Kaposi's Sarcoma

Last Updated: 2019-08-26

Author(s): Anzengruber, Navarini

Human Herpes Virus 8, HHV-8, Sarcoma idiopathicum haemorrhagicum multiplex, M. Kaposi, Angiomatosis Kaposi, idiopathic multiple pigment sarcoma Kaposi, teleangiectatic pseudosarcoma, Kaposi syndrome, angioreticulomatosis, Kaposis sarcoma.

Multifocally proliferating tumor of spindle-shaped, lymphatic endothelial cells.

Men are affected significantly more frequently than women.

  • Classic/sporadic/chronic Kaposi sarcoma:
  • Especially in male patients coming from Poland, Russia, Southeast Europe or the Mediterranean region (often Turkish patients). Also frequent among Ashkenazi Jews.
  • Association with HLA DR5.
  • M: F = 10:1.
  • First manifestation from the age of 50 to 60.
  • Manifestation at the distal extremities (especially at the feet and legs) with centripetal spread.
  • Visceral infestation: 5-20% of cases.
  • Decades, spontaneous remission possible.
  • Lymphoma incidence increased.

 

  • HIV-induced/epidemic Kaposi's sarcoma:
  • In HIV-positive patients.
  • Especially young, male, homosexual patients.
  • Disseminated skin infestation (besides trunk, extremities also nose, ear, glans penis).
  • Mucosal involvement in 30% of patients.
  • Frequent extracutaneous infestation.
  • Mostly variable course, but often unfavourable courses.
  • Frequent organ involvement (lymph nodes, gastrointestinal tract, lungs).

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

Early stage (good prognosis): when all the following conditions are met:

Late stage (poor prognosis): when any of the following conditions apply:

1. tumour (T): 0: Kaposi's sarcoma on skin and/or lymph nodes;

if necessary minimal oral involvement (not sublime lesions on the hard palate)

1. tumour (T): 1. pulmonary or gastrointestinal

Kaposi's sarcoma; extensive oral infestation;

tumor-related edema or ulcerations

2nd immune status (I): 0: CD4 cells ≥ 200/μl

2nd immune status (I): 1: CD4 cells < 200/μl

3. Symptoms (S): 0: none opportunistic

infections, no oral thrush, no B symptoms**

the HIV infection

3. Symptoms (S): 1: In the anamnesis opportunistic

Infections, oral thrush, malignant

lymphoma or HIV-associated neurological

Diseases, B symptoms of HIV infection*

* B symptoms = unclear fever, night sweats or diarrhoea lasting longer than 2 weeks, weight loss 10%.

Source: Vogt, T. (2016). AWMF: Detail Awmf.org. Retrieved 10 May 2016, from http://www.awmf.org/leitlinien/detail/ll/032-025.html

 

  • Iatrogenic Kaposi's sarcoma in immunosuppressed patients:
  • Patients under medication with:
  • Corticosteroids, azathioprine, sirolimus, ciclosporin A.
  • Also possible in rheumatoid diseases, sarcoidosis and lupus erythematosus and after transplantation.
  • Aggressive course.
  • Spontaneous regression possible after discontinuation or dose reduction.
  • Skin changes occur more often with Ciclosporin than with Azathioprin. Remission is described after conversion to off-label therapy with mycophenolate mofetil.

 

  • Endemic/African Kaposi's sarcoma:
  • Four clinical types: nodular (more favorable course), florid (often exophytic growing, aggressive variant), infiltrative (fibrosating, deep-reaching changes, aggressive variant, especially extremities and lymph node infestation) and lymphadenopathic (especially in adolescents).
  • Also occurring in children.
  • Mostly lethal course.
  • Only lymph node infestation possible.

A multifactorial development can be assumed: HHV-8 virus infection, genetic predisposition (HLA-DR5), immunosuppression and various molecular pathogenetic factors.

Usually initially reddish to black-brown, asymptomatic maculae, then plaques and nodules, which are arranged along the skin cleft lines. Bleeding and partly necrotic ulcerations occur in the course of the disease. In addition, pronounced edema and swelling can occur in the area of infiltrating nodules and confluent plaques. Predilection sites for this are the extremities and the face. The Palatum durum is particularly affected.

General symptoms are not visible for a long time.

  • Anamnesis (risk group, origin, underlying diseases).
  • Clinic.
  • Dermatopathological protection.
  • HIV serology.
 

