Prognostic factors based on histological categorization of desmoplastic reactions in pancreatic cancer.

BACKGROUND/PURPOSE: In colorectal cancer, the morphological categorization of fibrotic cancer stroma in the invasive frontal zone of the primary tumor is well reflected in the prognosis. Conversely, the histological characteristics of pancreatic cancer (PC) reveal fibrotic hyperplasia of stroma known as desmoplasia; however, its characterization is unknown. Therefore, this study aimed to evaluate the prognostic factors according to the histological categorization of desmoplastic reactions in PC. METHODS: We retrospectively enrolled 167 patients who underwent curative resection for PC. The desmoplastic pattern was histologically classified as mature, intermediate, or immature. Clinicopathological features were evaluated, and disease-free and overall survival (OS) were analyzed in the three groups. Prognostic factors were assessed using univariate and multivariate analyses. RESULTS: In total, 19 mature, 87 intermediate, and 61 immature desmoplastic patterns were evaluated. Jaundice decompression, white blood cell count, and platelet/lymphocyte ratio were significantly different among the groups. The mature group had a better disease-free survival (DFS) prognosis than the other two groups; however, OS did not differ between the groups. Desmoplastic patterns showed significant differences between the three groups for DFS. CONCLUSIONS: Desmoplastic patterns are a prognostic factor of DFS for PC, with mature desmoplastic reactions associated with good prognosis. Thus, they may aid in individualized therapeutic approaches in patients with PC.

Calaxin is a key factor for calcium-dependent waveform control in zebrafish sperm.

Calcium is critical for regulating the waveform of motile cilia and flagella. Calaxin is currently the only known molecule involved in the calcium-dependent regulation in ascidians. We have recently shown that Calaxin stabilizes outer arm dynein (OAD), and the knockout of Calaxin results in primary ciliary dyskinesia phenotypes in vertebrates. However, from the knockout experiments, it was not clear which functions depend on calcium and how Calaxin regulates the waveform. To address this question, here, we generated transgenic zebrafish expressing a mutant E130A-Calaxin deficient in calcium binding. E130A-Calaxin restored the OAD reduction of calaxin -/- sperm and the abnormal movement of calaxin -/- left-right organizer cilia, showing that Calaxin's stabilization of OADs is calcium-independent. In contrast, our quantitative analysis of E130A-Calaxin sperms showed that the calcium-induced asymmetric beating was not restored, linking Calaxin's calcium-binding ability with an asymmetric flagellar beating for the first time. Our data show that Calaxin is a calcium-dependent regulator of the ciliary beating and a calcium-independent OAD stabilizer.

Malignant syphilis requiring differentiation from Kaposi's sarcoma.

Malignant syphilis (MS) is a rare variant of secondary syphilis. Also known as rupioid syphilis, MS is characterized by the presence of multiple papules, papulopustules, black lamellate crust that may resemble an oyster shell, or nodules with ulceration lacking central clearing. MS is often associated with immunodeficiency and frequently co-occurs with HIV infection. We here report a case of MS in a patient with HIV infection. HIV infection can cause atypical clinical symptoms of syphilis. In this case, unlike previous cases, cutaneous lesions of MS were limited to the face, making the diagnosis challenging based on clinical findings alone. However, his laboratory findings, appearance of the Jarisch-Herxheimer reaction, and a dramatic response to antibiotic therapy are characteristic of MS, making the diagnosis even more certain. Our case suggests the importance of physicians considering the possibility of MS when observing black-crusted lesions.

End-stage ADPKD with a low-frequency PKD1 mosaic variant accelerated by chemoradiotherapy.

Autosomal dominant polycystic kidney disease (ADPKD) is commonly caused by PKD1, and mosaic PKD1 variants result in milder phenotypes. We present the case of a 32 year-old male with chronic active Epstein-Barr virus who underwent bone marrow transplantation with chemoradiotherapy at age 9. Despite a low-frequency mosaic splicing PKD1 variant, he developed severe renal cysts and end-stage renal disease in his 30 s. This case highlights how environmental factors may contribute to the genetic predisposition to ADPKD.

