Solid-Pseudopapillary Neoplasm of Pancreas: Insights from Cytopathology

Abstract

Background:

Solid-pseudopapillary neoplasm (SPEN) is a rare pancreatic tumor, constituting 2–3% of all pancreatic neoplasms, primarily affecting young women with a median age of 30. Its prognosis is generally favorable due to the low incidence of metastasis and successful surgical resection. Accurate preoperative diagnosis is crucial, as its cytological features are distinctive.

Aim:

To elucidate the significance of cytopathology in the detection of SPEN, associated diagnostic pearls and pitfalls, and histopathologic correlation.

Materials and Methods:

All SPEN cases diagnosed through cytomorphology were retrieved from the hospital medical records, and relevant clinical information was compiled. Cytopathology and histopathology slides were obtained from the archives and reviewed.

Results:

All four cases were middle-aged women (mean age = 40 years) presenting with abdominal pain. Imaging showed solid-cystic lesions. The diagnosis of SPEN was rendered on fine needle aspiration cytology (FNAC), with characteristic papillary and glandular patterns. Histology confirmed the diagnosis with 100% cytohistological concordance in all four cases.

Conclusion:

FNAC is an effective tool for the detection of SPEN, allowing precise diagnosis, guiding surgery, and reducing the need for extensive resection.

INTRODUCTION

Solid-pseudopapillary neoplasm (SPEN) is an extremely uncommon pancreatic tumor, accounting for approximately 2–3% of all pancreatic neoplasms and 1–3% of exocrine pancreatic neoplasms.[1] It is most commonly observed in young women (90%) with a median age of 30 years.[2] The prognosis is usually favorable due to the low incidence of metastases and the high percentage of long-term survival attained by surgical resection of these tumors.[3,4] Hence, an accurate preoperative diagnosis is highly desirable in these tumors. The cytological characteristics of this tumor are quite distinctive, and hence it is imperative for the pathologists not to miss this diagnosis.[5] This study hammers home the essence of this pathological awareness.

MATERIALS AND METHODS

All cases of SPEN that had been diagnosed on cytomorphology between January 2019 and July 2024 were retrieved from the electronic medical record of the hospital, and the relevant clinical details were cataloged. The corresponding cytopathology and histopathology slides were fetched from the pathology department archives and reviewed.

RESULTS

All four cases were middle-aged females with a mean age of 40 years (age range: 35–47 years). They all presented with a chief complaint of abdominal pain to the gastroenterology department of our institute. Imaging was performed in all four cases, which revealed heterogeneously enhancing, circumscribed, and solid-cystic lesions ranging from 4.5 to 11.5 cm in greatest dimension. In three of the patients, the tumor was located in the head of the pancreas, while in one patient, it was in the body of the pancreas.

Cytological characteristics

In all four patients, ultrasonography -guided fine needle aspiration cytology (FNAC) was performed. The diagnosis of SPEN was rendered on cytology by fine needle aspiration, based on which surgical resection of the masses was performed. The morphological examination of the cytology smears revealed cells arranged in papillae with central capillaries, as well as in a glandular pattern [Figure 1]. The cells were mostly uniform in appearance, with round to oval-shaped nuclei displaying overlapping and overcrowding, fine chromatin, and a small to moderate amount of cytoplasm. Nuclear grooves and hyaline globules were present in two of our cases. Rosettes were seen in only one case [Figure 2]. Necrosis was not seen in any of our cases, whereas mitoses were occasional or absent. Cercariform cells were not observed in any of the cases that we reported.

Figure 1.

(a) Smears are paucicellular and show few papillary clusters (hematoxylin and eosin [H&E], 100×). (b) Papillary clusters lined by uniform round to oval cells showing overlapping and overcrowding, mild anisokaryosis, regular nuclei, fine chromatin, and a moderate amount of cytoplasm (H&E, 400×)

Figure 2.

