Non-Neoplastic Mediastinal Cysts.

Primary mediastinal cysts are infrequent lesions that can arise from a variety of mediastinal organs or structures. Most of these are congenital in origin and incidental findings during investigations for unrelated conditions. Histologically, the cysts may be composed of various tissues, including bronchogenic, pericardial, thymic, enteric, Müllerian, lymphatic, and parathyroid types. Mediastinal cysts typically demonstrate a benign clinical course and patients are cured after complete surgical resection. In this review, the embryogenesis, clinical, radiologic, and pathologic characteristics of non-neoplastic mediastinal cysts are examined with discussion of the role of immunohistochemistry and the most pertinent differential diagnosis.

Nebulized hypertonic saline triggers nervous system-mediated active liquid secretion in cystic fibrosis swine trachea.

Inhaled hypertonic saline (HTS) treatment is used to improve lung health in patients with cystic fibrosis (CF). The current consensus is that the treatment generates an osmotic gradient that draws water into the airways and increases airway surface liquid (ASL) volume. However, there is evidence that HTS may also stimulate active secretion of ASL by airway epithelia through the activation of sensory neurons. We tested the contribution of the nervous system and airway epithelia on HTS-stimulated ASL height increase in CF and wild-type swine airway. We used synchrotron-based imaging to investigate whether airway neurons and epithelia are involved in HTS treatment-triggered ASL secretion in CFTR-/- and wild-type swine. We showed that blocking parasympathetic and sensory neurons in airway resulted in ~50% reduction of the effect of HTS treatment on ASL volume in vivo. Incubating tracheal preparations with inhibitors of epithelial ion transport across airway decreased secretory responses to HTS treatment. CFTR-/- swine ex-vivo tracheal preparations showed substantially decreased secretory response to HTS treatment after blockage of neuronal activity. Our results indicated that HTS-triggered ASL secretion is partially mediated by the stimulation of airway neurons and the subsequent activation of active epithelia secretion; osmosis accounts for only ~50% of the effect.

99mTc-MIBI Uptake in a Benign Thymic Cyst.

A 34-year-old man with end-stage renal failure status post rejection of a deceased donor kidney transplant presented with bone pain in the setting of elevated serum parathyroid hormone and calcium levels. A Tc-MIBI SPECT/CT was performed before planned subtotal parathyroidectomy. SPECT/CT imaging revealed a 1.9-cm anterior mediastinal lesion with radiotracer uptake on both the immediate and delayed images. Surgical pathology of the lesion showed a benign thymic cyst with no parathyroid component.

Thoracoscopic Resection of Multiple Müllerian Cysts.

Müllerian cysts in the mediastinum were first described by Hattori in 2005 [1]. We report the first known case of multiple müllerian cysts in the thorax in a 35-year-old woman with cough and an abnormal chest roentgenogram. Multiple bilateral cysts were resected thoracoscopically. Histologic examination showed benign ciliated tubal epithelium that stained positive with immunohistochemical stains for estrogen receptor (ER), cancer antigen 125 (CA-125), Wilms' tumor protein 1 (WT-1), and paired box gene 8 (PAX8), confirming müllerian origin. We also review the embryogenesis and pathologic characteristics of müllerian cysts and the rare occurrence of their migration to the thorax.

Conditioned deletion of ephrinB1 and/or ephrinB2 in either thymocytes or thymic epithelial cells alters the organization of thymic medulla and favors the appearance of thymic epithelial cysts.

Our understanding about medullary compartment, its niches composition and formation is still limited. Previous studies using EphB2 and/or EphB3 knockout mice showed an abnormal thymic development that affects mainly to the epithelial component, including the cortex/medulla distribution, thymic epithelial cell (TEC) morphology and different epithelial-specific marker expression. We have already demonstrated that the lack of ephrinB1 and/or ephrinB2, either on thymocytes or on TECs, alters the cell intermingling processes necessary for thymus organization and affect cortical TEC subpopulations. In the present work, we have used the Cre-LoxP model to selectively delete ephrinB1 and/or ephrinB2 in thymocytes (EfnB1(thy/thy), EfnB2(thy/thy), EfnB1(thy/thy)EfnB2(thy/thy) mice) or TECs (EfnB1(tec/tec), EfnB2(tec/tec), EfnB1(tec/tec)EfnB2(tec/tec) mice) and have analyzed their role on the medullary compartment. In all the studied mutants, medullary areas are smaller and more compact than in the wt thymuses. In most of them, we observe abundant big cysts and a higher proportion of UEA(hi)MTS10(-) cells than in wt mice, which are often forming small cysts. On EfnB1(tec/tec)EfnB2(tec/tec), changes affecting organ size and medullary compartment start at perinatal stage. Our data shed some light on knowledge about wt medulla histological structure and cysts meaning and formation process and on the role played by ephrinB in them.

