Pulmonary Tumor Thrombotic Microangiopathy: A Clinical ...

1317

□ ORIGINAL ARTICLE □

Pulmonary Tumor Thrombotic Microangiopathy:A Clinical Analysis of 30 Autopsy Cases

Hironori Uruga 1,4,5, Takeshi Fujii 2,4, Atsuko Kurosaki 3, Shigeo Hanada 1, Hisashi Takaya 1,

Atsushi Miyamoto 1, Nasa Morokawa 1, Sakae Homma 5 and Kazuma Kishi 1,4

Abstract

Objective Pulmonary tumor thrombotic microangiopathy (PTTM) is a unique, rare and fatal form of pul-

monary arterial tumor embolism. The aim of this study was to evaluate the clinical characteristics and patho-

logical and immunohistochemical findings of PTTM.

Methods Autopsy records dated between January 1983 and May 2008 in our hospital were reviewed, and

those of patients who died from pulmonary tumor embolism resulting from malignant neoplasm were re-

trieved. The relevant tissue slides were reevaluated and examined immunohistochemically to confirm the di-

agnosis.

Results Among 2,215 consecutive autopsy cases of carcinoma, 30 patients (1.4%) were diagnosed with de-

finitive PTTM. The common symptom was progressive dyspnea. A hypercoagulative state was observed in all

measured cases (n = 21). The chest computed tomography findings (n = 6) included consolidation, ground-

glass opacity, small nodules and a tree-in-bud appearance. Perfusion scans were performed in seven patients,

six of whom demonstrated multiple small defects. The median survival time after the initiation of oxygen

supplementation was nine days. The most frequent primary site was the stomach (n = 18 ; 60%), and the

most frequent histological type was adenocarcinoma (28/30 ; 93.3%). The immunohistochemical findings for

tumor cells located within the tumor emboli were positive for vascular endothelial growth factor (28/29 ;

96.6%) and tissue factor (29/29 ; 100%).

Conclusion Clinicians should suspect PTTM in cancer patients who exhibit acute worsening respiratory in-

sufficiency accompanied by a hypercoagulative state without embolism in major pulmonary arteries. The

PTTM patients evaluated in our study had very poor prognoses. Vascular endothelial growth factor and tissue

factor may play important roles in PTTM.

Key words: pulmonary tumor thrombotic microangiopathy, pulmonary tumor embolism, vascular endothelial

growth factor, tissue factor, pulmonary hypertension

(Intern Med 52: 1317-1323, 2013)(DOI: 10.2169/internalmedicine.52.9472)

Introduction

Pulmonary tumor thrombotic microangiopathy (PTTM) is

a rare form of pulmonary arterial tumor embolism. It is his-

tologically characterized by fibrocellular intimal proliferation

of small pulmonary arteries and arterioles in patients with

metastatic carcinoma and is associated with the development

of clinical signs of pulmonary hypertension that result in

acute or subacute cor pulmonale and subacute respiratory

failure (1). The pathogenesis begins with the formation of

microscopic tumor cell emboli that induce local activation of

coagulation and fibrocellular intimal proliferation. Eventu-

ally, stenosis and/or occlusion occur, along with an increase

in pulmonary vascular resistance that results in pulmonary

hypertension, hemolytic anemia and disseminated intravas-

１Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital, Japan, ２Department of Pathology, Toranomon Hospital, Japan,３Department of Diagnostic Radiology, Toranomon Hospital, Japan, ４Okinaka Memorial Institute for Medical Research, Japan and ５Department

of Respiratory Medicine, Toho University Omori Medical Center, Japan

Received for publication December 5, 2012; Accepted for publication February 21, 2013

Correspondence to Dr. Hironori Uruga, [email protected]

Intern Med 52: 1317-1323, 2013 DOI: 10.2169/internalmedicine.52.9472

1318

cular coagulation. In some cases, metastatic carcinoma is not

diagnosed before death, and the condition is diagnosed as

pulmonary hypertension of unknown origin. However, the

clinical manifestations of PTTM are not fully understood

because previous literature on PTTM primarily includes

pathological analyses or case reports. In this study, we re-

viewed autopsy cases to evaluate the clinical characteristics

of PTTM and reevaluated stored tissue samples using patho-

logical and immunohistochemical analyses.

