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Background: Pulmonary tumour thrombotic microangiopathy (PTTM) is a fatal disease in which tumour cells embolize to the pulmonary vasculature leading to pulmonary hypertension and right heart failure. Early diagnosis is essential for timely treatment which can reduce intimal pulmonary vascular proliferation and prolong survival, improve the symptoms. Due to rare occurrences and no clear diagnostic guidelines the disorder usually is found post-mortem. We present a review of this rare disease and a case of post-mortem diagnosed pulmonary tumour thrombotic microangiopathy in a young female.Case Presentation: 51 years old woman presented with progressively worsening dyspnea, right ventricular failure signs and symptoms. Computerized tomography denied pulmonary embolism. 2D transthoracic echocardiography demonstrated right ventricle dilatation and dysfunction, severely increased systolic pulmonary pressure. Right heart catheterization revealed pre-capillary pulmonary hypertension with mean pulmonary artery pressure of 78 mmHg, pulmonary wedge pressure of 15 mmHg, reduced cardiac output to 1.78 L/min with a calculated pulmonary vascular resistance of 35 Wood units, and extremely low oxygen saturation (26%) in pulmonary artery. Because of worsening ascites, pelvic magnetic resonance imaging was performed, tumours in both ovaries were diagnosed. Due to the high operative risk, detailed tumour diagnosis surgically was not established. The patient developed progressive cardiorespiratory failure, unresponsive to optimal heart failure drug treatment. A postmortem morphology analyses revealed tumorous masses in pre-capillary lung vessels, right ventricle hypertrophy, ovary adenocarcinoma.Conclusions: An early diagnosis of PTTM is essential. Most cases are lethal due to respiratory failure progressing rapidly. Patients with a history of malignancy, symptoms and signs implying of PH should be considered of having PTTM. If detected early enough, combination of chemotherapy with specific PH therapy is believed to be beneficial in reducing intimal proliferation and prolonging survival, along with improving the symptoms. [ABSTRACT FROM AUTHOR]

We experienced a case of breast cancer in which liver metastases spread rapidly and the patient died of pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is a fatal cancer-associated respiratory complication disease. To reveal genetic alterations of the clinical course, we performed next generation sequencing of the serial specimens using the Ion AmpliSeqTM Comprehensive Cancer Panel and RNA sequencing for transcriptomic data, followed by gene set analysis. The analysis revealed an oncogenic TP53 R213* mutation in all specimens and STK11 loss in tissues sampled after disease progression. Immunohistochemistry with an anti-STK11 antibody confirmed no STK11 expression in the samples after progression. Transcriptome analysis showed a significant downregulation of proteins associated with apoptosis in the specimens with STK11 loss. STK11 loss may have triggered the rapid progression of PTTM from a comprehensive genomic analysis. [ABSTRACT FROM AUTHOR]

Aims: Pulmonary tumour thrombotic microangiopathy (PTTM) is a fatal disease of patients with cancer that causes progressive pulmonary hypertension (PH). Its pathology is characterised by fibrocellular intimal proliferation and thrombosis caused by tumour emboli in microscopic pulmonary arteries. However, such PTTM‐like lesions often appear incidentally. We sought to identify features that distinguished PTTM from incidental pulmonary tumour emboli, and to gain an overall picture of PTTM morphology in terms of its pathogenesis. Methods and results: Twenty‐five PTTM cases were classified into two groups: (i) a definite group (n = 14), clinically diagnosed with PH; and (ii) a suspicious group (n = 11) with respiratory symptoms but without a clinical evidence of PH. As a control group, autopsy cases with PTTM‐like lesions lacking progressive respiratory symptoms were selected (n = 7). PTTM‐like lesions in these groups were studied and a diagnostic guide for PTTM formulated as follows: PTTM‐like lesions with >17 affected vessels observed in a 1‐cm2 area of lung specimen, and the absence of pulmonary metastatic nodules. PTTM due to gastric cancers was shown to have a significantly shorter course and larger arterial involvement than cases with non‐gastric cancers. Serial sections revealed a PTTM lesion to be a longitudinal obstruction that accumulated in microscopic pulmonary arteries and that showed a proximal extension via supernumerary arteries. Conclusion: We suggest novel pathological diagnostic characteristics for PTTM deduced from a study of 25 autopsy cases. This includes PTTM‐like lesions with >17 affected vessels in a 1‐cm2 area of lung specimen and the absence of pulmonary metastatic nodules. [ABSTRACT FROM AUTHOR]

Background: Pulmonary tumour thrombotic microangiopathy (PTTM) is a rare complication of metastatic cancer with a distinct histological appearance which presents with dyspnoea and pulmonary arterial hypertension and leads to death in hours to days. It is a challenging diagnosis to make ante mortem, in part due to the rapid clinical decline. Herein, we report a case of a young woman initially felt to have pulmonary sarcoidosis but who then died eight days later from what was found at post mortem to be PTTM. Case presentation: A 41 year old Caucasian woman presented with progressive dyspnoea. Computed tomography of her thorax showed diffuse tiny centrilobular nodules in a tree-in-bud appearance along with small volume mediastinal lymphadenopathy. A presumptive diagnosis of pulmonary sarcoidosis was made; bronchoscopy with transbronchial lung biopsy was arranged to confirm the diagnosis. However, she rapidly deteriorated and died eight days later. Post mortem examination revealed metastatic poorly differentiated gastric adenocarcinoma with PTTM being the final cause of death. Conclusion: This case demonstrates the diagnostic difficulties in such a rare and rapidly fatal oncological complication; a greater awareness amongst clinicians may help make a positive diagnosis in the short window of time available. Little is known about its pathogenesis, and even less about optimal management strategies. We review the literature to demonstrate the clinical characteristics that might provide clues towards an ante mortem diagnosis, and highlight how imatinib may provide the key to treating PTTM. [ABSTRACT FROM AUTHOR]

Background: Pulmonary tumour thrombotic microangiopathy (PTTM) is a rare complication of metastatic cancer with a distinct histological appearance which presents with dyspnoea and pulmonary arterial hypertension and leads to death in hours to days. It is a challenging diagnosis to make ante mortem, in part due to the rapid clinical decline. Herein, we report a case of a young woman initially felt to have pulmonary sarcoidosis but who then died eight days later from what was found at post mortem to be PTTM. Case presentation: A 41 year old Caucasian woman presented with progressive dyspnoea. Computed tomography of her thorax showed diffuse tiny centrilobular nodules in a tree-in-bud appearance along with small volume mediastinal lymphadenopathy. A presumptive diagnosis of pulmonary sarcoidosis was made; bronchoscopy with transbronchial lung biopsy was arranged to confirm the diagnosis. However, she rapidly deteriorated and died eight days later. Post mortem examination revealed metastatic poorly differentiated gastric adenocarcinoma with PTTM being the final cause of death. Conclusion: This case demonstrates the diagnostic difficulties in such a rare and rapidly fatal oncological complication; a greater awareness amongst clinicians may help make a positive diagnosis in the short window of time available. Little is known about its pathogenesis, and even less about optimal management strategies. We review the literature to demonstrate the clinical characteristics that might provide clues towards an ante mortem diagnosis, and highlight how imatinib may provide the key to treating PTTM. [ABSTRACT FROM AUTHOR]

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