Thymic Metastasis of Ovarian Cancer 33 Years After Primary Surgery.

This report describes a case of an extremely late recurrence of thymic metastasis after radical resection of ovarian cancer. Chest computed tomography demonstrated anterior mediastinal nodules with a smooth marginal area in a 56-year-old woman who had undergone an oophorectomy for ovarian cancer 33 years earlier. Because imaging findings suggested a thymic epithelial tumor, a partial thymectomy was performed. Histopathologic results led to the diagnosis of thymic metastasis of ovarian cancer. In patients with a medical history of ovarian cancer, thymic metastasis should be considered in the differential diagnosis of thymic tumor.

Thymic cancer in lynch syndrome: an unusual association.

Lynch syndrome has been associated with predominantly colorectal, endometrial, and ovarian cancer. We report hereby an unusual case of thymic carcinoma in a patient with Lynch syndrome. A 45-year-old Caucasian woman with a personal history of Lynch syndrome (MLH1 heterozygous mutation) presented with dyspnea, chest pain, and dysphagia. CT chest showed a bulky anterior mediastinal mass, pulmonary nodules, and pericardial effusion. Lung biopsy demonstrated a poorly differentiated carcinoma with squamous features with extensive necrosis, favouring thymic origin. Genomic studies on the tumour revealed deficient mismatch repair status with a two-copy deletion of MLH1 at 3p22.2 and c-Kit mutation. She received carboplatin and paclitaxel, with initial clinical improvement, but then died within 3 months after diagnosis. This case highlights that thymic cancer may be one of the malignancies associated with Lynch syndrome, and MLH1 gene mutation may have a role in the pathogenesis of thymic cancer.

Successful treatment of combined thymic epithelial tumor with hepatic metastasis: a long disease-free survival case.

A 73-year-old man presented with multiple liver nodules on an abdominal echogram. Fluorine-18-fluorodeoxyglucose (FDG)-positron emission tomography computed tomography (PET-CT) showed multiple nodules in his anterior and posterior mediastinum, and liver. Following thymothymectomy with lymph node dissection, the liver nodules were completely resected. Finally, he was diagnosed with combined thymic tumor (small cell carcinoma and type B3 thymoma) with multiple mediastinal lymph nodes and liver metastases by type B3 thymoma. Follow-up PET-CT scan revealed multiple rib and celiac lymph node metastases, six courses of chemotherapy (paclitaxel and carboplatin) were administered, and the patient survived without any recurrence for 15 years after initial surgery.

Multiple atypical thymic carcinoids with paraneoplastic giant cell arteritis.

Multiple thymic carcinoids are rare, and giant cell arteritis (GCA) is one of the less recognized paraneoplastic diseases. The co-occurrence of these two diseases is therefore extremely rare. We report herein a patient with multiple atypical thymic carcinoids and asymptomatic paraneoplastic GCA. All the thymic carcinoids were diagnosed histopathologically as atypical thymic carcinoids with an intrathymic metastasis. Treatment consisted of a complete tumor resection followed by observation of the GCA without any adjuvant therapy. Subsequent positron emission tomography revealed a decrease in F-fludeoxyglucose accumulation in the systemic arteries. Based on these findings, paraneoplastic GCA was diagnosed. Thymic carcinoids rarely involve intrathymic metastasis or cause neopleonastic GCA. However, when they do, a complete tumor resection is the best option for management.

Superior Vena Cava Replacement for Thymic Malignancies.

