Adrenocortical Adenoma With Protrusion Into the Inferior Vena Cava Initially Suspected to Be Adrenocortical Carcinoma.

Adrenal tumors with invasion into the inferior vena cava (IVC) are typically malignant. Here, we present a case of adrenocortical adenoma with protrusion into the IVC. A 70-year-old man was referred to our hospital after his magnetic resonance imaging scan of the abdomen coincidently revealed a right adrenal tumor invading the IVC. We suspected an aggressive adrenal carcinoma and tumor resection was performed. However, all 3 existing pathological criteria (Weiss, modified Weiss, and Helsinki) suggested the tumor was benign. Immunohistochemistry for CD31 showed the tumor inside the central adrenal vein (CAV), right adrenal vein (RAV), and IVC was entirely covered with CD31-positive vascular endothelial cells. The CAV is known to sometimes lack smooth muscle in its walls and normal adrenocortical cells covered by endothelial cells sometimes protrude into the CAV from this gap. These findings suggest that this tumor likely protruded into the IVC by pushing against the CAV wall, rather than by invasion into the vascular wall. In the case with adrenal tumors protruding into the IVC, the fact that the tumor surface was covered by vascular endothelial cells was considered supportive of its benign nature.

A patient alive without disease 32 months after conversion surgery following lenvatinib treatment for hepatocellular carcinoma with a tumor thrombus originating in the middle hepatic vein and reaching the right atrium via the suprahepatic vena cava: a case report.

Conversion surgery for initially unresectable hepatocellular carcinoma appears to be increasing in incidence since the advent of new molecular target drugs and immune checkpoint inhibitors; however, reports on long-term outcomes are limited and the prognostic relevance of this treatment strategy remains unclear. Herein, we report the case of a 75-year-old man with hepatocellular carcinoma, 108 mm in diameter, accompanied by a tumor thrombus in the middle hepatic vein that extended to the right atrium via the suprahepatic vena cava. He underwent conversion surgery after preceding lenvatinib treatment and is alive without disease 51 months after the commencement of treatment and 32 months after surgery. Just before conversion surgery, after 19 months of lenvatinib treatment, the main tumor had reduced in size to 72 mm in diameter, the tip of the tumor thrombus had receded back to the suprahepatic vena cava, and the tumor thrombus vascularity was markedly reduced. The operative procedure was an extended left hepatectomy with concomitant middle hepatic vein resection. The tumor thrombus was removed under total vascular exclusion via incision of the root of the middle hepatic vein. Histopathological examination revealed that more than half of the liver tumor and the tumor thrombus were necrotic.

Interobserver agreement of pathologic classification and grading of tumoral intraductal pre-invasive neoplasms of the bile duct.

Current WHO terminology and recent publications have classified tumoral (grossly visible) intraductal pre-invasive neoplasms of bile duct (TIDN) into three categories: intraductal papillary neoplasm of bile duct (IPNB), intraductal papillary oncocytic neoplasm (IOPN), and intraductal tubulopapillary neoplasm (ITPN). A total of 227 cases of TIDN and related lesions ≥3 mm in height were examined by 10 biliary pathologists referring to these 3 categories and two pathologic gradings: two-tiered system (low- and high-grade dysplasia) and modified types 1 and 2 subclassification. Among them, IPNB was the most frequent (183 cases), followed by IOPN (28 cases), while ITPN was rare (2 cases), and interobserver agreement in this classification was "substantial" (κ-value, 0.657). The interobserver agreement of two-tiered grading system of TIDN was "slight" (κ-value, 0.201), while that of modified types 1 and 2 subclassification was "moderate" (κ-value, 0.515), and 42 % were of type 1, and 58 % were of type 2. Type 1 TIDN showed occasional stromal invasion (6.7 %), whereas type 2 TIDN was frequently associated with stromal invasion (49.6 %) (p < 0.01). In conclusion, the classification of TIDN into three categories and modified types 1 and 2 subclassification are a practically applicable classification and grading system for TIDN.

