Anlotinib dramatically improved pulmonary hypertension and hypoxia caused by Pulmonary Tumor Thrombotic Microangiopathy (PTTM) associated with gastric carcinoma: a case report.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related respiratory complication, demonstrating rapid progression of pulmonary hypertension (PH) and respiratory failure. Although a number of treatments have been attempted for patients diagnosed with or suspected of having PTTM, successful-treated cases of PTTM were mainly from imatinib therapy, which was a PDGF receptor inhibitor. Anlotinib was a novel tyrosine kinase inhibitor that targets VEGFR, FGFR, PDGFR, and c-kit. CASE PRESENTATION: We reported a patient of PTTM associated with gastric carcinoma, whom were treated with anlotinib, thereby exhibiting significant improvement of PH and respiratory dysfunction. CONCLUSION: Our case provides a new understanding of therapy to PTTM, with implications for defining anlotinib as candidate drug for PTTM. Clinical diagnosis and prompt initiation of anlotinib might be one of the strategies in patients with unstable PTTM.

Pulmonary tumor thrombotic microangiopathy during good response to immuno-chemotherapy for advanced non-small cell lung cancer: a case report.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy is a rapidly progressive and fatal disease in which tumor cells embolize to the pulmonary microvasculature. This condition is characterized by severe dyspnea and right heart failure. Although pulmonary tumor thrombotic microangiopathy typically occurs in patients with untreated and/or advanced cancer, its occurrence in patients who are responding well to medical therapy is poorly documented. CASE PRESENTATION: A 68-year-old Japanese woman who had received four cycles of immuno-chemotherapy (pembrolizumab, carboplatin, and pemetrexed) followed by three cycles of maintenance therapy (pembrolizumab and pemetrexed) for advanced non-small cell lung cancer and had achieved a partial response with a stable clinical course was admitted to the emergency ward because of worsening breathlessness and general fatigue for 1 week. Chest computed tomography showed no evidence of tumor progression or any new lung lesion. Two-dimensional transthoracic echocardiography demonstrated right atrial and ventricular dilatation, tricuspid regurgitation, and a high trans-tricuspid pressure gradient of 65 mmHg. Despite her percutaneous oxygen saturation being 96% on room air at the time of admission, it worsened rapidly; the patient requiring 8 L/min of oxygen within 4 h. Repeat computed tomography with contrast medium revealed no evidence of pulmonary embolism. The patient developed progressive respiratory failure that was unresponsive to optimal cardio-pulmonary supportive therapy. An autopsy revealed tumorous clusters in pre-capillary lung vessels, whereas the primary lesion had shrunk to the point of almost complete resolution. CONCLUSION: Pulmonary tumor thrombotic microangiopathy occurs not only in patients with advanced and/or uncontrolled cancer but also in those whose primary lesion seems to have been well controlled by medical treatment.

Pulmonary tumor thrombotic microangiopathy in occult early gastric cancer that was undetectable on upper endoscopy: a case report and review of similar cases.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM), a rare manifestation of metastatic cancer with poor prognosis, is characterized by subacute/acute fatal pulmonary hypertension. The main cause of PTTM is gastric cancer, and cases of early gastric cancer confirmed using autopsy have been reported. Moreover, several cases of early gastric cancer that are undetectable on endoscopy or macroscopic postmortem examination have been reported. CASE PRESENTATION: A previously healthy 50-year-old man presented with progressive dyspnea and cough for 1 month. Echocardiography suggested pulmonary hypertension. Computed tomography revealed diffuse lymphadenopathy, whereas blood work revealed an elevation in several serum tumor marker levels. Despite normal upper endoscopic findings, a presumptive diagnosis of PTTM due to gastric cancer was made based on pathological findings of cervical lymph node biopsy, which indicated signet ring cell carcinoma. Imatinib and tegafur/gimeracil/oteracil plus oxaliplatin therapy were started on day 7. The patient's condition was initially stable. However, his symptoms suddenly progressed, and the patient died on day 8. Macroscopic postmortem examination revealed no abnormal gastric wall findings. Microscopically, PTTM was confirmed, and multiple serial sections of the stomach revealed early gastric cancer. CONCLUSIONS: Despite normal endoscopic findings, micro-occult gastric cancer can lead to PTTM. Physicians should be aware of this disease presentation. Taking prompt action is needed when PTTM is suspected, even if the patient appears stable.