BACKGROUND: Advanced-stage thymic tumors infiltrating the superior vena cava (SVC), when radically resectable, can be surgically treated by SVC prosthetic replacement within a multimodality therapeutic approach. We hereby present our series of patients undergoing SVC resection and prosthetic reconstruction for stage III or IV thymic malignancies. METHODS: Between 1989 and 2015, 27 patients with thymic tumors (21 thymoma, 6 thymic carcinoma) infiltrating the SVC underwent radical resection with a SVC prosthetic replacement by a bovine pericardial conduit in 12 cases, a polytetrafluoroethylene conduit in 13, a porcine pericardial conduit in 1, and a saphenous vein conduit in 1. All the patients underwent vascular conduit reconstruction by the cross-clamping technique. RESULTS: Six patients were myasthenic. All resections were complete (R0). Twelve patients received induction treatment. Pulmonary resection was associated in 16 patients (11 wedge, 5 pneumonectomy). Twenty-two patients were Masaoka stage III and 5 were stage IVa. Mortality rate was 7.4%; no mortality was related to the vascular reconstruction. Major complication rate was 11.1%. At a median follow-up of 58 (range, 4 to 134) months, recurrence occurred in 9 (36%) patients. Three- and 5-year overall survival rates were 80% and 58.1%, respectively. Three-and 5-year cancer-specific survival were 90.5% and 75.4%. Cancer-specific survival rates of thymoma patients at 5 years were 93.8%. Five-year cancer-specific survival of all stage III patients was 77.1%. Thymic carcinoma histology was a negative prognostic factor. Long-term patency of the pericardial conduits was 100%. CONCLUSIONS: En bloc resection and conduit reconstruction of the SVC is a good option to allow radical resection of locally advanced thymic tumors. A heterologous pericardial conduit represents the favorite option in our experience.

Metastatic thymic tumor arising from spermatic cord leiomyosarcoma.

We report the first known case of a metastatic thymic tumor arising from spermatic cord leiomyosarcoma, occurring in a 35-year-old man. He had undergone an orchiectomy 24 months previously and a surgical excision of a subcutaneous metastasis 4 months prior to his current presentation. Computed tomography revealed a 1.5-cm, round-shaped anterior mediastinal mass. A thymectomy was performed and the diagnosis of metastatic leiomyosarcoma was made.

Solitary thymic metastasis of breast cancer 13 years after surgery.

A 59-year-old woman was noted to have an anterior mediastinal mass on computed tomography at a regular follow-up 13 years after initial surgery for left breast cancer. Magnetic resonance imaging showed an anterior mediastinal mass. A total thymectomy with excision of surrounding lymphoid tissue was performed. Pathological examination of the resected tumor confirmed the diagnosis of thymic metastasis from breast cancer. The patient has been alive for 6 years after thymectomy. Metastases to the thymus are rare, but long-term survival can be expected with appropriate treatment.

Lymph node metastases in thymic malignancies: a Chinese Alliance for Research in Thymomas retrospective database analysis.

OBJECTIVES: Lymphatic involvement is believed to be relatively rare in thymic epithelial tumours. The incidence and prognostic significance of nodal metastases are still unclear. The goal of this study was to define the incidence and prognostic relevance of nodal metastasis in patients with thymic epithelial tumours, using a nationwide retrospective database of the Chinese Alliance for Research in Thymomas. METHODS: Patients who underwent upfront surgical resection without preoperative therapy were enrolled for the study. The International Thymic Malignancies Interest Group proposal of a new staging system for thymic epithelial tumours was used to redefine the pathological stage. The incidence of nodal metastasis and its relationship with clinicopathological characteristics and its impact on survival were examined accordingly. RESULTS: A total of 1617 patients were enrolled in this study. Lymph node metastasis was identified in 35 patients (2.2%). No nodal involvement was found in type A, AB or B1 thymomas. The incidence of nodal metastasis in thymoma (B2/B3) and thymic carcinoma was 1.3% and 7.9%, respectively, and it was most commonly seen in patients with neuroendocrine thymic tumours (16.7%, P < 0.001). According to the primary tumour invasion stage, incidences of nodal metastasis were 0.2% in T1, 6.9% in T2, 8.5% in T3 and 7.4% in T4 tumours (P < 0.001). Gender, pleural or distant metastasis and resection status were also correlated with nodal metastasis (P < 0.05) in univariable analysis. Multivariable analysis revealed that patients with non-thymoma histological characteristics (P < 0.001) and tumours in non-T1 stage (P < 0.001) had significantly greater risk of developing nodal metastasis. The overall survival of patients without nodal metastasis was significantly higher than that of patients with nodal involvement (P < 0.001). Disease-free survival of patients after R0 resection without nodal metastasis was also significantly higher than those with nodal metastasis (P < 0.001). On multivariable analysis, overall survival was significantly associated with histology of the tumour (P = 0.019) and complete resection (P = 0.047), and there was a trend towards significance (P = 0.052) in the association between overall survival and nodal involvement. CONCLUSIONS: Lymph node metastasis in low-grade, early stage thymic tumours is a rare phenomenon. However, it is not uncommon in tumours with a higher stage or a higher histological grade, especially in neuroendocrine thymic tumours. Nodal involvement as well as tumour invasion and histological grade may denote worse prognosis. Lymph node dissection may be warranted in selected high-risk patients.

