Paraganglioma

* Approximately 5% to 10% of paragangliomas occur in extra-adrenal sites, which can extend from the upper cervical region to the pelvis, parallel to the autonomic nervous system. This distribution corresponds to the embryologic development of the paraganglia from neural crest cells. Rarely, extra-adrenal paragangliomas can also occur aberrantly outside this distribution. We report such a case of extra-adrenal paraganglioma occurring in the anterior mesentery in a 76-year-old man. Two case reports exist in the literature describing extra-adrenal paragangliomas in the posterior mesentery. Normal paraganglionic tissue has been described at the roots of the superior and inferior mesenteric arteries, theoretically explaining the origin of the posterior mesenteric paragangliomas. Our case can best be attributed to the ventral migration of paraganglionic tissue through these vessels to reach the anterior mesentery, where they could potentially give rise to paragangliomas in this site.

(Arch Pathol Lab Med. 2002;126:362-364)

Solid tumors originating in the mesentery are rare and are usually metastatic. Only a handful of case reports describe primary solid tumors of the mesentery, predominantly including fibromatoses, followed by neurofibromas, teratomas, carcinoid tumors, germ cell tumors, and primary neoplasms composed of either smooth muscle, blood vessels, or fat.1,2 We report a case of solitary primary paraganglioma arising in the anterior small bowel mesentery. We found only 2 previously published case reports describing mesenteric paragangliomas, both of which occurred in the posterior mesentery.3,4 Thus, our case is unique because of the unusual location of the paraganglioma in the anterior mesentery; to our knowledge, this case report is the first description of its kind.

REPORT OF A CASE

A 76-year-old man was admitted to Mount Sinai Hospital (New York, NY) for resection of a mesenteric mass. The patient's medical history was significant for hypertension of 20 years duration, which was controlled with medications. He also had undergone a left nephrectomy 15 years earlier for renal cell carcinoma.

During routine sonographic evaluation of the prostate gland, an abdominal/pelvic mass was appreciated. Results of a followup colonoscopy were unremarkable. Computed tomographic scan of the abdomen/pelvis confirmed a mass in the anterior mesentery (Figure 1), which was aspirated and, based on cytologic features, thought to be consistent with a neuroendocrine tumor. The patient denied symptoms of nausea, vomiting, diarrhea, flushing, palpitations, or weight loss. His vital signs and findings of a physical examination were within normal limits.

The patient tolerated exploratory laparotomy with resection of a segment of small bowel and attached mesentery. His vital signs were noted to be stable and consistent intraoperatively and postoperatively.

PATHOLOGIC FINDINGS

The resected specimen consisted of a segment of normal-appearing small intestine measuring 64 cm in length and 4.2 cm in diameter with an attached wedge of mesentery, which contained a well-circumscribed ovoid mass measuring 8.5 x 8.0 x 2.0 cm. The external surface of the mass was smooth and covered by delicate ramifying blood vessels. On cut surface, the mass consisted of a spongy, maroon, encapsulated mass with delicate septae coursing through it (Figure 2). The mass was distinct from the small bowel.

Histologically, the tumor was composed of uniform small round cells (chief cells) arranged in discrete cohesive lobules (zellballen). These nests of tumor cells were peripherally encircled by spindle cells consistent with sustentacular cells. The stroma was highly vascular. Altogether, these features were diagnostic of a paraganglioma (Figure 3). Immunohistochemistry confirmed the presence of 2 cell populations: the chief cells stained with neuron-specific enolase and chromogranin, whereas the sustentacular cells stained with 5100 protein. Ultrastructural studies performed on the tumor showed that the cells contained a uniform population of small dense neurosecretory granules (Figure 4), measuring approximately 150 (mu)m, confirming the diagnosis of paraganglioma.

COMMENT

The parenchymal cells of the paraganglia and other elements of the autonomic nervous system arise from neural crest cells. They are derived from the neuroblastic anlage associated with the dorsal roots of vertebral somites or primitive cells associated with cranial nerve ganglia.5 From these sites, the neural crest cells migrate (1) to the head and neck, adjacent to blood vessels and cranial nerves; (2) from the neck to the pelvis, close to the distribution of the sympathetic plexus and chains; (3) to the visceral autonomic system, which comprises a less welldefined group occurring in association with blood vessels or visceral organs; and (4) to the adrenal gland.

