Micronodular Thymic Carcinoma with Lymphoid Stroma: A Case Report
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Background. Micronodular thymic carcinoma (MTC) with lymphoid hyperplasia is believed to be the malignant counterpart of micronodular thymoma (MT) with lymphoid hyperplasia. Since MT and MTC share a similar morphology, MTC is considered a malignant form of MT; there have been a few malignant transformations from MT to MTC. We report a case of MTC with lymphoid hyperplasia. Case presentation. A 53-year-old woman presented with an incidental tumor on a chest X-ray. The resected tumor consisted of nodular epithelial nests and lymphoid tissue within a surrounding germinal center. Some epithelial nests showed apparent malignant morphology. Atypical epithelial cells with large vesicular nuclei formed nests, some of which showed comedo necrosis. These cells showed transition continuously to low-grade type B thymoma-like cells, demonstrating cord-like arrangements. Carcinomatous elements, expressed GLUT1, CD5, KIT, and BCL2; conversely, low-grade nests displayed attenuated expression of these markers. GTF2I point mutation and Langerhans/dendritic cells, which are indicators of favorable thymoma prognosis, were not detected. Due to pleural metastasis, the patient was treated with lenvatinib 27 months postoperatively. Conclusions. This is the first report of a partially low-grade, GTF2I-negative MTC. Histological and genetic findings might be predictive of tumor prognosis.Keywords:
Thymic carcinoma
Ectopic micronodular thymoma (MNT) is a rare tumor. We described a 76-year-old woman, who was referred to our institutional for a mass in the left cervical region. The Magnetic Resonance Imaging (MRI) scan showed a 3.7 cm × 1.7 cm × 2.0 cm mass. The neoplasm was composed of epithelial tumor cells arranged in a micronodular growth pattern set in a stroma showing lymphoid hyperplasia with germinal centers. Immunohistochemical studies showed that the neoplastic epithelial cells were reactive for AE1/AE3, CK5/6, P63, and the lymphoid component to be of mixed B- and immature T-cell lineage. Langerhans cells were confirmed within epithelial nodules for the first time with langerin, S-100, CD1a expression. We report a case of cervical ectopic MNT to emphasize the langerhans cells proliferation and the histopathologic features and differential diagnosis of the rare lesion to promote a better and broader understanding of this less understood subject.
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Lymphoid hyperplasia
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Herein, we report a case of micronodular thymoma with lymphoid stroma in a previously healthy 73-year-old male. Thymectomy was performed. The solid and macrocystic masses were encapsulated with focal invasion. The solid portion consisted of nodules of bland-looking spindle or round epithelial cells in lymphoid stroma containing prominent germinal centers. The epithelial cells had moderate amount of cytoplasm and occasional mucin production. The cystic portion was lined with cuboidal epithelium. According to World Health Organization (WHO) classification, the mass was diagnosed as a micronodular thymoma with lymphoid stroma accompanied by a pre-existing multilocular thymic cyst. Micronodular thymoma with lymphoid stroma, a possible variant of type A thymoma, is an extremely rare tumor. This so-called "unusual" variant may imply the schematic weakness of the current WHO classification that cannot cover all morphologic types. Further study is recommended for clarification of this variant and its incorporation into the current classification.
