EUS-FNA of Mediastinal Masses

Fig. 3.1

Substernal goiter. Sheets of bland-appearing follicular epithelial cells and colloid (a). Focal oxyphilic change is also present (b). (DiffQuik stain, high magnification)

Thymoma

Thymoma is a neoplasm of thymic epithelial cells that occurs almost exclusively in adults. Familial forms are exceptional. Patients may be asymptomatic, have local thoracic manifestations of thoracic mass compression, or have a paraneoplastic syndrome, myasthenia gravis being the most common, or erythroid hyperplasia or aplasia among others. Myasthenia gravis is an autoimmune disease with circulating autoantibodies that bind to the nicotinic acetylcholine receptor (AChR) located in the subsynaptic membrane of the neuromuscular junction or motor end plate.

Histopathology

Histologically, thymomas show an admixture of neoplastic epithelial cells and nonneoplastic lymphocytes in various proportions (Fig. 3.2a). The epithelial cells may be plump, stellate, or spindle-shaped. Invasion of the tumor beyond the capsule is required for identification of the tumor as an invasive thymoma, which does not exhibit cytologic features of malignancy. The third type of thymic neoplasm is thymic carcinoma, which is rare, has a large variety of histologic patterns (epidermoid, sarcomatoid, clear-cell, basaloid, edenoid cystic, mucoepidermoid, papillary, anaplastic), has obvious cytologic features of malignancy, is rarely associated with myasthenia gravis, and, in contrast to thymomas shows neuroendocrine differentiation.

Fig. 3.2

Thymoma. Histology of a benign thymoma (a). Smears show cohesive elongated and epithelioid cells along with small lymphocytes and a background of proteinaceous fluid (b, c). (a, H&E stain intermediate magnification; b, c, DiffQuik and Papanicolaou stain, respectively, both high magnification)

Immuno-Profile

Epithelial cells are keratin, EMA, CEA, and p63 positive. Lymphocytes are of T-cell phenotype and express CD3 and CD4. TdT may be variably expressed. Co-expression of BCL2 and p53 is seen in most thymomas with a stronger reactivity in clinically aggressive tumors. Thymic carcinomas are CD5 +, CD117 +, CD70 + (member of the tumor necrosis factor family), and GLUT-1 +; thymomas are rarely positive for these markers.

Molecular Profile

Aberrations of chromosome 6 are common in thymomas, mostly in region 6q25.2. Thymic carcinomas show loss of 16q, 6, 3p, and 17p and gain of 1q, 17q, and 18.

FNA Findings

Smears show variable cellularity and a characteristic dual population of epithelial and lymphoid cells. Epithelial cells may be tightly or loosely cohesive and round to polygonal or even spindle-shaped, simulating a mesenchymal neoplasm (Figs. 3.2b, c). Invasive thymomas have bland cytologic features, and the diagnosis is made histologically on the resected specimen. Thymic carcinomas have a malignant cytomorphology that may resemble nonepithelial tumors such as sarcoma.

EUS Features

Imaging studies show a lobulated mass in the anterosuperior mediastinum that may be calcified. In a reported case of recurrent malignant thymoma (thymic carcinoma) diagnosed by EUS-guided trucut biopsy, the EUS demonstrated two hypoechoic heterogeneous masses with a focal, lobulated, and ill-defined edge, and measured 20 × 10 mm and 15 × 13 mm.

Rare Thymic Tumors

Neuroendocrine tumors, i.e., carcinoid, small-cell neuroendocrine carcinoma, and large-cell neuroendocrine carcinoma as well as stromal tumors, i.e., thymolipoma, and thymic stromal sarcoma, have been described.

Mediastinal Cysts

Thymic cysts are acquired or congenital. Acquired thymic cysts are usually large, multiloculated with attenuated thymic tissue, and relatively rare. Cytology smears show squamous cells, variable numbers of lymphocytes and red blood cells, and debris. Treatment is complete resection, and recurrence is rare. Congenital thymic cysts occuring in the first two decades of life are unilocular, have a thin wall lined with cuboidal or ciliated epithelium, and contain a clear fluid (Fig. 3.3a, b, c). Excision is curative.

Fig. 3.3

Congenital thymic cyst. The epithelium is ciliated and lymphoid tissue is seen to the left side of frame (a). Smears show proteinaceous fluid, lymphocytes, and rare ciliated epithelial cells (b, c). (a, H&E stain, intermediate magnification; b, c, Papanicolaou and DiffQuik stain high magnification)

Parathyroid cysts may be large and permeate between tissue planes extending to the superior mediastinum , are often functioning, and aspirates show a water-like clear fluid and rare macrophages; measurement of parathyroid hormone levels in the cyst fluid (sample needs to be frozen immediately) will support the diagnosis.

