Myeloproliferative disorders: A retrospective cohort study

Abstract

Objectives

This study was aimed to identify the number, shape and distribution of megakaryocytes and to recognize blast cells and its location.Further, to identify presence of fibrosis or increased microvascularity.Also,study correlation between histological findings.

Methods

A retrospective was conducted between January 2016 to December 2018 at al-mouwasat university hospital. A total of 44 cases of myeloproliferative disorders using H&E and IHC stains were studied.Chi-square test was performed with descriptive statistics.

Results

Most of our patients were men younger than 75 years of age. 40 was the most prevalent as a median number of megakaryocytes in bone marrow biopsy with normal shape and diffuse pattern, most of biopsies were fibrotic, paratrabecular pattern and absent of hemosiderin deposits that correlate significantly to women patients.Minimal blast cells were more common with diffuse pattern.

Conclusion

Bone marrow biopsy is a useful investigation in myeloproliferative disorders. Evaluation of megakaryopoiesis, fibrosis, and localization of blasts are possible on a bone marrow biopsy.

Highlights

• •Myeloproliferative disorders originate in multipotent myeloid progenitors

• •There is increased production of one or more types of blood cells

• •The term “myeloproliferative disorders” include chronic myeloid leukemia, polycytethemia vera, essential thrombocythemia and marrow fibrosis.

• •The main treatment for myeloproliferative disorders is chemotherapy and bone marrow transplantation.

1. Introduction

Increased proliferative drive in the bone marrow is a common feature of myeloproliferative disorders.Also, variable transformation either to marrow fibrosis or acute leukemia.myeloproliferative disorders include chronic myeloid leukemia, polycythemia vera, essential thrombocytosis, and marrow fibrosis. Most originate from multipotent myeloid progenitors. there is considerable degree of clinical and morphological overlap among myeloproliferative disorders [1]. Under the category of myeloproliferative neoplasms (MPNs), the new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia-not otherwise specified and MPN, unclassifiable (MPN-U) [3]. The current problem remains to develop our understanding of histological findings of bone marrow biopsy and use it as a diagnostic and evaluating tool for patients with myeloproliferative disorders. (see Chart (1), Chart (2))

Chart (1).

This chart shows percentage of each morphology of megakaryocytes.

Chart (2).

This chart shows percentage of distribution of megakaryocytes.

2. Materials and methods

This is a retrospective cohort study. Bone marrow biopsy was done in forty four patients of myeloproliferative disorders. None of the patients were received any therapy at time of biopsy. The biopsy was stained with haematoxylin and eosin. Immunohistochemistry and special stains could not be done and genetic data were not available due to financial difficulties. This study was reported in line with STROCSS criteria [4].

A detailed study of the morphology and distribution of megakaryocytes was done as described by Burkhardt et al. [2] Megakaryocytes were classified as normal, dwarf, immature, giant, pleomorphic, blastic and pyknotic.The distribution was noted as diffuse, sheets or clustered.the fibrosis evaluated by increased angiogenesis.Blast cells identified by IHC and H&E stains. Statistical analysis was done by chi-square test. Also, descriptive statistics were performed. Chi-square test was done among different variables which are: Number,shape and distribution of megakaryocytes, fibrosis and its location, blasts and their location,hemosiderin and its location,age and sex.

3. Results

The main median number of megakaryocytes was 40 [Table 1] with normal shape being most common (n = 14, 31.8%) [Table 2] followed by pleomorphic shape (n = 10, 22.7%) [Table 2]. The most common distribution of megakaryocytes is diffuse type (n = 23, 52%) [Table 3] followed by cluster type (n = 10, 22.7%) [Table 3]. The highest cellularity ranged between 95% and 0% with the most common cellularity was 90% (n = 15, 34.1%) [Table 4] followed by 80% (n = 7, 15.9%) [Table 4].The most common finding in bone marrow biopsies was presence of fibrosis (n = 28, 63,3%) [Table 5] with location of trabecular pattern [Table 6] followed by diffuse fibrosis [Table 6]. Minimal blasts was more prevalent than high frequency of blasts (n = 37,84.1%) [Table 7] with diffuse type (n = 6,13.65%) [Table 8]. Hemosiderin deposition was less common than hemosiderin depletion (n = 27,61.4%) [Table 9 and Table 10]. Age of patients ranged between 75 and 1 year old [Table 11]. Most of patients were male (n = 23, 52.3%) [Table 12].

