Characteristics of bone marrow cell dysplasia and its effectiveness in diagnosing myelodysplastic syndrome

Figures & data

Table 1. Definition of the types and description of the morphological features for dysplasias in erythroid, megakaryocytic and granulocytic lineages.

Dysplastic type	Morphological description	Example picture
Erythroid lineage
Nucleus budding	At least one bud sprouts on nuclear periphery and its size should be less than 1/4 of the nucleus
Nuclear deformity	Irregular shape of nucleus
Howell-Jolly’s body	At least one diameter of 1–2 µm dark amaranthine round body in the cytoplasm of mature erythrocytes or nucleated erythroblasts
Petal nucleus	The shape of nucleus like petal (≥3 nuclear lobulations)
Binuclearity	Two nuclei are separated or separating, and their shapes and sizes are basically the same
Trinuclearity	Three nuclei are separated or separating, and their shapes and sizes are basically the same
Multi-nuclearity	More than three nuclei in the cytoplasm, and they distinctly separate from each other
Internuclear bridging	There is a bridge between the two separated nuclei, and it can appear in either the same cell body or two adjacent cell bodies
Megaloblastic changes	Cell body is larger than normal; nucleus chromatin is swollen and sparse; At least 1.5 times the cell size of the polychromatic erythrocyte or orthochromatic erythrocyte, with an increased karyoplasmic ratio; or the orthochromatic erythrocyte at least two times the cell size of a normal erythrocyte of the same maturational state
Abnormal fission	The nuclei are asymmetrically divided, when the red blood cell precedes mitosis
Asymmetrical nucleus	The two nuclei is not the same size, one is larger and one is smaller like mother and child, and the size of the small one is at least 1/2of the large one
Granulocytic lineage
Pseudo-Pelger-Huet	Bilobated type: two identical elliptical nuclei are connected by a spindly chromatin bridge; Its chromatin is same as the mature neutrophil's, and its cytoplasm is mature and neutrophilic pink
Binucleated granulocyte	Two nuclei (either identical or different) are completely separated with no chromatin bridge
Large bands granulocyte	Cell body is larger than normal and nucleus chromatin is swell and rarefaction
Hyergranulosis	A large number of dark small dense particles evenly distribute in cytoplasm, which is different from the toxic granules and basophils
Hyporgranulosis	Obvious absence of neutrophilic or basophilic granules, presenting as mature segmented nucleus but with either light blue or gray cytoplasm
Ringed Nucleus	Ringed nucleus with normal cytoplasm
Hyposegmentation	Hyposegmentation and chromatin condensation in neutrophils
Large Cell Body with Hypersegmentation	Cell body is larger than the mature granulocytes, with hypersegmentation (>5 nuclear lobulations)
Megakaryocytic lineage
Large-mononuclear megakaryocyte	Cell body size: >30 μm; Only one round or oval nuclear in cytoplasm
Small-mononuclear megakaryocyte	Cell body size: 15–30 μm; only one round or oval nuclear in cytoplasm
Megakaryocyte with small round separated nuclei	More than three small round separated nuclei
Lymphoid small megakaryocyte	Conspicuous dysplasia: single round megakaryocyte; lack of the characteristics of archaeocyte; Cell body size: 7–15 μm, could be either as same as or smaller than the promyelocyte
Binucleated micromegakaryocyte	The two nuclei are separated from each other; cell body size is either as same as or even smaller than the lymphoid small megakaryocyte
Hypersegmentation megakaryocyte	Hypersegmented nucleus
Bizarre megakaryocyte	Extremely irregular shape of nucleus

Figure 1. Comparison of PSDCs in patients with MDS and non-clonal anemia. Blue strips represent for MDS and red strips represent for non-cloned disorders. *P < 0.05, compared with that of non-clonal anemia.

Figure 2. ROC curve of the PSDC in six specific dysplastic types.

Table 2. Diagnostic efficacies of four specific dysplastic types for MDS.

