Thymic Imaging Pitfalls and Strategies for Optimized Diagnosis.

Thymic imaging is challenging because the imaging appearance of a variety of benign and malignant thymic conditions are similar. CT is the most commonly used modality for mediastinal imaging, while MRI and fluorine 18 fluorodeoxyglucose (FDG) PET/CT are helpful when they are tailored to the correct indication. Each of these imaging modalities has limitations and technical pitfalls that may lead to an incorrect diagnosis and mismanagement. CT may not be sufficient for the characterization of cystic thymic processes and differentiation between thymic hyperplasia and thymic tumors. MRI can be used to overcome these limitations but is subject to other potential pitfalls such as an equivocal decrease in signal intensity at chemical shift imaging, size limitations, unusual signal intensity for cysts, subtraction artifacts, pseudonodularity on T2-weighted MR images, early imaging misinterpretation, flow and spatial resolution issues hampering assessment of local invasion, and the overlap of apparent diffusion coefficients between malignant and benign thymic entities. FDG PET/CT is not routinely indicated due to some overlap in FDG uptake between thymomas and benign thymic processes. However, it is useful for staging and follow-up of aggressive tumors (eg, thymic carcinoma), particularly for detection of occult metastatic disease. Pitfalls in imaging after treatment of thymic malignancies relate to technical challenges such as postthymectomy sternotomy streak metal artifacts, differentiation of postsurgical thymic bed changes from tumor recurrence, or human error with typical "blind spots" for identification of metastatic disease. Understanding these pitfalls enables appropriate selection of imaging modalities, improves diagnostic accuracy, and guides patient treatment. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Paraneoplastic autoimmune neurologic disorders associated with thymoma.

Thymoma is often associated with paraneoplastic neurologic diseases. Neural autoantibody testing is an important tool aiding diagnosis of thymoma and its autoimmune neurologic complications. Autoantibodies specific for muscle striational antigens and ion channels of the ligand-gated nicotinic acetylcholine receptor superfamily are the most prevalent biomarkers. The autoimmune neurologic disorders associating most commonly with thymoma are myasthenia gravis (MG), peripheral nerve hyperexcitability (neuromyotonia and Morvan syndrome), dysautonomia, and encephalitis. Patients presenting with these neurologic disorders should be screened for thymoma at diagnosis. Although they can cause profound disability, they usually respond to immunotherapy and treatment of the thymoma. Worsening of the neurologic disorder following surgical removal of a thymoma may herald tumor recurrence. Prompt recognition of paraneoplastic neurologic disorders is critical for patient management. A multidisciplinary approach is required for optimal management of neurologic autoimmunity associated with thymoma.

[Clinical diagnosis and treatment analysis of 21 cases of intrathyroid thymic carcinoma].

Objective: To analyze the clinical efficacy of intrathyroid thymic carcinoma (ITTC). Methods: This study retrospectively analyzed the clinical data of 21 patients with ITTC diagnosed and treated at the First Affiliated Hospital of Zhengzhou University from January 2018 to July 2023, including 9 males and 12 females, with a median age of 52 years (40-60 years old). Results: There is a correlation between the maximum diameter of the tumor (≥40 mm) and lymph node metastasis (P=0.044). Seventeen patients received surgical treatment, and 4 patients only received chemotherapy. During the follow-up period, a total of 4 patients experienced death or progression, with a 2-year mortality or progression free survival rate of 74.8%. Conclusions: The prognosis of ITTC is good, and surgical treatment is the preferred treatment option, lymph node metastasis is significantly correlated with prognosis. The radiotherapy and chemotherapy of ITTC need to be determined based on the patient's condition.

Diagnostic utility of LMO2 immunohistochemistry in distinguishing T-lymphoblastic leukemia/lymphoma from thymoma.

Distinguishing T-lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) from thymomas (especially B1 or B2 type) can be challenging particularly in limited trucut biopsy material where appreciating architecture is difficult or the background epithelial component does not provide tangible evidence for definite diagnosis. As a pathologist, it is important to accurately diagnose these neoplasms because they have entirely distinct management protocols. Recent studies have reported that LIM Domain Only 2 (LMO2) is expressed in neoplastic lymphoblasts of T-ALL/T-LBL and is absent in thymocytes of normal thymuses or thymomas. An observational study was done to test the sensitivity and specificity of LMO2 in differentiating neoplastic lymphoblasts from thymocytes of thymomas/normal thymuses. Our study showed that LMO2 had sensitivity of 70% and specificity of 100% in diagnosing LBL. None of the thymomas (B1 or B2 type) showed expression of LMO2 in the neoplastic cells. LMO2 is a reliable marker of transformed T-cell precursors and should be routinely included in immunohistochemical panel when evaluating thymic/mediastinal neoplasms.

