Editorial,  Clin Oncol Case Rep Vol: 6 Issue: 9

Understanding Kaposi Sarcoma

Carlos A. Cardenas^1* , Jose Javier Bravo² , Andres David Rosero³

¹FORESC (Foundation For Research and Sciences), USA

²St. Francis Downtown Hospital, USA

³UCR Riverside Medical Research,USA

*Corresponding Author: Carlos A. Cardenas,
FORESC (Foundation For Research and Sciences)USA
E-mail: Karmed@live.com

Received: September 05, 2023; Manuscript No: COCR-23-116216 ;
Editor Assigned: September 07, 2023; PreQC Id: COCR-23-116216 (PQ) ;
Reviewed: September 16, 2023; QC No: COCR-23-116216 (Q);
Revised: September 18, 2023; Manuscript No: COCR-23-116216 (R) ;
Published: September 21, 2023; DOI: 10.4172/cocr.6(9).313;

Citation: Cardenas CA , Bravo JJ, Rosero AD (2023). Understanding Kaposi Sarcoma Clin Oncol Case Rep 6:9

Abstract

Keywords: Kaposi sarcoma; KSHV infection; AIDS; Clinical oncology

Introduction

Kaposi sarcoma, initially described by Moritz Kaposi in 1872, has gained significant attention due to its association with immunosuppression, particularly in patients with Acquired Immuno Deficiency Syndrome (AIDS) and organ transplant recipients [1,2]. With the discovery of HHV-8 as a causative agent in the 1980s, Kaposi sarcoma has become a subject of intense study [2]. This editorial explores the different clinical manifestations of Kaposi sarcoma, emphasizing their unique characteristics and progression over time.

Etiology

HHV-8, a ubiquitous presence in all variants of Kaposi sarcoma, assumes a central role in driving its pathogenesis. The viral agent responsible for Kaposi sarcoma disrupts normal cellular functions, requiring the involvement of co-factors such as cytokines and specific proteins for the complex development of the disease. Additionally, HHV-8 is associated with other malignancies, including plasmablastic multicentric Castleman disease and primary effusion lymphoma [3].

Epidemiology

Kaposi Sarcoma (KS) exhibits intricate variations among diverse populations, presenting itself as a complex mosaic with distinct patterns. These observations yield crucial insights that contribute to both clinical management approaches and the formulation of successful public health strategies.

Classic KS

Classic KS displays a notable gender bias, with a male-to-female ratio of 17:1. This form primarily affects individuals aged 50 and older, particularly those of Eastern European and Mediterranean heritage [4]. Intriguingly, these patients exhibit an increased susceptibility to secondary malignancies, further complicating the disease landscape. Notably, the prevalence of classic KS closely aligns with the distribution of human herpesvirus 8 (HHV-8). Kaposi Sarcoma (KS) manifests with an annual incidence of approximately 6 cases per million individuals in the United States, with a predominant occurrence among individuals living with HIV infection [5,6].

Endemic KS, also known as African sarcoma

Endemic Kaposi sarcoma presents a unique predilection for pediatric populations, often reflecting HHV-8 seropositivity rates. Endemic KS bears a resemblance to classic KS, yet it typically manifests in individuals at a younger age. Is a chronic condition that affects the feet and legs. Notably, in children who have not yet reached puberty, there can arise an especially aggressive form of endemic KS. Across different African regions, seropositivity among pediatric patients varies widely, ranging from a mere 2% in Eritrea to near-universal prevalence in the Central African Republic. Interestingly, the emergence of the HIV epidemic in Africa has led to a notable shift in the gender distribution of endemic KS cases, with the male-to-female ratio narrowing from 7:1 to 2:1. Consequently, endemic KS has become the most prevalent cancer among men and the second most prevalent among women in regions such as Uganda and Zimbabwe [7,8].

