Lymphocyte-Directed Immunomodulation Remits Thymoma-Associated Autoimmune Pneumonitis.

BACKGROUND: Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome. OBJECTIVES: To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation. METHODS: Two patients with thymoma were enrolled on IRB-approved protocols at the NIH Clinical Center. We performed history and physical examination; laboratory, radiographic, histologic and pulmonary function evaluations; and measurement of the lung-directed autoantibodies KCNRG and BPIFB1 prior to and at 1- and 6-months following initiation of lymphocyte-directed immunomodulation with azathioprine with or without rituximab. RESULTS: Combination T- and B-lymphocyte-directed immunomodulation resulted in improvement of clinical, functional, and radiographic parameters at 6-month follow-up evaluations in both patients with sustained remission up to 12-36 months following treatment initiation. CONCLUSION: Lymphocyte-directed immunomodulation remitted autoimmune pneumonitis in two patients with thymoma.

Ectopic cervical thymoma: a rare entity in the anterior neck.

Thymoma is a rare malignancy with usual location in the antero-superior mediastinum. Ectopic cervical thymoma (ECT) is an extremely rare tumor that originates from ectopic tissue, and is caused by the aberrant migration of the embryonic thymus. Our patient was a 56-year-old man who had a nodular lesion in the neck for several years. Computed tomography and Enhanced magnetic resonance imaging were performed. He underwent surgery, and a histological examination resulted in a diagnosis of type AB thymoma.

Ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis: a case report.

BACKGROUND: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis. CONCLUSION: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.

Intrathyroidal thymic carcinoma.

A young woman in her early 30s presented with a right thyroid mass and progressive hoarseness due to a right vocal cord palsy. The preoperative fine-needle aspiration cytology was classified as Bethesda V and she underwent a total thyroidectomy and neck dissection. Intraoperatively, the thyroid mass was adherent to the oesophagus, trachea and encasing the right recurrent laryngeal nerve which was sacrificed. Final histopathology diagnosed a rare subtype of thyroid cancer known as intrathyroidal thymic carcinoma (ITC). She was then sent for adjuvant radiotherapy after a multidisciplinary tumour board discussion. This case report highlights the difficulty in preoperative diagnosis of ITC and the importance of immunohistochemical staining in clinching the diagnosis. In view of its rarity, there have been no published consensus on the treatment of ITC, hence we would like to share some learning points through a comprehensive literature review.

Ectopic cervical thymoma in myasthenia gravis: a case report.

BACKGROUND: Ectopic cervical thymoma (ECT) is an extremely rare tumor, especially in association with myasthenia gravis (MG). CASE PRESENTATION: We report a case of myasthenia gravis with an ectopic thymoma in the neck, whose myasthenic symptoms significantly improved after complete removal of the mass. A 55-year-old woman with generalized myasthenia gravis (MG) experienced worsening neuromuscular weakness after abruptly discontinuing pyridostigmine. Testing revealed acetylcholine receptor-antibody (AChR-Ab) positivity and a cervical mass initially thought to be thyroid or parathyroid was identified as a thymoma, type A. Post-surgery and radiation therapy, her myasthenic symptoms improved significantly with less prednisone and pyridostigmine requirements over time and no need for additional immunotherapies. CONCLUSIONS: Diagnosing ECTs is challenging due to rarity, atypical locations, and inconclusive fine needle aspiration cytology (FNAC) results, often misinterpreted as thyroid or parathyroid lesions. As proper management of patients with MG, including thymectomy, offers favorable clinical outcomes such as significant improvement in myasthenic complaints and reduced immunosuppressive medication requirements, clinicians should be vigilant of the ectopic locations of thymomas to ensure timely diagnosis and intervention.

Thymic carcinoma presenting with overlap polyarthritis and myositis: A rare paraneoplastic syndrome in childhood.

Thymic tumors are very rare neoplasms in children and account for less than 1% of mediastinal tumors in pediatric patients. One-third of the pediatric patients present with symptoms related to the compression of the tumor mass on the surrounding anatomic structures, and paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, acquired hypogammaglobulinemia, and connective tissue disorders, which rarely occur in children with thymic tumors. Herein, we report a case of thymic carcinoma mimicking the symptoms of a connective tissue disease with symmetrical polyarthritis accompanying myositis, fever, weight loss, and malaise in a 15-year-old male patient. To our knowledge, this is the first case pediatric thymic carcinoma accompany with severe polyarthritis and myopathy, thus we have reviewed the current literature regarding the cases of thymic malignancies coexisting with paraneoplastic syndromes in children.

A case of thymoma presenting as pyrexia of unknown origin.

