A large mesenteric paraganglioma with lymphovascular invasion

Abstract

Mesenteric paraganglioma is a rare tumour with only 17 known published case reports so far. This is the second case that demonstrates lymphovascular invasion of the tumour and the third that exhibits its malignant potential. We present a case of a 69-year-old woman with a large palpable abdominal mass that was thought to arise from the ovary following a staging CT scan. Intraoperatively, a large ovoid mass measuring 18 cm×15 cm×11.5 cm was found on the small bowel mesentery. Histological examination revealed the characteristic Zellbalen pattern with lymphovascular involvement. Mesenteric paraganglioma is rare and remains a diagnostic dilemma. Although the majority of paragangliomas are non-functional and do not show any malignant potential, individual case-based management is needed in view of their unpredictable nature. A multidisciplinary approach with genetic counselling and long-term follow-up are usually necessary to monitor for future disease recurrence.

Background

Chromaffin cell derivative tumours are very rare with a prevalence rate of 0.2–0.6% in patients with hypertension.¹ These tumours can be further subdivided into two distinct groups: phaeochromocytomas, which arise from adrenomedullary chromaffin cells, and those that arise from the extra-adrenal chromaffin cells known as paragangliomas. Of these, paragangliomas only account for 15–20% of chromaffin cell derivative tumours.²

Paragangliomas can be further subclassified into two groups depending on their distribution and origin. The first group arises from chromaffin cells of parasympathetic ganglia, which originate around the glossopharyngeal and vagus nerve distribution at the base of the skull and neck.³ The second group arises from paravertebral sympathetic ganglia of the thorax, abdomen and pelvis (TAP).³ Of these, paragangliomas that arise from the abdominal mesentery are much less common. To the best of our knowledge, this is the 18th mesenteric paraganglioma case that has been reported and the second case that demonstrates lymphovascular invasion of the lesion, which was first described by Chetrit and colleagues in 2012. We present a case of this unusual tumour found unexpectedly intraoperatively at our unit.

Case presentation

A 69-year-old woman presented to her general practitioner with epigastric pain. A large, firm, non-tender fixed palpable mass was noted in her lower abdomen. The patient had a history of gastro-oesophageal reflux disease, hypertension and anxiety. She had no family history of ovarian malignancy, was not taking hormonal replacement therapy and had two previous normal vaginal deliveries.

She was later admitted under the oncogynaecologists for elective laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy for a large palpable pelvic mass with a presumptive diagnosis of ovarian cancer.

Investigations

Observations and blood investigations including tumour markers (CEA, Ca19–9 and Ca125) were all within normal limits. Initial abdominal radiograph showed increased opacity in the lower abdomen (figure 1).

Figure 1.

Abdominal radiograph on admission; green circle highlights the opacified area.

Preoperative staging CT of the TAP (figures 2–4) revealed a large, well-defined, midline mass measuring 18.5 cm×13.3 cm×18.2 cm with mixed attenuation arising from the pelvis. The mass was situated anteriorly, separate from the uterus and above the bladder, and was thought to arise from the ovary. Within the mass, multiple areas of hyperattenuation were seen, suggesting necrosis. No peritoneal disease, lymphadenopathy or other focus suggesting metastasis was found. Following this, decision for surgical intervention was made.

Figure 2.

Coronal view.

Figure 3.

Sagittal view.

Figure 4.

Axial view.

Treatment

Intraoperatively, the ovaries and the uterus were normal, but a large encapsulated mass was noted on the anterior surface of the small bowel mesentery (figures 5 and 6). The lesion was located 340 cm distally from the duodenojejunal flexure and 30 cm proximal to the terminal ileum. En bloc resection of the mass, small bowel mesentery and small bowel was performed with primary anastomosis.

Figure 5.

The mass on the anterior mesentery of the small bowel.

Figure 6.

The blood vessels supplying the mass mesentery.

Outcome and follow-up

Histopathological examination revealed 41 cm of normal small bowel with an 18 cm×15 cm×11.5 cm ovoid mass with intact and partially peritonealised capsule. An extra-adrenal paraganglioma with a fibrotic capsule, and variable solid to lobulated and nested pattern of uniform cells was observed (characteristic Zellbalen appearance figure 7). Immunohistochemical screening on this tumour was positive for chromogranin A, synoptophysin, CD56, S100 and Ki67 at 5% with one microscopic lymphovascular invasion on one block resection (figure 8).

Figure 7.

Zellbalen pattern.

Figure 8.

Lymphovascular invasion.

The patient had an uncomplicated postsurgical phase with normal blood pressure. The case was subsequently discussed at the local regional neuroendocrine multidisciplinary meeting where repeat imaging and annual follow-up was recommended to monitor for disease progression.

At the patient's 6-week postoperative follow-up appointment, no complications or variation in blood pressure was noted. Histopathology and the multidisciplinary team meeting outcome were discussed. The unpredictable nature of the disease and the necessity for annual follow-up with repeat imaging using CT to detect disease recurrence was emphasised. A follow-up telephone call several months later confirmed that the patient was continuing to do well and had regained a good quality of life. She is due for her first formal follow-up this year.

