Lymphoepithelioma-like Thymic Carcinoma Research Articles

Successful multimodal treatment of stage IV lymphoepithelioma-like thymic carcinoma.

Successful multimodal treatment of stage IV lymphoepithelioma-like thymic carcinoma.

AB003. Circulating EBV (cEBV) and metabolic imaging monitoring during therapy for thymic lymphoepithelioma-like carcinoma (tLELC): a case study

: EBV association with the rare and usually fatal tLELC has been well documented, but not thoroughly studied, in the literature. A symptomatic 16-year-old boy was admitted for a locally advanced, inoperable EBV-associated tLELC. The diagnosis was established by appropriate immunohistology and RNA in-situ hybridization (ISH) for EBNA. The patient responded to induction combination chemotherapy followed by consolidation irradiation course given to the primary mediastinal lesion. Later, upon disease progression, he was enrolled to an immunotherapy (pembrolizumab) phase II clinical trial. Under this therapy, disease control was regained and lasted about 8 months. Treatment was discontinued, due to disease progression, after completion of 13 courses. Disease evaluation included serial circulating plasma EBV titer as well as concomitant 18F-FDG PET-CT scintigraphy/scanning. We attempt herein to compare how well the four different measurement modalities employed, namely-RECIST 1.1., active FDG-avid tumor volume, SUVmax and cEBV reflect the clinical course of disease and tumor burden changes. Among these, FDG-avid tumor volume apparently conforms better than conventional bi-dimentional CT-based RECIST 1.1 to the actual tumor burden and clinical course. Similarly, cEBV titer seems sensitive to various therapeutic intervention including irradiation. Furthermore, being a subclinical sensor, it could provide lead-time and herald overt disease progression. Albeit the entity presented, namely EBV-associated tLELC is extremely rare, certain conclusions obtained could, when properly modified, be applied in the management of more common conditions.

Total thymectomy for thymic lymphoepithelioma-like carcinoma\u2014report of two cases

BackgroundThymic carcinoma has been classified into 12 subtypes, thymic lymphoepithelioma-like carcinoma (LELC) is a type of them, and has a pathological organization similar to that of lymphoepithelioma, an undifferentiated type of nasopharyngeal carcinoma. According to a report from the International Thymic Malignancy Interest Group (ITMIG), thymic LELC is a rare tumor and accounts for 6% of all thymic carcinoma cases. We report two cases of surgical resection for thymic LELC and perform a search of other reports of thymic LELC, and clinical manifestations and follow-up data thus obtained are summarized.Case presentationTwo patients underwent surgical resection for thymic LELC. In both, tumors were detected in the anterior mediastinum and a total thymectomy was performed. Each was diagnosed with thymic LELC and classified in accordance with the Masaoka staging system as modified stage II. In recent examinations, one patient was doing well after undergoing total resection, whereas early recurrence of distant lymph node metastasis was noted in the other at 5 months after the total resection procedure and died thereafter from a different disease.ConclusionWe report two cases of surgical resection for thymic LELC. A successful total resection may positively affect prognosis: thus, long-term follow-up examinations must be performed.

