A 51 year-old woman with a right middle lobe lung mass
Majed Pharaon, M.D., H. James Williams, M.D.
A 51 year-old woman smoker presents with a right middle lobe lung mass which was discovered incidentally during work up for right flank pain one year ago. Follow up with computed tomography (CT) scan of the chest revealed a slight increase in the size of the mass from 12 to 13 mm in greatest dimension (see arrow, Figure 1). As these features were concerning for malignancy, the patient underwent right middle lobectomy.
Sections of the right middle lobectomy specimen showed a single 1.2 x 1.2 x 1.1 cm tan, lobulated, encapsulated mass. Microscopic findings are illustrated in Figures 2-5.
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Primary pulmonary paraganglioma (PPP) is a rare tumor with less than 40 reported cases in the English-language literature. The first case was reported in 1958 by Heppleston [1, 2]. Paraganglioma generally arises from neural crest derived cells called paraganglia which are located anywhere along the sympathetic and parasympathetic chains . The largest collections of paraganglial cells are located in the adrenal gland medullas. Tumors arising from the adrenal medulla are known as pheochromocytomas. Traditionally, tumors originating from paraganglia located outside the adrenal gland are called extra-adrenal paragangliomas. The majority of the reported cases of PPP occurred in middle-age females but they can occur at any age .
Clinically, paragangliomas can be divided into two types depending on their origin within the autonomic nervous system. The first type is the functioning paraganglioma which arise from the sympathetic paraganglia located in the retroperitoneum and posterior mediastinum. These patients usually present with symptoms related to high levels of catecholamine secretion such as high blood pressure, palpitations, headache, and sweating . On imaging, rich blood supply and significant arterial enhancement is usually seen . The second type is the nonfunctioning paraganglioma which arise from the parasympathetic ganglia located in the head, neck, and anterior mediastinum . These patients are generally asymptomatic and the tumor is discovered incidentally when the patient undergoes imaging studies for an unrelated condition. A recently reported case of a patient with functional paraganglioma described diffuse alveolar hemorrhage caused by increased catecholamine secretion and continued hypertension . Hereditary pheochromocytomas and paragangliomas can be a component of different genetic syndromes. Examples include multiple endocrine neoplasia syndrome (MEN) type 2, paraganglioma-pheochromocytoma syndrome, von Hippel-Lindau disease, and Carney’s triad [5, 7].
Gross examination shows a firm, rubbery mass with a tan-brown cut surface. Large tumors can have areas of necrosis, hemorrhage, and/or cystic degeneration. Histologically, PPP is similar to extra-adrenal paragangliomas at other locations. The classic pattern is a diffuse, well-defined, nested arrangement of the neoplastic cells (referred to as Zellballen or cell balls) with a prominent vascularity surrounding the nests of tumor cells. Sustentacular cells comprise a network of supporting cells surrounding the neoplastic cells [2, 8]. The abundant cytoplasm is pale eosinophilic and has a granular appearance. The tumor cells are relatively uniform with distinct borders. Scattered single atypical cells with large, hyperchromatic nuclei are commonly present as is often seen in neuroendocrine tumors in general. Although the above mentioned histologic features are characteristic of paragangliomas, they can be seen in other tumors and are not considered pathognomonic . Immunohistochemically, all tumors react strongly to neuroendocrine markers such as synaptophysin, chromogranin, CD56, and NSE. Sustentacular cells stain positive for S-100 protein, a helpful feature in making the diagnosis. The tumor cells are negative for cytokeratin, vimentin, and smooth muscle actin .
The differential diagnosis includes typical carcinoid tumor, primary pulmonary carcinomas, metastatic carcinoma to the lung, or inflammatory processes. Paragangliomas tend to lack the classic histologic patterns of a carcinoid tumor such as the trabecular or ribbon-like patterns. In addition, carcinoid tumors are cytokeratin immunoreactive. In contrast to pulmonary carcinomas (including typical carcinoid) which are mostly found in a close relation to the bronchial tree, PPP is usually found in close proximity of the pulmonary vessels and nerves .
Metastatic paraganglioma is more common in the lung than PPP . Although extra-adrenal parangliomas have the potential to be malignant, only a few of the reported PPP cases are were found to be malignant. The only current reliable criterion for malignancy is the presence of distal metastasis [1, 3]. Local or vascular invasion, cellular atypia, and lymph node metastasis can be identified but they do not seem to affect the prognosis. Local excision with negative margins or lobectomy is usually curative .
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