloma: five-year experience at a University HospitalEinstein (So Paulo)201192145150

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H Irisawa Bone disease in multiple myelomaNihon Rinsho20157314246



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305-309


Authors Details

Naseeruddin Sheik, Sandhya Krupal Variganji, Venkata Renuka Inuganti, Pravallika Uppala, Phani Meghana Bolla


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