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Abstract Aim Pancreatic reconstruction after pancreaticoduodenectomy (PD) that leaves a small remnant pancreas is often difficult. Pancreatic fistula is a major complication after PD, and fistulas are rare in patients with hard pancreas. However, the clinical impact of non‐reconstructed small remnant after PD with hard pancreas is unknown. Methods We included all patients who underwent PD for pancreatic tumor without pancreatic reconstruction in two institutions supervised by one surgeon between January 2004 and March 2021. Their short‐ or long‐term outcome after surgery was retrospectively analyzed. Results PD was performed in 774 patients, of whom 16 patients were without reconstruction (2.1%) with negative margins at the pancreatic stump. Pancreatic transection was performed above or to the left of the superior mesenteric artery, with a median remnant pancreas length of 3.7 cm (range, 1.3–10.0). A major complication (≥ Clavien–Dindo Grade IIIa) occurred in one patient (6%). Fistula of grade B occurred in one patient (6%). After a median follow‐up of 44 months (95%CI, 10.6–77.3), insulin administration was unnecessary in 11 patients. Conclusion The preservation of a small pancreatic remnant without reconstruction after PD can be performed safely and may enable the keeping of pancreatic endocrine function for some selected patients with hard pancreas.

Abstract 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 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.

Abstract Background Fibrolamellar hepatocellular carcinoma (FL-HCC) is a liver tumor that occurs almost exclusively in young adults without underlying liver disease. In spite of its distinct clinical characteristics and specific imaging findings, preoperative diagnosis is often difficult due to the extremely low incidence of the tumor. Although FL-HCC shows particular morphological features on H&E-stained tissue sections, differential diagnosis from ordinary HCC, especially the scirrhous variant of HCC, and intrahepatic cholangiocarcinoma needs additional immunohistochemical (IHC) analyses and/or molecular genetic testing. Case presentation A 21-year-old male patient was referred to our hospital for further evaluation of a large liver mass. Abdominal ultrasound examination, contrast-enhanced computed tomography, and magnetic resonance imaging revealed a well-defined hypervascular lobulated liver mass, 11 × 11 cm in diameter, with a central scar and calcification, in segments 5/8. Under the diagnosis of FL-HCC, we carried out extended anterior sectorectomy, including a part of segment 4. On microscopic examination, the tumor was composed of proliferating polygonal cells with abundant eosinophilic granular cytoplasm containing nuclei with vesicular chromatin and enlarged nucleoli, in an abundant stroma. Collagen fibers arranged in a parallel lamellar pattern were seen in the tumor stroma. These findings, together with the results of subsequent IHC analyses using HAS, CK7, and CD 67, we made the diagnosis of FL-HCC, which was further confirmed by detection of the DNAJB1-PRKACA fusion gene in the tumor cells by RT-PCR. Conclusion FL-HCC shows distinct imaging appearances. Although it also has characteristic morphological features, combined use of IHC and/or molecular genetic studies are necessary for the final diagnosis.

Abstract Determination of the primary tumor in periampullary region carcinomas can be difficult, and the pathological assessment and clinicopathological characteristics remain elusive. In this study, we investigated the current recognition and practices for periampullary region adenocarcinoma with an indeterminable origin among expert pathologists through a cognitive survey. Simultaneously, we analyzed a prospective collection of cases with an indeterminable primary tumor diagnosed from 2008 to 2018 to elucidate their clinicopathological features. All cases with pathological indeterminable primary tumors were reported and discussed in a clinicopathological conference to elucidate if it was possible to distinguish the primary tumor clinically and pathologically. From the cognitive survey, over 85% of the pathologists had experienced cases with indeterminable primary tumors; however, 70% of the cases was reported as pancreatic cancer without definitive grounds. Interpretation of the main tumor mass varied, and no standardized method was developed to determine the primary tumor. During a prospective study, 42 of the 392 periampullary carcinoma cases (10.7%) were considered as tumors with a pathological indeterminable origin. After the clinicopathological conferences, 21 (5.4%) remained indeterminable and were considered final indeterminable cases. Histological studies showed that the tumors spread along both the bile duct and main pancreatic duct; this was the most representative finding of the final indeterminable cases. This study is the first to elucidate and recognize the current clinicopathological features of periampullary region adenocarcinomas with an indeterminable origin. Adequate assessment of primary tumors in periampullary region carcinomas will help to optimize epidemiological data of pancreatic and bile duct cancer.

