Pulmonary Tumor Thrombotic Microangiopathy Research Articles

Pulmonary tumor thrombotic microangiopathy: the role of a lung perfusion SPECT-CT study.

Pulmonary tumor thrombotic microangiopathy: the role of a lung perfusion SPECT-CT study.

Abstract PS16-31: SKT11 loss drives rapid cancer progression and fatal pulmonary tumor thrombotic microangiopathy (PTTM) in a breast cancer patient: A case report

Abstract Introduction: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare cancer-associated respiratory complication characterized by widespread tumor cell emboli in small arteries and arterioles of the lung. Breast cancer is the second most common cancer causing PTTM. The pathogenesis and molecular background of PTTM have not been clarified. Here we present a case of breast cancer that experienced early onset of liver metastasis after surgical resection of the primary tumor and rapid progression leading to death due to severe respiratory distress. Autopsy was performed and it revealed that the main cause of her death was PTTM. Comprehensive next generation sequencing (NGS) analysis of the tissue obtained serially during the clinical course was performed. Case Presentation: A 48-year-old woman was diagnosed with invasive ductal carcinoma of the left breast, which was ER positive, PgR negative, and HER2 negative. FEC followed by docetaxel was administered as preoperative chemotherapy. Her tumor dramatically shrunk with chemotherapy and left partial mastectomy with left axillary lymph node dissection was performed. Histopathological analysis of the resected breast tissue revealed that there were a lot of residual cancer cells, which were ER negative, PgR negative, HER2 negative, and the result indicated that response to preoperative chemotherapy was insufficient. Additional two courses of FEC therapy were performed. Postoperative radiation therapy including the left supraclavicular lymph node area was given and adjuvant endocrine therapy with anastrozole started at the same time. At 3 months of anastrozole administration, she presented hepatic dysfunction and abnormal CT findings in the liver. Liver biopsy revealed multiple liver metastasis of breast cancer. Unresponsive to weekly paclitaxel and bevacizumab, she developed rapid respiratory failure leading to her death in two weeks. Postmortem microscopic analysis revealed an intimal fibrocellular proliferation in the pulmonary arterioles regardless of microscopic tumor emboli and extensive sinusoidal metastasis of the whole liver. NGS Analysis: We analyzed four specimens, breast cancer biopsy specimen at diagnosis, surgical resection specimen, liver needle biopsy specimen, and liver specimen obtained at autopsy, with the Ion AmpliSeq Comprehensive Cancer Panel (Thermo Fisher). The results were compared with NGS analysis of her normal lung tissue to exclude single nucleotide polymorphisms. Deep sequencing revealed that only TP53 R213* was detected as an oncogenic mutation in all four specimens. There were no mutations associated with the development of liver metastasis and her death. Comparison of the samples obtained between before and after liver metastasis revealed that STK11 loss and IKBKE amplification were harbored only in the specimens after liver metastasis. RNA sequencing analysis with the samples of initial biopsy and liver biopsy showed that the RNA expression associated with apoptosis and adhesion molecules was strongly suppressed in the liver sample. Conclusion: STK11 encodes a serine/threonine kinase, which organizes cell polarity and inhibits tumor growth. In the present patient, STK11 loss had occurred during the treatment and could induce rapid progression of her disease and PTTM. Citation Format: Fumie Fujisawa, Kei Kunimasa, Rieko Kano, Hiroki Kusama, Minako Nishio, Saki Matsui, Tetsuhiro Yoshinami, Nobuyoshi Kittaka, Shigenori Nagata, Toshinari Yagi, Takahiro Nakayama, Yasuhiro Tamaki, Fumio Imamura. SKT11 loss drives rapid cancer progression and fatal pulmonary tumor thrombotic microangiopathy (PTTM) in a breast cancer patient: A case report [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-31.

