Diagnosis of Kaposi’s sarcoma via gastric biopsy leading to the detection of an AIDS case in a report

Introduction

Kaposi’s sarcoma (KS), a vascular proliferative neoplasm associated with Human Herpesvirus 8 (HHV-8) infection, was initially documented by the esteemed Hungarian dermatologist Moritz Kohn Kaposi. ¹ It generally impacts the integumentary system, lymphatic nodes, and visceral organs. The disease is categorized into four clinical and epidemiological types: classic KS, iatrogenic or immunosuppressive therapy-related KS, endemic or African KS, and epidemic or AIDS-related KS. ² Among these, epidemic, or AIDS-related KS (AIDS-KS), caused by Human Immunodeficiency Virus Type 1 (HIV-1) infection, is of particular relevance. AIDS-KS frequently involves the skin of the face, external genitalia, and lower extremities, as well as visceral sites such as the oral mucosa, lymph nodes, gastrointestinal tract, and lungs. ³ Notably, gastrointestinal KS (GI-KS) represents the most common extracutaneous manifestation of AIDS-KS. In the literature, the reported occurrence of GI-KS has been progressively rising among immunosuppressed populations, although it remains relatively uncommon overall. With the intensification of the AIDS epidemic, an increase in the prevalence of gastrointestinal KS has been documented. ⁴ Consequently, GI-KS is increasingly encountered in clinical practice, yet its diagnosis can be challenging due to nonspecific initial symptoms and endoscopic appearances, often leading to delay or misdiagnosis. This case report examines the clinical signs and pathological findings of a patient with gastrointestinal biopsy-confirmed KS, describes its clinicopathological features and differential diagnosis, and seeks to enhance pathologists’ comprehension of KS and AIDS.

Case report

In September 2024, a man in his mid-30s presented to the Gastroenterology Department of Jilin People’s Hospital, with a two-week history of dull, intermittent pain in the upper abdomen and periumbilical region, accompanied by nausea, vomiting, and significant weight loss (10 kg). His medical history included recurrent upper respiratory infections and chronic loose stools over the past year. Notably, for two months prior, he had developed multiple flat, dark brown papules on his left temple and bilateral upper limbs. A prior dermatological consultation had suggested lichen planus based on dermoscopy, but a confirmatory skin biopsy was not performed, leaving the nature of these lesions histologically unconfirmed. The reporting of this study conforms to CARE guidelines. ⁵

The diagnostic timeline proceeded as follows:

Day 1: An upper gastrointestinal endoscopy was performed, revealing white exudate covering the entire esophagus (Figure 1(a) and (b)) and suspicious erythematous raised lesions in the gastric body (Figure 1(c) and (d)).OPEN IN VIEWER

Day 2: Biopsy specimens from the esophagus and gastric body were submitted for pathological analysis. Histopathological findings of the esophagus are shown in Figure 2(a)–(d), and those of the gastric body are presented in Figure 3(a)–(c).OPEN IN VIEWER

OPEN IN VIEWER

Figure 3.

(a-c) Hematoxylin and eosin (H&E) staining of tissue of the gastric body mucosal lesion. (a) Low-power view (original magnification, ×100). (b) Medium-power view (original magnification, ×200). (c) High-power view (original magnification, ×400).

Day 6: The pathological report confirmed the diagnosis of Kaposi’s sarcoma (KS) based on histomorphology and positive immunohistochemical stains for CD31, CD34, and HHV-8 (Figure 4(a)–(c)). In light of this diagnosis, HIV testing was strongly recommended.OPEN IN VIEWER

Day 7: HIV antigen and antibody testing conducted at Jilin People’s Hospital returned a positive result. The patient was subsequently referred to the local Center for Disease Control and Prevention (Jilin City) for confirmatory testing and formal staging, which established the final diagnosis of AIDS-related KS.

