Factors affecting Kaposi's sarcoma-associated herpesvirus transmission in rural Ugandan households, a longitudinal study.

BACKGROUND: We report the impact of HIV infection within a household on oral Kaposi's sarcoma-associated herpesvirus (KSHV) shedding. METHODS: We enrolled 469 individuals from 90 households. Mouthwash rinse samples collected at three monthly visits were analyzed for KSHV DNA using quantitative polymerase chain reaction (qPCR). Generalized linear mixed effects logistic models were applied to analyze factors associated with KSHV ever shedding, and among shedders, always versus intermittent shedding. Linear mixed effects models were applied to models of KSHV viral loads. Intraclass correlation coefficients (ICCs) were calculated to assess the contribution of household-level factors to variations in shedding probabilities. Hotspot analyses of geospatial feature clusters were calculated using Getis-Ord Gi* statistic and visualized using inverse distance weighted interpolation. RESULTS: Analyses included 340 KSHV seropositive individuals, aged 3 + years, with qPCR results from 89 households. Forty households had 1 + persons living with HIV (PLWH), while 49 had none. Among participants, 149(44%) were KSHV ever shedders. Of 140 who shed KSHV at two or more visits, 34(24%) were always shedders. Increasing number of KSHV seropositive household members was significantly associated with ever shedding [Odds ratio(OR) (95% Confidence Interval(95%CI)):1.14(1.03,1.26);p = 0.013]. Among KSHV shedders, a statistically significant age-related trend was identified with 10-19 years being more likely to be always shedders (type III test p = 0.039) and to have higher viral loads (type III test p = 0.027). In addition, higher viral loads were significantly associated with increasing number of household members [coefficient(95%CI):0.06(0.01,0.12);p = 0.042], increasing number of KSHV seropositive members [coefficient(95%CI):0.08(0.01,0.15);p = 0.021], and living in households with 1 + PLWH [coefficient(95%CI):0.51(0.04,0.98);p = 0.033]. Always shedders exhibited higher viral loads than intermittent shedders [coefficient(95%CI):1.62(1.19,2.05);p < 0.001], and viral loads increased with the number of visits where KSHV DNA was detected in saliva (type III test p < 0.001). Household-level factors attributed for 19% of the variability in KSHV shedding (ICC:0.191;p = 0.010). Geospatial analysis indicated overlapping hotspots of households with more KSHV seropositive individuals and KSHV shedders, distinct from areas where PLWH were clustered. DISCUSSION: KSHV oral shedding is influenced by multiple factors at the individual, household, and regional levels. To mitigate ongoing KSHV transmission a comprehensive understanding of factors contributing to oral KSHV reactivation and transmission within households is needed.

Coexistence of HHV-8-Associated Plasmacytic Multicentric Castleman Disease, Kaposi's Sarcoma, and Multiple Myeloma in a HIV-Negative Patient.

Background: Multicentric Castleman disease (MCD) is a rare, aggressive lymphoproliferative disorder. Human herpesvirus-8 (HHV-8) has an important role in the pathogenesis of the disease and its association with Kaposi's sarcoma has been reported, especially in people living with human immunodeficiency virus (HIV). In this report, we present the case of HHV-8 positive MCD accompanied by Kaposi's sarcoma and multiple myeloma in an HIV-negative patient. Case Report: A 78-year-old man with Kaposi's sarcoma presented with B symptoms, pancytopenia, lymphadenopathy, and splenomegaly. The bone marrow biopsy demonstrated 70% lambda-restricted monotypic plasma cell infiltration consistent with plasma dyscrasia. Also, the patient was diagnosed with HHV-8 positive MCD as a result of inguinal lymph node excisional biopsy. Treatment was initiated including ganciclovir and methylprednisolone and followed by rituximab. The patient passed away at the 24th hour of rituximab infusion due to shock. Conclusions: MCD and associated malignancies are difficult to treat and have a poor prognosis. More studies and data are needed to manage these patients. LEARNING POINTS: Multicentric Castleman disease (MCD), often linked with human herpesvirus-8 (HHV-8) and Kaposi's sarcoma, is rare and aggressive condition, particularly in human immunodeficiency virus (HIV)-positive patients.The coexistence of MCD, Kaposi's sarcoma, and multiple myeloma is exceptionally rare in HIV-negative, immunocompetent patient.This case highlights the challenges in diagnosing and managing complex presentations of MCD and related malignancies, with poor outcomes despite treatment.