Pulmonary microvascular metastases in cervical carcinoma: A case series.

Pulmonary microvascular tumor embolism (PMTE), pulmonary tumor thrombotic microangiopathy (PTTM), and lymphangitis carcinomatosis (LC) have an intricate pathophysiology and usually occur with cancers of breast, stomach, and lung. Microvascular pulmonary metastases attributable to cervical cancer are a rarity. Clinical presentation and autopsy findings of patients with microvascular pulmonary metastases in cervical cancers were studied with a review of literature. Four patients (mean age of 55.5 years) with carcinoma cervix showed microvascular metastases. Three of whom presented with respiratory symptoms, and the fourth case was unresponsive on presentation. Each patient succumbed to their illness shortly after admission. Autopsy examination performed on each patient depicted varying combination of PMTE, PTTM, and LC, all with squamous histology. This case series highlights the rare association of carcinoma cervix with the aforementioned microvascular phenomena. Besides, it underscores the sequential mechanism of occurrence of microvascular pulmonary metastasis and the associated guarded prognosis.

Pulmonary tumor thrombotic microangiopathy and pulmonary veno-occlusive disease in a woman with cervical cancer treated with cediranib and durvalumab.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare cause of pulmonary hypertension that is associated with malignancies and is marked by the presence of non-occlusive tumor emboli and fibrocellular intimal proliferation of small pulmonary arteries leading to increased pulmonary vascular resistance and right heart failure. The diagnosis of PTTM is challenging to make pre-mortem and guidelines on treatment are lacking. CASE PRESENTATION: A 45-year-old woman with advanced squamous cell carcinoma of the cervix developed symptoms of dyspnea and evidence of right heart failure during a phase I clinical trial with cediranib and durvalumab. After an extensive evaluation, pre-capillary pulmonary hypertension was confirmed by right heart catheterization. Vasodilator therapy was initiated but resulted in the development of symptomatic hypoxemia and was discontinued. Despite continued supportive care, she continued to decline and was transitioned to hospice care. At autopsy, the cause of her right heart failure was found to be due to PTTM with features of pulmonary veno-occlusive disease (PVOD). CONCLUSION: PTTM and PVOD are important diagnoses to consider in patients with a malignancy and the development of right heart failure and may be manifestations of a spectrum of similar disease processes.

Case Report: Pulmonary Tumor Thrombotic Microangiopathy in a Cervical Cancer Patient.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive and often fatal pulmonary disease induced by tumor emboli within the small pulmonary arteries. PTTM presents clinically as progressive hypoxia and pulmonary hypertension. Most cases of PTTM are caused by an adenocarcinoma of the stomach. We present the first case report of PTTM caused by cervical squamous cell carcinoma. An 82-year-old woman presented with vaginal bleeding and exertional dyspnea. A cervical mass biopsy showed squamous cell carcinoma. Computed tomography revealed ground glass opacity of the bilateral peripheral lung fields. Hypoxia and pulmonary hypertension gradually worsened after admission. Treatment for acute heart failure was started, but was ineffective. She died of respiratory failure 31 days after admission. She was diagnosed at autopsy as having PTTM induced by cervical squamous cell carcinoma. PTTM needs to be considered in any patient with advanced cancer and lung-related issues to rule out metastatic disease, even in the absence of imaging findings.

[A Case of Pulmonary Tumor Thrombotic Microangiopathy in Castration-Resistant Prostate Cancer].

A man aged 83 years under treatment with enzalutamide for castration-resistant prostate cancer presented with general malaise and exertional dyspnea. The underlying cause could not be identified by further investigations. On the 5th hospital day, he died due to a sudden exacerbation of dyspnea. The results of an autopsy indicated tumor emboli and stenosis of small pulmonary arteries with the fibrocellular intimal thickening, and therefore our final diagnosis was pulmonary tumor thrombotic microangiopathy.