The Thymus in Experimental Mammary Carcinogenesis and Polychemotherapy.

Histological study of structural transformations in the thymus of Wistar females in induced carcinogenesis (N-methyl-N-nitrosourea injection in the right 2-nd mamma) and polychemotherapy (6 months after tumor growth initiation; cyclophosphamide, methotrexate, and 5-fluorouracyl) was carried out. The area of the cortical matter in the thymus decreased 6 months after carcinogenesis induction, the percentage of connective tissue elements and glandular tissue and the counts of immunoblasts and cells with pyknotic nuclei increased, this indicating the development of accidental involution of the thymus. Animals of the experimental tumor+chemotherapy group exhibited morphological signs of lymphocyte migration from the thymus and suppressed activities of the lymphoid and epithelial components (lesser area of connective tissue elements and glandular tissue, lesser density of parenchymatous cell elements, lesser counts of immunoblasts and small lymphocytes, and larger area of the medulla) in comparison with animals without chemotherapy.

Thymic and Mediastinal Lymph Node Metastasis of Colon Cancer.

Most anterior mediastinal tumors are thymomas. Thymic metastasis from other primary cancers is extremely rare. We report the case of a 72-year-old man who developed thymic and mediastinal lymph node metastases of cecum cancer. He had undergone laparoscopic ileocecal resection with regional lymph node dissection for primary cecum cancer 15 months previously. Follow-up computed tomography revealed tumors in the anterior mediastinum. Fluorodeoxyglucose positron emission tomography showed positive uptake in the tumors. Because thymoma or thymic carcinoma was suspected, we performed total thymectomy via a median sternotomy. Histologic findings of the anterior mediastinal tumors were compatible with metastasis of the previously resected cecum cancer.

Metastatic Thymic Carcinoma Presenting as a Posterior Fossa Mass: Case Report and Review of the Literature.

BACKGROUND: Thymic epithelial tumors (TETs) are uncommon lesions, and cerebral metastases from these tumors are even rarer. We report a case of a posterior fossa metastasis in a patient with a known history of thymic carcinoma. CASE DESCRIPTION: A 47-year-old man with a history of Hodgkin lymphoma and thymic carcinoma presented with headache, nausea, and ataxia. Imaging revealed a large posterior fossa mass. This lesion was completely resected without complications. Pathologic examination was consistent with metastatic thymic carcinoma. The patient's symptoms were relieved postoperatively. We reviewed the literature and identified an additional 44 cases of TETs with metastases to the brain. Although brain metastases are generally associated with a poor prognosis in patients with TETs, survival of more than 1 year may be accomplished with surgical resection and multimodality treatment. CONCLUSIONS: Metastasis should be considered in the differential of a patient with a TET and an intracranial mass lesion.

Ribosomal Protein Rpl22 Controls the Dissemination of T-cell Lymphoma.