Infant feeding and treatment practices could lead to enhanced transmission of Kaposi's sarcoma-associated herpesvirus (KSHV) and other orally shed infections via saliva, in rural south-western Uganda.

This qualitative sub-study investigated household practices affecting orally shed infections using Kaposi's sarcoma-associated herpesvirus (KSHV) as a focus. Participants enrolled from 50 households in rural south-western Uganda were followed monthly up to three times. At enrolment, in-depth interviews were completed, and venous blood collected. KSHV seropositivity was defined as anti-KSHV antibody detection to any of 25 antigens by multiplex bead-based assay. Mouthwash samples from every visit were tested by qPCR and KSHV shedders defined as individuals with KSHV DNA detected. At least one KSHV seropositive person was in 48/49(98%) households. Among those, 79% had 1+ KSHV shedders including 45% with 1+ always shedders and 92% with 1+ intermittent shedders, not mutually exclusively. All respondents reported feeding infants with pre-masticated hard food/fruits and testing food/tea temperature. Temperature was tested by tasting, pouring tea on their hand, or touching the cup to their cheek. Some cooled food/tea using a utensil or blowing over it. Food sharing amongst children and adults and using the same dish was common practice. To treat colic pain, carers/mothers reported chewing herbs and spitting into the child's mouth. Feeding and treatment practices did not vary by KSHV status. We identified potential KSHV transmission modes in rural Ugandan households.

Pulmonary Kaposi Sarcoma in the Era of Antiretroviral Therapy: A Case Series.

Kaposi sarcoma (KS) is an angioproliferative neoplasm that affects the skin and lymph nodes. Human herpesvirus-8 (HHV-8) triggers KS by infecting the endothelium and inducing angiogenesis through the production of vascular endothelial growth factors and cytokines. KS is characterized by purplish or hyperpigmented plaques involving the skin and mucous membranes, and visceral involvement is very rare. Pulmonary KS (PKS) is an exceedingly rare visceral manifestation of KS and has a poor prognosis. PKS often presents with cough, hemoptysis, pleuritic chest pain, fever, and weight loss. In this case series, we share our experience in diagnosing and treating two patients with PKS. We also provide a concise review of the epidemiology, signs and symptoms, diagnosis, and management of this rare condition.

Highly Heterogeneous Kaposi Sarcoma-Associated Herpesvirus Oral Shedding Kinetics Among People With and Without Kaposi Sarcoma and Human Immunodeficiency Virus Coinfection.

Background: An improved understanding of oral Kaposi sarcoma-associated herpesvirus (KSHV) viral dynamics could provide insights into transmission risk and guide vaccine development. Methods: We evaluated KSHV oral shedding dynamics in Ugandan adults stratified by Kaposi sarcoma (KS) and human immunodeficiency virus (HIV) status. Participants were followed for ≥4 weeks, with daily home oral swab collection to quantify KSHV using polymerase chain reaction. Shedding rates were defined by number of days with KSHV DNA detected divided by total days with swabs and compared by group using hurdle models. Results: Two hundred ninety-five participants were enrolled; median age was 35 years (range, 18-71 years), and 134 (45%) were male. KSHV was detected more frequently among participants with KS (HIV positive [HIV+]/KS+, 56/76 [74%]; HIV negative [HIV-]/KS+, 9/18 [50%]) than those without KS (HIV+/KS-, 36/125 [29%]; HIV-/KS-, 16/76 [21%]); odds of shedding did not differ significantly by HIV status. Among participants with KSHV detected, shedding rates did not differ significantly by group. Median per-participant viral loads among positive samples were lowest in HIV+/KS+ (3.1 log10 copies/mL) and HIV-/KS+ (3.3 log10 copies/mL) participants relative to HIV+/KS- (3.8 log10 copies/mL) and HIV-/KS- (4.0 log10 copies/mL) participants. All groups had participants with low viral load intermittent shedding and participants with high viral load persistent shedding. Within each group, individual KSHV shedding rate positively correlated with median KSHV log10 copies/mL, and episode duration positively correlated with peak viral load. Conclusions: Oral KSHV shedding is highly heterogeneous across Ugandan adults with and without KS and HIV. Persistent shedding is associated with higher median viral loads regardless of HIV and KS status.