Table 1.

This table reveals median number of megakaryocytes.

Statistics
median
N	Valid	44
	Missing	0
Mode		1.00
Range		40.00
Minimum		.00
Maximum		40.00

Table 2.

This table reveals different shapes of megakaryocytes.

shape
		Frequency	Percent	Valid Percent	Cumulative Percent
Valid	dwarf	4	9.1	9.1	9.1
	giant	5	11.4	11.4	20.5
	immature	4	9.1	9.1	29.5
	no	5	11.4	11.4	40.9
	normal	14	31.8	31.8	72.7
	pleomorphic	10	22.7	22.7	95.5
	pyknotic	2	4.5	4.5	100.0
	Total	44	100.0	100.0

Table 3.

This table reveals distribution of megakaryocytes.

distribution
		Frequency	Percent	Valid Percent	Cumulative Percent
Valid	cluster	10	22.7	22.7	22.7
	diffuse	23	52.3	52.3	75.0
	no	5	11.4	11.4	86.4
	sheet	6	13.6	13.6	100.0
	Total	44	100.0	100.0

Table 4.

This table reveals bone marrow cellularity.

cellularity
		Frequency	Percent	Valid Percent	Cumulative Percent
Valid	.00	5	11.4	11.4	11.4
	.30	1	2.3	2.3	13.6
	.40	1	2.3	2.3	15.9
	.50	2	4.5	4.5	20.5
	.70	5	11.4	11.4	31.8
	.75	2	4.5	4.5	36.4
	.80	7	15.9	15.9	52.3
	.85	2	4.5	4.5	56.8
	.90	15	34.1	34.1	90.9
	.95	4	9.1	9.1	100.0
	Total	44	100.0	100.0

Table 5.

This table reveals presence and abscence of fibrosis.

fibrosis
		Frequency	Percent	Valid Percent	Cumulative Percent
Valid	no	16	36.4	36.4	36.4
	yes	28	63.6	63.6	100.0
	Total	44	100.0	100.0

Table 6.

This table reveals location of fibrosis.

location of fibrosis
		Frequency	Percent	Valid Percent	Cumulative Percent
Valid	cells	5	11.4	11.4	11.4
	diffuse	7	15.9	15.9	27.3
	multifocal	1	2.3	2.3	29.5
	no	16	36.4	36.4	65.9
	paratrabecular	9	20.5	20.5	86.4
	perivascular	3	6.8	6.8	93.2
	unifocal	3	6.8	6.8	100.0
	Total	44	100.0	100.0

Table 7.

This table reveals maximal and minimal number of blasts.

blasts
		Frequency	Percent	Valid Percent	Cumulative Percent
Valid	no	37	84.1	84.1	84.1
	yes	7	15.9	15.9	100.0
	Total	44	100.0	100.0

Table 8.

This table reveals location of blasts.

location of blasts
		Frequency	Percent	Valid Percent	Cumulative Percent
Valid	diffuse	6	13.6	13.6	13.6
	no	37	84.1	84.1	97.7
	perivascular	1	2.3	2.3	100.0
	Total	44	100.0	100.0

Table 9.

This table reveals hemosiderin deposits.

hemosiderin
		Frequency	Percent	Valid Percent	Cumulative Percent
Valid	no	27	61.4	61.4	61.4
	yes	17	38.6	38.6	100.0
	Total	44	100.0	100.0

Table 10.

This table reveals location of hemosiderin.

hemosiderin location
		Frequency	Percent	Valid Percent	Cumulative Percent
Valid	central	8	18.2	18.2	18.2
	no	27	61.4	61.4	79.5
	peripheral	9	20.5	20.5	100.0
	Total	44	100.0	100.0

Table 11.

This table reveals age of study patients.

Statistics
Age
N	Valid	31
	Missing	13
Mode		50.00
Range		74.00
Minimum		1.00
Maximum		75.00

Table 12.

This table reveals sex category of study patients.

sex
		Frequency	Percent	Valid Percent	Cumulative Percent
Valid	F	21	47.7	47.7	47.7
	M	23	52.3	52.3	100.0
	Total	44	100.0	100.0

Significant association was found in the relationship between:

Median number and shape of megakaryocytes [Table 13].

Table 13.

