Endobronchial Kaposi Sarcoma.

Kaposi sarcoma (KS) is a low-grade mesenchymal tumor that is often encountered in acquired immune deficiency syndrome (AIDS)-associated malignancy. The typical manifestation is primarily cutaneous involvement before disseminating to other organs in patients with advanced AIDS. In ~45% of patients with cutaneous AIDS-related KS, thoracic involvement can occur. Thoracic involvement includes lung parenchyma, pleura, and intrathoracic lymph nodes.1 Since the entry into the era of antiretroviral therapy over the last few decades, KS presenting as an endobronchial lesion has been rarely reported in the literature. We present a case of endobronchial KS with cutaneous and pulmonary involvement in a young man with advanced AIDS. CASE REPORT A 24-year-old homosexual man with past medical history of AIDS diagnosed 6 years ago, secondary syphilis, and history of biopsy-proven cutaneous KS was admitted for evaluation of altered mental status. He had been noncompliant with antiretroviral therapy, with undetectable CD4 count and a human immunodeficiency virus (HIV)-1 viral load over 623,000 copies/mL. He underwent lumbar puncture. Varicella zoster virus was detected by polymerase chain reaction method from the cerebrospinal fluid. He was treated with intravenous acyclovir. His hospital course was complicated by complaints of dry cough and dyspnea on exertion. Physical examination was notable for oral thrush, hyperpigmented lesions over the nasal ridge and lower extremities. These findings were consistent with the known diagnosis of cutaneous KS (Fig. 1). Computed tomography (CT) of the chest demonstrated bilateral spiculated nodules in a peribronchovascular pattern, and an endotracheal lesion along the left upper endotracheal mucosa (Fig. 2). Fiberoptic bronchoscopy demonstrated a polypoid lesion attached to the endotracheal mucosa occluding approximately one-third of the endotracheal lumen with surrounding confluent areas of violaceous and erythematous mucosa (Fig. A). A biopsy was obtained to characterize the endobronchial lesion. Pathologic examination demonstrated a spindle cell proliferation. Immunohistochemistry demonstrated positive nuclear staining for ETS-related gene, a transcription factor expressed in vascular tumors such as angiosarcomas, epithelioid hemangioendothelomas, and KS.2 Nuclear staining for human herpes virus 8 (HHV-8) was also positive by immunohistochemistry (Fig. 3), supporting the diagnosis of endobronchial KS. The left upper lobe bronchoalveolar lavage was Gram stain, acid fast bacilli stain, and culture negative, excluding an infectious etiology. Antiretroviral therapy was initiated. The patient tolerated the treatment well without symptoms of immune reconstitution inflammatory syndrome. He was discharged home a week after antiretroviral therapy was initiated. He was readmitted 2 weeks later with acute brain stem infarct from complete occlusion of the basilar artery requiring emergent thrombectomy complicated by reocclusion of the basilar artery and locked-in-syndrome. He was mechanically ventilated for 2 weeks. The prognosis of him having meaningful neurological recovery was very poor. His health care proxy decided to change his code status to comfort care, and the patient ultimately passed away.FIGURE 1: A biopsy-proven cutaneous Kaposi sarcoma of the lower extremity.FIGURE 2: A, The H&E demonstrated a bland spindle cells proliferation, free of mitotic figures, marked atypia and tumor necrosis. B, Immunohistochemistry of ERG demonstrated positive nuclear staining for ERG, a transcription factor that has been linked to angiogenesis. C, Immunohistochemistry for HHV-8 demonstrated positive nuclear staining for HHV-8. ERG indicates ETS-related gene; H&E, hematoxylin and eosin; HHV-8, human herpes virus 8.FIGURE 3: Computed tomography of the chest demonstrated an endotracheal lesion along the left upper endotracheal mucosa (A) and irregular nodular opacities with a peribronchovascular distribution typically represents pulmonary Kaposi sarcoma (B).FIGURE A: Fiberoptic bronchoscopy demonstrated a polypoid lesion attached to the endotracheal mucosa occluding approximately one-third of the endotracheal lumen (A) with surrounding confluent areas of violaceous and erythematous