Complications of Untreated Advanced HIV/AIDS With Kaposi Sarcoma in a Young African American Male: A Case Report.

Kaposi sarcoma (KS) represents a neoplastic proliferation primarily affecting endothelial cells, characterized by the development of cutaneous lesions. However, its pathogenesis can extend beyond the skin, involving internal organs, lymph nodes, and mucous membranes. KS is associated with human herpesvirus 8 (HHV-8) and is often prevalent in immunocompromised patients, especially those with human immunodeficiency virus (HIV) and/or acquired immunodeficiency syndrome (AIDS). We present a case of a 29-year-old African American male who came into the emergency department (ED) with overall discomfort and a boil on his buttock, which was later found to be symptoms of KS in the context of progressed HIV infection. This case report highlights the complications that arise when HIV/AIDS is left untreated and subsequently leads to the development of KS. Early recognition and appropriate interventions are crucial in optimizing outcomes and guiding future care decisions.

Factors affecting Kaposi's sarcoma-associated herpesvirus transmission in rural Ugandan households, a longitudinal study.

Background: We report the impact of HIV infection within a household on oral Kaposi's sarcoma-associated herpesvirus (KSHV) shedding. Methods: We enrolled 469 individuals from 90 households. Mouthwash rinse samples collected at three monthly visits, were analyzed for KSHV DNA using quantitative polymerase chain reaction (qPCR). Generalized linear mixed effects logistic models were applied to analyze factors associated with KSHV ever shedding, and among shedders, always versus intermittent shedding. Linear mixed effects models were applied to models of KSHV viral loads. Intraclass correlation coefficients (ICCs) were calculated to assess the contribution of household-level factors to variations in shedding probabilities. Hotspot analyses of geospatial feature clusters were calculated using Getis-Ord Gi* statistic and visualized using inverse distance weighted interpolation. Results: Analyses included 340 KSHV seropositive individuals, aged 3 + years, with qPCR results from 89 households. Forty households had 1 + persons living with HIV (PLWH), while 49 had none. Among participants, 149(44%) were KSHV ever shedders. Of 140 who shed KSHV at two or more visits, 34(24%) were always shedders. Increasing number of KSHV seropositive household members was significantly associated with ever shedding [Odds ratio(OR) (95% Confidence Interval(95%CI)):1.14(1.03,1.26);p = 0.013]. Among KSHV shedders, a statistically significant age-related trend was identified with 10-19 years being more likely to be always shedders (type III test p = 0.039) and to have higher viral loads (type III test p = 0.027). In addition, higher viral loads were significantly associated with increasing number of household members [coefficient(95%CI):0.06(0.01,0.12);p = 0.042], increasing number of KSHV seropositive members [coefficient(95%CI):0.08(0.01,0.15);p = 0.021], and living in households with 1 + PLWH [coefficient(95%CI):0.51(0.04,0.98);p = 0.033]. Always shedders exhibited higher viral loads than intermittent shedders [coefficient(95%CI):1.62(1.19,2.05);p < 0.001], and viral loads increased with the number of visits where KSHV DNA was detected in saliva (type III test p < 0.001). Household-level factors attributed for 19% of the variability in KSHV shedding (ICC:0.191;p = 0.010). Geospatial analysis indicated overlapping hotspots of households with more KSHV seropositive individuals and KSHV shedders, distinct from areas where PLWH were clustered. Discussion: KSHV oral shedding is influenced by multiple factors at the individual, household, and regional levels. To mitigate ongoing KSHV transmission a comprehensive understanding of factors contributing to oral KSHV reactivation and transmission within households is needed.

Comparison of the indirect immunofluorescence assay and a commercial ELISA to detect KSHV antibodies.