Pericardial or celomic cysts are usually located at the right cardiophrenic angle, are unilocular, lined by a single mesothelial layer, and contain clear fluid.

Mediastinal foregut cysts account for ~ 20 % of mediastinal masses and are congenital anomalies from a structure destined to become part of the trachea or bronchi (bronchial cysts) or esophagus , stomach , and intestine (esophageal, gastric, and enteric cysts, respectively). Bronchial cysts commonly occur along the tracheobronchial tree, often superior to the carina, but may be found in the wall of the esophagus. These contain inspissated mucus and are lined with ciliated epithelium, although squamous metaplasia may be focally present. Esophageal cysts are commonly intramural and are located in the lower third of the esophagus. The lining epithelium may be squamous, ciliated, columnar, or a combination. Gastric and enteric cysts, lined with gastric and intestinal type epithelium, respectively, are located attached to or within the wall of the esophagus and are often associated with vertebral malformations. EUS confirms the cystic nature of these lesions, and EUS-FNA shows ciliated, squamous, or glandular cells, depending on the cyst type (Fig. 3.4a). Acute mediastinitis is a rare complication therefore prophylactic antibiotic therapy is recommended following EUS-FNA of mediastinal cysts.

Fig. 3.4

EUS-FNA and EUS features of mediastinal cysts. Smears show columnar (black solid arrow), and/or ciliated, and/or squamous (white arrow) cells along with proteinaceous fluid (red arrow), debris, and mucus (a). Cysts are markedly hypoechoic/ anechoic, round or oval and show sharply demarcated borders and posterior acoustic enhancement (b, c, linear EUS). (a, Romanowsky stain, high magnification)

EUS Features of Mediastinal Cysts.

US characteristics are similar to those seen in cysts of other organs, including oval or round shape, marked hypoechogenicity, sharply defined margins, and posterior acoustic enhancement (Fig. 3.4b, c). Heterogeneity may be present in the presence of a dense fluid. An echogenic mass of variable size may be identified attached to the wall when a solid phase mural component is present; the solid component has variable vascularity on Doppler exam.

Adenopathy of Unknown Etiology

EUS -FNA can readily identify and sample lymph nodes in the subcarinal, paraesophageal, and paratracheal regions, but not in the pretracheal space or intrapulmonary regions. EUS-FNA is often performed for sonographically benign or suspicious lymph nodes when an abnormal finding will alter management.

Metastasis

In patients with a history of extrathoracic malignancy, metastasis from such a source is the major cause of mediastinal involvement, and as a result surgical diagnostic procedures are often not indicated. Renal-cell carcinoma is capable of metastasizing to the lungs or mediastinum years after diagnosis of the primary tumor. On the contrary, in patients without previous malignancy and mediastinal adenopathy, EUS -FNA identifies benign or malignant processes with equal proportion. When malignancy of unknown origin is diagnosed involving the mediastinal lymph nodes , a lung primary is subsequently identified in > 80 % of cases.

Infectious Lymphadenopathy

It is the most frequently diagnosed cause of unexplained adenopathy by EUS -FNA in our experience (Midwest of USA), and Mycobacteria and Histoplasma are the most likely diagnoses. EUS-FNA alters the subsequent work-up and therapy in ~ 75 % of such patients, obviating the need for more invasive diagnostic studies such as thoracotomy. EUS-FNA smears show lymphocytes, granulomas, and necrosis in varying proportions (Fig. 3.5a, b). Special stains for fungus (i.e., methenamine silver and PAS) and mycobacteria (i.e., acid-fast and Fite) performed in the smears or cell block provide information for initiation of appropriate therapy until confirmatory cultures are available. A negative direct stain neither excludes an infectious process nor confirms a noninfectious inflammatory etiology. Similarly, absence of granulomas and presence of granular amorphous material and crystals in the aspirate smear does not exclude a fungal infection; on the contrary, these findings are not uncommon in histoplasmosis (Fig. 3.6a, b). Thus, granulomas, lymphocytes, and necrosis must be taken in the context of the patient’s clinical scenario, including geographic area of living. Large yeast forms with thick clear capsule and mucoid background are seen in Cryptococcus lymphadenitis, often seen in immunosuppressed individuals and often preceded by Cryptococcus meningitis (Fig. 3.7).