Gastric Mucormycosis: An Infection of Fungal Invasion into the Gastric Mucosa in Immunocompromised Patients

Primary gastric mucormycosis is a rare but potentially lethal fungal infection due to the invasion of Mucorales into the gastric mucosa. It may result in high mortality due to increased risk of complications in immunocompromised patients. Common predisposing risk factors to develop gastric mucormycosis are prolonged uncontrolled diabetes mellitus with or without diabetic ketoacidosis (DKA), solid organ or stem cell transplantation, underlying hematologic malignancy, and major trauma. Abdominal pain, hematemesis, and melena are common presenting symptoms. The diagnosis of gastric mucormycosis can be overlooked due to the rarity of the disease. A high index of suspicion is required for early diagnosis and management of the disease, particularly in immunocompromised patients. Radiological imaging findings are nonspecific to establish the diagnosis, and gastric biopsy is essential for histological confirmation of mucormycosis. Prompt treatment with antifungal therapy is the mainstay of treatment with surgical resection reserved in cases of extensive disease burden or clinical deterioration. We presented a case of acute gastric mucormycosis involving the body of stomach in a patient with poorly controlled diabetes and chronic renal disease, admitted with acute onset of abdominal pain. Complete resolution of lesion was noted with 16 weeks of medical treatment with intravenous amphotericin B and posaconazole.

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Checkpoint inhibition in immunosuppressed or immunocompromised patients with advanced cutaneous squamous cell carcinoma (CSCC): Data from prospective CemiplimAb-rwlc Survivorship and Epidemiology (C.A.S.E.) study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9547 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9547-9547

Author(s):

Guilherme Rabinowits ◽

Soo J Park ◽

David M. Ellison ◽

Francis P. Worden ◽

Rhonda W. Gentry ◽

...

Keyword(s):

Clinical Trials ◽

Checkpoint Inhibitors ◽

Hematologic Malignancy ◽

Objective Response ◽

Organ Transplant ◽

Immunosuppressed Patient ◽

Solid Organ ◽

Immunocompromised Patients ◽

Increased Risk ◽

Initial Cohort

9547 Background: Immunosuppressed and/or immunocompromised patients are at increased risk for solid tumors and cutaneous malignancies. Limited data exist on the safety and effectiveness of immune checkpoint inhibitors (ICIs) in these patients because they are frequently excluded from clinical trials. Here, we describe the safety and effectiveness results from the initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC enrolled in the C.A.S.E. study (NCT03836105). Methods: C.A.S.E. is a prospective, real-world, multi-center, longitudinal study evaluating the effectiveness, safety, quality of life, and survivorship in patients with advanced CSCC treated with cemiplimab. Patients received cemiplimab 350 mg intravenously every 3 weeks per routine standard of care. Patient demographics, disease characteristics, immunosuppression, and relevant medical history were collected. Immunosuppressive regimens varied amongst patients. Investigator assessment of objective response rate (ORR), safety, and tolerability was conducted. Data from 26 immunosuppressed and/or immunocompromised patients with advanced CSCC treated with cemiplimab are presented. Recruitment is ongoing. Results: As of November 17, 2020, 121 patients were enrolled in the C.A.S.E. study, of which 26 patients (median age: 74 years [IQR: 71-84]; 85% male; 89% Caucasian) were designated as immunocompromised or immunosuppressed due to a history of solid organ transplant (n = 6), autoimmune disorder (n = 11), or hematologic malignancy (n = 9). Median duration of cemiplimab exposure was 14 months (IQR: 9.1–42, range: 0, 67). Among 19 immunocompromised or immunosuppressed patients who enrolled in C.A.S.E. prior to their third dose of cemiplimab, ORR per investigator assessment was 47% (95% CI: 24–71); 1 (5%) patient had complete response; 8 (42%) had partial response. One patient had a treatment-related serious adverse reaction of organ transplant rejection. One (3.8%) patient discontinued treatment due to increased alanine aminotransferase (not treatment-related). Immune-related AEs (irAEs) occurred in 23% of patients. No treatment-related AEs led to death. Conclusions: The safety, tolerability, and effectiveness of cemiplimab in this initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC appear to be consistent with those observed in clinical trials that excluded these patients. Further follow-up and additional data would add to our general understanding of safety and effectiveness of anti-PD1 therapy in immunocompromised and/or immunosuppressed patient populations overall. Clinical trial information: NCT03836105.