High-grade Solid Pseudopapillary Neoplasms of the Pancreas: Distinct Clinicopathological Malignant Features With Intriguing Gene Alterations through a Comparison With the Conventional Type.

Pancreatic solid pseudopapillary neoplasm (SPN) is a low-grade malignant neoplasm with a good prognosis. Clinically aggressive SPNs have rarely been reported but have not been analyzed in detail. In this study, we referred to this highly malignant type of SPN as high-grade SPN (HG-SPN) and compared its clinicopathological and genetic characteristics with conventional SPN (C-SPN) using immunohistochemistry and gene panel analyses. Five HG-SPNs and 15 C-SPNs were evaluated in this study. HG-SPNs share many pathologic characteristics: macroscopically, solid/cystic appearances, microscopically, pseudopapillary/pseudorosette pattern (100%), tumor cell loose cohesiveness (100%), thin/delicate vasculature (100%), tumor cell cytoplasmic vacuolization (100%), immunohistochemical positivity for ß-catenin (nuclear expression) (100%), CD10 (80%), CD56 (80%), and vimentin (100%). Conversely, HG-SPNs showed distinct malignant features compared with C-SPNs: mean tumor size (11.7 vs. 2.9 cm, P <0.001); true necrosis (100% vs. 0%, P <0.001); high-grade nuclear atypia (100% vs. 0%, P <0.001); lymphatic and/or venous invasion (100% vs. 20%, P =0.004); mean mitotic count (4.38 vs. 0.05/high-power field, P <0.001); and mean Ki-67 labeling index (33.9% vs. 3.4%, P <0.001). All HG-SPN patients died of primary disease 3 to 36 months after surgery, while all C-SPN patients were alive without disease. Genetic studies have shown that all analyzed HG-SPNs have CTNNB1 mutations. Two HG-SPN cases showed RB1 mutations with altered immunohistochemical findings for RB1 and p16. Two HG-SPN cases had TP53 mutation and/or p53 overexpression. In conclusion, HG-SPNs show distinct malignant features and some genetic alterations that differ from C-SPNs, indicating the importance of differentiating between these 2 subtypes.

Essential roles of the hypothalamic A11 region and the medullary raphe nuclei in regulation of colorectal motility in rats.

The supraspinal brain regions controlling defecation reflex remain to be elucidated. The purpose of this study was to determine the roles of the hypothalamic A11 region and the medullary raphe nuclei in regulation of defecation. For chemogenetic manipulation of specific neurons, we used the double virus vector infection method in rats. hM3Dq or hM4Di was expressed in neurons of the A11 region and/or the raphe nuclei that send output to the lumbosacral defecation center. Immunohistological and functional experiments revealed that both the A11 region and the raphe nuclei directly connected with the lumbosacral spinal cord through descending pathways composed of stimulatory monoaminergic neurons. Stimulation of the hM3Dq-expressing neurons in the A11 region or the raphe nuclei enhanced colorectal motility only when GABAergic transmission in the lumbosacral spinal cord was blocked by bicuculline. Experiments using inhibitory hM4Di-expressing rats revealed that enhancement of colorectal motility caused by noxious stimuli in the colon is mediated by both the A11 region and the raphe nuclei. Furthermore, suppression of the A11 region and/or the raphe nuclei significantly inhibited water avoidance stress-induced defecation. These findings demonstrate that the A11 region and the raphe nuclei play an essential role in the regulation of colorectal motility. This is important because brain regions that mediate both intracolonic noxious stimuli-induced defecation and stress-induced defecation have been clarified for the first time.NEW & NOTEWORTHY The A11 region and the raphe nuclei, constituting descending pain inhibitory pathways, are related to both intracolonic noxious stimuli-induced colorectal motility and stress-induced defecation. Our findings may provide an explanation for the concurrent appearance of abdominal pain and defecation disorders in patients with irritable bowel syndrome. Furthermore, overlap of the pathway controlling colorectal motility with the pathway mediating stress responses may explain why stress exacerbates bowel symptoms.