A Case of Pulmonary Tumor Thrombotic Microangiopathy Differentiated From Acute Pulmonary Thromboembolism

A Case of Pulmonary Tumor Thrombotic Microangiopathy Differentiated From Acute Pulmonary Thromboembolism

Pulmonary Tumor Thrombotic Microangiopathy Diagnosed during the Postoperative Course of Breast Cancer—A Case Report—

Pulmonary Tumor Thrombotic Microangiopathy Diagnosed during the Postoperative Course of Breast Cancer—A Case Report—

TUMORAL PULMONARY HYPERTENSION: A RARE BUT DEADLY COMPLICATION OF METASTATIC CANCER

SESSION TITLE: Medical Student/Resident Pulmonary Vascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary tumor microembolism (PTE) and pulmonary tumor thrombotic microangiopathy (PTTM) are rare complications of metastatic cancer that can mimic acute pulmonary embolism (PE). They can present as fulminant right heart failure and are invariably fatal. They are usually associated with gastric and bronchogenic carcinomas. We report a patient with metastatic breast cancer who rapidly developed severe right ventricular failure with no evidence of PE on imaging, thought to be due to tumoral pulmonary hypertension (PH). CASE PRESENTATION: A 33-year-old female with recently diagnosed invasive ductal breast cancer with liver metastases presented with dyspnea for a few days. She had tachycardia, tachypnea and tender hepatomegaly, along with elevated D-dimer and liver enzymes. CT angiogram (CTA) of the lung was negative for PE. Echocardiogram (ECHO) showed severe PH and mildly dilated right ventricle (RV). She received one dose of paclitaxel. On day 3, the patient was intubated for worsening respiratory distress. Repeat CTA of the lung was negative for PE. ECHO now showed a severely dilated RV with decreased systolic function highly suggestive of thromboembolism for which alteplase was administered empirically. Despite thrombolysis and vasopressor support, she continued to deteriorate and developed multiorgan failure leading to death within 24 hours of intubation. DISCUSSION: Tumoral PH includes microvascular conditions (PTE and PTTM), tumor macroembolism, and intravascular invasion of tumors. PTE is the occlusion of small pulmonary arteries by tumor cells. PTE along with activation of coagulation and growth factors causing intimal proliferation becomes PTTM. PTTM is commonly seen in adenocarcinoma with only 3% cases occurring with breast cancer. Patients present with dyspnea, hypoxemia, and PH of unknown origin invariably progressing to right heart failure and death. Routine imaging such as CTA of the lung is usually normal. Cytology of the aspirate from a wedged pulmonary artery catheter has a reported sensitivity of 80–88% and a specificity of 82– 94%. However, there is rapid clinical deterioration and associated high mortality. High index of suspicion is required for diagnosis which is rarely made antemortem. Decreasing tumor burden with chemotherapy in combination with dexamethasone, warfarin and aspirin, also immunotherapy with PDGF inhibitor (imatinib) and VEGF inhibitor (bevacizumab) can be beneficial. CONCLUSIONS: Unexplained acute PH in patients with metastatic cancer should prompt concern for tumoral PH. Some advances in antemortem diagnosis have given hope for the treatment of this once thought to be an exclusively postmortem diagnosis. Treatment targeting growth factors looks promising and needs further investigation. Reference #1: Price LC, Seckl MJ, Dorfmüller P, Wort SJ. Tumoral pulmonary hypertension. Eur Respir Rev. 2019;28(151):180065. Published 2019 Feb 6. doi:10.1183/16000617.0065-2018 Reference #2: Mury, C., Schneider, A. G., Nobile, A., Rotman, S., & Liaudet, L. (2015). Acute Pulmonary Hypertension Caused by Tumor Embolism: A Report of Two Cases. Pulmonary Circulation, 5(3), 577-579. doi:10.1086/682225 Reference #3: Mury, C., Schneider, A. G., Nobile, A., Rotman, S., & Liaudet, L. (2015). Acute Pulmonary Hypertension Caused by Tumor Embolism: A Report of Two Cases. Pulmonary Circulation, 5(3), 577-579. doi:10.1086/682225 Ho, A. L., Szulakowsi, P., & Mohamid, W. H. (2015). The diagnostic challenge of pulmonary tumour thrombotic microangiopathy as a presentation for metastatic gastric cancer: A case report and review of the literature. BMC Cancer, 15(1). doi:10.1186/s12885-015-1467-7 DISCLOSURES: No relevant relationships by Kristin Fless, source=Web Response No relevant relationships by Delyse Garg, source=Web Response No relevant relationships by Davita Mabourakh, source=Web Response No relevant relationships by Nirav Mistry, source=Web Response No relevant relationships by Aditi Saha, source=Web Response No relevant relationships by Sohaib Tariq, source=Web Response No relevant relationships by Lalithaa Thirunavukarasu Murugan, source=Web Response