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Human Papillomavirus, Herpes Zoster, and Hepatitis B Vaccinations in Immunocompromised Patients: An Update for Pharmacists

Journal of Pharmacy Practice ◽

10.1177/0897190020958261 ◽

2020 ◽

pp. 089719002095826

Author(s):

Michelle R. Paulsen ◽

Nikitha R. Patel ◽

Carol Sulis ◽

Francis A. Farraye ◽

Shubha Bhat

Keyword(s):

Human Papillomavirus ◽

Herpes Zoster ◽

Hepatitis B ◽

Organ Transplant ◽

Current Evidence ◽

Solid Organ ◽

Cell Transplant ◽

Immunocompromised Patients ◽

Hematopoietic Stem ◽

Increased Risk

Purpose: Current evidence regarding efficacy and safety of human papillomavirus 9-valent (9vHPV), recombinant zoster (RZV), and CpG-adjuvanted recombinant hepatitis B (HepB-CpG) vaccines in adults with human immunodeficiency virus, inflammatory bowel disease, solid organ transplant, and allogeneic hematopoietic stem cell transplant is reviewed. Summary: Patients immunocompromised due to underlying disease or treatment are at increased risk for infections; however, insufficient understanding of various vaccines’ efficacy, safety, indications, and contraindications in this population has led to suboptimal vaccination rates. The Infectious Disease Society of America (IDSA) published guidelines on vaccines in immunocompromised populations in 2013. Since then, several advances have been made including an expanded indication with 9vHPV for use in males and females 9 to 45 years old, and the introduction of new vaccines for herpes zoster (RZV) and hepatitis B (HepB-CpG). Pharmacists are instrumental to vaccination efforts and may benefit from a review of recent vaccine updates. Conclusion: The 9vHPV can be used in men and women ages 9 to 45 years old regardless of immune status. RZV safety and efficacy in several immunocompromised populations has been demonstrated; however, manufacturers and major societies have yet to update their recommendations. HepB-CpG may be used in most immunocompromised patients yet remains under-utilized.

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Clinical Manifestations, Pathogenesis and Treatment of Hepatitis E Virus Infections

Journal of Clinical Medicine ◽

10.3390/jcm9020331 ◽

2020 ◽

Vol 9 (2) ◽

pp. 331 ◽

Cited By ~ 8

Author(s):

Sébastien Lhomme ◽

Olivier Marion ◽

Florence Abravanel ◽

Jacques Izopet ◽

Nassim Kamar

Keyword(s):

Hepatitis E Virus ◽

Hematologic Malignancy ◽

Antiviral Treatment ◽

Clinical Manifestations ◽

Hepatitis E ◽

Immunosuppressive Drugs ◽

New Drugs ◽

Renal Diseases ◽

Solid Organ ◽

Immunocompromised Patients

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis throughout the world. Most infections are acute but they can become chronic in immunocompromised patients, such as solid organ transplant patients, patients with hematologic malignancy undergoing chemotherapy and those with a human immunodeficiency virus (HIV) infection. Extra-hepatic manifestations, especially neurological and renal diseases, have also been described. To date, four main genotypes of HEV (HEV1-4) were described. HEV1 and HEV2 only infect humans, while HEV3 and HEV4 can infect both humans and animals, like pigs, wild boar, deer and rabbits. The real epidemiology of HEV has been underestimated because most infections are asymptomatic. This review focuses on the recent advances in our understanding of the pathophysiology of acute HEV infections, including severe hepatitis in patients with pre-existing liver disease and pregnant women. It also examines the mechanisms leading to chronic infection in immunocompromised patients and extra-hepatic manifestations. Acute infections are usually self-limiting and do not require antiviral treatment. Conversely, a chronic HEV infection can be cleared by decreasing the dose of immunosuppressive drugs or by treating with ribavirin for 3 months. Nevertheless, new drugs are needed for those cases in which ribavirin treatment fails.

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Clinical Characteristics and Radiologic Features of Immunocompromised Patients With Pauci-Bacillary Pulmonary Tuberculosis Receiving Delayed Diagnosis and Treatment

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz002 ◽

2019 ◽

Vol 6 (2) ◽

Cited By ~ 3

Author(s):

Joung Ha Park ◽

Jooae Choe ◽

Moonsuk Bae ◽

Sungim Choi ◽

Kyung Hwa Jung ◽

...