Poorly Differentiated Nonkeratinizing Squamous Cell Carcinoma of the Thymus

Thymic carcinoma represents a rare and poorly understood type of thymic epithelial neoplasm that has been the subject of much controversy. Poorly differentiated nonkeratinizing squamous cell carcinoma, also known as lymphoepithelioma-like thymic carcinoma, is a rare variant of thymic carcinoma that has not been adequately characterized in the literature. The clinicopathologic, immunohistochemical, ultrastructural, and molecular features of 25 cases are reported. The patients were 19 men and 6 women, ranging in age from 20 to 85 years (mean: 60 y). The tumors presented clinically as anterior mediastinal masses with chest pain and shortness of breath or were found incidentally on imaging studies. Tumor size ranged from 2.0 to 13.5 cm in greatest diameter. Most of the tumors were small, well-circumscribed and confined to the mediastinum. Five cases presented with large, bulky, and infiltrative masses. Histologically, the hallmark of these tumors was a neoplastic proliferation of large, round to oval cells with vesicular nuclei, prominent eosinophilic nucleoli, and scant cytoplasm. Two histologic growth patterns were identified: tumors with a heavy lymphoplasmacytic stroma (lymphoepithelioma-like pattern), and tumors showing abundant desmoplastic stroma (desmoplastic pattern). Immunohistochemical stains showed strong positivity of the tumor cells for cytokeratin AE1/AE3, CK5/6, CK18, MOC31, p16, p40, and p63. MIB-1 showed on average 35% nuclear positivity. CD117 was positive in 21/25 cases and CD5 in 20/25 cases. Epstein-Barr encoded RNA in situ hybridization was positive in only 1 case. Electron microscopy in 4 cases showed primitive round to oval cells with prominent nucleoli, scant cytoplasm and immature cell junctions. Molecular features were studied by next-generation sequencing using high quality sequence data obtained from 18 patients. Variants with allele frequency between 5% and 45% and quality scores >50 were classified as somatic. A total of 16/18 cases had one or more somatic variants of unknown significance. One case showed an IDH1 p. R132C mutation, also of unknown significance. No "actionable" genes amenable to currently available targeted therapies were identified in this cohort. Clinical follow-up was obtained in 20 patients; 14 patients were alive and well with no evidence of disease between 1.5 and 16 years after diagnosis (median survival: 4 y; mean: 5.5 y). Most survivors had relatively small tumors (<5 cm. diameter), were in stage I and II at diagnosis and showed clear surgical margins. Five patients died of their tumors with metastases to bone, brain, chest wall, lungs and lymph nodes; all were in advanced stages and showed positive margins. Prognosis for these tumors appears to be correlated with the staging and status of the margins at the time of initial surgery.

A rare highly aggressive tumour: lymphoepithelioma-like thymic carcinoma

Lymphoepithelioma-likethymic carcinoma is a rare neoplasm that presents with compressive symptoms or as an incidental radiological finding of an anterior mediastinal mass. It is an aggressive carcinoma with a high...

Response to chemotherapy with carboplatin plus albumin-bound paclitaxel in a patient with lymphoepithelioma-like thymic carcinoma: A case report.

Thymic carcinoma is a rare neoplasm with a poor outcome due to its aggressive characteristics. For patients who are not operable, radiation therapy and/or palliative chemotherapy are indicated. However, no optimal chemotherapy regimen has been established. The present study reports the case of a 22-year-old man with advanced lymphoepithelioma-like thymic carcinoma refractory to conventional chemotherapy with carboplatin plus solvent-based paclitaxel (sb-PAC) treatment. The patient was subsequently treated with carboplatin plus nanoparticle albumin-bound paclitaxel (nab-PAC). The treatment resulted in a partial response following three cycles of chemotherapy. Since only grade 3 neutropenia, but no other severe adverse effects, was observed, no dose reduction was required. To the best of our knowledge, the current study is the first to present the response to chemotherapy with carboplatin plus nab-PAC in a patient with lymphoepithelioma-like thymic carcinoma. Considering that no standard treatment has been established in thymic carcinoma, nab-PAC may merit further investigation in this rare, but aggressive disease.

Clinical outcome of thymic lymphoepithelioma-like carcinoma: Case report of a 14-year-old male.

Thymic carcinoma is a rare type of cancer, which arises from the thymic epithelium and accounts for ~1–4% of anterior mediastinal tumors in the USA. It rarely occurs in children, and is rarer among adults. Thymic lymphoepithelioma-like carcinoma (LELC) is an uncommon subtype of thymic carcinoma in children, however, it is one of the common histological subtypes of thymic carcinoma in adults. In the present study, a 14-year-old male patient presented to the Tokyo Metropolitan Cancer and Infectious diseases Center, Komagome Hospital (Tokoyo, Japan) with chest pain due to a large anterior mediastinal mass. The patient was histologically diagnosed with thymic LELC via a needle biopsy specimen, which was obtained from the primary site and indicated the Epstein-Barr virus infection, whose markers are also associated with oncogenesis. Immunohistochemical analysis demonstrated positive staining for keratin (AE1/AE3), epithelial membrane antigen, and latent membrane protein-1 and negative staining for cluster of differentiation 5. Thus, the patient was diagnosed with metastatic thymic LELC. First-line chemotherapy comprising of a cisplatin- and adriamycin-based chemotherapy regimen achieved a partial response, however, the patient succumbed within 10 months of the initial diagnosis due to rapid disease progression and refractory to subsequent cycles of chemotherapy. Thus, the current study, as well as previously reported cases, demonstrates that pediatric patients with thymic LELC continue to have a poor prognosis.