Gene expression profiling of pancreatic neuroendocrine carcinoma and mixed neuroendocrine-non-neuroendocrine neoplasm.

Pancreatic neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are rare pancreatic malignant tumors, and comprehensive gene analyses are scarce. In this study, six NECs and six MiNENs were collected, immunohistochemistry for synaptophysin, chromogranin A, INSM1, Ki-67, and Rb was conducted, and KRAS mutational status was examined. Among these cases, comprehensive gene expression analysis of oncogene pathways using nCounter® were performed with six NECs and four MiNENs, and those data were compared with that of three pancreatic ductal adenocarcinomas (PDACs), with that of three normal pancreatic ducts, and with each other. By dividing NEC and MiNEN cases into KRAS-mutated group and KRAS-wild group, the difference of clinicopathological data and gene expression profiling data were examined between the two groups. Compared to the data of normal pancreatic epithelium, all 13 cancer-related pathways were upregulated in PDAC, MiNEN, and NEC group with more upregulation in this order. Compared to the data of PDAC, genes of DNA Damage repair pathway was most upregulated both in NECs and MiNENs. Regarding the difference between KRAS-mutated and KRAS-wild groups, several genes were differentially expressed between the two, where MMP7 was the upregulated gene with highest p-value and NKD1 was the downregulated gene with highest p-value in KRAS-mutated group. From the extent of upregulation of 13 pathways, MiNEN was considered more progressed stage than PDAC, and NEC was considered more progressed than MiNEN. From the comparison of KRAS-mutated and KRAS-wild NECs and MiNENs, several differentially expressed genes were identified in this study.

Prospective evaluation of common hepatic duct histopathology at the time of choledochal cyst excision ranging from children to adults.

PURPOSE: To evaluate common hepatic duct just distal to the HE anastomosis (d-CHD) prospectively for mucosal damage, inflammation, fibrosis, dysplasia, carcinoma in situ, malignant transformation, effects of serum amylase, and symptoms at presentation in CC cases ranging from children to adults. METHODS: Cross-sections of d-CHD obtained at cyst excision 2018-2023 from 65 CC patients; 40 children (< 15 years old), 25 adults (≥ 15) were examined with hematoxylin and eosin, Ki-67, S100P, IMP3, p53, and Masson's trichrome to determine an inflammation score (IS), fibrosis score (FS), and damaged mucosa rate (DMR; damaged mucosa expressed as a percentage of the internal circumference). RESULTS: Mean age at cyst excision ("age") was 18.2 years (range: 3 months-74 years). Significant inverse correlations were found for age and DMR (p = 0.002), age and IS (p = 0.011), and age and Ki-67 (p = 0.01). FS did not correlate with age (p = 0.32) despite significantly increased IS in children. Dysplasia was identified in a 4-month-old girl with cystic CC. Serum amylase was elevated in high DMR subjects. CONCLUSIONS: High DMR, high IS, and evidence of dysplasia in pediatric CC suggest children are at risk for serious sequelae best managed by precise histopathology, protocolized follow-up, and awareness that premalignant histopathology can arise in infancy.

MR Fingerprinting for Contrast Agent-free and Quantitative Characterization of Focal Liver Lesions.

