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A Woman in Her 30s With a Past History of HIV Disease Presented With Recurrent Fever, Night Sweats, and Small Bilateral Pulmonary Nodules FREE TO VIEW

Hafiz Rizwan Talib Hashmi, MD; Masooma Niazi, MD; Muhammad Adrish, MD, FCCP
Author and Funding Information

Affiliated with Icahn School of Medicine at Mount Sinai, New York, NY.

CORRESPONDENCE TO: Muhammad Adrish, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Bronx Lebanon Hospital Center, 1650 Selwyn Ave, Ste 12 F, Bronx, NY 10457


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(6):e177-e182. doi:10.1016/j.chest.2016.02.665
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A woman in her 30s presented with recurrent low-grade fever and cough (onset, 1 week). She reported occasional night sweats and weight loss of approximately 20 pounds over the past 4 months. She denied nausea, vomiting, diarrhea, or any urinary complaints. Her past medical history was significant for chronic hepatitis C and HIV infection, the latter diagnosed in 2001. She was noncompliant with highly active antiretroviral therapy for more than 4 years and had pneumocystis pneumonia 2 years prior to this presentation. She had a 10-pack per year smoking history and reported active use of cocaine and heroin. The patient denied any occupational exposures.

Figures in this Article

Vital signs were as follows: BP, 109/72 mm Hg; respiratory rate, 16 breaths/min; heart rate, 94 beats/min; arterial oxygen saturation on room air, 95%. Physical examination was remarkable for cachexia with evidence of muscle wasting. Lung examination revealed mild scattered rhonchi in lung bases. There was no hepatosplenomegaly, lymphadenopathy, skin lesions, or pedal edema.

Laboratory investigations demonstrated hemoglobin level of 11.1 mg/dL, WBC count of 2,200/mL, and CD4+ cell count < 20 cells/mm3. Chest radiography did not reveal any effusions, infiltrates, or nodules (Fig 1). The patient was started on empiric antibiotic treatment for recurrent fever. Chest CT imaging was performed for recurrent fever and cough and revealed small bilateral pulmonary nodules both in the upper and lower lobes (Fig 2). Bacterial culture and acid-fast smears of induced sputum were done, and the results were negative. In view of persistent nonresolving symptoms, recurrent fever, bilateral pulmonary nodules, and patient’s preference, bronchoscopy with bronchoalveolar lavage and transbronchial biopsy of the apical segment of the right upper lobe was performed. Gross examination of the bronchial mucosa revealed a pale-colored mucosa, without any evidence of endobronchial abnormalities (Fig 3). Histopathologic analysis revealed monomorphic spindle cells arranged in ill-defined fascicles and slit-like vessels containing erythrocytes. Immunohistochemical staining revealed nuclear positivity for latency-associated nuclear antigen 1 (LANA-1 or LNA-1) (Figs 4, 5).

Figure 1
Figure Jump LinkFigure 1 Chest radiograph, anteroposterior view: No evidence of nodules, infiltrates, or effusions.Grahic Jump Location
Figure 2
Figure Jump LinkFigure 2 CT imaging of the chest. A, Axial view, showing solid nodules in both upper lobes. B, Axial view, showing solid-appearing parenchymal and subpleural nodules in superior segment of left lower lobe. C, Axial view showing solid nodule in right lower lobe. D, Axial view showing mediastinal window, at the level of the aortic arch, which did not reveal lymphadenopathy. Also noted was the absence of ground-glass attenuation or consolidation in CT images A-C.Grahic Jump Location
Figure 3
Figure Jump LinkFigure 3 Gross examination of bronchial mucosa. No obvious endobronchial abnormality or lesion can be appreciated.Grahic Jump Location
Figure 4
Figure Jump LinkFigure 4 Histopathologic findings from transbronchial biopsies (hematoxylin and eosin staining), showing monomorphic spindle cells arranged in ill-defined fascicles and slit-like vessels containing erythrocytes.Grahic Jump Location
Figure 5
Figure Jump LinkFigure 5 Histopathologic findings from transbronchial biopsies (immunohistochemical staining), showing spindle cells with nuclear positivity for latency-associated nuclear antigen 1.Grahic Jump Location

What is the diagnosis?

