Original Research Article

Bone marrow examination findings in cases of pancytopenia- a study from central

India
Sandeep Ojha1,*, Amit Haritwal2, Farah J. Meenai3, Sonam Gupta4
1Assistant Professor, 2,3Associate Professor, 4Tutor, Dept. of Pathology, Chirayu Medical College & Hospital, Bhopal

*Corresponding Author:
Email: [email protected]

Abstract
Background and Objectives: Pancytopenia is one of the most common indications for bone marrow (BM) examination. There
are spectrums of condition involving the bone marrow (BM) that can present with pancytopenia and include malignant as well as
benign diseases. The objective of this study is to evaluate the BM findings in cases of pancytopenia.
Materials and Methods: This was a retrospective study of 156 cases of pancytopenia presenting over a period of 3 years. Data
were retrieved from laboratory and clinical records and were analysed.
Results: Out of 156 cases, the most common cause for pancytopenia in this study was megaloblastic anemia (25.6%), followed
by acute leukemia (16%), hypoplastic marrow (14%), metastatic solid tumors (8.9%), myelodysplastic syndrome (MDS) (7.1%),
lymphomas (5.7%), plasma cell dyscrasia(3.8%). Along with these there were many benign yet rare causes which may present
with pancytopenia like Hemophagocytic syndrome (1.2%), Histoplasmosis (0.6%), Leishmaniasis (0.6%) and Gaucher’s disease
(0.6%). Bone marrow examination (combining both aspirate and biopsy) alone was sufficient in diagnosing 55% of cases, while
remaining cases require additional details like clinical findings (for cases of MDS, viral infection, hypersplenism, autoimmune,
septicemia) and special investigations like hemoglobin electrophoresis for hemoglobinopathy. In only 3.8% cases, BME was
inconclusive.
Conclusion: BME is an important investigation in diagnostic work up of cases of pancytopenia. In majority of cases, it can
provide an accurate diagnosis or at least can guide the approach towards diagnosis and management. Thus, it should be
performed in all cases of persistent pancytopenia and should be evaluated in light of clinical details and supportive investigations.

Keywords: Pancytopenia, Bone marrow aspiration biopsy, Causes, Clinical presentation

Access this article online Bone marrow examination not only helps in final
Quick Response diagnosis but can also help in indicating the approach to
Code: Website: diagnosis based on various parameters like cellularity
www.innovativepublication.com (hypocellular or hypercellular), Blasts (for leukemias),
abnormal cells (lymphoma, plasma cells, carcinoma
cells, histiocytes), organisms (fungus, parasite),
DOI: dysplastic changes in cells (MDS) or megaloblastic
10.5958/2394-6792.2016.00089.2 maturation.
Correlation with bone marrow biopsy is also
important in cases where aspirate is hemodiluted or in
Introduction hypocellular marrows. Biopsy also helps in many
Pancytopenia is an important clinical entity which conditions which focally involve the bone marrow like
is defined as reduction in the number of all the three metastatic carcinomas or lymphomas or tuberculosis.
series (WBC’s, RBC’s and platelets) in peripheral This study is performed at a tertiary care centre and
blood1. medical college in India and is intended to look at BM
Pancytopenia is a clinical outcome of many findings in cases of pancytopenia so that one should
diseases that involve bone marrow either primarily or keep in mind various differentials that can present with
secondarily. Management of pancytopenia cases pancytopenia.
depends on the severity of pancytopenia and treatment
of the underlying pathology2. Materials and Methods
There are various mechanisms for development of This was a retrospective study performed at a
pancytopenia and this include reduced or ineffective tertiary care centre and medical college over a period of
hematopoiesis and increased destruction by either three years in Department of pathology. Laboratory
sequestration or destruction by antibodies3. data from all the cases who presented with
In cases of pancytopenias, patient usually presents pancytopenia (hemoglobin< 10gm/dl total leukocyte
with clinical features attributable to decreased number count < 4000/mm3 and platelet count /150,000/mm3)
of RBC’s, platelets or WBC’s i.e., pallor, easy were retrieved. Clinical details were obtained from
fatiguability, bleeding, weight loss, or repeated patient’s case file and was tabulated, analyzed and
infections leading to fever4. correlated with that of laboratory parameters. Cases of
Indian Journal of Pathology and Oncology, July-September 2016;3(3);479-484 479
Sandeep Ojha et al. Bone marrow examination findings in cases of pancytopenia- a study from central India