Hyperparathyroidism due to eutopic PTH secretion from an ectopic intrathymic parathyroid cyst.

Parathyroid cysts rarely cause hyperparathyroidism. In addition, they rarely occur in the thymus. We report a 56-year-old woman with hypertension on telmisartan and hydrochlorothiazide, who developed symptomatic hypercalcemia for a month. Initial serum calcium was 15.6 mg/dL, together with inappropriately elevated intact PTH at 437 pg/mL. Coincidentally, an anterior mediastinal mass on chest imaging was found. Biopsy of the mass revealed parathyroid tissue. She was treated sequentially with saline rehydration and frusemide calciuresis, intravenous pamidronate and calcitonin, which lowered her calcium to 11.1 mg/dL. Normocalcemia was finally achieved following surgical extirpation of the mass. Histology confirmed an intrathymic parathyroid cyst. Definitive treatment by resection of the mass is potentially curative.

Thymic carcinoma associated with multilocular thymic cyst: a clinicopathologic study of 7 cases.

We present 7 cases of thymic carcinoma associated with a multilocular thymic cyst (MTC). The patients were 5 men and 2 women aged 22 to 71 years (mean, 49.3 y). Clinically, 6 patients presented with chest, sternal, or upper extremity pain, and in 1 patient the tumor was an incidental finding. Grossly, 4 tumors were described as multilobulated solid-cystic masses, whereas 3 cases were described as solid tumors with a white-yellow cut surface and areas of hemorrhage and necrosis. The tumor size ranged from 7.0 to 10.0 cm (mean, 8.1 cm). Histologically, 4 cases were classified as squamous cell carcinoma, and 1 each as sarcomatoid (spindle) cell carcinoma, papillary carcinoma, and basaloid carcinoma. In addition to the tumor component, prominent MTC changes were observed in the adjacent remnant thymic tissue. Immunohistochemical studies were conducted in 2 cases of squamous cell carcinoma. The neoplastic cells were positive for cytokeratin (CK), CK5/6, and p63, and showed variable reactivity for CK7 and CD5. Clinical follow-up showed that 4 patients were alive and well, 2 to 63 months after diagnosis, and 3 patients were alive with disease, 13 to 33 months after diagnosis. This study expands the morphologic spectrum of thymic carcinoma associated with MTC, detects a higher incidence than previously believed, and highlights the importance of adequate sampling and proper evaluation of all cystic lesions of the anterior mediastinum so as not to mistake malignancy for a benign cystic process.

Metabolite signature of developmental foregut cyst on in vivo and in vitro (1)H MR spectroscopy.

Foregut duplication cysts are developmental anomalies of the bronchopulmonary foregut and are common cystic lesions of the mediastinum. We describe a case of mediastinal foregut duplication cyst with in vivo (1)H MR spectroscopy on a 1.5T magnet showing a large metabolite peak at 2.02 ppm, attributable to N-acetylated compounds, in addition to a smaller peak at 1.33 ppm, considered to represent lipids. In vitro NMR spectroscopy (7.05T) of cyst fluid confirmed the presence of these peaks. In addition, a broad multiplet centered at 3.7 ppm, possibly from various protons of the hexose ring system, was also noted. Chemical analysis of the cyst fluid demonstrated the presence of N-acetylhexosamines, proteins, and lipids. Again, in vitro spectra of pure samples of N-acetylglucosamine and N-acetylgalactosamine were obtained for comparison, which better resolved the N-acetyl peak and the peaks at 3.7 ppm. The mucus secreted by respiratory epithelium and the mucous glands of the foregut cysts contains glycoproteins that have N-acetylhexosamines as components and lipid breakdown products that are thought to contribute to the observed spectrum. This information might be useful in predicting the cyst content and, in turn, the lining of the epithelium and the glandular elements.

