Lymphangitic Carcinomatosis Research Articles

Neoplastic pulmonary lymphangitis: Symptomatic treatment and quality-of-life evaluation in a prospective palliative care series

19536 Background: Neoplastic lymphangitis, or lymphangitis carcinomatosa, is a rare and distressing form of lung metastasis, for which symptom improvement is strongly necessary. Since measuring quality of life is an important step toward improving symptom management in cancer patients, and dyspnea in pulmonary lymphangitis is a complex syndrome in end-of-life care, we focused on evaluating a cohort of those individuals. Methods: 52 consecutive patients with neoplastic pulmonary lymphangitis (NPL) were prospectivelly followed in 3 services, with quality of life (QoL) evaluation also, using Medical Outcomes Study 36-item Short-Form Health Survey (SF- 36) and Saint George's Respiratory Questionnaire (SGRQ). Results: 65% (34) of patients were female; age ranged from 37 to 84 years (median: 60). Primary tumor sites were: 28 lung (54%), 18 breast (35%), 5 digestive (9%) and 1 bone cancer. Histological findings were of adenocarcinoma in most cases (71%). Karnofsky performance scale ranged from 10 to 90% (median: 60%); 52% (27) patients had other comorbidities (Charlson index ranged from 6–10; median 7); 48% (25) were previous smokers; hemoglobin levels ranged from 4.9 to 16.7 g/dL (median: 12). We also evaluated 33 patients with echocardiography, and 13 (43%) of them had signs of associated pulmonary hypertension; ejection fraction ranged from 46 to 83% (median: 69%); diastolic dysfunction was present in 22 and pericardial effusion in 10 patients. At accrual, median QoL scores were of: 32% (range: 0–84%) for SF-36 (scale with 0 worst) and 66% (range: 0–100%) for SGRQ (scale with 100% worst). Treatment is showed in a table below. Median survival was of 4 months (range: 0.2–40+ months); 22 (42%) of the patients had an unusual longer survival of more than 6 months, still showing good QoL scores. Conclusions: Despite the fact that QoL is generally poor and survival is short for patients with NPL, some patients may have longer survival time and some improvement is possible with active palliative care. [Table: see text] No significant financial relationships to disclose.

Adenocarcinoma de pulmón simulando una enfermedad pulmonar intersticial en un varón de 30 años

A case of a 30-year-old man is presented. He had a past medical history of asthma and presented with cough, shortness of breath, fever and chest pain. The chest X-ray showed cardiomegaly and a interstitial pattern. The echocardiogram revealed a severe pericardial effusion that required performing a pericardiocentesis. A CT scan showed mediastinal adenopathies and reticulonodular interstitial pattern. A bronchoscopy could not be completed because of non-tolerance. Finally a lung biopsy allowed us to reach a final diagnosis of lung adenocarcinoma. Following, some aspects of lung cancer in young people are commented, especially its incidence, histology, symptoms and a prognosis. A few aspects of the interstitial lung disease are also addressed and the differential diagnosis with lymphangitic carcinomatosis.