Clinical

 

Clinical

Solitary cutaneous, angiomatous (rich in vessels, livid)

Cell-rich or thrombosed angiomas, granuloma teleangiectaticum, hematomas, angiokeratomas, angiosarcomas

 

Solitary cutaneously spindle-cellular (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 tattooing
 

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-Bluefarb syndrome, bacillary angiomatosis

Source: Vogt, T. (2016). AWMF: Detail. Awmf.org. Retrieved 10 May 2016, from http://www.awmf.org/leitlinien/detail/ll/032-025.html

  • Blot stage: Bloodless fissures around vessels or adnexa. Characteristic are siderophages and plasma cells, which represent a pseudogranulomatous pattern. Orthokeratotic keratinization, mostly lymphocytic and macrophagocytic infiltrate.

 

  • Plaque stage: Typical is the occurrence of spindle cell fascicles, blood-filled slits and dilated vessels. Orthokeratotic keratinization, mostly lymphocytic and macrophagocytic infiltration.   

 

  • Tumorstadium: Man trifft auf eine erhöhte Zahl an Mitosen der Spindelzellknoten, ohne nennenswerte Kernatypien. Häufig sind intrazytoplasmatische, hyaline Globi. HHV-8-DNA Sequenzen sind nachweisbar. Die Tumorzellen sind Vimentin, oftmals auch Faktor VIII positiv und CD31-positiv. 
  • No consistent therapy.
  • Treatment of the underlying disease, if possible.
  • Possible surgical excision for a few lesions.
  • Radiotherapy for solitary infestation (success rate: 90%, GD:20-30 Gy, ED: 4-5 Gy).
  • Cryotherapy: suitable for superficial application.

 

  • Topical retinoids
  • Tretinoin
  • Airol® Cream 0.05% 1-2x daily
  • Airol® Lotio 0.05% 1-2x daily
  • Off-label-use
  • Application 1-2x daily, if necessary 1x daily or every 2nd day for sensitive skin. Use for at least 6-14 weeks.
  • CI: acute dermatitis, rosacea, pregnancy, lactation.
  • Laser (argon): only recommended for small macular efflorescences.

 

In case of rapid progress or resistance to therapy:

 

Examples of palliative systemic therapy modalities in angiosarcoma (AS)

Pharmacone/

Scheme

Dosage

Response rate

Notes/

(reference)

Paclitaxel

80 mg/m2 per day 1,8,15

4 weeks

30 patients

PFS of 74%

or 45% of the total

after 2 or 4

Months

ANGIOTAX Study

(Penel et al., JCO

26:5269-74, 2008)

Paclitaxel

Various schemes

(retrospective analysis)

32 patients

RR of 62%

(all AS)

up to 75% (scalp)

EORTC Study

(Schlemmer et al., Eur J

Cancer 44:2433-6, 2008)

Gemcitabine

1000 mg/m2weekly

Where. 1 - 3, all 4 Where.

25 patients

CR + PR was here

at 68%.

(Stacchiotti et al., Ann

Oncol, 2011)

Paclitaxel

 

Doxorubicin,

PEG liposomal

140 mg/m2 cont. intravenously over 6

Days every 4 weeks.

50 mg/m2 d1 every 4 weeks.

3 PR, 2 CRs,

3 PDs

3 PR, 2 SD, 1 PD

(Skubitz et al., Cancer

2005)

Trofosfamid

Rofecoxib*

Pioglitazone

3 x 50 mg p.o. daily long-term therapy

25 mg p.o. daily long-term therapy

45 mg p.o. daily long-term therapy

2 CR, 1 PR, 3 SD

Mainly "second

line" according to the above pre-therapies,

low toxicity,

outpatient p.o.

(Vogt et al., Cancer 2003)

Source: Vogt, T. (2016). AWMF: Detail. Awmf.org. Retrieved 10 May 2016, from http://www.awmf.org/leitlinien/detail/ll/032-025.html

 

Aftercare

  • Classic Kaposi's sarcoma:
  • Patients usually die of other diseases.
  • Dermatological examination every 6 months, except when skin changes occur again.

 

  • HIV-associated Kaposi's sarcoma:
  • Despite great effort, only short-term remission is to be expected.
  • Checks of the skin, mucous membranes, lymph nodes (every 3 months).
  • Thoracic x-ray, haemocult test, sonography or endoscopy of the GI system if necessary (every 6-12 months).
  • Often lethal.

 

  • Endemic Kaposi sarcoma:
  • Both indolent and aggressive courses are described.

 

  • Iatrogenic Kaposi's sarcoma:
  • If the immunosuppression can be revoked or the medication is changed, the prognosis is usually very good.
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