chemotherapy induced pancytopenia (whether benign ranged from 2 months to 70 years. Out of 156 cases of
or malignant) were excluded from this study. Bone pancytopenia, 41 patients (26.3%) were in pediatric age
marrow aspiration was performed from posterior group (<18 years) and remaining 115 patients (73.7%)
superior iliac spine. Slides were prepared and stained were adults (>18 years).
with leishman stain. Biopsy was processed as per Most common presentation (Table 2) was pallor
laboratory protocol for bone marrow. Special stains (70.5%) followed by fever (30.1%), splenomegaly
were performed wherever required. (23.1%), hepatomegaly (19.8%) and associated
lymphadenopathy (17.3%) while only 5.7% cases were
Results asymptomatic.
In our institute we receive a total of 610 bone Peripheral smear findings (Table 3) in most of the
marrow specimens over 3 year duration of which we cases show presence of anisocytosis (41%) followed by
studied around 156 cases who presented with lymphocytosis (32.1%), nucleated red blood cells
pancytopenia (Table 1). Male: female ratio was 1.6:1 (31.4%), and poikilocytosis (20.5%). Blasts were seen
with 97 males and 59 females. The age of the patients in 15.4% cases.

Table 1: Bone marrow aspiration findings in pancytopenia (n= 156)

Diagnosis Total number of cases Total
<18 year >18 year
Male Female Male Female
Megaloblastic anemia 6 4 20 10 40 (25.6%)
Acute leukemias 5 4 14 2 25(16%)
Hypoplastic marrow 8 1 5 8 22(14%)
Metastasis 1 0 7 6 14(8.9%)
Myelodysplastic syndrome 0 0 3 8 11(7.1%)
Lymphoma infiltration 0 0 8 1 9(5.7%)
Plasma cell dyscrasia 0 0 3 3 6(3.8%)
Viral 1 1 1 0 3(1.9%)
Hypersplenism 0 1 1 1 3(1.9%)
Autoimmune (ITP, SLE) 0 2 0 1 3(1.9%)
Hairy cell leukemia 0 0 2 0 2 (1.2%)
Haemophagocytic syndrome 0 0 2 0 2(1.2%)
Myelofibrosis 0 0 1 1 2(1.2%)
Septicemia 0 0 1 1 2(1.2%)
Leishmaniasis 0 0 1 0 1 (0.6%)
Histoplasmosis 0 0 1 0 1(0.6%)
Malaria 0 0 1 0 1(0.6%)
Gauchers Disease 0 1 0 0 1(0.6%)
Tuberculosis 1 0 0 0 1(0.6%)
Hemoglobinopathy 0 1 0 0 1(0.6%)
Inconclusive 3 1 1 1 6(3.8%)
Total 25 16 72 43 156

Table 2: Clinical findings in cases of pancytopenia

Diagnosis Pallor Fever Petechiae lymphadenopathy Splenomegaly Hepatomegaly Asymp
tomatic
Megaloblastic 40 1 0 0 0 0 0
anemia (40)
Acute leukemias 20 15 2 12 20 24 0
(25)
Hypoplastic 22 13 2 0 0 0 1
marrow (22)
Metastasis (14) 0 0 0 0 0 0 2
Myelodysplastic 3 0 0 0 2 2 0
syndrome (11)
Lymphoma 6 2 0 9 0 0 0
infiltration (9)
Plasma cell 2 1 0 0 0 0 3
dyscrasia (6)
Indian Journal of Pathology and Oncology, July-September 2016;3(3);479-484 480
Sandeep Ojha et al. Bone marrow examination findings in cases of pancytopenia- a study from central India

