Cutaneous lymphoma, Kaposi sarcoma and vascular lesions

• A primary cutaneous lymphoma is a lymphoma that begins in the skin, with no evidence of spread elsewhere at baseline; mycosis fungoides is the commonest and usually presents as patches and plaques before any tumour or nodal disease. ^{[6] [14]}
• Mycosis fungoides is staged by its skin findings (patch, plaque, tumour) plus node, blood and visceral involvement; management stays skin-directed for early stages and escalates to systemic therapy for advanced or refractory disease. ^[3]
• Kaposi sarcoma is an angioproliferative tumour driven by human herpesvirus 8 (HHV-8/KSHV), most often in the setting of HIV; antiretroviral therapy is the backbone of care, with chemotherapy for symptomatic or advanced disease. ^[4]
• Most vascular skin lesions are harmless and need no treatment: a cherry angioma is a dome-shaped benign papule that may bleed if caught. Malignant vascular tumours are rare but must be recognised in any rapidly growing or ulcerated vascular lesion.
• Sezary syndrome is the erythrodermic, leukaemic form of cutaneous T-cell lymphoma; it is defined by erythroderma, generalized lymphadenopathy and a circulating clonal CD4+ T-cell population. ^[1]

By the end of this page you should be able to:

1. Distinguish primary cutaneous lymphoma from secondary skin involvement, and identify the main T-cell and B-cell entities.
2. Describe the evolution of mycosis fungoides from patch through plaque to tumour, and state what makes Sézary syndrome different.
3. Explain why Kaposi sarcoma is an HHV-8 disease and how HIV alters its behaviour, incidence and management.
4. Recognise benign vascular lesions (cherry angioma, spider telangiectasia, pyogenic granuloma) and the malignant vascular lesions that mimic them.
5. Plan the work-up of suspected mycosis fungoides or Kaposi sarcoma and stage either disease.
6. Outline the management pathway for patch-plaque mycosis fungoides and for HIV-related Kaposi sarcoma, including where chlormethine gel and systemic therapy fit.
7. Counsel a patient on expected course, complications and follow-up.

This topic compares three very different families of skin lesion that often reach the skin from different starting points: primary cutaneous lymphoma (a neoplasm of skin-homing lymphocytes), Kaposi sarcoma (a virus-driven vascular tumour that flares with immunosuppression) and benign vascular lesions that form the bulk of everyday outpatient referrals. They are grouped here because the book page and the differential diagnosis of an acquired vascular or violaceous skin lesion overlap: erythematous plaques, brown or violaceous nodules and angioma-like papules can all be seen in any of the three groups. ^[1][2]

A primary cutaneous lymphoma is a lymphoma that is confined to the skin at presentation, without systemic disease; secondary cutaneous involvement of a systemic lymphoma is staged and treated differently. Primary cutaneous lymphomas are the second most common extranodal non-Hodgkin lymphomas and, in classic epidemiology, about 75 to 80% of them are T-cell derived and 20 to 25% B-cell derived. ^[1][2]

The most important clinical cutaneous T-cell lymphomas are mycosis fungoides (MF) and its four-grade leukaemic counterpart Sézary syndrome (SS), with other entities including primary cutaneous anaplastic large-cell lymphoma, lymphomatoid papulosis, subcutaneous panniculitis-like T-cell lymphoma, and aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. Cutaneous B-cell lymphomas are primary cutaneous follicle-centre lymphoma, primary cutaneous marginal zone lymphoma or lymphoproliferative disorder, and primary cutaneous diffuse large B-cell lymphoma, leg type. Modern classifications have moved several indolent conditions from the term "lymphoma" to "lymphoproliferative disorder" so that patients are not overtreated. ^[1][2]

Kaposi sarcoma (KS) is a multifocal angioproliferative tumour driven by human herpesvirus 8 (HHV-8; it is also known as KSHV). It is organised clinically into four subtypes: classical KS (elderly men, Mediterranean and Eastern European origin), endemic African KS (children and young adults in sub-Saharan Africa), iatrogenic or transplant-related KS (immunosuppressive drugs), and epidemic HIV-related KS. ^[4][7]