Endoscopic and pathological findings: Upper endoscopy showed white exudate adherent to the entire esophageal mucosa (Figure 1(a) and (b)). The gastric body mucosa exhibited a red-and-white appearance with scattered congested, edematous regions and erosions (Figure 1(c)), as well as localized raised lesions without ulceration (Figure 1(d)). Endoscopic diagnosis comprised fungal esophagitis and chronic atrophic gastritis with erosions. Pathological analysis of the esophageal biopsy confirmed fungal esophagitis (Figure 2(a)–(d)). Examination of the background gastric mucosa (away from the KS lesion) showed mild chronic inactive gastritis with no evidence of Helicobacter pylori-like organisms on routine H&E stain; no viral cytopathic effects suggestive of cytomegalovirus (CMV) infection were identified. There were also no histologic features of autoimmune gastritis, such as severe oxyntic gland atrophy, enterochromaffin-like cell hyperplasia, or lymphocytic infiltration concentrated in the deep mucosa. A specific H. pylori stain was not performed, and CMV immunohistochemistry was not pursued. In the submucosa of the gastric body, tumor tissue consisting of spindle cells arranged in a crisscross pattern was identified. Hematoxylin and eosin staining(H&E) revealed that these spindle cells contained red blood cells, exhibited ambiguous nuclear atypia, lacked mitotic figures, and were associated with infiltration of lymphocytes and plasma cells, alongside a reduction in gastric mucosal glands (Figure 3(a)–(c)). Immunohistochemistry demonstrated strong expression of CD31, CD34, and HHV-8 in tumor cells (Figure 4(a)–(c)), corroborating the diagnosis of KS.

We have obtained written informed consent from the patient for publication of this case report and any accompanying images. We also obtained written, signed consent for treatment, including endoscopic and biopsy procedures, prior to the interventions.

Following the pathological diagnosis of KS through gastroscopic biopsy, further blood HIV antigen and antibody testing was conducted to ascertain the underlying etiology, yielding positive results. A complete blood count (CBC) indicated that the patient’s total white blood cell count was 3.3×10⁹/L (reference interval: 3.5–9.5 × 10⁹/L) and the absolute lymphocyte count was 0.73×10⁹/L (reference interval: 1.1–3.2 × 10⁹/L), both of which were below the normal reference range. This case was identified as AIDS-related KS based on the complete laboratory findings.

Following the diagnosis, standard treatment involving combined antiretroviral therapy (cART) and assessment for systemic chemotherapy was recommended, and the patient was referred to the specialist AIDS care unit. Unfortunately, he was subsequently lost to follow-up, and thus details regarding treatment initiation and clinical outcome are unavailable.

Discussion

KS is a locally aggressive tumor originating from vascular endothelial cells, primarily induced by infection with human herpesvirus 8 (HHV-8). HHV-8, or KS-associated herpesvirus (KSHV), was initially isolated in the tissues of individuals with AIDS-related KS in 1994. ⁶ It can be identified in more than 95% of KS patients. KSHV, like other herpesviruses, is transmitted by saliva and sexual contact ⁷ ; nevertheless, it can also be transferred via blood transfusions.HHV-8 demonstrates various biological functions, including involvement in cell cycle regulation and modulation of cytokine concentrations. Gene products in the latent phase predominantly govern the cell cycle, whereas those in the lytic phase are chiefly engaged in viral propagation. ⁸ In these transitional phases, the virus enhances growth factors and stimulates the differentiation and proliferation of endothelial cells, which are critical events in the development of KS. ⁹ It also circumvents the immunological response by blocking B cell receptor signaling and reducing B cell activation. ¹⁰ In immunocompromised conditions, especially in individuals with AIDS, this virus may provoke cancer.

Histological examination of GI-KS in this instance demonstrated mucosal red nodules and elevated lesions. The lesions were polypoid, measuring around 5 mm in diameter. The neoplasm consisted of spindle cells organized in bundles, with mild nuclear atypia and few mitotic figures. A multitude of irregular cleft-like vascular formations lined with endothelial cells was detected, accompanied by extravasation of red blood cells and hemosiderin deposition surrounding the blood vessels. Dispersed lymphocytic and plasmacytic infiltrates were observed in the stroma. PAS-positive eosinophilic bodies were observed within or adjacent to spindle cells, possibly indicating lysed red blood cells or immunological complexes. Regarding the reported skin findings, it is important to note that they were not biopsied and their relationship to the systemic HHV-8 infection or KS remains speculative. Immunohistochemical staining revealed the expression of endothelial cell markers (e.g., CD31, CD34, ERG (ETS-related gene), FLi-1(Friend leukemia integration 1)), and nuclear positivity for the particular marker HHV-8 was essential for diagnosis. And unexplained gastrointestinal symptoms warrant direct investigation via endoscopy and biopsy, irrespective of concurrent unconfirmed cutaneous findings.