This table reveals chi square tests between different variables.

	value	df	A sym.sig.(2-sided)
median ∧ shape	131.117	102	0.028
median ∧ distribution	92.549	51	0
median ∧ cellularity	191.348	153	0.019
median ∧ fibrosis	18.38	17	0.365
median ∧ blasts	17.66	17	0.411
median ∧ location of blasts	57.698	34	0.006
median ∧ hemosiderin	19.195	17	0.317
median ∧ Age	344.875	330	0.275
median ∧ sex	20.237	17	0.262
shape ∧ distribution	60.771	18	0
shape ∧ cellularity	76.334	54	0.024
shape ∧ fibrosis	3.101	6	0.796
shape ∧blasts	6.198	6	0.401
shape ∧hemosiderin	2.665	6	0.85
shape ∧age	115.918	132	0.839
shape ∧sex	1.999	6	0.92
distribution ∧ cellularity	42.101	27	0.032
distribution ∧ fibrosis	4.193	3	0.241
distribution ∧ blasts	2.043	3	0.564
distribution ∧ hemosiderin	2.359	3	0.501
distribution ∧ age	70.846	66	0.319
distribution ∧ sex	0.821	3	0.844
cellularity ∧ fibrosis	7.71	9	0.564
cellularity ∧ blasts	6.198	9	0.72
cellularity ∧ hemosiderin	8.369	9	0.49
cellularity ∧ age	177.968	176	0.444
cellularity ∧ sex	9.071	9	0.431
fibrosis ∧ location of fibrosis	44	6	0
fibrosis ∧ blasts	4.423	1	0.035
fibrosis ∧ hemosiderin	0.277	1	0.598
fibrosis ∧ age	22.264	22	0.444
fibrosis ∧ sex	0.052	1	0.82
blasts ∧ location of blasts	44	2	0
blasts ∧ hemosiderin	0.036	1	0.803
blasts ∧ age	19.912	22	0.589
blasts ∧ sex	1.224	1	0.269

Median number and distribution of megakaryocytes [Table 13].

Median number of megakaryocytes and total cellularity [Table 13].

Median number of megakaryocytes and location of blasts [Table 13].

Shape of megakaryocytes and its distribution [Table 13].

Shape of megakaryocytes and total cellularity [Table 13].

Distribution of megakaryocytes and total cellularity [Table 13].

Fibrosis and location of fibrosis [Table 13].

Fibrosis and blasts [Table 13].

Blasts and location of blasts [Table 13].

Hemosiderin and its location [Table 14].

Table 14.

This table reveals chi square tests between available variables.

	value	df	A sym.sig.(2-sided)
hemosiderin ∧ location of hemosiderin	44	2	0
hemosiderin ∧ age	21.516	22	0.489
hemosiderin ∧ sex	3.201	1	0.074
age ∧ sex	18.988	22	0.646

Hemosiderin and sex [Table 14].

4. Discussion

In this study, we investigated the number,shape,and distribution of megakaryocytes in bone marrow biopsy from patients with myeloproliferative disorders and also evaluated the presence of fibrosis and blasts.Our study found that the average age of patients was 51.The most common distribution of megakaryocytes was in diffuse pattern followed by cluster pattern in contrast to the german study which the megakaryocytes were clusters rather than diffusely distributed [2]. Most of our cases were men who were younger than 75 years of age in contrast to german study [2] which were women comprising the majority.It is important to note that in the present study 63.3% of cases were fibrotic paratrabecular pattern which consists with the german study [2].Majority of cases that we encountered showed absence of blasts with high frequency and most being presented in diffuse pattern. Also, consists with the german study [2]. Our study has some limitations are lack of clinical information and insufficient immunohistochemical stains.

5. Conclusion

Evaluation of megakaryopoiesis,fibrosis and blasts with their location are novel findings should be studied in every bone marrow biopsy so we recommend to use bone marrow biopsy in patients with myeloproliferative disorders as it provides many information that maybe of clinical significance.

Sources of funding

No funds

Ethical approval

This is retrospective cohort study. Ethical approval not needed.

Trial registry number.

• 1.Name of the registry: Research Registry.
• 2.Unique Identifying number or registration ID: Research registry 6952

https://www.researchregistry.com/browse-the-registry#home/registrationdetails/60e4866179ebc8001f90c2b3.

Consent

No consent obtained as consent form was not applicable to our study.

This is retrospective study, collecting data from file of patients.

Declaration of competing interest

Author has no conflict of interest.

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Not commissioned, externally peer reviewed.

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Appendix A. Supplementary data

The following is the supplementary data to this article: