Gastric cytomegalovirus disease mimicking locally advanced gastric adenocarcinoma in a patient with newly diagnosed AIDS: A case report and literature review

Abstract

Introduction

Gastric cytomegalovirus (CMV) disease is an uncommon manifestation of tissue-invasive CMV infection and, in rare instances, may mimic gastric malignancy. Recognition of this pseudomalignant presentation is important to prevent misdiagnosis and inappropriate oncologic management.

Case Presentation

A 65-year-old woman presented with abdominal pain, diarrhea, recurrent post-prandial vomiting, poor oral tolerance, and a 20-kg weight loss over one year. Upper gastrointestinal endoscopy showed a large ulcerated antral mass with raised borders, highly suspicious for gastric adenocarcinoma. Endoscopic ultrasound (EUS) demonstrated a hypoechoic prepyloric/pyloric lesion with mural thickening extending to the subserosa and regional lymphadenopathy, resembling locally advanced gastric malignancy. Diagnostic laparoscopy, ascitic fluid cytology, and omental biopsy showed no malignancy. Histopathological review of gastric biopsies revealed severe CMV cytopathic changes in endothelial, epithelial, and stromal cells, confirmed by CMV immunohistochemistry. Cytokeratin markers were negative in atypical stromal cells, supporting exclusion of poorly differentiated adenocarcinoma. Subsequent evaluation revealed newly diagnosed advanced HIV infection with profound CD4 lymphopenia (initial CD4 count, 24.5 cells/µL), CMV viremia (31,000 copies/mL), HIV-1 RNA viremia (192,129 copies/mL), and CMV retinitis. The patient was treated with intravenous ganciclovir 250 mg twice daily for approximately 32 days, followed by oral valganciclovir 900 mg twice daily, together with antiretroviral therapy and intravitreal ganciclovir 2 mg for left-eye CMV retinitis. Follow-up demonstrated clearance of CMV viremia, subsequent suppression of HIV viremia to undetectable levels, CD4 recovery to 120 cells/µL, complete endoscopic healing of the gastric ulcers, and no evidence of neoplasia on repeat biopsies.

Conclusion

Gastric CMV disease can closely mimic locally advanced gastric adenocarcinoma on endoscopy and EUS. In immunocompromised patients with malignant-appearing gastric lesions, repeat tissue sampling and CMV immunohistochemistry should be considered before committing to oncologic treatment, with cytokeratin staining performed when histologically indicated.

Introduction

Cytomegalovirus (CMV) is a ubiquitous herpesvirus that can cause tissue-invasive disease in immunocompromised patients, particularly in individuals with advanced human immunodeficiency virus (HIV) infection, in solid-organ transplant recipients and in patients receiving immunosuppressive therapy [1,2]. In patients with HIV/AIDS, clinically significant CMV disease most commonly occurs in the setting of profound cellular immunosuppression, especially when CD4 counts fall below 50 cells/µL [1]. Gastrointestinal involvement is a well-recognized manifestation of CMV disease, with the colon and esophagus being the most frequently affected sites; CMV involvement of the stomach is less common and may present with nonspecific symptoms such as abdominal pain, nausea, vomiting, gastrointestinal bleeding, or weight loss [[2], [3], [4]]. The endoscopic appearance of gastric CMV disease is variable and may include erythema, erosions, ulceration, mucosal nodularity, or, rarely, mass-like and pseudotumoral lesions [[3], [4], [5], [6]]. In such cases, CMV-related inflammatory and ulcerative changes can closely resemble gastric malignancy, creating a diagnostic challenge. This distinction is clinically important because malignant-appearing gastric lesions may prompt extensive staging procedures, surgical exploration, or oncologic planning before a definitive tissue diagnosis is established [5,6]. We report a case of gastric CMV disease in a newly diagnosed patient with advanced AIDS that presented as a large ulcerated antral mass with endoscopic ultrasound (EUS) findings mimicking locally advanced gastric adenocarcinoma. Compared with previously reported malignancy-mimicking cases, this case is distinctive because the lesion was not only endoscopically suspicious for cancer but also showed an EUS appearance resembling cT3N2Mx disease if malignant, with deep mural extension to the subserosa and regional lymphadenopathy, prompting diagnostic laparoscopy before malignancy was excluded. The diagnosis was established by histopathological examination and CMV immunohistochemistry, while negative cytokeratin staining in the atypical stromal cells supported the exclusion of poorly differentiated adenocarcinoma. We also performed a narrative literature review of PubMed and Google Scholar to identify reported adult cases of gastric CMV disease with mass-like, pseudotumoral, obstructive, ulcerative, or malignancy-mimicking presentations in immunocompromised patients.

Case presentation

A 65-year-old woman presented with abdominal pain, diarrhea, poor oral tolerance, recurrent post-prandial vomiting, and a 20-kg weight loss over one year. Her medical history was notable for hypertension treated with losartan. She had no known history of immunodeficiency, malignancy, transplantation, or chronic immunosuppressive therapy. Her father had died of gastric cancer at the age of 41. Physical examination revealed no palpable lymphadenopathy or organomegaly.

Initial laboratory evaluation showed mild inflammatory marker elevation, with unremarkable renal and liver function tests. Initial upper gastrointestinal endoscopy and superficial biopsies were non-diagnostic, showing chronic inflammatory and regenerative changes without evidence of malignancy or Helicobacter pylori infection. Because detailed serial creatinine/eGFR values were not available in the clinical documentation used for this case report, renal-dose adjustment during the subsequent ganciclovir course could not be retrospectively documented in detail.

One month later, repeat endoscopy demonstrated a large ulcerated mass with raised borders in the gastric antrum, grossly suspicious for gastric adenocarcinoma (Fig. 1). Multiple punch biopsies were obtained. Endoscopic ultrasound showed a hypoechoic lesion involving the inferior and anterior pyloric wall and extending through all gastric wall layers to the subserosa, with a maximal thickness of 10 mm. Six regional lymph nodes, the largest measuring 8 mm, were identified near the lesion and in the subdiaphragmatic and celiac regions. The liver and pancreas were uninvolved, and no aortocaval or mediastinal lymphadenopathy was detected. Overall, the EUS findings were highly suspicious for locally advanced gastric malignancy and would have corresponded to cT3N2Mx disease if the lesion had been malignant (Fig. 2).

Fig. 1.

Initial endoscopic appearance of the gastric antral lesion. (A–D) Representative upper gastrointestinal endoscopic images of the gastric antrum showing a large, ulcerated lesion with irregular raised borders and a mass-like, malignant-appearing morphology, highly suspicious for gastric adenocarcinoma. Multiple biopsies were obtained for histopathological evaluation.

Fig. 2.

Endoscopic ultrasound evaluation for locoregional staging. (A–D) Radial endoscopic ultrasound showed a hypoechoic lesion involving the prepyloric and pyloric region, with mural thickening extending through the gastric wall to the subserosa and associated regional lymph nodes. The overall appearance was highly suspicious for a locally advanced gastric malignancy. A, prepyloric region; B, pyloric channel; C, regional lymph node; D, pancreatic head.

The patient underwent diagnostic laparoscopy because of the strong suspicion of locally advanced gastric malignancy. Ascitic fluid cytology was negative for malignant cells, and omental biopsy showed no tumor. Review of the repeat gastric biopsies revealed no evidence of adenocarcinoma. Instead, severe cytomegalovirus (CMV) cytopathic changes were identified in endothelial, epithelial, and stromal cells and were confirmed by CMV immunohistochemistry (Fig. 3). Pan-cytokeratin, CAM 5.2, and CK AE1/AE3 were negative in the atypical stromal cells, supporting the exclusion of poorly differentiated adenocarcinoma.

Fig. 3.

