Thymoma-Linked Good’s Syndrome Diagnosed After Severe Neutropenia and Herpes Infection

Doctors in Colombia have reported a rare and diagnostically treacherous case in which a 54-year-old woman’s long-standing chest mass turned out to be the trigger for a profound, combined failure of her immune system. The patient arrived with a year of watery diarrhea, severe neutropenia, fever, painful oral and genital ulcers, and unintentional weight loss of eight kilograms over three months. The eventual diagnosis was Good’s syndrome, an uncommon adult-onset immunodeficiency defined by the coexistence of a thymoma with hypogammaglobulinemia, near-total loss of circulating B cells, and T-cell dysfunction. The case, published as an open-access report in Discover Medicine, illustrates both how the syndrome can masquerade as unrelated problems and how a carefully monitored immunomodulatory intervention was used to bridge the patient to definitive surgery.

Good’s syndrome is far from a household name even within medicine. Fewer than 400 cases have been reported worldwide, and its estimated prevalence is roughly one per 700,000 individuals per year. It arises in the context of thymoma, a rare epithelial tumor of the thymus that can disrupt normal thymopoiesis, in part through reduced expression of the autoimmune regulator gene known as AIRE. That disruption is thought to impair central immune tolerance and dysregulate T-cell development, which in turn may interfere with B-cell maturation and plasma-cell differentiation. The result is a defect that touches both arms of adaptive immunity, humoral and cellular, and that distinguishes Good’s syndrome from purely antibody-deficient conditions such as common variable immunodeficiency.

The clinical spectrum of the syndrome has been sharpened by a large systematic review cited in the report, in which Shi and Wang analyzed 162 cases published between 2010 and 2020. The median age at diagnosis was 58 years, with no significant sex predominance. Infections were the most common manifestation, occurring in approximately 92.6 percent of patients. Sinopulmonary infections led the list at 67.3 percent, followed by gastrointestinal infections at 27.3 percent, skin and soft tissue infections at 18 percent, and mucosal infections at 14 percent. Infection remained the leading cause of mortality, accounting for more than 90 percent of deaths, and the estimated ten-year overall survival was approximately 53.7 percent. The review also identified three distinct clinical subgroups based on infection patterns, underscoring that Good’s syndrome is a heterogeneous entity rather than a uniform one.

The Colombian patient’s story began about a year before admission, when a right mediastinal mass was identified on imaging. Repeated attempts to obtain a tissue biopsy were delayed by lack of insurance authorization and significant socioeconomic limitations, so the mass was never characterized histopathologically before hospitalization. Roughly ten days before admission her condition deteriorated, with foul-smelling watery stools, intermittent fevers reaching 38 degrees Celsius, and ulcerating lesions. On examination she appeared pale and dehydrated, with grade 1 mucositis and multiple ulcerated lesions on the right labia majora and left buttock, each with a depressed whitish center and raised, hyperpigmented, scaly borders.

Laboratory evaluation painted a stark immunological picture. She had hypogammaglobulinemia, with IgG measured at 473 mg/dL and undetectable IgM below 21 mg/dL. Flow cytometry showed an absence of circulating B cells, with CD19-positive cells below one percent. Her CD4 count was 180 cells per microliter, her CD8 count was elevated at 1250 cells per microliter, and the CD4/CD8 ratio was inverted at 0.14. A bone marrow biopsy revealed preserved trilineage hematopoiesis with mature lymphoid aggregates and reactive interstitial changes, without dysplasia or evidence of hematologic malignancy. That combination, severe peripheral neutropenia in the setting of a cellular marrow, suggested an immune-mediated mechanism of neutrophil destruction rather than primary bone marrow failure, although the authors emphasize that this interpretation remained inferential.

Imaging clarified the anatomy. Chest computed tomography revealed a well-defined anterior mediastinal mass measuring 8 by 5.5 centimeters in the right paracardiac region, compressing the adjacent right middle lobe and the anterior segment of the right lower lobe, an appearance that initially mimicked pulmonary involvement. Surgical exploration later confirmed the mass was confined to the anterior mediastinum without intrinsic lung invasion. HIV infection was ruled out, and common variable immunodeficiency was considered unlikely given the absence of a history of recurrent infections, no lymphadenopathy or splenomegaly on imaging, and the presence of a thymoma with an inverted CD4/CD8 ratio, features not characteristic of CVID.