Diffuse Pulmonary Meningotheliomatosis

Minute pulmonary meningothelial nodules are rare lesions histologically composed of small nests of epithelioid cells located within the interstitium of the lung. These nodules are generally asymptomatic and are usually found incidentally at autopsy or in surgical specimens resected for unrelated causes. The lesions are most often single, although multiple lesions with unilateral involvement of one or even all lobes of the same lung have been described. To our knowledge, cases of meningothelial nodules with disseminated bilateral pulmonary involvement associated with clinical symptoms of restrictive pulmonary disease and radiologic evidence of diffuse reticulonodular pulmonary infiltrates have not been previously documented. We have studied 5 patients presenting with diffuse bilateral pulmonary involvement by numerous minute pulmonary meningothelial nodules. The patients were 4 women and a man aged 54 to 75 years who presented clinically with dyspnea and shortness of breath and the lesions were discovered on open lung biopsies performed for the evaluation of diffuse bilateral interstitial lung infiltrates found on chest x-rays and computed tomography scans. In 3 patients, there was a previous history of malignancy and the radiologic findings were suspected of representing diffuse metastatic disease. Histologically, the lesions were composed of small clusters of epithelioid cells with round to oval nuclei devoid of atypia and surrounded by abundant eosinophilic cytoplasm. Immunohistochemical studies showed positivity of the tumor cells for epithelial membrane antigen and vimentin, and negative staining for cytokeratin, actin, S-100 protein, CD34, chromogranin, and synaptophysin. Electron microscopic examination in 1 case confirmed the ultrastructural features of meningothelial cells, including complex cytoplasmic interdigitations joined by well-developed desmosomes and abundant intracytoplasmic intermediate filaments. The diffuse bilateral involvement of lung parenchyma in the present cases can lead to confusion on clinical and radiologic grounds with a variety of interstitial pulmonary processes, including idiopathic interstitial pneumonia and lymphangitis carcinomatosa. Diffuse pulmonary meningotheliomatosis should be considered in the clinical differential diagnosis of diffuse interstitial pulmonary infiltrates.

A Patient with Pulmonary Lymphangitic Carcinomatosis Successfully Treated with TS-1 and Cisplatin

A 37-year-old man was referred to our hospital with complaints of dyspnea and general fatigue. Chest radiograph and CT scan revealed thickness of bronchovascular bundles in both lungs. In spite of various examinations, the primary lesion was not identified. He received chemotherapy containing TS-1 and cisplatin. Pulmonary lymphangitic carcinomatosis disappeared and the patient achieved a good partial response. He survived for 14 months after the chemotherapy. We believe the combination of TS-1 and cisplatin is one of the attractive options for patients with cancer of unknown primary site.

Pneumonia lipóide exógena: importância da história clínica no diagnóstico

Lipoid pneumonia is a rare disease resulting from the micro-aspiration of lipid formulations. Making a diagnosis of lipoid pneumonia requires a high degree of clinical suspicion. Herein, we report the case of a female patient with a history of breast cancer, presenting progressive dyspnea and cough, together with radiological findings of bilateral pulmonary infiltrate. The working diagnosis of lymphangitic carcinomatosis, for which chemotherapy would be indicated, was called into question based on the high-resolution computed tomography findings and on the fact that the patient had a history of chronic ingestion of laxatives containing mineral oil. A lung biopsy confirmed a diagnosis of lipoid pneumonia, which should always be considered in patients with diffuse lung disease having been exposed to potential causative agents.

Pulmonary Lymphangitic Carcinomatosis (PLC): Spectrum of FDG-PET Findings

The lungs are among the most common sites for metastases from a multitude of cancers. The majority of pulmonary metastases appear nodular on radiologic images. Interstitial spread of tumor through pulmonary lymphatics, also known as pulmonary lymphangitic carcinomatosis (PLC), is not uncommon and constitutes approximately 7% of pulmonary metastases. PLC is most often seen with adenocarcinoma of a variety of histologies such as thyroid carcinoma, and melanoma. It is usually noted in late stages of malignancy and therefore is indicative of a poor prognosis. Diagnosis of PLC is usually based on a combination of clinical and radiologic findings. However, the diagnosis is difficult when patients have limited clinical findings or have a history of or the possibility of other interstitial lung diseases. High-resolution computed tomography (HRCT) has been the modality of choice in the radiologic diagnosis of PLC. Imaging features of PLC on HRCT include thickening of interlobular septa, fissures, and bronchovascular bundles. Distribution of PLC may be focal or diffuse, unilateral or bilateral, and symmetric or asymmetric. Although FDG-PET has been extensively used in primary or secondary lung malignancies, its role and appearance in PLC have not been well determined in the literature. In this communication, we describe a spectrum of FDG-PET and CT findings in 5 cases with PLC. Similar to CT, the distribution of PLC can be extensive or limited on the FDG-PET. Diffuse, lobar, or segmental FDG uptake in the lungs is seen in extensive PLC. In limited PLC, a linear or a hazy area of FDG uptake extending from the tumor can be seen. Recognition of various patterns related to PLC on FDG-PET may allow accurate diagnosis of disease and could potentially influence the management of these patients.

