Chylothorax in a patient with metastatic Kaposi sarcoma ... · Chylothorax is a relatively uncommon...

IntroductionChylothorax is a relatively uncommon cause of pleural

effusion (1). Lymph in the thoracic duct originates at the cisterna chyli and then passes from the abdomen into the mediastinum through the aortic hiatus. It then ascends su-periorly in the posterior mediastinum and, at the level of T5-T6, the thoracic duct crosses to the left side to enter the superior mediastinum (1, 2). Chylous pleural effusions can

be diagnosed on CT or MRI. The CT finding of chylous effusions is typically a large unilateral effusion of water attenuation and may demonstrate fat. The MRI findings may demonstrate high signal intensity on T1WI due to fat content.

The causes of chylous effusions can be congenital, trau-matic, iatrogenic, malignant, idiopathic, infectious, or in-flammatory (1, 2). Congenital chylothorax occurs more due to congenital malformations than to trauma during deliv-ery (1). Chylothorax is predominantly seen following trauma or cardiothoracic surgery (2, 3). Traumatic injury to the thoracic duct is more common with penetrating trauma than blunt trauma, and is seen with hyperextension injuries (2, 4). Generally, an injury to the lower third of the thoracic duct causes a right chylous effusion, to the upper two-thirds of the thoracic duct causes a left chylous effu-sion, and to the thoracic duct (as it crosses midline) causes bilateral chylous effusions. The thoracic duct can be ob-structed from lymphadenopathy (including lymphoma, sarcoidosis, lung cancer, and tuberculosis) (5). We review the less common causes of chylothorax, including lym-phangioma, lymphangectasis, and lymphangioleiomyoma-

RCR Radiology Case Reports | radiology.casereports.net 1 2015 | Volume 10 | Issue 2

Chylothorax in a patient with metastatic Kaposi sarcoma: Differential diagnostic considerationsRyan Alexander, DO; Magda Rizer, DO; William Burke, MD; and Lawrence Ciment, MD

Kaposi sarcoma (KS) is a low-grade mesenchymal tumor involving blood and lymphatic vessels. There are four types, based on clinical presentation: classic, endemic (Africana), iatrogenic (typically, involving renal allograft recipients), and AIDS-associated (epidemic). Kaposi’s sarcoma-associated herpes virus in-fection has been linked along with other factors to the development of KS. The Kaposi’s sarcoma-associated herpes virus interacts and encodes for numerous molecular proteins that play a role in the pathogenesis of KS, including latency-associated nuclear antigen, viral G protein-coupled receptor, viral FLICE inhibitory protein, and viral IL-6. KS primarily affects the skin and causes disseminated disease in a variety of organs. Involvement of visceral organs other than the lining of the alimentary tract is ex-tremely rare. While the chylous pleural effusions of KS may resemble other pulmonary diseases (includ-ing lymphangioma, lymphangectasis, and lymphangioleiomyomatosis) with chylous effusions at thoracic CT, differentiating features may allow for more prompt diagnosis and treatment. The presumptive diag-nosis of AIDS-related pulmonary KS is often clinical. A tissue diagnosis is not required to establish the diagnosis of pulmonary KS. There are a variety of causes of chylothorax. The primary finding is a near-water-attenuating pleural effusion. The secondary findings of chylothorax can help differentiate the etiology.

Citation: Alexander R, Rizer M, Burke W, Ciment L. Chylothorax in a patient with metastatic Kaposi sarcoma: Differential diagnostic considerations. Radiology Case Reports. (Online) 2015;10(2);1098.

Copyright: © 2015 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 2.5 License, which permits reproduction and distribution, provided the original work is properly cited. Commercial use and derivative works are not permitted.

Drs. Alexander, Rizer, and Burke are in the Department of Diagnostic Radiology, and Dr. Ciment is in the Department of Pulmonary and Critical Care Medicine, all at Mount Sinai Medical Center, Miami Beach, FL. Contact Dr. Alexander at [email protected].

Competing Interests: The authors have declared that no competing interests exist.

DOI: 10.2484/rcr.v10i2.1098

Radiology Case ReportsVolume 10, Issue 2, 2015

tosis (LAM). Familiarity with these entities may lead to more prompt recognition and diagnosis.