Materials and Methods

Between January 1983 and May 2008, a total of 4,389

autopsies were performed at Toranomon Hospital in Tokyo,

Japan. Among these cases, malignant neoplasms were found

in 2,215 cases, including lung cancer in 575 cases and gas-

tric cancer in 283 cases. We selected cases with malignant

neoplasms in which the autopsy records described the pres-

ence of tumor microembolism in the lungs and reexamined

the relevant tissue slides. PTTM was diagnosed according to

the characteristic histopathological findings reported by von

Herbay et al. (1), which include the presence of tumor em-

bolism as well as fibrocellular intimal proliferation, organi-

zation and recanalization of the arteries and arterioles within

the lungs. Next, we studied the clinical data obtained from

the medical charts and radiographs. Computed tomography

(CT) was performed using Aquilion 16 (Toshiba Medical

Systems). High-resolution CT (HRCT) was reconstructed

from 1.0-mm slices obtained every 5 or 10 mm. The CT im-

ages were reevaluated independently by a pulmonary radi-

ologist (A. K.) without prior knowledge of the clinical histo-

ries of the patients. Antibodies against vascular endothelial

growth factor (VEGF)-A (VG-1 ; Delta Biolabs, Gilroy, CA,

USA; at 1 : 50 dilution), tissue factor (FL295 ; Santa Cruz

Biotechnology, CA, USA; at 1:200 dilution), placental

growth factor (Abcam, Cambridge, UK; at 1 : 500 dilution),

platelet-derived growth factor (PDGF ; Spring Bioscience,

Pleasanton, CA, USA; at 1 : 100 dilution) and osteopontin

(X-20 ; Santa Cruz Biotechnology; at 1 : 50 dilution) were

used to perform the immunohistochemical analysis in order

to evaluate the previously suggested pathogenesis of

PTTM (2-5). Reports of Cases 29 and 30 have been pub-

lished in Japanese journals (5, 6). Detailed clinical informa-

tion was unavailable in Case 2 because the patient died in

another hospital and the autopsy only was performed in our

hospital. An immunohistochemical analysis of Case 28

could not be performed because the specimens were insuffi-

cient. This retrospective study was approved by the Institu-

tional Review Board of Toranomon Hospital (No. 525).

Results

Clinical presentation

Of the 2,215 consecutive autopsy patients with carcinoma,

170 (7.7%) had pulmonary tumor embolism, and 91 (4.1%)

had fatal multiple pulmonary tumor embolism. Among the

fatal cases, 30 (1.4%) patients, including 19 men and 11

women with a median age of 58.5 years (range, 34-80

years), were microscopically diagnosed with PTTM. The

symptoms included progressive dyspnea (n = 26 ; 86.7%),

coughing (n = 20 ; 66.7%) and hemoptysis (n = 4 ; 13.3%)

(Table 1). Elevated serum levels of D-dimer were observed

in five patients and elevated levels of fibrin degradation

products (FDP) were observed in 21 patients. A diagnosis of

disseminated intravascular coagulation (DIC) was made in

14 patients (46.7%). The serum VEGF level was examined

in one patient (Case 30) and was found to be within the

normal range (<16.5 U/mL). The median survival time fol-

lowing oxygen supplementation was nine days (range, 1-69

days).

All 30 patients were diagnosed with malignant cancer be-

fore death, three of whom were diagnosed with pulmonary

hypertension of unknown origin. An antemortem diagnosis

of PTTM was made in only one patient (Case 29) based on

the findings of a CT-guided needle biopsy. The patient had

received chemotherapy consisting of carboplatin and pacli-

taxel, which had resulted in improvement of the associated

consolidation. The survival time after diagnosis of PTTM in

this patient was seven months.

Physiological study

Electrocardiography demonstrated the presence of right

atrial overload or ventricular hypertrophy in 13 of the 24

patients examined (Table 1), and echocardiography demon-

strated pulmonary hypertension in three of the five patients

examined.

