Solid serous cystadenoma of the pancreas: A rare tumor with challenging differential diagnosis

Lu Srgoni , Crlo Alerto Pilio , , Dvide Cvliere , Frneso Limrzi ,Cludio Isopi , Giorgio Erolni ,

a Pathology Unit, Morgagni-Pierantoni Hospital, AUSL Romagna, Via Carlo Forlanini 34, 47121, Forlì, Italy

b General and Oncologic Surgery Unit, Morgagni-Pierantoni Hospital, AUSL Romagna, Via Carlo Forlanini 34, 47121, Forlì, Italy

c Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy

To the Editor:

Cystic tumors of the pancreas are rare, accounting for 1%-5% of exocrine pancreatic tumors. Serous cystadenoma (SCA) was firstly described by Compagno and Oertel in 1978 as a benign glycogenrich neoplasm [1] . In 1996 Perez-Ordonez et al. [2] reported the first case of a solid variant of SCA; since then, 23 cases of this extremely uncommon tumor variant were reported. Due to its rarity and unusual imaging appearance, a correct differential diagnosis is difficult and can lead to mistaken diagnosis and unnecessary treatment. According to Surgical CAse REport (SCARE) Guidelines [3] ,we present the second case of pancreatic solid SCA (SSCA) reported in Italy, the first surgically treated with a robotic approach worldwide.

A 52-year-old woman with a past medical history of thyroidectomy for papillary carcinoma was submitted to a routine abdominal ultrasound with incidental finding of a pancreatic solid mass.The patient had an unremarkable family history, and did not report alcohol consumption nor smoking habit and her body mass index was within normal range (22.8 kg/m2). Routine laboratory exams and neoplastic markers did not show any alteration. Magnetic resonance (MR) imaging showed a 14-mm solid mass within the body of the pancreas, with contrast enhancement in arterial phase and wash-out in venous phase ( Fig. 1 ). The magnetic resonance cholangiopancreatography (MRCP) showed a solid lesion not connected to pancreatic ductal system ( Fig. 2 ). Suspecting a pancreatic neuroendocrine tumor (pNET), a positron emission tomography-computed tomography (PET-CT) scan with68Ga-DOTANOC was performed, revealing a weak standard uptake value(SUV) of the lesion (SUVmax = 7.3). Chromogranina A, calcium,parathyroid hormone and glucose plasmatic levels were all within normal range. She was evaluated by our reference endocrinologist who performed a routine neck ultrasonography, finding no clinical alteration. The lesion was further investigated with an endoscopic ultrasound with fine needle aspiration biopsy. The endoscopic ultrasound showed a round hypoechoic 15 mm mass, with irregular borders, within the isthmus-body of the pancreas, in close proximity to the spleno-mesenteric confluence. The evaluation with intravenous ultrasound contrast (Sonovue) exhibited a homogenous arterial enhancement with late washout; the lesion was then biopsied with a 25G needle for on-site cytopathology and with a 22G needle for final histology. The cytology was inconclusive, containing only a small number of epithelial cells with round, regular nuclei and scant to moderate (sometimes clear) cytoplasm. The specimen did not allow an immunohistochemical analysis due to the very low number of epithelial cells. The histology revealed a lowgrade epithelial neoplasm, with an acinar growth pattern within fibrous tissue. Neoplastic cells were regular with no evident mitoses.The immunohistochemical analysis showed positive stains for cytokeratin 7 and alpha-1 antitrypsin, while stains for chromogranin A, synaptophysin andβ-catenin were negative.

Due to the uncertain diagnosis, also in order to exclude an acinar cell carcinoma, a distal pancreatectomy with splenectomy was proposed to the patient. Surgery was performed through a threearm robotic approach with Da Vinci Si platform and performing an intraoperative ultrasound. Postoperative course was characterized by pancreatic fistula grade B, managed conservatively. Patient was discharged with a drain on the 7th postoperative day.

At pathology, examination of the specimen disclosed a single,solid, brownish nodular lesion with pushing margin and stretched elastic consistency, measuring 20 mm on its greater axis. It was well-circumscribed and similar to a NET. There was no evidence of cystic changes. Microscopically the lesion was composed by cells with clear cytoplasm, no signs of atypia, no necrosis and no mitosis(low proliferative index assessed by Ki-67 staining). The cells were organized in tubular/acinar structures, with small/absent lumina. A delicate network of fibrous septa was intermingled with the tubular structures ( Fig. 3 ). Immunohistochemical findings were as follows: cytokeratin 7 + , cytokeratin 19 + ( Fig. 4 ), MUC6 + ,β-catenin-,chromogranin A-, synaptophysin- and cytokeratin 20-. PAS staining was positive in the cytoplasm, while PAS-diastase staining was negative, indicating the presence of abundant intra-cytoplasmatic glicogen. In the light of the morphological and immunohistochemical data, the case was diagnosed as a solid serous adenoma (according to 2019 WHO classification).