Case report A 21-year-old homosexual male presented with a chief

complaint of abdominal pain and bright red blood per rec-tum over the preceding three weeks. He had nausea with-out vomiting, bloody diarrhea, and 10 bowel movements per day. He denied any weight loss, fever, chest pain, or shortness of breath. Colonoscopy with rectal biopsies demonstrated KS on pathology. The rectal bleeding was self-limited. He was managed for a left pleural effusion with

a left pleural drain (Fig. 1). Laboratory testing confirmed that he was HIV-positive with a CD4 count of 12 cells/μL (427–1625 cells/μL). He was subsequently discharged home in stable condition.

As an outpatient, a metastatic evaluation was performed starting with PET/CT (Fig. 2), which demonstrated exten-sive lymphadenopathy. His newly diagnosed HIV was managed with Highly Active Antiretroviral Therapy (HAART), and chemotherapy was initiated for his KS as an outpatient. He then had excision of a right level-five cervi-

cal lymph node that was positive for metastatic KS. Over the next five months, the patient experienced shortness of breath with upper- and lower-extremity edema responsive to diuretic therapy (Fig. 3).

He was admitted five months later from his original ad-mission for exacerbations of these symptoms (Figs. 3, 4). He developed recurrent bilateral bloody chylous pleural effusions with progressive shortness of breath and extensive peripheral lymphedema. He was tachycardiac with increas-ing oxygen requirements requiring BiPAP, and eventually was intubated.

The effusions were resistant to serial thoracentesis and pleural drains (Fig. 4). Multiple samples were sent for cytol-ogy, which was negative for atypical and malignant cells. The location of thoracic duct involvement by KS was to be assessed by lymphoscintigraphy before ligation of the duct. There was such extensive inguinal lymphadenopathy that the radiotracer remained at the level of the upper thighs 24 hours post injection (Fig. 5). The thoracic duct at the cis-terna chyli was found to be infiltrated with tumor on the chest CT (Fig. 6). The thoracic duct was unable to be safely ligated due to extensive infiltration of the tumor; therefore, bilateral decortications with chest tube placement were performed instead in an attempt to control the chylous effusions. Bronchoalveolar lavage (BAL) demonstrated hemorrhagic secretions with erythema of the bronchioles. An infectious evaluation was negative. The patient expired from cardiopulmonary arrest.

Chylothorax in a patient with metastatic Kaposi sarcoma: Differential diagnostic considerations


Fig 2. PET/CT. Note extensive hypermeta-bolic lymphadenopathy extending from the up-per cervical regions throughout all nodal stations of the supra-clavicular, axillary, me-diastinal, hilar, retroperi-toneal, mesenteric, iliac, and inguinal regions.

Fig 1. Loculated left pleural effusion on original admission.

Fig 3. Note interval progression of subcutaneous and mes-enteric edema over five months from original admission (A) to readmission (B) due to infiltration of the cisterna chylis.

DiscussionKS is a low-grade mesenchymal tumor involving blood

and lymphatic vessels (6, 7). There are four types based on clinical presentation: classic, endemic (Africana), iatrogenic (typically renal allograft recipients) and AIDS-associated (epidemic). Human herpesvirus-8 (HHV8) infection has been linked along with other factors to the development of KS (6). KS is considered an AIDS-defining illness.

Involvement of visceral organs other than the lining of the alimentary tract is extremely rare (7, 8). Chylothorax is a rare manifestation of KS involving the thoracic duct (9). KS with chylothorax was initially postulated to develop due to metastatic KS to the thoracic duct; more recent findings suggest that this may arise because of in-situ KS in this region (10, 11). KS-related chylothoraces frequently de-velop with concomitant upper-airway KS disease (9).



Fig. 5. Lymphoscintigraphy. An interdermal injection between the web spaces of the toes was performed using Sulfur Colloid bound to the radiotracer Tech-99M. There is migration of Tech-99M filtered Sulfur Colloid radiotracer to the level of the upper thighs within one hour that persists at this level up to 24 hours post injection (arrows). No radiotracer is seen reaching the tho-rax (arrowheads).

Fig 4. Recurrent chylous pleural effusions status post-chest-tube placement and talc sclerotherapy. A. Increased right and loculated left pleural effusion on readmission. B. Status post-talc sclerotherapy and removal of right-sided chest tube with worsening loculated right pleural effusion. Note increased loculated and complex left pleural effusion with pleural thickening. Also note consolidative change involving almost the entire left lower lobe, lingual, and left upper lobe.

