Anticytokine autoantibody-associated immunodeficiency.

Anticytokine autoantibodies are an emerging mechanism of disease in previously healthy adults. Patients with these syndromes demonstrate a unique infectious phenotype associated with neutralizing autoantibodies that target a specific cytokine. Examples include anti-interferon (IFN)-γ autoantibodies and disseminated nontuberculous mycobacteria; anti-granulocyte macrophage colony-stimulating factor autoantibodies and cryptococcal meningitis; anti-interleukin (IL)-6 autoantibodies and staphylococcal skin infection; and anti-IL-17A, anti-IL-17F, or anti-IL-22 autoantibodies and mucocutaneous candidiasis in the setting of either APECED (autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy syndrome) or thymoma. Other anticytokine autoantibodies may contribute to an infectious phenotype such as anti-granulocyte colony stimulating factor and anti-IFN-α autoantibodies, although the strength of the association is less clear. Their identification not only affects disease management but also may uncover key mechanisms of host defense against specific organisms. Furthermore, it raises the possibility that currently idiopathic diseases will someday be explained by a yet unidentified anticytokine autoantibody. This review focuses on the current understanding, both clinical and mechanistic, of anticytokine autoantibody-associated immunodeficiency.

DNA methylation as a new tool for the differential diagnosis between T-LBL and lymphocyte-rich thymoma.

T-lymphoblastic lymphoma (T-LBL) and thymoma are two rare primary tumors of the thymus deriving either from T-cell precursors or from thymic epithelial cells, respectively. Some thymoma subtypes (AB, B1, and B2) display numerous reactive terminal deoxynucleotidyl transferase-positive (TdT+) T-cell precursors masking epithelial tumor cells. Therefore, the differential diagnosis between T-LBL and TdT+ T-lymphocyte-rich thymoma could be challenging, especially in the case of needle biopsy. To distinguish between T-LBL and thymoma-associated lymphoid proliferations, we analyzed the global DNA methylation using two different technologies, namely MeDIP array and EPIC array, in independent samples series [17 T-LBLs compared with one TdT+ lymphocyte-rich thymoma (B1 subtype) and three normal thymi, and seven lymphocyte-rich thymomas compared with 24 T-LBLs, respectively]. In unsupervised principal component analysis (PCA), T-LBL and thymoma samples clustered separately. We identified differentially methylated regions (DMRs) using MeDIP-array and EPIC-array datasets and nine overlapping genes between the two datasets considering the top 100 DMRs including ZIC1, TSHZ2, CDC42BPB, RBM24, C10orf53, and MACROD2. In order to explore the DNA methylation profiles in larger series, we defined a classifier based on these six differentially methylated gene promoters, developed an MS-MLPA assay, and demonstrated a significant differential methylation between thymomas (hypomethylated; n = 48) and T-LBLs (hypermethylated; n = 54) (methylation ratio median 0.03 versus 0.66, respectively; p < 0.0001), with MACROD2 methylation status the most discriminating. Using a machine learning strategy, we built a prediction model trained with the EPIC-array dataset and defined a cumulative score taking into account the weight of each feature. A score above or equal to 0.4 was predictive of T-LBL and conversely. Applied to the MS-MLPA dataset, this prediction model accurately predicted diagnoses of T-LBL and thymoma. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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.

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.

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 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.

Multiple Postoperative Lung Infections after Thymoma Surgery Diagnosed as Nontuberculous Mycobacterial Infection.

BACKGROUND: Thymomas are thymic epithelial-derived, most common primary anterior mediastinal masses. Non-tuberculous mycobacteria (NTM) are species that do not cause leprosy and belong to species outside the Mycobacterium tuberculosis complex. METHODS: With the clinical application of targeted next-generation sequencing (tNGS), we promptly confirmed a case of NTM infection combined with NTM infection after thymoma surgery, and we performed a joint literature analysis of the two diseases to improve clinicians' understanding and recognition of lung infections after thymoma surgery. RESULTS: Chest CT of both lungs showed multiple hyperdense shadows. Sputum bacterial culture and characterization detected Neisseria Dryad and Streptococcus Grass Green. The presence of Mycobacterium abscessus infection was confirmed by alveolar lavage fluid sent for second-generation macro gene sequencing. CONCLUSIONS: The body's immune function decreases after thymoma surgery. When empirical anti-infection treatment for recurrent pneumonia in the lungs is ineffective, we should be alerted to the possibility of the presence of pulmonary non-tuberculous mycobacterial infection, and next-generation sequencing should be performed promptly to arrive quickly at a diagnosis.