A phase II study of combined chemotherapy with methotrexate, 5-fluorouracil, and low-dose cisplatin (MFP) for histologically diffuse-type advanced and recurrent gastric cancer (KDOG9501)

Histologically diffuse-type gastric cancer is well known to have a poor prognosis and is often complicated with abdominal and pleural effusions. We evaluated the efficacy of a low dose of cisplatin combined with methotrexate and 5-fluorouracil (MFP therapy) in diffuse-type advanced gastric cancer. The study group comprised 47 patients. Patients with pleural effusion or ascites were actively enrolled. Methotrexate (30 mg/m(2) per day) plus 5-fluorouracil (600 mg/m(2) per day) was administered on days 1 and 8. Cisplatin (6 mg/m(2) per day) was given daily for 14 days after which there was 14 day's rest. Calcium leucovorin (15 mg) was administered after methotrexate. The overall response rate was 38.3%. Ascites disappeared or decreased in 15 of 23 patients (disappeared in 9). Pleural effusion disappeared or decreased in 6 of 8 patients (disappeared in 4). Of the 21 patients with poor oral intake at study entry, 15 (71.4%) were able to orally ingest food. Hematologic toxicity of grade 3 or higher comprised leukopenia in 10 patients (21.3%) and neutropenia in 9 (19.1%). Nonhematologic toxicity included anorexia and nausea/vomiting, in 1 patient each (2.1%). The median survival time was 211 days. MFP therapy is useful for the management of diffuse-type inoperable and recurrent gastric cancer, even in patients with conditions such as pleural effusion, ascites, or lymphangitis carcinomatosa who have a poor prognosis or cannot eat solid food.

Successful re-treatment with gefitinib for carcinomatous meningitis as disease recurrence of non-small-cell lung cancer

We report the case of a woman with gefitinib-sensitive lung adenocarcinoma, who was successfully re-treated with gefitinib for carcinomatous meningitis as the disease recurrence. The good response to gefitinib treatment was supported in part by the existence of epidermal growth factor receptor mutation in carcinoma cells in the specimen obtained from transbronchial lung biopsy, in which E709G in exon 18 and L858R in exon 21 were shown. Although carcinomatous meningitis had been well controlled by the treatment with gefitinib, serum carcinoembryonic antigen (CEA) level increased with re-growth of primary tumor and development of lymphangitic carcinomatosis. Immunohistochemical findings revealed de novo emergence of CEA-producing carcinoma cells in the biopsy specimen taken after recurrence of pulmonary lesion during re-treatment of gefitinib, but revealed little or no CEA expression in the specimen obtained at first presentation. These facts may suggest the possibility of oligo clonality of carcinoma cells in this case.

Pictorial Essay: Multinodular Disease

The evaluation of patients presenting with multinodular pulmonary disease provides an important clinical challenge for physicians. The differential diagnosis includes an extensive list of benign and malignant processes making the management of these cases frequently problematic. With the introduction of high-resolution CT (HRCT) scanning, the ability to assess various patterns of diffuse multinodular disease has evolved into an essential part of the diagnostic process. The purpose of this article is to develop an approach to the diagnosis of multinodular parenchymal disease using HRCT scan pattern recognition as a point of departure.

