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There was no associated edema or mucosal involvement&#46; The general blood test results were normal and serology for hepatitis C virus &#40;HCV&#41;&#44; HBV&#44; and human immunodeficiency virus &#40;HIV&#41; was negative&#46; Ultrasound showed numerous solid subcutaneous lesions in both legs&#46; The findings were heterogeneous&#44; with a mixture of hyperechogenic and strongly hypoechogenic lesions without detectable flow&#46; Histologic examination showed a well-circumscribed nodule composed of spindle cells with varying degrees of atypia &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; in the subcutaneous tissue&#44; in addition to large irregular&#44; dilated vascular channels with a prominent endothelium and abundant hematic content &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Immunohistochemistry was positive for CD31 and HHV-8&#46; Positron emission tomography&#8211;computed tomography &#40;PET-CT&#41; ruled out lymph node and visceral involvement and confirmed exclusive involvement of the subcutaneous tissue&#46; A diagnosis of primary KS of the subcutaneous tissue was established&#46; Considering the absence of disease spread and severe symptoms&#44; it was decided to adopt a watch-and-wait approach&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">KS is a multifocal systemic disease that mainly affects the skin and mucous membranes&#46; Although it is characterized by a proliferation of endothelial cells&#44; it is not yet known whether these cells are derived from lymphatic or blood endothelium&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> KS is etiologically associated with HHV-8 infection combined with factors such as an altered immune system and an inflammatory&#47;angiogenic environment&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> It is classified into 4 clinical&#47;epidemiological groups&#58; classic KS&#44; endemic &#40;African&#41; KS&#44; HIV-associated KS&#44; and immunosuppression-associated KS&#46; HIV-associated KS tends to show a multicentric pattern&#44; with greater mucocutaneous&#44; gastrointestinal&#44; lymph node&#44; visceral&#44; and atypical involvement&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In KS&#44; endothelial transformation typically occurs in the dermis &#40;superficial more often than deep&#41;&#44; giving rise to classic lesions&#44; such as macules&#44; papules&#44; and nodules&#44; or violaceous tumors affecting the skin or mucous membranes&#46; Involvement of the subcutaneous tissue and other deep soft tissues and even bone is generally the result of deep extension by superficial lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Visceral and nodal involvement is uncommon and has been mainly described in immunosuppressed patients&#44; who usually have cutaneous&#47;mucosal lesions&#46; Exclusive extracutaneous KS is rare&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2</span></a> as is primary involvement of the subcutaneous tissue&#46; We found just 6 other cases of patients with subcutaneous nodules without overlying skin involvement in the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#8211;7</span></a> All the patients were men and they were all HIV-positive but one&#46; Five of them had a classic KS lesion at another site&#44; facilitating diagnosis&#46; Just 1 patient&#44; a 43-year-old HIV-positive man&#44; had subcutaneous involvement only&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The mechanism underlying the development of primary KS of the subcutaneous tissue is unknown&#46; Some authors have proposed that chronic lymphedema could have an etiologic role in lymphangiogenesis and immune injury&#44;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;8</span></a> but no signs of lymphedema have been detected in the cases described to date&#46; In addition&#44; many patients with classic KS on the legs have edema but do not develop subcutaneous lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Trauma to the subcutaneous tissue might also have a role in the development of KS&#44; particularly in solitary or very localized lesions&#46; This hypothesis is based on reports of KS arising in scars&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The differential diagnosis for subcutaneous tissue lesions is broad&#46; In immunosuppressed patients&#44; primary KS of the subcutaneous tissue without skin lesions can be difficult to distinguish from other lesions&#44; particularly in patients with infections and other proliferative disorders&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Although skin biopsy is necessary for establishing a definitive diagnosis&#44; imaging studies are essential for guiding diagnosis and determining the extent of disease before treatment initiation&#46; PET-CT is the best tool currently available for assessing subcutaneous disease&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> as lesions show uptake of F-18-fluorodeoxyglucose&#46; It is also useful for assessing visceral&#44; nodal&#44; soft tissue&#44; and bone involvement&#46; CT alone is also useful for assessing visceral &#40;mainly lung&#41; involvement&#44; but it is less valuable in soft tissue lesions&#46; T1-weighted &#40;T1W1&#41; magnetic resonance imaging &#40;MRI&#41; shows an isointense signal to muscle while T2W2 scanning shows a mainly hyperintense signal that is enhanced with gadolinium&#46; MRI is less sensitive&#44; however&#44; to small lesions in the subcutaneous tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Scintigraphy has also proven useful for determining the presence and extent of cutaneous and extracutaneous KS associated with HIV infection&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Skin ultrasound is a useful complementary test&#44; as it provides information on structural and vascular lesions and can also be used to guide biopsy&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">We have presented a new case of primary KS of the subcutaneous tissue and the first-ever case described in an immunocompetent woman&#46; It is important to be familiar with uncommon presentations of KS&#44; such as primary KS of the subcutaneous tissue&#44; to avoid diagnostic and therapeutic delays&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors report no conflicts of interest&#46;</p></span></span>"
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Case and Research Letters
Primary Kaposi Sarcoma of the Subcutaneous Tissue: A Rare Clinical Variant
Sarcoma de Kaposi subcutáneo primario, una rara variante clínica
M. Franco-Muñoza,
Corresponding author
monse.franco.m@gmail.com

Corresponding author.
