Solid and Pseudopapillary Tumor of the Pancreas—Review and New Insights Into Pathogenesis

Abstract

Solid pseudopapillary tumors (SPT) of the pancreas are rare neoplasms that occur mostly in young women. Despite of a low malignant potential, 10% to 15% of the cases have aggressive behavior with metastatic dissemination possibly leading to death. To date, no pathological factor can reliably predict the outcome of these tumours. Galectin-3, a major actor in the carcinogenesis of pancreatic ductal adenocarcinoma, has not been investigated in SPT. The presence of progesterone receptors is frequently reported in SPT, whereas that of estrogen receptor (ER) is unclear. We studied 5 cases of SPT consisting of 4 pancreatic tumors and 1 metastatic case. The morphological distinctive feature of metastatic nodules was the presence of polygonal or spindle cells with pleiomorphic nuclei and high mitotic count exhibiting a diffuse, infiltrative growth pattern. We found a strong expression of galectin-3 in all SPTs, whereas, interestingly, it was lower in metastatic nodules. Conversely, no galectin-3 expression was found in normal pancreatic endocrine cells or in neuroendocrine tumors. We suggest therefore that galectin-3 is a useful marker to distinguish SPT from neuroendocrine tumor, and also indicator of behavior because its low expression is associated with metastatic spreading. Moreover, the presence of galectin-3 in both SPT and pancreatic ducts rises the hypothesis of a posible ductal origin of these tumors. Specific antibodies for anti-ERalpha and anti-ERbeta demonstrated a strong expression of ERbeta whereas ERalpha was not detected. In conclusion, the present study brings the first evidence of the involvement of galectin-3 in SPT but also brought up clues which allowed to reconcile previously conflicting results on the presence of ER.

Expression and functional consequences of oestrogen and progesterone receptors in human insulinomas

“…The use of 'traditional' ER antibodies with no anti-b activity could explain why ER has previously been scarcely found in pancreatic tumours. ERb is reported to be relatively more expressed than ERa in papillary cystic neoplasms of the pancreas (Morales et al 2003), solid pseudopapillary tumours (Geers et al 2006) and human pancreatic cancer cell lines (Konduri & Schwarz 2007). Our study shows for the first time that there is a considerably high expression of ER in human insulinomas and it is predominantly of the ERb isoform.…”

Tumor sólido pseudopapilar de pâncreas: relato de um caso com apresentação incomum

“…É mais comum em pacientes na segunda e terceira décadas de vida, com (8) , ocorrendo na maioria dos casos no sexo feminino (2,3,(6)(7)(8)(9)(10) , contrapondo-se ao presente estudo, com paciente do sexo masculino de 37 anos. Devido a essa predominância no sexo feminino foi proposto que os hormônios sexuais pudessem fazer parte da gênese tumoral, entretanto ensaios imuno-histoquímicos não são unânimes na demonstração de receptores de estrógeno nessas células.…”

Limited usefulness of histopathological features in identification of a clinically aggressive solid-pseudopapillary neoplasm of the pancreas

“…Other investigators found differences in IHC pattern between primary and secondary deposits of SPN. Geers et al observed weak/negative CD10, CD56, galectin-3 and PR staining in liver metastasis of SPN [70]. In other report, primary SPN and metachronous liver metastasis showed focally positive and negative CD10 staining, respectively [22].…”

“…Some nuclear morphometric features may also be useful for prediction of clinical aggressiveness of SPN as well [69]. Some researchers tested IHC stains as potential predictors of aggressive behavior: CD10, CD56, PgR, synaptophysin, p53, Ki-67, α1-antitrypsin, α1-antichymotrypsin, neuron-specific enolase, galectin-3, vimentin, chromogranin, pan-cytokeratin, Cam5.2, and epithelial membrane antigen (EMA) [11,24,32,33,70,71].…”

“…Continue ar features (size, chromatin pattern, nucleoli, atypia) and nuclear grade were described according to the definitions by Nishihara et al [49]; (f) marked nuclear pleomorphism was recognized when variation of nuclear size was 4-fold or larger [7]; (g) ENETS tumour grade was assessed using criteria based on mitotic count and Ki-67 proliferative index [1,76]; (h) SPC criteria were based on 2000 WHO publication [15]; (i) undifferentiated component was defined as area of diffuse growth pattern, tumour necrosis, nuclear atypia and 'unusually high' mitotic rate [33,59]; (j) ENETS and AJCC tumour stage criteria were applied based on reference publications [76,77]; and (k) histopathological score was documented as proposed by Nishihara et al [49]. Additionally, cases were examined also for presence of clear cells (vacuolization change) [4,25,70,78,79], rhabdoid morphology [25], spindle cells [80,81], oncocytic cells [14], eosinophilic (hyaline) globules [2], cholesterol clefts and foamy cells [2], as well as microcystic/ pseudoglandular growth pattern [4,13,25,82]. The number of histological slides containing neoplastic tissue among study cases ranged from 2 to 12 (median 5).…”