Calaxin stabilizes the docking of outer arm dyneins onto ciliary doublet microtubule in vertebrates.

Outer arm dynein (OAD) is the main force generator of ciliary beating. Although OAD loss is the most frequent cause of human primary ciliary dyskinesia, the docking mechanism of OAD onto the ciliary doublet microtubule (DMT) remains elusive in vertebrates. Here, we analyzed the functions of Calaxin/Efcab1 and Armc4, the two of five components of vertebrate OAD-DC (docking complex), using zebrafish spermatozoa and cryo-electron tomography. Mutation of armc4 caused complete loss of OAD, whereas mutation of calaxin caused only partial loss of OAD. Detailed structural analysis revealed that calaxin-/- OADs are tethered to DMT through DC components other than Calaxin, and that recombinant Calaxin can autonomously rescue the deficient DC structure and the OAD instability. Our data demonstrate the discrete roles of Calaxin and Armc4 in the OAD-DMT interaction, suggesting the stabilizing process of OAD docking onto DMT in vertebrates.

Duodenal gastric-type neoplasm with uncertain malignant potential in a lipoma.

The pathologic diagnosis of duodenal tumors is a developing field; however, its overview remains unclear. We describe a rare case of a duodenal gastric-type neoplasm in a 50-year-old woman. She visited her primary care doctor with complaints of upper abdominal pain, tarry stools, and shortness of breath on exertion. She was admitted owing to a stalked polyp with erosion and hemorrhage in the descending part of the duodenum. Endoscopic mucosal resection (EMR) was performed on the polyp. Histologically, the resected polyp was a lipomatous lesion in the submucosal layer, composed of mature adipose tissues. Scattered irregular lobules of Brunner's gland-like structures with well-preserved construction but mildly enlarged nuclei and occasional conspicuous nucleoli of the constituent cells were observed. The resection margin was negative. EMR findings of the duodenal polyp showed a gastric epithelial tumor within a lipoma, a rare histological type that has not been reported previously. This tumor may be classified as a "neoplasm with uncertain malignant potential" in a lipoma, an intermediate category between adenoma and invasive adenocarcinoma. There is no consensus on treatment, and careful follow-up is recommended. This is the first report of a duodenal gastric-type neoplasm with uncertain malignant potential in a lipoma.

A case of hemophagocytic lymphohistiocytosis in a hemodialysis patient with coronavirus disease 2019.

During the treatment of a patient on hemodialysis with severe coronavirus disease 2019 (COVID-19), the patient was weaned from extracorporeal membrane oxygenation, which was used to treat severe COVID-19 pneumonia. However, the patient's condition worsened after the peak infection phase of COVID-19 because of acute respiratory distress syndrome with suspected hemophagocytic lymphohistiocytosis (HLH). After a bone marrow biopsy confirmed the diagnosis, methylprednisolone pulse therapy, followed by combination therapy (including oral prednisolone and cyclosporine) was immediately administered, and the patient survived. Because HLH can occur a month or more after the onset of COVID-19, even if the viral load is reduced to the point of being undetectable by reverse transcriptase-polymerase chain reaction, it can be considered to correspond to the "post-acute COVID-19 syndrome," which has recently been proposed. Early intervention is necessary, because HLH can be fatal. Therefore, it is important to know that HLH can occur at any stage of COVID-19 and to pay attention to the patient's progress over time, including checking the HScore.

Glenoid wear after humeral head replacement with using a single implant in patients with cuff tear arthropathy more than five years.

