Kaposi's sarcoma (overview) C46.-

Authors: Prof. Dr. med. Peter Altmeyer, Prof. Dr. Dr. H. c. Peter Karl Kohl

All authors of this article

Last updated on: 18.12.2020

Dieser Artikel auf Deutsch

Synonym(s)

angiomatosis Kaposi; Angioreticulomatosis; idiopathic multiple pigment sarcoma Kaposi; Kaposi's disease; Kaposi's sarcoma; Kaposi's Sarcoma; M. Kaposi; Pigmentary sarcoma Kaposi idiopathic multiple; Pseudosarcoma teleangiectatic; Sarcoma idiopathicum Kaposi; Sarcoma idiopathicum multiplex haemorrhagicum; teleangiectatic pseudosarcoma

History
This section has been translated automatically.

Kaposi, 1872

Definition
This section has been translated automatically.

Rare multifocal angioproliferative neoplasia occurring primarily in the skin and secondarily also in other organs. Kaposi's sarcoma occurs spontaneously or as part of an HIV infection.

Classification
This section has been translated automatically.

Clinical forms:

  1. Classical/sporadic Kaposi sarcoma: Occurs mainly in men from Southeast Europe; association with HLA DR5; onset beyond the age of 50. Localization on the distal extremities, centripetal spread, organ or mucosa involvement in 5-20% of cases. Mostly course over decades.
  2. African/endemic Kaposi's sarcoma: Mainly in African children; a distinction is made between skin and lymph node type; usually fulminantly aggressive course.
  3. HIV-associated, epidemic Kaposi's sarcoma: In AIDS patients(especially male homosexuals). Disseminated skin infection (extremities, trunk, acra) and mucous membrane involvement in 30% of patients. Mostly variable course, often organ involvement (lymph nodes, gastrointestinal tract, lungs). See Table 1.
  4. Kaposi's sarcoma in immunosuppressed patients (also iatrogenic Kaposi's sarcoma): iatrogenic, after organ transplantation or in various diseases, e.g. lupus erythematosus, systemic or severe atopic eczema. Especially in men, similar course as the HIV-associated Kaposi sarcoma.

Staging according to Mitsuyasu and Groopman (stage and clinical findings):

  • Stage I: circumscribed cutaneously (< 10 foci or one anatomical region)
  • Stage II: Disseminated cutaneously (> 10 foci or > 1 anatomical region)
  • Stage III: Exclusively visceral
  • Stage IV: Cutaneous and visceral
    • Stage IV A: Without general symptoms
    • Stage IV B: With fever and/or weight loss.

ACTG stage classification of HIV-associated Kaposi sarcomas see table

Occurrence/Epidemiology
This section has been translated automatically.

Incidence (classic Kaposi sarcoma): 1/10 million inhabitants/year. Incidence of HIV-associated epidemic Kaposi's sarcoma: Kaposi's sarcoma is the characteristic disease of MSM. In 5-7% of HIV infected persons. Before cART, 20% of men were affected.

Etiopathogenesis
This section has been translated automatically.

Vascular proliferation whose aetiology has not yet been clearly clarified. Among others, genetic disposition (association with HLA-DR5; frequent occurrence in Mediterranean populations), expression of growth factors (especially Oncostatin M, IL-1 beta, Basic Fibroblast Growth Factor), viral genesis (HHV-8) and immunosuppression are discussed. The prevalence of KS in organ transplant patients is 0.5-5.3%, which is 500 times higher than in control groups, and the prevalence of HHV-8 is 20%! In HIV-infected patients with HIV-associated epidemic Kaposi's sarcoma, associations with the tat protein of HIV-1 have been described.
Molecular pathologically, HIV-induced Kaposi's sarcoma is preceded by an inflammatory response due to infection with HHV-8. HHV-8 suppresses the expression of p53 (see below tumour suppressor genes) via its LNA-1 (latent nuclear antigen). Furthermore, it inhibits proliferation blockade by the RB protein (retinoblastoma protein; see below tumour suppressor genes) and transforms endothelial cells with the Ras oncogene(proto-oncogene). As a result, a number of inflammatory cytokines are produced (e.g. TNF-alpha, IL-1 and other interleukins), which initiate the expression of the angiogenic growth factor bFGF (= basic fibroblast growth factor; see growth factors below) by the endothelia, forcing them to proliferate continuously. However, endothelia do not only need a proliferation signal for their growth, but also a topological orientation signal (e.g. fibronectin). The tat protein(= trans-acting transcriptional activator) expressed by HIV-1 viruses mimics this fibronectin effect. Endothelial cells express certain integrins(belonging to the adhesion molecules) which act as tat receptors. At the same time, the tat protein is able to initiate the formation of collagenases so that the neoplastic endothelial cells can infiltrate the collagenous tissue.