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.

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.

[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.

Proteomic analysis identifies argininosuccinate synthetase 1 and special AT-rich sequence binding protein 1 as reliable markers for the immunohistochemical distinction between WHO types A and B3 thymomas.

AIMS: The reliable classification of type A versus type B3 thymomas has prognostic and therapeutic relevance, but can be problematic due to considerably overlapping morphology. No immunohistochemical markers aiding in this distinction have been published so far. METHODS AND RESULTS: We identified and quantified numerous differentially expressed proteins using an unbiased proteomic screen by mass spectrometry in pooled protein lysates from three type A and three type B3 thymomas. From these, candidates were validated in a larger series of paraffin-embedded type A and B3 thymomas. We identified argininosuccinate synthetase 1 (ASS1) and special AT-rich sequence binding protein 1 (SATB1) as highly discriminatory between 34 type A and 20 type B3 thymomas (94% sensitivity, 98% specificity and 96% accuracy). Although not the focus of this study, the same markers also proved helpful in the diagnosis of type AB (n = 14), B1 (n = 4) and B2 thymomas (n = 10). CONCLUSIONS: Mutually exclusive epithelial expression of ASS1 in 100% of type B3 thymomas and ectopic nuclear expression of SATB1 in 92% of type A thymomas support the distinction between type A and type B3 thymomas with 94% sensitivity, 98% specificity and 96% accuracy.

Loss of YAP1 C-terminus expression as an ancillary marker for metaplastic thymoma: a potential pitfall in detecting YAP1::MAML2 gene rearrangement.

AIMS: Metaplastic thymoma is a rare thymic tumour characterized by Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) gene fusions resulting from an intrachromosomal inversion of chromosome 11. Immunohistochemistry with an antibody directed against the C-terminus of YAP1 has shown loss of expression in YAP1-rearranged vascular neoplasms, poromas, and porocarcinomas. This study aimed to validate an anti-YAP1 C-terminal antibody as an ancillary immunohistochemical marker for the diagnosis of metaplastic thymoma. MATERIALS AND METHODS: Ten metaplastic thymomas were selected for the current study. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed to detect YAP1::MAML2 fusions. We then performed immunohistochemistry to detect YAP1 C-terminus expression in 10 metaplastic thymomas, 50 conventional thymomas (10 each of type A thymoma, type AB thymoma, type B1 thymoma, type B2 thymoma, and type B3 thymoma) and seven thymic carcinomas. RESULTS: All 10 cases showed narrow split signals with a distance of nearly two signal diameters and sometimes had false-negative results in YAP1 and MAML2 break-apart FISH (BA-FISH). Abnormal colocalized signals of the YAP1::MAML2 fusion were observed in all 10 cases using fusion FISH (F-FISH) assays. Eight of 10 cases with adequate nucleic acids were successfully sequenced and all showed YAP1::MAML2 fusions; in two cases the fusions were detected by both DNA and RNA sequencing and in six cases by RNA sequencing only. YAP1::MAML2 fusion transcripts were identified in four cases by RT-PCR. Metaplastic thymoma showed loss of YAP1 C-terminus expression in all 10 (100%) cases. All other thymic neoplasms showed retained YAP1 C-terminus expression. CONCLUSION: YAP1 C-terminus immunohistochemistry is a highly sensitive and specific ancillary marker that distinguishes metaplastic thymoma from its mimics. BA-FISH assays could not effectively detect YAP1::MAML2 fusions due to the proximity of the two genes. Loss of YAP1 C-terminus expression is a reliable surrogate for the detection of YAP1::MAML2 fusions in metaplastic thymoma.

Ultrahigh-performance liquid chromatography-high-resolution mass spectrometry-based plasma metabolomics study of thymoma and thymic hyperplasia.

