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.

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.

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.

Papillary carcinoma thyroid with metastasis to ectopic cervical thymus.

Papillary carcinoma of thyroid is the most common type of thyroid neoplasm which is usually confined to the thyroid and tends to metastasize to regional lymph nodes. Distant metastasis occur in up to 15% of cases. Thymic metastasis from any malignant carcinoma is extremely rare with only four cases reported in medical literature. We report a case of papillary carcinoma of thyroid metastasizing to ectopic cervical thymus which has not been previously reported.

[Thymic metastasis of laryngeal cancer].

A 70-year-old man visited the Department of Head and Neck Surgery with a chief complaint of dysphagia. A tumor was observed in the epiglottis and vocal cord, and was diagnosed as squamous cell carcinoma by biopsy. Computed tomography (CT) showed a tumor mainly in the vocal cord. CT scans revealed a tumor centered on the vocal cord, with bilateral cervical lymph node metastases and a well-circumscribed 20-mm tumor in the anterior mediastinum. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed uptake in the primary lesion, left cervical lymph nodes, and anterior mediastinal tumor, which suggested a lymph node metastasis but did not exclude thymoma. The patient underwent video-assisted thoracic surgery (VATS) resection of the anterior mediastinal tumor with total laryngectomy, total thyroidectomy, and bilateral cervical lymph node dissection. The final pathological diagnosis was laryngeal cancer (glottic cancer, pT4aN2M1, pStage IVC) with thymic metastasis (presenting as an anterior mediastinal tumor). Thymic metastasis of laryngeal cancer is rare, and appears difficult to preoperatively differentiate from other mediastinal tumors.

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.

Is thymectomy worthwhile in central lymph node dissection for differentiated thyroid cancer?

BACKGROUND: Clinical guidelines edited in 2006 by the American Thyroid Association (ATA) and stated in the European Thyroid Association Consensus (ETA) recommend routine central lymph node dissection (level VI neck dissection) in addition to thyroidectomy for the surgical treatment of differentiated thyroid cancer. This central dissection increases the incidence of postoperative hypocalcemia, which is related to the resection or devascularization of the inferior parathyroids together with bilateral thymectomy. Some authors perform unilateral thymectomy in order to minimize this complication. Our aim was to study the benefit/risk (incidence of thymic lymph node metastases versus postoperative hypocalcemia) of both procedures. METHODS: We retrospectively reviewed the records of 138 patients who underwent total thyroidectomy with central neck lymph node dissection for differentiated thyroid cancer between 2004 and 2007. Bilateral thymectomy was performed in 45 patients (group 1, 15 males and 30 females) and unilateral thymectomy was performed in 93 patients (group 2, 27 males and 66 females). Forty-two papillary and 3 medullary cancers were found in group 1, and 75 papillary, 2 follicular, and 17 medullary cancers were found in group 2. The presence of thymic metastases at pathology and the occurrence of postoperative hypocalcemia were reviewed. RESULTS: Two cases of papillary thymic metastases were found in group 1. These were lymph node micrometastases localized in the ipsilateral side of the primary tumor in both cases. Transient hypocalcemia was significantly more frequent (P < 0.001) in group 1 than in group 2: 16 patients (35.5%) versus 10 (10.7%). There was one case of permanent hypocalcemia in group 1 after the follow-up period. CONCLUSIONS: Bilateral thymectomy risk outweighs any likely carcinologic benefit. We do not recommend routine bilateral thymectomy during central neck dissection for differentiated thyroid cancer.

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.

Prognostic predictors and long-term outcome of postoperative irradiation in thymoma: a study of 241 patients.

The purpose of this study was to identify the prognostic predictors treated with postoperative irradiation in patients with thymoma. Two hundred forty-one patients with histologically confirmed thymoma were collected and retrospectively reviewed in this study. Fifty-four patients had stage I disease; 57, stage II; 120, stage III; 10, stage IV. One hundred sixty patients underwent total thymectomy; 63, partial resection; 18, debulking or biopsy. Patients were irradiated after surgery with median dose of 50 Gy by conventional fractionation. The overall survival rates at 5 and 10 years were 83.1% and 72.6%, respectively. The 10-year overall survival was 87% for stage I, 78.7% for stage II, 57.4% for stage III, and 24.3% for stage IV. The conclusions were drawn from this analysis. For stage I, the role of postoperative irradiation needed further investigation. For stage II-III, surgery and postoperative irradiation should be part of standard care. The favorable prognostic predictors were female, early stage, and surgical extirpation.

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.

Thymic metastasis in breast cancer: a case report.

A malignant tumor is generally believed to be very unlikely to metastasize to the thymus. Only three cases of thymic metastases have been reported so far in the medical literature. We report here a rare case of metastatic breast cancer to the thymus, which was detected by CT and PET scanning, and the metastasis was also confirmed by video-assisted thoracic surgery biopsy. Recognition of an unusual breast cancer metastasis, such as to the thymus, as well as the usual patterns of breast cancer metastasis will facilitate an accurate, prompt diagnosis and its 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.

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.

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.

Appearance of intrathymic parathyroid adenomas on pinhole sestamibi parathyroid imaging.

OBJECTIVES: Ectopic inferior parathyroid adenomas (PAs) are frequently located in the anterior mediastinum, quite often in the thymus gland. Correct preoperative localization is particularly helpful for surgical planning. Clinical follow up has shown that most intrathymic adenomas were visualized on pinhole views and located closer to the thyroid than expected. We reviewed the typical appearance of intrathymic PA on pinhole views. METHODS: We retrospectively reviewed sestamibi pinhole parathyroid imaging performed on 163 patients with primary hyperparathyroidism and final diagnoses established by surgery, histology, intraoperative PTH monitoring, and clinical follow up. Studies showing focal increased activity in the lower pole region of the thyroid were selected and divided into 2 groups, group A (foci that are visually not separable from the thyroid) and group B (foci that are completely separated from the thyroid), and correlated with the final diagnoses. RESULTS: Of the 163 patients, 102 had 103 clearly abnormal foci in the lower pole region (bilateral lower pole foci in one study). There were 93 foci in group A and 10 foci in group B. Of the 93 foci in group A, there were 80 normally situated inferior PA, 6 descended superior PA, 3 intrathyroidal PA, one hyperplastic parathyroid gland, one thyroid adenoma, one unidentified, and one intrathymic PA. Of the 10 foci in group B, 3 were eutopic inferior PA and 7 were intrathymic PA. CONCLUSION: Focal increased activity completely separated from the lower pole of thyroid (regardless of the distance of separation) on sestamibi pinhole images indicates a high probability of intrathymic parathyroid adenoma.