Imaging study

Chest CT was performed in six patients, three of whom

were administered contrast media. The remaining three pa-

tients underwent HRCT. The CT findings of PTTM included

consolidation, ground-glass opacity, small nodules and a

tree-in-bud appearance (Table 1). Contrast-enhanced CT

showed negative findings for acute pulmonary embolism in

three patients.

Perfusion scans were performed in seven patients, six of

whom demonstrated multiple small defects. The other pa-

tient (Case 26) demonstrated a subsegmental defect.18 F-fluorodeoxyglucose-positron emission tomography

(18F-FDG-PET) was performed in one patient (Case 29) who

demonstrated uptake in the area of primary lung cancer and

consolidation that was pathologically proven to be PTTM.

Autopsy findings

The primary site of cancer included the stomach (n= 18;

60.0%), lungs (n = 5 ; 16.7%), esophagus, liver, common

bile duct, pancreas, breasts, paranasal sinus and parotid

gland(n = 1 for each ; 3.3%, Table 2). The histological types

were adenocarcinoma (n = 28 ; 93.3%), adenosquamous car-

cinoma (n = 1 ; 3.3%) and carcinoma (salivary duct carci-

noma) ex pleomorphic adenoma (n = 1 ; 3.3%). Five lung


1319

Table　1.　Clinical Presentation and Radiographic Findings of Pulmonary Tumor Thrombotic Microangiopathy

DIC: disseminated intravascular coagulation, FDP: fibrinogen degradation product, NE: not examined

Case Age Sex Cough Hemop-tysis Dyspnea DIC

Survival after

onset of dyspnea(days)

Survival after

supple-mentaloxygen(days)

Right atrial overload

or ventricu-lar hypertro-

phyon ECG

Pulmonary hy-pertension on

echocardiogram

Chest CT find-ings

Perfusionscan

1 43 M ＋－＋＋ 14 24 ＋ NE NE NE2 80 F NE NE NE NE NE NE NE NE NE NE3 47 F ＋－＋－ 74 22 －＋ NE NE4 55 M ＋－＋－ 18 18 ＋ NE NE NE5 34 M ＋－＋＋ 23 23 － NE NE NE6 80 F ＋－＋－ 5 1 ＋ NE NE Defect(+)7 60 F －－＋＋ 9 9 NE NE NE NE8 65 F ＋－＋－ 9 8 ＋ NE NE NE9 50 M ＋＋＋＋ 5 5 NE NE NE NE

10 75 M ＋－－＋－ 69 ＋ NE NE NE11 47 M ＋－＋＋ 3 3 NE NE NE NE12 47 F －－＋－ 10 10 － NE NE NE13 61 F ＋＋＋＋ 10 10 － NE NE NE14 60 M ＋－＋－ 9 9 － NE NE NE15 64 M ＋＋＋＋ 7 1 NE NE NE NE16 40 M ＋－＋－ 37 33 － NE NE NE17 63 M －－－－－ 4 ＋ NE NE NE18 43 M －－＋＋ 4 3 － NE NE NE19 73 F －－＋＋ 9 9 ＋－ NE NE20 34 M ＋－＋－ 13 10 － NE NE NE21 75 F ＋－＋－ 3 1 － NE NE NE22 57 M ＋－＋－ 12 12 － NE NE Defect(+)

23 68 M －－＋＋ 41 2 ＋－Ground-glass

opacity, pleural effusion, , atelec-

tasis

Defect(+)

24 74 M ＋－＋－ 23 7 ＋ NE Ground-glass opacity Defect(+)

25 66 M －－＋－ 2 7 ＋ NE NE NE

26 69 M －－－＋－ 56 － NE

Ground-glass opacity, pleural

effusion, atelecta-sis, thickening of bronchovascular

bundles

Defect(+)

27 45 F ＋－＋－ 14 14 NE NE NE NE

28 39 M －－＋－ 4 2 ＋ NE Consolidation,single nodule NE

29 47 F ＋＋＋＋ 7 2 ＋＋Consolidation,

tree-in-budappearance

Defect(+)

30 53 M ＋－＋＋ 55 3 ＋＋ Ground-glass opacity Defect(+)

cancers were identified histologically to be adenocarcinoma.