Diagnosis: Pulmonary Kaposi sarcoma

Clinical Discussion

Pulmonary diseases are common in individuals infected with HIV and cause significant morbidity and mortality. Kaposi sarcoma (KS) is a multicentric angioproliferative neoplasm and is the most prevalent neoplasm in patients with AIDS. KS was first described more than a century ago; however, it received most attention in the early 1980s after its association with AIDS was identified. The etiologic agent, KS herpesvirus or human herpesvirus 8 (HHV8), was identified in 1994 by Chang et al. The incidence of KS in the general population is about 1 in 100,000; however, this increases to 1 in 20 among patients infected with HIV. There are four recognized epidemiologic-clinical forms of KS, which predominantly involve men: (1) Classic KS, a rare cutaneous form, primarily affects older men of Jewish and Mediterranean origin; (2) endemic KS, reported mainly in Africa, often affects children; (3) iatrogenic KS, which develops in immunosuppressed individuals; and (4) epidemic or AIDS-associated KS, which is a major AIDS-defining condition.

KS originates from the endothelium and has significant clinical and pathologic heterogeneity. The disease can demonstrate indolent behavior with mucocutaneous involvement but also possesses the ability to progress or regress, based on host immune factors.

AIDS-associated KS is more aggressive, and visceral involvement occurs in more than one-half of cases. Pulmonary KS can be seen as a part of a systemic disease in about 77% to 95% of cases; reports of isolated pulmonary disease have rarely appeared in the literature. When symptomatic, patients with pulmonary KS can present with cough and dyspnea as the most common symptoms. Patients with advanced disease can also present with rapidly progressive infiltrate leading to respiratory failure and hemoptysis. Rapid progression of KS (also called KS flare) can occur in the setting of glucocorticoid use for other conditions in individuals with HIV infection or subsequent to the immune reconstitution syndrome that can occur after initiating highly active antiretroviral therapy (HAART).

Parenchymal pulmonary KS should be suspected in patients presenting with classic radiographic involvement, endobronchial KS lesions, and in the absence of evidence of opportunistic infections. A lung biopsy may not be necessary in such patients. However, when parenchymal lesions occur in the absence of endobronchial involvement or when a patient presents with an atypical endobronchial lesion, a biopsy may be indicated. Keep in mind that significant hemorrhage can occur in up to 30% of patients and that the bleeding risk is greatest for centrally located lesions. Because of the patchy nature of KS, the diagnostic yield for both endobronchial and transbronchial biopsies can vary between 26% and 60%. The diagnostic yield for a bronchoscopic biopsy decreases to 14% to 31% for pulmonary nodules ≤ 2 cm. Furthermore, the histologic appearance can resemble that of normal tissue, as KS lesions are mainly composed of spindle cells and blood vessels, thus making bronchoscopic diagnoses challenging. Bronchoalveolar lavage can increase the bronchoscopic yield up to 60% in immunocompromised patients with pulmonary involvement. Transthoracic needle aspiration has better diagnostic yield for small pulmonary nodules (up to 77%), but the chance of pneumothorax is high (up to 28%). Video-assisted thoracoscopic biopsy may be indicated when other modalities are nondiagnostic or not indicated, and the diagnostic yield varies with the size and location of the nodule.

Introduction of HAART has greatly reduced the incidence of KS and the severity of the disease and should be the first step in therapy. At present, there is no cure for KS. Local therapy with radiation is an option in patients with locally advanced disease or unacceptable cosmetic lesions. Other options include surgical excision for cosmetic purposes, intralesional Vinca alkaloid therapy, laser photocoagulation, or cryotherapy. Chemotherapy with liposomal anthracyclines and taxanes can be used for patients with widespread skin involvement, rapidly progressive disease course, symptomatic visceral involvement, and KS flare. Thalidomide, interferon-α, imatinib, matrix metalloproteinase inhibitors, and antiherpes therapy have also been tried with some success. Although HHV8 in the lytic phase appears susceptible to antiviral drugs such as ganciclovir, the virus may become harbored in its latent phase in KS cells. For iatrogenic KS, adjustment of the patient’s immunosuppressive regimen and addition of sirolimus may be needed.