Antemortem diagnosis of pulmonary tumor thrombotic microangiopathy in a patient with recurrent breast cancer: a case report.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM), a rare complication of advanced cancer, is histologically characterized by tumor embolisms and fibrocellular intimal proliferation of small pulmonary arteries and arterioles. PTTM usually has an extremely poor prognosis, and antemortem diagnosis is very difficult. CASE PRESENTATION: A 65-year-old woman with a 5-year history of clinical stage IIA (T2N0M0) invasive ductal carcinoma of the left breast was hospitalized for worsening shortness of breath, hemoptysis, and cough since 2 months. She had previously received neoadjuvant chemotherapy and left mastectomy. Because the cancer cells were positive for human epidermal growth factor receptor 2 (HER2), four cycles of trastuzumab had been administered as adjuvant chemotherapy. On admission, chest computed tomography (CT) showed peripheral consolidations in both the lower lobes and a mediastinal mass. Specimens obtained on video-assisted thoracoscopic surgical biopsy revealed tumor cell embolism, intimal fibrocellular proliferation of small arteries, fibrin thrombi, recanalization, and infarction in the left lower lobe, as well as metastasis to the mediastinal pleura. Immunohistochemical staining of the tumor cells revealed positivity for HER2, and a diagnosis of recurrent breast cancer with PTTM was made. Four cycles of trastuzumab resulted in rapid improvement of her symptoms and CT findings of peripheral consolidations and the mediastinal mass. CONCLUSION: An antemortem diagnosis of PTTM was made in a patient with HER2-positive recurrent breast cancer. Trastuzumab was effective for not only breast cancer but also PTTM.

Pulmonary Tumor Thrombotic Microangiopathy With Versican Expression in a Patient With Advanced Gastric Cancer: A Case Report of a Rare Autopsy.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but fatal complication of a malignant tumor that causes rapidly progressive pulmonary hypertension (PH). We report the case of a 70-year-old Japanese man who died of respiratory failure during chemotherapy for gastric cancer and was diagnosed with PTTM at autopsy. The autopsy revealed PTTM-specific histological findings, such as tumor emboli with fibrin-rich clots and fibrocellular intimal proliferation in the vessels. The cancer cells were immunohistochemically positive for vascular endothelial growth factor and platelet-derived growth factor, whereas the thickened intima of the pulmonary arteries was positive for versican (VCAN). As VCAN is an extracellular matrix proteoglycan that is dramatically increased in vascular lesions of pulmonary arterial hypertension, this case demonstrates that VCAN is also involved in the pathophysiology of PTTM.

Pulmonary tumor thrombotic microangiopathy due to early gastric carcinoma in a patient with no antemortem findings suggestive of primary malignancy.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare and critical malignancy-related disease characterized by acute progressive pulmonary hypertension (PH). In most cases of PTTM, the cancer can be diagnosed in advance. Identification of the primary cancer is valuable for PTTM diagnosis. Here, we present the case of a patient with PTTM due to early gastric carcinoma in whom the diagnosis of malignant cancer was not revealed until macroscopic autopsy findings. This case highlights the importance of recognizing causative occult early gastric cancer leading to PTTM in cases of acute progressive PH.

An autopsy case of pulmonary tumor thrombotic microangiopathy that developed during chemotherapy for salivary duct carcinoma of the parotid gland.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive cancer-related disease with a dismal clinical course. The patient in this report was a 43-year-old man with metastatic salivary duct carcinoma arising from the parotid gland. Combined androgen blockade therapy was administered started as first-line treatment, but failed after 5 months, followed by docetaxel plus carboplatin therapy as second-line treatment, which failed after 3 months. Genomic profiling revealed a BRAF V600E mutation, and combined BRAF and MEK inhibitor therapy was started as third-line treatment. The cancer remained stable during the first 10 months of third-line treatment, but treatment was subsequently discontinued due to the onset of symptoms of fatigue, myalgia and arthritis. Twenty days after the onset of these symptoms and interruption of third-line treatment, the patient was urgently admitted to hospital with respiratory distress and severe thrombocytopenia. CT images at the time of admission led our radiologist to the possibility of PTTM, but the patient died the day after admission and autopsy findings indicated that PTTM was the cause of death. This report describes a very informative case of PTTM with sequential imaging and detailed autopsy findings were available and provides a literature review.

