Pulmonary tumor thrombotic microangiopathy of hepatocellular carcinoma: A case report and review of literature

Table 1 Laboratory examination

Hematology		Biochemistry		Marker
WBC	4840/μL	TP	8.0 g/dL	HBs Ag	-
Neutro	70.5 %	Alb	3.4 g/dL	Anti-HBs	-
Lymp	16.9 %	BUN	14 mg/dL	Anti-HBc	-
Eos.	3.7 %	Cre	0.59 mg/dL	Anti-HCV	-
Bas.	0.4 %	T-Bil	1.0 mg/dL
Mon.	8.5 %	D-Bil	0.2 mg/dL	AFP	67183 ng/mL
RBC	392 × 104 /μL	AST	74 IU/L	AFP-L3	37.2 %
Hb	12.4 g/dL	ALT	31 IU/L	PIVKA-II	> 75000 mAU/mL
Ht.	35.9 %	ALP	828 IU/L	KL-6	300 IU/mL
Plt.	8.0 × 104 /μL	LDH	432 IU/L	SP-D	87.6 ng/mL
		γ-GTP	737 IU/L
		ChE	165 IU/L
		NH3	92 μL/dL
		Na	130 mEq/L	Blood Gas Analysis of 6th day (O2 2L)
		K	3.8 mEq/L	SpO2	91%
		Cl	100 mEq/L	pH	7.456
Coagulation		P	3.3 mg/dL	pCO2	35.2 mmHg
PT%	76 %	Ca	9.0 mg/dL	pO2	62.9 mmHg
PT-INR	1.15	CRP	5.37 mg/dL	HCO3	24.3 mmol/L
APTT	36.3 sec	FBS	103 mg/dL	BE	0.7 mmol/L
		HbA1c	5.5 %
		TG	58 mg/dL
		HDL-C	50 mg/dL
		LDL-C	138 mg/dL

PT: Prothrombin time activity; APTT: Activated partial thromboplastin time; BUN: Blood urea nitrogen; Cre: Creatinine; T-Bil: Total bilirubin; D-Bil: Direct bilirubin; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; LDH: Lactate dehydrogenase; γ-GTP: γ-glutamyltransferase; ChE: Cholinesterase; NH3: Ammonia; CRP: C-reactive protein; FBS: Fasting blood sugar; HbA1c: Hemoglobin A1c; TG: Triglyceride; HDL-C: High density lipoprotein; LDL-C: Low density lipoprotein; AFP: α-fetoprotein; PIVKA-II: Protein induced by vitamin K absence or antagonist II; KL-6: Sialylated carbohydrate antigen; SP-D: Surfactant Protein-D; SpO₂: Percutaneous oxygen saturation; BE: Base excess; HCV: Hepatitis C virus.