Purpose To evaluate the feasibility of liver MR fingerprinting (MRF) for quantitative characterization and diagnosis of focal liver lesions. Materials and Methods This single-site, prospective study included 89 participants (mean age, 62 years ± 15 [SD]; 45 women, 44 men) with various focal liver lesions who underwent MRI between October 2021 and August 2022. The participants underwent routine clinical MRI, non-contrast-enhanced liver MRF, and reference quantitative MRI with a 1.5-T MRI scanner. The bias and repeatability of the MRF measurements were assessed using linear regression, Bland-Altman plots, and coefficients of variation. The diagnostic capability of MRF-derived T1, T2, T2*, proton density fat fraction (PDFF), and a combination of these metrics to distinguish benign from malignant lesions was analyzed according to the area under the receiver operating characteristic curve (AUC). Results Liver MRF measurements showed moderate to high agreement with reference measurements (intraclass correlation = 0.94, 0.77, 0.45, and 0.61 for T1, T2, T2*, and PDFF, respectively), with underestimation of T2 values (mean bias in lesion = -0.5%, -29%, 5.8%, and -8.2% for T1, T2, T2*, and PDFF, respectively). The median coefficients of variation for repeatability of T1, T2, and T2* values were 2.5% (IQR, 3.6%), 3.1% (IQR, 5.6%), and 6.6% (IQR, 13.9%), respectively. After considering multicollinearity, a combination of MRF measurements showed a high diagnostic performance in differentiating benign from malignant lesions (AUC = 0.92 [95% CI: 0.86, 0.98]). Conclusion Liver MRF enabled the quantitative characterization of various focal liver lesions in a single breath-hold acquisition. Keywords: MR Imaging, Abdomen/GI, Liver, Imaging Sequences, Technical Aspects, Tissue Characterization, Technology Assessment, Diagnosis, Liver Lesions, MR Fingerprinting, Quantitative Characterization Supplemental material is available for this article. © RSNA, 2023.

Premalignant/malignant histology in excised choledochal cyst specimens from children. Experience and literature review.

BACKGROUND: Dysplasia, carcinoma in situ, and other malignant transformation or premalignant/malignant histopathology (PMMH) seem uncommon in pediatric choledochal cyst (CC). A literature review and the authors' experience are presented. METHODS: All reports about PMMH in CC patients 15 years old or younger published in English and all cases of PMMH in specimens excised from CC patients 15 years old or younger by the authors were reviewed. RESULTS: Of 20 published reports, PMMH was adenocarcinoma (n = 4), sarcoma (n = 4), and dysplasia (n = 12). Treatment for malignancies was primary pancreaticoduodenectomy (PD; n = 2) or cyst excision/hepaticojejunostomy (Ex/HJ; n = 6). Outcomes at the time of writing for malignancies: 2 deaths, 4 survivors after follow-up of 2 years, and 2 lost to follow-up. No dysplasia case has undergone malignant transformation. The authors have experienced 7 cases of PMMH; adenocarcinoma in situ (AIS; n = 1) and dysplasia (n = 6). CONCLUSIONS: The present study identified the youngest cases of AIS and dysplasia from specimens excised when they were 3 years old and 4 months old, respectively. Both are published for the first time as evidence that PMMH can complicate CC in young patients. Long-term protocolized postoperative follow-up is mandatory when PMMH is diagnosed in pediatric CC.

Pathological survey of precursor lesions in cholangiocarcinoma.

BACKGROUND: To clarify the pathological significance of two precursors (high-grade biliary intraepithelial neoplasm [BilIN] and intraductal papillary neoplasm of bile duct [IPNB]) in cholangiocarcinomas (CCAs). METHODS: Ninety-one cases of CCA (47 distal CCAs [dCCAs], 31 perihilar CCAs [pCCAs] and 13 intrahepatic CCAs of large duct type [LD-iCCAs]) were examined for their association with precursors. Neoplastic intraepithelial lesions without underlying infiltrating carcinoma in the surrounding mucosa of CCAs were considered to reflect high-grade BilIN. High-grade BilIN and IPNB were subdivided into gastric, biliary, intestinal and oncocytic subtypes, while CCAs were subdivided into gastrobiliary, intestinal and oncocytic subtypes. The postoperative overall survival (OS) was examined. RESULTS: Fifty-four and 8 of 91 CCAs were associated with high-grade BilIN and IPNB, respectively, while these precursors were unidentifiable in the remaining CCAs. A majority of CCAs were of the gastrobiliary subtype, while the intestinal subtype was occasionally detected, and the oncocytic subtype was rare. CCAs with high-grade BilIN showed a similar postoperative OS to CCAs without precursors, while CCAs with IPNB showed a favorable postoperative OS compared to CCAs without precursors. CONCLUSIONS: CCAs were frequently associated with precursors; high-grade BilIN may be a major precursor and IPNB a minor one. CCAs with IPNB showed a favorable postoperative OS compared to CCAs with high-grade BilIN.

