Constant p.L424H Mutation in GTF2I in Micronodular Thymomas With Lymphoid Stroma: Evidence Supporting Close Relationship With Type A and AB Thymomas.

Micronodular thymoma with lymphoid stroma is a rare thymic neoplasm characterized by discrete nodules of epithelial tumor cells separated by abundant lymphoid stroma. The genetic features of micronodular thymoma with lymphoid stroma remain largely unexplored. Owing to the interference of abundant intratumoral, nonneoplastic lymphoid cells, a highly sensitive approach is necessary to study genetic changes in these tumors. In this study, we used a highly sensitive next-generation sequencing assay using the molecular barcoding Ion AmpliSeq HD technology to study the most commonly mutated genes in thymomas, including GTF2I, HRAS, NRAS, KRAS, and TP53. A total of 12 cases of micronodular thymomas with lymphoid stroma were tested, and 2 cases also had areas of type A thymoma in their tumor bed. Two micronodular thymic carcinomas with lymphoid stroma, a histological mimic of micronodular thymoma, were also included for comparison. Recurrent p.L424H mutations in GTF2I were found in all the cases of micronodular thymoma with lymphoid stroma but not in the cases of micronodular thymic carcinomas. In addition, 3 cases of micronodular thymoma with lymphoid stroma also had concomitant HRAS and/or KRAS mutations. Our study showed that p.L424H mutations in GTF2I is a constant genetic feature of micronodular thymoma with lymphoid stroma. This finding strongly suggests that micronodular thymoma with lymphoid stroma is closely related to type A and AB thymomas because they all share p.L424H mutations in GTF2I.

Micronodular Thymic Carcinoma with Lymphoid Stroma: A Case Report.

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.

Two Thymomas of Different Histological Subtypes Arising in a Giant Thymolipoma: Case Report and Review of the Literature.

Thymolipoma is a rare benign tumor of the anterior mediastinum. Only a few reports describing thymoma arising within a thymolipoma have been documented in the literature. We report herein a detailed description of thymolipoma giving rise to 2 thymomas of different histological subtypes. A 74-year-old male with history of metastatic papillary thyroid carcinoma gradually developed 2 soft tissue nodules within a large right hemithorax fatty mass that was present for the past 20 years. Computed tomography (CT)-guided needle biopsy revealed one of the soft tissue nodules to be a thymoma, and the entire mass was surgically resected. Final pathological examination demonstrated the mass to be a thymolipoma containing a micronodular thymoma with lymphoid stroma as well as a WHO type B1 thymoma. No evidence of disease recurrence was seen at the time of his 7-year follow-up. This case documents a rare presentation of thymolipoma harboring 2 thymomas of different histological subtypes and highlights the need for early surgical resection of thymolipomas, as they may harbor malignant nodules.

Micronodular Thymoma with Lymphoid Stroma: A Mediastinal Mass Masquerading as a Pericardial Mass.

A 61-year-old man presented to the emergency room with lower extremity edema. Physical exam was only remarkable for a diastolic murmur in the right carotid area and left lower extremity edema. Venous Doppler revealed a deep venous thrombosis in the left lower extremity. Chest computed tomography (CT) with intravenous contrast ruled out pulmonary embolism but showed a mediastinal mass adjacent to the pericardium. Further imaging with cardiac magnetic resonance imaging (CMR) and cardiac CT angiography (CCTA) enabled localization and evaluation of the structural characteristics of the mass. The decision was made to excise the mass due to increasing size compared with its measurements on prior chest CTs and a high degree of vascularization seen on CMR and CCTA, which was concerning for an enlarging arteriovenous malformation or a hemangioma. However, histopathologic analysis of the mass revealed it to be a micronodular thymoma.

Difference in the distribution of tumor-infiltrating CD8+ T cells and FOXP3+ T cells between micronodular thymoma with lymphoid stroma and micronodular thymic carcinoma with lymphoid stroma.

Micronodular thymoma with lymphoid stroma (MNT) is a rare thymic epithelial neoplasm subtype characterized by a micronodular tumor cell growth pattern and abundant lymphoid stroma. Micronodular thymic carcinoma with lymphoid stroma (MNCA) is considered as a malignant counterpart of MNT and exhibits a growth pattern similar to that of MNT but has histologic features reminiscent of thymic squamous cell carcinoma, such as cytologic atypia and CD5 and CD117 immunoexpression. Although both MNT and MNCA are characterized by abundant lymphoid stroma, it remains unknown whether there are differences in infiltrating lymphocytes between MNT and MNCA. We analyzed the immune microenvironment profile in eight MNT and three MNCA cases. The cell density of CD8-positive T cells was significantly higher in MNT than in MNCA, whereas that of FOXP3-positive T cells was significantly higher in MNCA than in MNT. There was no significant difference in the cell density of programmed death protein 1-positive T cells and programmed death ligand 1 expression between the MNT and MNCA cases. Our findings indicated that the immune microenvironment of MNCA differed from that of MNT and, compared with the T-cell profile of MNT, that of MNCA was more suppressive to patients' antitumor immune response.

Surgical treatment of micronodular thymoma with lymphoid stroma.

This case was about a 71-year-old man presented to our clinic for an anterior mediastinal mass found on routine chest computed tomography (CT). CT scan showed a lobulating contoured mass in the anterior mediastinum. A preliminary diagnosis was thymoma. The patient underwent subxiphoid uniportal video-assisted thoracoscopic surgery for the extended thymectomy and complete excision of the tumour. The pathological examination showed a micronodular thymoma with lymphoid stroma (MTWLS). In conclusion, this report described an extremely rare tumour, MTWLS, and MTWLS might be considered in the differential diagnosis of mediastinal tumour, especially thymoma.

Micronodular thymic tumor with lymphoid stroma: A case report and review of the literature.

BACKGROUND: Micronodular thymic tumors with lymphoid stroma include micronodular thymoma with lymphoid stroma (MNT) and micronodular thymic carcinoma with lymphoid hyperplasia (MNC), whose micromorphological features are lymphoid stromal hyperplasia and nodular arrangement of tumor epithelial cells. This type of tumor is rare; therefore, the corresponding clinical guidelines, histopathological diagnostic criteria, prognostic factors, and therapeutic regimens have not been established. CASE SUMMARY: This study covers a novel presentation of MNC in a patient and summarizes the clinicopathological characteristics of this type of tumor by using pooled-analysis methods. Morphologically, this tumor type is a series of benign to malignant pedigrees. We establish the following criteria for the classification of micronodular thymic tumors with lymphoid stroma: (1) Tumor cells with moderate-to-severe dysplasia; (2) Tumor cell mitotic figures > 2/10 high-power fields; (3) Appearance of neoplastic necrosis; (4) No terminal deoxynucleotidyl transferase-positive immature T lymphocytes within the tumor; (5) Tumor cells with a Ki-67 index ≥ 10%; and (6) Tumor cells express CD5. Cases that fall into the borders of two categories in terms of morphology are attributed to atypical MNT. It is proposed that the diagnosis of MNT should be established on the diagnostic criteria mentioned above. CONCLUSION: Our diagnostic algorithm can effectively distinguish malignant tumors from benign tumors and provides a potent basis for predicting a prognosis, which offers a practical reference for oncologists and pathologists.

Micronodular thymoma with lymphoid stroma diagnosed 10 years after the first operation: a case report.

INTRODUCTION: Micronodular thymoma with lymphoid stroma is a rare subtype of thymoma. Here we report a case of micronodular thymoma with lymphoid stroma that was completely resected after incomplete resection 10 years earlier. CASE PRESENTATION: A 70-year-old Japanese woman who had undergone resection for a thymic cyst 10 years earlier was found to have a solid nodule with a multilocular lesion at the site of the previous operation. We suspected that the tumor was a malignant tumor and performed trans-sternal radical thymectomy and diagnosed the lesion as micronodular thymoma with lymphoid stroma pathologically. When we reassessed the thymic cyst that had been resected 10 years earlier, a few lesions of micronodular thymoma with lymphoid stroma were found in the cyst wall. Based on these findings, we concluded that only the cystic component of micronodular thymoma with lymphoid stroma had been removed, and that the residual lesion grew locally over the next 10 years before being completely resected by reoperation. CONCLUSION: We experienced an unusual case of micronodular thymoma with lymphoid stroma, which is a rare subtype of thymoma. Greater care should be taken to exclude a thymoma with a cystic lesion, even if a thymic cyst is strongly suspected on computed tomography and magnetic resonance imaging.

Micronodular thymoma with lymphoid stroma: report of two cases and review of literature.

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.

Micronodular thymoma with lymphoid stroma: Two cases, one in a multilocular thymic cyst, and literature review.

Micronodular thymoma with lymphoid stroma (MTWLS) is a rare type of thymoma that shows a similar pattern but varied morphology and immunophenotype of tumor cells. Because of the extremely limited number of cases reported, the pathology and biology of MTWLS are equivocal. Herein, we report two cases located in the anterior mediastinum: Case 1: a 58-year-old woman with a cystic mass measuring 5 × 3.0 × 2.5 cm in Mosaoka stage I; and Case 2: a 50-year-old man with a solid mass measuring 2.5 × 2.5 × 2.0 cm in stage IIb. Both patients were treated by thymectomy and are alive without recurrence or metastasis 15 and 17 months after surgery, respectively. Regardless of the spectrum of pathology and stage of MTWLS, this unique type of thymoma has a homogeneously favorable prognosis.

Ectopic micronodular thymoma with lymphoid stroma in the cervical region: a rare case associated with Langerhans cells proliferation.

Micronodular thymoma (MNT) with lymphoid stroma is a rare thymic epithelial neoplasm with the characteristics of multiple nodules separated by abundant lymphoid stroma. MNTs mainly arise in the anterior mediastinum and thymus, while ectopic MNTs are extremely rarely seen. Here, we report an ectopic MNT that occurred in the neck of a 62-year-old woman. There were also scattered eosinophilic granulocytes and S100(+)/CD1a(+) Langerhans cells within the tumor. This case provides a better understanding of such rare, poorly understood cases.

Micronodular thymoma with lymphoid stroma: an immunohistochemical study of the distribution of Langerhans cells and mature dendritic cells in six patients.

AIMS: Micronodular thymoma with lymphoid stroma (MNT) is an uncommon variant of thymoma, characterized by multiple small nodules consisting of type A thymoma-like cells, which are separated by abundant B lymphocytes. The aim of the study was to elucidate the pathogenesis of the stromal lymphoid hyperplasia, which is currently unclear. METHODS AND RESULTS: We retrieved six cases of MNT, and immunohistochemically examined the number and distribution of Langerhans cells (LCs) and mature dendritic cells (DCs), and compared them with those in type A and type AB thymomas. Many LCs were present within the small tumour nests, but LCs were rarely seen in the stroma (75.5/HPF versus 6.1/HPF, P < 0.0001). In contrast, mature DCs were present mainly in the surrounding stroma rather than within the tumour nodules (63.5/HPF versus 6.0/HPF, P < 0.0001), forming clusters with mature T lymphocytes adjacent to lymphoid follicles. In large nodules, as well as in type A and type AB thymomas, a few scattered LCs and DCs were identified. All patients were still alive and well. CONCLUSIONS: Our results suggest that LCs take up tumour antigens and migrate to the stroma, where they mature and form clusters with T lymphocytes to activate them, resulting in lymphoid follicle formation. The favourable clinical behaviour may be attributable to the immune response induced by LCs.