Vascular lesions are a broad descriptive group. A cherry (Campbell de Morgan) spot is a small dome-shaped red papule produced by a proliferating capillary lobule; it is benign. Other common acquired lesions are spider telangiectases (arteriolar radiations), venous lakes, pyogenic granulomas (lobular capillary haemangiomas that bleed easily), glomus tumours and angiokeratomas. Unlike the above, angiosarcoma and Kaposi sarcoma are malignant or potentially aggressive vascular neoplasms and enter the differential of any atypical vascular lesion. ^[8][9]

Primary cutaneous lymphomas are rare: the annual Western incidence is about 1 per 100,000, while mycosis fungoides and Sézary syndrome together occur in several cases per million people, with the highest rates in men over 50. Reported incidence rates for primary cutaneous T-cell and B-cell lymphomas are under 10 per million persons and have been increasing. ^{[1][2] [3]}

Mycosis fungoides accounts for most primary cutaneous lymphomas, while Sézary syndrome is much rarer. Recognised contributors include long-term ultraviolet exposure, smoking and some medications, and possibly prior chronic inflammation of the skin; clinical exposure to a variety of environments has been described in series. A few families are affected, and particular HLA alleles have been reported in both sporadic and familial mycosis fungoides. Patients with cutaneous lymphoma have a significantly higher risk of secondary malignancy, particularly melanoma, so their follow-up should include appropriate skin surveillance. ^[1]

Kaposi sarcoma changed epidemiology dramatically with HIV. Before the antiretroviral era, roughly 20 to 30% of people diagnosed with AIDS developed Kaposi sarcoma. ^[4] HHV-8 seroprevalence is strongly regional: below 10% in northern Europe, Asia and the United States, intermediate (10 to 30%) around the Mediterranean, and above 40% in much of sub-Saharan Africa. In 2018 there were approximately 42,000 new cases of Kaposi sarcoma and 20,000 deaths worldwide. ^[4] Endemic Kaposi sarcoma also occurs in children in sub-Saharan Africa, suggesting that infection early in life is important in those regions.

Kaposi sarcoma behaves differently at different immune levels. It can occur in people with well-controlled HIV and normal or high CD4 counts, and between 2007 and 2011 15% of Kaposi sarcoma cases occurred with CD4 counts above 500 cells per microlitre. ^[4] Starting, and not interrupting, combination antiretroviral therapy is protective. The SMART trial showed higher Kaposi sarcoma incidence when antiretroviral therapy was interrupted, and the START trial (4,685 HIV-positive people with CD4 counts above 500 per microlitre) showed that immediate rather than deferred treatment reduced new Kaposi sarcoma. ^[4]

Benign vascular lesions become more common with age. Cherry angiomas are extremely common in older adults, spider telangiectases occur in pregnancy and with chronic liver disease, and pyogenic granulomas occur in children, young adults and pregnant women. Their exact prevalence is less important clinically than distinguishing the benign lesion from a copycat.

Mycosis fungoides is a malignancy of skin-homing CD4+ T cells that accumulate in the epidermis and superficial dermis. The characteristic cell shows a convoluted "cerebriform" nucleus. Histologically, the neoplastic T cells often lose pan-T-cell antigens such as CD2, CD5 or CD7, and identical T-cell clones on polymerase chain reaction from two separate sites strongly support the diagnosis. A population of CD4+ cells lacking CD2, CD5 or CD7 is more than 90% specific for mycosis fungoides. ^[1] Skin-directed treatments applied before biopsy can remove neoplastic cells and other findings for 2 to 4 weeks, so a drug history matters. ^[1]

The disease usually progresses slowly through its morphological stages. Its evolution from patch to plaque and finally to tumour is driven by changes in the tumour microenvironment that allow immune evasion, with T-helper-2 skewing and local immunosuppression becoming more marked as plaques and tumours appear. ^[3] Ultraviolet-driven mutation patterns in the skin, environmental exposures, rare familial clustering and certain medications have all been suggested as contributing factors, but no single causal agent is proven. ^[1]