Intraepithelial involvement of non-neoplastic glands in papillary preinvasive neoplasms of the biliary tract: a potential diagnostic pitfall.

Intracholecystic papillary neoplasms of the gallbladder (ICPN) and intraductal papillary neoplasms of the bile duct (IPNB) show intramural neoplastic growths in addition to intraluminal papillary or polypoid neoplastic growth. Such intramural growths include intraepithelial involvement of non-neoplastic glands by preinvasive neoplastic epithelia (glandular involvement) as well as stromal invasive carcinoma. A total of 29 ICPN cases and 84 IPNB cases were pathologically examined for their glandular involvement. Glandular involvement was characterized by intramural neoplastic glands (1) showing cytological and phenotypical similarities to intraluminal preinvasive papillary neoplasms and (2) showing reminiscent configurations of non-neoplastic glands, such as (i) a mixture of preinvasive neoplastic epithelia and non-neoplastic epithelia within the same glands, (ii) neoplastic glands close to or within clustered non-neoplastic glands, or (iii) continuous growth of intraluminal preinvasive neoplastic glands into the walls. Such glandular involvement was found in 16 of 29 ICPN and 48 of 84 IPNB, and 15 of the former and 28 of the latter were not associated with invasive carcinoma. Non-invasive ICPN and IPNB with glandular involvement showed a favorable postoperative overall survival (OS). Glandular involvement by preinvasive neoplastic epithelia was frequently found in ICPN and IPNB. Such lesions may be diagnostic pitfalls in ICPN and IPNB referring to invasion. Glandular involvement without invasive carcinoma was not associated with an unfavorable postoperative OS in ICPN and IPNB. Recognition of glandular involvement may thus prevent overestimation of invasive carcinoma in ICPN and IPNB.

Inflammatory Myofibroblastic Tumor (IMT) of the Trachea Excised by Transtracheal Surgery: Case Report.

This report describes an extremely rare case of a primary inflammatory myofibroblastic tumor of the trachea. The patient underwent surgical resection by a transtracheal approach and reconstruction with esophageal tracheoplasty. This case report highlights the rarity of such tumors and a minimally invasive and safe surgical technique for tumors around the central neck structures.

MR Fingerprinting for Liver Tissue Characterization: A Histopathologic Correlation Study.

Background Liver MR fingerprinting (MRF) enables simultaneous quantification of T1, T2, T2*, and proton density fat fraction (PDFF) maps in single breath-hold acquisitions. Histopathologic correlation studies are desired for its clinical use. Purpose To compare liver MRF-derived metrics with separate reference quantitative MRI in participants with diffuse liver disease, evaluate scan-rescan repeatability of liver MRF, and validate MRF-derived measurements for histologic grading of liver biopsies. Materials and Methods This prospective study included participants with diffuse liver disease undergoing MRI from July 2021 to January 2022. Participants underwent two-dimensional single-section liver MRF and separate reference quantitative MRI. Linear regression, Bland-Altman plots, and coefficients of variation were used to assess the bias and repeatability of liver MRF measurements. For participants undergoing liver biopsy, the association between mapping and histologic grading was evaluated by using the Spearman correlation coefficient. Results Fifty-six participants (mean age, 59 years ± 15 [SD]; 32 women) were included to compare mapping techniques and 23 participants were evaluated with liver biopsy (mean age, 52.7 years ± 12.7; 14 women). The linearity of MRF with reference measurements in participants with diffuse liver disease (R2 value) for T1, T2, T2*, and PDFF maps was 0.86, 0.88, 0.54, and 0.99, respectively. The overall coefficients of variation for repeatability in the liver were 3.2%, 5.5%, 7.1%, and 4.6% for T1, T2, T2*, and PDFF maps, respectively. MRF-derived metrics showed high diagnostic performance in differentiating moderate or severe changes from mild or no changes (area under the receiver operating characteristic curve for fibrosis, inflammation, steatosis, and siderosis: 0.62 [95% CI: 0.52, 0.62], 0.92 [95% CI: 0.88, 0.92], 0.97 [95% CI: 0.96, 0.97], and 0.74 [95% CI: 0.57, 0.74], respectively). Conclusion Liver MR fingerprinting provided repeatable T1, T2, T2*, and proton density fat fraction maps in high agreement with reference quantitative mapping and may correlate with pathologic grades in participants with diffuse liver disease. © RSNA, 2022 Online supplemental material is available for this article.