Focal ground glass opacity of the lung in metachronous prostate and gastric cancer: A case report.

Chest computed tomography (CT) revealed a focal ground glass opacity (GGO) with a minimal solid area in a 75-year-old man. The shadow was located in the periphery of the right upper lobe and measured 11 mm in diameter. The patient had a medical history of metachronous prostate and gastric cancers. The patient had been treated with androgen deprivation therapy for prostate cancer for 12 years and underwent subtotal gastrectomy for triple gastric cancers 7 months before. Since primary lung adenocarcinoma was suspected, CT-assisted percutaneous needle biopsy was performed. Histology revealed the sheet-like and trabecular proliferation of atypical cells, suggesting that the lesion was moderately to poorly differentiated adenocarcinoma. Adenocarcinoma cells showed subepithelial extension causing the thickening of alveolar walls. A tumor thrombus was not detected in the blood or lymphatic vessels. Immunohistochemistry revealed that carcinoma cells were negative for cytokeratin 7 (CK7), CK20, thyroid transcription factor-1 and CDX2 and positive for prostate-specific antigen and P504S. Based on these findings, the patient was diagnosed with metastatic carcinoma from prostate cancer. The disease remained stable for 4 months after the diagnosis, and no new lesions were observed on chest CT. Metastatic carcinoma rarely presents with focal GGO. Lung biopsy is necessary to identify the pathology of the lesion, and the primary site needs to be confirmed by immunohistochemistry with specific markers, particularly in a case of metachronous multiple cancers. A tumor thrombus, which is suggestive of lymphangitic carcinomatosis or pulmonary tumor thrombotic microangiopathy, also needs to be evaluated.

Pulmonary Tumor Thrombotic Microangiopathy Suspected to be COVID-19 Vaccine-Related Myocarditis: A Case Report.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a very rare condition that can lead to acute severe pulmonary hypertension and circulatory failure. It is caused by tumor cell microvascular obstruction and is usually difficult to diagnose; in fact, it is often diagnosed after death. We report the case of a patient who experienced a sudden cardiac arrest and developed severe pulmonary hypertension two days after receiving the coronavirus disease (COVID-19) vaccine. The patient was initially diagnosed with vaccine-associated myocarditis, and venoarterial extracorporeal membrane oxygenation (VA-ECMO) implantation with median sternotomy was performed. The patient survived for more than two weeks. PTTM was later diagnosed during a pathological autopsy.

Pulmonary Tumor Thrombotic Microangiopathy in a Patient with Rapid Progressive Triple-Negative Breast Cancer.

Introduction: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare complication of metastatic carcinoma, which occurs in patients with pulmonary arterial hypertension, and is mostly fatal. Circulating tumor cell clusters have been recognized as critical factors during breast cancer progression. Case Presentation: An 80-year-old woman with triple-negative breast cancer was admitted to our hospital with progressive dyspnea and lower back pain. Breast cancer treatment included mastectomy, neoadjuvant and adjuvant chemotherapy as well as adjuvant radiotherapy, receiving her last cycle of radiotherapy 8 days before death. At admission, D-dimers were strongly elevated and platelets were low. NT-pro-BNP was moderately elevated. A CT scan of the chest did not show pulmonary embolism but revealed interlobular septal thickening, centrilobular consolidation, and distension of the pulmonary arteries. Moreover, new skeletal and most likely lymphatic metastasis was described. Treatment with oxygen and oral glucocorticoids was initiated, assuming radiotherapy-induced pneumonitis. Due to low expression of PD-L1 and her markedly bad performance status, tumor-specific therapy was not possible, and the treatment regimen was changed to best supportive care. The patient died 8 days after admission. Autopsy revealed numerous events consistent with tumor emboli in the pulmonary vessels, suggesting PTTM. Conclusion: PTTM is a rare and mostly fatal complication in malignant breast cancer. As an early detection is difficult, further investigation is needed. Circulating tumor cluster cells may be one way to detect PTTM early and improve patients' survival.

