Dynamics of the neutrophil­to­lymphocyte ratio during lenvatinib treatment for unresectable hepatocellular carcinoma.

Lenvatinib is an approved therapy for advanced hepatocellular carcinoma (HCC). Recently, immune checkpoint inhibitors have been approved as frontline chemotherapies for HCC, and the tumor immune microenvironment (TIME) has been demonstrated to significantly affect HCC treatment. The neutrophil-to-lymphocyte ratio (NLR) is associated with the TIME, and the dynamics of the NLR are associated with prognosis or treatment efficacy in various cancer types. The present study investigated the dynamics of the TIME using the NLR in 101 patients with HCC treated with lenvatinib. Immunostaining for CD8+ tumor-infiltrating lymphocytes (TILs) was also performed in 9 patients who underwent liver tumor biopsy prior to subsequent chemotherapy for progression or discontinuation due to adverse events on lenvatinib treatment. The NLR values measured at the start of treatment (SOT), after 1 month of treatment and after 3 months of treatment were 2.78±2.20, 2.61±1.86 and 2.66±2.36, respectively (P=0.733). Among the patients with no reduction in the initial dose, there was no significant difference between the NLR after 1 month (2.34±0.25) and that at the SOT (2.86±2.33) (P=0.613). In patients who achieved a complete or partial response, the NLR at the time of the best tumor response was 1.65±0.56, which was significantly lower than that at the SOT (2.05±0.78) (P=0.023). In patients who did not respond to lenvatinib, the NLR at the time of disease progression was 3.68±3.19, which was significantly higher than that at the SOT (2.78±1.79) (P=0.043). Overall, 5 out of the 6 patients who did not respond to lenvatinib had low CD8+ TIL counts at disease progression. Although the present study included a limited number of patients, the NLR was associated with the therapeutic effects of lenvatinib. These findings suggest the potential of lenvatinib as an immunomodulator.

Efficacy and histologic frequencies of endoscopic ultrasonography-guided tissue acquisition using conventional fine-needle aspiration needles for gastric subepithelial hypoechoic mass.

Introduction/Purpose: For gastric subepithelial lesions (GSELs) showing a hypoechoic mass (HM) on endoscopic ultrasonography (EUS) imaging, the utility of EUS-guided tissue acquisition using conventional fine-needle aspiration needles (EUS-TA-CFNAN) and the frequency of histological types remain unclear. This study aimed to examine this issue. Methods: This prospective observational study enrolled 291 consecutive patients who underwent EUS-TA-CFNAN for GSELs showing an HM (GSELHM) on EUS imaging. Immunohistochemical analysis was performed for all EUS-TA-CFNAN and surgically resected specimens. The main outcome measures were the technical results of EUS-TA-CFNAN and the frequency of histological types in GSELHM. Results: The endoscopic ultrasound-guided tissue acquisition using conventional fine-needle aspiration needle diagnosis rate for GSELHM was 80.1% (95% confidence interval [CI]: 75.0-84.5, 233/291). It was significantly lower for antrum (P = 0.004) and lesions smaller than 2 cm (P = 0.003). There were no adverse events. The immunohistochemical diagnoses of EUS-TA-CFNAN included 149 cases of gastrointestinal stromal tumour (GIST) (51.2%), 48 cases of leiomyoma (16.5%), 11 cases of schwannoma (3.8%), 8 cases of the ectopic pancreas (2.7%), 5 cases of subepithelial lesion like cancer (1.7%), 12 cases of other lesions (4.1%), and 58 cases of undiagnosable lesions (19.9%). The frequency of malignant or potentially malignant tumour in GSELHM was 55.0% (95% CI: 49.1-60.8, 160/291). Surgery was performed in 149 patients according to the conclusive EUS-TA-CFNAN results, in which the diagnostic accuracy of EUS-TA-CFNAN was 97.3% (95% CI: 94.7-99.9, 145/149). Conclusion: The use of EUS-TA-CFNAN for GSELHMs is safe and accurate. Gastric subepithelial lesions showing a hypoechoic mass have a reasonably high possibility of containing malignant or potentially malignant tumours, including GISTs.

Obstructive Shock Due to a Crushed Left Atrium and Pulmonary Vein by Pulmonary Artery Intimal Sarcoma Successfully Treated with Pulmonary Vein Stenting.

