Acinar neoplasms of the pancreas—A summary of 25 years of research

Klimstra, David S.; Adsay, Volkan

doi:10.1053/j.semdp.2016.05.009

Cited by 50 publications

(33 citation statements)

References 84 publications

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“…Similarly, IOPN can exhibit a solid or tubular growth pattern but ITPN lacks the abundant granular eosinophilic cytoplasm of IOPN. The back-to-back tubules of ITPN, each of which has a relatively small lumen, closely simulate the pattern of acinar neoplasms 63–67 . Most acinar cell carcinomas are large solid lesions and demonstrate no involvement of the native pancreatic ducts.…”

Section: Discussionmentioning

confidence: 78%

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Intraductal Tubulopapillary Neoplasm of the Pancreas

Basturk¹,

Adsay

Askan³

et al. 2017

American Journal of Surgical Pathology

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Background Intraductal tubulopapillary neoplasm (ITPN) is a relatively recently described member of the pancreatic intraductal neoplasm family. Thus, the literature on its histologic and immunohistochemical features, clinical behavior, and its similarities and differences from other pancreatic neoplasms is limited. Design Thirty-three cases of ITPN, the largest series to date, were identified. Immunohistochemical labeling for cytokeratins, glycoproteins, pancreatic enzymes, markers for intestinal and neuroendocrine differentiation, and antibodies associated with genetic alterations previously described in pancreatic neoplasms were performed. Clinicopathologic features and survival was assessed. Results Seventeen patients were female, fourteen were male. Mean age was 55 years (range, 25–79). Median overall tumor size was 4.5 cm (range, 0.5–15). Forty-five percent of the tumors occurred in the head, 32% in the body/tail, and 23% showed diffuse involvement. Microscopically, the tumors were characterized by intraductal nodules composed of tightly packed small tubular glands lined by cuboidal cells lacking apparent mucin. Although it was often challenging to determine its extent, invasion was present in 71%. Almost all tumors labeled for CAM5.2, CK7 and CK19; most expressed CA19.9, MUC1 and MUC6. CDX2, MUC2, trypsin, chymotrypsin, chromogranin and synaptophysin were not expressed. SMAD4 expression was retained in 100%, p16 expression and p53 overexpression was seen in 33% and 27%. Follow-up information was available for twenty-two patients (median follow-up, 45 months; range, 11–173). Two patients with invasive carcinoma died of disease at 23 and 41 months. One patient died of unrelated causes at 49 months. Twelve patients were alive with disease. Seven patients were alive with no evidence of disease. The overall 1-, 3- and 5-year survival rates were 100% in patients without an invasive component and 100%, 91% and 71% in patients with an invasive component (p=0.7). Conclusions ITPN is a distinct clinicopathologic entity in the pancreas. Despite the difficulties of determining the extent of invasive carcinoma in many cases, the overall outcome appears relatively favorable and substantially better than that of conventional ductal adenocarcinoma, even when only the cases with invasive carcinoma are considered.

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Section: Discussionmentioning

confidence: 78%

“…Fortunately, immunohistochemistry is very helpful. Acinar cell carcinomas consistently express pancreatic enzymes such as trypsin, chymotrypsin, and lipase and generally lack expression of CK19 63–67 . ITPNs consistently fail to express pancreatic enzymes.…”

Section: Discussionmentioning

confidence: 99%

Intraductal Tubulopapillary Neoplasm of the Pancreas

Basturk¹,

Adsay

Askan³

et al. 2017

American Journal of Surgical Pathology

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“…However, rare cases have been described in which an intraductal growth pattern is present either focally or extensively. Some in fact show papillary formations within the native ducts (137,141,142). Acinar cell carcinomas with intraductal spread can be difficult to distinguish from ITPN by routine microscopy, but immunohistochemistry is very helpful.…”

Section: Differential Diagnosismentioning

confidence: 99%

Intraductal neoplasms of the pancreas: an update

Aşkan

Bağcı²,

Memiş³

et al. 2017

TJPATH

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ABStRACtwith improvements in imaging to detect silent pancreatic lesions and increases in the number of centers now performing pancreatic surgery, more surgeries have been performed for indications other than invasive carcinoma. This has enormously added to our knowledge of the intraductal neoplasms of the pancreas. In addition, our understanding of the genetics of these lesions has expanded with the introduction of routine molecular genetic analyses. In this review, we provide an update into the most common intraductal neoplasms, namely intraductal papillary mucinous neoplasm and intraductal tubulopapillary neoplasm. we first focus on their clinicopathologic and molecular features of relevance to the practicing pathologist and then discuss their differential diagnoses.

