DIAGNOSIS IN ONCOLOGY
Arthur Skarin, MD, Consultant Editor
Nonmalignant Diagnoses in Patients
CASE 1. MEDIASTINAL LYMPHADENOPATHY ASSOCIATED WITH CONGESTIVE HEART FAILURE
A 66-year-old man with dilated cardiomyopathy secondary to coronary artery disease was noted to have diffuse mediastinal lymphadenopathy on computed tomography (CT) scan during evaluation for an orthotopic heart transplant. The patient had pulmonary congestion, recurrent ventricular tachycardia that required automatic internal cardioverter-defibrillator, atrial fibrillation, and a history of non-insulin-dependent diabetes. He reported a 75 pack-year smoking history but had ceased smoking more than 20 years earlier. Cardiac catheterization revealed a 15% left ventricular ejection fraction and reversible pulmonary hypertension. The chest CT showed enlargement of multiple mediastinal nodes in the precarinal, subcarinal, pericardial, anterior-posterior window, and hilar lung regions. Nodes measured 1 to 1.5 cm and included a 2 to 3-cm subcarinal lymph node (Fig 1, arrow). The chest CT also demonstrated cardiomegaly and a “ground glass” appearance in the lung fields consistent with pulmonary edema. After receiving medical therapy for congestive heart failure, a repeat CT scan showed improved pulmonary edema but no change in mediastinal lymphadenopathy. A third chest CT showed persistent mediastinal lymphadenopathy. Because of the persistent adenopathy and the potential for heart transplantation, a mediastinoscopy with biopsies of both the subcarinal and paratracheal nodes was performed. Histopathology revealed no evidence of malignancy and was only significant for anthracosis with numerous histiocytes containing carbon particles, consistent with his smoking history (Fig 2). A follow-up chest CT 8 months later showed increased bulky lymphadenopathy in the mediastinum. A subcarinal lymph node was estimated to be 4 × 2 cm. Abdominal, pelvic, and head CTs revealed no evidence of further lymphadenopathy or malignancy. A bone marrow biopsy showed normal morphology and iron stores. Cultures of the marrow for fungi and mycobacteria were negative. Because repeat cardiac evaluation showed fixed pulmonary hypertension, the patient was withdrawn from the organ transplant list. The patient has remained stable with advanced congestive heart failure.
The demonstration of mediastinal lymphadenopathy on chest CT as a result of congestive heart failure is not widely recognized. Slanetz et al1 reported one series of 46 patients who underwent chest CT during periods of symptomatic congestive failure. Some degree of mediastinal node enlargement was observed in 55% of cases. In a subset of 17 patients who had documented elevated pulmonary capillary wedge pressures within 24 hours of the CT scan, some degree of lymphadenopathy was observed in 82%. No patient was known to develop lymphoma or other malignancy during clinical follow-up of 2 years. Storto et al,2 however, failed to draw the association between congestive heart failure and mediastinal lymphadenopathy in a report of seven patients studied with high-resolution CT imaging. The pathogenesis of mediastinal lymphadenopathy in congestive heart failure is not known. In an experimental study, Drake et al3 used rapid ventricular pacing to induce heart failure in sheep. They demonstrated that efferent lymph flow was impeded when venous pressures exceeded 15 cm of water. A chronic impairment of lymph efferent flow might presumably lead to passive congestion of the node, resulting in lymphadenopathy in addition to the other more well-known findings of congestive heart failure on CT. Other than congestive failure, we found little evidence for another cause of bulky adenopathy in our patient. Although captopril, one of the patient’s chronic medications, has been associated with adenopathy, we would not expect that to be restricted to the mediastinal and hilar nodes.4
The differential diagnosis of mediastinal lymphadenopathy includes infectious, inflammatory, or neoplastic processes. It should be emphasized that patients with advanced congestive heart failure may demonstrate significant mediastinal lymphadenopathy on chest CT. Traditionally, 1.0 cm has been used as the upper limit of normal for the short axis of a mediastinal node in the transverse plane as detected on CT scan.5 Slanetz et al1 suggest that cases such as the one reported here in which the lymph nodes are larger than 2 cm or fail to decrease after resolution of pulmonary edema may warrant further investigation by biopsy. Ultimately, the decision to biopsy enlarged mediastinal nodes must be individualized for each patient, and further noninvasive studies, including gallium or positron-emission tomography scan, might help guide the clinician and avert unnecessary or further invasive procedures.