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus involved in several diseases. The gold standard for KSHV sero diagnosis remains the indirect immunofluorescence assay (IFA), which is time-consuming and operator-dependent. We compared this method with an enzyme-linked immunosorbent assay (ELISA) targeting solubilized KSHV whole-genome extract among positive (n = 49, including 76% of HIV-infected patients) and negative (n = 14) control groups. We also included 14 sera with equivocal IFA results. ELISA showed better performance in detecting KSHV antibodies (McNemar's test, P = 0.0455). The sensitivity and specificity of both methods were 79% (64-89) and 100% (66-100) for the IFA, respectively, and 94% (83-99) and 100% (66-100) for ELISA, respectively. All IFA equivocal results were either negative or positive with ELISA. ELISA is more reliable and could be a good alternative for determining KSHV serological status, particularly in the context of immunocompromised patients and equivocal serology with the IFA.IMPORTANCEKaposi's sarcoma-associated herpesvirus (KSHV) sero status remains challenging because no perfect reference is available for the detection of KSHV antibodies. The current gold-standard method, the indirect immunofluorescence assay (IFA), has a very good specificity of close to 100%, but a lower sensitivity of around 80-85%, which decreases to 64-67% in immunocompromised patients. Additionally, this method is time-consuming and operator-dependent compared with new serological assays such as the enzyme-linked immunosorbent assay (ELISA). Thus, further research is still needed to improve KSHV sero diagnosis. Here, we compare the KSHV IgG ELISA kit assay (Advanced Biotechnologies Inc) with the gold-standard IFA, targeting the LANA-1 protein from latent BC-3 cell lines.

Continuous therapy in HHV-8 negative Multicentric Castleman Disease and prolonged progression-free survival.

The optimal treatment endpoints and duration of continuous therapy for multicentric Castleman disease (MCD) remain controversial. We retrospectively analyzed data from 123 patients with Human Herpesvirus (HHV)-8 negative MCD. We demonstrated that continuous therapy significantly enhanced progression-free survival (PFS) in patients who achieved an optimal response after initial treatment. These findings underscore the critical role of continuous therapy in HHV-8 negative MCD. Further studies with larger cohorts are required to validate these findings.

The role of autologous bone marrow transplantation in primary effusion lymphoma: a case report and literature review.

Primary effusion lymphoma (PEL) is an aggressive and rare type of diffuse large B-cell lymphoma (DLBL) that commonly presents itself as pleural, pericardial or peritoneal effusion without lymph node or extranodal involvement in immunosuppressed patients, such as HIV-positive or transplanted receptors. On rare occasions, it may be found in solid sites without effusion, in an immunophenotypically and morphologically similar neoplasm well-known as extracavitary PEL (EC-PEL). Both PEL and EC-PEL are associated with extremely poor prognosis. Due to the rarity of these entities, ther e are no gold standard treatments . Here we discuss the role of autologous bone marrow transplant (auto-BMT) in the treatment of these patients as well as report the case of a young HIV-positive male diagnosed with both PEL and EC-PEL, who underwent a salvage therapy with auto-BMT and achieved complete and sustained remission eight years after the diagnosis.

Exploring the interplay between Kaposi's sarcoma and SARS-CoV-2 infection: A case series and systematic review.

Kaposi's sarcoma (KS) is an angio-proliferative disease with a viral etiology and a multifactorial pathogenesis that results from immune dysfunction. In patients affected by latent viral infections such as herpesviruses, SARS-CoV-2 infection may result in lytic cycle reactivation in host cells. A robust immune system response is crucial for eliminating pathogens and resolving both latent and non-latent viral infections. We report a case series of KS characterized by tumor progression after SARS-CoV-2 infection. We performed a systematic literature review of the PubMed/MEDLINE and EMBASE databases. The keyword terms included "SARS-CoV-2," "HHV-8," "Kaposi's sarcoma," "IL-6," and "COVID-19." English language restriction was applied. Items not covered by our study were excluded. KS is a complex disease linked to an impaired immune system. Conditions that result in temporary or permanent immunodeficiency can trigger viral reactivation or exacerbate an existing disease. It is feasible that the increase in cytokine levels in COVID-19 patients, coupled with lymphocyte downregulation and treatment that induces herpesvirus lytic reactivation, may contribute to the progression of KS after SARS-CoV-2 infection. These observations suggest that patients with KS should be clinically monitored both during and after SARS-CoV-2 infection. Nevertheless, prospective data should be collected to validate this hypothesis and enhance our understanding of the mechanisms implicated in the onset or progression of KS.

The Cytokine Storm of Multicentric Castleman Disease.