Sézary syndrome is the leukaemic form. It combines an erythrodermic skin picture with generalized lymphadenopathy, intractable pruritus, palmoplantar keratoderma and circulating clonal Sézary cells. A Sézary count of at least 1,000 cells per microlitre is classified as B2 disease in the ISCL/USCLC/EORTC TNMB system. ^[1] Flow cytometry typically shows CD3+CD4+CD8- cells with loss of CD7 and/or CD26; loss of both CD7 and CD26 in more than 40% of peripheral blood CD4+ T cells is 100% specific for Sézary syndrome. ^[1]

HHV-8 establishes lifelong infection, maintaining a latent phase in which LANA and other latency genes are expressed, and a lytic phase that releases infectious virus. Immunosuppression is the decisive cofactor: low CD4 counts and impaired cellular immunity allow infected cells to proliferate and for the virus to drive angiogenesis and cytokine signalling through pathways such as mTOR and STAT3. ^[4] The result is a spindle-cell and vascular tumour with slit-like spaces, extravasated red cells and haemosiderin, supplied by HHV-8-positive endothelial cells.

HIV excites the process in several ways. Sustained viraemia produces chronic activation of macrophages and other immune cells, which secrete pro-inflammatory and pro-angiogenic cytokines (TNF-alpha, IL-6) that help create a permissive tumour microenvironment. ^[4] Immune reconstitution inflammatory syndrome (IRIS) can unmask or worsen KS in the first months after starting antiretroviral therapy. In a European cohort the risk of KS in the first three months after starting combination antiretroviral therapy was about 3.94-fold higher than in untreated controls; pulmonary involvement and thrombocytopenia at follow-up are adverse features. ^[4] Critically, KS-IRIS is not a reason to stop antiretroviral therapy. ^[4]

Cherry angiomas are benign collections of small vessels in the dermis with no systemic disease; their prevalence climbs steeply with age but there is no known malignant potential. Spider telangiectases represent dilated superficial arterioles draining into a venule and are cutaneous markers rather than diseases in themselves. Pyogenic granulomas are rapidly growing lobular capillary proliferations that often bleed after trivial injury. The risk in these conditions comes from missing an imitator such as amelanotic melanoma, bacillary angiomatosis or Kaposi sarcoma. ^[8][9]

Patch-stage disease consists of flat, slightly scaly erythematous or hypopigmented or hyperpigmented patches, often in covered areas and in a "bathing suit" distribution. Plaques are raised, slightly indurated and sometimes intensely pruritic. Both are usually slowly progressive. Tumours arise most often in plaques that have been present for years, are dome-shaped, firm and may ulcerate. Rare variants include folliculotropic mycosis fungoides (which can be more aggressive when dense), pagetoid reticulosis (localized, excellent prognosis) and granulomatous slack skin. Presentation can be mistaken for eczema, psoriasis, parapsoriasis, pityriasis or drug eruptions for several years. ^[1][2] In skin of colour, lesions are often polychromic, with hyperpigmentation, lichenification or a silvery hue. ^[1]

Sézary syndrome looks different clinically: generalized erythroderma (often with islands of spare skin), intractable itch, ectropion and palmoplantar keratoderma. Lymph nodes may be enlarged. Extracutaneous (nodal, visceral, blood) involvement is what marks it as stage IV. ^[1]

Lesions begin as dusky pink or violaceous macules or patches and evolve into plaques and nodules, often on the lower limbs and facial skin. They may be asymmetric, multiple and variably shaped. Oral lesions, lymphoedema and disfiguring plaques are common in advanced disease. The number of lesions, their depth and any visceral involvement determine the stage. HIV-related disease can be aggressive and multifocal; endemic childhood disease often involves lymph nodes. ^[4][7]

• Cherry angioma: bright red to purple dome, blanches partly, fills again quickly, sometimes pedunculated; may trickle blood when traumatized.
• Spider telangiectasia: bright red central arteriole with radiating legs; blanches on pressure and refills from the centre.
• Venous lake: dark blue, compressible, on the lip or ear; often in older men.
• Pyogenic granuloma: bright red lobulated papule or nodule with a collarette, bleeds profusely; it can look alarming.
• Glomus tumour: small blue-red nodule, exquisitely tender to cold or pressure.
• Angiokeratoma: dark red to black hyperkeratotic papule.