mucosa (B).DISCUSSION The most common HIV-associated malignancy is KS, although the incidence has been declining since the start of antiretroviral therapy era. It is most often seen in male individuals (male to female ratio close to 3:1). It is diagnosed with an increased rate in individuals from the Mediterranean basin, Central and Eastern Europe.3 HHV-8 infection is recognized as an essential factor in the development of KS, as KS is thought to originate from HHV-8 infected endothelial cells. This is especially true with the type A HHV-8 strain which is associated with rapid progression of KS and higher blood viral loads compare to other genotypes.4 In addition, other risk factors for KS include immunosuppression, either acquired as in the case of HIV, or iatrogenic such as in solid organ transplantation.3 Our patient had both AIDS and HHV-8 infection in the airway endothelial cells. There are 4 different types of KS characterized by the clinical setting in which they occur, including classic type usually seen in the middle-aged to elderly population, endemic type established in sub-Saharan Africans, iatrogenic type caused by immunosuppressive drugs, and AIDS-associated epidemic KS. The lesions of KS are highly vascularized and have a propensity to bleed because they are comprised of distinctive spindle cells that line blood vessels.1,5 Chest CT findings of AIDS-related KS is classically described as bilateral and symmetric ill-defined nodules in a peribronchovascular distribution, also known as flame-shaped lesions, as demonstrated in our patient’s CT chest.6 The typical bronchoscopic appearance of endobronchial KS is described as erythematous, violaceous, maculopapular lesions in a discrete or confluent distribution.7 Yoo et al7 evaluated 35 patients with endobronchial KS, of which only one patient had a mass lesion appearance on bronchoscopy. Our patient had an endotracheal mass which partially occluded the trachea. We performed an endobronchial biopsy because KS presenting as an endobronchial mass is rare. Moreover, other common etiologies of endotracheal lesions, such as infection and HIV-associated malignancies, needed to be excluded. Endobronchial KS could progress to total occlusion of the tracheobronchial tree if not appropriately treated. Other diagnostic possibilities in AIDS patients with a radiologic presentation of diffuse pulmonary nodules include infections such as mycobacterial tuberculosis; opportunistic infection from pneumocystis pneumonia or cytomegalovirus pneumonia; and noninfectious etiologies such as non-Hodgkin lymphoma, adenocarcinoma, or sarcoidosis. We excluded these causes by way of a negative bronchoalveolar lavage stain, culture, and endobronchial biopsy. There is no official staging system for KS. Our literature review found that for epidemic or AIDS-related KS, a scoring system was developed by the AIDS Clinical Trials Group of the National Institute of Health. This system utilizes 3 variables that include tumor extent, immune status, and systemic symptoms.8 The staging system for classic KS is based on the disease distribution and speed of disease evolution.9 Prognosis is dependent on the type of KS. Nevertheless, our patient had disseminated disease with visceral involvement of the most aggressive form, which portends a poor prognosis. The lesions may regress in size and number with antiretroviral therapy. Literature review suggests treatment of KS with pegylated liposomal doxorubin or paclitaxel, the first and second line chemotherapeutic agents, respectively.9–11 Our patient was not a candidate for chemotherapy because of the diagnosis of a brain stem infarct complicated by lock-in syndrome and history of noncompliance to antiretroviral therapy. CONCLUSIONS This case highlights the importance of considering bronchopulmonary KS in the differential diagnoses in advanced AIDS patients presenting with a polypoid endobronchial mass. Bronchoscopy should be performed for airway inspection and to exclude other infectious or noninfectious etiologies in HIV/AIDS patients. If the diagnosis remains in question, transbronchial or endobronchial biopsy should be cautiously performed because of the increased risk of bleeding from the angiogenic effect of vascular tumors such as KS.