Kaposi's sarcoma
Author: Dr Sayeda Nahar
Editors: Dr Daniel Keith and Dr Kalina Bridgewater
Introduction
Kaposi’s Sarcoma (KS) is an atypical vascular tumour with low-grade malignant potential, first described by Moritz Kaposi, a Viennese dermatologist. It is characterised by multicentric proliferation of angiogenic spindle cells infected with Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8 (HHV-8). HHV-8 is mainly transmitted through saliva and semen. In endemic regions, high seroprevalence among children suggests horizontal transmission via saliva, whereas in low-prevalence countries, transmission is primarily sexual and correlates with multiple partners or a history of sexually transmitted infections. Although incidence has declined with widespread antiretroviral therapy, KS remains the most common neoplasm associated with HIV/AIDS, affecting around 20% of patients.
Types
KS is classified into five clinical variants: classic (sporadic), endemic, epidemic (HIV/AIDS-related), iatrogenic (immunosuppression-related), and non-epidemic KS.
Classic KS
A slow, indolent form primarily affecting men of Mediterranean or Eastern European descent, typically in later adulthood. Lesions are usually confined to the distal extremities as isolated cutaneous nodules or plaques, with limited progression and low mortality.
Endemic KS
Predominantly seen in sub-Saharan Africa, where HHV-8 seroprevalence exceeds 90%. Transmission occurs mainly through saliva, often affecting children and young adults (male predominance). Compared to classic KS, it more frequently involves lymph nodes and visceral organs, leading to a more aggressive clinical course.
Epidemic KS
The most common HIV-associated malignancy and an AIDS-defining condition. Its incidence has decreased with antiretroviral therapy, but when present, it is often aggressive and disseminated, correlating with CD4+ T-cell depletion and HIV-induced enhancement of HHV-8 replication.
Iatrogenic KS
Occurs in individuals receiving immunosuppressive therapy, particularly organ transplant recipients. The risk is 50–500 times higher than in the general population. Lesions may regress upon reduction or withdrawal of immunosuppressive agents.
Non-Epidemic KS
A recently described subtype seen in HIV-negative men who have sex with men (MSM). Lesions are usually limited and associated with a favourable prognosis.
Across all subtypes, HHV-8 infection is a prerequisite, and disease progression correlates with the degree of immunosuppression. There is an overall male predominance.
Macroscopic Features
Cutaneous KS lesions typically present as pink-purple angiomatous macules, papules, nodules, or plaques that are non-blanching, non-pruritic, and painless. They range from 0.5–2 cm, often following Langer’s lines symmetrically. Over time, they evolve from flat macules to infiltrated purplish plaques or nodules; in darker skin tones, they may appear brown to black.
Commonly affected areas include the face (periorbital, perioronasal, retroauricular), trunk, and lower limbs (especially plantar and periungual regions). At the neck and trunk, lesions often align in a linear “fir branch” pattern.
Mucosal involvement (oral, conjunctival, genital) is frequent, particularly in epidemic KS—60% of patients develop oral lesions, which may be the initial manifestation of HIV infection. Visceral progression can present with haemoptysis, haematemesis, or melena.
Lymphoedema, particularly of the lower limbs, occurs in about 17% of endemic KS cases, resulting from lymphatic obstruction. The Stemmer sign (inability to pinch the skin at the base of the second toe) is pathognomonic.
Dermoscopic Features
Major reported Dermoscopic findings include:
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Bluish-red discolouration
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Rainbow pattern = ‘back-to-back’ vascular networks with minimal intervening stromal and cellular tissue, forming a honeycomb-like pattern, seen as polychromatic colour change with polarised dermoscopy
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Scaly surface
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Small brown globules
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White lines, white clods (in patch and plaque lesions)
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Collarette sign (also seen in pyogenic granuloma, melanoma, basal cell carcinoma, angiokeratoma, Spitz naevus, eccrine poroma)
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Dotted, coiled and curved vessels
White areas reflects the absence of melanin, dermal sclerosis, keratin structures and hypergranulosis. White lines and white clods are mainly seen in patch and plaque lesions.