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Thymus Neoplasm
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Objective: To investigate the clinicopathologic features of micronodular thymoma with lymphoid stroma(MNT). Methods: Five cases of MNT diagnosed from January 2007 to December 2016 in Henan Provincial People's Hospital were collected.Hematoxylin-Eosin staining and immunohistochemistry were used to evaluate the histological and immunophenotypic characteristics in 5 MNT cases. Epstein-Barr virus (EBV) status was detected by in situ hybridization for EBV-encoded small RNA (EBER). Polymerase chain reaction was used to detect the rearrangement of immunoglobulin genes. Results: Five cases were MNT, including 3 male and 2 female patients, mean aged 59 years (from 43 to 63 years). All patients had ananterior mediastinal mass, with no myasthenia gravis and autoimmune diseases, and underwent surgical resection.Half to ten years follow-up showed no recurrence.Grossly, the tumors were solid in 4 cases, and cystic and solid in 1 case; the border was clear. Histologically, the tumors presented as a distribution of micronodules separated by abundant lymphoid stroma with prominent germinal centers. The nodules were composed of neoplastic spindle, oval cells containing bland, oval nuclei.Immunohistochemical study showed strong positivity of the tumor cells for CKpan, CK19, CK5/6 and p63. Stains for EMA, CD117, calretinin, TTF1 were negative in the tumor cells.Scattered CD3, CD1a, and TdT positive immature T lymphocytes were noted in and around tumor nodules. Many lymphocytes in the stroma, including germinal centers, were positive for CD20.The bcl-2 was also detected in lymphocytes in the stroma, mantle and marginal zone of lymphoid follicles, and in part of tumor cells. Tumor cells and lymphocytes were negative for EBER. Immunoglobulin genes rearrangement analysis showed that B lymphocytes were polyclonal. Conclusions: MNT is a rare thymoma, which occurs in the elderly and has no obvious symptom. After complete resection, the prognosis is very good. The diagnosis should be based on a combination of clinicopathologic features, and other types of thymoma should be excluded.目的： 探讨伴淋巴样间质的微结节型胸腺瘤(MNT)临床病理学特点。 方法： 收集河南省人民医院2007年1月至2016年12月诊断的5例MNT的患者资料，采用HE染色、免疫组织化学EnVision法染色观察组织形态特征及免疫表型情况，EB病毒编码小RNA(EBER)原位杂交检测EB病毒感染情况，PCR法检测免疫球蛋白(Ig)基因重排，并对患者进行随访。 结果： 5例MNT患者平均年龄59(43～63)岁，男性3例，女性2例，均为前纵隔占位性病变，均无重症肌无力、自身免疫疾病，均行手术切除，术后随访0.5～10.0年，均未见复发。肿物4例实性，1例囊实性，边界较清，局部有包膜。上皮样瘤细胞呈微结节状分布，形态温和，间质见丰富的淋巴细胞及淋巴滤泡。瘤细胞广谱细胞角蛋白(CK)、CK19、CK5/6、p63阳性，CD117、钙网膜蛋白、甲状腺转录因子1、上皮细胞膜抗原阴性；肿瘤结节内及周边见个别CD3、CD1a、末端脱氧核苷酸转移酶阳性的不成熟T细胞，间质大量CD20阳性的B细胞，套区、边缘区及部分肿瘤细胞bcl-2阳性，肿瘤细胞及淋巴细胞EBER均阴性。Ig基因重排检测提示B细胞为多克隆增生。 结论： MNT是一种罕见的胸腺瘤，好发于中老年人，无明显症状，完整切除后，预后良好，诊断需结合临床及病理，排除其他类型的胸腺瘤。.
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Background. Micronodular thymic carcinoma (MTC) with lymphoid hyperplasia is believed to be the malignant counterpart of micronodular thymoma (MT) with lymphoid hyperplasia. Since MT and MTC share a similar morphology, MTC is considered a malignant form of MT; there have been a few malignant transformations from MT to MTC. We report a case of MTC with lymphoid hyperplasia. Case presentation. A 53-year-old woman presented with an incidental tumor on a chest X-ray. The resected tumor consisted of nodular epithelial nests and lymphoid tissue within a surrounding germinal center. Some epithelial nests showed apparent malignant morphology. Atypical epithelial cells with large vesicular nuclei formed nests, some of which showed comedo necrosis. These cells showed transition continuously to low-grade type B thymoma-like cells, demonstrating cord-like arrangements. Carcinomatous elements, expressed GLUT1, CD5, KIT, and BCL2; conversely, low-grade nests displayed attenuated expression of these markers. GTF2I point mutation and Langerhans/dendritic cells, which are indicators of favorable thymoma prognosis, were not detected. Due to pleural metastasis, the patient was treated with lenvatinib 27 months postoperatively. Conclusions. This is the first report of a partially low-grade, GTF2I-negative MTC. Histological and genetic findings might be predictive of tumor prognosis.