Keyword(s):

Pulmonary Tuberculosis ◽

Hematologic Malignancy ◽

Diagnostic Delay ◽

Organ Transplant ◽

Delayed Diagnosis ◽

Tertiary Hospital ◽

The Other ◽

Solid Organ ◽

Immunocompromised Patients ◽

Radiologic Features

Abstract Background Pauci-bacillary pulmonary tuberculosis (TB) can be delayed to diagnose and start anti-TB therapy, especially in immunocompromised patients. We therefore evaluated the clinical and radiologic features of these delayed cases. Methods Immunocompromised adult patients with pauci-bacillary pulmonary TB were retrospectively enrolled in a tertiary hospital in an intermediate–TB burden country over a 5-year period. We defined “missed TB” or “not-missed TB” patients as those who started anti-TB therapy after or before positive mycobacterial culture results, respectively. Results Of 258 patients, 134 (52%) were classified in the missed TB group, and 124 (48%) in the not-missed TB group. Positive results of molecular tests including MTB polymerase chain reaction and/or Xpert TB/RIF were only obtained in the not-missed TB group (54/106, 54%). The median diagnostic delay in the missed TB group was longer than in the other group (30 vs 6 days; P < .001). In the missed TB group, the most common working diagnoses were pneumonia (46, 34%) and lung metastasis of malignancy (40, 30%). Typical radiologic findings for TB, such as upper lobe predominance and centrilobular nodules with tree-in-bud appearance, were less common in the missed TB group than in the other group. Old age (odds ratio [OR], 1.03), solid organ transplant (OR, 3.46), solid tumor (OR, 3.83), and hematologic malignancy (OR, 4.04) were independently associated with missed TB. Conclusions Care is needed to differentiate pauci-bacillary TB, especially in immunocompromised patients with the mentioned risk factors, even without the usual radiologic features of TB. Additional rapid diagnostic tests to rule out pauci-bacillary TB are urgently needed.

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1404. The FilmArray Meningitis/Encephalitis (FA ME) May Be of Higher Yield in the Immunocompromised Patient Population

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1268 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S511-S511

Author(s):

Nirja Mehta ◽

Jesse T Jacob ◽

Christina Dean ◽

Zanthia Wiley ◽

Eileen Burd ◽

...

Keyword(s):

Cryptococcal Meningitis ◽

Chart Review ◽

Hematologic Malignancy ◽

False Negative ◽

Small Sample ◽

Cns Infection ◽

Steady Increase ◽

Solid Organ ◽

Immunocompromised Patients ◽

Immunocompetent Patients

Abstract Background The FilmArray® Meningitis/Encephalitis (FA ME) panel is a PCR-based assay that rapidly detects 14 pathogens directly from CSF specimens. After the introduction of this assay at our institution, there was a steady increase in requests for use; however, the positivity rate remained stable. We sought to understand the characteristics of the patients most likely to have a positive FA ME panel, with particular interest in the immune status of each patient. Methods A retrospective chart review was conducted on 124 patients with suspected infectious meningitis/encephalitis at a large academic tertiary referral center who received FA ME testing between October 2016 and November 2018. Patients were considered immunocompromised if they had received chemotherapy, were solid-organ transplant recipients, or were diagnosed with HIV, autoimmune diseases on immunosuppressants, uncontrolled diabetes, cirrhosis, or hematologic malignancy. Clinical CNS infection was determined using chart review based on culture, serologic, or molecular data. Results 60 (48%) patients were immunocompromised and 64 (52%) patients were immunocompetent. Clinical CNS infection occurred in ~25% of immunocompetent (17, 26%) and immunocompromised (17, 28%) patients. However, only 6 immunocompetent patients were found to have a positive FA ME; this accounts for only 35% of the total number of positive FA ME assays during this study period (P = 0.08). Notably, 4 out of 6 patients with cryptococcal meningitis had false-negative results on the FA ME. Conclusion In spite of the relatively small sample size, there was a trend toward significance in the accurate yield of the FA ME panel in the immunocompromised population compared with the immunocompetent. Our immunocompromised patients appear to be more likely to have an infection which is tested for on the panel. The rates of confirmed CNS infections in both populations were very similar, indicating that immunocompromised patients may benefit more from use of this assay. In our study, immunocompetent patients were more likely to have West Nile infection, for example, which is not on the panel. Additionally, had cryptococcal meningitis been accurately diagnosed by the FA ME, an even greater number of immunocompromised patients would have had a positive FA ME. Disclosures All authors: No reported disclosures.