Obstructive jaundice caused by secondary pancreatic tumor from malignant solitary fibrous tumor of pleura: A case report

A 77-year-old man on systemic chemotherapy against postoperative bilateral multiple lung metastases of malignant solitary fibrous tumor of the pleura suffered from pruritus and jaundice. Blood examination showed elevated levels of hepatobiliary enzymes. Abdominal computed tomography showed a tumor with peripheral enhancement in the pancreatic head, accompanied with the dilatation of intra- and extra-hepatic bile ducts. He was diagnosed as having obstructive jaundice caused by a pancreatic head tumor. The pancreatic head tumor was presumably diagnosed as the metastasis of malignant solitary fibrous tumor of the pleura, because the findings on the pancreatic head tumor on abdominal CT were similar to those on the primary lung lesion of malignant solitary fibrous tumor of the pleura. The pancreatic tumor grew rapidly after the implantation of metallic stent in the inferior part of the common bile duct. The patient died of lymphangitis carcinomatosa of the lungs. Autopsy revealed a tumor that spread from the pancreatic head to the hepatic hilum. Microscopically, spindle-shaped cells exhibiting nuclear atypicality or division together with collagen deposition were observed. Immunohistochemically the pancreatic head tumor cells were negative for staining of alpha-smooth muscle actin (alpha-SMA) or CD117, but positive for vimentin, CD34 and CD99. These findings are consistent with those on malignant solitary fibrous tumor of the pleura. We report the first case of obstructive jaundice caused by a secondary pancreatic tumor from malignant solitary fibrous tumor of the pleura.

Duodenal lymphangitis carcinomatosa: Endoscopic characteristics and clinical significance

Duodenal lymphangitis carcinomatosa has been sporadically described, but so far little attention has been paid to duodenal lymphangitis carcinomatosa. Four cases with duodenal lymphangitis carcinomatosa were endoscopically and histologically examined. The four cases exhibited multiple polypoid lesions along the Kerckring's folds and/or were covered by characteristically granular, non-ulcerated mucosa upon thickening. The granularity seems to been caused by dilated lymph vessels containing the carcinoma cells. The lesions were microscopically characterized by: (i) involvement of lymph vessels located in the upper portion of the lamina propria; (ii) no inflammatory changes; and (iii) no desmoplastic changes. Primary sites were thought to be the stomach in case 1, the pancreas in cases 2 and 4, and unknown in case 3. All patients died within 6 months after admission or endoscopic examination. As duodenal lymphangitis carcinomatosis shows characteristic endoscopic appearance, endoscopic diagnosis is not difficult. We should realize that the lesion represents extremely poor prognosis, and it should be distinguished from ordinary metastatic duodenal carcinoma.

Tunneled Pleural Catheters for Palliation of Malignant Pleural Effusions

Tunneled Pleural Catheters for Palliation of Malignant Pleural Effusions

Can Maximum Intensity Projection Images With Multidetector-Row Computed Tomography Help to Differentiate Between the Micronodular Distribution of Focal and Diffuse Infiltrative Lung Diseases?

The objective of this study was to evaluate whether maximum intensity projection (MIP) images increased the ability of experienced and resident radiologists to differentiate between the micronodular distribution of focal and diffuse infiltrative lung diseases. The cases used in the study were those of 26 patients with focal or diffuse micronodular lung diseases, including 7 cases of sarcoidosis, 6 of miliary tuberculosis, 3 of pulmonary tuberculosis, 3 of chronic bronchitis, 2 of human T-lymphotropic virus type 1-associated bronchoalveolar disorder, 2 of diffuse aspiration bronchiolitis, 1 of atypical mycobacterial infection, and 1 of lymphangitic carcinomatosis. Scans of the entire lung during a single breath hold at 1.25-2.5 mm thickness and a pitch of 6 were performed using a multidetector-row computed tomography (MDCT) apparatus with a 4-row detector. Additional MIP image slabs were produced from the initial axial images on all study patients on a workstation according to a protocol that incorporated a slab thickness of 10 mm, a reconstructed interval of 10 mm, and a window width of -1500 Hounsfield units. The ability of 10 radiologists (5 board-certified radiologists and 5 radiology residents) to interpret contiguous thin-section CT scans and additional MIP images was then studied in an observer performance study. The results of both sets of observer performances were compared using receiver operating characteristic analysis. In the resident observers, the mean area under the receiver operating characteristic curve (Az) value increased significantly from 0.654 without the MIP images to 0.753 with the MIP images (P < 0.01). In the board-certified radiologists, however, the mean Az values remained unchanged at 0.867 without the MIP images and 0.846 with the MIP images. This study showed that MIP images may help radiologists in training to differentiate between the micronodular distribution of focal and diffuse infiltrative lung diseases.