Radiologic Discussion

Thoracic disease can be found in up to 45% of patients with mucocutaneous AIDS-related KS. Chest radiography can demonstrate reticulonodular opacities and parenchymal nodules, mainly in the perihilar and lower lung zones. Pleural effusions can be seen in up to two-thirds of patients with parenchymal involvement and can be unilateral or bilateral. These effusions can present as transudative or exudative effusions and are often hemorrhagic because of the vascular nature of the disease. Pulmonary disease due to KS demonstrates a predilection for the peribronchovascular spaces, usually extending peripherally from the hila, and can often be difficult to appreciate on a routine chest radiograph. CT examination has the further advantage of allowing detailed analysis of the thoracic cavity and can identify lesions such as small parenchymal nodules, lytic lesions of the sternum or spine, invasion of subcutaneous fat, and pleural involvement that can be missed on routine chest radiography.

The characteristic appearance of pulmonary nodules in patients with AIDS can favor the presence of a certain underlying etiology. Features such as subcentimeter size, centrilobular distribution, and cavitation usually indicate opportunistic infection, whereas larger nodules are often neoplastic. Peribronchovascular distribution is usually seen with KS.Pneumocystis jirovecii pneumonia can exhibit several radiographic patterns of which the ground-glass patchwork pattern and the interstitial pattern are the most commonly seen. Thickening of interlobular septa due to lymphatic obstruction or tumor invasion is often seen. KS lesions can progress to large masses or areas of consolidation, which can demonstrate surrounding ground-glass density due to hemorrhage in the adjacent areas. Lymphadenopathy due to KS can be present in up to 30% to 35% of patients, and endobronchial lesions can also be appreciated on CT scans. Scintigraphy can sometimes be used to differentiate KS lesions from infection and lymphoma. Gallium uptake is usually negative for KS but positive for lymphoma and infection. However, thallium uptake is usually positive in KS and lymphoma but negative for infection. Magnetic resonance imaging features of AIDS-related KS include reduced signal intensity on T2-weighted images, hyperintense areas on T1-weighted images, and strong tumor enhancement after gadopentetate dimeglumine injection.

Pathologic Discussion

The histopathology of KS is nearly identical in the various epidemiologic types. However, some studies have reported minor histopathologic differences between patients with AIDS-related KS and those with non-HIV KS. AIDS-related KS lesions exhibit more extensive dissecting vessels whereas mitoses and cellular anaplasia are more common in HIV-negative KS. Early KS skin lesions (also called the patch stage) are characterized by abnormal vessels lined with thin endothelial cells dissecting the dermis. Sparse chronic inflammatory cells, red blood cells, and hemosiderin-laden macrophages are often present in these lesions. This presentation can also be seen in other vascular disorders and therefore is not pathognomonic for KS. Advanced KS lesions are characterized by proliferation of spindle cells and blood vessels and can consist of several fascicles of these spindle-shaped tumor cells mixed with chronic inflammatory infiltrate and hemosiderin-laden macrophages. KS nodules often display a sieve-like appearance because of transection of spindle cells with intervening slit-like spaces. Hyaline globules positive for periodic acid-Schiff reagent are commonly seen in advanced KS lesions. Analysis by electron microscopy can reveal occasional Weibel-Palade bodies in the lesional cells and fragmented erythrocytes intracellularly, which are believed to correspond to hyaline globules seen on light microscopy. Typical lesions of KS usually lack significant cellular pleomorphism, necrosis, and marked mitotic figures. Immunohistochemically, KS lesional cells stain positive for CD31 (platelet/endothelial cell adhesion molecule 1, PECAM-1), CD34, and factor VIII-related antigen. In advanced lesions of KS, CD34 expression is stronger than CD31 expression. KS spindle cells also express lymphatic markers such as LYVE-1 (lymphatic vessel endothelial hyaluronan receptor 1), VEGFR-3 (vascular endothelial growth factor receptor-3), M2A, and Prox-1 (Prospero-related homeobox 1). HHV8 identification and localization within KS lesional cells by immunostaining for LANA-1 (or LNA-1) is the most helpful diagnostic test in differentiating KS from other KS-mimicking diseases. However, LANA-1 (or LNA-1) can also be expressed at high levels in body cavity lymphoma and Castleman disease. HHV8 has also been detected in certain angiosarcomas, dermatofibromas, and hemangiomas. Interestingly, HAART can lead to partial or complete regression of KS lesions, and spindle cells might be absent in completely regressed lesions.