The therapeutic dilemma was acute. With profound neutropenia, at one point a neutrophil count of 130 cells per microliter, and active mucocutaneous lesions suggestive of opportunistic infection, both colonoscopy and mediastinal biopsy carried substantial risk. Filgrastim alone had failed to restore neutrophils during the first 48 hours. After multidisciplinary risk-benefit assessment, the team initiated temporary immunomodulatory therapy: rabbit antithymocyte globulin at a cumulative dose of 3.5 mg/kg divided over five days, cyclosporine at 3 mg/kg per day in two divided doses targeting trough levels of 150 to 250 ng/mL, and filgrastim, alongside intravenous immunoglobulin replacement. Because of active herpes simplex infection, intravenous acyclovir at 5 mg/kg every eight hours was given concurrently. Cytomegalovirus reactivation was monitored by serial plasma PCR, with antifungal prophylaxis using fluconazole and Pneumocystis prophylaxis with trimethoprim-sulfamethoxazole initiated after neutrophil recovery. No viral reactivation or invasive fungal infection was detected during treatment.

The authors are candid that giving rATG to a patient with pre-existing combined immunodeficiency is an immunobiological paradox. rATG is a potent polyclonal anti-T-cell preparation that induces profound and prolonged T-cell depletion, which superimposed on the T-cell defects of Good’s syndrome carries a theoretical risk of catastrophic opportunistic infection, including CMV reactivation, Pneumocystis pneumonia and invasive fungal disease. The decision rested on three considerations: the failure of filgrastim monotherapy, the absence of primary marrow failure on biopsy indicating a peripheral immune-mediated target, and the limited evidence base for cyclosporine alone in rapidly progressive immune-mediated agranulocytosis. Less lymphotoxic alternatives, including high-dose corticosteroids and cyclosporine monotherapy, were considered but deemed insufficient. After eight days of treatment, the neutrophil count recovered to over 1000 cells per microliter, enough to permit invasive procedures.

What followed confirmed the diagnosis. Colonoscopy revealed ulcerative proctitis, and rectal biopsies confirmed herpes simplex virus infection by immunohistochemistry. Video-assisted thoracoscopic surgery identified a 7 by 4 centimeter pedunculated encapsulated mass adherent to the middle mediastinum and pericardium, which was completely resected. Twenty-three days later, histopathological and immunohistochemical examination confirmed a type A thymoma, establishing Good’s syndrome. Following thymectomy and the initiation of regular intravenous immunoglobulin replacement, the patient has not experienced any new opportunistic infections. She was discharged with outpatient oncological follow-up after her gastrointestinal symptoms resolved and her hematological parameters recovered.

The authors stress the limits of what a single case can show. The report is descriptive, antineutrophil antibody testing was not performed so the immune-mediated mechanism remains inferential, and T-cell receptor clonality analysis and STAT3 mutation testing were unavailable, meaning T-cell large granular lymphocytic leukemia could not be completely excluded, though it was considered less likely. Serial post-treatment laboratory values were not available, and long-term follow-up data are lacking. Their conclusions are correspondingly measured: Good’s syndrome should be suspected in patients with thymoma who present with hypogammaglobulinemia, absent or markedly reduced B cells, an inverted CD4/CD8 ratio and opportunistic infections, and in selected patients with severe presumed immune-mediated neutropenia refractory to granulocyte colony-stimulating factor, temporary rATG and cyclosporine may be considered as a rescue approach, but its efficacy and safety cannot be established from one case and require further investigation.

Subject of Research: A case report of thymoma-associated Good's syndrome presenting with combined immunodeficiency, severe neutropenia and opportunistic infection

Article Title: Thymoma associated good syndrome presenting with combined immunodeficiency severe neutropenia and opportunistic infection

Article References: Alvarado, D. P., Bonilla, D. M., Tafurt, G. P. R., Correa, S. V., & Liscano, Y. (2026). Thymoma associated good syndrome presenting with combined immunodeficiency severe neutropenia and opportunistic infection. Discover Medicine, 3(1), Article 164. https://doi.org/10.1007/s44337-026-00724-3

Image Credits: AI Generated

DOI: 10.1007/s44337-026-00724-3

Keywords: Good's syndrome, thymoma, immunodeficiency, neutropenia, hypogammaglobulinemia, herpes simplex, rATG, thymectomy, intravenous immunoglobulin, case report, CD4/CD8 ratio, opportunistic infections