Dramatic Improvement of Pulmonary Tumor Thrombotic Microangiopathy in a Breast Cancer Patient Treated With Bevacizumab.

A 47-year-old woman diagnosed with stage IV left-sided breast cancer (T3N3aM1; OSS, HEP, LYM) 6 months back presented with respiratory distress. On admission, she developed respiratory failure, requiring 4 L of oxygen support. Pulmonary embolism was ruled out because computed tomography revealed no obvious pulmonary artery thrombus. Transthoracic echocardiography revealed a significant enlargement of the right ventricle and atrium. Pulmonary hypertension was confirmed via right heart catheterization. Pulmonary artery wedge aspiration cytology revealed adenocarcinoma cells. Based on these findings, we diagnosed the patient with pulmonary tumor thrombotic microangiopathy (PTTM) caused by breast cancer. Immediate chemotherapy (paclitaxel and bevacizumab) for breast cancer and concurrent treatment for pulmonary hypertension and disseminated intravascular coagulation were initiated. We could successfully control her condition with paclitaxel and bevacizumab for a year, and the patient survived for 1 year and 8 months. PTTM is a rare disease characterized by pulmonary hypertension and hypoxemia arising due to tumor embolization of the peripheral pulmonary arteries. PTTM is a rapidly progressing condition with no established treatment guidelines; its pathogenesis involves vascular endothelial growth factor (VEGF). This report highlighted the potential of bevacizumab, known for its anti-VEGF effect, in improving the pathological condition of patients with PTTM caused by breast cancer.

Pulmonary Tumor Thrombotic Microangiopathy Caused by Metastatic Ovarian Cancer: An Antemortem Diagnosis with Pulmonary Aspiration Cytopathology.

A 48-year-old woman with advanced ovarian cancer was diagnosed with pulmonary tumor thrombotic microangiopathy (PTTM) by antemortem pulmonary wedge aspiration cytopathology. Despite the initiation of anti-cancer treatment, she unfortunately died due to progressive respiratory failure. Histopathology of the autopsied lung revealed multiple tumor embolization with fibrin-rich clot and fibro-cellular intimal proliferation at the pulmonary arteriole. The embolized tumor showed strong immune-positivity for pro-thrombotic and fibrotic factors (tissue factor and vascular endothelial growth factor), suggesting the underlying mechanisms of PTTM development. This case suggests that a quick antemortem diagnosis and the early induction of specific treatments might ensure a better prognosis of PTTM.

Antemortem diagnosis of pulmonary tumor thrombotic microangiopathy associated with gastric cancer and response to immediate chemotherapy.

Pulmonary tumor thrombotic microangiopathy is a rare and fatal complication of cancer that features widespread tumor cell-derived embolisms in the small arteries and arterioles of the lung and is often associated with thrombus formation. We describe the case of a 43-year-old woman who was hospitalized with cough and respiratory distress that lasted for 2 months. Computed tomography findings demonstrated multiple areas of interlobular septal thickening and ground-glass opacities in both lungs. Transthoracic echocardiography demonstrated a D-shaped left ventricle suggesting right heart overload, and pulmonary blood flow scintigraphy revealed multiple small, peripheral, and patchy areas of reduced blood flow. Upper gastrointestinal endoscopy revealed a signet-ring carcinoma. The patient was diagnosed with pulmonary tumor thrombotic microangiopathy based on her clinical presentation and treatment with tegafur, gimeracil oteracil potassium, oxaliplatin, and an anticoagulant was initiated on the 3rd day after admission. The symptoms improved rapidly after treatment initiation. The patient was discharged 28 days after initiation of chemotherapy without the need for supplemental oxygen. This case suggests that the immediate use of chemotherapy and anticoagulants for treating pulmonary tumor thrombotic microangiopathy may improve patient survival.

An unexpected cause of pulmonary hypertension in a young woman: a case report.