Discussion

Based on the current 18 case reports (table 1), with the assumption that it follows the normal distribution in the population, the mean age for mesenteric paraganglioma is 55.83 years old, with a confidence level of 95% (46.96, 64.71 years old). From the series, the authors also noted a propensity of females over males (2:1), which has been previously stated by Fujita and colleagues.

Table 1.

Summary of case reports for mesenteric paraganglioma

Number	Authors	Year	Sex	Age (year old)	Tumour size (cm)	Metastasis
1	Areán and Arellano4	1956	Male	32	10.0	None
2	Carmichael et al5	1970	Female	62	3.2	None
3	Tanaka et al6	1991	Female	29	10.0×9.0×7.0	Liver
4	Ishikura et al7	1996	Female	33	15.0×15.0×15.0	Unknown
5	Onoue et al8	1999	Female	38	4.5×3.2×3.0	None
6	Jaffer and Harpaz9	2002	Female	76	8.5×8.0×2.0	None
7	Muzaffar et al10	2002	Female	76	20.0×15.0	None
8	Ponsky and Gill11	2002	Female	35	5.5	Unknown
9	Canda et al12	2004	Male	70	18.0	None
10	Nobeyama et al13	2004	Male	53	15.0×10.0×7.0	Unknown
11	Kudoh et al14	2005	Female	72	10.0×10.0×9.0	None
12	Matsumoto et al15	2006	Female	77	7.0×5.5	Unknown
13	Svajdler et al16	2007	Male	65	12.0×9.0×8.0	None
14	Guo et al17	2009	Female	22	11.5×6.0×11.5	None
15	Jacob et al18	2012	Female	63	10.0	Unknown
16	Chetrit et al19	2012	Male	55	11.5×9.5×6.5	2 Lymph node
17	Fujita et al20	2013	Female	78	3.0×1.5×1.5	None
18	Current	–	Female	69	18×15×11.5	1 Lymphovascular

The ability of paragangliomas to metastasise varies widely depending on their site of origin, and can be as low as 10–22%.²¹ In this case, there were no features of coagulative tumour necrosis and no high degree of mitotic activity; <1/10 high power field with the Ki67 level of 5%, which was initially encouraging. Unfortunately, one of the specimen blocks revealed a capsular microscopic lymphovascular invasion (figure 8).

Due to its ability to present with various clinical manifestations and as a silent non-functional tumour, diagnosis of a paraganglioma requires a high index of suspicion. When functional, paragangliomas have the ability to secrete either catecholamines, epinephrine, norepinephrine or dopamine.^{1 3 22} In this case, there were no issues intraoperatively regarding the patient's blood pressure control. Retrospectively, this could possibly mean that this mesenteric paraganglioma was non-functioning. Recent clinical guidelines have recommended assaying plasma free metanephrine when the patient has been supine for 30 min or a 24 h urine fractionated metanephrine with urinary creatine as the first step in establishing the diagnosis of phaeochromocytoma or paraganglioma if a patient fits certain criteria (figure 9).¹ Nevertheless, clinicians need to be aware that certain medications will cause a false-positive test in the biochemical investigations.⁴ Meanwhile, silent paragangliomas or those with the SDHx mutation could produce a false-negative test.¹

Figure 9.

Recommended biochemical testing for phaeochromocytoma or paraganglioma.¹

Once there is a clear biochemical diagnosis of phaeochromocytoma or paraganglioma, imaging should be performed. Currently, there is no consensus on the best imaging modality, but CT is the most readily available first-line imaging modality. As shown from this case report, diagnosing paraganglioma based on CT imaging alone can be challenging without clinical suspicion as the mass can appear homogenous or heterogeneous, or solid, cystic or necrotic.²² Nevertheless, paragangliomas and phaeochromocytomas will show an area of higher attenuation with >10 Hounsfield Units.^{1 22 23} MRI does have a role in assessing for paraganglioma of the head and neck region.¹ On MRI, malignant lesions and phaeochromocytomas will show high-signal intensity and marked enhancement on the T2-weighted phase.²² Functional imaging modalities, for example, I-metaiodobenzylguanidine scintigraphy or positron emission tomography with CT could have a role in detecting small lesions during the staging process or for assessing disease recurrence.

Traditionally, the ‘rule of 10’ dictates that 10% of phaeochromocytomas will be malignant, extra-adrenal, bilateral, occur in children, are inherited and will not be associated with hypertension. With the advent of advanced genetics, that statement has now come under challenge, as 8–24% of the classified ‘sporadic’ phaeochromocytomas and paragangliomas might have an underlying germline mutation or may be associated with autosomal dominant familial syndromic disease with variable penetrance.²² Recent published guidelines recommend that all newly diagnosed paraganglioma or phaeochromocytoma patients should be counselled for genetic testing, as one-third of the patients will have disease-causing germline mutations while those with the SDHB mutation will have a 40% risk of developing metastatic disease.¹ Early recognition of the mutations and hereditary syndrome patterns should allow earlier disease detection and intervention.

Learning points.

• Mesenteric paraganglioma is a rare tumour and diagnosing a non-functional paraganglioma remains a challenging scenario for clinicians.

• Be aware of the patients’ criteria for phaeochromocytoma or paraganglioma screening.

• Consider the role of genetic screening for future prognosis.

• Bear in mind the importance of a multidisciplinary approach and long-term follow-up following the diagnosis.