Abstract Histopathological diagnosis of pancreatic ductal adenocarcinoma (PDAC) on endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) specimens has become the mainstay of preoperative pathological diagnosis. However, on EUS-FNB specimens, accurate histopathological evaluation is difficult due to low specimen volume with isolated cancer cells and high contamination of blood, inflammatory and digestive tract cells. In this study, we performed annotations for training sets by expert pancreatic pathologists and trained a deep learning model to assess PDAC on EUS-FNB of the pancreas in histopathological whole-slide images. We obtained a high receiver operator curve area under the curve of 0.984, accuracy of 0.9417, sensitivity of 0.9302 and specificity of 0.9706. Our model was able to accurately detect difficult cases of isolated and low volume cancer cells. If adopted as a supportive system in routine diagnosis of pancreatic EUS-FNB specimens, our model has the potential to aid pathologists diagnose difficult cases.

Abstract Standardized pathological evaluation of the regression assessment of neoadjuvant pancreatic cancer is necessary to improve prognostication and compare treatment outcomes in clinical trials. However, appropriate tissue sampling from surgically resected pancreatic cancer after neoadjuvant therapy has not been elucidated. We compared the tumor regression scores in the largest cancer slide determined macroscopically or histologically. We reviewed all slides and macroscopic photos of cut surfaces from resected pancreas of patients treated with neoadjuvant chemotherapy (n = 137; chemoradiotherapy or chemotherapy). The tumor regression scores (the Evans, College of American Pathologists, Japanese Pancreas Society grading systems, and Area of Residual Tumor [ART] score) were evaluated for the largest tumor slide determined by macroscopy or histologically as well as all slides from the resected pancreas. The largest cancer slides determined macroscopically and histologically were discrepant in 26% of the cases. Cancer cells were not detected in the largest macroscopically defined cut slides in 3%. Only ART scores assessed in the largest histological slides displayed significant difference in overall survival. We recommend obtaining the largest histological slides to provide adequate assessment for regression of neoadjuvant-treated pancreatic cancer. Sufficient sampling to detect the largest histological slides would be mandatory.

Abstract Background Pancreaticoduodenectomy after esophageal resection is technically difficult, because blood flow of the gastric conduit should be preserved. Celiac axis stenosis (CAS) is also a problem for pancreaticoduodenectomy, because arterial blood supply for the liver comes mainly through the collateral route from the superior mesenteric artery (SMA) via the gastroduodenal artery (GDA). Herein, we report the case of a patient with pancreatic head cancer who underwent a pancreaticoduodenectomy after esophagectomy with concomitant CAS. Case presentation A 76-year-old man with pancreatic head cancer was referred to our department. He had a history of esophagectomy with retrosternal gastric conduit reconstruction for esophageal cancer. Computed tomography showed severe CAS and a dilated collateral route between the SMA and the splenic artery (SPA). We prepared several surgical options depending on the intraoperative findings, and performed radical pancreaticoduodenectomy with concomitant resection of the distal gastric conduit. The right gastroepiploic artery (RGEA) of the remnant gastric conduit was fed from the left middle colic artery (MCA) with microvascular anastomosis. Despite CAS, when the GDA was dissected and clamped, good blood flow was confirmed, and the proper hepatic artery did not require reconstruction. The patient was discharged on postoperative day 90. Conclusions We successfully performed radical pancreaticoduodenectomy after esophagectomy with concomitant CAS, having prepared multiple surgical options depending upon the intraoperative findings.

Abstract Background Endosalpingiosis in the lymph nodes of the mesocolon is very rare. We reported a case with appendiceal endometriosis who had endosalpingiosis in the lymph nodes of the mesocolon that was found during laparoscopic ileocecal resection. Case presentation The patient was a 44-year-old woman who had visited a physician for fever, bloody stool, and abdominal pain 1 year earlier. She was diagnosed with ulcerative colitis on colonoscopy, and symptoms improved with oral treatment. A colonoscopy performed 2 months after diagnosis detected a hard, 20-mm submucosal tumor (SMT) in the cecum. On abdominal contrast CT, an intensely stained mass, including a low-density region, was observed in the cecum. A boring biopsy was performed after mucosal resection of the cecal SMT at our hospital, but diagnosis could not be made. Since the possibility of a malignant lesion could not be ruled out, laparoscopic ileocecal resection was performed. In the resected specimen, a 29 × 27 × 21-mm mass was present in the appendicular root. On histopathological examination, appendiceal endometriosis and endosalpingiosis in the lymph nodes around the ileocolic artery were observed. The postoperative course was favorable, and the patient was discharged 7 days after surgery. Conclusion Differentiation of endosalpingiosis in lymph nodes in the mesocolon from lymph node metastasis of adenocarcinoma is important in patients with an abdominal mass.

This study describes an autopsy case of pancreatic/peripancreatic myeloid sarcoma in a 70-year-old man, initially presenting with obstructive jaundice. Pathologically, diffuse infiltration of round cells containing atypical nuclei with marked cleavage was observed mainly in the pancreas head, peripancreatic lymph nodes, spleen, bilateral lung, and bone marrow. Immunohistochemically, the tumor cells were negative for CD20, CD79a, CD3, CD5, c-kit, CD34, and TdT and positive for myeloperoxidase, CD33, CD68, and CD163. Flow cytometry of the peripheral blood showed underexpression of CD11c and aberrant expression of CD56 in the monocyte subset. The peripheral blood smear showed an increase in monocytes and atypia in neutrophils and monocytes, as well as enlarged platelets and polychromatic erythroblasts. Hence, it was suggested that the myeloid sarcoma was derived from the acute transformation of chronic myelomonocytic leukemia. Myeloid sarcoma is an extramedullary-mass-forming hematologic malignancy that is difficult to diagnose, especially when the initial presentation is a pancreatic mass. However, early diagnosis is important for appropriate therapy. Although bone marrow examination could not be performed because of the patients’ severe condition, the pathological specimen obtained with autopsy helped subtype the patient’s leukemia. The immunohistochemical features of this case merit attention.

Biliary atresia (BA) is characterized by the inflammation and obstruction of the extrahepatic bile ducts (EHBDs) in newborn infants. SOX17 is a master regulator of fetal EHBD formation. In mouse Sox17+/− BA models, SOX17 reduction causes cell-autonomous epithelial shedding together with the ectopic appearance of SOX9-positive cystic duct-like epithelia in the gallbladder walls, resulting in BA-like symptoms during the perinatal period. However, the similarities with human BA gallbladders are still unclear. In the present study, we conducted phenotypic analysis of Sox17+/− BA neonate mice, in order to compare with the gallbladder wall phenotype of human BA infants. The most characteristic phenotype of the Sox17+/− BA gallbladders is the ectopic appearance of SOX9-positive peribiliary glands (PBGs), so-called pseudopyloric glands (PPGs). Next, we examined SOX17/SOX9 expression profiles of human gallbladders in 13 BA infants. Among them, five BA cases showed a loss or drastic reduction of SOX17-positive signals throughout the whole region of gallbladder epithelia (SOX17-low group). Even in the remaining eight gallbladders (SOX17-high group), the epithelial cells near the decidual sites were frequently reduced in the SOX17-positive signal intensity. Most interestingly, the most characteristic phenotype of human BA gallbladders is the increased density of PBG/PPG-like glands in the gallbladder body, especially near the epithelial decidual site, indicating that PBG/PPG formation is a common phenotype between human BA and mouse Sox17+/− BA gallbladders. These findings provide the first evidence of the potential contribution of SOX17 reduction and PBG/PPG formation to the early pathogenesis of human BA gallbladders. This article has an associated First Person interview with the joint first authors of the paper.

Understanding the pathogenesis and carcinogenesis of gallbladder adenocarcinoma is important. The fifth edition of the World Health Organization’s tumor classification of the digestive system indicates three types of preinvasive neoplasm of the gallbladder: pyloric gland adenoma (PGA), biliary intraepithelial neoplasia (BilIN), and intracholecystic papillary neoplasm (ICPN). New terminologies have also been introduced, such as intracholecystic papillary-tubular neoplasm, gastric pyloric, simple mucinous type, and intracholecystic tubular non-mucinous neoplasm (ICTN). Pancreatobiliary maljunction (PBM) poses a markedly high risk for bile duct carcinoma, which was analyzed and investigated mainly by Asian researchers in the past; however, recent studies have clarified a similar significance of biliary carcinogenesis in Western countries as well. In this study, we reviewed and summarized information on three gallbladder neoplastic precursors, PGA, BilIN, and ICPN, and gallbladder lesions in patients with PBM.

Generally, lesions of rectal neuroendocrine tumors (NETs) 10 mm or smaller are less malignant and are indicated for endoscopic therapy. However, the vertical margin may remain positive after conventional endoscopic mucosal resection (EMR) because NETs develop in a way similar to submucosal tumors (SMTs). The usefulness of EMR with a ligation device, which is modified EMR, and endoscopic submucosal dissection (ESD) was reported, but no standard treatment has been established. We encountered 2 patients in whom rectal NETs were completely resected by combined dissection and resection of the circular muscle layer using the ESD technique. Case 1 was an 8-mm NET of the lower rectum. Case 2 was NET of the lower rectum treated with additional resection for a positive vertical margin after EMR. In both cases, the circular muscle layer was dissected applying the conventional ESD technique, followed by en bloc resection while conserving the longitudinal muscle layer. No problems occurred in the postoperative course in either case. Rectal NETs are observed in the lower rectum in many cases, and it is less likely that intestinal perforation by endoscopic therapy causes peritonitis. The method employed in these cases, namely combined dissection and resection of the circular muscle layer using the ESD technique, can be performed relatively safely, and it is possible to ensure negativity of the vertical margin. In addition, it may also be useful for additional treatment of cases with a positive vertical margin after EMR.