Pathologies of Precursor Lesions of Biliary Tract Carcinoma.

Carcinomas and precursor lesions of the biliary tract belong to a spectrum of pancreatobiliary neoplasms that share common histology and cell lineages. Over the past two decades, preinvasive precursors to biliary tract carcinomas (BTCs) have been identified such as high-grade biliary intraepithelial neoplasm (high-grade BilIN), intraductal papillary neoplasm of bile duct (IPNB) and intracholecystic papillary neoplasm of the gallbladder (ICPN). While a majority of these precursors may arise from the biliary tract mucosa, some originate from the peribiliary glands and Rokitansky-Aschoff sinuses in the walls of the biliary tract. High-grade BilIN is a microscopically identifiable intraepithelial neoplasm of the biliary tract, whereas IPNB and ICPN are grossly visible intraductal or intraluminal preinvasive neoplasms in the bile duct and gallbladder, respectively. These neoplasms show characteristic histologic features according to four cell lineages and two-tiered grading, and show intraepithelial spreading to the surrounding mucosa and involve non-neoplastic glands in the walls of the biliary tract. These precursors are not infrequently associated with stromal invasion, and high-grade BilIN, in particular, are frequently identified in the surrounding mucosa of BTCs. Taken together, it seems likely that progression from these precursors to invasive carcinoma is a major process in biliary carcinogenesis.

Pathologic patterns of invasive carcinoma associated with intraductal papillary neoplasms of bile duct (IPNB).

The pathologic features of invasive carcinoma associated with IPNB remain to be clarified. By using 82 cases of IPNB, the pathologic spectrum of associated invasive carcinoma and its correlation with their post-operative overall survival (OS) were examined. Invasive carcinoma was found in 52 cases (63 %) of IPNB and was classifiable into three patterns (patterns A, B and C). Pattern A was characterized by microscopic foci of invasive carcinoma in the fibrovascular stalks or confined to the bile duct mucosa and wall beneath the intraluminal pre-invasive neoplastic components of IPNB (23 cases) and pattern B by invasive carcinoma in the periductal connective tissue and in the adjacent organ(s) mainly near or beneath the intraluminal component(s) of IPNB (15 cases). Pattern C showed nodular invasive carcinoma considerably involving the intraluminal pre-invasive components and the bile duct mucosa and wall adjacent to the intraluminal pre-invasive components of IPNB (14 cases). Recognition of these three patterns of invasive carcinoma associated with IPNB may expand the pathologic spectrum of IPNB. IPNBs without invasive carcinoma showed a favorable post-operative-OS compared with those with invasion as a whole and those of pattern B and C, respectively, but showed a similar post-operative-OS to that of pattern A. IPNB of pattern B and C showed an unfavorable post-operative outcome, though there was no difference between pattern B and C. Understanding of the pathologic spectrum of associated invasive carcinoma may facilitate further pathological analysis of IPNB.

Focal pancreatic parenchyma atrophy is a harbinger of pancreatic cancer and a clue to the intraductal spreading subtype.