Mutations in ribosomal proteins cause bone marrow failure syndromes associated with increased cancer risk, but the basis by which they do so remains unclear. We reported previously that the ribosomal protein Rpl22 is a tumor suppressor in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), and that loss of just one Rpl22 allele accelerates T-cell lymphomagenesis by activating NF-κB and inducing the stem cell factor Lin28B. Here, we show that, paradoxically, loss of both alleles of Rpl22 restricts lymphoma progression through a distinct effect on migration of malignant cells out of the thymus. Lymphoma-prone AKT2-transgenic or PTEN-deficient mice on an Rpl22(-/-) background developed significantly larger and markedly more vascularized thymic tumors than those observed in Rpl22(+/+) control mice. But, unlike Rpl22(+/+) or Rpl22(+/-) tumors, Rpl22(-/-) lymphomas did not disseminate to the periphery and were retained in the thymus. We traced the defect in the Rpl22(-/-) lymphoma migratory capacity to downregulation of the KLF2 transcription factor and its targets, including the key migratory factor sphingosine 1-phosphate receptor 1 (S1PR1). Indeed, reexpression of S1PR1 in Rpl22-deficient tumor cells restores their migratory capacity in vitro The regulation of KLF2 and S1PR1 by Rpl22 appears to be proximal as Rpl22 reexpression in Rpl22-deficient lymphoma cells restores expression of KLF2 and S1P1R, while Rpl22 knockdown in Rpl22-sufficient lymphomas attenuates their expression. Collectively, these data reveal that, while loss of one copy of Rpl22 promotes lymphomagenesis and disseminated disease, loss of both copies impairs responsiveness to migratory cues and restricts malignant cells to the thymus. Cancer Res; 76(11); 3387-96. ©2016 AACR.

Toward a Preoperative Classification of Lymph Node Metastases in Patients with Small Intestinal Neuroendocrine Tumors in the Era of Intestinal-Sparing Surgery.

INTRODUCTION: In patients with small intestinal neuroendocrine tumors (siNETs), surgical resection of the primary tumor and associated mesenteric lymph nodes (LNs) is recommended, but is not well standardized and can be risky in patients with superior mesenteric vessel involvement. OBJECTIVE: We aimed to evaluate the correlation between the length of resected small bowel and the number of removed LNs, and to propose a preoperative morphological classification of siNET-associated LNs. METHODS: The records of patients operated on for siNETs at two expert centers between August 2005 and November 2013 were analyzed. Two specialist radiologists reviewed the preoperative imaging and classified mesenteric LNs into five stages according to their proximity to the trunk and/or branches of the superior mesenteric artery. RESULTS: 72 patients were included. The mean number of removed LNs was 12 ± 15 and the length of removed small intestine was 53 ± 43 cm. No correlation existed between the length of small bowel resection and the number of removed LNs. Overall, 9 (12%), 13 (18%), 36 (50%), 14 (19%) and 0 patients were classified into LN stages 0, I, II, III and IV. The correlation rate between the two observers was 0.98. Patients with LN stage III (hardly resectable) had more removed LNs than those with LN stages 0, I or II (easily removable). CONCLUSION: Optimal lymphadenectomy is not always associated with extended small bowel resection. In the era of small bowel-sparing surgery, the preoperative classification of mesenteric LNs could help to standardize the surgical management of patients with siNETs.

Spindle epithelial tumor with thymus-like differentiation: A case report and comprehensive review of the literature and treatment options.

BACKGROUND: Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare cancer of thymic origin with little information available for treating clinicians. METHODS: We performed a comprehensive literature search and updates were requested from all authors. We report one recent case. RESULTS: We present the most comprehensive review of the clinical literature for SETTLE. We identified 41 published cases. SETTLE usually presents as an asymptomatic neck mass. Most patients successfully underwent surgical resection of the primary tumor. The mean latency to develop metastasis was 10 years. SETTLE is uniformly responsive to radiotherapy and combination chemotherapy in the rare cases where response data are available. CONCLUSION: Although SETTLE is initially indolent, it has the capacity to metastasize late in its course. The malignant potential of this tumor might be underestimated because of the lack of long-term follow-up. In cases in which complete surgical resection is not possible, radiotherapy or combination chemotherapy is effective.

Thymoma patients with pleural dissemination: nationwide retrospective study of 136 cases in Japan.