As described throughout this book, different triggers can elicit a variety of different cytokine storm disorders that share overlapping clinical features (Fig. 31.1). Even within a particular cytokine storm disorder, multiple different triggers can elicit the syndrome. Like HLH, multicentric Castleman disease (MCD) serves as a great example of this as it can be caused by a viral infection, neoplastic cell population, or an unknown cause. Furthermore, the idiopathic subtype of MCD (iMCD) provides one of the first examples of a cytokine storm disorder that could be abrogated with targeted neutralization of a single cytokine when inhibition with the anti-interleukin-6 (IL-6) receptor monoclonal antibody tocilizumab was shown to effectively treat iMCD in the 1990s. Of course, this "iMCD treatment," tocilizumab, has been used in a variety of cytokine storm settings over the last 30+ years.

Combined Flow-Fluorescence in situ hybridization to HHV-8 and EBV reveals the viral heterogeneity of primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare B-cell non-Hodgkin lymphoma associated with Kaposi Sarcoma-associated herpesvirus (KSHV/HHV8) infection. Lymphoma cells are coinfected with Epstein-Barr virus (EBV) in 60-80% of cases. Tools allowing a reliable PEL diagnosis are lacking. This study reports PEL diagnosis in 4 patients using a Flow-Fluorescence in situ hybridization (FlowFISH) technique that allowed detection of differentially expressed EBV and HHV8 transcripts within the same sample, revealing viral heterogeneity of the disease. Moreover, infected cells exhibited variable expressions of CD19, CD38, CD40, and CD138. Therefore, FlowFISH is a promising tool to diagnose and characterize complex viral lymphoproliferations.

The cellular Notch1 protein promotes KSHV reactivation in an Rta-dependent manner.

The cellular Notch signal transduction pathway is intimately associated with infections by Kaposi's sarcoma-associated herpesvirus (KSHV) and other gamma-herpesviruses. RBP-Jk, the cellular DNA binding component of the canonical Notch pathway, is the key Notch downstream effector protein in virus-infected and uninfected animal cells. Reactivation of KSHV from latency requires the viral lytic switch protein, Rta, to form complexes with RBP-Jk on numerous sites within the viral DNA. Constitutive Notch activity is essential for KSHV pathophysiology in models of Kaposi's sarcoma (KS) and Primary Effusion Lymphoma (PEL), and we demonstrate that Notch1 is also constitutively active in infected Vero cells. Although the KSHV genome contains >100 RBP-Jk DNA motifs, we show that none of the four isoforms of activated Notch can productively reactivate the virus from latency in a highly quantitative trans-complementing reporter virus system. Nevertheless, Notch contributed positively to reactivation because broad inhibition of Notch1-4 with gamma-secretase inhibitor (GSI) or expression of dominant negative mastermind-like1 (dnMAML1) coactivators severely reduced production of infectious KSHV from Vero cells. Reduction of KSHV production is associated with gene-specific reduction of viral transcription in both Vero and PEL cells. Specific inhibition of Notch1 by siRNA partially reduces the production of infectious KSHV, and NICD1 forms promoter-specific complexes with viral DNA during reactivation. We conclude that constitutive Notch activity is required for the robust production of infectious KSHV, and our results implicate activated Notch1 as a pro-viral member of a MAML1/RBP-Jk/DNA complex during viral reactivation. IMPORTANCE: Kaposi's sarcoma-associated herpesvirus (KSHV) manipulates the host cell oncogenic Notch signaling pathway for viral reactivation from latency and cell pathogenesis. KSHV reactivation requires that the viral protein Rta functionally interacts with RBP-Jk, the DNA-binding component of the Notch pathway, and with promoter DNA to drive transcription of productive cycle genes. We show that the Notch pathway is constitutively active during KSHV reactivation and is essential for robust production of infectious virus progeny. Inhibiting Notch during reactivation reduces the expression of specific viral genes yet does not affect the growth of the host cells. Although Notch cannot reactivate KSHV alone, the requisite expression of Rta reveals a previously unappreciated role for Notch in reactivation. We propose that activated Notch cooperates with Rta in a promoter-specific manner that is partially programmed by Rta's ability to redistribute RBP-Jk DNA binding to the virus during reactivation.

Primary Classic Penile Kaposi's Sarcoma in a Middle Age Circumcised HIV-Negative Patient: Presentation of an Unusual Case.