, M. García-Arpaa, B. Lozano-Masdemonta, I. Lara-Simónb
a Departamento de Dermatología, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
b Departamento de Anatomía Patología, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
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There was no associated edema or mucosal involvement&#46; The general blood test results were normal and serology for hepatitis C virus &#40;HCV&#41;&#44; HBV&#44; and human immunodeficiency virus &#40;HIV&#41; was negative&#46; Ultrasound showed numerous solid subcutaneous lesions in both legs&#46; The findings were heterogeneous&#44; with a mixture of hyperechogenic and strongly hypoechogenic lesions without detectable flow&#46; Histologic examination showed a well-circumscribed nodule composed of spindle cells with varying degrees of atypia &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; in the subcutaneous tissue&#44; in addition to large irregular&#44; dilated vascular channels with a prominent endothelium and abundant hematic content &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Immunohistochemistry was positive for CD31 and HHV-8&#46; Positron emission tomography&#8211;computed tomography &#40;PET-CT&#41; ruled out lymph node and visceral involvement and confirmed exclusive involvement of the subcutaneous tissue&#46; A diagnosis of primary KS of the subcutaneous tissue was established&#46; Considering the absence of disease spread and severe symptoms&#44; it was decided to adopt a watch-and-wait approach&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">KS is a multifocal systemic disease that mainly affects the skin and mucous membranes&#46; Although it is characterized by a proliferation of endothelial cells&#44; it is not yet known whether these cells are derived from lymphatic or blood endothelium&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> KS is etiologically associated with HHV-8 infection combined with factors such as an altered immune system and an inflammatory&#47;angiogenic environment&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> It is classified into 4 clinical&#47;epidemiological groups&#58; classic KS&#44; endemic &#40;African&#41; KS&#44; HIV-associated KS&#44; and immunosuppression-associated KS&#46; HIV-associated KS tends to show a multicentric pattern&#44; with greater mucocutaneous&#44; gastrointestinal&#44; lymph node&#44; visceral&#44; and atypical involvement&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In KS&#44; endothelial transformation typically occurs in the dermis &#40;superficial more often than deep&#41;&#44; giving rise to classic lesions&#44; such as macules&#44; papules&#44; and nodules&#44; or violaceous tumors affecting the skin or mucous membranes&#46; Involvement of the subcutaneous tissue and other deep soft tissues and even bone is generally the result of deep extension by superficial lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Visceral and nodal involvement is uncommon and has been mainly described in immunosuppressed patients&#44; who usually have cutaneous&#47;mucosal lesions&#46; Exclusive extracutaneous KS is rare&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2</span></a> as is primary involvement of the subcutaneous tissue&#46; We found just 6 other cases of patients with subcutaneous nodules without overlying skin involvement in the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#8211;7</span></a> All the patients were men and they were all HIV-positive but one&#46; Five of them had a classic KS lesion at another site&#44; facilitating diagnosis&#46; Just 1 patient&#44; a 43-year-old HIV-positive man&#44; had subcutaneous involvement only&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The mechanism underlying the development of primary KS of the subcutaneous tissue is unknown&#46; Some authors have proposed that chronic lymphedema could have an etiologic role in lymphangiogenesis and immune injury&#44;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;8</span></a> but no signs of lymphedema have been detected in the cases described to date&#46; In addition&#44; many patients with classic KS on the legs have edema but do not develop subcutaneous lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Trauma to the subcutaneous tissue might also have a role in the development of KS&#44; particularly in solitary or very localized lesions&#46; This hypothesis is based on reports of KS arising in scars&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The differential diagnosis for subcutaneous tissue lesions is broad&#46; In immunosuppressed patients&#44; primary KS of the subcutaneous tissue without skin lesions can be difficult to distinguish from other lesions&#44; particularly in patients with infections and other proliferative disorders&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Although skin biopsy is necessary for establishing a definitive diagnosis&#44; imaging studies are essential for guiding diagnosis and determining the extent of disease before treatment initiation&#46; PET-CT is the best tool currently available for assessing subcutaneous disease&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> as lesions show uptake of F-18-fluorodeoxyglucose&#46; It is also useful for assessing visceral&#44; nodal&#44; soft tissue&#44; and bone involvement&#46; CT alone is also useful for assessing visceral &#40;mainly lung&#41; involvement&#44; but it is less valuable in soft tissue lesions&#46; T1-weighted &#40;T1W1&#41; magnetic resonance imaging &#40;MRI&#41; shows an isointense signal to muscle while T2W2 scanning shows a mainly hyperintense signal that is enhanced with gadolinium&#46; MRI is less sensitive&#44; however&#44; to small lesions in the subcutaneous tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Scintigraphy has also proven useful for determining the presence and extent of cutaneous and extracutaneous KS associated with HIV infection&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Skin ultrasound is a useful complementary test&#44; as it provides information on structural and vascular lesions and can also be used to guide biopsy&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">We have presented a new case of primary KS of the subcutaneous tissue and the first-ever case described in an immunocompetent woman&#46; It is important to be familiar with uncommon presentations of KS&#44; such as primary KS of the subcutaneous tissue&#44; to avoid diagnostic and therapeutic delays&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors report no conflicts of interest&#46;</p></span></span>"
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