BACKGROUND: The aim of this study was to investigate glenoid wear in patients with humeral head replacement with a smaller humeral head, who were observed for >5 years, and to examine the relationship between radiographic changes and clinical outcome. METHODS: In this study, 41 shoulders of 41 patients (13 men, 28 women) were followed up for >5 years. The mean patient age at the time of surgery was 70.5 years. The average follow-up period at short-term was 26.0 months, and intermediate-term was 66.5 months. We classified glenoid wear into four grades (i.e., Grade 0 to Grade 3). Age, sex, clinical scores, and range of motion were investigated in relation to the grade of glenoid wear. Radiographs of glenoid wear evaluated in the short-term were subsequently compared to radiographs obtained in the intermediate-term period. RESULTS: At the final follow-up, 16 (39%) patients had Grade 0 wear, 11 (27%) patients had Grade 1 wear, 10 (24%) patients had Grade 2 wear, and 4 (10%) patients had Grade 3 wear. The University of California-Los Angeles score, Japanese Orthopaedic Association score, and active forward flexion were significantly lower in the Grade 3 patients; however, Grade 3 patients did not have significant pain. No significant difference in age, sex, Constant score, active external rotation, and active internal rotation in relation to the grade of glenoid wear was observed. In total, 25 (61%) patients showed a progression of glenoid wear. Cases in which glenoid wear progressed after 4 years after surgery were rare. Two patients of Grade 3 underwent total shoulder arthroplasty revision at 16 months and 38 months, respectively. CONCLUSIONS: Glenoid wear occurred in 61% of patients at 5 years follow-up. Pain of Grade 3 patients was mild, therefore, if pain is not severe, revision surgery may not be necessary.

Chronic Osteomyelitis of the Cranial Vault in an Adolescent Female: A Case Report.

We report an 18-year-old female patient who developed left temporal headache and fever one month after administration of isotretinoin for acne. Imaging studies demonstrated osteolytic change in the left frontal bone, and the lesion showed gadolinium contrast enhancement. Biopsy confirmed the diagnosis of osteomyelitis, and the symptoms improved after 8 months of medication with antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). However, the pain recurred when isotretinoin was resumed. Isotretinoin sometimes causes excessive inflammation, which may have been the reason for the osteomyelitis in this case. Although osteomyelitis is usually caused by bacterial infection, a non-bacterial mechanism should also be suspected if the condition is resistant to antibiotics.

Pancreatic hamartoma: detection of harbouring NAB2::STAT6 fusion gene.

Hamartomas in the pancreas are rare and are often histologically and morphologically similar to solitary fibrous tumours (SFTs). We examined the differences between hamartomas and SFTs at the molecular level. METHODS AND RESULTS: Thirteen patients histopathologically diagnosed with pancreatic hamartoma were included in the study. We also performed STAT6 immunohistochemistry (IHC), which is used in the diagnosis of SFT. Furthermore, for the three cases in which RNA was extracted, reverse transcription polymerase chain reaction to search for NAB2::STAT6 fusions was used. Macroscopically, 13 patients had well-demarcated tumour lesions. Histologically, no islets of Langerhans were observed in the lesions, acinar tissue and ducts were unevenly distributed and elastic fibres were not observed around the ducts by Elastica van Gieson staining. One case contained a lipomatous hamartoma composed mainly of adipose tissue. Seven of the 13 cases demonstrated expression of STAT6 in the nuclei of intervening spindle cells. NAB2::STAT6 fusions were observed in two of the three cases in which RNA was extracted. These two cases also demonstrated STAT6 expression in spindle cells using STAT6 IHC. In one case of lipomatous hamartoma, we did not confirm NAB2::STAT6 fusion or STAT6 expression in STAT6 IHC. CONCLUSION: Of the 13 patients histopathologically diagnosed with hamartoma, two demonstrated NAB2::STAT6 fusions, suggesting the existence of pancreatic hamartomas with molecular-level components identical to those of SFT.

Concordance of the histological diagnosis of type 1 autoimmune pancreatitis and its distinction from pancreatic ductal adenocarcinoma with endoscopic ultrasound-guided fine needle biopsy specimens: an interobserver agreement study.

The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss' к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis.

Diagnostic Categories and Key Features for Pathological Diagnosis of Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy Samples of Pancreatic Lesions: A Consensus Study.