In the fetus, paraganglionic tissue is derived from pheochromoblasts, the largest concentration present at a level extending from either the root of the inferior mesenteric artery or the renal artery to the aortic bifurcation, known as the organ(s) of Zuckerkandl. The fetal adrenal gland is composed primarily of neuroblasts, with an inconspicuous amount of pheochromoblasts. In contrast, in the adult, the mature adrenal medulla replaces the involuted organ(s) of Zuckerkandl to form the largest collection of paraganglionic tissue. Thus, neoplasms arising from paraganglia occur most frequently in the adrenal medulla, where they are known as pheochromocytoma. The remaining small amount of normal paraganglionic tissue occurs in extra-adrenal sites extending from the upper cervical region to the pelvis, paralleling the autonomic nervous system. Neoplasms derived from paraganglionic tissue in these sites are known as paragangliomas and arise mostly from remnants of the organ(s) of Zuckerkandl. Small amounts of paraganglionic tissue have been described in usual sites outside the conventional distribution, such as in the interatrial septum of the heart, liver hilus, gallbladder, urinary bladder, prostatic capsule, and mesenteric vessels,6 potentially capable of giving rise to paragangliomas in these unusual sites. Under the Glenner and Grimley classification,5 these paraganglia may qualify as the viscero-autonomic type, a group of poorly defined paraganglia that occur in association with visceral organs or blood vessels. Rare paragangliomas have also been described in locations outside the distribution of the autonomic nervous system, where normal paraganglionic tissue has not yet been characterized, such as the genitourinary tract, spermatic cord, sacrococcygeal area, anus, renal capsule, broad ligament of the uterus, ovary, and the vaginal wall.6 These findings are difficult to explain, but can best be explained by the dispersed migratory property of the neural crest.7

We report a case of solitary paraganglioma without evidence of metastases, arising in the anterior mesentery. To our knowledge, the literature contains only 2 case reports of mesenteric paragangliomas to date, both of which were present in the posterior mesentery.3,4 Given that the majority of extra-adrenal intra-abdominal paragangliomas occur in the superior para-aortic region,7 it is not surprising that normal paraganglionic tissue has been described close to the duodenum and at the root of the superior mesenteric artery.8,9 Normal paraganglionic tissue has also been described at the root of the inferior mesenteric artery, which serves as the superior limit of the organ of Zuckerkandl.8,9 The presence of paraganglionic tissue at these sites could theoretically explain the location of these tumors in the posterior mesentery. However, our case of a paraganglioma occurring in the anterior mesentery can best be explained by the ventral migration of paraganglionic cells from the roots of either the superior and inferior mesenteric arteries, through them to reach the anterior small bowel mesentery. These cells could settle in this site to form a collection of paraganglionic cells and, thus, potentially give rise to paragangliomas in the anterior mesentery, as seen in our case. As with other paragangliomas described outside the distribution of paraganglionic tissue, our case can best be explained by the currently incompletely understood migration patterns of the widely dispersed neural crest cells.

References

1. Rosai J. Ackerman's Surgical Pathology. 8th ed. St Louis, Mo: CV Mosby Co; 1997: 2153-2154.

2. Yannopulos K, Stout AP Primary solid tumors of the mesentery. Cancer. 1963;16:914-927.

3. Arean VM, Ramirez de Arellano GA. Intra abdominal non chromaffin paragangliomas. Ann Surg. 1956;144:133-137.

4. Saharia S, Nawaz SK, Mittal VK, Mitra S, Khanna SK, Banarjee AK. Mesenteric tumour with features of phaeochromocytoma: a case report. Cancer. 1976;13:88-91.

5. Glenner GG, Grimley PM. Tumors of the extraadrenal paraganglionic system (including chemoreceptors). Washington, DC: Armed Forces Institute of Pathology; 1974. Atlas of Tumor Pathology, 2nd series, fascicle 9.

6. Smetana H, Scott WF. Malignant tumors of non chromaffin paraganglia. Mil Surg. 1951;109:330.

7. Lack EE. Extraadrenal paragangliomas of the sympathoadrenal neuroendocrine system. In: Tumors of the Adrenal Gland and Extra-adrenal Paraganglia. Washington, DC: Armed Forces Institute of Pathology; 1997:269-282. Atlas of Tumor Pathology, 3rd series, fascicle 19.

8. Taylor HB, Helwig EB. Benign non chromaffin paragangliomas of the duodenum. Virchows Arch Pathol Anat. 1962;335:356-366.

9. Elliot GB. Glomus like bodies on the superior mesenteric artery. Can Med Assoc]. 1965;92:1303-1305.

Shabnam Jaffer, MD; Noam Harpaz, MD

Accepted for publication August 8, 2001.

From the Department of Pathology, Mount Sinai Medical Center, New York, NY.

Reprints: Shabnam Jaffer, MD, The Mount Sinai Medical Center, One Gustave L. Levy Place, Department of Pathology, Box 1194, New York, NY 10029 (e-mail: Shabnam_Jaffer@mssm.edu).

Copyright College of American Pathologists Mar 2002
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