PTTM is a fatal complication of malignancy causing progressive pulmonary hypertension (PH) or right heart failure. It is considered as a rare disease, but a growing number of cases have been reported. The pathogenesis is hypothesized that widespread cancer emboli in microscopic pulmonary arteries activate fibrocellular intimal proliferation and thrombosis. Adenocarcinomas, especially gastric ones, are the major cause. Pathological diagnosis of PTTM is apparently easy. However, microscopic pulmonary tumor emboli are a sporadic finding of cancer patients, which can resemble PTTM when followed by intimal changes and other pulmonary diseases. The increase of misdiagnosis is a concern as PTTM becomes better known. The purpose of this study is to build diagnostic criteria of PTTM.
24 cases diagnosed as PTTM in multiple institutions were collected and classified into two groups; (1) a definite group (n = 13), those who had been clinically diagnosed as PH, and (2) a suspicious group (n = 11), those who revealed respiratory symptoms but lacked clinical assessment of PH. As a control group, autopsy cases with PTTM-like lesions but who were lacking progressive respiratory symptoms were selected (n = 7). PTTM-like lesions in these groups was observed and counted.
The numbers of PTTM-like lesions (fibrocellular intimal proliferation and thrombi with tumor cells) in the definite and non-PTTM group were 26.5-68.8 and 0.5-5.9/cm2 area of lung specimen. In definite cases, peripheral arterioles smaller than 150 μm in diameter were predominantly involved. In the suspicious group, 7 of 11 cases had as many lesions (25.4-68.9/cm2) in small arterioles as in the definite cases, while the remaining 4 had as few lesions (1.3-9.6/cm2) as the non-PTTM group. Lymphangitis carcinomatosa was seen in these 4 cases.
We suggest that the pathological criteria of PTTM is as follows: 1) fibrocellular intimal proliferation and thrombi with tumor cells 2) involvement of microscopic pulmonary arteries and arterioles, predominantly small ones in alveolar septa (<150 μm in diameter), and 3) the innumerable spreading of more than approximately 100 lesions/5 cm2 area of lung specimen.
Clinical trial identification
Legal entity responsible for the study
A Grant-in-Aid for the Promotion of Occupational Health for the Post Graduate Student of the University of Occupational and Environmental Health.
All authors have declared no conflicts of interest.