Intrathyroidal epithelial thymoma/carcinoma showing thymus‐like differentiation; comparison with thymic lymphoepithelioma‐like carcinoma and a possibility of development from a multipotential stem cell

The purpose of our article is to describe the immunohistochemical findings of intrathyroidal epithelial thymoma/carcinoma showing thymus-like differentiation (ITET/CASTLE) of the thyroid in detail, to clarify the difference between ITET/CASTLE and thymic lymphoepithelioma-like carcinoma (LELC), and to discuss the pathogenesis of ITET/CASTLE. We immunohistochemically examined five ITET/CASTLE and eight LELC cases. All of ITET/CASTLE cases were strongly positive for CD5, P63, high-molecular-weight cytokeratin and B-cell CLL/lymphoma-2. Carcinoembryonic antigen-positive carcinoma cells were found in four ITET/CASTLE cases. Neuroendocrine marker-positive carcinoma cells were scattered in all cases. Immunohistochemical findings in thymic LELC were essentially similar to those in ITET/CASTLE, but the sensitivity was different. There is a possibility that ITET/CASTLE and thymic LELC are not the quite same disease entity. We think that ITET/CASTLE is derived from ectopic thymus, but not related to solid cell nests.

Epstein-Barr Virus (EBV) Associated Lymphoepithelioma-Like Thymic Carcinoma Associated With Paraneoplastic Syndrome of Polymyositis

Thymic carcinomas are rare neoplasms representing less than 1% of all thymic malignancies arising from thymic epithelium. Lymphoepithelioma-like thymic carcinoma is a high grade neoplasm with aggressive features and frequent metastasis. Association of lymphoepithelioma-like thymic carcinomas with Epstein-Barr virus was observed in several previously reported case reports. Paraneoplastic syndromes have been reported with lymphoepithelioma-like thymic carcinoma. We report a case of rare association of paraneoplastic syndrome of polymyositis with lymphoepithelioma-like thymic carcinoma. The case highlights generalized increase in fluoro-deoxy-glucose uptake in the skeletal muscles indicating biopsy proven polymyositis-a paraneoplastic syndrome.

Pathophysiological lessons from rare associations of immunological disorders

Rare associations of immunological disorders can often tell more than mice and rats about the pathogenesis of immunologically mediated human kidney disease. Cases of glomerular disease with thyroiditis and Graves’ disease and of minimal change disease with lymphoepithelioma-like thymic carcinoma and lymphomatoid papulosis were recently reported in Pediatric Nephrology. These rare associations can contribute to the unraveling of the pathogenesis of membranous nephropathy (MN) and minimal change disease (MCD) and lead to the testing of novel research hypotheses. In MN, the target antigen may be thyroglobulin or another thyroid-released antigen that becomes planted in the glomerulus, but other scenarios can be envisaged, including epitope spreading, polyreactivity of pathogenic antibodies, and dysregulation of T regulatory cells, leading to the production of a variety of auto-antibodies with different specificities [immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX syndrome)]. The occurrence of MCD with hemopathies supports the role of T cells in the pathogenesis of proteinuria, although the characteristics of those T cells remain to be established and the glomerular permeability factor(s) identified.

Lymphoepithelioma-like thymic carcinoma in a 16-year-old boy with nephrotic syndrome—a case report

Nephrotic syndrome can occur as a consequence of, among others, malignancy. In this report we describe a 16-year-old boy with secondary nephrotic syndrome associated with lymphoepithelioma-like thymic carcinoma, an extremely rare subtype ofthymic carcinoma with poor prognosis.

Thymic Lymphoepitheliomalike Carcinoma in Children: Clinicopathologic Features and Molecular Analysis

Thymic lymphoepitheliomalike carcinoma (LELC) in children is extremely rare and we report 2 such cases with molecular analysis of Epstein-Barr virus (EBV) and its encoded latent membrane protein-1 as well as a literature review. Both of our patients were male, presented with a huge anterior mediastinal mass, expired within a year after diagnosis despite treatment. There were altogether 9 cases of thymic LELC in children. Their common clinical features include a male predominance, large tumor size, advanced clinical stage, and poor clinical outcome. All cases were associated with EBV and nearly half developed concurrent hypertrophic osteoarthropathy (HOA). Thymic LELC in children is an aggressive EBV-associated malignant tumor frequently accompanied by HOA. We proposed that EBV might play a role in the development of HOA through the interactions of latent membrane protein-1, vascular endothelial growth factor, and cyclooxygenases-2.