A 46-year-old patient who had undergone right pneumonectomy for pulmonary artery intimal sarcoma presented with hypoxemia. The recurrent sarcoma in the mediastinum revealed external compression to the left pulmonary veins (PVs), leading to obstructive shock and cardiac arrest. Venous artery extracorporeal membrane oxygenation (VA-ECMO) was initiated; however, withdrawal was difficult, and the patient's survival seemed hopeless. However, the patient's condition improved with stenting for the compressed PV; therefore, VA-ECMO was discontinued, and he was discharged on foot. This is the first case report of obstructive shock due to critical PV stenosis caused by compression of a malignant tumor that responded to PV stenting.

Minocycline-Induced Hyperpigmentation: Importance of Early Diagnosis.

A 75-year-old woman on hemodialysis for end-stage renal failure due to polycystic kidney disease developed dark spots on her limbs. She had been treated for extended spectrum beta-lactamase-producing Escherichia coli bacteremia by a rectovaginal fistula and was on long-term oral minocycline (cumulative dose 45 g). Physical examination revealed dark patches on her forearms and lower legs but no trunk hyperpigmentation or visual impairment. Blood tests were normal. Skin biopsy confirmed minocycline-induced hyperpigmentation. Minocycline-induced pigmentation is categorized into types I-IV, each with unique clinical and histopathological features. Types I and II are reversible upon discontinuing minocycline, whereas types III and IV are permanent. The patient was diagnosed with type II pigmentation, generally occurring with a cumulative dose exceeding 70-100 g; however, her lower dose (45 g) led to pigmentation, possibly influenced by her vitamin D deficiency. Clinicians should evaluate the antimicrobial indication and treatment period, considering not only the benefits but also the side effects and antimicrobial resistance. If minocycline is used, attention should be paid to minocycline-induced hyperpigmentation, and this possibility should be communicated to patients to enable early detection.

Endoscopic Ultrasonography-Guided Fine-Needle Aspiration for Duodenal Subepithelial Lesions Showing a Hypoechoic Mass on Endoscopic Ultrasound Imaging.

BACKGROUND/AIMS: For duodenal subepithelial lesions showing a hypoechoic mass on endoscopic ultrasound imaging, the utility of endoscopic ultrasound-guided fine-needle aspiration and the frequency of histological types have not been the focus of previous literature. This study aimed to clarify this. MATERIALS AND METHODS: This prospective observational study enrolled 22 consecutive patients who underwent endoscopic ultrasoundguided fine-needle aspiration for duodenal subepithelial lesions with hypoechoic mass on endoscopic ultrasound. Immunohistochemical analysis was performed for all endoscopic ultrasound-guided fine-needle aspiration and surgically resected specimens. The main outcome measures were the technical results of endoscopic ultrasound-guided fine-needle aspiration and the frequency of histological types of duodenal subepithelial lesions with hypoechoic mass. RESULTS: Thirteen fine-needle aspiration specimens were obtained from the duodenal bulb and eight from the descending duodenal region. The puncture was not performed because of intervening vessels in one patient. The diagnostic rate was 81% (95% confidence interval: 58.1-94.6, 17/21 patients). In 12 patients receiving surgical resection (excluding one cancellation of endoscopic ultrasoundguided fine-needle aspiration), the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration was 75% (95% confidence interval: 42.8-94.5, 9/12 patients). No complications were observed. The histopathological diagnoses included 11 cases of gastrointestinal stromal tumor (50%), 2 cases of leiomyoma (9%), 2 cases of metastatic cancer (9%), 2 cases of benign inconclusive, and 1 case each of carcinoid, malignant lymphoma, leiomyosarcoma, gauzeoma, and aberrant pancreas (4.5% each). The frequency of malignant tumors in the duodenal subepithelial lesions with hypoechoic mass group was 73% (16/22 patients). CONCLUSIONS: Endoscopic ultrasound-guided fine-needle aspiration for duodenal subepithelial lesions with hypoechoic mass was safe and accurate. As duodenal subepithelial lesion with hypoechoic mass has a reasonably high possibility of containing malignant tumors, it is desirable to perform endoscopic ultrasound-guided fine-needle aspiration.

