There is currently no established therapeutic approach for advanced or metastasized atypical fibroxanthoma. The case study described underlines the importance of individual treatment recommendations. The second case report presents clinical cases in which patients with Kaposi’s sarcoma responded to an innovative alternative treatment strategy after failing chemotherapy.
Together with pleomorphic dermal sarcoma (PDS), atypical fibroxanthoma (AFX) is one of the most common soft tissue sarcomas of the skin (Box) . They are rare neoplasms of the skin and are histomorphologically, genetically and epigenetically variants of a tumor spectrum [1]. Kaposi’s sarcoma (KS) is a rare tumor disease of lymphatic endothelial cells that occurs on the skin, mucous membranes and internal organs and is induced by the human herpesvirus-8 (HHV-8)/Kaposi’s sarcoma-associated herpesvirus (Box) [2].
| The prevalence of Kaposi’s sarcoma (KS) correlates with the prevalence of HHV-8 infections. Classic KS occurs predominantly in men over the age of 50. Since the beginning of the HIV pandemic, epidemic, HIV-associated KS has been the most frequently diagnosed KS subtype. Following the introduction of antiretroviral therapy (ART), the incidence and prevalence of HIV-associated CS have fallen dramatically. Nevertheless, HIV-associated KS is still the most common AIDS-defining neoplasm. |
| according to [2] |
Recurrence of histologically confirmed AFX in an 82-year-old patient
The gold standard in the treatment of atypical fibroxanthoma (AFX) is micrographically controlled surgery. In the case of recurrent, inoperable or metastatic atypical AFX/PDS, there is currently no established procedure [3]. Recently, two cases of advanced PDS successfully treated with anti-PD-1 antibodies were published [3]. In the present case, this treatment strategy was used in a patient with AFX.
The 82-year-old patient presented for the first time in 04/22 with a histologically confirmed AFX (high frontal) at the Department of Dermatology of the University Hospital Essen (D) [3]. The micrographically controlled R0 excision was performed in accordance with the guidelines. Histologically, a cell-dense spindle cell tumor was found. Immunohistochemically, the tumor was positive for CD10 and actin, and negative for CKplus, CD31, CD34 and SOX10. The results of a molecular pathological mutation analysis and immunohistochemical staining to determine PD-L1 expression are still pending. The patient opted for secondary wound healing, resulting in a non-irritated wound surface on the high front.
In 01/23, the patient presented in an emergency with a tumor hemorrhage at the capillitium. A rapidly progressive exophytic tumor, which had grown to a size of 4×4×2 cm, was found in the high frontal area of the secondary healing wound. The histologic result of a sample biopsy showed pleomorphic spindle cells with hyperchromatic nuclei and numerous mitoses consistent with AFX recurrence. Due to the clinical suspicion of a deep infiltration, a CT of the skull was performed, which confirmed a bony infiltration of the tumor. A CT of the thorax showed a metastatic osteolytic lesion in the scapula.
| Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS ) are tumors that typically occur in chronically light-exposed skin as non-specific, skin- to flesh-colored, often ulcerated nodules in very old men. AFX often presents as a fast-growing but well-circumscribed tumor. PDS, for which rapid, but sometimes slower progression has also been described, is blurred and often more aggressively infiltrative. |
| according to [1] |
Treatment with anti-PD-1 antibodies: The interdisciplinary tumor board then recommended treatment with an anti-PD-1 antibody. In view of the extensive tumor involvement with bony infiltration and the highly suspected osteolytic metastasis, the patient received the first dose of off-label therapy with nivolumab in March 2023. After the first infusion of immunotherapy, a partial tumor response is clinically evident.
Chemotherapy-refractory Kaposi’s sarcoma: 81- and 76-year-old patients
There are 5 subtypes of Kaposi’s sarcoma (KS): (i) the endemic (African), (ii) the epidemic (HIV-associated), (iii) the iatrogenic one, (iv) the sporadic type and (v) the form in men who have sex with men. The literature distinguishes between local and systemic therapies, in particular chemotherapies such as taxanes or liposomal encapsulated pegylated doxorubicin. Interferon-a (2a,b) is also an option; in addition to immunomodulatory effects, it also has antiangiogenic and antiproliferative effects. While there are numerous reports on non-pegylated interferon in KS, the use of pegylated interferon, which is now only available, has hardly been established.
Therapy with pegylated interferon-a: In the dermatology department of the Johannes Wesling Clinic, Minden (Germany), two male patients with classic KS were treated with pegylated interferon-a 135 μg s.c. (1×/week) after relapse following chemotherapy [4]. The patients were 81 and 76 years old respectively at the start of treatment. Both have so far shown a partial response with mild side effects such as dizziness, fatigue and a rise in temperature during the first doses. Patient 1 initially received paclitaxel for 3 months. If there was a good response and pronounced side effects, the therapy was discontinued. 14 months later, a relapse occurred and treatment with pegylated interferon was initiated. This resulted in a partial response, which has lasted for 7 months. Patient 2 received two courses of electrochemotherapy with bleomycin 15 mg/m2 body surface area (KOF), 4× local excisions of recurrences and a total of 11 courses of Caelyx 20 mg/m2 KOF. Pegylated interferon-a was initiated in the case of a local recurrence that was ultimately inoperable. A partial response was observed within 2 months, which continued after 4 months.
Literature:
- Helbig D, et al.: S1-Leitlinie Atypisches Fibroxanthom (AFX) und pleomorphes dermales Sarkom (PDS). JDDG 2022 Feb; 20(2): 235–245.
- Esser S, et al.: S1-Leitlinie: Kaposi-Sarkom. JDDG 2022; 20(6): 892–905.
- Scheib C, et al.: Ausgedehntes Rezidiv eines atypischen Fibroxanthoms, eP118, ADO–Jahrestagung, 06.–09.09.2023.
- Khoshandam S, et al.: Erfolgreiche Therapiemit pegyliertem Interferon-a beim Kaposi-Sarkom: zwei Fallbeispiele. ADO–Jahrestagung, 06.–09.09.2023.
DERMATOLOGIE PRAXIS 2024; 34(1): 28