Background: Pulmonary hypertension (PH) is defined as a progressive disease that leads to right heart failure and death if untreated. This case report presents a young woman with reversible precapillary PH in the setting of a gastric cancer. Case summary: A 37-year-old woman presented with exertional dyspnoea and syncope. The transthoracic echocardiographic findings were consistent with a cor pulmonale. Right heart catheterization (RHC) proved a precapillary PH. Specific PH therapy with macitentan and tadalafil was initiated. Shortly thereafter, a gastric carcinoma was diagnosed, and oncologic treatment with neoadjuvant chemotherapy and subsequent gastrectomy was promptly initiated. Retrospectively, we considered a pulmonary tumour thrombotic microangiopathy the most probable cause of PH. Follow-up after successful oncologic treatment and cumulative 10 months of specific PH medication showed an excellent clinical response with complete remission of PH confirmed by RHC at rest. Discussion: Tumour-related PH is very rare and might be largely underdiagnosed as the clinical course often results in a rapid deterioration and fatal outcome before diagnostics are completed. Post mortem studies have documented tumoural emboli in pulmonary microcirculation in ∼26% of patients with a solid tumour, markedly associated with adenocarcinoma. Prompt initiation of cancer treatment on tumoural PH is essential. To our knowledge, this report documents the first full recovery of tumoural PH at rest after successful cancer treatment and temporary specific PH medication. We therefore conclude that a multidisciplinary approach with an initially combined oncologic and PH therapy may be most beneficial with the potential of complete remission of PH.

Pulmonary tumor thrombotic microangiopathy caused by metastatic ovarian high-grade serous carcinoma: a case report and literature review.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare entity with poor prognosis, and often diagnosed postmortem. PTTM is resulting from tumor emboli induced activation of coagulation cascade, fibrin clot formation and fibrocellular intimal proliferation in pulmonary microvasculature. CASE: The patient was a 65-year-old female, with past medical history of ovarian high-grade serous carcinoma, presented with chest pain and shortness of breath. The chest computed tomography (CT) revealed innumerable new lung nodules as well as small hazy and patchy opacities compared to the chest CT 2 months before current presentation. She developed progressive respiratory failure and expired. A lung-restricted autopsy showed diffuse subcentimetric nodules in bilateral lungs grossly. Microscopic examination revealed the lung parenchyma demonstrated numerous tumor emboli consisting of pleomorphic tumor cells with varying degrees of fibrin deposition and fibrocellular intimal proliferation in the pulmonary arterioles, small arteries, and capillaries in the alveolar septa. Immunohistochemistry confirmed the ovarian origin of the tumor cells. The findings were consistent with PTTM secondary to metastasis of ovarian high-grade serous carcinoma. Literature review of PTTM caused by ovarian cancer was conducted. CONCLUSION: PTTM is a fatal entity with rare association with primary ovarian malignancy. This case study demonstrates the clinicopathological features of PTTM associated with high-grade serous carcinoma, and it will be the second case of PTTM with this association in the literature.

Pulmonary Tumor Thrombotic Microangiopathy Caused by Esophageal Adenocarcinoma: A Case Report.

Pulmonary tumor thrombotic microangiopathy (PTTM ) is a rare condition of uncertain incidence given its likely underdiagnosis. PTTM has been described most frequently in association with gastric adenocarcinoma, but other primary malignancies have been identified. The prognosis of PTTM is very poor, and patients often die within days or weeks of diagnosis. There are, however, several medications currently being used with unknown therapeutic benefits. The case presented below describes a patient with PTTM and esophageal adenocarcinoma, which may be the first report of its kind. One other case of esophageal cancer associated with PTTM was found in the literature review, but it is of squamous cell carcinoma histology. Herein, we report a case of a male with rapidly progressive pulmonary hypertension and right heart failure who, in the course of treatment/evaluation, was found to have esophageal adenocarcinoma. While early diagnosis may not alter the course of the disease, antemortem diagnosis may identify better therapeutic options and better inform patients of their prognosis, allowing them to maintain autonomy in their medical decisions.