In any vascular lesion ask about speed of growth, pain, bleeding, immunosuppression or organ transplant, known cancer, and whether the lesion blanches and refills normally. A biopsy is needed if the lesion is new, rapidly enlarging, ulcerated, pigmented, atypical or located in an immunosuppressed or previously irradiated patient. ^[9]

A violaceous or erythematous papule, plaque or nodule can be cutaneous lymphoma, Kaposi sarcoma, melanoma, a benign vascular lesion (cherry angioma, spider telangiectasia, pyogenic granuloma, venous lake), bacillary angiomatosis, a drug eruption, contact dermatitis, psoriasis, eczema, lichenoid dermatoses, an infectious granuloma, or metastatic disease. The combination of lesion morphology, site, immunosuppression and, crucially, biopsy with immunohistochemistry separates them. ^[1][8][9]

Figure 1Angioma

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Long description

A photograph described as 'A picture of a cherry angioma on my left leg. It's been measured as approximately 7mm x 3mm.'

Figure 2Erythrodermic-mycosis-fungoides

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Long description

A clinical photograph captioned Erythrodermic mycosis fungoides. Advanced stage of mycosis fungoides in a 25-year-old man.

Figure 3Kaposis sarcoma 01

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Long description

Kaposi's sarcoma with characteristic violaceous plaques on the alar and tip of the nose in an HIV-positive female patient.

Diagnosis is clinicopathological. Take a 4–6 mm punch biopsy that includes reticular dermis; avoid biopsy through skin that has just been treated with potent topical steroid, because steroid eliminates neoplastic cells for 2 to 4 weeks. ^[1] Immunohistochemistry documents a CD4-predominant infiltrate with loss of CD2, CD5 or CD7. TCR gene rearrangement studies by polymerase chain reaction, and identical clones from two sites, strongly support the diagnosis, although reactive clones can occur and some cases are clone-negative. ^[1] Blood involvement is assessed by flow cytometry for aberrant pan-T-cell antigen loss and high-resolution TCR-Vbeta or TRBC1 analysis, plus a Sézary count.

The contemporary ISCL/USCLC/EORTC TNMB staging combines skin (T), node (N), viscera (M) and blood (B) status. Patch stage is T1–T2 depending on the surface area covered; plaque stage is also T2 or T3 depending on extent; tumour stage is T3 when discrete tumours arise in patches or plaques. Nodal and visceral involvement (N1–N3, M1) and blood involvement (B1/B2) move the patient into stage III–IV disease. ^[1][5]

Biopsy is the gold standard: spindle cells, slit-like vascular channels and HHV-8 latent nuclear antigen-1 (LANA-1) positivity. HIV testing, CD4 count and viral load are required in every patient. Visceral (gastrointestinal, pulmonary) and lymph-node disease is assessed clinically and, when suspected, with imaging and bronchoscopy or endoscopy. Histopathology also excludes bacillary angiomatosis. ^[4][7]

A biopsy is usually unnecessary for a classic cherry angioma. For any atypical, bleeding or rapidly changing vascular lesion, biopsy (punch or excisional) with appropriate stain for platelet endothelial markers or HHV-8 is required, with culture and Warthin-Starry staining if bacillary angiomatosis is possible. ^[8][9]

Early disease (stages IA–IIA). The aim is control of skin lesions and symptoms with skin-directed therapy. First-line options include high-potency topical corticosteroids for patches and plaques, narrowband UVB, PUVA, localised radiotherapy for a stubborn plaque, and intralesional or topical treatments. ^{[3][10][11][12]}

