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We report the histopathological, immunohistochemical (IHC), and molecular findings in 3 patients with adult pancreatoblastoma, including 2 with autopsy features. The tumors were located in the tail and body of the pancreas, and the 2 autopsy examinations revealed liver and lung metastases. Histopathologically the neoplasms were composed of solid epithelial elements with nested or trabecular growth patterns, fibrous stroma, and squamoid clusters. Keratin 19 was positive mainly in squamoid corpuscles, and trypsin or chymotrypsin was positive in the acinar component. Neuroendocrine differentiation was observed in all tumors, and nuclear β-catenin expression in 2 tumors. Despite nuclear β-catenin expression, CTNNB1 mutation was found only in tumor 2. APC mutation was detected in tumor 1, and SMAD4 as well as MEN1 mutations in tumor 3. This last tumor also revealed chromosomal instability with many chromosomal losses and gains. The follow-up showed regional or distant metastases in all patients. Two patients died of disease after 3 and 26 months of follow-up and 1 patient is alive with no evidence of disease 6 years and 2 months after surgery. Adult pancreatoblastoma can display genetic heterogeneity, diverse histological appearance, and overlapping IHC findings. As a result, the differential diagnosis with other adult pancreatic tumors, such as acinar cell carcinoma, neuroendocrine neoplasm, solid pseudopapillary neoplasm, and mixed tumors may be challenging, especially when dealing with limited tumor tissue. The identification of squamoid corpuscles is essential for diagnosis. Although molecular findings might provide useful information, the integration of clinical, radiological, and histopathological findings is essential in pancreatoblastoma diagnosis. [ABSTRACT FROM AUTHOR]

Mesenchymal neoplasms with GLI1 alterations (rearrangements and/or amplification) have been reported recently in several anatomic locations, which include head and neck, soft tissue, and gastrointestinal tract. Herein, to the best of our knowledge, we describe the first three cases of superficial/subcutaneous mesenchymal neoplasm with GLI1 amplification. The neoplasms exhibited low‐grade cytologic features with predominant round cell morphology, glomangioma‐like areas and a rich background capillary network. There were two to three mitotic figures per 10 HPF and focal necrosis in one case. The tumors exhibited variable expression of CDK4, MDM2, STAT6, D2‐40, CD56 and cyclin D1. p16 had strong and diffuse nuclear and cytoplasmic expression in two cases. Numerous other stains were negative. Fluorescence in situ hybridization detected GLI1, DDIT3, and CDK4 coamplification in all cases, while next generation sequencing did not detect a GLI1 gene fusion. The overall features were compatible with a GLI1‐amplified mesenchymal neoplasm. In Case 1 a new distant skin lesion appeared 1 month after the surgery exhibiting similar morphology albeit with a higher mitotic index. In Cases 2 and 3, there is no evidence of local recurrence or systemic disease after 8 years and 1 month of follow‐up, respectively. These new cases of superficial GLI1‐amplified neoplasm expand its clinical spectrum and enter the realm of dermatopathology. The combination of CDK4, cyclin D1, D2‐40, and p16 expression with variable MDM2, STAT6, CD56, and S100 immunoreactivity in a low‐grade neoplasm with round/ovoid cytomorphology resembling a vascular or adnexal neoplasm may suggest the possibility of GLI1‐amplified neoplasm. [ABSTRACT FROM AUTHOR]

The clinical evolution of solitary fibrous tumors (SFTs) is often uncertain and several risk stratification systems (RSS) have been proposed. The Demicco et al. RSS is the most frequently implemented. In this study we aim to validate two alternative RSS (Sugita et al. and G-Score) using results for the Demicco RSS from a previous study of 97 SFTs. In addition, we aim to determine whether reclassified cases had any distinctive molecular features. As the Sugita et al. system substitutes mitotic count with Ki-67 index we also investigated whether Ki-67 results for tissue microarrays are comparable to those obtained using whole tissue sections. In the present study we detected that many cases classified by Demicco RSS as low-risk were reclassified as intermediate risk using the new system (G-score RSS). Kaplan-Meier survival plots for G-Score RSS showed that the low-risk and intermediate-risk SFTs had a similar evolution that contrasted with the more aggressive high-risk group. Moreover, the similar evolution in both low and intermediate-risk groups occurred despite the G-score system being stricter in classifying low-risk tumors. We observed that Sugita RSS does not provide any better risk stratification in comparison with the Demicco RSS, and testing both RSS in our series produced similar Kaplan-Meier survival data. We found some discordant results when comparing whole sections and the corresponding tissue microarrays samples, finding the hotspot areas easier to locate in whole sections. Forty-one SFTs with initial low-risk assigned by the Demicco RSS were reclassified as intermediate-risk by G-score finding both TP53 and HTER mutations in four cases, only HTER mutation in 11 cases, and only TP53 mutation in 2 cases. All six cases of SFT classified as high-risk by both the Demicco and G-score RSS suffered recurrence/metastasis, and half showed both TP53 and HTER mutations. Five SFTs were categorized as low-risk by both Demicco and G-score, of which 4 cases revealed HTER mutation. Regarding the outcome of these 5 patients, two were lost to follow-up, and one of the remaining three patients suffered recurrence. We believe that although the presence of both TP53 and HTER mutations may confer or be related to poor evolution, the isolated presence of HTER mutation alone would not necessarily be related to poor outcome. The G-score RSS more accurately identified low-risk patients than the other two risk models evaluated in the present series. Late recurrence/metastasis may occasionally be observed even in low-risk SFTs categorized by stricter classification systems such as the G-score RSS. These findings support the possibility that additional, as yet unknown factors may influence the clinical evolution of SFTs. In conclusion, given the possibility of late recurrence, long-term follow-up is recommended for all SFT patients, even in cases classified as low risk by the stricter G-score system. An integration of clinical, radiological, pathological, and molecular findings may improve SFT risk stratification and better predict patient outcome. [ABSTRACT FROM AUTHOR]