(a) Smears are markedly cellular and show a tumor disposed in papillary patterns with prominent fibrovascular core, glandular pattern as well as singly scattered in a background of hemorrhage (hematoxylin and eosin [H&E], 100×). (b) Individual cells are largely monomorphic, round to oval in shape, with uniform chromatin, occasional nuclear grooves, and a scant to moderate amount of cytoplasm (H&E, 400×). (c) Hyaline globules noted as well as vague rosettes in the background (H&E, 400×)

Histomorphology and immunohistochemistry

The histomorphology of all four cases revealed similar findings on light microscopic assessment of the surgical resection of the neoplasms. All the cases displayed tumor cells arranged in a pseudopapillary arrangement, vague glands, and perivascular arrangement. Individual cells were monomorphic, small, round with centrally placed nuclei, fine to stippled chromatin, inconspicuous nucleoli, and moderate eosinophilic cytoplasm [Figure 3]. Immunohistochemistry (IHC) was performed in three out of four cases. Markers which disclosed immunoreactivity were vimentin, beta-catenin, synaptophysin, CD10, CD56, and cyclin D1 [Figure 4].

Figure 3.

(a and b) Section shows tumor cells arranged in pseudopapillary arrangement, vague glands, and perivascular arrangement (hematoxylin and eosin [H&E], 100×). (c) Tumor cells are monomorphic, small round with centrally placed nuclei, fine to stippled chromatin, inconspicuous nucleoli, and moderate eosinophilic cytoplasm (H&E, 400×)

Figure 4.

(a) Immunohistochemistry for beta-catenin shows nuclear positivity in tumor cells (IHC, 100×). (b) IHC for cyclin D1 shows nuclear positivity in tumor cells (IHC, 100×). (c) IHC for CD10 shows membranous positivity in tumor cells (IHC, 100×). (d) IHC for E-cadherin shows loss of membranous staining in tumor cells (IHC, 100×). IHC = immunohistochemistry

Cytohistological correlation

The final impression in all four cases on histopathology echoed the diagnosis rendered on cytopathology, thus registering a 100% concordance.

DISCUSSION

SPENs of the pancreas are uncommon tumors with distinct clinical and pathological features. They are also known as “Frantz tumors,” named after Dr. Frantz, who first described them in 1959.[6] SPEN should be considered in adolescent or young adult females who present with an abdominal mass and a radiologically identified cystic or partially cystic, well-defined pancreatic mass.[7] Most of these neoplasms are either benign or exhibit very low-grade malignant behavior, leading to a favorable prognosis following surgical removal. However, up to 15% of patients may experience metastasis, with the most common sites being regional lymph nodes, the liver, mesentery/omentum, and the peritoneum.[8]

An analysis of the surveillance epidemiology and end results database indicated that SPENs in females exhibit a bimodal age-frequency distribution, with an early onset peak at 28 years and a later peak at 62 years. In contrast, male patients demonstrate a unimodal peak at 64 years.[9] In our study, due to the limited number of cases, we noted a narrow age range among the patients, and all of them were females.

Most patients with SPENs are reported to have nonspecific symptoms, and some are found incidentally.[10] Most of our patients presented with abdominal pain or discomfort. The tumors in our cohort had an average size of 7.5 cm, which is similar to the dimensions reported in other studies.[11] These tumors are typically solitary and are more commonly found in the tail of the pancreas,[10], whereas in our cases, they were mostly located in the head region.

Cytology has become a crucial component in the evaluation and diagnosis of pancreatic tumors.[12] Accurately identifying SPENs through cytology is essential to avoid unnecessary aggressive treatments, such as preoperative chemoradiation and radical surgery. Aspirates typically divulge small, loosely cohesive groups, microacini, and isolated tumor cells. Notably, thin and delicate or thick and hyalinized branching fibrovascular papillae are characteristic of SPENs. These vascular stalks are lined by one or more layers of uniform cuboidal neoplastic cells with indistinct cell borders. The nuclei are consistent in appearance, being round or oval, with finely dispersed chromatin, subtle nucleoli, and occasional intranuclear grooves. Another distinctive feature is the presence of metachromatic hyaline globules, which comprise amorphous myxoid material and can be found intracellularly, extracellularly, or within the microacinar lumina. The presence of cercariform cells is a key cytological characteristic of SPENs and plays a vital role in differentiating them from neuroendocrine pancreatic tumors.[13] Pseudoreosette formation is also described. In our study, all the cases showed papillary fragments with pseudo-rosettes identified in one case, while hyaline globules were noted in two cases.