Viral (3) 0 3 0 2 0 0 0
Hypersplenism(3 3 0 0 0 3 0 0
)
Autoimmune 3 1 0 0 0 0 0
(ITP, SLE) (3)
Hairy cell 2 0 0 1 2 0 0
leukemia (2)
Haemophagocyti 2 2 0 0 2 1 0
c syndrome(2)
Myelofibrosis(2) 2 1 0 0 2 2 0
Septicemia (2) 0 2 0 0 0 0 0
Leishmaniasis 0 1 0 0 1 1 0
(1)
Histoplasmosis( 1 1 0 1 1 0 0
1)
Malaria (1) 1 1 0 0 1 0 0
Gauchers 1 0 0 1 1 1 0
Disease (1)
Tuberculosis (1) 0 1 0 1 0 0 0
Hemoglobinopat 1 0 0 0 0 0 0
hy (1)
Inconclusive (6) 1 2 0 0 1 0 3
Total (156) 110 47(30. 4 (2.5%) 27 (17.3%) 36 (23.1%) 31 (19.8%) 9
(70.5 1%) (5.7%)
%)

Table 3: Peripheral blood findings in cases of pancytopenia

Diagnosis Anisocytosis Poikilocytosis Nucleated RBC’s Blasts Lymphocytosis
Megaloblastic anemia 35 25 15 0 0
(40)
Acute leukemias (25) 10 2 10 23 0
Hypoplastic marrow 0 0 3 0 20
(22)
Metastasis (14) 10 0 10 0 4
Myelodysplastic 1 0 6 1 0
syndrome (11)
Lymphoma infiltration 0 0 0 0 7
(9)
Plasma cell dyscrasia 0 0 0 0 6
(6)
Viral (3) 0 0 0 0 3
Hypersplenism(3) 3 3 0 0 0
Autoimmune (ITP, 0 0 0 0 3
SLE) (3)
Hairy cell leukemia 0 0 0 0 2
(2)
Haemophagocytic 0 0 2 0 0
syndrome(2)
Myelofibrosis(2) 0 0 0 0 2
Septicemia (2) 1 0 1 0 0
Leishmaniasis (1) 0 0 0 0 0
Histoplasmosis(1) 0 0 1 0 0
Malaria (1) 1 1 0 0 0
Gauchers Disease (1) 0 0 0 0 1
Tuberculosis (1) 1 0 0 0 1

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Sandeep Ojha et al. Bone marrow examination findings in cases of pancytopenia- a study from central India

Hemoglobinopathy (1) 1 1 0 0 0
Inconclusive (6) 1 0 1 0 1
Total (156) 64 (41%) 32 (20.5%) 49 (31.4%) 24 50 (32.1%)
(15.4%)