The frequency of PTTM was 6.4% (18/283) in all gastric

cancer cases, 8.1% (18/223) in advanced gastric cancer

cases and 0.9% (5/575) in all lung cancer cases. Mucin pro-

duction was found in 20 of the 29 tumors (69.0%). Lym-

phangitis carcinomatosa was coincidentally present in 18 of

the 30 PTTM patients.

Immunohistochemical findings

The tumor cells were immunoreactive for VEGF-A (28/

29 ; 96.6%), tissue factor (29/29 ; 100%), placental growth

factor (14/29 ; 48.3%), PDGF (18/29 ; 62.1%) and osteo-

pontin (18/29 ; 62.1%) (Table 2) (Figs. 1, 2).

Discussion

To the best of our knowledge, this study is the largest

case series focusing on clinical manifestations of PTTM. Al-

though it is extremely difficult to diagnose PTTM antemor-

tem, we believe that PTTM should be suspected in cancer

patients with acute worsening respiratory insufficiency and

elevated levels of D-dimer or FDP in the absence of embo-

lism in major pulmonary arteries on enhanced CT scans. In

this study, the most common symptom was progressive


1320

Table　2.　Immunohistochemical Findings of Pulmonary Tumor Thrombotic Microangiopathy at Autopsy

case Age Sex Primary site Histological type Metastasis identified at autopsy Mucus VEGF TF PlGF PDGF OPN

1 43 M StomachAdenocarcinoma, moderately

differentiatedBones, kidney, spleen, pleura ＋＋＋＋－＋

2 80 F StomachAdenocarcinoma, poorly

differentiated

Adrenal gland, kidney, liver, ovary, pancreas, peritoneum, thyroid

－＋＋－＋＋

3 47 F Breast Invasive ductal carcinoma Bones, liver, pituitary spleen, stomach ＋＋＋＋－＋