An Imaging Feature Predicts Efficacy of Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: Systemic chemotherapy with atezolizumab plus bevacizumab is approved for unresectable hepatocellular carcinoma (HCC). It is necessary to identify probable predictive biomarkers for chemotherapies. HCC with rim arterial-phase enhancement (APHE) has been linked to aggressive tumor activity. PATIENTS AND METHODS: We studied the efficacy of atezolizumab plus bevacizumab for HCC using computed tomography (CT) or magnetic resonance imaging (MRI) imaging features. In total, 51 HCC patients who underwent CT or MRI were classified by the feature of rim APHE. RESULTS: Clinical responses to chemotherapy were evaluated, and among those who received atezolizumab plus bevacizumab, there were 10 (19.6%) patients with rim APHE and 41 (80.4%) patients without rim APHE. We found that patients with rim APHE had a better response than those without rim APHE, and patients with rim APHE had longer median progression-free survival compared with those without rim APHE (p=0.026). Furthermore, liver tumor biopsy showed that HCC with rim APHE had a higher proportion of CD8+ tumor-infiltrating lymphocytes (p<0.01). CONCLUSION: Rim APHE in CT/MRI imaging might be a noninvasive biomarker for predicting response to atezolizumab plus bevacizumab.

High-grade Serous Carcinoma can Show Squamoid Morphology Mimicking True Squamous Differentiation.

Tubo-ovarian high-grade serous carcinoma (HG-SC) and ovarian endometrioid carcinoma (EC) can show overlapping morphologic features, such as glandular and solid patterns. The differential diagnosis of these subtypes is thus sometimes difficult. The existence of "squamous differentiation" tends to lead to a diagnosis of EC rather than HG-SC. We noticed that HG-SC can contain a "squamoid component," but its nature has been poorly investigated. This study was thus established to clarify the nature of this "squamoid component" in HG-SC by investigating its frequency and immunohistochemical features. We reviewed hematoxylin and eosin-stained slides of 237 primary untreated cases of tubo-ovarian HG-SC and identified 16 cases (6.7%) of HG-SC with "squamoid component." An immunohistochemical staining panel (CK5/6, CK14, CK903, p40, p63, WT1, ER, and PgR) was used to analyze all of these 16 cases. We also selected 14 cases of ovarian EC with "squamous differentiation" as a control. The "squamoid component" in HG-SC was completely p40-negative and showed significantly lower expression of CK5/6, CK14, CK903, and p63 than the "squamous differentiation" in EC. The immunophenotype of the "squamoid component" in HG-SC was concordant with the conventional HG-SC component (WT1-positive/ER-positive). Furthermore, all 16 tumors were confirmed to be truly "HG-SC" by the findings of aberrant p53 staining pattern and/or WT1/p16 positivity, and the lack of mismatch repair deficiency and POLE mutation. In conclusion, HG-SC can on rare occasions show a "squamoid component" mimicking "squamous differentiation." However, the "squamoid component" in HG-SC does not represent true "squamous differentiation." The "squamoid component" is one part of the morphologic spectrum of HG-SC, which should be interpreted carefully for the differential diagnosis of HG-SC and EC. An immunohistochemical panel including p40, p53, p16, and WT1 is a useful adjunct to achieve a correct diagnosis.

Tumor­infiltrating CD8+ T cells as a biomarker for chemotherapy efficacy in unresectable hepatocellular carcinoma.

Atezolizumab plus bevacizumab and lenvatinib are approved frontline therapies for advanced hepatocellular carcinoma (HCC). Patients with advanced HCC continue to have a poor prognosis despite these therapeutic choices. Previous studies have reported CD8+ tumor-infiltrating lymphocytes (TILs) as a biomarker to predict responsiveness to systemic chemotherapy. The present study investigated whether evaluating CD8+ TILs by immunohistochemistry staining of liver tumor biopsy tissues could help predict the response of patients with HCC to atezolizumab plus bevacizumab and lenvatinib. In total, 39 patients with HCC who underwent liver tumor biopsy were classified into high and low CD8+ TILs groups and were then divided by therapy type. The clinical responses to treatment in both groups were evaluated for each therapy. There were 12 patients with high-level CD8+ TILs and 12 patients with low-level CD8+ TILs among those who received atezolizumab plus bevacizumab. An improved response rate was observed in the high-level group compared with the low-level group. The high-level CD8+ TILs group had a significantly longer median progression-free survival compared with the low-level group. Among the patients with HCC who received lenvatinib, five had high-level CD8+ TILs and 10 had low-level CD8+ TILs. There were no differences in response rate or progression-free survival between these groups. Although the present study included only a limited number of patients, the findings suggested that CD8+ TILs could be a biomarker for predicting response to systemic chemotherapy in HCC.