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“…1 In addition to characteristic morphological features, the diagnostic hallmark of acinar cell carcinomas is the immunohistochemical expression of acinar-specific exocrine enzymes, such as trypsin and chymotrypsin. 2 The common genetic aberrations of ductal adenocarcinomas, such as mutations in KRAS, DPC4, and TP53 genes, are generally absent or uncommon in pancreatic acinartype neoplasms. Alterations in the APC/β-catenin pathway, either through activating mutations of CTNNB1 gene or truncating mutations of APC gene, have been reported in a subset of pancreatic acinar-type neoplasms (20-50%).…”

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confidence: 99%

“…Alterations in the APC/β-catenin pathway, either through activating mutations of CTNNB1 gene or truncating mutations of APC gene, have been reported in a subset of pancreatic acinar-type neoplasms (20-50%). 2 As chemo and radiation therapies have limited efficacy against these tumors, exploring genetic aberrations in pancreatic acinar-type neoplasms to identify actionable molecular targets may trigger the development of novel therapies.…”

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confidence: 99%

A FISH assay efficiently screens for BRAF gene rearrangements in pancreatic acinar-type neoplasms

et al. 2018

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Approximately 1-2% of pancreatic neoplasms are acinar cell carcinomas. Recently, BRAF gene rearrangements were identified in over 20% of acinar-type neoplasms, which included both pure acinar cell carcinomas and mixed carcinomas with acinar differentiation, using next-generation sequencing-based platforms, providing a potential therapeutic target for patients with these neoplasms. Thus, it is clinically important to develop a rapid, cost- and material-efficient assay to screen for BRAF gene fusions in pancreatic acinar-type neoplasms. We developed a dual color, break-apart FISH assay to detect BRAF gene rearrangements in these neoplasms and evaluated its performance in comparison to next-generation sequencing-based studies. A blinded BRAF rearrangement FISH investigation was performed on 31 acinar-type neoplasms that had been studied previously by next-generation sequencing-based analysis as well as on 18 additional acinar-type neoplasms that were accrued over the past 2 years. In total, BRAF fusions were identified in 12/49 (24%) acinar-type neoplasms by FISH. BRAF fusion partners were uncovered by using targeted next-generation sequencing studies in 11 FISH-positive cases that had sufficient material for next-generation sequencing studies. SND1 was the most frequent fusion partner involved in BRAF-fusion acinar-type neoplasms (50%), followed by HERPUD1 (18%). No BRAF fusions were identified by next-generation sequencing in any of the FISH-negative cases investigated. FISH analysis showed that BRAF rearrangements were diffusely present across tumor-rich areas in BRAF-fusion acinar-type neoplasms, which is consistent with an oncogenic driver alteration pattern. Thus, we demonstrated that, in comparison to targeted next-generation sequencing-based technologies, the FISH assay is highly sensitive and specific as well as time- and cost-efficient in the detection of BRAF fusions in acinar-type neoplasms. The FISH assay can be easily implemented in diagnostic settings to identify acinar-type neoplasms patients potentially suitable for targeted therapy to inhibit MAPK pathway activity.

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Acinar neoplasms of the pancreas—A summary of 25 years of research

Cited by 50 publications

References 84 publications

Intraductal Tubulopapillary Neoplasm of the Pancreas

Intraductal Tubulopapillary Neoplasm of the Pancreas

Intraductal neoplasms of the pancreas: an update

A FISH assay efficiently screens for BRAF gene rearrangements in pancreatic acinar-type neoplasms

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