Clinical features
This section has been translated automatically.

Initially brown-red to violet spots, from which plaque-like and nodular tumours develop. Tendency to confluence and formation of new foci in the marginal area. Tendency to ulceration (especially mucous membrane lesions). In case of trunk infestation mostly exanthematic spread of the skin lesions with characteristic arrangement along the skin cleft lines. Disturbed lymph drainage leads to elephantiasis-like oedemas. Infestation of lymph nodes, more rarely of the gastrointestinal tract, liver, lungs or heart is possible.

Histology
This section has been translated automatically.

In the patch and plaque stage , there are in the upper and middle dermis under a mostly unchanged epidermis with orthokeratotic keratinization, blurred proliferates of endothelial cells and fibroblasts; formation of atypical slit-like vascular structures with erythrocyte extravasations and hemosiderin deposits; furthermore, a lymphocytic and macrophagocytic infiltrate is usually detectable.

In the plaque stage spindle cell formations are in the foreground, which are bundled into fascicles or strands that penetrate the entire dermis. The tumor cells are HHV-8, vimentin, in early lesions also factor VIII and CD31 and CD34 positive. Frequently, immunohistological staining is the only way to determine the complete extent of vascularization.

In the nodular or tumor stage , a cell-rich nodule is made up of densely packed turflike fascicles that penetrate the entire dermis. Included are slit-shaped endothelium-free clefts with erythrocyte clusters. Only moderate nuclear atypia. Mitoses are common.

In the lymphangioma-like variant of Kaposi's sarcoma the "angiomatous character" of the new formations is more strongly expressed. There are irregular, partially anastomosing vessels with prominent "hobnail" endothelials. In paraffin sections, HHV8-LNA (latent nuclear antigen) can be detected very reliably in all forms of Kaposi's sarcoma by immunohistiochemical means.

Diagnosis
This section has been translated automatically.

  • Clinic, histology, skin sonography, exclusion of infestation of internal organs (especially lungs).
  • Detection of Kaposi's sarcoma herpes virus (HHV-8) serologically or from tissue by PCR (diagnostically not necessarily conclusive, as neoplasia such as Castleman's lymphoma or "body-cavity based B-cell-lymphoma" HHV-8 may also be associated).

Differential diagnosis
This section has been translated automatically.

Clinical image/localization/histology Differential diagnoses
Clinical Solitaire cutaneous, angiomatous (vascular, livid) Cell-rich or thrombosed angiomas; granuloma teleangiectaticum; haematomas; angiokeratomas; angiosarcomas
Solitary cutaneous spindle cell (spindle cell-rich, skin-coloured, reddish) dermatofibroma; dermal melanocytic nevi; lymphomas; more rarely: melanomas; pigmented basaliomas; on the lower legs: acroangiodermatitis
Oral Oral angiomas, bleeding, amalgam tattoo
Lymphatic Lymphomas; Syphilis II; EBV infection
Disseminated cutaneous cutaneous T-cell lymphoma; cutaneous B-cell lymphoma; syphilis II; bacillary angiomatosis
Histological Angiomatous and spindle cell forms Various benign and malignant vascular tumors: angiomas; angiokeratomas; angiosarcomas; granuloma teleangiectaticum; inflammatory granulation tissue; acroangiodermatitis Mali; Stewart's bluefarb syndrome; bacillary angiomatosis

Therapy
This section has been translated automatically.