Discussion sarcoma was the primary tumor producing

Pancytopenia is a common hematological finding pancytopenia. In most of these cases (10) peripheral
seen in many diseases and diagnosis still remains a blood showed circulating nucleated RBC’s.
challenge for pathologist as well as to clinician. In this study, Myelodysplastic syndrome was found
Accurate diagnosis is very crucial for management of as a cause of pancytopenia in 11 cases, lymphoma
patient. Bone marrow examination is very important infiltration in 9 cases and marrow plasmacytosis in 6
investigation in patients of pancytopenia and should be cases.
looked carefully to achieve proper diagnosis. Even in We found 2 cases of hairy cell leukemia presenting
the absence of a final diagnosis, BME can help clinician with pancytopenia and one was diagnosed outside as
in approach to diagnosis and management of the hypocellular marrow with marrow fibrosis on biopsy.
patient. He was referred to our hospital with worsening
In our study, out of total 610 cases of BME symptoms and marrow was repeated and showed
performed, 25.6% cases presented with pancytopenia hypocellular marrow with atypical lymphoid cells (Fig.
which is slightly higher than that in literature.5-7 2). Flow cytometry was asked for and it showed
Male: Female ratio in our study was 1.6:1 which is features of Hairy cell leukemia. This is important to
comparable to some studies6,8 while few study showed discuss that irrespective of myelofibrosis on biopsy, if
slightly female preponderance9. atypical lymphoid cells are seen on aspirate; special
In this study most common isolated cause of investigations like flow cytometry must be performed
pancytopenia was megaloblastic anemia which is as Hairy cell leukemia can frequently cause bone
comparable to many studies performed8,10-13 while few marrow fibrosis.
studies found hypoplastic marrow as the most common We found 2 cases presented to us with
cause of pancytopenia6,14-16. pancytopenia, persistent fever, splenomegaly. On
In a study17, they found neoplastic diseases as most laboratory work up one case showed blood culture
common cause of pancytopenia. In our study also, positive for pseudomonas and other patient was a
combined total of all neoplastic cases exceed that of known case of carcinoma ovary with suspected
megaloblastic anemia because this medical college has metastasis to bone marrow in view of decreasing
a separate cancer unit that caters predominantly to counts. Bone marrow from both these cases showed
cancer patients and many cancers when involve bone scattered histiocytic cells showing hemophagocytosis
marrow, presents with pancytopenia. (Fig. 3). No metastasis was found in cases suspected of
In our study second most common cause was acute metastatic carcinoma. In view of significant histiocytes
leukemia which includes both acute myeloid and acute showing hemophagocytosis serum ferritin was asked
lymphoblastic leukemias. Blasts were seen in peripheral for and was raised in both the cases. Thus, the final
blood smears in 23 cases while two showed absence of diagnosis was made as hemophagocytic syndrome
blasts on PBS (aleukemic leukemia). These two cases (HPS) as these cases fulfilled 5 criteria of the
turned out to be acute promyelocytic leukemia (APML) hemphagocytic syndrome as mentioned in literature18.
with few promyelocytes on PBS and around 80% One patient succumbed to the disease irrespective of
promyelocytes and 10% blasts on BME. Out of 23 treatment. It is important to discuss that this is a very
cases, 8 cases showed mildly reduced count with few severe disease and prognosis and survival is very poor
blasts on PBS (5-10%) and bone marrow in all these if treatment is not initiated early. Thus, patient with
cases show features of acute leukemia with > 50% presence of hemophagocytosis in BM should be
blasts. evaluated for HPS.
Hypoplastic marrow was 3rd most common cause Other causes which we found as a cause of
and all these cases were confirmed on biopsy. Majority pancytopenia were viral induced, autoimmune
of these cases (20) show reduced count with (idiopathic thrombocytic purpura- 2cases and systemic
predominantly lymphocytes on peripheral blood smears lupus erythematosus- 1 case), myelofibrosis,
and similar findings on BME. The diagnosis was septicemia, leishmaniasis (Fig. 4), histoplasmosis (Fig.
confirmed on bone marrow biopsy and was in 5), Hypersplenism, malaria, tuberculosis, Gaucher’s
correlation with aspirate findings. disease (Fig. 6) and thalassemia.
In our study metastasis of solid tumors (Fig. 1) was
seen as reason for pancytopenia in 14 cases with lung,
breast and prostate as the most common site of primary
in adults while in a single pediatric case ewing’s

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Sandeep Ojha et al. Bone marrow examination findings in cases of pancytopenia- a study from central India

Fig. 1: Smears showing clusters of small round cells Fig. 4: Scattered and intra-cytoplasmic parasite
in a known case of small cell carcinoma (BM, 400x) consistent with leishmaniasis (BM, 1000x)

Fig. 5: Cytoplasmic fragment showing intracellular

Fig. 2: Hypocellular marrow showing scattered histoplasma organisms (BM, 1000x)
atypical lymphoid cells with cytoplasmic projections
(BM, 1000x)

Fig. 6: Gaucher’s cells with inset showing PAS

positive intacellular accumulation (BM, 1000x)
Fig. 3: Histiocytic cells showing phagocytosis of
nucleated red blood cells (BM, 1000x) Conclusion
Bone marrow examination is an important
investigation to be performed in cases of pancytopenia.
Diagnosis can be made in majority of cases and in few
cases it can direct the clinician to approach the disease.
Most common cause of pancytopenia are megaloblastic
anemia, leukemias and lymphomas, hypoplastic
marrow and metastasis. In addition, specific causes of
pancytopenia (e.g. Hemophagocytic syndrome, storage
disorders, Hairy cell leukemia, fungal or parasitic
Indian Journal of Pathology and Oncology, July-September 2016;3(3);479-484 483
Sandeep Ojha et al. Bone marrow examination findings in cases of pancytopenia- a study from central India

infections) should be kept in mind as some of them can lymphohistiocytosis. Pediatr Blood Cancer. 2007;48
be life threatening. Correlation of clinical, peripheral (2):124-131.
smear finding and bone marrow aspirate findings are
required to arrive at final diagnosis.

Conflicts of interest: Nil

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