Thymoma-associated autoimmune encephalitis with myasthenia gravis: Case series and literature review.

OBJECTIVES: This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their clinical characteristics. METHODS: Clinical records of 3 AE patients in the first affiliated hospital of Sun Yat-sen University were reviewed. All of them were diagnosed with AE between 1 November 2021 and 1 March 2022, and clinical evidence about thymoma and MG was found. All published case reports were searched for comprehensive literature from January 1990 to June 2022. RESULTS: A total of 18 cases diagnosed with thymoma-associated autoimmune encephalitis (TAAE) and thymoma-associated myasthenia gravis (TAMG) were included in this complication, wherein 3 cases were in the first affiliated hospital of Sun Yat-sen University and the other 15 were published case reports. 5/18 patients had alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibody (AMPAR-Ab) in their serum and cerebrospinal fluid (CSF). All of them had positive anti-acetylcholine receptor antibody (AChR-Ab). And 12/18 patients showed a positive response to thymectomy and immunotherapy. Besides, thymoma recurrences were detected because of AE onset. And the shortest interval between operation and AE onset was 2 years in patients with thymoma recurrence. CONCLUSIONS: There was no significant difference in the clinical manifestations between these patients and others with only TAMG or TAAE. TAAE was commonly associated with AMPAR2-Ab. Significantly, AE more commonly heralded thymoma recurrences than MG onset. And the intervals of thymectomy and MG or AE onset had different meanings for thymoma recurrence and prognoses of patients.

Erythroderma in a Patient With Thymoma-Associated Myasthenia Gravis.

A woman in her 30s with myasthenia gravis diagnosed at age 27 years presented to the emergency department with severe erythroderma over the past 2 months. What is your diagnosis?

Pure white cell aplasia before and after thymectomy in the rare conundrum of thymoma: A case report and review of the literature.

RATIONALE: Pure white cell aplasia (PWCA) is a rare paraneoplastic syndrome that occurs in patients with thymomas. Currently, the pathogenesis and treatment of this disease remain in the exploratory stage. PATIENT CONCERNS: We report a 68-year-old woman with thymoma experienced PWCA involvement as her first presentation. The patient had high fever and agranulocytosis at the onset of the disease. The white blood cell count in the complete blood count was 1.9 × 109/L with a neutrophil of 0.1 × 109/L. The bone marrow aspirates showed decreased granulocyte proliferation. Computed tomography showed a large mass in the anterior mediastinum. DIAGNOSES: The final diagnosis of our patient was PWCA and thymoma. INTERVENTIONS: She underwent a thymectomy and cyclosporine A administration during first remission. OUTCOMES: Long-term remission was achieved following the readministration of cyclosporine A after the disease recurrence. LESSONS: PWCA or agranulocytosis with thymoma has been confirmed to be an extremely rare disease. Thymomas with PWCA correlate with autoimmunity. From this case study and the literature review, we concluded that the pathogenesis of thymomas in PWCA is mainly related to the activation of autoreactive T cells. Thymectomy and the immunosuppressive drug, cyclosporine A, were chosen for treatment. The patient's granulocyte levels were unable to recover after surgery because of the inability to promptly clear activated T cells. After surgery, cyclosporine A continued to take for a long time. Thymectomy combined with prolonged cyclosporine A administration may be an effective method for treating this rare disease.

A Rare Case of Metaplastic Thymoma Presenting With Myasthenia Gravis.