Ann Partridge, Selim Nasser, and Sunny Dzik Departments of Medicine and Pathology; Dana-Farber Cancer Institute, Massachusetts General Hospital, and Harvard Medical School; Boston, MA
Copyright 2000 American Society of Clinical Oncology
Journal of Clinical Oncology, Vol 18, No 13 (July), 2000: pp 2635-2639
REFERENCES
1. Slanetz PJ, Truong M, Shepard JOA, et al: Mediastinal lymph- adenopathy and hazy mediastinal fat: New CT findings of congestive heart failure. AJR Am J Roentgenol 171:1307-1309, 1998
2. Storto ML, Kee ST, Golden JA, et al: Hydrostatic pulmonary edema: High-resolution CT findings. AJR Am J Roentgenol 165:817- 820, 1995
3. Drake RE, Dhother S, Teague RA, et al: Lymph flow in sheep with rapid cardiac ventricular pacing. Am J Physiol 272:R1595-1598, 1997
4. Aberg H, Morlin C, Frithz G: Captopril-associated lymphadenop- athy. Br Med J (Clin Res Ed) 283:1297-1298, 1981
5. Glazer GM, Gross BH, Quint LE, et al: Normal mediastinal lymph nodes: Number and size according to American Thoracic Society mapping. AJR Am J Roentgenol 144:261-265, 1985
CASE 2. LUNG CANCER WITH MEDIASTINAL LYMPHADENOPATHY DUE TO AMYLOIDOSIS
A 69-year-old man with chronic obstructive pulmonary disease and a history of asbestos exposure and heavy cigarette smoking presented with progressive dyspnea and scant hemoptysis. Chest x-ray revealed a lesion in the right mid-lung suspicious for primary lung cancer. Chest computed tomography showed a spiculated 3-cm right lower-lobe mass. Extensive mediastinal lymphadenopathy was also present (Fig 1). As part of preoperative staging, bronchoscopy and mediastinoscopy were performed, and pathologic examination of a needle biopsy of the right lower-lobe mass revealed poorly differentiated non-small-cell lung carcinoma. Biopsies of a right paratracheal lymph node revealed fibrous tissue and amorphous material exhibiting green birefringence of congo red-stained tissue, consistent with amyloid (Figs 2A and 2B). Subsequent studies revealed liver metastases. He was treated palliatively and eventually succumbed to progressive disease.
Primary mediastinal and pulmonary amyloidosis occurs infrequently and may be confused with other tumors that are more commonly found in the chest.1 Amyloidosis of the mediastinal lymph nodes has been associated with other malignancies, including multiple myeloma and nonpulmonary squamous cell carcinoma.2,3 In one series of patients with systemic amyloidosis, four (67%) of the six cases were associated with an underlying malignancy.3 In three of the cases, malignant cells were admixed with the amyloid, and in another case, malignancy was present at a distant site. The presence of an associated neoplasm must be considered in the differential diagnosis of amyloid deposits in lymph nodes. Furthermore, mediastinal lymph node involvement in the absence of pulmonary involvement is extremely rare and should be a diagnosis based on pathologic confirmation.4 The differential diagnosis of other benign causes of mediastinal lymphadenopathy includes tuberculosis, sarcoidosis, Castleman’s disease, and other granulomatous and infectious diseases. In the workup of lung cancer patients, surgical staging with cervical and/or anterior mediastinoscopy is considered critical at many institutions for deciding multimodality management. Both sensitivity and specificity of computed tomography staging for mediastinal
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disease range from 70% to 80%.5-7 Recent data from positron-emission tomography scanning may improve the diagnostic accuracy of noninvasive studies for evaluating the mediastinum for the presence of regional metastases.8
Ann Partridge, Mairin Mcmenamin, and David Sugarbaker Departments of Medicine, Pathology, and Surgery; Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School; Boston, MA
Copyright 2000 American Society of Clinical Oncology
REFERENCES
1. Plockinger B, Muller MR, Eckersberger F: Isolated amyloidosis of hilar lymph nodes. Langenbecks Arch Chir 378:167-179, 1993
2. Melato M, Antonutto G, Falconieri G, et al: Massive amyloidosis of mediastinal lymph nodes in a patient with multiple myeloma. Thorax 38:151-152, 1983
3. Halliday BE, Silverman JF, Finley JL: Fine-needle aspiration cytology of amyloid associated with nonneoplastic and malignant lesions. Diagn Cytopathol 18:270-275, 1998
4. Naschitz JE, Yeshurun D, Pick AI: Intrathoracic amyloid lymph- adenopathy. Respiration 49:73-76, 1986
5. Weng E, Tran L, Rege S, et al: Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer. Am J Clin Oncol 23:47-52, 2000
6. McLoud TC, Swenson SJ: Lung carcinoma. Clin Chest Med 20:697-713, vii, 1999
7. Lau CL, Harpole DH: Noninvasive clinical staging modalities for lung cancer. Semin Surg Oncol 18:116-123, 2000
8. Kim S, Park CH, Han M, et al: The clinical usefulness of F-18 FDG coincidence PET without attenuation correction and without whole-body scanning mode in pulmonary lesions comparison with CT, MRI, and clinical findings. Clin Nucl Med 24:945-949, 1999
CASE 3. RIGHT ATRIAL THROMBUS ASSOCIATED WITH A CENTRAL VENOUS CATHETER IN A PATIENT WITH METASTATIC ADRENOCORTICAL CARCINOMA
A 28-year-old man presented with facial swelling, muscle weakness, and hypertension. His urinary cortisol level was greater than 3,000 µg/d and he was diagnosed with Cushing’s syndrome. Abdominal computed tomography (CT) showed a 13-cm right adrenal mass, which was found on surgical resection to be a primary adrenocortical carcinoma. Restaging CT scans 3 months later revealed new metastases in his liver, retroperitoneal lymph nodes, and lungs. A double-lumen central venous line (Port-A-Cath; SIMS Deltec, Inc, St Paul, MN) was inserted into the right subclavian vein, confirmed by chest radiography. He was treated with chemotherapy for 4 months, first with a regimen of mitotane, cisplatin, etoposide, and doxorubicin and subsequently with weekly paclitaxel, but his disease progressed. He subsequently participated in a phase I trial of a farnesyl transferase inhibitor for 2 months. Although he experienced no new symptoms, a routine follow-up chest CT showed progression of pulmonary metastases. Also noted, however, was a 2.5-cm low-attenuation region in the right atrium around the tip of the central venous catheter (Fig 1, arrow). A transthoracic echocardiogram was obtained, which confirmed the presence of a 2 X 1.5-cm echo density attached to the right atrial indwelling catheter (Fig 2, thrombus). The patient was admitted to the hospital and subsequently proceeded to right atriotomy and thrombus removal, requiring cardiopulmonary bypass. A 2.5-cm mass adherent to the right atrial (RA) wall was resected. Pathology showed a section of RA myo- and endocardium with adherent organizing thrombus, with neovascularization and granulation tissue. He recovered without complications.