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Immunohistochemical markers CDX2, CK20, CK7 in the evaluation of severity lesions of the gastric mucosa in schoolchildren with gastritis

Experimental and Clinical Gastroenterology ◽

10.31146/1682-8658-ecg-175-3-54-59 ◽

2020 ◽

pp. 54-59

Author(s):

V. A. Vshivkov ◽

T. V. Polivanova ◽

E. V. Kasparov ◽

O. V. Peretyatko

Keyword(s):

Gastric Mucosa ◽

Morphological Changes ◽

Statistical Significance ◽

The Body ◽

Immunohistochemical Method ◽

Immunohistochemical Markers ◽

Increased Risk ◽

The Republic ◽

H Pylori ◽

Qualitative Characteristics

The aim is study the association of CDX2, CK20, CK7 with morphological changes in the gastric mucosa at children of aboriginal and newcomer population of the Republic of Tuva with gastritis.Materials and methods. We examined of children with gastroenterological complaints by 2 ethnic groups: 69 aboriginal and 34 immigrants. All underwent esophagogastroduodenoscopy with sampling of biopsies from the antral region and the body of the stomach. Diagnosis of gastritis was carried out according to the modified Sydney classification. H. pylori was determined of coloring the biopsies by Gimza. Expression of biomarkers was recorded by immunohistochemical method (CDX2, CK20, CK7). The analysis of the statistical significance of differences in qualitative characteristics was carried out using the criterion χ2.Results. We had determined the expression of CDX2 in 4 schoolchildren in the Republic of Tuva. This is can be examined as a marker for dynamic observation with a poor prognosis, because marker CDX2 tight connect with metaplasia and atrophy in gastric mucosa at adults. Association of the expression of CK20 and CK7 was established with the activity of gastritis, infection H. pylori, metaplasia of gastric mucosa, what more expressed by Tuva population. This has been testifying of the intensification proliferative processes in the gastric mucosa. This fact explaining the acceleration of progression the inflammatory process into the body of stomach. All it’s associated with an increased risk of dystrophy and atrophy at the gastric mucosa.Conclusion. CDX2 CK20, CK7 can to act as biomarkers of development the precancerous damage of stomach in schoolchildren of Tuva, especially by Tuvans. The presence of atrophy, metaplasia or CDX2 protein is a prognostically unfavorable factor.

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Association of prior epidemiologic exposures with cytogenetic risk in adult acute myeloid leukemia (AML).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.7047 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 7047-7047

Author(s):

Laura Elizabeth Finn ◽

Lisa Ostrosky Sproat ◽

Michael Heckman ◽

Liuyan Jiang ◽

Nancy N. Diehl ◽

...

Keyword(s):

Hematologic Malignancy ◽

Multivariable Analysis ◽

Solid Organ Transplantation ◽

Risk Groups ◽

Solid Organ ◽

Case Control Studies ◽

Logistic Regression Models ◽

Increased Risk ◽

Therapeutic Study ◽

Risk Categories

7047 Background: In addition to secondary AML (sAML), important lifestyle and environmental exposures associated with increased risk of AML development have been identified in recent case-control studies including obesity (BMI>30kg/m2), smoking, regular acetaminophen use, and rural/farm habitat. The association of these exposures with AML cytogenetic risk groups is unknown. We therefore evaluated relevant exposures in a cohort of 301 AML patients with confirmed central cytogenetics analysis diagnosed and treated at Mayo Clinic FL and AZ since 1995. Methods: Documented patient exposures were extracted from central electronic medical records, including: prior chemotherapy/radiation or hematologic malignancy, occupation, select medications, “toxins” (esp. benzene) and solid organ transplantation (SOT). Standard cytogenetic risk categories (including intermediate abnormal) were applied. The association of epidemiologic exposures with cytogenetic risk was evaluated on multivariable analysis using logistic regression models. Results: sAML was significantly associated with cytogenetic risk groups, as was prior SOT, healthcare occupation, farm habitat and toxin exposures [see Odds Ratios (OR), Table). In contrast, prior radiation for epithelial malignancies, smoking and BMI were not independently associated with specific cytogenetic risk categories. Conclusions: Specific epidemiologic exposures are significantly associated with AML cytogenetic risk categories suggesting a unique clinical phenotype. This supports a link to leukemogenesis and requires validation in a controlled prospective therapeutic study. [Table: see text]