OBJECTIVES: This study aimed to establish a reliable and reproducible categorized diagnostic classification system with identification of key features to achieve accurate pathological diagnosis of endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) samples of pancreatic lesions. METHODS: Twelve pathologists examined virtual whole-slide images of EUS-FNAB samples obtained from 80 patients according to proposed diagnostic categories and key features for diagnosis. Fleiss κ was used to assess the concordance. RESULTS: A hierarchical diagnostic system consisting of the following 6 diagnostic categories was proposed: inadequate, nonneoplasm, indeterminate, ductal carcinoma, nonductal neoplasm, and unclassified neoplasm. Adopting these categories, the average κ value of participants was 0.677 (substantial agreement). Among these categories, ductal carcinoma and nonductal neoplasm showed high κ values of 0.866 and 0.837, respectively, which indicated the almost perfect agreement. Key features identified for diagnosing ductal carcinoma were necrosis in low-power appearance; structural atypia/abnormalities recognized by irregular glandular contours, including cribriform and nonuniform shapes; cellular atypia, including enlarged nuclei, irregular nuclear contours, and foamy gland changes; and haphazard glandular arrangement and stromal desmoplasia. CONCLUSIONS: The proposed hierarchical diagnostic classification system was proved to be useful for achieving reliable and reproducible diagnosis of EUS-FNAB specimens of pancreatic lesions based on evaluated histological features.

A case of intravascular lymphoma diagnosed with a primary vitreoretinal lymphoma-like fundus lesion.

PURPOSE: We report a case of intravascular lymphoma with primary vitreoretinal lymphoma-like fundus findings. CASE: A 61-year-old man with a one-week history of temporal visual field defect in the left eye was referred by a local ophthalmologist to our department. A yellowish-white raised patchy lesion was found in the nasal fundus of the left eye. Vitreoretinal lymphoma was suspected, and vitrectomy was performed in the left eye for diagnostic purpose. However, vitreous interleukin-10 concentration was low and no significant result was obtained. He had fever of around 38 °C, and respiratory failure that started 2 weeks before ophthalmological examination, worsened. Intravascular lymphoma was diagnosed from the results of histopathological examinations of transbronchial lung biopsy, bone marrow biopsy and random skin biopsy. With the start of systemic chemotherapy, the subretinal lesions shrank gradually and systemic condition was stable. However, 5 months after the start of chemotherapy, spread to the central nervous system was observed, and chimeric antigen receptor T cell (CAR-T) therapy was started in another hospital. After the start of CAR-T therapy, the subretinal lesions shrank further. CONCLUSIONS: Intravascular lymphoma may be accompanied by primary vitreoretinal lymphoma-like intraocular lesions. If intraocular lesions are accompanied by systemic symptoms such as fever of unknown origin, the possibility of intravascular lymphoma should be suspected and systemic work-up should be performed.

Knowledge and Attitude towards Cervical Cancer and Human Papillomavirus among Pharmacists in Japan.

OBJECTIVE: The objective of this study was to assess the knowledge and attitude towards cervical cancer and human papillomavirus (HPV) among pharmacists in Japan. METHODS: Questionnaires were disseminated to 788 pharmacists employed by the Tsuruha Holdings Inc. A total of 617 pharmacists responded, generating a response rate of 78.3%. RESULT: Of the 362 females and 255 males, vaccination rates were 14.4% and 0.8%, respectively. In terms of cervical cytology, 35.1% of females received it once every two years, and 26.2% received it irregularly. As for HPV testing, 12.2% of females received it once every two years, and 16.6% received it irregularly. The rate of "school curriculum" as an information source was significantly higher among younger pharmacists; while "internet", "media", "training seminar for pharmacist", "advertisement in medical institution", "internal manual", and "others" were significantly higher among older pharmacists. The proportion of pharmacists with knowledge on general questions, except for those about HPV testing, was significantly higher among females than males. The vaccination rates of younger pharmacists were significantly higher than those of older pharmacists. The screening rates of cervical cytology were significantly higher among older than younger pharmacists, and also among those with at least 10 years of experience than those with less. There were no differences in the screening rates of HPV testing according to age or pharmacist experience. CONCLUSION: The proportion of pharmacists with knowledge about cervical cancer and HPV significantly varied depending on sex, age, and experience as a pharmacist. This study suggested that spreading the knowledge about cervical cancer and HPV might be effective for increasing the rates of cervical cancer screening.