Thymomas are tumors of the mediastinum often associated with autoimmune conditions, in particular myasthenia gravis. In contrast, among the fewer than 40 reports of metaplastic thymoma, myasthenia gravis is rarely found. We describe the fourth patient, and first man, with metaplastic thymoma and myasthenia gravis. A 34-year-old had acute onset of double vision with associated dysphagia and was found to have an elevation of serum acetylcholine receptor antibodies. He underwent a transsternal thymectomy. Tissue sections showed a biphasic proliferation of keratin-positive epithelial cells with a complement of spindle cells confirming the diagnosis of metaplastic thymoma. Terminal deoxynucleotidyl transferase (TDT)-positive T lymphocytes were rare and only found in the periphery of the tumor, consistent with thymic remnant. A YAP1::MAML2 gene fusion, with an in-frame fusion between genes YAP1 Exon5 (NM_001130145) and MAML2 Exon2 (NM_032427) was found, supporting further the diagnosis of metaplastic thymoma (Anchored multiplex RNA sequencing [Archer Dx, Boulder, CO] assay). The patient's gender and relatively young age, the presence of an autoimmune condition, and the lack of lymphocytic infiltrate all contribute unusual features to this case and suggest avenues for further exploration.

Metabolic signatures of thymomas: potential biomarkers and treatment targets.

OBJECTIVES: A study of tumour metabolic reprogramming has revealed disease biomarkers and avenues for therapeutic intervention. Metabolic reprogramming in thymoma is currently understudied and largely unknown. This study utilized metabolomics and isotope tracing with 13C-glucose to metabolically investigate thymomas, adjacent thymic tissue and benign thymic lesions. METHODS: From 2017 to 2021, 20 patients with a suspected thymoma were recruited to this prospective Institutional Review Board approved clinical trial. At the time of surgery, 11 patients were infused with 13C-glucose, a stable, non-radioactive tracer which reports the flow of carbon through metabolic pathways. Samples were analysed by mass spectrometry to measure the abundance of >200 metabolites.13C enrichment was measured in patients who received 13C-glucose infusions. RESULTS: Histological analysis showed that 9 patients had thymomas of diverse subtypes and 11 patients had benign cysts. In our metabolomic analysis, thymomas could be distinguished from both adjacent thymus tissue and benign lesions by metabolite abundances. Metabolites in pyrimidine biosynthesis and glycerophospholipid metabolism were differentially expressed across these tissues.13C-glucose infusions revealed differential labelling patterns in thymoma compared to benign cysts and normal thymus tissue. The lactate/3PG labelling ratio, a metabolic marker in aggressive lung tumours correlated with lactate uptake, was increased in thymomas (1.579) compared to normal thymus (0.945) and benign masses (0.807) (thymic tissue versus tumour P = 0.021, tumour versus benign P = 0.013). CONCLUSIONS: We report metabolic biomarkers, including differential 13C labelling of metabolites from central metabolism, that distinguish thymomas from benign tissues. Altered glucose and lactate metabolism warrant further investigation and may provide novel therapeutic targets for thymoma.

GOOD SYNDROME: CYTOMEGALOVIRUS RETINITIS CASE CHALLENGE.

PURPOSE: To describe cytomegalovirus retinitis in a patient with Good syndrome (hypogammaglobulinemia and thymoma), ocular progression despite treatment and fatal outcome. METHODS: A 71-year-old woman with unilateral panuveitis of unknown cause and a history of thymoma resection was referred to the clinic. Visual acuity was 20/100 in her right eye and light perception in her left eye. In slit-lamp examination, the right eye had inferior, fine, pigmented keratic precipitates, 2+ anterior chamber cells, cataract, and 2+ vitreous cells, with no fundus detail and normal ocular ultrasound results. Left eye presented a white cataract, chronic hypotony, and increased choroidal thickness with calcifications. Laboratory evaluations showed normal or negative results for common causes of infection and inflammation. Prednisolone acetate eye drops were started, with improvement of AC inflammation. Cataract surgery was performed, reaching visual acuity of 20/30. Two years later, visual acuity had decreased and 2+ vitritis and retinitis were found. On clinical suspicion of masquerade syndrome, a vitrectomy biopsy was performed; pathologic assessments reported no data on ocular lymphoma. Leukopenia and lymphopenia were found: immunoglobulin levels, CD4 count, and viral load revealed systemic immunosuppression. The aqueous tap was positive for cytomegalovirus. Oral valganciclovir and intravitreal ganciclovir were initiated. RESULTS: In a patient with previous resection of thymoma and hypogammaglobulinemia, final diagnosis was Good syndrome, with cytomegalovirus retinitis being secondary to immunosuppression. Despite treatment, cytomegalovirus retinitis progressed and systemic deterioration resulted in mortal outcome. CONCLUSION: Good syndrome is an extremely rare disease, and association with cytomegalovirus retinitis is uncommon. To the authors' knowledge, only 14 cases exist in the literature.