Fig. 1. MR axial image showing a 14-mm solid mass within the isthmus of the pancreas.

Fig. 3. Low ( A , original magnification × 20) and high ( B , original magnification × 40) magnification view showing cells organized in tubules/acini, with no signs of atypia and no mitosis. The tubular/acinar structures are intermingled with fibrous stroma.

SCA has usually (more than 70% of cases) a characteristic polycystic honeycomb pattern (microcystic); a more uncommon pattern is the oligocystic (macrocystic), which has to be further differentiate from mucinous cystic tumors, intraductal papillary mucinous neoplasms or pseudocysts [ 4 , 5 ]. It should be remembered that SCA can occur with increased frequency in patients with Von Hippel-Lindau disease. Moreover, an extremely rare variant of SCA is the SSCA, with only 23 literature reported cases. SCA is almost invariably a benign tumor, except for some reported anecdotal case of malignancy, and it usually does not require a surgical resection.Unfortunately, SSCA presents an unusual imaging appearance, often misleads preoperative diagnosis and unnecessary surgical resection [6] . Table 1 contains the main clinical features of all the SSCA cases reported in literature. In summary, median age was 59.5 (range 39-74) years, female was slightly predominant (n= 14,58.3%) and in more than half of cases (n= 13, 54.2%) the SSCA was asymptomatic and incidentally found. The tumors were mainly located in pancreatic body-tail (n= 14, 58.3%) and the median size was 2.8 (range 1.6-8.0) cm. Regarding preoperative diagnosis,the most frequent diagnostic hypothesis was a pNET, which was at least one of the diagnosis taken into consideration in 18 cases(75.0%); other less frequent diagnoses were pancreatic ductal adenocarcinoma (PDAC), solid pseudopapillary tumor and metastasis.Only in one case, it was supposed a preoperative diagnosis of SSCA.Except three cases, in which the treatment is not reported, all the lesions underwent surgical resection.

The solid appearance of this benign neoplasm requires a complex differential diagnosis with other solid tumors of the pancreas,all with worse prognosis (pNET, PDAC). Differential diagnosis is made more difficult by the fact that SCA can show signs of aggressive behavior (vascular invasion, invasion of adjacent organs or adjacent lymph nodes). This, however, is not sufficient to pose a diagnosis of malignancy for this type of lesions, since the diagnosis of a malignant serous cystadenocarcinoma can be formulated only when distant metastasis is present [7] .

Fig. 4. Positive staining for cytokeratin 7 ( A and C ) and cytokeratin 19 ( B and D ) ( A and B , original magnification × 5; C and D , original magnification × 10).

Table 1 Clinical features of the 24 cases of pancreatic solid serous cystadenoma.

In 2012 Hayashi et al. [8] usefully reported three cases of SSCA,trying to identify its specific features on CT scan: they concluded that low density on unenhanced CT scan or on delayed phase and the presence of a fibrous capsule may represent useful signs to differentiate SSCA from a pNET. Moreover, in cases where sampling is possible, staining for chromogranin and synaptophysin must always be considered, to help rule out a diagnosis of pNET [9] . Our current case was the first one reported in the literature with a different preoperative diagnosis: after the diagnostic work-up, an acinar cell carcinoma, which is itself a rare pancreatic tumor with several specific features [10] , could not be excluded at all, leading the patient to surgery.

In conclusion, the solid histotype of SCA is very rare and has an unusual imaging appearance and non-specific histological findings,especially on small samples. All this contributes to an increased risk of misdiagnosis (mostly as a pNET, due to the similar radiological appearance) and unnecessary surgical treatment. For this reason, despite being a rare entity, it must be kept in mind by radiologists and pathologists alike.

Acknowledgments

None.

CRediT authorship contribution statement

Luca Saragoni: Conceptualization. Carlo Alberto Pacilio: Writing - original draft. Davide Cavaliere: Investigation. Francesco Limarzi: Writing - review & editing. Claudio Isopi: Data curation.Giorgio Ercolani: Supervision.

Funding

None.

Ethical approval

This study was approved by the Ethics Committee of Romagna(No. 5481/2020-I.5/263). Written informed consent was obtained from the patient.

Competing interest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.