微小な胃癌が原因となったpulmonary tumor thrombotic microangiopathyに対してEBUS-TBNAの有用性が示唆された1例

微小な胃癌が原因となったpulmonary tumor thrombotic microangiopathyに対してEBUS-TBNAの有用性が示唆された1例

Pulmonary tumor thrombotic microangiopathy: A systematic review of the literature

BACKGROUND Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare complication of cancer that was described almost 30 years ago. However, a minimal amount is known about this condition making pre-mortem diagnosis and treatment difficult. OBJECTIVES We aimed to systematically review and summarize the epidemiology, clinical manifestations, radiologic and hemodynamics features, diagnostic procedures and outcomes of PTTM. METHODS MEDLINE was searched (January 1990–November 2019) for case reports on PTTM. RESULTS A total of 132 studies were included (217 cases), including 126 case reports and 6 autopsy series. Gastric cancer (53%) and adenocarcinoma (87%) were the most common site of cancer and histological subtype, respectively. Mean age at presentation was 56 ± 16 years old. Most patients reported dyspnea, although symptoms were variable and nonspecific. Pulmonary hypertension was frequently documented either by transthoracic echocardiogram (97/103) or right heart catheterization (39/39). The diagnosis was made antemortem in only 29 patients using open lung biopsy (n = 12), transbronchial biopsy (n = 14) and CT-guided needle biopsy (n = 1), pulmonary microvascular cytology (n = 6); whereas, clinical presentation was suggestive of PTTM in 2 patients. Anticoagulation (n = 39), pulmonary hypertension-targeted treatments (n = 27), chemotherapy (n = 21), imatinib (n = 6) and thrombolysis (n = 5) were used as treatment strategies. Prognosis was poor with most patients dying within days or weeks of their admission. CONCLUSIONS PTTM is a rare syndrome that manifests as progressive dyspnea, pulmonary hypertension and right heart failure. PTTM is associated with a poor prognosis. Transbronchial biopsy and pulmonary microvascular cytology may represent alternatives to open lung biopsy to achieve an antemortem diagnosis of PTTM, although the best treatment strategy remains elusive.