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Effects of Monoclonal Gammopathy of Undetermined Significance (MGUS) on Outcomes after Solid Organ Transplant

Blood ◽

10.1182/blood.v124.21.3507.3507 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3507-3507

Author(s):

Teresa E Goebel ◽

Nicholas K Schiltz ◽

Aiswarya Chandran Pillai ◽

Paolo Caimi ◽

Siran M Koroukian ◽

...

Keyword(s):

Conflicts Of Interest ◽

Hematologic Malignancy ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Lymphoproliferative Disease ◽

Solid Organ ◽

Transplant Patients ◽

Diagnosis Codes ◽

Increased Risk ◽

Increase Risk

Abstract Background: MGUS is a precancerous condition which can progress to multiple myeloma (MM) or other hematologic malignancy. MGUS increases the risk of developing MM approximately 25-fold, and increases lifetime risk of infection, venous thromboembolism (VTE), and skeletal related events (SRE). Solid organ transplant requires immunosuppression, which is associated with overlapping risks, including hematologic malignancy such as post transplant lymphoproliferative disease (PTLD). Hypothesizing that MGUS would further increase risk of PTLD and other complications after transplant, we described risk of these outcomes in patients with MGUS prior to solid organ transplant (MGUS+) compared to those without MGUS (MGUS-). Methods: We used the 2005-2011 California State Inpatient, Emergency, and Ambulatory Databases. MGUS and complications were identified by ICD-9 diagnosis codes, and solid organ transplant by ICD-9 procedure codes. Patients with the ICD-9 diagnosis code 273.1 documented on or before the day of solid organ transplant surgery were defined as MGUS+. We used logistic regression to analyze complications in MGUS+ versus MGUS- transplant patients. Results: Of 24,358,669 patients, we identified 22,062 solid organ transplant patients. Transplant patients were 8.8% African American, 29.5% Hispanic, 43.4% White, 15.1% other, and 3.2% had data missing. 72 were MGUS+ prior to solid organ transplant. Median age of MGUS+ was 61.5 years versus 51 years for MGUS-. Outcomes are shown in table 1. Table 1. Transplant Patients Outcome MGUS + N=72 MGUS – N=21,990 Odds Ratio (95% CI) PTLD 0 161 n/a MM ≤10 37 34.90 (12.11, 100.61) Lymphoma 0 193 n/a VTE 20 3,202 2.26(1.35, 3.79) SRE 18 2,320 2.83(1.66, 4.83) Infection 50 11,612 2.03(1.23, 3.36) *Frequencies ≤10 are reported as such per the data use agreement. Conclusions: Compared to MGUS-, MGUS+ solid organ transplant patients had higher risk of VTE, SRE, and infection, but did not have higher risk of PTLD or other lymphomas. MGUS+ transplant patients are more likely to develop MM than MGUS-; however, this risk is similar to that historically attributed to MGUS, in patients who have not undergone transplant. These data show increased risk of certain complications in MGUS+ patients, and do not support screening for MGUS to assess risk of PTLD prior to solid organ transplant. Disclosures No relevant conflicts of interest to declare.

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223. Predicting Mortality Among Immunocompromised Patients Who Present With Bloodstream Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.298 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S130-S130

Author(s):

Oryan Henig ◽

Krishna Rao ◽

Rosemary KB Putler ◽

Twisha S Patel ◽

Owen Albin ◽

...