Fluorodeoxyglucose Positron Emission Tomography Pattern of Pulmonary Lymphangitic Carcinomatosis

The purpose of this study was to evaluate the F-fluorodeoxyglucose (FDG) positron emission tomography (PET) uptake in pulmonary lymphangitic carcinomatosis identified on computed tomography (CT) in patients with lung cancer. This was a retrospective analysis of F-FDG PET images in 7 patients (4 male and 3 female, mean age: 56.6 +/- 6.6 years) with lung cancer with a CT-based diagnosis of lymphangitic carcinomatosis. The F-FDG PET scans in a group of 7 patients (4 male and 3 female, mean age: 42.1 +/- 5.66 years) with normal chest CT scans served as a control group. Mean standardized uptake values (SUVs) were calculated based on average tumor uptake, initial injected activity, and body weight. The intensity of F-FDG uptake in diseased lung is significantly greater than in corresponding normal contralateral lung or in the lungs of normal controls (P = 0.003). The ratio of the SUV of lung with lymphangitic carcinomatosis to corresponding contralateral normal lung was significantly increased (P = 0.006), and the ratio of the SUV of mediastinal blood pool to lung with lymphangitic carcinomatosis was significantly decreased (P = 0.0002). There is diffuse increased FDG uptake in the lung corresponding to the CT pattern of lymphangitic carcinomatosis.

Diseases affecting the peribronchovascular interstitium: CT findings and pathologic correlation

Central bronchi and pulmonary arteries are surrounded and enveloped by a strong connective-tissue sheath termed the peribronchovascular interstitium, extending from the level of the pulmonary hila into the peripheral lung. Thickening of the peribronchovascular interstitium can be seen in a wide variety of diseases. The CT appearance can be smooth, nodular, or irregular depending on the underlying cause. Many of the diseases affecting the peribronchovascular interstitium are entities that show a predilection for lymphatic routes, such as sarcoidosis, pulmonary lymphangitic carcinomatosis, silicosis, and lymphoproliferative disorders. There are other entities that mainly affect the peribronchovascular interstitium without a predominant perilymphatic distribution, such as hydrostatic pulmonary edema, cryptogenic organizing pneumonia, Kaposi's sarcoma, interstitial pulmonary emphysema, and interstitial hemorrhage. Although there is an overlap in radiologic features, some CT findings are useful in differentiating among these entities. When CT shows mainly peribronchovascular abnormality, the differential diagnosis is considerably reduced, and it is generally possible to reach the correct diagnosis by considering the clinical context. We illustrate the CT findings and pathologic correlation for a number of different disorders that mainly affect the peribronchovascular interstitium.

A Case of Fatal Respiratory Failure after Surgery for Advanced Supraglottic Laryngeal Carcinoma

Pulmonary lymphangitic carcinomatosis (PLC) is an uncommon type of pulmonary metastasis from laryngeal carcinoma. We encountered a case of fatal respiratory failure after surgery for supraglottic laryngeal carcinoma with multiple cervical lymph node metastases. On day 25 postoperatively, the patient suddenly developed fever and noted slowly progressive difficulty in breathing. Laboratory data, radiological findings, and the clinical course of this patient were strongly suggestive of PLC. The patient refused fiberoptic bronchoscopy and glucocorticoid therapy, leading to rapid deterioration due to increasing respiratory distress, and died of respiratory failure on postoperative day 32. PLC should be considered a possible presentation of pulmonary metastasis associated with head and neck carcinoma. Chest CT may be needed to detect subclinical PLC, especially in cases of advanced head and neck carcinomas.