Pathophysiology/pathogenesisHuman herpes virus-8 (also known as Kaposi’s sarcoma-

associated herpes virus [KSHV]) was discovered by Chang and Moore and has been linked to the development of KS as well as lymphoproliferative disorders, including primary-effusion lymphoma and multicentric Castleman disease (12, 13). Infection with KSHV is necessary for the development of KS, although it is not sufficient by itself (13). HIV co-infection significantly increases the risk of KS (13). KS has been found to be more common among persons who are at greater risk for sexually transmitted infections, which led to a search for an infectious etiology (14). KS cells have been screened for infectious agents, including cytomegalovirus, Epstein Barr virus, human papilloma virus, and myco-plasma; these viral sequences are not uniformly found in KS.

KSHV interacts and encodes for numerous molecular proteins that play a role in the pathogenesis of KS, includ-ing latency-associated nuclear antigen (LANA), viral G protein-coupled receptor, viral FLICE inhibitory protein, and viral IL-6 (12, 13). LANA acts as a transcriptional regulator binding to tumor-suppressing proteins p53 and retinoblastoma protein, which promotes the replication of the latent viral episome (12). The viral G protein-coupled receptor leads to proangiogenic signals by the upregulation of hypoxia-inducible factor 1-alpha and the subsequent expression of vascular endothelial growth factor (VEGF)-A and activation of VEGF-receptor-2, which in turn activates PI3K-akt and the mammalian target of rapamycin (mTOR) pathway (13). Viral FLICE inhibitory protein is associated with constitutively activated nuclear factor-κB, where it then activates a large number of antiapoptotic genes (12). Viral IL-6 stimulates gp 130 coupled to the JAK-STAT pathway (13). It is secreted by KSHV-infected cells, allowing tumor cells to regulate their own growth through an autocrine pathway (13). A host of other pro-teins may play a role, including the HIV Tat protein, which has been shown to serve as a growth factor. In animal mod-els, the replication of the HIV virus may enhance the repli-cation of KSHV (13). HIV Tat promotes the migration and

proliferation of cytokine-activated endothelial cells, stimu-lating KS growth (13).

Clinical presentationKS primarily affects the skin and causes disseminated

disease in a variety of organs. Skin lesions range from sev-eral millimeters to several centimeters in size. The lesions are usually not painful or pruritic.

Involvement of visceral organs other than the lining of the alimentary tract is extremely rare. Gastrointestinal AIDS-related KS compromise is the most common visceral involvement in disseminated disease, being seen in up to 50% of patients (7). AIDS-related KS can affect any level of the gastrointestinal tract from the oropharynx to the rectum, including the gallbladder (7). The duodenum is the most frequently affected site (7).

Pulmonary involvement with KS, in the majority of cases, occurs in conjunction with extensive mucocutaneous disease (15). Pulmonary involvement can be the initial manifestation (8). Affected patients can present with short-ness of breath, fever, cough, hemoptysis, or chest pain, or pulmonary involvement may be asymptomatic. When a new diagnosis of KS is suspected in a patient with HIV infection, the degree of HIV-related immunosuppression is assessed by measuring the CD4 count and HIV viral load (7). In patients with AIDS-related KS, the CD4 count ap-pears to be the most important factor associated with the development of KS.

Imaging manifestationsKS can present with chylothorax. The typical pulmonary

CT findings in AIDS-related KS are the presence of bilat-eral, ill-defined nodules in a peribronchovascular distribu-tion (flame-shaped lesions representing tumor infiltration involving the bronchovascular bundles), areas of ground-glass opacities (representing edema and blood filling the airspace) surrounding nodules (the “halo sign”), peribron-chovascular and interlobular septal thickening (representing edema or tumor infiltration), fissural nodularity, mediasti-nal lymphadenopathy, pleural effusions (common), or pleu-ral implants (rare) (6, 7, 16). The nodules correspond to proliferation of neoplastic cells (6).