Non-polarised dermoscopic image Same lesion using polarised dermoscopy
Histological Analysis
Under the microscope, there is a dermal proliferation of atypical spindled endothelial cells, creating irregular slit-like vascular channels, which can infiltrate through dermal collagen. When these channels form around native blood vessels, this is referred to as the 'promontory sign', which is a classic but uncommon feature. Extravasated red blood cells are seen in the vascular channels. There is a mainly lymphocytic inflammatory infiltrate with occasional plasma cells, haemosiderin-laden macrophages and there may be PAS-positive hyaline globules. There may be epithelial hyperkeratosis or ulceration.
HHV-8 immunostaining remains the most specific diagnostic marker distinguishing KS from its mimics.
Histologic variants include anaplastic, lymphangioma-like, telangiectatic, ecchymotic, glomeruloid, intravascular, hyperkeratotic, lymphoedematous, keloidal, micronodular, and pigmented forms, each with distinct microscopic features.
The table below describes variants of KS and their histological features:
Immunohistochemistry
KS spindle cells express endothelial markers (CD31, CD34, Factor VIII) and lymphatic markers (D2-40, LYVE-1, VEGFR-3, Prox-1). Bcl-2 positivity supports resistance to apoptosis.
Immunostaining for HHV-8 LNA-1 confirms viral infection, though HHV-8 may rarely be found in other vascular tumours.
Diagnosis and Differentials
Diagnosis is based on clinical suspicion and confirmed by skin biopsy, with immunohistochemistry for HHV-8.
Differentials vary by stage:
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Patch stage: haemangioma, granuloma annulare, fibrous histiocytoma
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Plaque stage: acroangiodermatitis, haemangioma
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Nodular stage: bacillary angiomatosis, pyogenic granuloma, haemangioma
Clinical context (HIV status, transplantation history) is key to diagnosis.
The tables below reveal common differentials, their typical features and distribution:
You can access the above images sourced from DermNet here: https://dermnetnz.org/
You can access acroangiodermatitis images here: https://pmc.ncbi.nlm.nih.gov/articles/PMC4144224/
You can access bacillary angiomatosis images here: https://www.sciencedirect.com/science/article/pii/S0041134519317865?via%3Dihub
Management
Treatment aims to control symptoms, prevent progression, improve cosmesis, and minimise psychological distress. There is no definitive cure.
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Local therapy: surgical excision, radiotherapy, laser or cryotherapy, photodynamic therapy, topical alitretinoin, or intralesional vinblastine
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Systemic therapy: indicated for extensive disease (>25 lesions), oral or visceral involvement, rapid progression, or significant oedema
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HIV-associated KS: managed with antiretroviral therapy (HAART)
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Iatrogenic KS: dose reduction or cessation of immunosuppression; sirolimus may be used post-transplant to induce regression
References
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Dauguet M, Lebbé C, Vignes S. Lymphedema and Kaposi sarcoma: A narrative review. J Med Vasc. 2023;48(5-6):181-187. doi: 10.1016/j.jdmv.2023.10.007. Epub 2023 Nov 8.
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Radu O, Pantanowitz L. Kaposi sarcoma. Arch Pathol Lab Med. 2013 Feb;137(2):289-94. doi: 10.5858/arpa.2012-0101-RS.
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Iftode N, Rădulescu MA, Aramă ȘS, Aramă V. Update on Kaposi sarcoma-associated herpesvirus (KSHV or HHV8) - review. Rom J Intern Med. 2020 Dec 17;58(4):199-208. doi: 10.2478/rjim-2020-0017.
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Ertürk Yılmaz T, Akay BN, Okçu Heper A. Dermoscopic findings of Kaposi sarcoma and dermatopathological correlations. Australas J Dermatol. 2020 Feb;61(1):e46-e53. doi: 10.1111/ajd.13150. Epub 2019 Sep 8.