Histopathological and immunohistochemical confirmation of gastric cytomegalovirus infection. (A) Hematoxylin and eosin (H&E) staining of the gastric antral biopsy shows enlarged stromal/endothelial cells with viral nuclear inclusions. Characteristic “owl’s-eye” intranuclear inclusions are highlighted by the arrows, consistent with cytomegalovirus cytopathic effect (original magnification ×400). (B) Cytomegalovirus immunohistochemistry shows nuclear immunopositivity in affected cells (arrow), confirming tissue-invasive cytomegalovirus infection (original magnification ×200). Cytokeratin stains, performed separately and not shown, were negative in atypical stromal cells.

Further evaluation revealed newly diagnosed advanced HIV infection. Flow cytometry showed profound CD4 lymphopenia, with an initial absolute CD4 count of 24.5 cells/µL, later decreasing to 6.8 cells/µL at the referral center. HIV-1 RNA was initially 457,450 IU/mL (192,129 copies/mL) and later increased to 2,997,000 IU/mL. CMV viral load was 31,000 copies/mL, while EBV DNA was below the detection limit. The patient also developed blurred vision, and ophthalmologic examination demonstrated CMV retinitis.

Intravenous ganciclovir 250 mg twice daily, antiretroviral therapy with tenofovir/emtricitabine plus dolutegravir, pantoprazole, and cotrimoxazole prophylaxis were initiated. The patient underwent an anterior chamber tap and received intravitreal ganciclovir 2 mg for left-eye CMV retinitis. Intravenous ganciclovir was continued for approximately 32 days and was then discontinued in the setting of ganciclovir-associated pancytopenia. The patient received three doses of granulocyte colony-stimulating factor. Antiviral therapy was subsequently switched to oral valganciclovir 900 mg twice daily.

A follow-up endoscopy performed approximately 2 months later for occult gastrointestinal bleeding showed localized erythema, erosions, and a single 25-mm clean-based antral ulcer (Fig. 4). Biopsies demonstrated mixed inflammation, mucosal gland distortion, and scattered enlarged cells with CMV cytopathic changes, without evidence of neoplasia; CMV immunohistochemistry was faint-to-moderately positive (Fig. 5). The patient was discharged on valganciclovir, antiretroviral therapy, and supportive treatment, with follow-up arranged in infectious diseases and ophthalmology clinics.

Fig. 4.

Follow-up endoscopic appearance of the gastric antral ulcer. (A–D) Follow-up upper gastrointestinal endoscopy demonstrated residual localized erythema and erosions in the gastric antrum, with a clean-based antral ulcer. Multiple biopsies were obtained for histopathological reassessment.

Fig. 5.

Follow-up histopathology of the gastric antral ulcer. (A) Hematoxylin and eosin staining of the follow-up antral ulcer biopsy shows mixed inflammation, mucosal gland distortion, and scattered enlarged cells with residual cytomegalovirus cytopathic changes (arrow), including viral nuclear inclusions (original magnification ×200). (B) Cytomegalovirus immunohistochemistry demonstrates faint-to-moderate nuclear immunoreactivity in enlarged cells (arrow), supporting residual cytomegalovirus infection (original magnification ×200). No neoplasia is identified.

Three months after the follow-up endoscopy, repeat evaluation showed persistent pancytopenia and severe immunosuppression, with a CD4 count of 41 cells/µL. CMV viral load remained negative, although HIV viremia persisted. Repeat upper gastrointestinal endoscopy demonstrated marked improvement of the previously described ulcerated mass-like lesion, with residual localized erythema and erosions in the antrum (Fig. 6). Histopathological examination of repeat biopsies showed no evidence of neoplasia. At the most recent follow-up, both HIV and CMV viral loads were undetectable, the CD4 count had increased to 120 cells/µL, and repeat endoscopic assessment showed complete healing of the gastric ulcers. The patient was advised to continue her treatment regimen and remains under close clinical surveillance. The clinical timeline of diagnostic evaluation, treatment, and follow-up is summarized in Supplementary Table 1. This case report was prepared in accordance with the CARE guidelines.

