Recurrent duodenal gangliocytic paraganglioma with lymph node metastases

Brief reports

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Histopathology 1993, 22, 399-401

BRIEF REPORT

Recurrent duodenal gangliocytic paraganglioma with lymph node metastases D.B.DOOKHAN, M.MIETTINEN, G.FINKEL & Z.GIBAS Department of Pathology and Cell Biology, Thomas JeJjerson University, Philadelphia, Pennsylvania, U S A Date of submission 1 3 July 1992 Accepted for publication 9 November 1992

Keywords: gangliocytic paraganglioma, duodenum, immunohistochemistry

Introduction Gangliocytic paraganglioma is a rare tumour which occurs almost exclusively in the second portion of the duodenum',2. Histologically, it shows features reminiscent of paraganglioma, ganglioneuroma and carcinoid tumour. The lesion is composed of variable admixtures of three cell types: spindle cells with features of Schwann cells, ganglion-like cells and epithelioid cells. Gangliocytic paraganglioma is generally considered benign and most cases are cured by simple excision of the tumour mass. Metastatic spread to regional lymph nodes has been reported in five cases3-5.No instances of systemic metastatic spread or patient death attributed to the tumour are known. Here we report one additional case of duodenal gangliocytic paraganglioma which recurred in the mesentery 11 years following the original excision and also metastasized to the regional lymph nodes.

again presented with abdominal pain. Endoscopic examination of the duodenum was unremarkable. Computerized tomography scan of the abdomen revealed a 3 cm soft tissue density in the left peri-aortic region. Core biopsy of this mass was consistent with recurrent tumour. The patient subsequently underwent resection of the 4th portion of the duodenum and proximal jejunum with removal of a mesenteric mass. The postoperative course was unremarkable.

Case report A 41-year-old man was hospitalized in March 1981 for intermittent abdominal pain and constipation. His past medical history was unremarkable, except for chronic back pain. An upper gastro-intestinal examination with barium and additional small bowel examination revealed partial duodenal obstruction. Endoscopy showed an ulcerated polypoid mass in the second portion of the duodenum. The tumour was excised and the patient remained well until February 1992, when he Address for correspondence: Ur Zenon Gibas. Surgical Pathology Section, Department of Pathology and Cell Biology, 2 6 3 Main Building, 132 South 10th Street. Philadelphia PA 19 107, USA.

Figure 1. Ganglion-like cells with abundant cytoplasm and large nuclei with prominent nucleoli.

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Table 1. Immunohistochernical analysis

Cell type AntigenJantibody

Epithelial

Keratin 8 (CAM 5.2)* EMAt

Vimentint NSEJr

ChromograninS Synaptophysins Leu 7* CD56$ S- 100,polyclonalS

NF68s NF1605

NF2003 CFAPt

Ganglion

Spindle

-

-

-

+ + + -

-

-

+ + + -

-

+ + + + + + + + -

-

VIP$ GlucagonS Insulin$ Sornatostatint

* Beckton-Dickinson, Mt View, CA, USA. t Dako Corporation, Carpinteria, CA. USA. $ Atlantic Incstar, Minneapolis, MN, USA. 9 Boehringer, Mannheim, Indianapolis,IN, USA. EMA, epithelial membrane antigen; N S ~ ,neuron-specific enolase: GFAP, glial fibrillary acidic protein: VIP, vasoactive intestinal polypeptide.

PATHOLOGICAL FINDINGS

The specimen from the first excision consisted of a polypoid tumour mass measuring 2.5 x 2.0 x 2.0 cm. Haematoxylin and eosin stained sections revealed tumour predominantly in the mucosa and submucosa with infiltration of the muscularis propria. The lesion was non-encapsulated and showed an infiltrative margin. The tumour was composed predominantly of epithelioid cells arranged in nests, trabecula and gland-like structures. Ganglion-like cells were present singly and in small groups (Figure 1).The spindle cell component was inconspicuous and constituted less than 5% of the tumour. The specimen from the second excision consisted of a segment of the proximal jejunum and mesentery with a tumour mass located in the mesentery. The wall of the bowel was not involved. The tumour measured 5.5 x 4.2 x 4.0 cm and was well circumscribed. The sliced surface revealed solid, tan-white tissue with no evidence of haemorrhage or necrosis. Histologically, the tumour was similar to the original lesion with a