Summary: Myoepithelial carcinoma is rare and mostly originates from the major salivary glands. Sometimes, it is difficult to differentiate the benign from the malignant histologically, and its clinical behavior and histological features may vary. Here, we describe the case of a 55-year-old woman who presented with a massive myoepithelial carcinoma, which hung like a temple bell from her right side of the jaw, and she refused to go to the hospital for 3 years. Based on its size and location, we initially thought that, before surgical resection, neoadjuvant therapy would be necessary to reduce the tumor volume. However, after careful evaluation of the tumor characteristics (low-grade histology with outward expansion and little invasion of the adjacent tissues) and imaging findings, we decided that excision was possible. The tumor was encapsulated and had a clear border; it weighed 10.5 kg. By setting the incision line posterior to the equatorial plane and using the lengthened skin posterior to the tumor as a large local flap for the skin defect, we successfully reconstructed the skin defect without harvesting additional flap from other areas. No additional treatment was administered because a sufficient surgical margin was maintained, pathologically. She regained her daily life without recurrence or distant metastasis for 2 years. When treating a massive tumor, careful consideration of its characteristics and location is important, and in this case, we were able to use a simpler and less invasive treatment than we initially envisioned.

Mammary analogue secretory carcinoma (MASC) is a recently recognized tumor of salivary glands characterized by the ETV6-NTRK3 fusion gene. This tumor is very rare in children and adolescents. We report a case of MASC in a 15-year-old girl, the fifth youngest case so far reported. The patient complained of a left infra-auricular mass that gradually enlarged for a year. Fine-needle aspiration cytology/imprint cytology showed individual tumor cells that had faintly eosinophilic granular cytoplasm with secretion granules sometimes seen adjacent to the tumor cells. These cytological features overlapped between those of zymogen granule-poor acinic cell carcinoma (AciCC) and MASC. In addition to the case report, we present a review of the related literature with a focus on the cytological features of MASC. The differential diagnostic clues are also discussed.

Aims: Pleomorphic adenoma gene 1 (PLAG1) rearrangement is well known in pleomorphic adenoma (PA), which is histologically characterised by admixed epithelial and mesenchymal components. Multiple fusion variants of PLAG1 and HMGA2 have been reported; currently, however, little is known regarding the clinicopathological impacts of these fusion types Methods and results: We examined the PLAG1- and HMGA2-related fusion status in 105 PAs and 11 cases of carcinoma ex PAs (CXPA) arising from salivary glands and lacrimal glands to elucidate their correlation to the clinicopathological factors. Forty cases harboured PLAG1 fusion genes: CTNNB1--PLAG1 in 22 cases, CHCHD7--PLAG1 in 14 cases and LIFR--PLAG1 in four cases. Only two cases possessed HMGA2 fusion genes. The mean age of LIFR--PLAG1- positive cases was significantly higher than that of CTNNB1--PLAG1- and CHCHD7--PLAG1-positive cases (P = 0.0358). PAs located in the submandibular gland demonstrated CTNNB1--PLAG1 fusion at a significantly higher rate than other fusions (P = 0.0109). Histologically, PLAG1 fusion-positive cases exhibited chondroid formation and plasmacytoid features more commonly (P = 0.043, P = 0.015, respectively) and myxoid abundant feature less frequently (P = 0.031) than PLAG1 fusion-negative cases. For CXPAs, four CTNNB1--PLAG1 fusions were detected in two salivary duct carcinomas and two myoepithelial carcinomas. Ductal formation was observed frequently (90.9%) in residual PA. Conclusions: The presence of PLAG1 fusion was associated with specific histological features in PA. Detecting the PLAG1 fusion gene and searching residual ductal formation in salivary gland malignant tumours with extensive hyalinisation could be useful for diagnosis. [ABSTRACT FROM AUTHOR]