Thrombotic microangiopathy in cancer patients

Thrombotic microangiopathy (TMA) is a rare phenomenon, which is severe pathology based on systemic microvascular thrombosis. TMA is characterized by thrombocytopenia and signs of microangiopathic hemolytic anemia. The review presents a modern data on the pathogenesis of tumor-associated thrombotic microangiopathy, considers the interaction of various effectors related to both tumor growth and metastasis process ― immune system activation, endotheliopathy formation, use of chemotherapeutic agents and targeted therapy in the pathogenesis of various forms of TMA. The interaction between the tumor tissue, hemostasis and immune systems are of the type of cascade of mutual activation, thus leading to the formation of a vicious circle, resulting in damage to endothelium and thrombosis in the microcirculatory channel, that is, the development of TMA. The formation of thromboembolism, which includes tumor tissue in the microvessels of the lungs, contributes to the development of pulmonary tumor thrombotic microangiopathy (PTTM). Сancer patients have higher vWF levels and lower ADAMTS13 levels or/and activity than the general population, often also depending on the stage of cancer: vWF and ADAMTS13 have been shown to be associated with thrombotic complications in cancer patients, and ADAMTS13 shows prognostic potential. Increased expression of complement proteins and/or activation of complement during chemotherapy, infectious and inflammatory complications may also cause TMA development. Pathogenesis of thrombotic microangiopathy also is associated with numerous chemotherapeutic agents, such as mitomycin C, gemcitabine, cisplatin, carboplatin and Bevacizumab, an inhibitor of VEGF. This may be the result of both the direct toxic effect of the drug on endothelium and damage of it by immune complexes caused by expression of the VEGF-antibodies. Usage of number of chemotherapeutic agents, especially anti-VEGF and tyrosine kinase inhibitors, which have a direct toxic effect on endothelium, are associated with the development of TMA. Mechanisms causing the development of TMA are considered as components of the hemostasis system, leading to the development of chronic, long-lasting disorders of the hemostasis system (chronic DIC syndrome) and are associated with high incidence of thrombotic complications.

RAPIDLY PROGRESSIVE PULMONARY HYPERTENSION AND RESPIRATORY FAILURE FROM UNEXPECTED TUMOR THROMBOTIC MICROANGIOPATHY IN A YOUNG WOMAN

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Pulmonary tumor thrombotic microangiopathy is an uncommon disorder in which tumor cells embolize to the pulmonary vasculature, causing activation of coagulation and fibrocellular subintimal proliferation. Vascular stenosis causes pulmonary hypertension (PH), right heart failure, and death. We present a case of PH and respiratory failure in a young woman with tumor emboli from high risk type human papillomavirus (HPV)-associated cervical cancer. CASE PRESENTATION: A 30 year old woman with asthma but in good health presented with dyspnea and was diagnosed with pneumonia. When antibiotics did not help, lower extremity ultrasound identified deep venous thrombi. Despite anticoagulation with Apixaban, dyspnea worsened, and she was hospitalized for suspected CTEPH. Initial vitals were BP 103/61 mmHg, HR 117/min, RR 28/min, T 36.4C, and SaO2 95% (15 LPM O2). Lungs were clear, heart rhythm was regular with increased P2, and edema was absent. Labs included AST 64 U/L and BNP 450 pg/mL. Hypercoagulable testing, rheumatologic studies, pregnancy testing, and infectious work-up were negative. ECHO showed a severely dilated RV, reduced function, and RVSP 40-50 mmHg. RHC showed RAP 14 mm Hg, PAP 59/33 (mean 43) mmHg, PCWP 7 mmHg, PA saturation 38%. CT angiography showed bilateral ground-glass opacities and consolidation with a dilated pulmonary trunk but no significant lymphadenopathy or pulmonary embolism. Despite vasodilators, PH and heart failure worsened, and veno-arterial ECMO was initiated. CT abdomen, part of the transplant evaluation, showed pelvic adenopathy and an abnormal cervix. A 2-cm cervical mass was palpated, but biopsy showed benign squamous mucosa. A subsequent true-cut cervical biopsy showed moderately to poorly differentiated squamous cell carcinoma with lymphovascular invasion. Surgical lung biopsy, performed to help define the lung disease, showed metastatic squamous cell carcinoma with arterial and lymphatic tumor emboli resulting in pulmonary infarction. Chemotherapy (Taxol/Cisplatin) was given, but she did not improve. She opted for palliative care and died from malignancy-related complications. Of note, cervical cells were positive for type 18-HPV DNA. DISCUSSION: This case highlights several important considerations. A thorough PH clinical assessment is warranted when symptoms progress despite therapy. Among the etiologies of PH, malignancy should also be considered, regardless of age or the absence of apparent risk factors. Finally, it is noteworthy that vaccination might have prevented disease in this instance: available vaccines protect against several HPV types, and all protect against HPV types 16 and 18, which have the highest cervical cancer risk. CONCLUSIONS: Though uncommon, pulmonary tumor thrombotic microangiopathy should be considered in patients with respiratory failure and PH of unclear etiology, particularly when symptoms progress despite medical therapy. Reference #1: Price LC et al, Pulmonary tumour thrombotic microangiopathy. Curr Opin Pulm Med. 2016 Sep;22(5):421-8. Reference #2: Godbole R et al. Pulmonary Tumor Thrombotic Microangiopathy: Clinical, Radiologic, and Histologic Correlation. J Clin Imaging Sci. 2015 Jul 31;5:44. Reference #3: Martínez-Gómez X et al. Multidisciplinary, evidence-based consensus guidelines for human papillomavirus (HPV) vaccination in high-risk populations. Euro Surveill. 2019 Feb;24(7). DISCLOSURES: no disclosure on file for Charles Hoopes; No relevant relationships by Timothy Lewis, source=Web Response No relevant relationships by Tyler Reynolds, source=Web Response No relevant relationships by Victoria Rusanov, source=Web Response no disclosure on file for Jose Tallaj; no disclosure on file for Vincent Valentine; No relevant relationships by Raymond Wade, source=Web Response No relevant relationships by Keith Wille, source=Web Response