4 55 M EsophagusAdenosquamous, moderately

differentiatedBones, liver, pituitary, spleen, stomach ＋－＋－－＋

5 34 M StomachAdenocarcinoma, poorly

differentiated

Bone marrow, bones, esophagus, liver,peritoneum

＋＋＋－＋＋

6 80 F PancreasAdenocarcinoma, moderately

differentiatedAdrenal gland, bones, heart, ovary ＋＋＋＋－＋

7 60 F LungAdenocarcinoma, poorly

differentiatedAdrenal gland, brain, liver, pleura ＋＋＋－＋－

8 65 F StomachAdenocarcinoma, moderately

differentiated

Adrenal gland, diaphragm, esophagus, liver,pancreas, peritoneum, pleura

－＋＋＋＋＋


differentiatedBone marrow, liver, peritoneum ＋＋＋－－－

10 75 M LungAdenocarcinoma, well

differentiatedAdrenal gland, heart, liver, pancreas, pleura －＋＋－－－


differentiated

Adrenal gland, bone marrow, bowels, esoph-agus, heart, liver, kidney, pancreas,

peritoneum, prostate－＋＋＋＋＋


differentiated

Adrenal gland, bone marrow, liver,meninges, pancreas, peritoneum, pituitary,

pleura, skin, spleen, ovary＋＋＋－＋＋


differentiated

Adrenal gland, bone marrow, pericardium, peritoneum, spleen

＋＋＋－－－


differentiatedLiver ＋＋＋＋＋＋


differentiated

Adrenal gland, bone marrow, liver, meninges, pancreas

－＋＋－＋－


differentiated

Adrenal gland, bones, bowels, liver, pancreas, peritoneum

＋＋＋－－－

17 63 M LiverCholangiocellular adenocarci-

nomaAdrenal gland, bones, peritoneum ＋＋＋＋－－


differentiated

Adrenal gland , bone marrow, liver, pancreas, peritoneum, spleen

＋＋＋－＋＋

19 73 F LungAdenocarcinoma, well

differentiated

Adrenal gland, bones, kidney, pleura, thyroid

＋＋＋＋＋＋


differentiated

Bone marrow, liver, pancreas, pericardium,peritoneum, pleura

＋＋＋＋＋＋


differentiated

Adrenal gland , kidney, liver, meninges,skin, ovary, peritoneum

－＋＋－＋－


differentiatedBones, esophagus, peritoneum －＋＋－＋－

23 68 MSphenoid

sinus

Adenocarcinoma, poorly

differentiatedAorta, bone marrow, heart, meninges, pleura －＋＋＋＋＋


differentiatedNone ＋＋＋－＋－

25 66 MCommon bile

duct

Adenocarcinoma, poorly

differentiated

Adrenal gland, bones, heart, kidney, liver, pancreas, pituitary

＋＋＋＋－＋

26 69 M LungAdenocarcinoma, moderately

differentiated

Bones, heart, kidney, liver, ovary, peritoneum, pleura

－＋＋＋－＋


differentiated

Adrenal gland ,bones, bowels, heart, kidney, liver, spleen, ovary, uterine, thyroid

＋＋＋－＋－


differentiatedBile duct, bowels, liver, peritoneum － NE NE NE NE NE

29 47 F LungAdenocarcinoma, moderately

differentiatedPeritoneum, pleura ＋＋＋＋＋＋

30 53 M Parotid glandSalivary duct carcinoma ex

pleomorphic adenomaBones, liver ＋＋＋＋＋＋

VEGF: vascular endothelial growth factor, TF: tissue factor, PlGF: placental growth factor, PDGF: platelet-derived growth factor, OPN: osteopontin, NE: not examined


1321

Figure　1.　Histopathological findings of the lung specimens obtained at autopsy in Case 19: (a) tu-mor embolism in the pulmonary arterioles (Hematoxylin and Eosin staining, ×20), (b) fibrocellular intimal proliferation (Elastic van Gieson staining,×20), (c) immunohistochemical staining of tumor cells with antibodies against vascular endothelial growth factor (×20), (d) tissue factor (×20), (e) pla-cental growth factor (×20), (f) platelet-derived growth factor (×20) and (g) osteopontin (×20).

a b c

d e f

g

100m

dyspnea, and the laboratory data indicated a hypercoagula-

tive state, which possibly reflected the presence of tumor

embolism and DIC. The prognoses in our cases were ex-

tremely poor, a finding that is consistent with those of previ-

ous series (2, 7, 8). We used a CT-guided needle biopsy to

successfully make an antemortem diagnosis of PTTM in one

patient with lung cancer. This patient received standard

platinum doublet chemotherapy and survived seven months.

Apart from this case, only five patients were diagnosed with

PTTM before death based on either video-assisted thora-

coscopic surgical biopsies (n = 1) (9), right heart catheteri-

zation (n = 1) (10) or transbronchial lung biopsies (n =

3) (11-13). Three of the five patients who were diagnosed

with PTTM antemortem received chemotherapy, two of

whom survived for several months (9, 11). Whether patho-

logical changes occurred in the vascular lesions of these

PTTM patients due to chemotherapy is unknown ; however,

the CT findings improved following the administration of

chemotherapy (6, 9). Making an antemortem diagnosis or

having a high index of suspicion of PTTM in addition to

administering adequate treatment is mandatory for improv-

ing the prognoses of such patients.

Imaging studies, such as chest CT, perfusion scans and18F-FDG-PET, show various nonspecific findings in PTTM

cases. The CT findings of PTTM include consolidation,

ground-glass opacity, small nodules and a tree-in-bud ap-

pearance (9, 11-16). All of these findings were recognized

in our study. A tree-in-bud appearance usually suggests in-

fectious bronchiolitis ; however, this appearance is also seen

in patients with PTTM resulting from tumor embolism or fi-

brocellular intimal proliferation in the small arteries or arte-

rioles (14, 15). Perfusion scans performed in PTTM patients

are reported to show multiple small defects throughout the

bilateral lungs (11, 17), which was observed in six of seven

patients in this study. 18F-FDG-PET was performed in one

patient (Case 29) and showed high uptake in malignant le-

sions and PTTM. Tashima et al. (16) also presented a case

of PTTM that showed multifocal abnormal FDG uptake in

both lungs.