Dysplastic type (test variable)	PSDC (diagnostic Point)	1-Specificity (FPR)	Sensitivity (true positive rate)	Specificity	Sensitivity + Specificity
Petal nucleus	0.005	0.082	0.239	0.918	1.157
	0.015	0.000	0.109	1.000	1.109
	0.025	0.000	0.065	1.000	1.065
Internuclear bridging	0.005	0.010	0.239	0.990	1.229
	0.015	0.000	0.043	1.000	1.043
	0.025	0.000	0.022	1.000	1.022
Pseudo-Pelger-Huet	0.005	0.246	0.630	0.754	1.385
	0.015	0.016	0.239	0.984	1.223
	0.025	0.000	0.130	1.000	1.130
Lymphoid small megakaryocyte	0.005	0.016	0.217	0.984	1.201
	0.015	0.000	0.217	1.000	1.217
	0.030	0.000	0.065	1.000	1.065

Figure 3. Comparison of diagnostic efficacies of dysplasia in three hematopoietic cell lineages in patient with MDS and non-clonal anemia. Blue strips represent for erythroid lineage, red strips represent for granulocytic lineage, and green strips represent for megakaryocytic lineage.

Table 3. Case number and percentage of lineage dysplastic rate ≧10% in patients with MDS and non-clonal anemia

Dysplastic lineage	MDS (92)		Non-clonal anemia (122)
	Case Number	Proportion (%)	Case Number	Proportion (%)
Dyserythropoiesis ≧10%	32	34.78*	2	1.64
Dysgranulopoiesis ≧10%	7	7.61*	0	0
Dysmegakaryopoiesis≧10%	12	13.04*	0	0

*P < 0.05, compared with that of non-clonal anemia.

Table 4. Laboratory features of 92 MDS patients.

	n	Dysplastic lineages			Bone marrow blast ≥5%	Blood blast ≥1%	Ring sideroblasts ≥15%	del(5q)	−7/del(7q)	+8	−Y	del(20q)	del(7q)&+8& del(20q)	del(7q)& +8&del(20q) &-Y	del(9q)	t(6;9) (p23;q34)	t(11;16) (q23;p13.3)
		1	2	3
MDS-SLD	3	3							1	1							1
MDS-MLD	12		9	3						4	3	2		1	1	1
MDS-RS	26	11					26			2	3
MDS-EB	44	10			44	7 (Blas ≥2%)	11		4	5	1	2	2
MDS-U	3					3 (Blast = 1%)			3
MDS-5q-	4							4			1
Total	92		36				37	4	8	12	8	4	2	1	1	1	1

Table 5. Diagnostic efficacy of three lineage dysplastic rates for MDS

Dysplastic rate (test variable)	PSDC (Diagnostic point)*	1−Specificity (FPR)	Sensitivity (true positive rate)	Specificity	Sensitivity + Specificity
Dyserythropoiesis	0.045	0.164	0.543	0.836	1.380
	0.055	0.131	0.457	0.869	1.325
	0.065	0.049	0.326	0.951	1.277
	0.075	0.033	0.261	0.967	1.228
	0.085	0.033	0.196	0.967	1.163
	0.095	0.033	0.152	0.967	1.119
	0.105	0.033	0.109	0.967	1.076
Dysgranulopoiesis	0.025	0.164	0.370	0.836	1.206
	0.035	0.082	0.239	0.918	1.157
	0.045	0.049	0.174	0.951	1.125
	0.055	0.000	0.109	1.000	1.109
	0.065	0.000	0.087	1.000	1.087
	0.075	0.000	0.065	1.000	1.065
	0.085	0.000	0.022	1.000	1.022
Dysmegakaryopoiesis	0.025	0.066	0.239	0.934	1.174
	0.035	0.066	0.217	0.934	1.152
	0.050	0.016	0.196	0.984	1.179
	0.065	0.000	0.152	1.000	1.152
	0.085	0.000	0.130	1.000	1.130
	0.115	0.000	0.087	1.000	1.087

Annotation¹: According to the linear interpolation formula [5]: (R₁−R₂): [R₁−(R = x)] = (P₁−P₂):[P₁−P(R = x)](1), the desired diagnostic point was determined. In the formula (1), (R = x) was the FPR; P(R = x) was the corresponding diagnostic point corresponding to (R = x); R₁ was the FPR that was less than (R = x), but R₂ was greater than (R = x); P₁ and P₂ were the corresponding diagnostic points for R₁ and R₂, respectively.

Figure 4. Comparison of ISDs in patients with MDS and non-clonal anemia. Blue strips represent for MDS and orange strips represent for non-cloned disorders. *P < 0.05, compared with that of non-clonal anemia.

Figure 5. ROC curve of three lineage dysplastic rates in MDS. In MDS patients, the AUCs of dysgranulopoiesis rate, dyserythropoiesis rate and dysmegakaryopoiesis rate were all greater than 0.6 (P < 0.05), of which dyserythropoiesis rate was the largest one.

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