Wat U Moet Weten Over Kaposi-sarcoom - Huidziekte en Behandeling

Histopathology

Kaposi sarcoma progresses through 3 distinct clinical stages: patch, plaque, and nodular.

The patch stage of Kaposi sarcoma is characterized by a spindle cell proliferation of irregular, complex vascular channels dissecting through the dermis with the promontory sign, defined as ramifying proliferating vessels surrounding larger ectatic pre-existing vessels and skin adnexa.[20][3] Extravasated red blood cells, hemosiderin-laden macrophages, rare hyaline globules, and perivascular lymphocytes and plasma cells are also frequently identified.

Advancement to the plaque stage of Kaposi sarcoma has an increasing prominence of the features seen in the patch stage with extension into the subcutis, and more prominence of the hyaline globules intra- and extra-cellularly.[20][3] These hyaline globules are periodic acid-Schiff positive and demonstrate Weibel-Palade bodies by electron microscopy.[20] Cellular pleomorphism is minimal, and there are few mitotic figures.[20][3]

As Kaposi sarcoma develops into the nodular form, the pleomorphism increases and mitotic figures become more prominent [3]. The slit-like lumens are enhanced as well.[20][3]

Histologic variants of Kaposi sarcoma include: in situ Kaposi sarcoma, anaplastic Kaposi sarcoma, lymphangiectatic Kaposi sarcoma, bullous Kaposi sarcoma, ecchymotic Kaposi sarcoma, glomeruloid Kaposi sarcoma, and hyperkeratotic Kaposi sarcoma.[20]

The presence of HHV-8 can be confirmed with immunohistochemistry for LANA1.[14]

Behandlung des Kaposi-Sarkoms

Menschen mit HIV-Infektion sollten eine antiretrovirale Kombinationstherapie erhalten. In diesen Fällen kann eine Ausbreitung des Kaposi-Sarkoms unterbunden oder die Entstehung sogar ganz vermieden werden. Zeigt die Behandlung keinen Erfolg, kann eine Chemotherapie durchgeführt werden, da das Sarkom in der Regel gut auf Krebsmedikamente anspricht.

In einem frühen Stadium kann das HIV-assoziierte Kaposi-Sarkom auch chirurgisch entfernt (Exzision), mit Kältetherapie oder Strahlentherapie behandelt werden. Da das klassische Kaposi-Sarkom meistens lokal behandelt wird, kommen hier ebenfalls Bestrahlung der betroffenen Areale oder eine gezielte Kältetherapie sowie Chemotherapie infrage.

Entstand der Hautkrebs infolge der Einnahme von Medikamenten, die das Immunsystem unterdrücken, kann mit der*dem behandelnden Ärztin*Arzt besprochen werden, ob es abgesetzt werden soll. Es besteht die Chance, dass sich das Kaposi-Sarkom ohne weitere Behandlung wieder zurückbildet.

Da das Kaposi-Syndrom trotz Behandlung häufig erneut auftritt (Rezidiv), sind regelmäßige ärztliche Kontrolluntersuchungen notwendig.

Pathophysiology

HHV-8 is a double-stranded enveloped DNA virus with 6 major subtypes (A-F).[9]

Due to HHV-8 co-evolving with the human population for centuries, cofactors of immune defects and inflammation are required for the development of malignancy.[14] It is transmitted primarily via saliva in childhood and sexually, with some cases of infection via blood transfusion or intravenous drug use.[14] Seropositive family members will often infect other family members, particularly in areas where HHV-8 is endemic.[14][6]

After infecting endothelial cells, HHV-8 activates the mTOR pathway, alters the cells to have mesenchymal differentiation, and promotes aberrant angiogenesis [14]. Through immune suppression and inflammation, the HHV-8 infected cells can persist and proliferate. Expression of latency-associated nuclear antigen (LANA) causes binding of p53 and suppression of apoptosis [14][19]. LANA also maintains the viral episome and prevents Fas-induced programmed cell death.[19] NF-kB is activated by HHV-8 and up-regulates cytokine expression. Up-regulation of VEGF and bFGF results in neo-angiogenesis [19]. It induces c-kit expression and produces the spindled morphology of Kaposi sarcoma cells from their original cuboidal monolayer.[19] Matrix metalloproteinases are upregulated by HHV-8.[19]

Interestingly, Kaposi sarcoma is not monoclonal and different nodules within a patient have different clonal origins.[14]