Fig. 6.

Endoscopic response after antiviral therapy. (A–D) Follow-up endoscopy after treatment with intravenous ganciclovir followed by oral valganciclovir demonstrated marked improvement of the previously seen malignant-appearing antral lesion, with residual localized erythema and erosions. Follow-up biopsies showed no evidence of neoplasia.

Discussion

This case illustrates an uncommon and clinically important form of gastric CMV disease: a malignant-appearing antral mass with EUS features closely mimicking locally advanced gastric adenocarcinoma. Although gastrointestinal CMV disease is a recognized complication of advanced HIV infection and other immunocompromised states, gastric involvement is less common than colonic or esophageal disease and usually presents with nonspecific symptoms or ulcerative lesions [[1], [2], [3], [4]]. Gastric CMV lesions simulating malignancy have been reported previously in both immunocompetent and immunocompromised hosts [[5], [6], [7]]. However, the present case is distinctive because the lesion was not only endoscopically suspicious for cancer but also had an EUS appearance resembling cT3N2Mx disease if malignant, with deep mural extension to the subserosa and regional lymphadenopathy, prompting diagnostic laparoscopy before malignancy was excluded.

Histopathological identification of CMV cytopathic changes, confirmed by CMV immunohistochemistry, established the diagnosis, while negative cytokeratin staining in the atypical stromal cells supported the exclusion of poorly differentiated adenocarcinoma. This distinction is important because EUS-based staging findings, when interpreted without definitive histopathological confirmation, may lead to unnecessary oncologic planning or surgical intervention.

The malignancy-mimicking appearance of gastric CMV disease has been reported only rarely. In previously published cases, affected patients were typically severely immunocompromised, most commonly because of AIDS, solid-organ transplantation, hematologic malignancy, or immunosuppressive therapy. Reported lesions have most often involved the antrum, prepyloric region, or gastric body and have appeared as ulcerated masses, pseudotumoral lesions, thickened folds, or carcinoma-like ulcers. Some cases underwent extensive diagnostic or surgical procedures before CMV infection was established, underscoring the potential consequences of this diagnostic pitfall [[5], [6], [7]]. In our review of reported cases, gastric CMV disease mimicking malignancy showed heterogeneous endoscopic appearances but a recurring pattern of ulcerated or mass-like lesions in profoundly immunocompromised hosts (Table 1).

Table 1.

Reported cases of gastric cytomegalovirus disease with mass-like, obstructive, ulcerative, or malignancy-mimicking presentations in immunocompromised adults.