Classical/sporadic KS:

  • Compression bandages with short-stretch bandages to eliminate lymphedema (see compression therapy).
  • Excision if necessary (often only palliative), local recurrence rate high.
  • Radiation therapy: In the case of large-area or grouped lesions, use of fractionated soft X-ray therapy. The KS is very sensitive to radiation; single dose (ED) 3-5 Gy 3 times/week, total heart dose (GHD): 20-30 Gy (30-60 kV); X-ray irradiation of larger foci with a GHD of 30-50 Gy, ED: 5 Gy.
    Linear accelerator (or circulation accelerator): indicated for large-area Kaposi sarcomas with a penetration depth of < 2 cm and secondary lymphoedema due to lymphatic flow disturbance.
    In case of rapid tumour progression with multilocular occurrence, chemotherapy if necessary (see treatment of HIV-associated KS). Based on own experience, treatment with liposomal doxorubicin can be recommended in extensive, otherwise therapy-refractory, progressive cases.
  • Topical use of alitretinoin gel 0.1% (panretin) for the treatment of manifest classic cold sores and their recurrences.

African KS: Like classic/sporadic Kaposi sarcoma.

HIV-associated KS:

  • In case of exclusive skin infestation and < 10 lesions:
    • Camouflage (e.g. Dermacolor), especially in cases of cosmetically disturbing changes and lack of desire for therapy.
    • Laser therapy(argon laser) is only suitable for small macular lesions.
    • Cryosurgery (open spray method, 2 cycles, 30-60 sec.) is only suitable for macular lesions, wound healing 6-8 days, not plantar or genital.
  • Soft X-ray therapy: (GD 30 Gy, 43 KV, FHA 15 cm):
    • Fractionation: trunk or extremities: 6 times 5 Gy; face: 10 times 3 Gy; penis: 15 times 2 Gy.
    • In the following cases a break of at least 2 weeks should be made after 50% of the total dose: In the area of problem localisation (plantar, enoral, penis/scrotum, tongue, eyelids, conjunctiva)
    • After and under chemotherapy (danger of increased radiosensitivity)
    • Limits of Dermopan irradiation:
    • diameter > 12 cm
    • thickness > 1,5 cm
    • Extended lymphedema
    • Strongly curved surface
    • Enoral: diameter > 2,5 cm
    • Back third of the tongue.
    • Side effects are: radiodermatitis (2-3 weeks), pigmentation changes, alopecia. Prophylaxis of pigmentation: No simultaneous intake of β-carotene, no UV-exposure during and 4 weeks after therapy! Treatment of pigmentation: Vitamin A acid (e.g. Cordes VAS cream) locally.
  • Cobalt irradiation: lesions in the area of the oral mucosa and throat. Total dose 20 Gy, ED 2 Gy. After 50% of the total dose, rest for at least 2 weeks because of the risk of mucositis.
  • Irradiation with fast electrons: large-area Kaposi sarcomas (lower leg, groin region, face, occasionally accompanied by lymphedema). 20 Gy GHD, ED 2 Gy.
  • Intralesional interferon: Only in patients with > 200 CD4 cells/μl. Injection 3 times/week with 1 ml/cm2 for 4 weeks.
  • Intralesional chemotherapy (vinblastine or vincristine): dilution 1:9 with 1-2% xylocaine solution. Intralesional injection of 0.5-1 ml/cm2, max. 2 mg total dosage/session at 3 week intervals. Usually 3 sessions are required.

    Cave! Pain, sensitivity disorders, occasional superficial necrosis. Not indicated for acral Kaposi sarcoma.