Squamous cell carcinoma of the cervix presenting as lymphangitic carcinomatosis: a case report and review of the literature

Background. Lymphangitic carcinomatosis (LC) secondary to carcinoma of the cervix is rare. The presenting symptoms are misleading and nonspecific, which often leads to delayed diagnosis. Case. We present the case of a 24-year-old woman with dyspnea and lower back pain, who was found to have stage IIIb squamous cell carcinoma of the cervix complicated by pulmonary LC. Conclusions. Pulmonary LC is a rare but important manifestation of metastatic cervical cancer. Patients present with severe respiratory compromise, which mimics other, more common disease states. Diagnosis can be achieved by transbronchial biopsy. Optimal treatment of the patient with LC is not well defined, but a trial of chemotherapy and/or intravenous steroids may be warranted. Prognosis for this condition is poor.

Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis.

Radiation-induced lung disease (RILD) due to radiation therapy is common. Radiologic manifestations are usually confined to the lung tissue within the radiation port and are dependent on the interval after completion of treatment. In the acute phase, RILD typically manifests as ground-glass opacity or attenuation or as consolidation; in the late phase, it typically manifests as traction bronchiectasis, volume loss, and scarring. However, the use of oblique beam angles and the development of newer irradiation techniques such as three-dimensional conformal radiation therapy can result in an unusual distribution of these findings. Awareness of the atypical manifestations of RILD can be useful in preventing confusion with infection, recurrent malignancy, lymphangitic carcinomatosis, and radiation-induced tumors. In addition, knowledge of radiologic findings that are outside the expected pattern for RILD can be useful in diagnosis of infection or recurrent malignancy. Such findings include the late appearance or enlargement of a pleural effusion; development of consolidation, a mass, or cavitation; and occlusion of bronchi within an area of radiation-induced fibrosis. A comprehensive understanding of the full spectrum of these manifestations is important to facilitate diagnosis and management in cancer patients treated with radiation therapy.

Transmission of a pancreatic adenocarcinoma to a renal transplant recipient.

Transmission of donor tumours in solid organ transplant recipients is rare, but has been reported with fatal outcome in some cases depending on the original tumour type and location. We report a case of a pancreatic adenocarcinoma of donor origin presented as lymphangitis carcinomatosa of the lung in a renal transplant recipient 9 months after transplantation, which is likely to have contributed to the death of the patient 15 months after transplantation. The donor tumour was originally diagnosed on adrenal tissue removed from the donor kidney during bench preparation. At the time of the diagnosis this kidney and the liver of the multi-organ donor had been transplanted. The liver patient was urgently retransplanted within 24 h. The renal recipient opted not to have a transplant nephrectomy having been made aware of the risk of tumour transmission. The contralateral kidney was discarded. Management of recipients with potential transmission of initially undiagnosed donor malignancy is difficult. Early transplant nephrectomy may be the safest option.

Dramatic effect of ZD1839 (‘Iressa’) in a patient with advanced non-small-cell lung cancer and poor performance status

We describe the case of a 52-year-old Japanese woman with advanced adenocarcinoma of the lung, in whom once-daily treatment with 250 mg ZD1839 (‘Iressa’) demonstrated a marked antitumour effect. She had initially achieved a partial response with cisplatin-based combination chemotherapy, but had subsequently progressed and had failed to respond to salvage chemotherapy. She had also received whole-brain irradiation for brain metastases. On admission, the patient was confined to bed due to dyspnoea and had rapidly progressing hypoxia secondary to lymphangitis carcinomatosa and a massive right pleural effusion. She was treated with oxygen supplementation and oral ZD1839, which, within a week, led to marked tumour regression and gradually improving dyspnoea. The main adverse event observed was a grade 2 rash. A month after starting ZD1839 treatment, the patient was discharged without the need for oxygen supplementation and had since returned to full-time work. This is a demonstration of ZD1839 producing a dramatic clinical response when administered to a patient with poor performance status who had received extensive prior treatment with cytotoxic agents.‘Iressa’ is a trademark of the AstraZeneca group of companies.