No	Study	Age/Sex	Immune status / underlying condition	Site	Endoscopic/imaging findings	Histology	Treatment	Outcome	Ref
1	Cullen & Stansfeld, 1979	59/M	Immunoblastic malignant lymphoma; chemotherapy/steroids	Prepyloric/antral region	Barium/EGD: large prepyloric ulcer; antral deformity; heaped-up/swollen folds; suspicious for malignancy	Inflammation; atypical epithelial cells with CMV cytopathic change; initially misread as carcinoma; benign ulcer on surgical specimen	Chemotherapy stopped; partial gastrectomy and splenectomy; antiviral NR	Good recovery; well at 2 years	[8]
2	Elta et al., 1986	29/M	AIDS; CD4/CD8 ratio 0.36	Gastric antrum / prepyloric region	EGD/CT: non-obstructive 4-cm submucosal antral mass	Marked inflammation/edema; CMV inclusions in stromal and epithelial cells; overlying mucosal biopsies initially non-diagnostic	Exploratory laparotomy/open biopsy; antiviral therapy NR	Died 2 months after diagnosis	[9]
3	Rich et al., 1992	41/M	AIDS; prior cerebral toxoplasmosis	Gastric fundus	UGI/EGD: large focal fundal mass; 5-cm necrotic ulcerated mass	Chronic active gastritis/erosion; fibrotic submucosa; CMV inclusions in glandular epithelial cells; CMV immunoperoxidase positive; no neoplasm	IV ganciclovir induction × 2 weeks then maintenance	GI symptoms resolved; later died, not attributed to localized CMV	[10]
4	Tahan et al., 2000	40/M	Common variable immunodeficiency; recurrent infections	Stomach and esophagus; later small bowel strictures	EGD: gastric ulcer and esophageal ulcer; later intestinal obstruction/strictures	CMV inclusions; CMV-positive staining; no neoplasia reported	Jejunal resection + lymph node sampling; IV ganciclovir 5 mg/kg BID	Clinical improvement; regression of gastric/esophageal ulcers after ~2 months	[11]
5	Gupta et al. — Case 1, 2005	53/F	Live-related renal transplant; cyclosporine/prednisolone/MMF	Antrum and fundus	EGD: target lesions in antrum and fundus	CMV intranuclear inclusions in glandular epithelial cells	Ganciclovir 5 mg/kg BID × 21 days then maintenance × 3 months	Asymptomatic at 6 months	[12]
6	Gupta et al. — Case 2, 2005	66/M	Renal transplant	Antrum; lower esophagus also involved	EGD: antral gastritis; lower esophageal creamy white plaques	Antral CMV intranuclear inclusions; esophageal biopsy suggestive of CMV	Ganciclovir 5 mg/kg	Transient improvement; died of nosocomial pneumonia/septic shock	[12]
7	Gupta et al. — Case 3, 2005	58/F	Cadaveric renal transplant; HTN, hypothyroidism, sleep apnea, pulmonary HTN	Antrum	EGD: multiple antral ulcers with surrounding erythema	Ulcerated mucosa with neutrophilic exudate; numerous CMV intranuclear inclusions; CMV-PP65 positive	Ganciclovir continued for 6 months	Pain resolved; well at 1 year	[12]
8	Gupta et al. — Case 4, 2005	38/F	Cadaveric renal transplant; prednisolone/MMF/cyclosporine	Antrum; duodenum; ileocecal region	EGD: antral gastritis and duodenitis; colonoscopy: large ileocecal ulcer	CMV inclusions in gastric and ileocecal biopsies	Ganciclovir	Asymptomatic at 8 months	[12]
9	Gupta et al. — Case 5, 2005	40/M	HIV infection/AIDS; stopped HAART; CD4 5/µL	Antrum	EGD: extensive antral ulceration and surrounding erythema	H. pylori negative; inflammation and CMV intranuclear inclusions; CMV-PP65 positive	Ganciclovir then maintenance ganciclovir	Symptoms and endoscopic findings improved; well at 2 months	[12]