  • chemotherapy:
    • Interferon alfa-2a (e.g. Roferon; evidence level B III; remission rate 40-50%): 3-6 million IU s.c./day 3 times a week. Only in patients with > 200 CD4 cells/μl, because the response rate with fewer CD4 cells is only 7% and always in combination with HAART. Because of flu-like NW, the administration of paracetamol (ben-u-ron) 1000 mg 1 hour before injection is recommended.
    • Liposomal doxorubicin (e.g. Doxil; evidence level AI; remission rate: 60-80%): 20 mg/m2 KO i.v. every 2 weeks.
    • Alternative: Liposomal daunorubicin (e.g. DaunoXome; level of evidence AI; remission rate: approx. 60%) 40 mg/m2 KO i.v. every 2 weeks.
    • Paclitaxel (e.g. Taxol; level of evidence BII; remission rate: 50-60%): 100 mg/m2 KO i.v. every 3 weeks.
  • Antiretroviral therapy (for HIV infection)
    : Especially after initiation of highly active antiretroviral therapy (HAART), regression of Kaposi's sarcoma has been described. Since HAART has become available, the incidence of KS as an AIDS-defining disease has decreased.
  • Ciclosporin-based therapy regimens appear to be associated with a higher risk of KS in organ transplant patients than azathioprin-based regimens. A switch to mycophenolate mofetil may lead to regression of KS (off-label use).

Progression/forecast
This section has been translated automatically.

  • According to recent studies, CD4 cell count has no influence on the prognosis of Kaposi's sarcoma under HAART.
  • See Table 2

Tables
This section has been translated automatically.

Stage classification of HIV-associated epidemic Kaposi's sarcoma according to ACTG (AIDS Clinical Trial Group)

Risk

Early stage (good prognosis)

Late stage (poor prognosis)

If all the following conditions are met:

If any one of the following conditions applies:

T0 (good forecast)

Tumor (T0): Kaposi's sarcoma limited to skin and/or lymph nodes; minimal oral involvement if any (non raised lesions on the hard palate)

Tumor (T1): Pulmonary or gastrointestinal Kaposi sarcoma; extensive oral involvement; tumor-related edema or ulceration

T1 (poor prognosis)

I0 (good prognosis)

Immune status (I0): CD4 cells > 200/µl

Immune status (I1): CD4 cells < 200/µl

I1 (poor prognosis)

S0 (good prognosis)

Symptoms (S0): No opportunistic infections, no oral thrush, no B symptoms (b) of HIV infection

Symptoms (S1): In the medical history opportunistic infections, oral thrush, malignant lymphoma or HIV-associated neurological diseases, B-symptomatic (b) of HIV infection

S1 (poor prognosis)

(b) B-symptoms of HIV infection = unclear fever, night sweats or diarrhoea lasting longer than 2 weeks, weight loss > 10%.


Clinical type

Survival time after initial manifestation

Classical/sporadic Kaposi sarcoma

years - decades

African/endemic Kaposi sarcoma

Few months - years

HIV-associated, epidemic Kaposi sarcoma

Depending on the stage of HIV infection and the effectiveness of antiretroviral therapy options: Few months - years

Kaposi sarcoma (KS) in immunocompromised patients

months - years


Therapeutic agent

Dosage

Requirement

Remission rate (%)

Side effects

Level of evidence

References

Interferon alfa-2a or interferon alfa-2b

3 times/week 3-6 million IE s.c. (dose escalation possible depending on tolerance)

> 200 CD4 lymphocytes/μl

40-50

Fever. Rare: muscle aches, arthralgia, depressive moods

BIII

T1, I0, S0-1

(Pegylated) liposomal doxorubicin

20 mg/m2 KO i.v. at 2-week intervals

T1, I1, S0-1

60-80

Neutropenia, anemia. Rare: sensation of heat, shortness of breath, back pain, palmoplantar erythrodysesthesias

AI

Goebel, 1996; Nunez, 2001

daunorubicin liposomal

40 mg/m2 KO i.v. at 2-week intervals

T1, I1, S0-1

approx. 60

Neutropenia, anemia. Rare: sensation of heat, shortness of breath, back pain, palmoplantar erythrodysesthesias

AI

Rosenthal, 2002

Paclitaxel (Taxol)

100 mg/m2 KO i.v. in 2-week intervals or 135 mg/m2 KO i.v. every 3 weeks

T1, I1, S0-1

50-60

Neutropenia, peripheral neuropathy, allergic skin reactions. Rare: hypotension, ECG changes, alopecia

BII

Saville, 1995; Tulpule, 2002

* (if possible always in combination with antiretroviral combination therapy according to the currently valid guidelines)