ABSTRACT: Pyrexia of unknown origin can be caused due to numerous infective and noninfective causes. It poses a diagnostic dilemma to the clinicians and requires a myriad of investigations for the confirmation of diagnosis. Thymomas are rare mediastinal tumors that present as anterior mediastinal mass; however, thymomas presenting as pyrexia of unknown origin has rarely been reported in the literature. We report an interesting case of a middle-aged male who presented as pyrexia of unknown origin due to thymoma.

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.

The Role of [18F]FDG PET/CT in the Characterization of Thymic Epithelial Tumors at Initial Stage.

Purpose: The aim of this study was to evaluate the potential role of [18F]FDG positron emission tomography/computed tomography (PET/CT) in the characterization of thymic epithelial tumors (TETs). Materials and Methods: A total of 73 patients who underwent preoperative [18F]FDG PET/CT were included in this study. Visual total score (VTS), maximum standard uptake values (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI) parameters were analyzed to investigate the prediction of histopathologic grade and advanced stage. Results: The cohort included 26 patients with low-grade thymoma (LGT), 36 patients with high-grade thymoma (HGT), and 11 patients with thymic carcinoma (TC). Ninety-one percent of TC had VTS >2, whereas 31% of LGT and 75% of HGT had VTS >2. SUVmax, MTV, and TLG were statistically significantly higher in the TC group than in both thymoma and HGT. Using the cutoff value of 7.25 for SUVmax, TC was differentiated from thymomas with 91% sensitivity and 74% specificity. TC had significantly lower HI values than thymomas. HI parameters showed good diagnostic ability to differentiate TC from thymoma and TC from HGT. SUVmax, MTV, and TLG were significantly higher in advanced-stage disease than in early-stage disease. Conclusions: Visual and quantitative parameters can reliably predict both advanced disease and the grade of primary tumor in TETs. Therefore, as a promising metabolic imaging method, [18F]FDG PET/CT makes important contributions to preoperative evaluation in routine clinical practice.

[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.

Practical methods to differentiate thymic malignancies by positron-emission tomography and tumor markers.

PURPOSE: An accurate diagnosis of thymic malignancies is important, but challenging due to the broad range of differential diagnoses. This study aims to evaluate the efficacy of PET/CT and tumor markers for diagnosing thymic malignancies. METHODS: Patients admitted to our department between January 2012 and December 2021 with primary anterior mediastinal tumors were retrospectively evaluated. We evaluated the relationship between the maximum standardized uptake value (SUVmax), tumor markers, and pathological diagnosis in four groups: thymic carcinoma, thymoma, lymphoma, and others. RESULTS: In total, 139 patients were included in this study. The SUVmax was significantly higher in lymphoma, thymic carcinoma, and thymoma, in that order. The cytokeratin 19 fragment (CYFRA 21-1) was significantly higher in thymic carcinoma than in the other groups. An ROC curve analysis indicated that the optimal cut-off values of SUVmax for thymic carcinoma plus lymphoma and CYFRA 21-1 for thymic carcinoma were 7.97 (AUC = 0.934) and 2.95 (AUC = 0.768), respectively. Using a combination of cut-off values (SUVmax = 8, CYFRA 21-1 = 3), the accuracy rate for diagnosing thymic carcinoma was 91.4%. CONCLUSIONS: The SUVmax and CYFRA 21-1 levels are significant indicators for the diagnosis of thymic carcinoma. Combining these indicators resulted in a more accurate diagnosis of thymic malignancies, which could facilitate the decision-making process for determining the optimal treatment strategies.

Intrathyroidal thymic carcinoma not so indolent a neoplasm?

ABSTRACT: Intrathyroidal thymic carcinoma (ITC) is a very rare malignant epithelial tumor of the thyroid gland with thymic epithelial differentiation. Here, we are reporting the case of an eighty-year-old man who at presentation had extrathyroidal spread to the larynx and metastasis to regional lymph nodes. Though the tumor had a relatively low-grade morphology, there were areas of high mitotic activity with areas of necrosis. The classically described ivory-white gross appearance of the tumor, histomorphology of thick bands dividing the tumor into lobules, squamous cell differentiation, tight whorls of cells resembling Hassall's corpuscle, and areas showing dense lymphocytic infiltration, together with an immunoprofile of CD5, Ckit, Tumor protein 63 (p63), and B-cell lymphoma 2 gene (bcl2) positivity, helped in diagnosing this rare entity. Though classically ITC is said to have a good prognosis, cases with spread to adjacent organs and lymph node metastasis may not have an indolent course.

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.

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?