Kaposi's sarcoma should be considered in the differential diagnosis in young patients with penile lesions and no risk factors. A 37-year-old heterosexual man with no other medical history applied presented with a non-itchy and painless penile lesion, for three months. The HIV 1-2 serology was negative via ELISA test. Histopathological analysis of the lesion revealed a tumor composed of atypical spindle cells, below a partially ulcerated surface. There was also an abundance of plasma cells admixed within the neoplastic cells. The patient was diagnosed as HIV-negative, HHV-8 positive Kaposi sarcoma. Although penile Kaposi sarcoma is extremely rare, classical Kaposi sarcoma should be considered in the differential diagnosis of penile lesions.

Molecular detection and genotyping of human herpes virus 8 in blood donors in Congo.

OBJECTIVES: Human herpesvirus 8 (HHV8) is rarely studied in Congo, despite its prevalence in Africa. Among healthy individuals, HHV-8 does not always lead to a life-threatening infection; however, in immunocompromised individuals, it could lead to more severe disease. The distribution of HHV-8 genotypes varies depending on ethnicity and geographic region. METHOD: A prospective cross-sectional study included 265 samples from healthy blood donors from the National Blood Transfusion Center in Brazzaville, with an average age of 35 years, with extremes ranging from 18 to 60 years. After DNA extraction, a nested PCR was carried out for molecular detection, followed by genotyping by amplification of specific primers. RESULT: In this study, 4.9% were positive for molecular detection of HHV-8 DNA. All HHV-8 positive DNA samples that were subjected to genotyping by amplification with specific primers allowing discrimination of two major genotypes (A and B). Genotype A was identified in 5 (1.9%) samples and genotype B in 2 (0.7%) samples, indicating that both genotypes were predominant. The remaining viral DNA samples not identified as the major genotypes were classified as «indeterminate¼ and consisted of 6 (2.3%) samples. CONCLUSION: The results of the study suggest that Congo is an area where HHV-8 infection is endemic.

Pulmonary Kaposi sarcoma in a patient with bilateral lung transplant: An unexpected diagnosis on transbronchial fine needle aspiration and core biopsy.

Kaposi sarcoma (KS) is a low-grade vascular neoplasm that can be seen in various sites, most commonly seen in skin and mucosal tissues. Cytologic features of KS have been well-documented in the literature, however, since it is rarely seen in visceral organs, it could pose significant diagnostic challenges on fine needle aspiration (FNA) biopsies. We present a case of pulmonary KS diagnosed on transbronchial FNA biopsy in a 70-year-old female bilateral lung allograft recipient 11 months after transplantation. The aspirate smears showed a moderately cellular specimen containing a mixture of small, tightly cohesive clusters and loosely clustered groups of monomorphic, ovoid to spindled cells with moderate nuclear to cytoplasmic ratio. An extensive immunohistochemical panel on the concurrent core biopsy showed the tumor cells to be positive for ERG, KIT, and HHV8, confirming the diagnosis. We compared our case to previously published reports of confirmed pulmonary KS in lung allograft recipients.

Extracavitary primary effusion lymphoma presenting as a solitary brain mass.

Primary effusion lymphoma (PEL) is an uncommon B-cell lymphoma associated with human herpesvirus 8 and comprises 3-4% of all HIV-related lymphomas. It traditionally presents as a pleural, pericardial, and/or peritoneal effusion, though it can occasionally manifest as an extracavitary or solid mass in the absence of an effusion. The extracavitary or solid variant of primary effusion lymphoma has been reported in the skin, gastrointestinal tract, lung, and lymph nodes. However, very few cases have been reported in the central nervous system. We describe a case of extracavitary or solid variant of primary effusion lymphoma presenting as a brain mass in an HIV-positive man, highlighting the clinicopathologic and immunophenotypic findings of a rare entity.

Primary effusion lymphoma (PEL) is an uncommon and aggressive form of large B-cell lymphoma with a grim outlook, making up less than 1% of all lymphomas. PEL is linked to human herpesvirus 8 and predominantly impacts individuals with HIV or weakened immune systems. The typical presentation of PEL involves cancerous fluid accumulating in the chest or abdominal cavities. Occasionally, PEL can appear as a solid mass outside these cavities, termed extracavitary PEL (EC-PEL). The case we are describing highlights the difficulties in diagnosing PEL/EC-PEL. It is crucial for healthcare providers to consider EC-PEL when dealing with human herpesvirus 8-positive B-cell lymphomas, especially when patients have weakened immune systems and an unusual clinical scenario involving a solid mass, as seen in this case.