Neuroendocrine carcinoma of the common bile duct associated with congenital bile duct dilatation: a case report.

BACKGROUND: Cholangiocarcinoma is frequently observed in patients with congenital bile duct dilatation (CBDD). Most cholangiocarcinomas are adenocarcinomas. Other types, especially neuroendocrine carcinomas (NECs), are rare. To the best of our knowledge, this is the third reported case of an NEC of the common bile duct associated with CBDD and the first to receive adjuvant chemotherapy for advanced disease. CASE PRESENTATION: A 29-year-old woman presented with upper abdominal pain. Preoperative imaging indicated marked dilatation of the common bile duct and a tumor in the middle portion of the common bile duct. She was suspected of having distal cholangiocarcinoma associated with CBDD and underwent pylorus-preserving pancreaticoduodenectomy. Pathological and immunohistological findings led to a final diagnosis of large-cell NEC (pT3aN1M0 pStageIIB). The postoperative course was uneventful, and she was administered cisplatin and irinotecan every 4 weeks (four cycles) as adjuvant chemotherapy. She has remained recurrence-free for 16 months. CONCLUSIONS: NEC might be a differential diagnosis in cases of cholangial tumor associated with congenital bile duct dilatation. This presentation is rare and valuable, and to establish better treatment for NEC, further reports are necessary.

Perioperative Predictors of Early Recurrence for Resectable and Borderline-Resectable Pancreatic Cancer.

We aimed to identify the perioperative predictors of the early recurrence (ER) of resectable and borderline-resectable pancreatic ductal adenocarcinomas (PDACs). After surgery for a PDAC, most patients develop a recurrence. Predictive factors may therefore guide therapeutic decision-making. Patients (n = 234) who underwent a pancreatectomy for a PDAC between 2006 and 2019 were included. The postrecurrence survival (PRS) was estimated using Kaplan-Meier curves. Predictive factors for an ER were assessed using logistic regression analyses; 93 patients (39.7%) were recurrence-free at the last follow-up. Patients with an ER (n = 85, 36.3%), defined as a recurrence within the first 12 months after surgery, had 1- and 2-year PRS rates of 38.7% and 9.5%, respectively, compared with 66.9% and 37.2% for those with a late recurrence (n = 56, 23.9%; both p < 0.001). The most common site of an ER was the liver (55.3%) with a significantly shorter median overall survival time than that with either a local or a lung recurrence (14.5 months; p < 0.001). Preoperative and postoperative risk factors for an ER included a tumor size >3.0 cm (odds ratio (OR): 3.11, 95% confidence interval (CI): 1.35-7.14) and preoperative carbohydrate antigen 19-9 (CA19-9) levels >52 U/mL (OR: 3.25, 95% CI: 1.67-6.30) and a pathological tumor size >3.0 cm (OR: 2.00, 95% CI: 1.03-3.90) and postoperative carbohydrate antigen 19-9 levels >37 U/mL (OR: 2.11, 95% CI: 1.02-4.36), respectively. Preoperatively (>52 U/mL) and postoperatively (>37 U/mL) elevated CA19-9 and a tumor size >3.0 cm were independent predictors for an ER after a pancreatectomy for a PDAC.

Recognition and pathological features of periampullary region adenocarcinoma with an indeterminable origin.

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.

[A case of mucinous cystadenoma of the pancreas changed from multilocular to unilocular with cyst in cyst structure with an 8-year follow-up].

A 57-year-old woman presented with multilocular cysts like a bunch of grapes, 30mm in diameter, in the tail of the pancreas. The number of cysts has increased, and each one had grown. Eventually, they turned into a unilocular cyst with a cyst in the cyst structure of about 50mm in diameter. Laparoscopic distal pancreatectomy was performed, and the resected specimen was diagnosed with mucinous cystadenoma. We report the rare morphological change in this case and consider the mechanism of its occurrence based on pathological considerations.