PULMONARY TUMOR THROMBOTIC MICROANGIOPATHY: A RARE CAUSE OF PULMONARY HYPERTENSION

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: We present a case of a 64 year old male who was admitted to the hospital for rapidly progressive dyspnea. Imaging revealed bilateral mosaic attenuation, septal thickening and ground glass opacities. After an extensive work-up, the patient was diagnosed with pulmonary hypertension related to pulmonary tumor emboli mircoangiopathy(PTTM). CASE PRESENTATION: A 64-year-old male with a history of atrial fibrillation and OSA presented with dyspnea on exertion associated with hemoptysis and hematuria. The patient was in his usual state of health until the summer when he was diagnosed with atrial fibrillation as a part of his work physical. After of which he was referred to a cardiologist who attempted multiple unsuccessful cardioversions while on different anti-arrhythmic agents. During this time, he was also continued on rivaroxaban for anticoagulation. After his last cardioversion he was maintained in normal sinus rhythm but this unfortunately did little to help resolve his profound dyspnea on exertion. He then underwent a right heart catheterization as an outpatient and had a right atrial pressure of 3 mmHg, pulmonary artery pressure of 67/19 and a pulmonary capillary wedge pressure of 3 mmHg. As he was quickly worsening from a respiratory stand point, he was then referred to the emergency department for admission and pulmonary was consulted. Physical exam demonstrated clear lungs bilaterally with no palpable lymphadenopathy. Chest x-ray on admission showed clear lung fields with no infiltrate, effusions, or masses. CT chest revealed multiple ground glass opacities, mosaic attenuation and septal thickening. Differential diagnosis at the time included inflammatory, vasculitis, autoimmune, and malignant etiologies. Extensive lab work that included auto-immune serologies were all negative. Given radiologic findings and right heart catheterization report there was concern of an occlusive disease and the patient underwent a VATS wedge resection. Pathology showed metastatic poorly differentiated carcinoma involving pulmonary arteries and vein with immunohistochemical findings suggest urothelial carcinoma. DISCUSSION: Pulmonary hypertension in PTTM presents with rapidly progressive dyspnea and develops due to progressive vascular fibrointimal stenosis and occlusion. A unique abnormality that can be found on lab work in patients with PTTM is a ‘compensated DIC’ in which there is a slow consumption of clotting factors and platelets. This along with progressive RV dysfunction can clue a diagnostician to preform a RHC with a pulmonary artery wedge aspiration for cytology. This has a reported sensitivity of 80-88% and 82-94% specificity respectively. CONCLUSIONS: In patients where the severity of pulmonary hypertension is otherwise not explained by the severity of heart or lung disease, PH due to pulmonary artery obstruction needs to be considered in the differential diagnosis. Reference #1: Uruga, Hironori, et al. "Pulmonary tumor thrombotic microangiopathy: a clinical analysis of 30 autopsy cases.” Internal Medicine 52.12 (2013): 1317-1323. Reference #2: Roberts, Kari E., et al. "Pulmonary tumor embolism: a review of the literature.” The American journal of medicine 115.3 (2003): 228-232. Reference #3: Price, Laura C., Athol U. Wells, and Stephen J. Wort. "Pulmonary tumour thrombotic microangiopathy.” Current opinion in pulmonary medicine 22.5 (2016): 421-428. DISCLOSURES: no disclosure on file for Eliot Friedman; No relevant relationships by Kriti Pathak, source=Web Response No relevant relationships by Noor Salam, source=Web Response