Translocation of nuclear chromatin distribution to the periphery reflects dephosphorylated threonine-821/826 of the retinoblastoma protein (pRb) in T24 cells treated with Bacillus Calmette-Guérin.

The standard treatment for non-muscle-invasive bladder cancer is intravesical Bacillus Calmette-Guérin (BCG) therapy, which is considered the only intravesical therapy that reduces the risk of progression to muscle-invasive cancer. BCG unresponsiveness, in which intravesical BCG therapy is ineffective, has become a problem. It is thus important to evaluate the effectiveness of BCG treatment for patients as soon as possible in order to identify the optimal therapy. Urine cytology is a noninvasive, easy, and cost-effective method that has been used during BCG treatment, but primarily only to determine benign or malignant status; findings concerning the efficacy of BCG treatment based on urine cytology have not been reported. We investigated the relationship between BCG exposure and nuclear an important criterion in urine cytology, i.e., nuclear chromatin patterns. We used three types of cultured cells to evaluate nuclear chromatin patterns and the cell cycle, and we used T24 cells to evaluate the phosphorylation of retinoblastoma protein (pRb) in six-times of BCG exposures. The results revealed that after the second BCG exposure, (i) nuclear chromatin is distributed predominantly at the nuclear periphery and (ii) the dephosphorylation of threonine-821/826 in pRb occurs. This is the first report of a dynamic change in the nuclear chromatin pattern induced by exposure to BCG. Molecular findings also suggested a relationship between this phenomenon and cell-cycle proteins. Although these results are preliminary, they contribute to our understanding of the cytomorphological changes that occur with BCG exposure.

A critical review of "uterine leiomyoma" with subsequent recurrence or metastasis: A multicenter study of 62 cases.

AIM: Histopathologic diagnosis of a subset of uterine smooth muscle tumors is challenging. We report a critical review regarding the clinicopathological point of view of 62 cases of subsequently recurred or metastasized leiomyoma. METHODS: Medical records and glass slides of 62 cases of uterine smooth muscle tumor diagnosed as leiomyoma, which subsequently recurred or metastasized, were critically reviewed by pathologists specializing in gynecologic pathology and oncology. RESULTS: In 47 (75.8%) of 62 cases, the diagnosis of leiomyoma was confirmed, including 11 intravascular leiomyomatosis (IVL) and benign metastasizing leiomyoma (BML). In 29 cases (46.8%) laparoscopic surgery was performed, of which morcellator without a bag was employed in 23 cases. Fifteen cases (24.2%) appeared to be underestimated and were re-classified as smooth muscle tumor of uncertain malignant potential (STUMP), leiomyosarcoma, or other malignant mesenchymal tumors. Recurrences in seven cases (11.3%) were interpreted to be a malignant transformation, and one STUMP recurred as STUMP. CONCLUSION: The recurrence or metastasis in cases of "leiomyoma" is attributed to iatrogenic or under-evaluation of primary tumors, although a subset of cases is a rare example of biological progression.

Therapeutic efficacy of atezolizumab plus bevacizumab for hepatocellular carcinoma with WNT/ß-catenin signal activation.

Atezolizumab plus bevacizumab therapy has high response rates in patients with advanced hepatocellular carcinoma (HCC). It has been reported that HCC with immune exclusion associated with the signal activation of WNT/ß-catenin is resistant to immune checkpoint inhibitors; however, to the best of our knowledge, the effectiveness of atezolizumab plus bevacizumab for HCC with WNT/ß-catenin signal activation has not been reported. The present study aimed to analyze the efficacy of atezolizumab plus bevacizumab for HCC with WNT/ß-catenin signal activation. A total of 24 patients who underwent liver tumor biopsy for HCC were classified into WNT/ß-catenin signal activation and inactivation groups according to the expression levels of ß-catenin and glutamine synthetase, which are indicative of WNT/ß-catenin signal activation. The differences in the clinical responses to treatment between the groups were analyzed. A total of 15 patients had HCC with WNT/ß-catenin signal activation, whereas 9 patients had HCC with WNT/ß-catenin signal inactivation. There were no significant differences between both groups regarding objective responses (P=0.519) and disease control (P=0.586). In the WNT/ß-catenin signal activation group, the median progression-free survival rate was 6.9 months compared with 6.2 months in the WNT/ß-catenin signal inactivation group (P=0.674). Although a small number of patients was included in the present study, the present findings suggested that the efficacy of atezolizumab plus bevacizumab might be unaffected by WNT/ß-catenin signal activation.