10	Mohan et al., 2007	49/M	AIDS; HIV diagnosed after pathology	Gastric antrum	EGD: distorted gastric folds in body/antrum; flat ulcerative lesions; surgery: 5 × 3 cm antral mass	Ulcerated mucosa with granulation tissue; CMV inclusions in epithelial, endothelial and smooth muscle cells; CMV IHC-positive; reactive atypia; Cryptosporidia also present	Subtotal gastrectomy + Roux-en-Y gastrojejunostomy; antiviral therapy NR	Died on postoperative day 10 from overwhelming sepsis	[6]
11	Lin et al., 2008	43/F	Renal transplant; cyclosporine/MMF/methylprednisolone	Upper gastric body, lesser curvature	EGD: 3 × 3 cm gastric ulcer with irregular margins and hard surface; suspicious for carcinoma; massive bleeding	CMV inclusion bodies in gastric mucosa; no malignancy; CMV IgM/IgG and PCR positive	Surgery for persistent bleeding; ganciclovir	Died 1 week after surgery	[13]
12	Boteon et al., 2015	39/M	Advanced AIDS, stage C3; tuberculosis; H. pylori co-infection	Prepyloric region / pyloric channel / gastric outlet	EGD: prepyloric ulcer causing pyloric stenosis/GOO; pseudotumoral deformity	CMV cytopathic effect/inclusion bodies in ulcerated mucosa; H. pylori also detected initially	IV ganciclovir 5 mg/kg BID × 21 days; H. pylori therapy; later Roux-en-Y gastroenteroanastomosis	Good postoperative recovery; asymptomatic at 6 months with weight gain	[7]
13	Wong et al., 2018	63/M	Renal transplant; immunosuppression; DM; ischemic heart disease; prior UGIB	Greater curvature of stomach	Barium/EGD/NBI: large plaque-like/polypoidal lesion; hypervascular distorted pit pattern; suspicious for malignancy	Numerous CMV inclusions in hyperplastic gastric mucosa; CMV IHC-positive; no dysplasia or neoplasm	IV ganciclovir followed by oral valganciclovir; immunosuppression reduced	Reflux symptoms resolved; lesion decreased	[14]
14	Corti et al., 2019	30/M	Newly diagnosed AIDS; CD4 16/µL; disseminated histoplasmosis; esophageal candidiasis	Subcardial/fundus/body; antral wall involvement on imaging	EGD: thickened distorted gastric folds; irregular ulcers; hemorrhagic suffusions; pseudoneoplastic appearance; CT/US: antral wall thickening/narrowing	Eroded/ulcerated mucosa; CMV inclusions; IHC-positive; Histoplasma identified by Grocott	Ganciclovir + foscarnet × 21 days; amphotericin B; fluconazole; ART	Symptomatic and radiologic improvement; discharged in good condition	[15]
15	Lovingood et al., 2025	60/F	Newly diagnosed AIDS; CD4 34/µL; pancytopenia; malnutrition; hypothyroidism	Gastroesophageal junction	EGD: erythematous gastric mucosa; large cratered GE-junction ulcer with rolled irregular border and deep-appearing invasion	CMV inclusions; CMV IHC-positive; no malignancy	Valganciclovir 900 mg BID × 6 weeks; PPI; ART initiated	Discharged to skilled nursing facility; later transitioned to hospice	[16]
16	Present case	65/F	Newly diagnosed AIDS; profound CD4 lymphopenia; CMV viremia; CMV retinitis	Gastric antrum / prepyloric-pyloric region	EGD/EUS: large ulcerated antral mass with raised border; EUS appearance highly suspicious for locally advanced gastric malignancy, resembling cT3N2Mx disease if malignant	CMV cytopathic changes in endothelial, epithelial, and stromal cells; CMV IHC-positive; negative cytokeratin staining in atypical stromal cells; no malignancy	IV ganciclovir followed by oral valganciclovir; ART; intravitreal ganciclovir for CMV retinitis	CMV/HIV viral loads undetectable; CD4 increased to 120 cells/µL; complete endoscopic ulcer healing; no neoplasia on repeat biopsy.	-