BACKGROUND/OBJECTIVES: Radiological evidence of focal pancreatic parenchymal atrophy (FPPA) may presage early pancreatic ductal adenocarcinoma (PDAC) development. We aimed to clarify the incidence of FPPA and the clinicopathological features of PDAC with FPPA before diagnosis. METHODS: Data on endoscopic ultrasound-guided fine-needle biopsies and surgical samples from 170 patients with pancreatic cancer histologically diagnosed between 2014 and 2019 were extracted from the pathology database of Komagome Hospital and Juntendo University hospital and retrospectively evaluated together with 51 patients without PDAC. RESULTS: FPPA was identified in 47/170 (28%) patients before PDAC diagnosis and in 2/51 (4%) patients in the control group (P < 0.01). The median duration from FPPA detection to diagnosis was 35 (interquartile range [IQR]:16-63) months. In 24/47 (51%) patients with FPPA, the atrophic area resolved. The lesion was in the head and body/tail in 7/40 and 67/56 of the patients with (n = 47) and without FPPA (n = 123), respectively (P < 0.001). Histopathologically confirmed non-invasive lesions in the main pancreatic duct and a positive surgical margin in the resected specimens occurred in 53% vs. 21% (P = 0.078) and 29% vs. 3% (P = 0.001) of the groups, respectively. The PDAC patients with FPPA accompanied by a malignant pancreatic resection margin had high-grade pancreatic intraepithelial neoplasia. CONCLUSIONS: FPPA occurred in 28% of the PDAC group at 35 months prediagnosis. The FPPA area resolved before PDAC onset. Benchmarking previous images of the pancreas with the focus on FPPA may enable prediction of PDAC. PDAC with FPPA involves widespread high-grade pancreatic intraepithelial neoplasia requiring a wide surgical margin for surgical excision.

Investigation of -PRKACA/-PRKACB fusion genes in oncocytic tumors of the pancreatobiliary and other systems.

Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreatobiliary system are tumors comprising oncocytic cells, in which three types of fusion genes involving -PRKACA/-PRKACB were recently identified. IOPNs infrequently combine with other histological subtypes of pancreatic intraductal papillary mucinous neoplasms (IPMNs) and intraductal papillary neoplasms of the bile duct (IPNBs). This study aimed to confirm the sensitivity/specificity of the fusion genes for IOPNs and to examine their significance in other oncocytic lesions. An RT-PCR, followed by DNA sequencing, was undertaken to examine the fusions in 18 histologically diagnosed IOPNs, including four combined IOPNs. Moreover, in two IOPN cases, invasive carcinomatous lesions were separately examined on their fusion status. Oncocytic thyroidal (n = 10), renal (n = 10), and salivary gland (n = 3) lesions and IPMNs (n = 9)/IPNBs (n = 4) with focal oncocytic changes were examined as controls. Fluorescence in situ hybridization using PRKACA break-apart probes was conducted for the combined IOPN cases. Target sequencing of KRAS exon2/3 and GNAS exon 8/9 was performed for IOPN cases. Fusions were detected in all IOPN cases including invasive lesions/none of the control cases. The fusion event was confirmed also in non-IOPN component in one of the four combined cases. Regarding mutation events, 5.6%/0% of IOPNs were KRAS-mt/GNAS-mt, respectively, and both components of combined IOPNs were all KRAS-wt/GNAS-wt. In conclusion, our study confirmed the sensitivity and specificity of these fusions for IOPNs. Here, we analyzed the roles of these fusion genes in combined IOPNs, proposing the possibility of IOPN development via IPMNs/IPNBs. Further studies with more combined cases are warranted.

DNMT1 Expression and DNA Methylation in Intraductal Papillary Neoplasms of the Bile Duct.