The pathological challenge of establishing a precise diagnosis for pulmonary tumour thrombotic microangiopathy: identification of new diagnostic criteria.

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. 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. 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.

Pulmonary tumor thrombotic microangiopathy: a systematic review.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal disease process in which pulmonary hypertension (PH) develops in the setting of malignancy. The purpose of this study is to present a detailed analysis of cases of PTTM reported in literature in the hopes of achieving more ante-mortem diagnoses. We conducted a systematic review of currently published and available cases of PTTM by searching the term “pulmonary tumor thrombotic microangiopathy” on the Pubmed.gov database. Seventy-nine publications were included consisting of 160 unique cases of PTTM. The most commonly reported malignancy was gastric adenocarcinoma (94 cases, 59%). Cough and dyspnea were reported in 61 (85%) and 102 (94%) cases, respectively. Hypoxemia was reported in 96 cases (95%). Elevation in D-dimer was noted in 36 cases (95%), presence of anemia in 32 cases (84%), and thrombocytopenia in 30 cases (77%). Common findings on chest computed tomography (CT) included ground-glass opacities (GGO) in 28 cases (82%) and nodules in 24 cases (86%). PH on echocardiography was noted in 59 cases (89%) with an average right ventricular systolic pressure of 71 mmHg. Common features of PTTM that are reported across the published literature include presence of dyspnea and cough, hypoxemia, with abnormal CT findings of GGO, nodules, and mediastinal/hilar lymphadenopathy, and PH. PTTM is a universally fatal disease process and this analysis provides a detailed examination of all the available published data that may help clinicians establish an earlier diagnosis of PTTM.

Tumoral pulmonary hypertension.

Tumoral pulmonary hypertension (PH) comprises a variety of subtypes in patients with a current or previous malignancy. Tumoral PH principally includes the tumour-related pulmonary microvascular conditions pulmonary tumour microembolism and pulmonary tumour thrombotic microangiopathy. These inter-related conditions are frequently found in post mortem specimens but are notoriously difficult to diagnose ante mortem The outlook for patients remains extremely poor although there is some emerging evidence that pulmonary vasodilators and anti-inflammatory approaches may improve survival. Tumoral PH also includes pulmonary macroembolism and tumours that involve the proximal pulmonary vasculature, such as angiosarcoma; both may mimic pulmonary embolism and chronic thromboembolic PH. Finally, tumoral PH may develop in response to treatments of an underlying malignancy. There is increasing interest in pulmonary arterial hypertension induced by tyrosine kinase inhibitors, such as dasatanib. In addition, radiotherapy and chemotherapeutic agents such as mitomycin-C can cause pulmonary veno-occlusive disease. Tumoral PH should be considered in any patient presenting with unexplained PH, especially if it is poorly responsive to standard approaches or there is a history of malignancy. This article will describe subtypes of tumoral PH, their pathophysiology, investigation and management options in turn.

