ENDOCRINE SOCIETY
OXFORD
Retroperitoneal Solid Pseudopapillary Tumor Mimicking Adrenal Malignant Tumor in a 67-Year-Old Man
Takahiro Ishii, 1,2 Tomohiro Terasaka, 1,20D Kenji Nishida,3 and Jun Wada 1,2(D
1Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan
2Endocrine Center, Okayama University Hospital, Okayama, 700-8558, Japan
3Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, 700-8558, Japan
Correspondence: Tomohiro Terasaka, PhD, MD, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. Email: terasakat@okayama-u.ac.jp.
Abstract
Solid pseudopapillary tumor (SPT) is a low-grade malignant tumor of the pancreas. SPT typically affects women and can occur in ectopic pancreatic region; however, it also occurs rarely in retroperitoneum. The tumor may be bulky at the time of diagnosis since there is no specific clinical manifestation. Here we present an older male case with retroperitoneal SPT. A 67-year-old man consulted for intermittent fever and lumbago. His basal hormonal profile screened out a functional tumor. Computed tomography (CT) showed a gigantic mass in his left adrenal region. A normal left adrenal gland was not identified, and the tumor’s feeding artery was recognized as the left adrenal artery by the contrast-enhanced CT. Adrenal malignant tumor was suspected, and tumor resection was performed. The resected tumor size was 15 x 10 x 9 cm. Histologically, epithelial-like cells with round nuclei and a small amount of eosinophilic cytoplasm proliferated in papillary (around the blood vessels) or uniformly solid form. By immunostaining, tumor cells were vimentin, CD56, cytokeratin AE1/AE3, CD10, ß-catenin in the nucleus, cyclin D1, and PgR positive. These findings led to the diagnosis of SPT. Although rare, SPT should be considered as a differential diagnosis in cases of a mass arising from the adrenal region.
Key Words: solid pseudopapillary tumor, adrenal incidentaloma, adrenocortical carcinoma, metastatic tumor, adrenal artery
Abbreviations: ACTH, adrenocorticotropic hormone; ALP, alkaline phosphatase; CRP, C-reactive protein; CT, computed tomography; y-GTP, y-glutamyl transpeptidase; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; PAC, plasma aldosterone concentration; PRA, plasma renin activity; SPT, solid pseudopapillary tumor.
Introduction
Adrenal incidentaloma is a commonly encountered feature when abdominal diagnostic imaging (CT, magnetic resonance imaging [MRI] and ultrasound) is performed (5% of these CT scans performed find adrenal incidentaloma), although since the numbers are from a selected population, this may be under- or overestimating some diagnoses. The vast majority of adrenal masses are adenoma (80%), and asymptomatic non- functioning adrenal adenoma is most likely (75%), followed by autonomously cortisol secreting (12%) and aldosterone- secreting (2.5%) [1]. Additionally, 7% of adrenal incidentalo- mas are pheochromocytoma, 8% adrenal carcinoma, and 5% metastasis [1]. In a previous study run by Italian Society of Endocrinology, the mass size of adrenal tumor is predictive of malignancy and the cutoff size of 4 cm was indicated as 93% sensitivity and 42% specificity for cancer. Other types of mass, such as myelolipoma, cyst, and ganglioneuroma, are sometimes diagnosed in the adrenal region [1].
Here we present the rare case masquerading as the adrenal artery feeding a gigantic adrenal tumor (15x10x9 cm), which was pathologically diagnosed as a solid pseudopapil- lary tumor (SPT) in a 67-year-old male patient.
Case Presentation
A 67-year-old man with impaired glucose tolerance and hyper- tension consulted a primary care physician for intermittent fever and lumbago for 1 month. He did not have the headaches, sweat- ing, and palpitations that indicate catecholamine elevation. After imaging study with CT and MRI, he was suspected to have a left adrenal malignant tumor and was referred to our hospital.
Diagnostic Assessment
A contrast-enhanced CT showed a 118 x 102 × 130 mm mass in the left adrenal region, which was heterogeneously enhanced due to necrotic areas. A normal left adrenal gland was not identified, and the tumor’s main feeding artery was considered as the left middle adrenal artery by the contrast-enhanced CT; therefore, the tumor was considered to be arising from the adrenal. There were no findings suggesting metastasis to other organs. On MRI, the inner area was heterogeneous, containing T1WI high- intensity areas and T2WI low-intensity areas (Fig. 1) [1-3]. I-metaiodobenzylguanidine (MIBG) scintigraphy showed no uptake in the mass. Blood testing showed increased levels of alka- line phosphatase (ALP; 369 IU/L), y-glutamyl transpeptidase
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T1WI
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T2WI
(Y-GTP; 141 IU/L), lactate dehydrogenase (LDH; 423 IU/L) and C-reactive protein (CRP; 5.15 x 104 µg/L: 5.15 mg/dL) without hypokalemia. Plasma renin activity, aldosterone, adrenocortico- tropic hormone (ACTH), cortisol, dehydroepiandrosterone sul- fate, and serum catecholamines and metanephrines were within normal limits (Table 1). In the analysis of 24-hour urine, fractions of catecholamine and metanephrine levels did not show signifi- cant elevation. He had not previously experienced any malignant tumor. An adrenal malignant tumor, such as adrenocortical car- cinoma or metastatic tumor of unknown origin, was initially sus- pected based on the adrenal artery feeding and the gigantic size of the tumor.