The incidence of PTTM among all autopsy patients with

carcinoma in the present study was 1.4%. This is similar to

the previously reported incidence of 0.9%-3.3% (1, 18). The

most frequent primary site and histological type were the

stomach and adenocarcinoma, respectively. Herbay et al. (1)


1322

Figure　2.　Histopathological findings of the lung specimens obtained at autopsy in Case 29: (a) tu-mor embolism in the pulmonary arterioles (Hematoxylin and Eosin staining, ×10), (b) fibrocellular intimal proliferation (Elastic van Gieson staining,×10), (c) immunohistochemical staining of tumor cells with antibodies against vascular endothelial growth factor (×10), (d) tissue factor (×10), (e) pla-cental growth factor (×10), (f) platelet-derived growth factor (×10) and (g) osteopontin (×10).

a b c

d e f

g

100m

reported that 19 of the 21 patients had adenocarcinoma and

11 of the 19 patients had gastric carcinoma. Our results are

in accordance with those results.

The hallmark of PTTM is changes in vascular architecture

induced by various molecules secreted by tumor cells. Previ-

ous immunohistochemical studies have shown that VEGF,

tissue factor, PDGF and osteopontin are key molecules in

the pathogenesis of PTTM. VEGF is an important molecule

for angiogenesis in mammalian fetuses (19, 20) and tumor

cells (3). Tissue factor is an initiator of coagulation in addi-

tion to factor VII, which plays a role in thrombosis, metasta-

sis, tumor growth and tumor angiogenesis in can-

cers (21, 22). The expression of VEGF and tissue factor by

tumor cells has recently been confirmed in many PTTM

cases (2, 4, 23-25). In addition, PDGF and osteopontin are

reported to be candidate molecules in the pathogenesis of

PTTM (4, 24). In our study, the rates of immunohistochemi-

cal positivity for tissue factor and VEGF were very high,

whereas that for PDGF was relatively low. We therefore

speculate that tissue factor and VEGF play important roles

in the pathogenesis of PTTM.

Conclusion

PTTM patients have a very poor prognosis. It is ex-

tremely difficult to make a definitive antemortem pathologi-

cal diagnosis of PTTM. PTTM should thus be suspected

when cancer patients exhibit an acute worsening of respira-

tory insufficiency with a hypercoagulative state in the ab-

sence of embolism in major pulmonary arteries on enhanced

CT scans. VEGF and tissue factor may play therefore im-

portant roles in the pathogenesis of PTTM.

The authors state that they have no Conflict of Interest (COI).

References

1. von Herbay A, Illes A, Waldherr R, Otto HF. Pulmonary tumor

thrombotic microangiopathy with pulmonary hypertension. Cancer

66: 587-592, 1999.

2. Chinen K, Kazumoto T, Ohkura Y, Matsubara O, Tsuchiya E. Pul-

monary tumor thrombotic microangiopathy caused by a gastric

carcinoma expressing vascular endothelial growth factor and tissue


1323

factor. Pathol Int 55: 27-31, 2005.

3. Kerbel RS. Tumor angiogenesis. N Engl J Med 358: 2039-2049,

2008.

4. Takahashi F, Kumasaka T, Nagaoka T, et al. Osteopontin expres-

sion in pulmonary tumor thrombotic microangiopathy caused by

gastric carcinoma. Pathol Int 59: 752-756, 2009.

5. Uruga H, Fujii T, Kurosaki A, et al. A case of pulmonary tumor

thrombotic microangiopathy caused by carcinoma (salivary duct

carcinoma) ex pleomorphic adenoma. Nihon Kokyuki Gakkai

Zasshi 48: 463-468, 2010 (In Japanese, Abstract in English).

6. Uruga H, Morokawa N, Enomoto T, et al. A case of pulmonary

tumor thrombotic microangiopathy associated with lung adenocar-

cinoma diagnosed by CT-guided lung biopsy. Nihon Kokyuki

Gakkai Zasshi 46: 928-933, 2008 (In Japanese, Abstract in Eng-

lish).

7. Hibbert M, Braude S. Tumour microembolism presenting as “pri-

mary pulmonary hypertension”. Thorax 52: 1016-1017, 1997.

8. Gavin MC, Morse D, Partridge AH, Levy BD, Loscalzo J. Clini-

cal problem-solving. Breathless. N Engl J Med 366: 75-81, 2012.

9. Miyano S, Izumi S, Takeda Y, et al. Pulmonary tumor thrombotic

microangiopathy. J Clin Oncol 25: 597-599, 2007.