Chlormethine (mechlorethamine) gel (0.016% w/w) is recommended by all the major guidelines as a first-line option for stage IA–IIA disease. ^[3] It is applied once daily to the affected skin, beginning at a small test area if the skin is sensitive, and the frequency is reduced temporarily in the event of a local reaction; no systemic absorption has been detected. ^[3] Limited body-surface involvement (up to about 30%) is the most convenient setting, but whole-body (neck-down) application is possible. ^[3] It may be combined with an offset schedule of narrowband UVB: narrowband UVB in the morning and gel at bedtime, or the two on alternate days. ^[3] For frictional or flexural lesions, alternate-day gel with a topical steroid (e.g. clobetasol) is often better tolerated. ^[3]

Advanced disease (stages IIB–IV). Skin-directed therapy alone is insufficient; add or switch to systemic treatment. Options include oral bexarotene or other retinoids, interferon (often pegylated interferon-alpha), low-dose methotrexate (typically weekly), and extracorporeal photopheresis for erythrodermic or Sézary syndrome. ^[1][3] For refractory, CD30-expressing or relapsing disease, add brentuximab vedotin, mogamulizumab (which can be combined with gel or topical steroids two to three times weekly for residual patches and plaques) or histone deacetylase inhibitors such as vorinostat or romidepsin. ^[1][3] Radiation and total skin electron beam therapy are used for cutaneous tumours; allogeneic stem-cell transplantation may be curative in selected patients with advanced or transformed disease. ^[1]

Sézary syndrome is approached with systemic therapy from the outset (retinoid plus interferon, extracorporeal photopheresis, or mogamulizumab) with skin-directed measures as adjuncts; organ involvement and performance status guide the intensity. ^[1]

For all of these agents, follow the licensed dose and local haematology-oncology protocols. The scheduling of these individual agents is set out in the major guidelines, which should be checked before prescribing. ^{[1][10][11][12]}

Antiretroviral therapy is the treatment of Kaposi sarcoma in the setting of HIV: sustained viral suppression reverses much of the disease and reduces progression, and IRIS should not trigger stopping or switching antiretroviral therapy. ^[4] General supportive care (compression and physiotherapy for lymphoedema, treatment of infection and Kaposi sarcoma–immune reconstitution syndrome) is part of management.

Limited (few cutaneous) disease may be controlled with local measures: intralesional vincristine, topical alitretinoin, cryotherapy, electrocautery, photodynamic therapy, radiotherapy or careful surgical excision. ^[7][9]

Advanced, symptomatic, rapidly progressive, extensive mucocutaneous or visceral disease requires systemic therapy on top of antiretroviral therapy: most commonly liposomal doxorubicin or paclitaxel as first-line systemic agents, with gemcitabine, vinblastine, etoposide or bleomycin-vincristine combinations in settings where the preferred agents are unavailable, and pomalidomide in selected patients. ^[4][7] Nodal, gastrointestinal or pulmonary involvement and severe lymphoedema push treatment towards systemic therapy. Immune-checkpoint inhibitors show activity in selected cases but still need controlled evidence. ^[4]

Most require no treatment. Cherry angiomas can be left alone; remove only if bleeding or troublesome by shave excision, laser or cautery. Spider telangiectases are treated only for cosmetic reasons or if associated with a significant systemic disease such as chronic liver disease or pregnancy-related angiomas; underlying liver disease should be investigated rather than the skin. Pyogenic granulomas usually stop bleeding temporarily with pressure, then are removed by shave excision with cautery; very small lesions may respond to imiquimod or timolol in selected cases. Lymphangiomas and venous malformations need specialist referral; cryosurgery, sclerotherapy and fractional laser each have a place. ^[8][9]