Tumor size

Therapy

Reference

Small area (≥ 1 cm² macular, nodular)

Cryosurgery

Schöfer, 1991; Tappero, 1991

vincristine intralesional

Schöfer, 1991; Odom, 1987

vinblastine intralesional

Newman, 1988; Epstein, 1993; Ramirez-Amador, 2002

Interferons intralesional

Trattner, 1993

Alitretinoin Gel 0.1% (Panretin)

Walmsley, 1999; Duvic, 2000; Bodsworth, 2001

Excision

Medium size (1-4 cm diameter; macular, nodular)

vinca alkaloids intralesional

Schöfer, 1991; Newman, 1988

Dermopan irradiation (fractionated)

Schöfer, 1991; Kaliebe, 1994

Large surface (> 4 cm diameter; nodular, infiltrating, oral)

Fast electrons, cobalt irradiation (fractionated)

Nisce and Kaufman, 1993; Stelzer and Griffin, 1993

on the lower leg additional compression treatment

All predominantly macular Kaposi sarcomas

Camouflage

Hundeiker and Kehling, 1985

Intraoral

Vinblastine intralesional, 3% sodium tetradecyl sulfate intralesional

Ramirez-Amador, 2002


Active principle

Substances

References

angiogenesis inhibitors

AGM 1470, TNP 470

Dezube, 1998

Glufanide disodium, IM 862

Tulpule, 2000

Thalidomide

Little, 2000

Metalloprotease inhibitors

Cianfrocca, 2002

Aromatic Retinoids

9-cis-retinoic acid, oral

Aboulafia, 2003; Miles, 2002

Liposomal tretinoin, oral

Amber, 2002

Hormonal agents

Urinary HCG, or HCG fractions

Pepper, 2002

Antiviral substances (against HHV-8)

Cidofovir

Little, 2003

Chemotherapeutics

Cidofovir

Little, 2003

Etoposide

Sprinz, 2001, Evans, 2002

Vinorelbine

Nasti, 2000

Aftercare
This section has been translated automatically.

  • HIV-associated, epidemic Kaposi sarcoma:
    • 3-monthly checks of the skin, mucous membranes, lymph nodes
    • 6-12-monthly check of the lungs (X-ray thorax) and the GI system (sonography, endoscopy).

Literature
This section has been translated automatically.

  1. Antman K, Chang Y (2000) Kaposi's sarcoma. N Engl J Med 342: 1027-1038
  2. Brenner B et al (2002) Classical Kaposi sarcoma: prognostic factor analysis of 248 patients. Cancer 95: 1982-1987
  3. Campistol J et al (2007) Kopsi`s sarcoma in renal transplant recipients-the impact of proliferation signal inhibitors. Nephrol Dial Transplant 22 (Suppl 1) i17-i22
  4. Kaposi M (1872) Idiopathic multiple pigment sarcoma of the skin. Arch Derm Syph 4: 265-273
  5. Rappasberger K, Tschachler E, Zonzits E et al (1990) Kaposi's sarcoma in human immunodeficiency virus type 1-seronegative persons: demonstration of retrovirus-like particles in cutaneous lesions. J Invest Dermatol 95: 371-381
  6. Schöfer H, Brockmeyer N (2002) German guideline: Kaposi's sarcoma.
  7. Rogena EA et al (2015) A review of the pattern of AIDS defining, HIV associated neoplasms and premalignant lesions diagnosed from 2000-2011 at Kenyatta National Hospital, Kenya. Infect Agent Cancer 10:28.

  8. Rohner E et al (2016) HIV and human herpesvirus 8 co-infection across the globe: Systematic review and meta-analysis. Int J Cancer 38: 45-54.

  9. Rohrmus B et al (2000) Outlook in oral and cutaneous Kaposi's sarcoma. Lancet 356: 2160
  10. Schulz TF et al (2015) Kaposi Sarcoma-associated Herpesvirus: mechanisms of oncogenesis. Curr Opin Virol14:116-128.

  11. Webster-Cyriaque J (2002) Development of Kaposi's sarcoma in a surgical wound. N Engl J Med 346: 1207-1210

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.