KS is a low-grade vascular tumor associated with HHV8 infection. Patients with AIDS-associated KS usually present with disseminated lesions and visceral involvement. The patient described here was unusual in her presentation of KS, as she had small pulmonary nodules in both the upper and lower lobes, which were not appreciable on chest radiography. This patient was even more unusual in that she presented with recurrent fever and night sweats, which usually favor an infectious etiology.

Financial/nonfinancial disclosures: None declared.

Other contributions:CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

Chang Y. .Cesarman E. .Pessin M.S. .et al Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science. 1994;266:1865-1869 [PubMed]journal. [CrossRef] [PubMed]
 
La Ferla L. .Pinzone M.R. .Nunnari G. .et al Kaposi’s sarcoma in HIV-positive patients: the state of art in the HAART-era. Eur Rev Med Pharmacol Sci. 2013;17:2354-2365 [PubMed]journal. [PubMed]
 
Kuhlman J.E. . Imaging pulmonary disease in AIDS: state of the art. Eur Radiol. 1999;9:395-408 [PubMed]journal. [CrossRef] [PubMed]
 
Joshi M. .Markelova N. .Palacio D. .Schapira R.M. . A patient with HIV, dyspnea, and multiple pulmonary nodules: pulmonary Kaposi sarcoma. Chest. 2006;130:1924-1928 [PubMed]journal. [CrossRef] [PubMed]
 
Feller L. .Anagnostopoulos C. .Wood N. .et al Human immunodeficiency virus-associated Kaposi sarcoma as an immune reconstitution inflammatory syndrome: a literature review and case report. J Periodontol. 2008;79:362-368 [PubMed]journal. [CrossRef] [PubMed]
 
Zibrak J.D. .Silvestri R.C. .Costello P. .et al Bronchoscopic and radiologic features of Kaposi’s sarcoma involving the respiratory system. Chest. 1986;90:476-479 [PubMed]journal. [CrossRef] [PubMed]
 
Meduri G.U. .Stover D.E. .Lee M. .Myskowski P.L. .Caravelli J.F. .Zaman M.B. . Pulmonary Kaposi’s sarcoma in the acquired immune deficiency syndrome: clinical, radiographic, and pathologic manifestations. Am J Med. 1986;81:11-18 [PubMed]journal
 
Baaklini W.A. .Reinoso M.A. .Gorin A.B. .Sharafkaneh A. .Manian P. . Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules. Chest. 2000;117:1049-1054 [PubMed]journal. [CrossRef] [PubMed]
 
Aboulafia D.M. . The epidemiologic, pathologic, and clinical features of AIDS-associated pulmonary Kaposi’s sarcoma. Chest. 2000;117:1128-1145 [PubMed]journal. [CrossRef] [PubMed]
 
Wingard J.R. .Hiemenz J.W. .Jantz M.A. . How I manage pulmonary nodular lesions and nodular infiltrates in patients with hematologic malignancies or undergoing hematopoietic cell transplantation. Blood. 2012;120:1791-1800 [PubMed]journal. [CrossRef] [PubMed]
 
Suzuki K. .Nagai K. .Yoshida J. .et al Video-assisted thoracoscopic surgery for small indeterminate pulmonary nodules: indications for preoperative marking. Chest. 1999;115:563-568 [PubMed]journal. [CrossRef] [PubMed]
 
Radu O. .Pantanowitz L. . Kaposi sarcoma. Arch Pathol Lab Med. 2013;137:289-294 [PubMed]journal. [CrossRef] [PubMed]
 
Ognibene F.P. .Steis R.G. .Macher A.M. .et al Kaposi’s sarcoma causing pulmonary infiltrates and respiratory failure in the acquired immunodeficiency syndrome. Ann Intern Med. 1985;102:471-475 [PubMed]journal. [CrossRef] [PubMed]
 
Edinburgh K.J. .Jasmer R.M. .Huang L. .et al Multiple pulmonary nodules in AIDS: usefulness of CT in distinguishing among potential causes. Radiology. 2000;214:427-432 [PubMed]journal. [CrossRef] [PubMed]
 
Allen C.M. .Al-Jahdali H.H. .Irion K.L. .Al Ghanem S. .Gouda A. .Khan A.N. . Imaging lung manifestations of HIV/AIDS. Ann Thorac Med. 2010;5:201-216 [PubMed]journal. [CrossRef] [PubMed]
 