AIDS = acquired immunodeficiency syndrome; ART = antiretroviral therapy; BID = twice daily; CMV = cytomegalovirus; CMV-PP65 = cytomegalovirus pp65 antigenemia; CT = computed tomography; DM = diabetes mellitus; EGD = esophagogastroduodenoscopy; EUS = endoscopic ultrasound; F = female; GE = gastroesophageal; GI = gastrointestinal; GOO = gastric outlet obstruction; HAART = highly active antiretroviral therapy; HIV = human immunodeficiency virus; HTN = hypertension; IHC = immunohistochemistry; IV = intravenous; M = male; MMF = mycophenolate mofetil; NBI = narrow-band imaging; NR = not reported; PCR = polymerase chain reaction; PPI = proton-pump inhibitor; UGI = upper gastrointestinal series; UGIB = upper gastrointestinal bleeding; US = ultrasonography.

The marked discrepancy between the malignant endoscopic and EUS appearance and the absence of epithelial malignancy on histopathology is the central diagnostic lesson of this case. In patients with atypical, refractory, or mass-like gastric ulceration, particularly when conventional causes such as Helicobacter pylori infection and malignancy are not confirmed on initial sampling, clinicians should maintain a low threshold for repeat biopsy and targeted ancillary testing. CMV immunohistochemistry and epithelial markers such as cytokeratin staining are particularly valuable for distinguishing tissue-invasive CMV disease with reactive atypia from poorly differentiated carcinoma. Blood CMV PCR may support systemic or disseminated CMV infection but should not replace tissue-based confirmation of gastric CMV disease.

Several mechanisms may explain why CMV gastritis can resemble gastric malignancy. CMV infects endothelial, epithelial, and stromal cells, leading to direct cytopathic injury, endothelial dysfunction, mucosal ischemia, ulceration, and intense inflammatory infiltration. In severe cases, these changes may produce marked wall thickening, mucosal distortion, raised ulcer borders, and mass-like inflammatory tissue. On imaging or EUS, such inflammatory thickening may simulate neoplastic infiltration, particularly when associated with regional lymphadenopathy. Therefore, EUS findings suggestive of deep mural involvement should be interpreted cautiously in immunocompromised patients when tissue diagnosis has not confirmed malignancy.

Histopathological confirmation remains central to diagnosis. The classic finding of CMV infection is cytomegalic cells with intranuclear inclusions and a perinuclear halo, often described as an “owl’s eye” appearance. However, these changes may be focal and may be missed on superficial or limited biopsies. Immunohistochemistry increases diagnostic sensitivity by highlighting infected cells and is particularly valuable when routine hematoxylin and eosin staining is equivocal. In the present case, CMV immunohistochemistry confirmed tissue-invasive CMV infection, while negative cytokeratin markers in atypical stromal cells supported exclusion of poorly differentiated adenocarcinoma. This distinction was essential because the endoscopic and EUS appearance alone strongly suggested advanced gastric cancer.

The prolonged history of abdominal pain, diarrhea, poor oral tolerance, recurrent post-prandial vomiting, and substantial weight loss preceded recognition of the underlying immunodeficiency. The initial endoscopy and superficial biopsies were non-diagnostic, showing chronic inflammation and regenerative changes without malignancy or Helicobacter pylori infection. The subsequent development of a large ulcerated, mass-like lesion with EUS features suggestive of locally advanced gastric cancer illustrates how tissue-invasive CMV can produce a pseudoneoplastic phenotype while the underlying immunodeficiency remains clinically occult. In this setting, progression of an unexplained gastric lesion despite an initially non-diagnostic biopsy should prompt repeat, adequately deep tissue sampling and consideration of opportunistic infections, including CMV, as well as evaluation for an underlying immunodeficiency. In our patient, pathological identification of CMV subsequently led to the diagnosis of advanced HIV infection, with profound CD4 lymphopenia, CMV viremia, and CMV retinitis. Thus, a pseudomalignant CMV presentation may be both a diagnostic pitfall and an important clinical clue to previously unrecognized severe immunosuppression.

This case also emphasizes the importance of considering occult immunodeficiency in patients with unusual gastric ulceration or pseudomalignant lesions. The diagnosis of advanced HIV infection was made only after pathological identification of CMV disease prompted further immunological evaluation. Profound CD4 lymphopenia, CMV viremia, and concomitant CMV retinitis supported disseminated CMV disease in the setting of newly diagnosed AIDS. Thus, gastric CMV disease may occasionally be the presenting manifestation that leads to recognition of severe underlying immunosuppression.

Treatment of tissue-invasive CMV disease requires systemic antiviral therapy and correction of the underlying immunosuppressive state when possible. In patients with advanced HIV infection, this includes anti-CMV therapy together with initiation of antiretroviral therapy and appropriate opportunistic infection prophylaxis. Our patient received intravenous ganciclovir followed by oral valganciclovir, antiretroviral therapy, and intravitreal ganciclovir for CMV retinitis. Follow-up evaluation showed clearance of CMV viremia, subsequent suppression of HIV viremia, immune recovery with an increase in CD4 count to 120 cells/µL, complete endoscopic healing of the gastric ulcers, and absence of neoplasia on repeat gastric biopsies, supporting the infectious and reversible nature of the lesion.