Treatment
An open left retroperitoneal tumor resection was performed. A 15x 10x9 cm tumor was resected. The cut surface was solid, and most of it was whitish, but some hemorrhages and necrotic foci were observed (Fig. 2A). Histologically, the tumor was composed of poorly cohesive cells with round nuclei and eosinophilic cytoplasm, forming pseudopapillary or uniformly solid structure (Fig. 2C and D). Some tumor cells showed pleomorphism. There were about 5 meioses per 10 high power fields. By immunostaining, tumor cells were positive for vimentin, CD56. Cytokeratin AE1/AE3, CD10, cyclin D1, and progesterone receptor were partially positive (Fig. 2E, 2F, and 2H). Some tumor cells showed nuclear/cytoplasmic expression of ß-catenin (Fig. 2G). These findings led to the diagnosis of solid pseudopapillary tumor (SPT).
Outcome and Follow-up
Although the tumor was adjacent to the parenchyma of adrenal gland, there was no definitive evidence of adrenal origin (Fig. 2B). A postoperative blood test showed a decreasing trend in ALP (216 IU/L), y-GTP (119 IU/L), LDH (127 IU/L), and CRP (1.00 × 104 µg/L: 1.00 mg/dL). SPT can recur and older age, male sex, and large tumor size are poor factors for recurrence; thus, we are planning to follow up. After the 6-month follow-up, there is currently no evidence of recurrence in this patient.
Discussion
Solid pseudopapillary tumor (SPT), first described by Frantz in 1959, is a low-grade tumor of the pancreas. SPT accounts for about 0.9% to 2.7% of pancreatic tumors and 5% of cys- tic pancreatic tumors [2]. The male to female ratio of SPT in- cidence is 1:9 and SPT mainly occurs in young women [2].
In adrenal incidentalomas, hormone-producing adrenal tu- mor can be screened for by the measurement of adrenal hor- mones and their upper-level hormones (such as ACTH, cortisol, plasma renin activity [PRA], and plasma aldosterone concentration [PAC]). Cushing syndrome patients autonomous- ly produce cortisol and the upper-level ACTH is suppressed (usu- ally <10 pg/mL). Similarly, primary aldosteronism patients autonomously produce aldosterone and the upper-level PRA is suppressed, that is, the aldosterone to renin ratio (PAC/PRA ra- tio) > 200 is the screening marker. Catecholamine fractions (adrenaline, noradrenaline, and dopamine) and metanephrine fractions (metanephrine and normetanephrine) are measured for screening adrenal pheochromocytoma. In this patient, no
| Hormone | Values | Normal range |
|---|---|---|
| ACTH | 49 pg/mL (10.78 pmol/L) | 7.2-63.3 pg/mL (1.58-13.93 pmol/L) |
| Cortisol | 15.4 µg/dL (424.8 nmol/L) | 7.1-19.6 µg/dL (195.9-540.7 nmol/L) |
| DHEA-S | 105 µg/dL (2.8 µmol/L) | - µg/dL (- µmol/L)ª |
| PRA | 0.7 ng/mL · hr (0.7 µg/L · hr) | 0.3-2.9 ng/mL · hr (0.3-2.9 µg/L · hr) |
| PAC | 35.3 pg/mL (97.8 pmol/L) | 4-82.1 pg/mL (11.1-227.4 pmol/L) |
| Free metanephrine | 21 pg/mL (110.5 pmol/L) | 0-130 pg/mL (0-683.8 pmol/L) |
| Free normetanephrine | 82 pg/mL (447.7 pmol/L) | 0-506 pg/mL (0-2762.8 pmol/L) |
| Adrenaline | <= 0.01 ng/ml ( <= 54.6 pmol/L) | 0-0.1 ng/ml (0-545.9 pmol/L) |
| Noradrenaline | 0.48 ng/ml (2837.3 pmol/L) | 0.1-0.5 ng/ml (591.1-2955.5 pmol/L) |
| Dopamine | 0.02 ng/ml (130.6 pmol/L) | 0-0.03 ng/ml (0-195.8 pmol/L) |
Abbreviations: ACTH, adrenocorticotropic hormone; DHEA-S, dehydroepiandrosterone sulfate; PAC, plasma aldosterone concentration; PRA, plasma renin activity;
“No reference range due to patient’s age (above 60)
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B
E
F
C
D
G
H
particular hormonal findings were detected for the adrenal func- tional analysis.