• Mycosis fungoides and Sézary syndrome: large-cell transformation, with a marked worsening of prognosis; secondary infection of ulcerated tumour; profound lymphoedema; and a higher incidence of secondary cancers, including melanoma, which warrants continued skin screening. ^[1]
• Kaposi sarcoma: Kaposi sarcoma–IRIS in the first months of antiretroviral therapy, lymphoedema, gastrointestinal or pulmonary bleeding, respiratory compromise from pulmonary lesions, severe disfigurement, and multicentric Castleman disease or primary effusion lymphoma driven by HHV-8. ^[4][7]
• Sézary syndrome: susceptibility to infection from skin failure and immunosuppression, and treatment toxicity.
• Vascular lesions: bleeding after minor trauma in pyogenic granulomas, bacterial superinfection, diagnostic delay when a malignant lesion is mistaken for a benign one, and iron-deficiency anaemia in very extensive vascular lesions.

In early mycosis fungoides (stages IA–IIA) life expectancy is measured in years and often decades, with treatment aimed at symptoms and appearance. Progression to advanced disease occurs in about a quarter of patients. ^[3] Advanced-stage mycosis fungoides (stage IIB–IV) has a median overall survival of only 2 to 5 years. ^[3] Sézary syndrome carries a poor prognosis, with most studies reporting median survival measured in a few years, heavily influenced by extracutaneous involvement. Folliculotropic disease in its dense infiltrative form behaves like tumour stage. ^[1][2]

Kaposi sarcoma prognosis in the antiretroviral era depends on immune status, extent of disease and visceral involvement. Patients with AIDS-related Kaposi sarcoma have markedly better survival if antiretroviral therapy is continued and systemic chemotherapy is used appropriately, but pulmonary Kaposi sarcoma carries high mortality. ^[4] Classical and endemic disease usually follows a slowly progressive course. ^[7]

Benign vascular lesions have an excellent prognosis; cherry angiomas rarely cause problems beyond cosmetic embarrassment or minor bleeding.

• There is no established screening test for mycosis fungoides or Sézary syndrome; diagnosis rests on biopsy of suspicious lesions, with long follow-up for lesions that mimic eczema. ^[1]
• The only proven preventive measure for Kaposi sarcoma is maintaining adequate control of HIV infection: early and sustained antiretroviral therapy reduces new Kaposi sarcoma formation, whereas interrupting therapy increases incidence. ^[4]
• In HIV-positive patients, particularly those with low CD4 counts or prior Kaposi sarcoma, regular skin and oral examination allows earlier detection; people in endemic regions may benefit from being seen promptly for persistent violaceous lesions.
• Routine dermatology follow-up after a diagnosis of cutaneous lymphoma should include assessment for secondary skin cancers, particularly melanoma. ^[1]
• Sun protection is good general advice but has not been shown to prevent mycosis fungoides.

Pregnancy. Kaposi sarcoma in pregnancy mimics other vascular lesions and can be investigated with biopsy; management follows the same HIV-based principles. Mycosis fungoides and Sézary syndrome are rare in pregnancy. Chlormethine gel has not been adequately studied in pregnancy or breastfeeding and should not be used in those settings. ^[3] Melanoma in pregnancy is managed in the usual dermatology-oncology framework; the AAD melanoma guideline covers pregnancy among its special topics. ^[13]

Children. Endemic African Kaposi sarcoma affects children. Benign vascular lesions are common in children, including port-wine stains and haemangiomas, which are mostly distinct from cherry angiomas. Primary cutaneous lymphoma is rare in children and, when it occurs, often signals an inherited predisposition or primary cutaneous CD4+ small or medium lymphoproliferative disorder. ^[2]

Older adults. Classical Kaposi sarcoma occurs predominantly in elderly men. Advanced age increases cherry angioma count and the frequency of vascular mimics. Treatment decisions for mycosis fungoides in frail older patients should favour skin-directed therapy and tolerability. ^[3]

Immunocompromised and transplant patients. Iatrogenic Kaposi sarcoma (transplant-related) is associated with immunosuppressive drugs and may improve on dose reduction or switching immunosuppression; first-line principles otherwise mirror HIV-related disease. ^[4][7]