Keyword(s):

Bloodstream Infection ◽

Risk Model ◽

Hematologic Malignancy ◽

Solid Organ Transplantation ◽

Baseline Risk ◽

Solid Organ ◽

Immunocompromised Patients ◽

Suspected Infection ◽

Dichotomous Variable ◽

Definition Of

Abstract Background The revised definition of sepsis (Sepsis-3) uses Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) to identify patients with sepsis instead of systemic inflammatory response syndrome (SIRS) criteria. Subsequent studies revealed contradictory results pertaining to qSOFA, and limited data are available for immunocompromised patients. The objectives of this study were to (1) evaluate the performance of Sepsis -3 in a cohort of immunocompromised patients with microbiologically-proven sepsis, defined as having received antibiotics and having bloodstream infection (BSI); and (2) to compare its performance in the BSI cohort to its performance in immunocompromised patients who received antibiotics but did not have BSI (Non-BSI cohort). Methods Adult patients with hematologic malignancy or solid transplant recipients admitted to Michigan Medicine between 2012–2017 with suspected infection were included based on criteria used in the Sepsis-3 study: having both a body fluid culture and having received intravenous antibiotics. SOFA, qSOFA and SIRS components within 1 day of the index date (culture date or antibiotic date, whichever came first) were extracted from the medical record. For each group, a baseline risk model for mortality was created including age, gender, race, and Charlson comorbidity index. Each score (SOFA ≥ 2, qSOFA ≥ 2, SIRS ≥ 2) was added to the baseline risk model as a dichotomous variable and AUROC values were calculated. Results 2822 patients with a mean age of 56.8±15.6 were included. 349 (12.4%) had BSI. The most common immune compromising conditions were solid-organ transplantation (47%), lymphoma (21.3%) and acute leukemia (17%). 14% of patients in the BSI cohort died during hospitalization compared with 6.6% in the non-BSI cohort (P < 0.001). For the BSI cohort, when SOFA ≥ 2, qSOFA ≥ 2, SIRS ≥ 2 scores were added to the model, the AUROC values were less than those for the non-BSI cohort (table). The addition of SOFA ≥6 to the baseline risk model produced the highest AUROC values in both the BSI and non-BSI cohorts (figure). Conclusion Among immunocompromised patients, an SOFA score ≥6 was the strongest predictor of mortality. Surprisingly, sepsis scores performed better in the non-BSI cohort than in the BSI cohort. Disclosures All authors: No reported disclosures.

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Epstein-Barr Virus associated gastric carcinoma in a patient with germline STAT3 gain-of-function mutation

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqab191.134 ◽

2021 ◽

Vol 156 (Supplement_1) ◽

pp. S65-S65

Author(s):

J Mahadik ◽

K Patel ◽

N Cortes-Santiago

Keyword(s):

Poor Response ◽

Posterior Wall ◽

Immune Dysregulation ◽

The Body ◽

Low Grade ◽

Solid Organ ◽

Muscularis Mucosa ◽

Gain Of Function ◽

First Case ◽

Increased Risk

Abstract Introduction/Objective Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in inflammation, proliferation, differentiation and survival. STAT3 gain-of-function (GoF) disorders are characterized by immune dysregulation and present with polyendocrinopathy, enteropathy, X-linked syndrome (IPEX)- or autoimmune lymphoproliferative syndrome (ALPS)-like features. While patients with STAT-3 GoF are known to have an increased risk for hematologic malignancies, neither solid tumors nor an increased risk for EBV-associated disorders have been described. We report the first case of an EBV-associated solid organ tumor in a patient with STAT-3 GoF. Methods/Case Report A 21-year-old male with germline mutation in STAT3 (variant p. M329K) presented with early satiety, abdominal pain and worsening of chronic anemia. Serology showed high EBV DNA PCR levels. Endoscopy showed multiple nodular lesions in the stomach, which were biopsied to reveal EBV-associated high-grade dysplasia and intramucosal adenocarcinoma. Initiation of chemotherapy with a poor response led to a total gastrectomy. Gross examination of the specimen showed a 7.9 x 6.5 x 1.8 cm tan-brown, exophytic mass in the posterior wall of the body and antrum, involving the greater curvature. Histology revealed an adenocarcinoma with tubulovillous morphology extending into the lamina propria, without invasion into the muscularis mucosa or submucosa. EBER in-situ hybridization was diffusely positive in the tumor cells. The background mucosa showed severe chronic active and atrophic gastritis with intestinal metaplasia and low-grade dysplasia. All the seventy examined lymph nodes were negative for metastasis. Helicobacter-like organisms were not seen. Results (if a Case Study enter NA) NA Conclusion This is the first report of a solid tumor in a patient with STAT3 GoF mutation. The role of the patient’s underlying immune dysregulation disorder in the development of EBV-associated gastric adenocarcinoma is unclear and warrants further investigation. The case also highlights the importance of a close clinical follow-up in this patient population, as unexpected malignancies can develop at younger ages.

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