SPT can occur in extra-pancreatic regions, such as the omentum, mesentery, retroperitoneum, ovary, stomach, and duodenum. There have been 5 (including this case) reports of SPT occurring in the retroperitoneal adrenal region (Table 2). Although contrast-enhanced CT preoperatively re- vealed that the tumor was considered to be fed from adrenal artery and resected adrenal tissue was observed adjacent to the tumor in this case, there were no findings that could be de- termined that the tumor was originated from the adrenal gland. The original cell type of SPT is unknown; however,
the majority of SPT cases are found in the pancreas region. So far, only a single case out of 5 reported cases of SPTs in the ad- renal region (Table 2) was reported to arise from ectopic pan- creas; however, the others did not contain ectopic pancreas [3]. As a possible explanation for this discrepancy, some similar- ities between SPT and ovarian surface cells are reported, and the proximity between germinal ridges and pancreatic primordia during early embryogenesis led to the hypothesis that SPT may be derived from genital ridge anlage-related cells that were incor- porated into the pancreas during organogenesis [5, 7]. This hy- pothesis may explain why most cases of retroperitoneal SPTs, including our present case, occur without ectopic pancreas.
| Author | Pub. year | Age | Sex | Tumor region | Size | Presentation | Ectopic pancreas | Procedure | Recurrence | (Ref.) |
|---|---|---|---|---|---|---|---|---|---|---|
| Miyazaki et al | 2012 | 22 | F | Left adrenal | 7 cm | Abdominal discomfort | — | TLESS | — | [4] |
| Junzu et al | 2012 | 37 | F | Right adrenal | 8.5*8.3* | Regular ultrasound exam | — | Open surgery | — | [5] |
| 7.9 cm | ||||||||||
| Zhu et al | 2013 | 22 | F | Left Adrenal | 6*6*5 cm | Regular ultrasound exam | + | Laparoscopic surgery | — | [3] |
| Guo et al | 2016 | 47 | F | Between left kidney, spleen, and intestine | 16*14 cm | Slight pain in her upper left abdomen, 5 kg weight loss | — | Open surgery | — | [6] |
| This case | 67 | M | Left adrenal | 11.8*10.2* 13 cm | Intermittent fever and lumbago | — | Open surgery | — |
Abbreviation: TLESS, transumbilical laparo-endoscopic single-site adrenalectomy.
The size of SPT may be large at the time of discovery, since there is no specific clinical manifestation, and it may be discov- ered incidentally. Zalatnai et al reviewed in the Pathol Oncol Res. [8], the average size is 6 to 8 cm, and the diameter may reach a maximum of 15 to 22 cm. Significantly, SPT is a round mass with a fibrous pseudo-capsule and shows various cystic de- generation. Necrosis and hemorrhage are detected in the cross section [2]. Pathologically, SPT is composed of poorly cohesive, uniform epithelial cells forming solid and pseudopapillary struc- tures [2]. Immunostaining features include nuclear and cyto- plasmic immunoreactivity to ß-catenin, positivity for CD10, progesterone receptor, cyclin D1, and vimentin and aberrant expression of E-cadherin. Cytokeratins, synaptophysin, and CD56 are positive in 30% to 70% of cases [9]. This patient had the above pathological findings (immunologically B-catenin, CD10, progesterone receptor, cyclinD1, vimentin, cy- tokeratin and CD56 positivity) and was diagnosed with SPT postoperatively.
SPT generally has a good prognosis, with a 5-year survival rate of approximately 97%, including those with metastases. Recurrence after radical surgery occurs in 2% to 10% of cases [10]. Factors that have been suggested to predict recurrence and patient outcome include gender, age, tumor size, resection margins, perineural invasion, vascular invasion, deep invasion into surrounding structures, and Ki-67 proliferation index, but no consensus has been reached. The meta-analysis in patients with SPT shows that men with SPTs may have a poorer prog- nosis, suggesting that this case requires careful follow-up in the future [10].
In conclusion, we experienced a case of retroperitoneal SPT in an older male. The preoperative diagnosis was malignant adrenal tumor because the tumor was large and considered to be fed by the left middle adrenal artery. Surgery was per- formed, and postoperative pathology revealed the diagnosis of SPT, which is a low-grade tumor with a generally good prognosis, although careful follow-up is needed. Although rare, SPT should be considered as a differential diagnosis in cases of a mass arising in the adrenal region.
Learning Points
· We reported a case of retroperitoneal SPT in a 67-year-old man, which was preoperatively diagnosed as malignant adrenal tumor.
· SPT generally has a good prognosis, with a 5-year survival rate of approximately 97%, including those with metastases.
. Although rare, SPT is one of the differential diagnoses in adrenal incidentalomas.
Acknowledgments
The authors deeply appreciate the staff at the endocrine center and the department of urology, Okayama University, for the dedicated efforts in retroperitoneal surgery tumor resection in this patient.
Contributors
Individual contribution of each author is as follows: T.I., T.T., and J.W. made decisions on the patient’s examinations and ther- apies. T.I., T.T., and J.W. reviewed previous publications and wrote the whole manuscript. K.N. is a pathologist and performed the immunohistologic examinations of the SPT. T.I., T.T., and J.W. contributed to the interpretation of the etiology and discus- sion. All authors read and approved the final manuscript.
Funding
None declared.
Disclosures
The authors declare that they have no competing interests.
Informed Patient Consent for Publication
Signed informed consent obtained directly from patient.
Data Availability Statement
Original data generated and analyzed for this case report are included in this published article.
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