HHV-8 Seropositivity: HHV-8 seropositivity rates exhibit remarkable geographic diversity. The highest rates are observed in Saharan Africa, reaching up to 40%, while regions such as Northern Europe, Southeast Asia, and the Caribbean report much lower rates, ranging from 2% to 4%. The Mediterranean region and the United States fall within an intermediate range, with roughly 10% and 5% to 20% of individuals, respectively, testing positive for HHV-8. This distinctive geographical distribution sets HHV-8 apart from other human herpesviruses [9,10].

Epidemic KS

Epidemic Kaposi sarcoma ranks as the second most common tumor in individuals with HIV and CD4 counts below 200 cells/ mm³ , serving as an AIDS-defining illness indicative of advanced immunosuppression [11]. Alarmingly, up to 30% of HIV-positive individuals who do not receive High-Activity Antiretroviral Therapy (HAART) may develop Kaposi sarcoma. Among HIVpositive male homosexuals, the risk of Kaposi sarcoma is elevated by 5-10-fold [12].

Iatrogenic KS

Iatrogenic Kaposi sarcoma, arising from medical interventions, demonstrates a distinct gender distribution with a male-to-female ratio of 3:1. Notably, over 5% of transplant recipients who develop de novo malignancies will encounter Kaposi sarcoma, representing a substantial 400-fold to 500-fold increase in risk compared to the general population [13]. Importantly, the risk profile varies based on the type of transplant, with bone marrow or peripheral blood stem cell recipients facing significantly lower risks than solid organ transplant recipients [14].

These epidemiological observations underscore the intricate nature of Kaposi sarcoma, shaped by a multifaceted interplay of viral infection, immunosuppression, and diverse population dynamics.

Pathophysiology

Kaposi Sarcoma (KS) represents a multifaceted malignancy characterized by intricate pathophysiological mechanisms. The presence of Human herpes virus 8 (HHV-8), an enveloped DNA virus with double-stranded genetic material, is closely intertwined with the human population through co-evolutionary processes. [15]. The development of malignancy in KS is intricately linked to immune defects and a state of chronic inflammation, serving as critical cofactors in the pathogenic cascade [15].

HHV-8, known to the scientific community as Kaposi Sarcoma Herpesvirus (KSHV), is disseminated primarily through saliva and sexual contact. Notably, familial transmission has been observed in areas endemic to the virus. Once HHV-8 infiltrates the host, it ensnares endothelial cells, which line the inner surfaces of blood and lymphatic vessels. These infected endothelial cells trigger a myriad of signaling pathways, giving rise to a tumultuous environment characterized by aberrant angiogenesis, immune suppression, and persistent inflammation [15]. These perturbations collectively foster the development and progression of Kaposi sarcoma.

Remarkably, within a single KS-afflicted individual, lesions may originate from distinct clonal lineages, underscoring the heterogeneity intrinsic to this malignancy.

Endothelial origin and clinical presentation

Kaposi sarcoma is characterized by the unbridled proliferation of cells residing within the walls of blood vessels and lymphatic vessels [16]. The linchpin of KS pathogenesis lies in the infection with KSHV, a member of the herpesvirus family, akin to Epstein-barr virus. This virus-infected milieu serves as the crucible for the inception of KS. The primary wellspring of KS lesions is the endothelial cells, the very cells that compose the inner lining of vascular structures. KS can manifest across various anatomical sites within the human body, encompassing the skin, lymph nodes, lungs, bowel, liver, and spleen [16]. A distinctive hallmark of KS is the preponderance of spindle cells within the tumor microenvironment, believed to have arisen from endothelial cell progenitors. Consequently, KS tumors predominantly harbor KSHV genomic material, with immunohistochemical markers unveiling an amalgamation of the lymphoid, spindle, and endothelial cell attributes within these lesions [16].

Koebner Phenomenon and Clinical Diversity.The fascinating Koebner phenomenon highlights the predisposition of Kaposi Sarcoma (KS) lesions to emerge in regions of skin that have experienced trauma. Clinically, KS lesions typically manifest on the skin, with a predilection for regions such as the face, arms, and legs.