BACKGROUND: Thymoma is a rare mediastinal tumor with relatively slow growth. However, advanced-stage cases with pleural dissemination are occasionally encountered. The outcome of surgical resection for thymomas with pleural dissemination has not been clearly determined. METHODS: We retrospectively investigated the clinical records of 2,835 patients with thymic epithelial tumors that were treated from 1991 to 2010 in 32 institutions that participated in the Japanese Association for Research on the Thymus. In this study, we analyzed the clinicopathologic factors and prognosis of thymoma patients with pleural dissemination who underwent surgical resection. RESULTS: The thymomas with pleural disseminations numbered 148 cases (5.2% in the 2,835 thymic epithelial tumors). Surgical resection was performed in 136 cases. Pathologic Masaoka stages were classified as IVA (n=118) and IVB (n=18). In Masaoka stage IVA disease, the small number of disseminated pleural nodules (10 or fewer) was related to the curative resection. The prognosis was also better in these cases than in those with greater than 10 disseminated pleural nodules (certified during the operation; p=0.0057). Patients who underwent macroscopic total resection of disseminated nodules had a better prognosis than those with residual tumors (p=0.037). In stage IVA cases with complete resection (n=42), the efficacy of adjuvant chemotherapy, radiotherapy, or both was not demonstrated. CONCLUSIONS: Macroscopic total resection of tumors appears to be a promising prognostic factor in Masaoka stage IVA thymomas. The number of disseminated pleural nodules correlated with resectability.

Thymic metastasis of breast cancer 22 years after surgery: a case report.

We report a rare case of thymic metastasis of breast cancer. A 68-year-old woman, who had undergone surgery for cancer in her right breast and had been free of recurrence for 22 years, was noted to have an abnormal shadow on a chest X-ray at a regular medical checkup. Further workup, including chest CT, revealed a 22 × 18-mm mass in the anterior mediastinum. Fluorine-18-fluorodeoxyglucose-PET showed increased fluorine-18-fluorodeoxyglucose uptake that was highly suggestive of thymoma. Thoracoscopic thymothymectomy was performed. The tumor had invaded the pericardium, which was also resected. A small nodule was found in the right lung, and it was also resected. The intraoperative frozen-section diagnosis was breast cancer metastasis to the thymus and lung. The pathological diagnosis was luminal A solid tubular carcinoma (strongly estrogen receptor and progesterone receptor positive, HER2 negative) with an MIB-1 index of less than 5%. After surgery, the patient was treated with an aromatase inhibitor. As of August 2013, she has been free of recurrence for more than 36 months. It is extremely rare for breast cancer to metastasize to the thymus more than 20 years after surgery.

Tumor-to-tumor metastasis: breast cancer metastatic to thymic epithelial tumor.

Tumor-to-tumor metastasis is a rare phenomenon, with around 150 cases being reported in the literature. Breast cancer is the second most commonly reported donor tumor after lung cancer, but thymic epithelial tumors have never been reported as recipient tumors. Furthermore, the thymus is rarely affected by metastases. To our knowledge, the present report is the first case of breast cancer metastatic to thymic epithelial tumor.

Unusual metastases from tall cell variant of papillary thyroid cancer.

BACKGROUND: Tall cell variant (TCV) cancer is considered more aggressive than the classic variant of papillary thyroid cancer (PTC). Distant metastases are more common among this variant and affect survival. Little is known about the molecular pattern of this histotype. METHODS: This is a report of 2 cases of unusual metastases from TCV, BRAF V600E-positive. RESULTS: A 38-year-old woman developed subcutaneous metastases during short-term follow-up; at medium-term follow-up, the patient showed detectable stimulated serum thyroglobulin without disease evidence at imaging. A 33-year-old man presented incidental thymic metastases at time of surgical treatment; this is the first case of not ectopic thymic metastases from PTC. CONCLUSION: TCV may present with unusual metastases already during early follow-up. The more aggressive behavior could be linked to the higher prevalence of BRAF point mutations, but only a long-term follow-up might clarify if this association could worsen the prognosis. Moreover, skin metastases have been predictive factors of worse outcome in our patients, but not thymic metastases.