Thymic carcinoma in children

Thymic epithelial neoplasms consist of thymomas, thymic carcinoids, and thymic carcinomas. Carcinomas are malignant tumors of the thymus characterized by obvious cytological anaplasia. They constitute only 4%-14% of thymic epithelial neoplams. Thymic carcinoma rarely occurs in children. Research in the English literature carried out for the present study revealed only 14 cases younger than 18 years-of-age. Here we have reported a 16-year old girl who presented with respiratory distress due to huge anterior mediastinal mass. Histological and immunohistochemical studies confirmed lymphoepithelioma-like thymic carcinoma. She received systemic chemotherapy and radiotherapy. However, she died within 15 months due to progressive disease.

Thymic Lymphoepithelioma-like Carcinoma Associated with Thymoma in a Patient with Ocular Myasthenia

A 65-year-old woman with ocular myasthenia was found to have three tumours in the anterior mediastinum, revealed by magnetic resonance imaging. All three lesions were radically resected. Histologically, one was a mixed-type thymoma, one a thymic lymphoepithelioma-like carcinoma, and the third had features of both these types. This appears to be the first reported case of coexisting thymic lymphoepithelioma-like carcinoma (TLC) and thymoma associated with ocular myasthenia.

Lack of Evidence of Pathogenetic Role of Epstein-Barr Virus in Thymic Lymphoid Hyperplasia and Thymomas in the Chinese Population of Hong Kong

A previous study from Hong Kong by McGuire et al. reported frequent demonstration of Epstein-Barr virus (EBV) DNA by Southern blot analysis in thymoma, thymic lymphoepithelioma-like carcinoma, and thymic lymphoid hyperplasia. This provoca tive finding, however, could not be confirmed by studies in the Western populations using the Southern blot technique and/or polymerase chain reaction to detect EBV- DNA or in situ hybridization to detect EBV encoded RNA (EBER), raising the possibility that the association with EBV may be restricted to Asians. This study was performed to clarify this issue by using a highly sensitive localization technique for EBER on a larger series from the Asian population of Hong Kong. Paraffin sections obtained from 10 cases of thymic lymphoid hyperplasia, 42 noninvasive thymomas (including one case previously reported to be EBV positive), 11 invasive thymomas, and 9 thymic carcinomas (including 5 cases of lymphoepithelioma-like carcinoma) were studied. EBER signal was not detected in the epithelial cells in any of the cases except for two cases of lymphoepithelioma-like carcinoma. In two thymomas, a few small lympho cytes (&lt;0.1%) were EBER positive. Failure to detect EBER was not an artifact due to RNA denaturation, because preserved mRNA could be demonstrated by oligo-dT labelling in 56 of the 72 cases. Thus, the results of this study on Hong Kong Chinese are in keeping with those reported in Caucasians, and more recently in Japanese and Taiwan Chinese, in that there is no association of EBV with thymic lymphoid hyperpla sia or thymoma, and that EBV may be demonstrated in a proportion of thymic lymph oepithelioma-like carcinomas. The positive results previously reported cannot be ex plained, because the occasional EBV-carrying lymphocytes detected in rare cases of thymoma should be insufficient to give a positive EBV result by Southern blot tech nique. Int J Surg Pathol 2(1):17-22, 1994

EBER‐1 expression in thymic carcinoma

The Epstein-Barr virus-encoded small nuclear RNA, EBER-1, has been shown to be a suitable target for the in situ hybridization detection of EBV in routinely processed tissue specimens. We evaluated the presence of EBV in thymic carcinoma and invasive thymoma using EBER-1 in situ hybridization on formalin-fixed paraffin-embedded tissue sections. EBER-1 expression was demonstrated in a case of lymphoepithelioma-like thymic carcinoma, but was not detectable in other thymic carcinomas including six squamous cell carcinomas, a clear cell carcinoma and seven invasive thymomas. As reported in three previous cases of EBV-associated thymic carcinoma, lymphoepithelioma-like thymic carcinoma was shown to be closely associated with EBV in our series.