Thymic epithelial tumours: histopathological classification and differential diagnosis.

The epithelial and lymphoid compartments of the thymus can give rise to a wide variety of tumours, including thymomas, thymic carcinomas, lymphoreticular proliferations, germ cell tumours, and sarcomas. While some of these have close similarity to their counterparts in other organs, both in terms of histology and immunohistochemistry, as well as molecular features, others are unique to the thymus. The epithelial tumours, which can develop in the thymus, will be discussed in this review, with a particular emphasis on resolving differential diagnosis by means of morphology, immunohistochemical profiles, and molecular diagnostics.

Disseminated thymoma in pleural fluid: An unusual case.

Thymic epithelial tumours show characteristic cytological features on fine-needle aspiration cytology, however the cytological features of thymoma in fluid cytology are not well described. We present the case of a 77 year-old-woman with known pleural dissemination of type B2/B3 thymoma presenting with shortness of breath and orthopnoea due to a pleural effusion. Cytological evaluation of the pleural fluid showed cellular smears composed of numerous small lymphocytes with small numbers of admixed mesothelial cells. There was no epithelial component. On immunohistochemical (IHC) staining the lymphocytes were T cells which were positive for CD3. CD1a and terminal deoxynucleotide transferase (TdT) were also positive, consistent with immature lymphocytes of thymic origin. Despite the lack of an epithelial component, this case was diagnosed as suspicious for recurrent/ metastatic thymoma. This is only the second published case of thymoma identified on pleural fluid cytology, and to our knowledge the first case describing thymoma in pleural fluid with no epithelial component, a potential pitfall with the more common differential diagnosis of a reactive lymphocytic effusion.

Unraveling the Natural History of Good's Syndrome: A Progressive Adult Combined Immunodeficiency.

BACKGROUND: Good's syndrome (GS) is a rare immune deficiency described almost 6 decades ago. Despite numerous published individual case reports and data collected in cross-sectional studies of small cohorts, the natural history and long-term outcomes of this disease remain unknown. OBJECTIVE: We aimed to determine the clinical and laboratory evolution of 8 adults diagnosed with GS and consecutively evaluated between 1983 and 2023. METHODS: In this prospective, longitudinal cohort study, newly diagnosed patients with GS were followed through repeated measures of clinical, immune, and hematologic changes, as well as targeted genetic screening. RESULTS: All patients reported a healthy childhood and adolescence with symptom onset during the third or fourth decade of life. All presented to our center with recurrent bacterial sinopulmonary infections, thymoma, hypogammaglobulinemia, and absence of B cells. The median age of GS diagnosis was 57 years. During follow-up, immunoglobin replacement therapy effectively minimized sinopulmonary infections. However, the majority experienced severe and systemic viral or fungal infections, 3 developed basal cell carcinomas, and 5 had progressive bronchiectasis and persistent splenomegaly. The most notable clinical feature was opportunistic infections and in vitro evidence of cellular immune deficiency, which resulted in the death of 2 individuals. We also report a statistically significant, multidecade progressive decline in lymphocytes, platelets, hemoglobin, and red blood cells in our cohort, suggesting gradual bone marrow failure. CONCLUSIONS: Knowledge of the unique phenotype and temporal evolution of GS has allowed us to develop a more comprehensive diagnostic framework. It can be investigated as part of broader research into disease pathophysiology.

A case report of dermatomyositis mimicking myasthenia gravis.

RATIONALE: Patients who have myasthenia gravis or dermatomyositis show clinical signs of muscular weakening. Ocular muscle involvement is uncommon, and symmetrical proximal limb weakness is the typical presentation of dermatomyositis. However, the earliest and most noticeable sign in those with myasthenia gravis is extraocular muscular paralysis. Dermatomyositis is frequently complicated by malignancy, and the common malignancies associated with dermatomyositis vary by region and ethnicity, while thymoma is relatively rare. About 10% to 15% of people with myasthenia gravis have thymoma, which is involved in the etiology of the disease. PATIENT CONCERNS: A 68-year-old female presented with ocular muscle weakness for 10 days that manifested as bilateral blepharoptosis with the phenomenon of "light in the morning and heavy in the evening." Imaging examination showed anterior mediastinal thymic tumor with metastasis. DIAGNOSES: After a thorough physical examination, we discovered bilateral upper limbs with grade IV muscle strength and the typical rash of dermatomyositis. In combination with elevated serum kinase levels and electromyography suggesting myogenic damage, the patient was finally diagnosed as dermatomyositis with multiple metastases of thymoma. INTERVENTIONS: The patient received oral hydroxychloroquine sulfate, topical corticosteroids, and tacrolimus ointment, but these did not work very well. Subsequently, the patient underwent surgery combined with radiotherapy for the thymoma. OUTCOMES: Muscle weakness in the patient improved after effective treatment of tumor, and the rash mostly disappeared. CONCLUSION: Ocular muscle weakness and thymoma are more common in myasthenia gravis, but we cannot ignore the possibility of dermatomyositis. To further establish the diagnosis, a thorough physical examination and laboratory findings are required. Further tumor screening should be performed for patients with dermatomyositis. Early detection and management of possible tumors are essential to the treatment of dermatomyositis linked to malignancies.