These lesions are distinguished by their varied hues, ranging from pink and red to purple and brown, reflecting the multifarious clinical presentations that characterize this malignancy [17].

Comprehending the pathophysiological intricacies of KS, particularly its endothelial cell origin and the pivotal role of KSHV infection, is paramount in steering the development of precise and effective therapeutic strategies [17].

Immune dysregulation in kaposi sarcoma

Kaposi Sarcoma (KS) is not only defined by its intricate pathophysiology but also by its complex interactions with the host immune system, which significantly influence its development and progression. Immune dysregulation emerges as a key protagonist in the KS narrative, intricately weaving itself into the tapestry of this malignancy's pathogenesis [18].

The role of immune suppression

Immune suppression, notably observed in individuals with Acquired Immuno Deficiency Syndrome (AIDS) or recipients of organ transplants under immunosuppressive regimens, emerges as a pivotal risk factor in the genesis of KS. This compromised immune milieu provides KSHV with an opportune environment for reactivation and unbridled proliferation, thereby contributing to the genesis and progression of KS tumors. In the context of HIV/AIDS, the diminishing counts of CD4⁺ T-cells further accentuate vulnerability to KSHV infection and the subsequent advancement of KS [19].

Evasion mechanisms employed by kshv

KSHV, the mastermind behind KS, employs an arsenal of strategies to subvert the host immune response, facilitating its persistence and exacerbating KS pathogenesis. These stratagems encompass the downregulation of Major Histocompatibility Complex (MHC) molecules, interference with antigen presentation, and modulation of cytokine signaling pathways. The establishment of latent infections within host cells by KSHV further compounds the challenge faced by the immune system in detecting and eliminating infected cells [20].

Inflammation and angiogenesis

Chronic inflammation stands as a defining hallmark of KS, with inflammatory cytokines and chemokines orchestrating the recruitment of immune cells into the tumor microenvironment. This inflammatory milieu, coexisting with KSHV, propels angiogenesis-a process vital for the formation of new blood vessels, a characteristic feature of KS tumors. These nascent vessels not only sustain tumor growth but also engender a pro-inflammatory environment, perpetuating the cycle of immune dysregulation [21].

Unraveling the interplay

Comprehending the intricate interplay between immune dysregulation and KSHV infection serves as a cornerstone for the development of innovative therapeutic approaches aimed at reinstating immune surveillance and controlling the trajectory of Kaposi sarcoma. This intricate dance underscores the imperative role of immune modulation as a promising avenue in the management of this multifaceted malignancy [22].

Clinical Presentation

Clinically, Kaposi sarcoma presents as violaceous pink to purple plaques on the skin or mucocutaneous surfaces, often accompanied by pain, lymphedema, and secondary infections. Lesions progress through three major stages: patch, plaque, and nodule. In addition to lymph nodes, Kaposi sarcoma can involve the lungs, gastrointestinal system, and other visceral organs, with respiratory involvement potentially leading to fatality [23].

Histopathology

From a histological perspective, Kaposi sarcoma displays distinctive features including the proliferation of spindle-shaped cells in blood vessels, the presence of irregular vascular channels, the leakage of red blood cells into the surrounding tissue, the accumulation of macrophages containing hemosiderin, the presence of hyaline globules, and the infiltration of lymphocytes and plasma cells around blood vessels. To confirm the presence of HHV-8, immunohistochemistry targeting LANA1 can be employed [24].

Diagnosis

To establish a conclusive diagnosis of Kaposi sarcoma, it is necessary to perform a biopsy or excision of suspicious lesions. Through pathological examination, we can evaluate the distinct spindle cell vascular proliferation that is characteristic of this condition. Additionally, the presence of HHV-8 can be confirmed by utilizing LANA1 immunohistochemistry [24].