Pulmonary tumour thrombotic microangiopathy in a patient with metastatic colorectal adenocarcinoma – a case report

Pulmonary tumour thrombotic microangiopathy (PTTM) is a rare end stage complication of malignancy with patients presenting with progressive and worsening dyspnoea secondary to increased pulmonary vascular resistance and subsequent right heart failure. First described by Herbay,1 PTTM is a clinicopathological diagnosis usually made post mortem, with the presence of tumour microemboli associated with fibrous intimal hyperplasia of the pulmonary vasculature. A high degree of clinical suspicion is required as the prognosis without treatment is grim, typically days to weeks. We report a 36-year-old male who presented with four days of dyspnoea on a background of recently diagnosed metastatic carcinoma of unknown primary. He was initially investigated for pulmonary embolus, however subsequent computed tomography pulmonary angiography (CTPA) showed no abnormality. Echocardiography revealed signs of acute right heart failure secondary to elevated pulmonary vascular resistance (PASP 82 mmHg, N 18–25). Despite anticoagulation, antibiotics and ICU support, the patient passed away within 24 hours of his admission. Autopsy revealed a sigmoid tumour, widespread lymphadenopathy and peritoneal deposits, with microscopy and immunohistochemistry confirming poorly differentiated colorectal adenocarcinoma within the sigmoid tumour and metastatic deposits. Atypical cells associated with thrombus and fibrous intimal hyperplasia in pulmonary vasculature confirmed PTTM as the cause of death.

A case of pulmonary tumor thrombotic microangiopathy which imatinib was effective

A case of pulmonary tumor thrombotic microangiopathy which imatinib was effective

Sudden Unexpected Death During Bronchoscopy of a Patient with Pulmonary Lymphangitic Carcinomatosis and Pulmonary Tumor Thrombotic Microangiopathy due to Gastric Cancer

Sudden Unexpected Death During Bronchoscopy of a Patient with Pulmonary Lymphangitic Carcinomatosis and Pulmonary Tumor Thrombotic Microangiopathy due to Gastric Cancer

1932P - Pulmonary tumor thrombotic microangiopathy (PTTM): 24 case series and its criteria for pathological diagnosis

1932P - Pulmonary tumor thrombotic microangiopathy (PTTM): 24 case series and its criteria for pathological diagnosis