Spindle-cell thymoma colliding with a bronchogenic cyst in a Yorkshire terrier.

An 8-year-old male Yorkshire terrier was presented to the Tufts Veterinary Hospital for evaluation of increased respiratory effort. A mediastinal mass composed of a spindle-cell thymoma within a bronchogenic cyst was diagnosed with computed tomography thoracic imaging, ultrasound-guided fine-needle aspirate biopsy, and histopathologic evaluation after surgical removal. Histologic evaluation showed a multilocular cyst structure as well as a mass characterized by spindle to polygonal thymic epithelial cells. The cyst was characterized by a lining of ciliated pseudostratified respiratory epithelium. To the authors' knowledge, this is the first report of a spindle-cell thymoma being associated with a mediastinal bronchogenic cyst in a dog.

Adenoid cystic carcinoma of the thymus gland.

BACKGROUND: Thymic carcinomas are rare and aggressive tumours. They constitute a heterogeneous group of tumours with various histological patterns and subtypes resembling epithelial tumours arising from other organs. CASE PRESENTATION: We hereby represent a case of primary thymic carcinoma with adenoid cystic carcinoma-like features (TCACC) which is an extremely rare variant of thymic adenocarcinoma. To date and to the best of our knowledge, there are nine reported cases in literature and ours is the tenth. Our case was treated surgically but the implementation of adjuvant chemoradiotherapy has been reported in few of the published cases. CONCLUSIONS: TCACC constitutes a rare entity of thymic adenocarcinoma with limited available literature. The current data is derived from few case reports and case series. The histological overlap of these tumours and primary ACC of salivary glands poses a diagnostic challenge. Radiological investigations, immunohistochemical phenotyping and genetic analysis are crucial in establishing the diagnosis.

Primary Thymic Hodgkin Lymphoma Coexisting with Thymoma and Myasthenia Gravis: A Case Report.

BACKGROUND Myasthenia gravis is a neuromuscular disorder that is strongly associated with thymoma. Although the presence of myasthenia gravis with other tumors is uncommon, approximately 50% of patients with thymoma have myasthenia gravis. Thymic Hodgkin lymphoma should be considered due to the multiple reported cases of patients with myasthenia gravis and Hodgkin lymphoma. In this report, we present the case of 24-year-old woman with myasthenia gravis who was incidentally found to have coexisting thymoma with thymic Hodgkin lymphoma. CASE REPORT A 24-year-old woman with a known case of vitiligo presented with a 2-year history of diplopia and incidental anterior mediastinal mass. Following investigations, myasthenia gravis was diagnosed and managed by pyridostigmine, prednisolone, and azathioprine. Regarding the anterior mediastinal mass, thymoma was suspected based on the presence of myasthenia gravis and radiological findings. She underwent extended transsternal thymectomy. The final histopathological report of the dissected thymus disclosed Hodgkin lymphoma pathology coexisting with thymoma. After the diagnosis of Hodgkin lymphoma nodular sclerosis type IIA was confirmed, 6 cycles of chemotherapy were administered. Four years of follow-up revealed no evidence of Hodgkin lymphoma. However, her symptoms of myasthenia gravis persisted despite Hodgkin lymphoma remission. CONCLUSIONS There is an unclear association between myasthenia gravies and Hodgkin lymphoma. Prior reports revealed regression of myasthenia gravies following Hodgkin lymphoma management, which suggests that myasthenia could be a complication of Hodgkin lymphoma. However, in our case, myasthenia gravis persisted after Hodgkin lymphoma management; therefore, further studies are needed to explore this association.