BACKGROUND/AIM: Intraductal papillary neoplasms of the bile duct (IPNB) are histologically and clinically classified as type 1 and 2. This study aimed to identify the differences between these two types. MATERIALS AND METHODS: Based on multiple gene expression analysis (MGEA) using type 1, type 2, and pancreatic intraductal papillary mucinous neoplasms (n=4, 6, and 5, respectively), immunohistochemistry of DNMT1 and methylation-specific PCR for p16, APC, BRCA1, hMLH1, TIMP3, and SOX17 were performed on type 1 and 2 IPNBs (n=14, each). RESULTS: The DNMT1 protein was highly expressed (p<0.001) in 28.6% of type 1 cases and all type 2 cases. The DNA methylation ratio for the six genes in total as well as for SOX17 was lower in type 1 than in type 2 (p<0.05 each). CONCLUSION: Type 2 IPNB showed increased DNMT1 protein expression and increased DNA methylation frequency of the examined tumor suppressor genes compared to type 1. DNMT1 IHC may be helpful in discriminating between these two types.

Intralobular distribution of ovarian-like stroma in pancreatic mucinous cystic neoplasms: a discussion on its tumorigenesis.

Pancreatic mucinous cystic neoplasm (MCN) has two histological components: tumor epithelia and ovarian-like stroma (OLS). To examine the progression and changes in pancreatic MCNs, we analyzed the distribution, amount, immunohistochemical phenotype, presence of theca cells of OLS, and tumor epithelium in 45 surgically resected MCN cases, comparing them with tumor sizes. The OLS data of female MCN cases were also compared between those who were ≤ 51 years old and those > 51 years old to see the effect of menopause on MCN histology. Non-mucinous type epithelium was present in all low-grade MCNs, but its ratio decreased with tumor size (p < 0.001), suggesting that epithelial mucinous changes are a progression phenomenon. The intralobular distribution of OLS was observed in 28.8% of MCN cases and was related to smaller tumor size (p < 0.0001), suggesting intralobular involvement of early MCNs. The nuclear expression of ß-catenin and the cytoplasmic expression of α-smooth muscle actin (SMA) was observed in almost all OLS. OLS tended to be lesser among female cases aged > 51 years than those ≤ 51 years old, however it did not reach statistical significance. This is the first study to show the intralobular distribution of OLS.

Survival comparison of invasive intraductal papillary mucinous neoplasm versus pancreatic ductal adenocarcinoma.

BACKGROUND: The aim of this study was to assess the relevance of highlighting T1a invasive intraductal papillary mucinous carcinoma as a separate subcategory and to compare the tumor biology between invasive intraductal papillary mucinous carcinoma and pancreatic ductal adenocarcinoma. METHODS: A total of 144 and 328 consecutive patients with intraductal papillary mucinous neoplasms and pancreatic ductal adenocarcinoma, respectively, were analyzed. RESULTS: Patients with T1a invasive intraductal papillary mucinous carcinoma comprised 25% (11/44) of the overall subject population with invasive intraductal papillary mucinous carcinoma with 5-year disease-specific survival rate being 100%. None of the patients with pancreatic ductal adenocarcinoma were classified as having T1a disease. When patients with invasive intraductal papillary mucinous carcinoma and pancreatic ductal adenocarcinoma were compared after excluding patients with T1a invasive intraductal papillary mucinous carcinoma, the 5-year disease-specific survival rates were 63% vs 40% in node-negative status (P = .018); and they were 20% vs 13% in node-positive status (P = .385). Subsequent analyses revealed that this survival superiority was limited to patients without evidence of lymphatic invasion. CONCLUSION: T1a invasive intraductal papillary mucinous carcinoma is a clinical entity specifically observed in patients with intraductal papillary mucinous carcinoma, but not in patients with pancreatic ductal adenocarcinoma, and is associated with excellent postoperative survival outcomes. In the survival comparison after exclusion of patients with T1a tumors, when the analysis was limited to patients without lymphatic invasion or lymph node metastasis, the disease-specific survival rate remained higher in patients with invasive intraductal papillary mucinous carcinoma compared with those with pancreatic ductal adenocarcinoma, and this difference was considered as being attributable to the intrinsic indolent biological behavior of invasive intraductal papillary mucinous carcinoma. However, this survival advantage was lost once lymphatic invasion occurred.