Jayaram et al.[14] considered the presence of intracytoplasmic inclusions as a distinctive feature of this neoplasm, a feature not evident in any of our cases. Cappellari et al.[15] considered the nuclear folds or grooves to be a characteristic of this tumor, as seen in two of our cases. Binucleation and multinucleation of tumor cells are also described, not present in any of our cases. Mucinous changes in the stalks of papillae, foamy cells, and multinucleated giant cells are also mentioned earlier in reports; however, none were seen in our cases. Mitosis is not a usual feature of this tumor, nor was it observed in our cases either.

The differential diagnosis of SPEN includes conditions such as pseudocyst, pancreatic mucinous neoplasms (PMN), well-differentiated ductal adenocarcinoma, pancreatic neuroendocrine tumor (PNT), and acinic cell carcinoma (ACC).

Pseudocysts do not have an epithelial lining, leading to hypocellular smears that display granular debris, hemosiderin, inflammatory cells, and pigmented macrophages. Additionally, fibrovascular stalks, papillae, and epithelial cells are absent in pseudocysts. Aspirations of PMN are paucicellular, displaying only a few sheets of columnar mucinous cells with small, uniformly located basally positioned nuclei, abundant apical cytoplasm, and clear cell borders. The lower cellularity, the presence of abundant thick colloid-type mucin, and the columnar cell morphology can help differentiate PMN from SPEN. PNT poses a significant challenge in differentiating from SPEN due to overlapping morphological and immunohistochemical features. Several studies have outlined reliable diagnostic approaches to distinguish between PNT and SPEN.[16] Key cytomorphological characteristics identifiable include the presence of cohesive and discohesive populations of neoplastic cells. Smears may reveal various patterns such as solid sheets, rosettes, pseudo-rosettes, or papillary formations. The nuclei are usually eccentrically located, giving the cells a plasmacytoid appearance, and the chromatin exhibits a characteristic granular or “salt and pepper” appearance. At times, the cytological and histomorphological similarities between PNT and SPEN can be so pronounced that IHC becomes necessary for accurate differentiation. Beta-catenin (nuclear expression in SPEN) and E-cadherin (loss of expression in SPEN) can be the only immuno-saviors in such a scenario, since SPEN can express neuroendocrine markers such as synaptophysin and CD56. ACC may exhibit similar cytomorphological features, such as monomorphism; however, key differences are evident in nuclear characteristics. ACC typically displays prominent nucleoli without a papillary configuration or a perivascular myxoid appearance. Additionally, ACC features abundant granular cytoplasm with indistinct cell borders.

Histopathological findings of SPEN mirror the cytological features. The vessels running through the solid nests of neoplastic cells observed in histology correspond to the fibrovascular stalks of the pseudopapillae identified in the aspirates. In histology, areas of cellular degeneration due to the discohesion of cells distant from the vasculature create a false papillary architecture, along with the degenerative background seen in the smears.

Our cases demonstrated a 100% histo-cytological correlation in the resection specimens. This finding aligns with the results of Wang et al.,[17] Jahangir et al.,[18] and Mehta et al.[19] who explored the cytohistological correlation in 17, 9, and 6 cases, respectively.

CONCLUSION

FNAC can be a very promising procedure in the detection of SPEN, provided the pathologists are aware of the diagnostic pearls and pitfalls. The successful confirmation of the initial cytologic diagnosis through histological evaluation of the resected specimens in all four patients who underwent surgery in our study reinforces this conclusion. A precise diagnosis on cytology itself can obviate the need for biopsy, aid the surgeon in unambiguous operative intervention, and thereby avoid debilitating extensive surgical resection.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.