10. Ota K, Matsuyama M, Kokuho N, et al. An autopsy case of pul-

monary tumor thrombotic microangiopathy complicated with inter-

stitial pneumonia and lipoid pneumonia. Nihon Kokyuki Gakkai

Zasshi 47: 518-523, 2009 (In Japanese, Abstract in English).

11. Ishiguro T, Takayanagi N, Ando M, Yanagisawa T, Shimizu Y,

Sugita Y. Pulmonary tumor thrombotic microangiopathy respond-

ing to chemotherapy. Nihon Kokyuki Gakkai Zasshi 49: 681-687,

2011 (In Japanese, Abstract in English).

12. Noguchi S, Imanaga T, Shimizu M, Nakano T, Miyazaki N. Case

of pulmonary tumor thrombotic microangiopathy diagnosed by

transbronchial lung biopsy. Nihon Kokyuki Gakkai Zasshi 46:

493-496, 2008 (In Japanese, Abstract in English).

13. Ueda A, Fuse N, Fujii S, et al. Pulmonary tumor thrombotic mi-

croangiopathy associated with esophageal squamous cell carci-

noma. Intern Med 50: 2807-2810, 2011.

14. Franquet T, Gimenez A, Prats R, Rodriguez-Arias JM, Rodriguez

C. Thrombotic microangiopathy of pulmonary tumors: a vascular

cause of tree-in-bud pattern on CT. AJR Am J Roentgenol 179:

897-899, 2002.

15. Guimaraes MD, Almeida MF, Brelinger A, Barbosa PN, Chojniak

R, Gross JL. Diffuse bronchiolitis pattern on a computed tomogra-

phy scan as a presentation of pulmonary tumor thrombotic mi-

croangiopathy: a case report. J Med Case Rep 5: 575, 2011.

16. Tashima Y, Abe K, Matsuo Y, et al. Pulmonary tumor thrombotic

microangiopathy: FDG-PET/CT findings. Clin Nucl Med 34: 175-

177, 2009.

17. Kinuya K, Yamanouchi K, Terahata S. Diagnosis: pulmonary tu-

mor thrombotic microangiopathy developing cor pulmonale. Ann

Nucl Med 16: 220, 2002.

18. Tamura A, Matsubara O. Pulmonary tumor embolism: relationship

between clinical manifestations and pathologic findings. Nihon

Kyobu Shikkan Gakkai Zasshi 31: 1269-1278, 1993 (In Japanese,

Abstract in English).

19. de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams

LT. The fms-like tyrosine kinase, a receptor for vascular endothe-

lial growth factor. Science 255: 989-991, 1992.

20. Shibuya M, Claesson-Welsh L. Signal transduction by VEGF re-

ceptors in regulation of angiogenesis and lymphangiogenesis. Exp

Cell Res 312: 549-560, 2006.

21. Kasthuri RS, Taubman MB, Mackman N. Role of tissue factor in

cancer. J Clin Oncol 27: 4834-4838, 2009.

22. Levi M. Disseminated intravascular coagulation in cancer patients.

Best Pract Res Clin Haematol 22: 129-136, 2009.

23. Chinen K, Tokuda Y, Fujiwara M, Fujioka Y. Pulmonary tumor

thrombotic microangiopathy in patients with gastric carcinoma:an

analysis of 6 autopsy cases and review of the literature. Pathol

Res Pract 206: 682-689, 2010.

24. Okubo Y, Wakayama M, Kitahara K, et al. Pulmonary tumor

thrombotic microangiopathy induced by gastric carcinoma:

morphometric and immunohistochemical analysis of six autopsy

cases. Diagn Pathol 6: 27, 2011.

25. Sato Y, Marutsuka K, Asada Y, Yamada M, Setoguchi T, Sumi-

yoshi A. Pulmonary tumor thrombotic microangiopathy. Pathol Int

45: 436-440, 1995.

Ⓒ 2013 The Japanese Society of Internal Medicine

http://www.naika.or.jp/imonline/index.html

Pulmonary Tumor Thrombotic Microangiopathy: A Clinical ...

Documents

Transcript of Pulmonary Tumor Thrombotic Microangiopathy: A Clinical ...