Spontaneous rupture of idiopathic thymic abscess with a markedly increased CA-125 level.

We report a rare case of spontaneous rupture of idiopathic thymic abscess into the pleural cavity. A 64-year-old woman was admitted to hospital with pleuritic retrosternal chest pain. Chest roentgenograms disclosed a small amount of bilateral pleural effusion, the examination of which exposed a sterile serous exudate with a markedly increased CA-125 level. Chest computed tomography revealed a large anterior mediastinal cystic mass with bilateral pleural effusions. Following complete resection of the mass, the histological examination revealed cavitary lesion with necrotic thymic tissue and inflammatory infiltrate surrounded by fibrous wall. The immunohistochemical staining for CA-125 displayed strong positivity at the Hassall's corpuscles. Cyst fluid also revealed a highly elevated CA-125 level. Her serum CA-125 concentration two months after surgery had fallen to 28 IU/L. She is now doing well without recurrence of the cyst five months after surgery.

Cysts of the posterior mediastinum showing müllerian differentiation (Hattori's cysts).

Cysts of probable müllerian origin have recently been recognized in the mediastinum by Hattori (Virchows Arch. 2005;446:82-84; Chest. 2005;128:3388-3390). In a retrospective study, we found 9 such cases, accounting for 5.5% of a series of 163 consecutive mediastinal nonneoplastic cysts operated in our institution. These cysts occurred in 9 women aged 40 to 58 years (mean, 50.6 years). These women often had overweight (n=4) or various gynecologic history (n=5). Cysts were paravertebral (n=8) or prevertebral (n=1). They were initially classified as bronchogenic or unspecified benign serous cysts. Their diameter measured 1.3 to 5 cm. Their thin wall contained smooth muscle. They were lined by a simple cylindrical or cuboidal, nonmucinous, and often ciliated epithelium resembling uterine tubal epithelium. This epithelium expressed cytokeratin 7, epithelial membrane antigen and estrogen and progesterone receptors. It was negative for cytokeratin 5/6. In the same series, there were 66 bronchogenic cysts, 6 being paravertebral. In conclusion, cysts with müllerian differentiation account for a small proportion of mediastinal cysts and have a usual but nonspecific paravertebral location.

High prevalence of estrogen and progesterone receptor expression in mediastinal cysts situated in the posterior mediastinum.

BACKGROUND: To identify and estimate the prevalence of mediastinal cysts lined by the epithelium expressing steroid receptors. METHODS: We retrieved 19 mediastinal cysts from our pathology files from 1996 to 2004, and examined estrogen receptor (ER) and progesterone receptor (PR) expressions in the cysts. RESULTS: Three paravertebral cysts, all in women, one bronchogenic cyst in a woman, nine thymic cysts, and six pericardial cysts were found in the pathology files. Paravertebral cysts were situated in the posterior mediastinum and were attached either to the left or the right of the vertebral column. All cysts were radiologically diagnosed before surgery as neurogenic tumors. They were excised by video-assisted thoracoscopic surgery. The epithelial lining of the cyst in all three cases was strongly positive for both ER and PR. A thymic cyst in one woman was weakly positive only for the ER. In all other cases, the lining was entirely negative for both ER and PR. CONCLUSIONS: Posterior mediastinal paravertebral cysts characteristically express ER and PR. They should be recognized as a distinct type of mediastinal cyst because they are biologically different from bronchogenic cysts, seem not to be infrequent, and sometimes are misdiagnosed as a neurogenic tumor.

Cysts in human thymus: maturational forms of Hassal's corpuscles?

