Clinical manifestations and multi-slice computed tomography characteristics of solid pseudopapillary neoplasms of the pancreas between males and females

Solid-pseudo papillary tumor of pancreas (SPNP) is a rare pancreatic tumor that mainly occurs in young women with the ages of 20–30 years old. Indeed, more than 90% of the cases are in females and 85% are in females < 30 years of age [1]. SPNP is an indolent tumor and its prognosis is very good, with reported 5-year survival of 95–100% [1, 2]. An exceptional feature of SPNP is that it is rare in males. In fact, SPNP is not even considered as a differential diagnosis in men with pancreas lesions, leading to inaccurate preoperative diagnosis, staging, and prognosis [3‐5]. Nevertheless, it has been suggested that SPNP could be more aggressive in men than in women [6‐11], but the rarity of the disease in men limits the data regarding them. SPNP is a rare benign or lowly malignant tumor that originate from pancreatic pluripotent stem cells [12], and accounts for about 0.3–2.7% of all pancreatic tumors. The pathogenesis of SPNP is unclear, but it has been suggested that the development of SPNP is associated with estrogen [13].It has been reported that tumor stroma and gene mutations exist gender difference [14]. Some researchers suggested that the malignancy of SPNP is associated with the mitosis rate of the tumor cells, as well as nuclear atypia [15].

Most previous studies considered the clinical and pathological characteristics of SPNP; only one study examined the computed tomography (CT) features pf SPNP between males and females [3]. At imaging, the differential diagnosis in male patients should include pancreatic cancer, pancreatic pseudocyst, and nonfunctional neuroendocrine tumor.

Improving our knowledge about the imaging features of SPNP could improve its diagnosis in male patients. Ever improving technologies could help achieve this goal. Therefore, the aim of this retrospective study was to analyze the clinical and multi-slice computed tomography (MSCT) data of patients with SPNP according to sex. The differences in the clinical manifestations and MSCT characteristics of the male and female patients were compared to improve the understandings of SPNP and help increasing the diagnostic accuracy.

SPNP are rare in men and are often misdiagnosed. Therefore, the aim of this study was to analyze the clinical and MSCT features of patients with SPNP, and examine the differences between males and females. The results suggest that the imaging features of male SPNP are distinct from that of female patients. In males with pancreatic lesions, MSCT generally shows relatively small lesions with higher percentages of solid components and calcification, with typical enhancement suggesting SPNP.

The previous study with the largest sample size [1] reported that SPNP is more common in young females, and that the ratio of males to females was 1:9.78. The mean age of their patients was 22 years. In the present study, median age at presentation was 30 years, and the male to female ratio was 1:3.1. The exact reasons for the age discrepancy could be that the patients seek medical attention later than in the West. Regarding the sex distribution, the bias could be due to the small sample size. In the present study, many male patients were diagnosed by histopathological examination of the surgical specimen. Indeed, as SPNP lacks typical clinical manifestations and as most radiologists are unaware of the imaging presentations in male SPNP patients, the rate of imaging misdiagnosis of SPNP is very high [3].

In this study, the median age of the male SPNP patients was 56 years at, and five of the seven patients were > 50 years of age, which was significantly higher than in the female patients, as supported by Lin et al. [6]. For most of the male SPNP patients (5/7), a capsule was found and the margins were clear, but it was not significantly different from the female SPNP patients. The size of the lesions was smaller in the male SPNP group. These observations indicated that men seem to have a later occurrence of SPNP and suggested that there is a difference in the developmental stage between men and women. In addition, percentage of solid tumors was higher, while percentages of hemorrhagic and cystic changes were lower in the male group than in the female group, which was in agreement with the findings reported by Lam et al. [7]. Zou et al. [14] found that collagen tend to be the main component of tumor stroma in SPNP males,while hyaluronan (HA) composed a considerable proportion in females, which was consistent with the conventional characteristics of SPNP [16]. McCarthy et al. [17] reported that HA in stroma could promote tumor cell proliferation,which may explain the growth pattern and the degenetive changes in females in our study. MSCT scanning showed punctate calcifications or striped calcifications in the SPNP lesions. The calcifications in the tumor could be caused by the degeneration of tumor and deposition of calcium. Calcification could appear in the tumor or at the capsule. Previous studies reported that about 30% of the SPNPs are found with calcification [1, 18]. In this study, we found that the percentage of calcification was as high as 71.4% in the male SPNP patients, which was significantly higher than the 31.8% in the female patients. The difference could be associated with female hormones, as estrogens have been shown to play a role in the development of SPNP [13]. Researchers has reported that a much stronger expression of androgen receptor (AR) was found in males [14], and he also found mutations of CTNNB1 exon 3 was observed in all 30 cases, which distributed at codon 32,33 and 37 in both genders and 34,31 and 62 in females, and this might be a clue to the underlying mechanism of the gender difference. In addition, the relatively sample size of this study could also play a role. Anil et al. [5] and Choi et al. [19] suggested that the rich blood vessels and small blood sinuses in the solid components of the tumor could contribute to the high propensity of hemorrhage. In this study, hemorrhage was found in the SPNPs in both males and females, but the difference between the two groups was not significant. In addition, the capacity of CT of displaying hemorrhage is lower than that of magnetic resonance imaging [20, 21], and thus further examinations were needed for the final diagnosis.

The interior components of SPNP could be solid dominant, cystic and solid, and cystic dominant. For the cases with solid dominant SPNP, the cystic components could be covered by the capsule. For the cases with cystic and solid SPNP, the tumor could show a “floating cloud” sign that the solid components seemed to float in the cystic components, or the tumor was chequered with solid components and cystic components [5]. While for the cystic dominant SPNP, the solid components were mainly shown as the mural nodules. The enhancement pattern of typical SPNP is low enhancement in the AP, with the enhancement degree lower than the normal pancreatic tissues; while the VP and DP show progressive enhancement, with the area of enhancement increase gradually [5, 21, 22]. In this study, the pattern and degree of enhancement in the male patients were similar to the typical SPNP. The interior components of SPNP, as well as the enhancement pattern, were not significantly different between the male and female patients. Nevertheless, no “floating cloud” sign was found in the male SPNP patients, which could be associated with the lesser extent of cystic changes in the male patients. A previous study has reported that relatively large tumor at the pancreatic head could compress the pancreatic and bile ducts, and induce the dilation of such ducts, but would not induce the atrophy of the distal end of pancreas [12]. In this study, nine patients were found with the SPNP at the pancreatic head, among which two were found with dilation of the pancreatic and bile ducts, and one was with atrophy of the pancreatic tail, which was in agreement with the findings reported by Hu et al. [3]. We speculated that such changes could be associated with the relatively slow growth of the tumor, or the neuroendocrine origin tumors which were mainly in the pancreatic parenchyma and tended to grow outward [23]. Therefore, the pancreatic ducts and the surrounding structures were generally compressed.

The present study has limitations. First, it was a retrospective study of a rare condition and conducted in a single center. Hence, the sample size was small. A porspective study is needed to validate the results in multiple centers. Second, there is no genetic and molecular level of auxiliary experiments, and so it is not possible to clarify the causal relationship between genetic mutations and MSCT characteristics. Therefore, it is necessary to expand the statistical samples, and improve the study on gene and molecular level.

In summary, SPNP is rare in male patients. The clinical and imaging features of SPNP are different between male and female patients. Specifically, the male SPNP patients are older and the tumors are smaller. In addition, the tumors contain higher percentage of solid components and calcifications. SPNP should be considered for male patients with pancreatic mass.