Introduction: Zeta-chain-associated protein kinase 70 (ZAP70) is a tyrosine kinase that plays a crucial role in T-cell activation via the T-cell receptor/CD3 complex and contributes to B-cell signaling. ZAP70 variants can cause a range of immunodeficiencies with variable clinical presentations, including infections and malignancies. Case Presentation: A 4-year-old boy presented with chronic cough, dyspnea, recurrent chest infections, and failure to thrive. Chest radiography revealed diffuse bilateral opacities, suggesting a diagnosis of diffuse familial bronchiectasis. Immunological workup at 18 years of age showed CD4⁺ and CD8⁺ T-cell lymphopenia, and genetic analysis revealed a homozygous pathogenic ZAP70 splice-site mutation (c.402 + 2 T>C). The patient then developed headaches, dizziness, and double vision, and Epstein–Barr virus (EBV) polymerase chain reaction (PCR) testing revealed a viral load of 700 IU/mL. Magnetic resonance imaging (MRI) revealed three brain lesions, and brain biopsy confirmed EBV-positive CD20 + diffuse large B-cell lymphoma (DLBCL). Despite aggressive chemotherapy and palliative radiotherapy, the patient’s condition deteriorated, resulting in death. Discussion: To our knowledge, this is the first known case of primary central nervous system DLBCL in a patient with a novel ZAP70 variant. ZAP70 deficiency is typically associated with combined immunodeficiency and rarely with malignancies such as leukemia or lymphoma. Genetic screening at earlier stages could have potentially identified this underlying immunodeficiency sooner and altered the management course. Conclusion: This case underscores the diagnostic challenges and aggressive course of ZAP70-related disease and highlights the need for increased clinical suspicion, immunologic surveillance, early genetic screening, and development of targeted therapies.

Background: Coronavirus disease 2019 (COVID-19) vaccines have significantly reduced global morbidity and mortality. While generally safe, rare immune-mediated liver injuries, including autoimmune hepatitis (AIH) and drug-induced liver injury have been reported post-vaccination. Case series: We present three cases that developed liver injury following Pfizer-BioNTech (BNT162b2) COVID-19 vaccination. Case 1 describes a 64-year-old female with new-onset AIH confirmed by serology, histology, and clinical response to corticosteroids. Case 2 is a 36-year-old female who developed transient liver injury that resolved without immunosuppressive therapy. Case 3 involves a 35-year-old male with a history of AIH in remission who experienced a flare, requiring intensification of immunosuppressive treatment. Discussion: The mechanisms underlying liver injuries following COVID-19 vaccination remain incompletely understood, and a causal relationship has not been definitively established. One possible mechanism is molecular mimicry, in which the immune system targets liver cells after recognizing similarities with viral spike proteins. Vaccine adjuvants may also contribute to immune dysregulation in individuals with certain genetic factors like HLA-DR3 and HLA-DR4, which have been linked to AIH. Multiple reviews of vaccine-associated liver injury suggest that the majority of patients improve with immunosuppressive therapy, although there have been rare reports of severe presentations, including progression to liver failure. Conclusion: Although rare, COVID-19 vaccines may be associated with various forms of liver injury. This case series highlights the heterogeneous clinical spectrum and disease course of COVID-19 vaccine-associated liver injuries, ranging from transient liver enzyme abnormalities to more persistent disease ,such as autoimmune hepatitis, requiring treatment. While causality can not be established, these findings emphasize the importance of clinical vigilance and individualized assessment in at-risk populations.

Glassy cell carcinoma (GCC) is a rare, highly aggressive subtype of poorly differentiated adenocarcinoma, primarily affecting the cervix but also reported in other anatomical sites such as the lung, pancreas, and uterus. Due to its rarity, little is known about the optimal management and prognostic factors influencing outcomes. This retrospective study utilized the SEER database to analyze 43 confirmed cases of GCC from 1992 to 2021, aiming to clarify demographic, clinical, and treatment-related factors associated with survival. The analysis revealed that GCC primarily affects females (90.7%) with a median age of 43 years, and most commonly arises in the cervix (74.4%). Survival analysis using Kaplan-Meier and Cox proportional hazards models indicated that disease stage at diagnosis and age were significant prognostic factors. Specifically, distant-stage disease (HR = 8.44, P < 0.001) and advanced age (HR = 1.043, P = 0.001) were associated with poorer survival. In contrast, treatment modalities such as chemotherapy and radiotherapy did not significantly impact survival outcomes, suggesting that traditional approaches may be inadequate for this carcinoma type. These findings underscore the need for improved early detection and tailored therapeutic strategies. GCC’s unique biological behavior and limited response to conventional treatments highlight the potential value of exploring targeted therapies to enhance patient outcomes in this rare malignancy.

Introduction and importance: An overlap syndrome is a condition when there is coexistence of two or more autoimmune connective tissue disease, which is very rare and diagnostically challenging. Dermatomyositis is an autoimmune condition that presents with skin manifestations, progressive muscular weakness, and inflammation. Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune condition mainly affecting skin, joints, kidneys, and brain. Early recognition and therapeutic intervention are necessary in overlap syndromes to prevent the patient from having severe cardiopulmonary problems. Case presentation: This is a case of a 32-year-old woman diagnosed with SLE who developed progressive muscle weakness (3/5 strength proximally) and a distinctive rash, classic signs of dermatomyositis from last 2 months. Laboratory tests have shown elevated creatine kinase (3500 U/l), positive ANA (1:640), anti-dsDNA, and anti-Jo-1 antibodies, along with visible myopathic alterations on electromyographs; unique results on muscle and skin biopsies were all confirmed by investigations. Clinical discussion: After confirming the diagnosis of dermatomyositis, the patient condition was managed by high dose corticosteroids (prednisolone 1 mg/kg/day), intravenous immunoglobulin for severe muscle weakness, methotrexate, high-dose corticosteroids, and physical therapy. Conclusion: This case highlights the complexity of diagnosis in distinguishing the true dermatomyositis from SLE associated inflammatory myopathy in young adults. It emphasizes the importance of early recognition of DM-SLE overlap syndrome through targeted investigations integrating clinical, serological, and histopathological assessment; that can alter the disease trajectory. The case emphasizes the importance of maintaining high clinical suspicion in patients with autoimmune diseases while guiding the immunosuppressive therapy.