Diagnosis of pulmonary microvascular metastases by cytologic evaluation of pulmonary artery catheter-derived blood specimens

doi:10.1016/0046-8177(94)90197-X

Human Pathology

Volume 25, Issue 3, March 1994, Pages 257-262

https://doi.org/10.1016/0046-8177(94)90197-X Get rights and content

Abstract

Pulmonary microvascular tumor embolization is a recognized cause of respiratory distress in cancer patients that is rarely diagnosed antemortem. Previous studies with relatively few patients have reported high diagnostic yield using wedged pulmonary artery catheter-derived blood samples to evaluate dyspneic cancer patients for possible microembolization. From 1991 to 1993, 21 cancer patients with respiratory distress of relatively acute onset and varying severity who required pulmonary artery catheterization for hemodynamic monitoring were evaluated using this technique. Pulmonary microvascular cytology (PMC) was interpreted as positive for malignant cells in nine of 21 patients presenting with a range of tumor types, including carcinomas of the breast, colon, and pancreas as well as non-Hodgkin's lymphoma. In 11 patients the PMC was interpreted as negative. One case was considered nondiagnostic. Megakaryocytes, noted in most PMC specimens as well as in several samples of simultaneously drawn peripheral blood, may mimic epithelial tumor cells. Immunocytochemical stains for factor VIII and cytokeratins were used to resolve occasional diagnostic dilemmas. Clinical and/or pathologic follow-up information was available for all patients. Diagnostic accuracy was highest for epithelial malignancies. Two false-negative results occurred in patients with metastatic choriocarcinoma and breast carcinoma. Circulating malignant cells in the peripheral blood of a patient with non-Hodgkin's lymphoma led to one false-positive diagnosis. Benign lymphoid elements in PMC generally have a reactive and variable appearance that should not be misinterpreted as lymphoma. We conclude that PMC is a useful tool in the evaluation of dyspneic cancer patients requiring pulmonary artery catheterization for hemodynamic monitoring and its use potentially avoids additional diagnostic procedures.

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Antemortem diagnosis of PTTM is difficult and, to date, the condition has been detected at autopsy. However, recent studies have reported the possibility of antemortem diagnosis with the help of pulmonary microvascular cytology on samples drawn through a wedged pulmonary artery catheter, with a reported sensitivity of 80%–88% and specificity of 82%–94%.3 Godbole et al. reported that common findings on chest CT included GGOs and nodules.4
Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare, rapidly progressive, and often fatal complication of cancer, particularly prostate cancer. A 67-year-old man with advanced prostate cancer developed dyspnea. Chest computed tomography revealed ground-glass opacities across bilateral lung fields, and echocardiography showed right heart failure. As PTTM was suspected, docetaxel chemotherapy was administered immediately. His respiratory condition and right heart failure improved; however, 2-months later his respiratory symptoms were exacerbated, causing death. Autopsy showed fibrocellular intimal proliferation of the small pulmonary arteries, which confirmed PTTM induced by prostate cancer. Although PTTM is fatal, early diagnosis and treatment would improve the prognosis.
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Le syndrome de microangiopathie thrombotique tumorale pulmonaire est une entité clinicopathologique rare où des micro-emboles de cellules tumorales dans la microcirculation pulmonaire induisent une microangiopathie thrombotique, une insuffisance respiratoire et un tableau de cœur pulmonaire aigus ou subaigus. Ses caractéristiques histologiques comprennent des micro-emboles tumoraux dans les petites artères et artérioles du poumon, associés à une prolifération fibrocellulaire et fibromusculaire de l’intima et parfois à la formation de thrombus. Le diagnostic est extrêmement difficile avant le décès. Ainsi, un grand nombre des observations rapportées reposent sur des données autopsiques. De très rares observations de diagnostics réalisés avant le décès suggèrent l’éventuelle efficacité d’une chimiothérapie. De nombreux détails restent à élucider, la recherche interdisciplinaire étant une priorité avec une étroite collaboration entre pathologistes et cliniciens afin de mieux comprendre ce syndrome le plus souvent mortel. Grâce à cette collaboration, il est éventuellement possible que ce syndrome ne soit plus considéré comme toujours ultimement fatal, l’utilisation de thérapeutiques ciblées permettant des survies de plusieurs mois après le diagnostic.
Pulmonary tumor thrombotic microangiopathy syndrome is a rare clinicopathological entity in which tumor cell micro-emboli in the pulmonary microcirculation induced thrombotic microangiopathy. This can cause respiratory failure, and acute or sub-acute right heart failure. Histological features include micro tumor emboli in the small arteries and arterioles of the lung associated with thrombus formation and fibro-cellular and fibro-muscular intimal proliferation. The diagnosis is however extremely difficult to make before death. Thus, most of the observations reported are based on autopsy data. Very rare diagnostic observations made before death suggest the potential effectiveness of chemotherapy. Many details remain to be elucidated, interdisciplinary research is a priority with close collaboration between pathologists and clinicians to better understand this, often fatal, syndrome. It may be that the use of targeted therapies will improve the very poor prognosis allowing survival of several weeks or months after diagnosis.
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It is difficult to differentiate between tumor embolism and thromboembolism. Pulmonary wedge aspiration cytology has been reported to be useful in the diagnosis of pulmonary tumor embolism [5,6]. In our case, we think that pulmonary embolism was caused by the thrombus induced by osimertinib and not from the metastatic lung cancer, because the thrombus immediately disappeared only after anticoagulation therapy.
Pulmonary embolism (PE) can be life-threatening, and it is challenging to diagnose because of its nonspecific signs and symptoms. PE is also an important potential risk of osimertinib treatment, however, clinical courses regarding retreatment after osimertinib-induced acute pulmonary embolism remain unclear. We described a 77-year-old woman with postoperative recurrent lung adenocarcinoma who developed osimertinib-induced acute PE. She received apixaban and was later successfully retreated with osimertinib. This case suggests that retreatment with osimertinib after osimertinib-induced acute PE may be a treatment option when alternative therapeutic options are limited.
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Radiological findings are frequently minimal or non-specific [21,22]. To establish the diagnosis, both open or transbronchial lung biopsy and microvascular pulmonary cytology of blood samples drawn from a wedged pulmonary artery catheter have been proposed [23,24]. However, these procedures are invasive and therefore not always feasible in severely ill patients with advanced cancer.
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^☆: Presented at the Annual Meeting of the United States and Canadian Academy of Pathology, New Orleans, LA, 1993.

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Original contributionDiagnosis of pulmonary microvascular metastases by cytologic evaluation of pulmonary artery catheter-derived blood specimens☆

Abstract

Chest

Chest

Am J Med

Chest

Chest

Hum Pathol

Subacute cor pulmonale due to tumor embolization to the lungs

Angiology

Subacute cor pulmonale due to tumor embolization

Arch Pathol Lab Med

Tumor cell embolism to pulmonary alveolar capillaries—Cause of sudden cor pulmonale

Arch Pathol Lab Med

Original contribution
Diagnosis of pulmonary microvascular metastases by cytologic evaluation of pulmonary artery catheter-derived blood specimens☆