The differential diagnosis for spindle cell lesions in the gastrointestinal tract is broad and includes gastrointestinal stromal tumor (GIST), inflammatory fibroid polyp (IFP), leiomyoma, and other vascular neoplasms. Among these, GIST and IFP are the most relevant considerations. GISTs are the predominant mesenchymal tumors of the GI tract; their cellular morphology is characterized by elongated spindle cells, low nuclear atypia, relatively homogeneous chromatin, and an interwoven or herringbone arrangement. Critically, the potential expression of CD117 in KS represents a major diagnostic pitfall, as it can lead to misdiagnosis as GIST. In a study of 62 GI-KS cases from Xinjiang, China, CD117 was positive in 13/59 (22.0%) of KS cases, ¹¹ highlighting that CD117 alone is insufficient for differentiation. Therefore, the combination of HHV-8 (positive in KS) and DOG1 (Discovered on GIST-1, positive in the majority of GISTs) is highly discriminatory. In our case, the co-expression of CD31/CD34 with strong nuclear HHV-8 positivity, in the absence of DOG1 expression, effectively ruled out GIST.

The diagnosis of GI - KS is complicated by non - conventional histologic patterns mimicking benign inflammatory or reactive conditions. In a multi - institutional study by Zheng et al., ¹² 7 distinct histomorphologic variants were identified in 46 cases of GI-KS. Five inconspicuous patterns (lymphangioma/lymphangiectatic-like, mucosal hemorrhage/telangiectatic-like, mucosal inflammation-like, granulation tissue-like, and mucosal prolapse - like) are easily overlooked, and the other two variants resemble gastrointestinal stromal tumor and inflammatory myofibroblastic tumor. These variants can be misdiagnosed without considering KS and performing HHV-8 immunohistochemistry. Mitchell ¹³ reported that 64% of 44 GI-KS biopsies from immunocompromised patients showed non-classic histology mimicking inflammatory patterns. 91% of endoscopically non-specific inflammatory cases had non-classic histology, and GI-KS preceded cutaneous diagnosis in 54% of patients. These studies emphasize that KS should be in the differential diagnosis even without conventional features, especially in immunocompromised patients’ limited biopsy specimens. Consistent use of HHV-8 immunohistochemistry is essential to avoid misdiagnosis and management delays.

Early-stage gastrointestinal Kaposi sarcomas may be asymptomatic, often identified incidentally during gastrointestinal endoscopy or imaging examinations. Symptoms frequently manifest as nonspecific, including dyspepsia, nausea, vomiting, stomach discomfort, diarrhea, and anorexia, so substantially impeding early diagnosis and treatment. Advanced-stage gastrointestinal KS can induce anemia, hematemesis, or melena as a result of mucosal ulceration or rupture of tumor-associated vessels, presenting a significant risk to patient health. GI-KS can affect any segment of the gastrointestinal tract. Literature indicates that the gastric body is the most frequently involved site, accounting for approximately 25% of AIDS-associated KS cases. ¹⁴ This case exhibited uncommon clinical signs, predominantly upper abdominal discomfort and loose stools-characteristics that might often result in misdiagnosis. As described in the literature, endoscopic findings of GI-KS are often nonspecific. They may range from red-blue or brown flat plaques to polypoid or nodular elevations of varying dimensions. More advanced lesions have been reported to resemble ulcerated, volcano-like tumors with contact bleeding, while in other cases, only subtle mucosal erosion may be seen—presenting a significant diagnostic challenge. Consequently, doctors must exercise heightened monitoring for gastrointestinal symptoms in immunocompromised patients. Thus, endoscopic examination and pathological biopsy should be the primary screening and diagnostic methods for high-risk patients, irrespective of the existence of cutaneous KS lesions. ¹⁵