Figure 2. NF160 expression in gangliocytic paragangliorna. The 160 kD subunit positivity is seen in ganglion-like cells and axon-like cell processes.

prominent epithelioid cell component and scattered ganglion-like cells. In addition, unlike the original tumour, numerous psammoma bodies were present. The tumour had a n infiltrative margin and extended into the mesenteric fat. Small fragments of pancreatic tissue infiltrated by the tumour were also identified. Two lymph nodes attached to the tumour showed metastatic deposits of gangliocytic paraganglioma. The metastases were histologically similar to the recurrence, including the presence of numerous psammoma bodies. The results of immunohistochemical studies are summarized in Table 1. Both epithelial and neuroendocrine markers were expressed in the tumour cells. There was also evidence of neural differentiation (Figure 2). Electronmicroscopy showed tumour cells with abundant cytoplasm and cytoplasmic processes with abundant neuroendocrine granules (Figure 3 ) . The granules measured approximately 200 nm in diameter and showed a dense core with a small halo and a distinct membrane. Moderately developed cell junctions and scattered intermediate filaments were also present.

Brie/ reports

Figure 3. Abundant neuroendocrine granules are present in the cytoplasm of most of the tumour cells in gangliocytic paraganglioma. x 18 000.

Discussion This case showed the three cell types typical of gangliocytic paraganglioma including a prominent epitheliallike component, clusters and single ganglion cells and a scant spindle cell component. The epithelioid cells expressed both epithelial (cytokeratin and epithelial membrane antigen) and neuroendocrine (neuron-specific enolase, Leu 7, synaptophysin) markers. Cytokeratin expression in gangliocytic paraganglioma has also been observed by other authors in approximately 52% of cases’. Ganglion cells showed positive staining for neurofilaments and neuroendocrine markers. Spindle cells, apparently representing the sustentacular cell population, were positive for S-100 protein and vimen-

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tin. This corresponds to the findings of paragangliomas at other sites, such as the carotid body. The presence of a ganglion cell component positive for neurofilament subunits (predominantly 68 kD and 1 6 0 kD), but negative for epithelial markers, verifies the presence of true neural differentiation. In addition, axon-like structures were identified with antibody to the 200 kD subunit. The histological appearances of the primary and recurrent tumours were similar, with the exception of psammoma bodies which were present only in the recurrence. Psammoma bodies are characteristic feature of a subset of duodenal carcinoids called psammomatous somatostatinomas. However, psammoma bodies have also been observed in rare cases of gangliocytic paragangliomaj. An unusual feature of this case was that it recurred in the mesentery and metastasized to mesenteric lymph nodes. The recurrent mesenteric tumour may represent a lymph node metastasis with complete replacement of the lymphoid tissue and capsular penetration. The composite histological picture of gangliocytic paraganglioma gives rise to speculation as to the histogenesis of this unusual lesion. While some authors consider it to be a true neoplasm4, others view it as a hamartoma derived from maldeveloped pancreatic tissues1. The presence of metastatic spread to regional lymph nodes, the potential for recurrence and an infiltrative growth pattern are, in our opinion, indicative of the true neoplastic nature of this lesion.

References 1. Perrone T, Sibley RK. Rosai J. Duodenal gangliocytic paraganglioma. An imrnunohistochemical and ultrastructural study and a hypothesis concerning its origin. Am. I. Surg. Pathol. 1985: 9; 3 141. 2. Schethauer BW. Nora FE. Lechago J et al. Duodenal gangliocytic paraganglioma. Clinicopathologic and immunohistochemical study of 11 cases. Am. I. Clin. Pathol. 1986: 86; 559-565. 3 . Burke AP. Helwig EB. Gangliocytic paraganglioma. Am. 1. Clin. Pathol. 1989: 92: 1-9. 4. Barbareschi M. Frigo B, Aldovini D. Leonardi E. Cristina S, Falleni M. Duodenal gangliocytic paraganglioma. Report of a case and review of the literature. Virchows Arrhiv. [ A ] 1989: 416: 81-89. 5 . Inai K, Kobuke T, Yonehara S,Tokuoka S. Duodenal gangliocytic paraganglioma with lymph node metastasis in a 17-year-old boy. Cancer 1989; 63; 2540-2545.