Small cell lung carcinoma (SCLC) usually grows in a pure form with no other associated histological components. However, combined small cell lung carcinoma (cSCLC), which is accompanied by other histological components (cSCLCs) may sometimes occur. Herein, we analyzed the tumorigenesis of cSCLC containing a demarcated area of pure SCLC. A 76-year-old man had a 25-mm mass in the perihilar portion of his right upper lung. Histologically, the cSCLC contained two relatively demarcated areas: one area composed of pure SCLC cells and another area of SCLC, squamous-like component (SLC), and spindle cell carcinoma (SpCC) cells. Loss of heterozygosity (LOH) was observed at allele 3p in all tumor components and at 22q in the pure SCLC component. Histological and immunohistochemical analysis and LOH study suggested that all components were likely to be monoclonal in origin and revealed that the pure SCLC component was not the precursor of the cSCLC. In the tumorigenesis of this case, the pure SCLC and the cSCLC may have originated from a common pluripotent tumor cell and then diverged, although we cannot state this conclusively. Further studies with more cases are necessary to test this theory. [ABSTRACT FROM AUTHOR]

A case of prenatally diagnosed, giant cord hemangioma is reported, which was accompanied by the elevation of maternal serum alpha-fetoprotein (MS-AFP) and human chorionic gonadotropin (MS-hCG) levels. A 30-year-old woman without a previous history of gravida or para, presented with intermittent abdominal pain at 26 weeks of gestation. Doppler studies showed the fetus developing heart failure as the tumor grew larger. Caesarian section was performed at 29 weeks of gestation. Macroscopic examination of the placenta revealed a 17.0 × 10.0 × 7.0 cm tumor localized at the placental end of the umbilical cord. Microscopically, the tumor was composed of small arborizing vessels proliferating in the myxoid background, and the tumor cells were positive for AFP by immunohistochemistry. Extramedullary hematopoiesis was seen in the tumor vascular channels. The present case is one of the largest umbilical cord hemangiomas reported in the literature, and the first hemangioma case with MS-hCG elevation, extramedullary hematopoiesis, and positive AFP staining in the cord hemangioma. Its clinical course and detailed pathological findings are presented along with a review of the related literature. [ABSTRACT FROM AUTHOR]

Background Human papillomavirus-associated oropharyngeal carcinoma (HPV-OPC) is clinicopathologically distinct entity from the HPV-unassociated one (nHPV-OPC). This study aimed to determine the relationship between histological subtypes of OPC and HPV status for Japanese cases and to identify histological structures of HPV-OPC. Methods 66 OPC cases were categorized into conventional squamous cell carcinoma (SCC) and the variants. Conventional SCC was subcategorized into keratinizing (KSCC), non-keratinizing (NKSCC), and hybrid SCC (HSCC). HPV status of all cases was determined using p16- immunohistochemistry and HPV-DNA ISH. Results Two histological subtypes, NKSCC and HSCC, tended to be HPV-OPC and KSCC tended to be nHPV-OPC with statistical significance. Two histological structures, abrupt keratinization, defined in the text, and comedo-necrosis among non-maturing tumor island, were observed for 58.1% and 38.7% of HPV-OPC, and tended to exist for HPV-OPC with statistical significance. Conclusions This study showed the association of NKSCC/HSCC with HPV-OPC in Japanese cases, and two histological structures, abrupt keratinization and comedo-necrosis among non-maturing island, were considered characteristic histological features of HPV-OPC. [ABSTRACT FROM AUTHOR]

Abstract  Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a rare inflammatory tumor-like lesion composed of vascular nodules and non-neoplastic stroma including spindle cells and inflammatory cells. The focus of our study was on the stromal proliferating process in SANT. Nine cases of SANT were examined. All cases showed α-smooth muscle actin (α-SMA) and vimentin on the spindle cells but not CD21, CD31, CD34, CD68, desmin, S100, human herpes virus-8, or anaplastic lymphoma kinase-1. In one case, 20–30% of the myofibroblasts in Epstein–Barr-virus (EBV)-positive spindle cells were detected using double-labeling immunohistochemistry for α-SMA and EBV-encoded small RNA in situ hybridization. A quantitative analysis of IgG and IgG4-positive plasma cells (pPCs) in SANT was performed. The median densities of IgG-pPCs and IgG4-pPCs in SANT were approximately four-fold and 13-fold higher than those in the normal spleens, respectively. In addition, there was a statistically significant increase of IgG4/IgG-pPCs ratio in SANT in comparison to the control specimens. In conclusion, the fibrogenesis in a subset of SANT may be associated with EBV-infected myofibroblasts in an overlapping immune reaction indicated by the presence of infiltrating IgG4-pPCs. Further investigation is needed to elucidate the association between SANT and IgG4-related sclerosing disease. [ABSTRACT FROM AUTHOR]