INVISIBLE BUT FATAL: A CASE OF PULMONARY TUMOR EMBOLISM

SESSION TITLE: Lung Pathology 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Pulmonary tumor embolism (PTE) is a rare and potentially fatal cause of dyspnea in patients with malignancy. It has been reported in 3 -26% of autopsies in patients who died with solid tumors. We present a case of metastatic breast cancer complicated by PTE. CASE PRESENTATION: A 54- year- old woman presented with worsening dyspnea of 4 days duration. Medical history was significant for recurrent, metastatic breast cancer treated with Abraxane. She developed a secondary thrombocytopenia and Abraxane was held four weeks prior to presentation. On exam, her blood pressure was normal but she was tachycardic, tachypneic, and hypoxic to low 80s on room air. Arterial blood gas revealed hypoxemia. Laboratory work-up showed platelets of 34,000 and troponin of 0.2 which peaked at 1. EKG had T-wave inversions in V1-V4. CT Angiography of chest revealed new right pleural effusion, right hilar and mediastinal lymphadenopathy and no pulmonary embolism. She was diagnosed with a non- ST elevation myocardial infarction and heparin drip was initiated. Transthoracic echocardiogram showed hypokinetic and dilated right ventricle, moderate pulmonary hypertension (PH) and normal ejection fraction without wall motion abnormalities. Myocardial perfusion scan was negative for ischemia and heparin drip discontinued on hospital day (HD) 2. Right heart catheterization was pursued; pulmonary artery pressure was compatible with severe PH at 78mmHg. Wedge pressure was 18mmHg. Pulmonary Artery Wedge Cytology (PAWC) was done. On HD 4 she developed severe dyspnea, was transferred to the ICU and quickly deteriorated to cardiac arrest and died. Cytology obtained from PAWC showed metastatic breast adenocarcinoma. Autopsy confirmed tumor studding of right posterior lungs, parietal and visceral pleura with no pulmonary emboli or bronchial tumor obstruction. There was also evidence of hemorrhagic plaque on left anterior descending coronary artery, suspicious for tumor embolization to the coronaries. No pathology was done at autopsy. DISCUSSION: PTE typically presents with progressive dyspnea in the setting of PH and right-sided heart failure without evidence of pulmonary embolism. The pathogenesis is related to intravascular activation of coagulation cascade with production of cytokines, including platelet derived growth factors (PDGF), leading to arteriolar remodeling and stenosis. Diagnosis can be made with PAWC or open lung biopsy but it is often a post-mortem diagnosis. Treatment is directed at the primary malignancy but there are case reports showing benefit with Imatinib, a tyrosine kinase inhibitor, and corticosteroids. CONCLUSIONS: PTE is a rare complication of solid cancers. Clinicians must have a high index of suspicion in patients with malignancies presenting with unexplained dyspnea. Timely diagnosis and initiation of therapy is crucial in decreasing mortality in these patients. Reference #1: Roberts KE, Hamele-Bena D, Sagi A, Stein CA, Cole RP. Pulmonary tumor embolism: a review of the literature. The American Journal of Medicine, August 2003. Reference #2: Kubota K, Shinozaki T, Imai Y, Kario K. Imatinib dramatically alleviates pulmonary tumor thrombotic microangiopathy induced by gastric cancer. BMJ Case Report. 2017 Sep 7;2017 Reference #3: Miyazaki S, Ikeda T, Ito G, Inoue M, Nara K, Nishinaga Y, Hasegawa Y. Pulmonary tumor thrombotic microangiopathy successfully treated with corticosteroids: a case report. Journal of Medicine, Case Report. 2017; 11: 356 DISCLOSURES: No relevant relationships by Deborah Akanya, source=Web Response No relevant relationships by Olufunmilayo Falade, source=Web Response No relevant relationships by Sonali Gupta, source=Web Response No relevant relationships by Edward Herman, source=Web Response No relevant relationships by Erica Rabold, source=Web Response No relevant relationships by Soumya Thumma, source=Web Response

Pulmonary Tumor Thrombotic Microangiopathy: A Rare Sequela of End-Stage Colon Cancer

This report aims to raise awareness of pulmonary tumor thrombotic microangiopathy (PTTM), a diagnosis made almost exclusively postmortem. The etiology of colon cancer has only been documented in a small number of articles. Furthermore, the distinctive morphological and behavioral features in this particular adenocarcinoma are compared and contrasted to those of other primary malignancies that have been previously described. A full autopsy including brain performed on a middle-aged man after sudden death revealed an undiagnosed colon cancer. Gross and microscopic findings demonstrated pulmonary tumor embolism with associated PTTM as the cause of death. During a hospital admission for neurological symptoms, a 60-year-old male became progressively hypotensive and developed acute shortness of breath. He subsequently developed cardiac arrest and expired shortly after. The major autopsy discovery was a moderate to poorly differentiated rectosigmoid colon adenocarcinoma with widespread metastasis. Extensive tumor emboli occluding small peripheral pulmonary blood vessels bilaterally were presumed to be the immediate cause of death. Cardiomegaly with pulmonary and hepatic congestion suggested cor pulmonale. Similar in presentation as venous thromboembolism, pulmonary tumor embolism should be included in the clinical differential diagnosis for cause of sudden death after progressive dyspnea especially in patients with malignancies. PTTM refers to the wall thickening of pulmonary arteries as a reactive change to tumor thrombi. Over time, pulmonary hypertension and consequent cor pulmonale follow. Morphologically, the poorly differentiated population of tumor cells in this report is comparable to the signet-ring cell carcinoma of the stomach and previously reported colonic adenocarcinomas of the same grade that is typically associated with PTTM. However, it was the population of moderately differentiated tumor cells of this case that metastasized and formed thrombi.

CT manifestation of pulmonary tumor thrombotic microangiopathy: a case report

CT manifestation of pulmonary tumor thrombotic microangiopathy: a case report