RA thrombosis as a complication of central venous catheters has been reported rarely in adults, although there is a much larger literature in infants and children.1 This difference may in part be due to the size of the catheter relative to the cross-sectional area of the blood vessels, at least in premature infants.2 Of 156 children with cancer and indwelling catheters screened with two-dimensional echocardiography, 13 (8.8%) had RA thrombi.3 Treatment included atriotomy and thrombus removal in two and anticoagulation, observation, or catheter removal in the remaining patients.
In adults, cases of RA thrombus have been reported in patients with a permanent pacing catheter4 and ventriculoatrial shunt5 as well as noncancer patients receiving total parenteral nutrition.6 Other cases of catheter-related RA thrombus have
IF -30.0
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been reported, with treatment including heparin, thrombolysis,7 endovascular embolectomy,8 and right atriotomy. A prospective study was performed of 55 patients who had transesophageal echocardiogram 1 and 6 to 8 weeks after Hickman catheter placement. Thirteen patients had the tip of the catheter in the RA, eight at the RA-superior vena cava junction, and 27 in the superior vena cava. Six thrombi (12.5%) were detected in the 48 patients successfully imaged, all of whom were in the group with the catheter tip in the RA (or 46% of this group). All patients were asymptomatic.9 No studies have been performed that address the incidence of symptomatic RA thrombus, the risk of thrombus migration after catheter placement, the association of RA thrombus with specific cancers, and differences in RA thrombus formation depending on catheter type.
In summary, we report a case of a patient with adrenocortical carcinoma who was noted on routine chest CT scan to have an RA thrombus associated with a central venous catheter. Although he responded well to surgical removal of the thrombus, optimal management of this problem remains unclear and may include some combination of observation, anticoagulation, thrombolysis, endovascular thrombectomy, catheter removal, or right atriotomy. The decision of how to proceed for a cancer patient with a line-associated RA thrombus should be individualized until this problem is investigated further.
William K. Oh, Benjamin H. Lee, and Nancy K. Sweitzer Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA Copyright 2000 American Society of Clinical Oncology
REFERENCES
1. Ross P, Ehrenkranz R, Kleinan CS, et al: Thrombus associated with central venous catheters in infants and children. J Pediatr Surg 24:253-256, 1989
2. Alkalay AL, Mazkereth R, Santulli T, et al: Central venous line thrombosis in premature infants: A case management and literature review. Am J Perinatol 10:323-326, 1993
3. Korones DN, Buzzard CJ, Asselin BL, et al: Right atrial thrombi in children with cancer and indwelling catheters. J Pediatr 128:841- 846, 1996
4. Kinney EL, Allen RP, Weidner WA, et al: Recurrent pulmonary emboli secondary to right atrial thrombus around a permanent pacing catheter: A case report and review of the literature. Pacing Clin Electrophysiol 2:196-202, 1979
5. Yavuzgil O, Ozerkan F, Erturk U, et al: A rare cause of right atrial mass: Thrombus formation and infection complicating a ventricu- loatrial shunt for hydrocephalus. Surg Neurol 52:54-60, 1999
6. Turrentine MA, Smalling RW, Parisi VM: Right atrial thrombus as a complication of total parenteral nutrition in pregnancy. Obstet Gynecol 84:675-677, 1994
7. Nani R, Novello P, Decasello M, et al: [Right atrial thrombosis with concurrent thrombus attached to a central venous catheter: Clinical case.] Minerva Anestesiol 63:209-212, 1997 (Italian)
8. Beregi JP, Aumegeat V, Loubeyre C, et al: Right atrial thrombi: Percutaneous mechanical thrombectomy. Cardiovasc Intervent Radiol 20:142-145, 1997
9. Gilon D, Schecter D, Rein AJ, et al: Right atrial thrombi are related to indwelling central venous catheter position: Insights into time course and possible mechanism of formation. Am Heart J 135:457-462, 1998