RATIONALE: Thymoma is a rare malignant tumor but it is the most common primary tumor of the anterior mediastinum. The current imaging methods for thymoma screening suffer from false positive rate problems, and thymoma pathogenesis remains elusive. Study of thymoma metabolic characteristics could provide clues for improving the diagnosis and understanding the pathogenesis of thymoma. METHODS: Metabolic profiling of plasma from thymoma and thymic hyperplasia patients was performed using ultrahigh-performance liquid chromatography combined with high-resolution mass spectrometry in both positive and negative ionization modes. After pre- and post-processing, the dataset was divided into three age groups and statistical analysis was performed to select differential metabolites of thymoma. For feature identification, experimental tandem mass spectra were matched to those of databases and available chemical standards, and also manually annotated with plausible chemical structures to ensure high identification confidence. RESULTS: A total of 47 differential metabolites were identified in thymoma. Significantly higher levels of histidine, sphinganine 1-phosphate, lactic acid dimer, phenylacetylglutamine, LPC (18:3) and LPC (16:1), and significantly lower levels of phenylalanine, indole-3-propionic acid (IPA), hippuric acid and mesobilirubinogen were associated with thymoma. Tryptophan level in thymoma-associated myasthenia gravis (TAMG) was significantly lower than that of the MG(-) group. IPA and hippuric acid abundances exhibited increasing trends from indolent to aggressive thymoma. CONCLUSIONS: Our study revealed aberrant aromatic amino acid metabolism and fatty acid oxidation might be associated with thymoma. The identified unique metabolic characteristics of thymoma may provide valuable information for study of the molecular mechanism of thymoma pathogenesis, and improvement of diagnosis and discovery of new therapeutic strategies for thymoma.

Intrathyroid thymic carcinoma: A clinicopathological analysis of 22 cases.

OBJECTIVE: Intrathyroid thymic carcinoma (ITTC) is a rare malignancy. The current understanding of ITTC is inadequate, and there is no standard treatment for ITTC. In the present study, we aimed to explore the clinicopathological characteristics of ITTC and identify potential therapeutic targets. METHODS: The clinicopathological characteristics of 22 ITTC patients at our institution were reviewed. The expression of DNA mismatch repair (MMR) proteins and PD-L1 in ITTC were assessed by immunohistochemistry (IHC). RESULTS: All patients underwent surgery. There were nine females and 13 males, with a slight male predominance. Their ages ranged from 42 to 79 years (average, 54. 1 years). The diameters of the neck masses ranged from 10 to 100 mm (average, 39 mm). Ipsilateral lymph node (LN) dissection was performed in 18 patients: 12 demonstrated LN metastasis, six showed no LN metastasis, and no lymph nodes were dissected in four. One patient had liver metastasis. CK5/6, P63, CD5, and CD117 were expressed in all cases. All cases were negative for TTF1, PAX8, thyroglobulin, and BRAF V600E. DNA MMR protein expression was retained in all tested tumors, and EBV-encoded small RNA (EBER) in situ hybridization was consistently negative. The Ki67 proliferation index ranged from 10 to 70 %. All patients were followed-up for 14-134 months, four died, six were lost to follow-up, and the remaining patients survived without disease. The PD-L1 combined positive score ranged from 10 to 80 (average: 40). CONCLUSION: Our results confirm that CD5 and CD117 co-expression support a diagnosis of ITTC. All tumors in this cohort were DNA MMR-proficient and were not associated with Epstein-Barr virus (EBV) infection. A high CPS for PD-L1 suggests that immune checkpoint inhibitor therapy may be worthy of further exploration in patients with ITTC.

An unusual cause of diarrhea and colorectal ulcers.

Good syndrome (GS) is a rare entity that associates the existence of thymoma with immunodeficiency. Gastrointestinal symptoms is one of the most common clinical manifestations. However, colorectal ulcers in GS were extremely rare. Herein, we present a case of GS presenting with diarrhea and colorectal ulcers to inform readers.

Isaacs' syndrome as the initial presentation of malignant thymoma and associated with double-positive voltage-gated potassium channel complex antibodies, a case report.

BACKGROUND: Isaacs' syndrome is a peripheral nerve hyperexcitability (PNH) syndrome due to peripheral motor nerve instability. Acquired Isaacs' syndrome is recognized as a paraneoplastic autoimmune disease with possible pathogenic voltage-gated potassium channel (VGKC) complex antibodies. However, the longitudinal correlation between clinical symptoms, VGKC antibodies level, and drug response is still unclear. CASE PRESENTATION: A 45-year-old man had progressive four limbs soreness, muscle twitching, cramps, and pain 4 months before admission. Electromyography (EMG) studies showed myokymic discharges, neuromyotonia, and an incremental response in the high-rate (50 Hz) repetitive nerve stimulation (RNS) test. Isaacs' syndrome was diagnosed based on clinical presentations and EMG reports. Serum studies showed positive VGKC complex antibodies, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies. The acetylcholine receptor antibody was negative. Whole-body computed tomography (CT) and positron emission tomography revealed a mediastinal tumor with the great vessels encasement, right pleura, and diaphragm seeding. Biopsy confirmed a World Health Organization type B2 thymoma, with Masaoka stage IVa. His symptoms gradually improved and both LGI1 and CASPR2 antibodies titer became undetectable after concurrent chemoradiotherapy (CCRT) and high dose steroid treatment. However, his Isaacs' syndrome recurred after the steroid was reduced 5 months later. Follow-up chest CT showed probable thymoma progression. LGI1 antibody turned positive again while CASPR2 antibody remained undetectable. CONCLUSIONS: Our patient demonstrates that Isaacs' syndrome could be the initial and only neuromuscular manifestation of malignant thymoma. His Isaacs' syndrome is correlated well with the LGI1 antibody level. With an unresectable thymoma, long-term immunosuppressant therapy may be necessary for the management of Isaacs' syndrome in addition to CCRT for thymoma.