Table 2 Summary of the cases reported

Case	Ref.	Age (yr)	Gender	Etiology	Child-Pugh score	BCLC stage	Symptom	Respiratory failure	SIRS score	Invasion to IVC	Diagnosis	Treatment	Steroid	Outcome	Prognosis (d)	Image of lung	Pathology of lung	Pathology of liver
1	Uruga et al[1]	60	F	HCV	B	C	Dyspnea	+	2	N/A	Autopsy	Oxygen	+	Death	4	Mild elevation of CT number	Moderately differentiated HCC in lung small blood vessels	N/A
2	Nakamura et al[4]	52	M	Alcohol	B	C	Fever, dry cough	+	3	+	Lung scintigraphy	Decompression	+	Death	330	Multiple plaques on both lungs	Multiple tumor embolism of both pulmonary arteries	Undifferentiated HCC
3	Sato et al[5]	58	M	N/A	B	C	Dyspnea	+	3	N/A	Autopsy	Oxygen	-	Death	15	No imaging	Multiple pulmonary arterial tumor, thrombus	N/A
4	Shinzato et al[6]	56	M	N/A	N/A	C	Dyspnea, consciousness disorder	+	2	+	Autopsy	N/A	-	Death	2	Blurred nodular shadow, airbronchogram	Tumor embolism, hemorrhagic necrosis	differentiated HCC
5	Ohta et al[7]	62	M	Alcohol + HCV	B	C	Chest pain	+	N/A	+	Autopsy	N/A	-	Death	60	Enhancement of pulmonary artery	Multiple pulmonary artery tumor embolism	Medium to well-differentiated HCC
6	Koskinas et al[8]	30	F	HBV	N/A	C	Shortness of breath	+	3	N/A	Autopsy	Oxygen	-	Death	0	No imaging	Invasion of vein by the carcinoma	N/A
7	Jäkel et al[9]	48	M	Alcohol	N/A	C	Ascites	N/A	N/A	+	Autopsy	N/A	-	Death	16	Unremarkable	Multiple pulmonary artery tumor embolism	N/A
8	Yamauchi et al[10]	58	M	HBV	N/A	C	Dyspnea	+	0	+	Autopsy	Oxygen	-	Death	5	Coin lesion	Tumor thrombi in both pulmonary arteries	sarcomatoid HCC
9	Tanaka et al[11]	76	M	HCV	B	C	Dyspnea	+	N/A	N/A	Autopsy	Antibiotic, FOY	-	Death	13	Many ground-glass patterns and partly consolidation in both lung field multiple defect (lung scintigraphy)	Venous thrombi of the poorly differentiated hepatocellular carcinoma	poorly HCC
10	Nepal et al[12]	59	M	Alcohol + HCV	B	C	Abdominal fullness	0	1	+	N/A	N/A	N/A	N/A	N/A	Unremarkable	N/A	N/A
11	Chan et al[13]	52	M	HBV	N/A	C	Malaise, loss of appetite	0	N/A	+	Autopsy	N/A	N/A	N/A	N/A	No imaging	Massive necrotic tumor emboli in both pulmonary trunks.	Moderately differentiated
12	Diaz Castro et al[14]	71	M	HCV	N/A	C	Chest pain	+	N/A	+	Autopsy	Urokinase	-	Death	4 d	No imaging	Tumor thrombi in pulmonary arteries	N/A
13	Gutiérrez-Macías et al[15]	41	M	Alcohol	N/A	C	Dyspnea, chest pain, sweating	+	3	N/A	Autopsy	Antibiotic, antithrombotic therapy	+	Death	2	Filling defect in the left pulmonary artery	Small blood vessels occluded by clusters of malignant cells	N/A
14	Wilson et al[16]	65	M	N/A	N/A	C	Dyspnea	+	N/A	+	Embolic material	Antithrombotic therapy, embolic material recovery	-	Survive	N/A	No imaging	N/A	N/A
15	Mularek-Kubzdela et al[17]	49	M	HBV	N/A	C	Shortness of breath, lower extremity edema	+	N/A	+	CT,lung scintigraphy, United States	N/A	N/A	N/A	N/A	No imaging	N/A	N/A
16	Lin et al[18]	57	M	HBV	B	C	Chest pain、dyspnea	+	N/A	+	Autopsy, echocardiography	Surgery	-	Death	40	Multiple segmental perfusion defects (lung scintigraphy)	N/A	N/A
17	Papp et al[19]	63	M	HBV or HCV	N/A	C	Fever	-	N/A	+	Autopsy, echocardiography	Surgery	-	Death	N/A	No imaging	Tumor embolism, right atrium tumor embolism	small round cell HCC
18	Clark et al[20]	65	M	HCV	N/A	C	Dyspnea, abdominal pain, malaise	+	N/A	+	Autopsy	Comfort care	-	Death	4	No imaging	The large right atrial tumor thrombus and multiple pulmonary emboli	N/A
Our case	N/A	72	M	Alcohol	A	C	Dyspnea	+	2	N/A	Autopsy	Oxygen	+	Death	37	Glass shadow of bilateral lungs	Micropulmonary artery tumor embolism in both lung	Moderate to poorly differentiated HCC

BCLC: Barcelona Clinic Liver Cancer; SIRS: Systemic inflammatory response syndrome; IVC: Inferior vena cava; HBV: Hepatitis B virus; HCV: Hepatitis C virus; N/A: Data not available; FOY: Gabexate mesylate; HCC: Hepatocellular carcinoma.