• Where biopsy or HHV-8 immunohistochemistry is unavailable, a characteristic violaceous vascular lesion in an immunosuppressed patient may be treated as Kaposi sarcoma while awaiting referral.
• Antiretroviral therapy and lamivudine–doxorubicin-type programmes vary in availability; a pragmatic approach is early antiretroviral therapy, then add systemic chemotherapy according to the national HIV oncology protocol.
• For mycosis fungoides, high-potency topical steroids, simple UVB phototherapy and, where available, chlormethine gel are the practical first-line tools; complex agents (brentuximab, mogamulizumab, ECP) are reserved for referral centres.
• Biopsy equipment, patch-testing for contact dermatitis and flow cytometry are the limiting factors; central review of pathology and shared decision making fill part of the gap. ^[4][9]

Mycosis fungoides differs from eczema or psoriasis by its persistent discrete patches in covered areas, loss of pan-T-cell antigens, and clonal T-cell receptor rearrangement. ^[1] Sézary syndrome differs from erythrodermic eczema by T-cell clonality, aberrant loss of CD7 and CD26, and the specific morphology of Sézary cells. ^[1] Kaposi sarcoma differs from bacillary angiomatosis by spindle cells, vascular slits and HHV-8 positivity. ^[4] Angiosarcoma differs from Kaposi sarcoma and from benign vascular lesions by its aggressive, infiltrative behaviour. ^[9] A classic cherry angioma differs from melanoma by its uniform colour, sharp dome shape and stable size, but any doubt should prompt excision. ^[13]

Related topics: melanoma and the ABCDE screen; dermatology of HIV infection; extracorporeal photopheresis; phototherapy; pigmented purpuric dermatoses; reactive lymphoid hyperplasia of the skin.

• Primary cutaneous lymphoma begins in the skin; secondary skin involvement of a systemic lymphoma is staged and treated differently.
• Mycosis fungoides progresses slowly from patch to plaque to tumour; most patients present with early-stage patch or plaque disease.
• Median time from first symptoms to a definite diagnosis of mycosis fungoides is 3 to 4 years and can be much longer; biopsy after recent steroid use is misleading. ^[1]
• A significant CD4+ population lacking CD2, CD5 or CD7 is over 90% specific for mycosis fungoides; identical T-cell clones in two sites strongly support it. ^[1]
• Sézary syndrome is an erythrodermic, leukaemic disease: a Sézary count of at least 1,000 cells per microlitre is B2, and combined loss of CD7 and CD26 in over 40% of peripheral blood CD4+ cells is 100% specific. ^[1]
• Stage IA–IIA mycosis fungoides is managed with skin-directed therapy first; chlormethine 0.016% gel once daily is a recommended first-line option. ^[3]
• Stage IIB–IV or refractory mycosis fungoides needs systemic therapy; common agents include retinoids, interferon, methotrexate, extracorporeal photopheresis, brentuximab vedotin, mogamulizumab and histone deacetylase inhibitors. ^[1][3]
• Kaposi sarcoma is an HHV-8-driven angioproliferative tumour with classical, endemic, iatrogenic and HIV-related forms. ^[4][7]
• Before ART, about 20 to 30% of people diagnosed with AIDS developed Kaposi sarcoma; HHV-8 seroprevalence is below 10% in northern Europe, Asia and the USA, intermediate in the Mediterranean and over 40% in much of sub-Saharan Africa. ^[4]
• Kaposi sarcoma can occur at normal or high CD4 counts; between 2007 and 2011 15% of cases had a CD4 count above 500 cells per microlitre. ^[4]
• Antiretroviral therapy is the backbone for HIV-related Kaposi sarcoma; IRIS after starting ART is not a reason to stop treatment. ^[4]
• Advanced Kaposi sarcoma is treated with liposomal doxorubicin or paclitaxel in addition to antiretroviral therapy. ^[4][7]
• Vascular lesions are mostly benign; cherry angiomas need treatment only for symptoms.
• Low-dose radiotherapy (4–8 Gy) can be used for indolent cutaneous lymphoproliferative disorders instead of higher doses. ^[2]