Primary Classic Kaposi’s Sarcoma Of Lymph Nodes In Ultrasound Resembling Lymphatic Metastases Of A Malignant Tumor And Successful First-Line Therapy With Ipilimumab

Abstract

We report on a 71-year-old patient with a classic, primary Kaposi’s sarcoma of the lymph nodes. He presented with an inguinal lymphadenopathy. An ultrasound examination showed suspicious lesions (oval lymph nodes with a single, round, homogeneous hypoechoic structure with peripheral and diffuse vascularization), yet typical sonomorphological criteria for lymph node metastases of a solid malignant tumor such as melanoma (round lymph nodes with a round hypoechoic area that often contains hyperechoic structures due to necrosis and a peripheral vascularization) were not fully met. Nevertheless, due to the suspicious findings, inguinal lymph nodes were extirpated. Histologically, there were formations of a malignant tumor that led to the diagnosis of a nodal Kaposi’s sarcoma. Skin examinations, HIV testing and imaging procedures presented no pathological findings. A therapy with ipilimumab (3mg/kg every three weeks for four times) was initiated, which resulted in durable tumor control. Sonomorphological patterns for Kaposi’s sarcoma of the lymph nodes are not yet defined. We report on this case to describe the specific sonomorphological structures in our patient as a first step towards establishing sonomorphological criteria for nodal Kaposi’s sarcoma. Furthermore, this is the first case to report on a successful first-line therapy with the immune checkpoint inhibitor ipilimumab in classical Kaposi’s sarcoma. Avens Publishing Group Inviting Innovations Citation: Kraehnke J, Bogumil A, Grabbe S, Loquai C, Weidenthaler-Barth B, et al. Primary Classic Kaposi’s Sarcoma Of Lymph Nodes In Ultrasound Resembling Lymphatic Metastases Of A Malignant Tumor And Successful First-Line Therapy With Ipilimumab. J Clin Investigat Dermatol. 2019;7(2): 5 J Clin Investigat Dermatol 7(2): 5 (2019) Page 02 ISSN: 2373-1044 The course of the disease is dependent on the subtype. Classic Kaposi’s sarcoma mostly has a chronic, indolent course and rarely impacts survival. Sometimes, however, it has an acute onset with rapid progression or a previously indolent disease can undergo sudden worsening, causing significant morbidity and mortality [1214]. In 5-20% of cases there is a mucosal and/or organic involvement [15]. Since there is no treatment to cure classic KS, the treatment generally aims to achieve symptom palliation, improving function and delaying or preventing progression [9]. Local therapy includes excision even though local recurrences are common [15]. KS is radiosensitive, so radiation therapy of cutaneous tumors is a good option. Topical therapy with retinoids, imiquimod, nicotine patches, rapamycin and beta blockers is only marginally efficient [9]. Systemic treatments such as chemotherapy are used in cases of rapid progression or multilocular disease. Standard treatment includes pegylated liposomal doxorubicin or paclitaxel, docetaxel, bleomycin, vinblastine, vincristine, gemcitabine, and etoposide as second line [9,16,17]. However, chemotherapy is mostly palliative. Immunomodulatory agents as interferon alpha and immunomodulatory imide drugs (as thalidomide) have been used in single cases with variable efficacy [16,18]. Recently published case reports indicate that a therapy with anti-PD-1 agents might be a new and successful therapy option [17,19,20]. Case Report We report on a 71-year-old patient with a classic, primary Kaposi’s sarcoma of the lymph nodes. Due to palpable inguinal lymphadenopathy the patient presented at the clinic. On ultrasound, lymph nodes presented suspicious being hyperechoic, oval shaped with a single, round, homogeneous hypoechoic structure. The hypoechoic structure showed a strong peripheral and diffuse vascular pattern (Figure 1). These sonographic findings, albeit not entirely typical, resembled those of lymph node metastases which regularly present as hyperechoic, round shaped lymph nodes with a round, nonhomogeneous hypoechoic area due to necrotic parts of the metastases and a mainly peripheral vascularization (Figure 2). However, due to missing hyperechoic parts within the round, hypoechoic structure and a strong diffuse vascularization, criteria for lymph node metastases were only partially met. Furthermore, the bilateral appearance of suspicious lymph