Presence of extracellular cystic cavities in the thymus of many vertebrates has long been known. Various forms of such structures in human thymus were observed and examined thoroughly on immunostained and serial semithin sections. We grouped these structures into five categories according to their most characteristic features. The lympho-epithelial content of the cysts clearly reflected the structural features and antigenic profile of thymic cortical parenchyma in both elongated and ovo-spherical cysts. Our findings suggest that the various types of cystic structures observed in human thymus may represent maturational stages of classical Hassal's corpuscles. Presence of cortical lympho-epithelial content and its gradual replacement with debris material also suggests a unique mechanism of thymocyte disposal.

Mediastinal thoracic duct cyst.

A healthy 34-year-old man had a mediastinal cyst on the imaging study. Surgical treatment was performed. The cyst was diagnosed as a thoracic duct cyst from its anatomic location and contents. Pathologic examination found it to be consistent with thoracic duct cyst. Endothelial cells on its luminal surface were identified by an immunohistologic stain with the factor VIII-related antigen. Twenty-six cases of thoracic duct cysts have been reported. We report an additional case and review the previously reported cases. We found that the ligation of the inferior pedicle of the cyst is essential to prevent postoperative chylothorax.

Multilocular thymic cysts associated with thymoma. A case report.

The association of multilocular thymic cysts (MTC) with thymoma is exceedingly rare, and the pathogenesis of this combination is controversial. We describe the case of a 42-year-old man with an anterior mediastinal mass found to contain MTC and thymoma. A multilocular cystic mass, measuring 13 x 6.5 x 2 cm, was found in the right lobe of the thymus, and contained a 4.7 x 2 cm thymoma in its center. Microscopic thymomas, lipomatously involuted remaining thymic tissue, and lymphoid follicles with germinal centers were found in the walls of MTC as well as in the left thymic lobe. Non-specific chronic inflammation was also present in the walls. In addition, microcysts, which were only found at the periphery of the thymoma and covered with epithelium, might have been formed secondarily by dilatation of the perivascular spaces and of Hassall's corpuscles. These findings suggest that a chronic inflammatory process was responsible for the early formation and enlargement of this patient's MTC, and that while the cavities of the MTC expanded to various degrees, the thymoma, which originated from one of the microscopic thymomas in the walls of MTC, increased in size, and grew to involve the remaining thymic tissue.

[A case of thymic cyst showing elevated CEA, SLX and CA125 levels in the cystic fluid associated with non-invasive thymoma].

A 66-year-old woman, who had complained of left ptosis and been diagnosed as having myasthenia gravis (ocular type) 9 years previously, was admitted to our hospital for further examination of an abnormal mass shadow on chest X-ray film. Chest computerized tomography (CT) revealed a cystic tumor in the anterior mediastinum and thoracotomy was performed to make a definitive diagnosis. The tumor could be removed completely and was diagnosed histologically as a thymic cyst with thymoma. The cyst was 32 x 30 x 28 mm in size and contained about 10 ml of brown turbid fluid. The levels of CEA (61.3 ng/ml), SLX (24,000 U/ml) and CA125 (1300 U/ml) were markedly increased in the cystic fluid, while those in serum were not elevated. Immunohistochemical staining demonstrated the epithelial cells lining the cyst to contain SLX. The findings suggest that SLX was produced in the epithelial cells of the cyst. However, neither CEA nor CA125 was positive in the epithelial cells. From our review of reported cases of thymic cyst showing elevated levels of tumor markers in the cystic fluid, the main mechanism of marked elevation of tumor markers seems to be condensation in the cystic fluid rather than increased production in epithelial cells lining the cyst. Cases of thymic cyst with thymoma are extremely rare, but our case was concluded to be incidentally associated with non-invasive thymoma.

[Two cases of mediastinal goiter with progressive deviation of the trachea by its growth and their thyroid hormone values in the fluid of the cystic lesions].

We reported two operated cases (a 35-year-old male and 52-year-old male) of mediastinal goiter accompanied by marked tracheal deviation. The two patients did not have any clinical symptoms. CT, MRI, ultrasonography and angiography finding of the two cases are presented. Fluid was obtained from the cystic lesions by ultrasonically guided needle aspiration. The levels of thyroid hormones (T3, T4) in the fluid were not high in comparison with serum levels. Surgical resection was performed on the 35-year-old male case by collar incision and on the 52-year-old male case by median sternotomy.