Essential thrombocythaemia with aggressive megakaryocytosis after myelofibrotic transformation

Figures & data

Figure 1. Bone marrow histology in low-power (a and c; x100) or high-power (b and d ∼ h; x400) fields at diagnosis (a ∼ d), transformation into fibrosis (e and g) and the exaggerated thrombocytosis phase (f and h). a, b: H-E staining revealed slightly hyperplastic bone marrow with an increased number of dysplastic megakaryocytes. Two distinct types of dysplastic megakaryocytes were observed. One type exhibited abundant and mature cytoplasm and deeply and hyperlobulated nuclei (staghorn-like), whereas the other type exhibited an altered nuclear:cytoplasmic ratio with abnormal chromatin clumping and plump (cloud-like) or bulbous (balloon-shaped) lobulation of the nuclei. These two types of abnormal megakaryocytes formed loose clusters. Arrows and arrowheads indicate abnormal megakaryocytes with staghorn-like and cloud-like nuclei, respectively. c, d: Silver staining of the initial bone marrow biopsy revealed a very loose network of reticulin fibre, and the condition was categorized as grade 0 myelofibrosis (MF-0) based on the criteria of the European consensus on grading bone marrow fibrosis. e, f: H-E staining revealed infiltration of dysplastic megakaryocytes in the secondary (e) and tertiary (f) analyses. g, h: Silver staining of the secondary (g) and tertiary (h) bone marrow biopsy revealed obvious fibrosis. Compared with the secondary biopsy (g), the tertiary sample (h) exhibited more prominent fibrosis.

Figure 2. Clinical course.

Table 1. Laboratory findings.

Complete blood count		Biochemistry		Serology
WBC	19,600 /µL	AST	25 U/L	CRP	< 0.4 mg/dL
Stab	5.5%	ALT	30 U/L	IgG	1530 mg/dL
Seg	74.5%	ALP	7.8 KAU	IgA	275 mg/dL
Eo	2.0%	LDH	489 U/L	IgM	113 mg/dL
Ba	1.0%	T-Bil	0.5 mg/dL	IgD	<1.0 mg/dL
Mo	3.5%	TP	7.5 g/dL	IgE	35 mg/dL
Lym	13.5%	ChE	390 U/L	IEP (serum)	M-protein(-)
RBC	592 × 10^4 /µL	UN	14 mg/dL
Hb	18.2g/dL	Creat	1.1 mg/dL	others
Ht	54.70%	Na	142 mEq/L	Vitamin B12	760 pg/ml (230 - 800)
MCV	92.3fl	K	5.7 mEq/L	EPO	13.8 mU/ml (8 - 36)
MCH	30.7pg	Cl	103 mEq/L
MCHC	33.30%	Ca	4.9 mEq/L	Abdominal ultrasonography
Plt	66.6  × 10^4 /µL	IP	4.2 mg/dL	mild hepatomegaly
Reticlocyte	2.4%			splenomegaly (SI: 55 x180 mm)
Bone marrow				Circulating red blood cell volume	24.6 ml/kg
NCC	51.5 × 10^4 /µl
Mgk	900 /µl
Blast	2.2%			Arterial blood gas analysis
M:E	3.3			pH	7.417
Ebl	21.2%			paCO2	42.2 mmHg
				paO2	87.7 mmHg
Chromosome 46 XY, [10/10]				BE	2.9 mmol/L
FISH analysis BCR-ABL: negative

Figure 3. H-E staining of the bone marrow (a), liver (c), spleen (e), thrombus (g) and lung (i) at autopsy. Infiltration of dysplastic megakaryocytes was confirmed with anti-CD42b immunostaining in the bone marrow (b), liver (d), spleen (f), thrombus (h) and lung (j). Arrows and arrowheads indicate abnormal megakaryocytes with staghorn-like and cloud-like nuclei, respectively (a).