nodes at the same time was not impossible but uncommon for metastases. The presenting lymph nodes seemed to be a mixture of metastases (due to the hypoechoic structure with peripheral perfusion) and reactive lymph nodes (due to the additional, strong diffuse perfusion). Due to these ultrasound findings, imaging was extended. A CT showed soft-tissue masses, unknown pulmonary lesions and suspect inguinal, iliac and axillary lymph nodes. A bilateral extirpation of inguinal lymph nodes was done. Histologically, there were formations of a malignant tumor with siderosis and a mesenchymal proliferation of atypical spindleshaped endothelial cells (Figure 3 and 4). The vascular markers CD34, CD31, D2-40/Podoplanin as well as HHV8 showed a positive result Table 1: Four variants of Kaposi’s sarcoma. We focus on classic Kaposi’s sarcoma (primarily nodal) in this paper. Types of Kaposi’s sarcoma Risk group Affected organs Staging systems Treatments Classic Elderly Mediterranean/ eastern European men mainly skin/mucous membranes seldom lymphatic tissue (also as primary nodal KS) or internal organs Mitsuyasu and Groopman: Stage I: < 10 cutaneous lesions/ one anatomic region Stage II: > 10 cutaneous lesions/ > 1 anatomic region Stage III: visceral lesions only Stage IV: cutaneous and visceral lesions Stage IV A: without general symptoms Stage IV B: with fever and/or weight loss Local: excision, radiation therapy Topic: retinoids, imiquimod, nicotine patches, rapamycin and beta blockers Systemic: chemotherapy (e.g. pegylated liposomal doxorubicin or paclitaxel, docetaxel, bleomycin, vinblastine, vincristine, gemcitabine) immunomodulatory agents as interferon alpha and thalidomide Endemic Indigenous African children and adults -mainly skin/mucous membranes -seldom lymphatic tissue or internal organs Mitsuyasu and Groopman: see above Local: excision, radiation therapy Topic: retinoids, imiquimod, nicotine patches, rapamycin and beta blockers Systemic: chemotherapy (e.g. pegylated liposomal doxorubicin or paclitaxel, docetaxel, bleomycin, vinblastine, vincristine, gemcitabine) immunomodulatory agents as interferon alpha and thalidomide Iatrogenic/ immunosuppressive Related to immunosuppressive therapy / immunosuppressive diseases -mainly skin/mucous membranes -seldom lymphatic tissue or internal organs Mitsuyasu and Groopman: see above Local: excision, radiation therapy Topic: retinoids, imiquimod, nicotine patches, rapamycin and beta blockers Systemic: reconstitution of the immune system AIDS-associated HIV positive patients -mainly skin/mucous membranes -seldom lymphatic tissue or internal organs AIDS Clinical Trials Group (ACTG) staging criteria (including tumor extent, systemic symptoms and immune status) Local: excision, radiation therapy Topic: retinoids, imiquimod, nicotine patches, rapamycin and beta blockers Systemic: HAART Citation: Kraehnke J, Bogumil A, Grabbe S, Loquai C, Weidenthaler-Barth B, et al. Primary Classic Kaposi’s Sarcoma Of Lymph Nodes In Ultrasound Resembling Lymphatic Metastases Of A Malignant Tumor And Successful First-Line Therapy With Ipilimumab. J Clin Investigat Dermatol. 2019;7(2): 5 J Clin Investigat Dermatol 7(2): 5 (2019) Page 03 ISSN: 2373-1044 in the immunohistochemical staining (Figure 5 and 6). Histologically, the diagnosis of a Kaposi’s sarcoma was rendered. Skin examinations, HIV testing and blood tests that were done to rule out other organ manifestations and immunodeficiency were without pathological findings. An esophagogastroduodenoscopy was performed due to intermitting sickness. A gastritis was diagnosed but there was no sign of mucosal tumor lesions. The patient also had not received any immunosuppressive therapy. Therefore he was diagnosed with a classic primary Kaposi’s sarcoma of the lymph nodes, an exceptionally rare sub-type of classic KS since in most cases the diagnosis is rendered due to skin lesions (i.e. not primarily nodal). A therapy with ipilimumab (3mg/kg body weight, 4 cycles, every 3 weeks) was given from June to August 2014. It was well tolerated except for a transient hypophysitis as an immune-related adverse event. The last staging was done in 2019 and showed ongoing regressive lymph nodes and no other pathological findings. The soft tissue masses that were apparent upon primary staging had also fully resolved after therapy with ipilimumab. Thus no further therapy was initiated up to now.