Treatment and management

Management of Kaposi sarcoma varies depending on the clinical form. Skin involvement is treated with local excision, liquid nitrogen, and vincristine injection. Chemotherapy is a mainstay for endemic and systemic forms, with HAART showing promise in HIV-related Kaposi sarcoma. Iatrogenic Kaposi sarcoma management involves balancing immunosuppression reduction and sarcoma treatment [25].

Ongoing research and future prospects

Numerous ongoing studies are dedicated to investigating novel treatment approaches for Kaposi sarcoma. These include the exploration of immunotherapies, VEGF inhibitors, tyrosine kinase inhibitors, and matrix metalloproteinases. Promising research avenues encompass intralesional nivolumab, combined administration of pomalidomide with liposomal doxorubicin, as well as immunotherapies such as pembrolizumab and the ipilimumab/nivolumab combination therapy [26].

Prognosis

The prognosis of Kaposi Sarcoma (KS) is multifaceted, influenced by a variety of factors that collectively shape the outlook for affected individuals [5].

Survival rates for KS are not uniform and can vary significantly based on specific determinants:

Stage of cancer

The stage at which KS is diagnosed plays a pivotal role in prognosis. For localized KS, the 5-year relative survival rate stands at a relatively promising 81%. However, when the disease has progressed to a regional stage, this rate drops to 65%. In caseswhere KS has reached a distant stage, the prognosis becomes more challenging, with a 5-year relative survival rate of 47% [27].

Age and general health

An individual's age and overall health condition are important considerations in predicting prognosis. Those in better health and at a younger age may have more favorable outcomes [27].

Treatment efficacy

The effectiveness of the chosen treatment plan significantly impacts prognosis. Successful treatments can improve survival prospects.

Pulmonary Kaposi sarcoma introduces an additional layer of complexity, with variable survival times ranging from 4 to 19 months following diagnosis. Respiratory-related complications, such as upper airway obstruction or parenchymal destruction, often contribute to fatalities in these cases [27].

For classic Kaposi sarcoma, the prognosis carries a mortality rate that typically ranges from 10% to 20%. Several factors come into play when assessing prognosis, including [27].

Disease presentation stage

The stage at which the disease manifests itself plays a crucial role in determining the prognosis. Timely detection and diagnosis can lead to more favorable outcomes.

CD4 count

In cases associated with Human Immunodeficiency Virus (HIV) infection, the CD4 count, which reflects immune function, is a critical factor. Lower CD4 counts indicate greater immunosuppression, which can impact the progression of Kaposi sarcoma.

Opportunistic infections

The presence of opportunistic infections can complicate the prognosis, especially in the context of HIV/AIDS. These concurrent infections further compromise the immune system.

Involvement of Visceral Organs

The participation of vital organs can significantly worsen the prognosis, as it signifies more extensive disease and potential systemic complications.

The prognosis for Kaposi sarcoma exhibits a high degree of variability, influenced by factors such as the clinical stage, immune status, presence of infections, and the extent of organ involvement.

Conclusion

Kaposi Sarcoma (KS) represents a multifaceted soft tissue tumor that exhibits a complex relationship with the Human herpes virus/ Kaposi sarcoma herpesvirus (HHV-8). The present editorial has furnished insights into the etiology, epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and prognosis of KS. It has underscored the significance of comprehending the viral underpinnings that underlie pathogenesis, the disparities in incidence among diverse populations, and the intricate interplay between immune dysregulation and KSHV infection. The evolving therapeutic landscape, encompassing localized excisions, systemic chemotherapies, and state-of-the-art immunotherapies, has been expounded upon. Ongoing research endeavors and future prospects, inclusive of immunotherapies and targeted therapies, hold promise for enhanced treatment modalities. Prognostication in KS is contingent upon factors such as cancer stage, age, general health, and treatment efficacy. This editorial aims to provide a thorough understanding of the intricate nature of Kaposi sarcoma and its evolving research landscape, offering valuable insights for clinicians, researchers, and healthcare practitioners.

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