Lee V.W. .Fuller J.D. .O’Brien M.J. .Parker D.R. .Cooley T.P. .Liebman H.A. . Pulmonary Kaposi sarcoma in patients with AIDS: scintigraphic diagnosis with sequential thallium and gallium scanning. Radiology. 1991;180:409-412 [PubMed]journal. [CrossRef] [PubMed]
 
Khalil A.M. .Carette M.F. .Cadranel J.L. .Mayaud C.M. .Akoun G.M. .Bigot J.M. . Magnetic resonance imaging findings in pulmonary Kaposi’s sarcoma: a series of 10 cases. Eur Respir J. 1994;7:1285-1289 [PubMed]journal. [CrossRef] [PubMed]
 
Ackerman A.B. . Subtle clues to diagnosis by conventional microscopy: the patch stage of Kaposi’s sarcoma. Am J Dermatopathol. 1979;1:165-172 [PubMed]journal. [CrossRef] [PubMed]
 
Pantanowitz L. .Grayson W. .Simonart T. .Dezube B.J. . Pathology of Kaposi’s sarcoma. J HIV Ther. 2009;14:41-47 [PubMed]journal. [PubMed]
 
Mattsson K. .Kiss C. .Platt G.M. .et al Latent nuclear antigen of Kaposi’s sarcoma herpesvirus/human herpesvirus-8 induces and relocates RING3 to nuclear heterochromatin regions. J Gen Virol. 2002;83:179-188 [PubMed]journal. [CrossRef] [PubMed]
 
Pantanowitz L. .Pinkus G.S. .Dezube B.J. .Tahan S.R. . HHV8 is not limited to Kaposi’s sarcoma. Mod Pathol. 2005;18:1148-1150 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 Chest radiograph, anteroposterior view: No evidence of nodules, infiltrates, or effusions.Grahic Jump Location
Figure Jump LinkFigure 2 CT imaging of the chest. A, Axial view, showing solid nodules in both upper lobes. B, Axial view, showing solid-appearing parenchymal and subpleural nodules in superior segment of left lower lobe. C, Axial view showing solid nodule in right lower lobe. D, Axial view showing mediastinal window, at the level of the aortic arch, which did not reveal lymphadenopathy. Also noted was the absence of ground-glass attenuation or consolidation in CT images A-C.Grahic Jump Location
Figure Jump LinkFigure 3 Gross examination of bronchial mucosa. No obvious endobronchial abnormality or lesion can be appreciated.Grahic Jump Location
Figure Jump LinkFigure 4 Histopathologic findings from transbronchial biopsies (hematoxylin and eosin staining), showing monomorphic spindle cells arranged in ill-defined fascicles and slit-like vessels containing erythrocytes.Grahic Jump Location
Figure Jump LinkFigure 5 Histopathologic findings from transbronchial biopsies (immunohistochemical staining), showing spindle cells with nuclear positivity for latency-associated nuclear antigen 1.Grahic Jump Location

Tables

References

Chang Y. .Cesarman E. .Pessin M.S. .et al Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science. 1994;266:1865-1869 [PubMed]journal. [CrossRef] [PubMed]
 
La Ferla L. .Pinzone M.R. .Nunnari G. .et al Kaposi’s sarcoma in HIV-positive patients: the state of art in the HAART-era. Eur Rev Med Pharmacol Sci. 2013;17:2354-2365 [PubMed]journal. [PubMed]
 
Kuhlman J.E. . Imaging pulmonary disease in AIDS: state of the art. Eur Radiol. 1999;9:395-408 [PubMed]journal. [CrossRef] [PubMed]
 
Joshi M. .Markelova N. .Palacio D. .Schapira R.M. . A patient with HIV, dyspnea, and multiple pulmonary nodules: pulmonary Kaposi sarcoma. Chest. 2006;130:1924-1928 [PubMed]journal. [CrossRef] [PubMed]
 
Feller L. .Anagnostopoulos C. .Wood N. .et al Human immunodeficiency virus-associated Kaposi sarcoma as an immune reconstitution inflammatory syndrome: a literature review and case report. J Periodontol. 2008;79:362-368 [PubMed]journal. [CrossRef] [PubMed]
 
Zibrak J.D. .Silvestri R.C. .Costello P. .et al Bronchoscopic and radiologic features of Kaposi’s sarcoma involving the respiratory system. Chest. 1986;90:476-479 [PubMed]journal. [CrossRef] [PubMed]
 