DiagnosisThe presumptive diagnosis of AIDS-related pulmonary

KS is often clinical (16). A tissue diagnosis is not required to establish the diagnosis of pulmonary KS. Bronchoscopy is frequently performed to diagnose pulmonary KS with stains, culture, and cytology (which are frequently nega-tive). The bronchoscopic appearance of endobronchial KS is considered to be characteristic enough to allow a diagno-sis (6). Parenchymal lesions may occur in the absence of tracheobronchial lesions detected by bronchoscopy. Endo-bronchial KS lesions typically appear violaceous and are macular or papular, often at airway bifurications (8). Alveo-lar hemorrhage is frequently diagnosed during BAL (7, 8). Endobronchial and transbronchial biopsies have a low di-



Fig. 6. Cisterna Chyli infiltrated with tumor. The cisterna chyli is identified adjacent to the right side of the abdominal aorta and posterior to the inferior vena cava. The cisterna chyli appears enlarged and complex in attenuation (arrow).

agnostic yield for KS, with the risk of significant hemor-rhage following biopsy (8, 17, 18).

In the setting of worsening pulmonary status, the pri-mary diagnostic role of thoracentesis may be to exclude an underlying infection caused by mycobacterium or fungus. KS lesions are found on the visceral but not parietal pleura (7). Pleural fluid cytology and biopsies are not helpful in diagnosis (19).

When chylous effusions are identified at thoracic CT, imaging findings allow lymphangioma, lymphangectasis, and LAM to be differentiated. Lymphangioma can present with chylothorax. The imaging findings of lymphangioma are typically a homogeneous, thin-walled, well-defined, low-attenuating cystic mass, though increased attenuation occurs with high protein content, hemorrhage, or infection. Calcification or contrast enhancement is atypical. These lesions insinuate and cause displacement as they spread throughout the mediastinum, which also makes complete resection difficult (4). The most common location is the superior aspect of the anterior mediastinum. Other rare locations include the pulmonary hila, pericardium, and intrapulmonary.

Lymphangectasis can present with chylothorax. The im-aging findings of lymphangectasis include bilateral ground-glass opacities, smooth interlobular septal thickening, marked pleural thickening, and mediastinal soft-tissue infil-tration. The imaging findings resemble those of LAM; however, lymphangectasis presents at a younger age with a much more progressive course (2, 4). LAM has dilated lym-phatics like lymphangectasis but also has increased number of lymphatics.

LAM can present with chylothorax. The imaging find-ings of LAM include diffuse, thin-walled, uniform lung cysts (20). LAM is indistinguishable on imaging from tuber-ous sclerosis complex. It can cause recurrent pneumothorax.

TreatmentThere is increasing evidence that HAART and an im-

proved immune response are associated with complete or partial regression of KS lesions (6, 8, 16). Some studies showed that HAART alone can lead to stabilization and regression of KS, often eliminating the need for chemora-diation therapy (6, 16, 19).

For asymptomatic pulmonary KS, typical treatment is initiated with ART without concomitant chemotherapy. For progression of pulmonary KS after initiation of ART or symptomatic pulmonary KS at presentation, systemic che-motherapy is then generally indicated in addition to ART (11). Radiation therapy has been shown to improve symp-tomatic control, though long-term survival remains poor (8).

Pleural effusions have been managed with repeat thora-centesis in combination with ART and chemotherapy. If the pleural effusion rapidly reoccurs despite thoracentesis, an indwelling pleural catheter can be installed, or talc pleu-rodesis performed. Chylous effusions respond poorly to chemical pleurodesis (21).

ConclusionKS is a low-grade mesenchymal tumor involving blood

and lymphatic vessels. Kaposi’s sarcoma-associated herpes virus (KSHV) infection has been linked along with other factors to the development of KS. KSHV interacts and encodes for numerous molecular proteins that play a role in the pathogenesis of KS, including latency-associated nu-clear antigen (LANA), viral G protein-coupled receptor, viral FLICE inhibitory protein, and viral IL-6. KS primar-ily affects the skin and causes disseminated disease in a va-riety of organs. Involvement of visceral organs other than the lining of the alimentary tract is extremely rare. While the chylous pleural effusions of KS may resemble other pulmonary diseases with chylous effusions at thoracic CT including lymphangioma, lymphangectasis, and LAM, differentiating features may allow for more prompt diagno-sis and treatment. The presumptive diagnosis of AIDS-related pulmonary KS is often clinical. A tissue diagnosis is not required to establish the diagnosis of pulmonary KS. There are a variety of causes of chylothorax. The primary finding is a near-water-attenuating pleural effusion on tho-racic CT. It is the secondary findings of chylothorax that can help differentiate the etiology.

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Chylothorax in a patient with metastatic Kaposi sarcoma ... · Chylothorax is a relatively uncommon...

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