Thymic carcinoma
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Aim To elucidate the clinicopathological and immunohistochemical characteristics of micronodular thymomas (MNTs) and micronodular thymic carcinomas (MNCs) with lymphoid stroma. Methods We examined four cases of MNTs and three cases of MNCs pathologically and immunohistochemically. Results There were prominent cystic changes infive of the seven cases. The neoplasms contained epithelial tumour cells arranged in a micronodular growth pattern lined by cystic walls and separated by abundant lymphoid stroma. Only the tumour cell component of MNCs showed signs of malignancy characterised by cytological atypia and increased mitotic activity. Neoplastic MNC epithelial cells showed strong positivity for CD5 and CD117. However, no immature lymphocytes (TdT-positive and CD99-positive) were present in and around the tumour nodules. None of the patients died or suffered from disease due to MNTs or MNCs. Conclusion MNTs and MNCs are rare and less aggressive forms of thymic tumours and can be differentially diagnosed by immunohistochemistry.
Thymic carcinoma
CD117
CD5
Atypia
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Mantle zone
Reticular fiber
Hematopathology
Parenchyma
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Micronodular thymoma with lymphoid stroma (MNT) is a rare subtype of organoid thymic epithelial tumor that occurs in middle-aged and elderly people. Histologically, MNT is characterized by multiple epithelial nodules that are scattered or fused and abundant lymphocyte stroma with prominent germinal centers. It has a benign course and a good prognosis, and its diagnosis mainly depends on histopathologic and immunohistochemical markers. This article reports two cases of MNT to explore its clinicopathologic features, diagnosis and differential diagnosis to improve understanding of this subtype. In addition, we review previously reported cases of MNT.
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The spectrum of micronodular thymic epithelial tumours with lymphoid B‐cell hyperplasia Aims : A rare type of thymoma, micronodular thymoma with lymphoid B‐cell hyperplasia, was recently reported by Suster and Moran. Thymic epithelial tumours with a similar pattern but with varied cytological features of the tumour cells are analysed. Methods and results : A total of 11 cases of thymic epithelial tumours characterized by micronodular proliferation of tumour cells separated by abundant lymphoid stroma with prominent germinal centres were reviewed clinicopathologically and examined immunohistochemically. The presence of Epstein–Barr virus (EBV) genome was also examined by in‐situ hybridization. Based on the morphology of tumour epithelial cells, cases were subdivided into four groups: group 1 (two cases) having spindle epithelial cells; group 2 (two cases) showing an admixture of spindle and polygonal epithelial cells; group 3 (five cases) having polygonal epithelial cells, with mild to moderate cytological atypia in four cases, and group 4 (two cases) representing lymphoepithelioma‐like carcinoma. The degree of cytological atypia and the number of tumour cells positive for MIB‐1 and p53 gradually increased towards group 4. The abundant lymphoid stroma in all cases contained many CD20‐positive B‐cells and CD3 and CD45RO‐positive T‐cells. CD99‐positive immature T‐cells were present in all cases of groups 1 and 2 and in most cases of group 3, but not in both cases of group 4 tumours. IgG, IgM and IgD‐positive plasma cells and lymphocytes were also present in all cases, more prominent in those of groups 3 and 4. The EBV genome was detected in only a few lymphocytes in five cases. Conclusions : The tumours in this series belong to a distinct category of thymic epithelial tumours and each of the above groups may constitute a spectrum in the continuum of cytological atypia. The aetiological relationship of EBV with these tumours could not be proved. The lymphoid B‐cell hyperplasia may result from a host immune response and may suggest a favourable clinical course of this type of tumour.
Lymphoid hyperplasia
Atypia
Thymic carcinoma
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