T-Lymphoblastic Leukemia/Lymphoma and Thymoma: A Case Report and Review of the Literature of a Rare Association.

The co-occurrence of thymoma and T-lymphoblastic lymphoma/leukemia is an extremely rare but previously reported association that poses a diagnostic and therapeutic challenge. We describe a 67-year-old patient with long-standing untreated B1 thymoma that presented with constitutional symptoms and a painless soft tissue mass on the right chest wall. Pathological analysis of the biopsy from the mass demonstrated T-lymphoblastic leukemia/lymphoma. The patient went through a complicated course, was refractory to several lines of therapy, and eventually underwent allogeneic hematopoietic stem cell transplantation in complete remission from a matched related donor. The association between thymoma and malignant neoplasms has been described in the literature, most notably with colorectal adenocarcinoma and thyroid cancer. Thymoma-associated leukemia is, however, extremely unusual, with limited reports in the literature. Distinguishing between thymoma and leukemia can be challenging and often requires meticulous diagnostic efforts. For patients with a past history of thymoma, awareness of this particular association should be bared in mind to allow earlier diagnosis and therapy.

Pretracheal ectopic thymoma: A diagnostic challenge in endobronchial ultrasound-guided transbronchial needle aspiration cytology.

Ectopic thymomas (ETs) are rare thymic neoplasms that arise from atypical anatomical sites and present a diagnostic challenge for clinicians as they can be mistaken for other pathological entities on fine needle aspiration (FNA) cytology.

Liver metastasis mimicking a liver cyst of a thymoma in a 38-year-old immunocompromised patient.

Cystic liver lesions (CLL) are common and, in the majority of cases, benign. However, the range of differential diagnoses of CLL is wide. A combination of medical history, blood test results, and imaging can help find the correct diagnosis. We report the case of a 38-year-old immunocompromised female patient with a history of thymectomy and postoperative radiation 3 years prior due to thymoma. Subsequently, the patient was referred to our department for clarification of a cystic liver lesion. During short-term follow-up, the lesion increased in size, and due to the contrast agent behavior in the ultrasound and MRI examination, the suspicion of a biliary cystadenocarcinoma was considered.Furthermore, imaging showed several subcentimetric liver lesions of unknown dignity. Finally, pericystectomy and atypical partial liver resection was performed. Histology revealed a cystic metastasis of the malignant B3 thymoma and a cavernous hemangioma. Liver metastases of a thymoma are rare, and this is the first case of a cystic liver metastasis of a thymoma. The presented case illustrates that in the management of CLLs beside imaging techniques, the medical history with previous conditions should be considered, especially in past malignancies.

Spindle cell tumors of the mediastinum.

Spindle cell tumors originating in the mediastinum are extremely rare. Due to the profusion of structures and organs located in the mediastinum, a wide variety of spindle cell neoplastic processes can develop in this location. These include various different tumor types including epithelial, vascular, lipomatous, fibroblastic and neural tumors among others. Many of these different tumor types are associated with specific immunohistochemical and molecular genetic profiles that help differentiate them from each other. Although spindle cell morphology has traditionally been associated with mesenchymal neoplasms, in the mediastinum the most common spindle cell tumor is spindle cell thymoma, an epithelial rather than mesenchymal neoplasm. Except for neurogenic tumors originating in the posterior mediastinum, mesenchymal neoplasms are quite rare in mediastinal locations and require clinical correlation to rule out the possibility of a metastasis from an extra-mediastinal soft tissue or somatic sarcoma. Herein we will review the most common types of spindle cell neoplasms that occur in the mediastinum, with particular emphasis in their differential diagnosis and the role of ancillary techniques for diagnosis.