Meduri G.U. .Stover D.E. .Lee M. .Myskowski P.L. .Caravelli J.F. .Zaman M.B. . Pulmonary Kaposi’s sarcoma in the acquired immune deficiency syndrome: clinical, radiographic, and pathologic manifestations. Am J Med. 1986;81:11-18 [PubMed]journal
 
Baaklini W.A. .Reinoso M.A. .Gorin A.B. .Sharafkaneh A. .Manian P. . Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules. Chest. 2000;117:1049-1054 [PubMed]journal. [CrossRef] [PubMed]
 
Aboulafia D.M. . The epidemiologic, pathologic, and clinical features of AIDS-associated pulmonary Kaposi’s sarcoma. Chest. 2000;117:1128-1145 [PubMed]journal. [CrossRef] [PubMed]
 
Wingard J.R. .Hiemenz J.W. .Jantz M.A. . How I manage pulmonary nodular lesions and nodular infiltrates in patients with hematologic malignancies or undergoing hematopoietic cell transplantation. Blood. 2012;120:1791-1800 [PubMed]journal. [CrossRef] [PubMed]
 
Suzuki K. .Nagai K. .Yoshida J. .et al Video-assisted thoracoscopic surgery for small indeterminate pulmonary nodules: indications for preoperative marking. Chest. 1999;115:563-568 [PubMed]journal. [CrossRef] [PubMed]
 
Radu O. .Pantanowitz L. . Kaposi sarcoma. Arch Pathol Lab Med. 2013;137:289-294 [PubMed]journal. [CrossRef] [PubMed]
 
Ognibene F.P. .Steis R.G. .Macher A.M. .et al Kaposi’s sarcoma causing pulmonary infiltrates and respiratory failure in the acquired immunodeficiency syndrome. Ann Intern Med. 1985;102:471-475 [PubMed]journal. [CrossRef] [PubMed]
 
Edinburgh K.J. .Jasmer R.M. .Huang L. .et al Multiple pulmonary nodules in AIDS: usefulness of CT in distinguishing among potential causes. Radiology. 2000;214:427-432 [PubMed]journal. [CrossRef] [PubMed]
 
Allen C.M. .Al-Jahdali H.H. .Irion K.L. .Al Ghanem S. .Gouda A. .Khan A.N. . Imaging lung manifestations of HIV/AIDS. Ann Thorac Med. 2010;5:201-216 [PubMed]journal. [CrossRef] [PubMed]
 
Lee V.W. .Fuller J.D. .O’Brien M.J. .Parker D.R. .Cooley T.P. .Liebman H.A. . Pulmonary Kaposi sarcoma in patients with AIDS: scintigraphic diagnosis with sequential thallium and gallium scanning. Radiology. 1991;180:409-412 [PubMed]journal. [CrossRef] [PubMed]
 
Khalil A.M. .Carette M.F. .Cadranel J.L. .Mayaud C.M. .Akoun G.M. .Bigot J.M. . Magnetic resonance imaging findings in pulmonary Kaposi’s sarcoma: a series of 10 cases. Eur Respir J. 1994;7:1285-1289 [PubMed]journal. [CrossRef] [PubMed]
 
Ackerman A.B. . Subtle clues to diagnosis by conventional microscopy: the patch stage of Kaposi’s sarcoma. Am J Dermatopathol. 1979;1:165-172 [PubMed]journal. [CrossRef] [PubMed]
 
Pantanowitz L. .Grayson W. .Simonart T. .Dezube B.J. . Pathology of Kaposi’s sarcoma. J HIV Ther. 2009;14:41-47 [PubMed]journal. [PubMed]
 
Mattsson K. .Kiss C. .Platt G.M. .et al Latent nuclear antigen of Kaposi’s sarcoma herpesvirus/human herpesvirus-8 induces and relocates RING3 to nuclear heterochromatin regions. J Gen Virol. 2002;83:179-188 [PubMed]journal. [CrossRef] [PubMed]
 
Pantanowitz L. .Pinkus G.S. .Dezube B.J. .Tahan S.R. . HHV8 is not limited to Kaposi’s sarcoma. Mod Pathol. 2005;18:1148-1150 [PubMed]journal. [CrossRef] [PubMed]
 
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