Inflammatory fibroid polyps (IFPs) are another important entity in the differential diagnosis. IFPs consist of morphologically homogeneous spindle cells organized in a whorled or concentric arrangement around blood vessels, exhibiting positive CD34 staining. Unlike KS, IFPs typically lack HHV-8 expression, do not show red blood cell extravasation, and are not associated with immunocompromised states. The inflammatory infiltrate in IFPs is often eosinophil-rich, in contrast to the plasmacytic infiltrate seen in KS. Distinction from KS in our case relied on the characteristic histology (e.g., red blood cell extravasation and slit-like vascular spaces in KS) and, most definitively, the positive HHV-8 immunostaining in the KS lesion, which is consistently negative in IFPs. Other spindle cell tumors such as leiomyomas (positive for desmin and SMA, negative for CD34 and HHV-8) and glomus tumors (positive for smooth muscle actin and calponin) were also excluded. Thus, a structured immunohistochemical panel including CD31, CD34, HHV-8, DOG1, and CD117 is essential for accurate diagnosis. ¹⁶

The cornerstone of treatment for AIDS-related KS is the initiation or optimization of combined antiretroviral therapy (cART), which can lead to regression of lesions through immune reconstitution.^12,17 Effective immune reconstitution with cART can stabilize or even cause regression of KS lesions and is fundamental to management. For patients with symptomatic, widespread, or rapidly progressive disease, systemic chemotherapy is indicated in conjunction with cART. Liposomal doxorubicin is widely regarded as first-line chemotherapy due to its efficacy and favorable toxicity profile; other options include paclitaxel or oral etoposide. Local therapies such as endoscopic resection or radiation may be considered for isolated, bleeding, or obstructive lesions, but they do not address systemic disease. The prognosis of AIDS-KS has dramatically improved in the cART era, with outcomes closely tied to HIV control, KS tumor stage, and the presence of other opportunistic infections (e.g., the fungal esophagitis in this case). Unfortunately, in the present case, the patient was lost to follow-up after diagnosis, precluding evaluation of treatment response and long-term outcome. This underscores a common real-world challenge and highlights the critical need for effective patient referral and retention systems.

Pathological examination is the definitive method for diagnosing gastric KS. In this patient, the presence of white exudate throughout the esophagus, along with clinical symptoms and pathological results confirming fungal esophagitis, signified an aberrant immune status. The KS diagnosis was confirmed by integrating the pathological features of the gastric body with immunohistochemistry for CD31, CD34, and HHV-8. ¹⁸ Subsequent HIV laboratory tests yielded positive results, establishing the diagnosis of AIDS-related KS. This case demonstrates a succinct diagnostic pathway: from initial gastrointestinal symptoms to histological confirmation of KS and subsequent HIV diagnosis within eight days. This timeline underscores the pivotal role of timely endoscopic biopsy and a high index of suspicion for uncovering occult systemic disease like AIDS. Regarding co-infections, examination of the background gastric mucosa revealed only mild chronic inactive gastritis without histologic evidence of H. pylori, CMV, or autoimmune gastritis, though specific stains were not performed—a limitation of this study. This case also improves comprehension of AIDS-related KS among digestive endoscopists and pathologists, aiding in the prevention of missed and erroneous diagnoses.

Conclusion

This case highlights gastrointestinal Kaposi’s sarcoma (KS) as a potential sentinel presentation of undiagnosed HIV/AIDS. The key learning points are:

1. Unexplained gastrointestinal symptoms (e.g., abdominal pain, weight loss) in patients with signs of potential immunosuppression (e.g., concurrent opportunistic infection) warrant a high index of suspicion for visceral KS.

Therefore, a vigilant approach integrating clinical suspicion, timely endoscopy with biopsy, and targeted immunohistochemistry can unravel a dual diagnosis of KS and occult HIV, facilitating life-saving antiretroviral therapy and specific oncologic care.