The present case has several practical implications for gastroenterologists. First, CMV should be included in the differential diagnosis of malignant-appearing gastric lesions in patients with known or suspected immunosuppression. Second, when endoscopic or EUS findings strongly suggest malignancy but biopsies are negative or atypical, repeat sampling with adequate tissue depth and ancillary studies is warranted. Third, immunohistochemistry and cytokeratin staining can help distinguish CMV-related stromal or endothelial atypia from poorly differentiated carcinoma. Finally, recognition of this entity may prevent unnecessary oncologic treatment or major gastric surgery in patients whose lesions are infectious and potentially reversible. This report has limitations. First, it describes a single patient, and therefore the findings cannot define the frequency of this presentation. Second, although follow-up endoscopy and biopsies supported treatment response and exclusion of malignancy, longer-term surveillance remains important because of the initially malignant-appearing lesion.

Conclusion

Gastric CMV disease is an uncommon but important mimic of gastric malignancy in severely immunocompromised patients. This case demonstrates that CMV-related gastric ulceration and inflammatory wall thickening can closely resemble locally advanced gastric adenocarcinoma on endoscopy and endoscopic ultrasound. In patients with malignant-appearing gastric lesions, particularly when immunosuppression is known or suspected, repeated tissue sampling, careful histopathological assessment, CMV immunohistochemistry and, when histologically indicated, epithelial markers should be considered before committing to oncologic management. Early recognition of this entity may prevent unnecessary surgical or oncologic intervention and allow appropriate antiviral therapy.

Learning points

• •Gastric CMV disease can rarely present as a malignant-appearing ulcerated mass and mimic locally advanced gastric adenocarcinoma on endoscopy and endoscopic ultrasound.
• •In immunocompromised patients, including those with newly diagnosed advanced HIV infection, CMV should be considered in the differential diagnosis of pseudomalignant gastric lesions.
• •Negative or atypical biopsies in a lesion highly suspicious for gastric cancer should prompt repeat tissue sampling and ancillary studies rather than immediate commitment to oncologic treatment.
• •CMV immunohistochemistry and cytokeratin staining can help distinguish tissue-invasive CMV disease with reactive atypia from poorly differentiated adenocarcinoma.

Patient perspective

The patient described the diagnostic process, particularly the initial concern for gastric malignancy, as stressful. She expressed relief after the final diagnosis of cytomegalovirus-related gastric disease was established and after treatment led to virologic response, immune recovery, and complete healing of the gastric ulcers. She reported feeling clinically improved at the latest follow-up and appreciated the ongoing medical care and follow-up.

Ethics declaration

This case report was conducted in accordance with relevant institutional and ethical standards and applicable local regulations. The patient’s privacy and confidentiality were protected throughout the preparation of the manuscript.

CRediT authorship contribution statement

Mehrdad Nikmanesh: Writing – original draft, Writing – review & editing, Project administration, Data curation. Payam Tabarsi: Supervision, Methodology, Investigation. Meghdad Sedaghat: Methodology, Investigation. Mihan Pourabdollah: Methodology, Investigation, Data curation. Esmaeil Mortaz: Writing – review & editing, Writing – original draft, Supervision. Davood Mansouri: Supervision, Methodology.

Consent

Written informed consent for publication of this case report and accompanying anonymized clinical images was obtained from the patient.

Ethical approval

This case report was approved by the Ethics Committee of Masih Daneshvari Hospital.

Declaration of Generative AI and AI-assisted technologies in the writing process

The authors used ChatGPT (OpenAI) for limited language editing and structural refinement, and assistance with manuscript proofreading. No AI tool was used to generate clinical data, perform data analysis, select references, interpret endoscopic or histopathological findings, or create images. All outputs were critically reviewed and verified by the authors, who take full responsibility for the final content.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary material

Supplementary material