Long-term follow up after sentinel node biopsy alone for early-stage cervical cancer.

OBJECTIVE: Sentinel node biopsy alone (SNB) reduces the postoperative complications of pelvic lymphadenectomy, such as lymphedema and lymphangitis; however, the long-term prognosis after SNB is unclear. The objective of this study was to evaluate the long-term outcome and complications of patients with early-stage cervical cancer who underwent SNB for hysterectomy or trachelectomy. METHODS: We performed SNB for cervical cancer using a radioisotope method in 181 patients between 2009 and 2017. If the intraoperative sentinel lymph node evaluation was negative for metastasis, no further lymph nodes were removed. RESULTS: The median age of the patients was 34 years (range, 21-73 years). The International Federation of Gynecology and Obstetrics 2008 stage was IA1 in 6 patients, IA2 in 18, IB1 in 154, and IIA1 in 3. Of the 181 patients (44 with hysterectomy, 137 with trachelectomy), 8 did not undergo pelvic lymphadenectomy because of a false-negative intraoperative diagnosis, 20 received adjuvant therapy after surgery, and 4 (2.2%) experienced recurrence over a median follow-up period of 83.5 months (range, 25-145 months). In the four recurrent cases, recurrence occurred in the pelvis, lung, and bone in one patient each, while the remaining patient developed pelvic and para-aortic lymph node metastases. Of these four patients, one died, and the remaining three are alive without disease after multidisciplinary therapy. The 5-year progression-free and overall survival rates were 98.8% and 99.4%, respectively. Postoperative complications, such as lymphedema, were very low rate. CONCLUSIONS: SNB for early-stage cervical cancer might be safe and effective, with no increase in the recurrence and postoperative complications rate.

Evaluation of Clinical Significance of Lymphovascular Space Invasion in Stage IA Endometrial Cancer.

INTRODUCTION: The prognostic significance of lymphovascular space invasion (LVSI) in stage IA endometrial cancer remains unclear. The aim of this study was to evaluate the clinical significance of LVSI in stage IA endometrial cancer. METHODS: Clinical data of patients with stage IA endometrial cancer who underwent initial surgery at our institution between January 2008 and December 2018 were reviewed retrospectively. Information of patients, surgery, and characteristics of cancer were obtained from medical records and pathological reports. RESULTS: Two hundred ninety-seven patients were enrolled in this study. With a median follow-up of 60 months, 15 patients experienced recurrence (5.1%) and 4 patients died of endometrial cancer (1.3%). The recurrence and mortality rates did not differ significantly between the LVSI-positive and -negative groups (p = 0.07 and p = 0.41, respectively). Recurrence-free survival and endometrial cancer-specific survival also did not differ significantly between these groups (p = 0.11 and p = 0.49, respectively). The 5-year endometrial cancer-specific survival rates for tumors with and without LVSI were 97.0% and 98.9%, respectively. Among patients with low-grade tumors, recurrence-free survival and endometrial cancer-specific survival did not differ significantly between patients with tumors with and without LVSI (p = 0.92 and p = 0.72, respectively). The 5-year endometrial cancer-specific survival rates for low-grade tumors with and without LVSI were 100% and 99.3%, respectively. CONCLUSION: LVSI was not a prognostic factor of not only stage IA endometrial cancer but also stage IA low-grade cancer.

Endometrial endometrioid carcinoma, grade 1, is more aggressive in the elderly than in the young.

AIMS: The aim of this study was to characterise grade 1 (G1) endometrioid carcinoma in the elderly, by using clinicopathological features and immunohistochemical features of surrogate markers of molecular subtypes. METHODS AND RESULTS: We retrospectively analysed tumour samples from 268 patients with G1 endometrioid carcinoma (<40 years, n = 24; 40-59 years, n = 169; ≥60 years, n = 75) for whom long-term clinical follow-up data were available. G1 endometrioid carcinoma in the elderly (≥60 years) was characterised by frequent deep myometrial invasion, less frequent endometrioid intraepithelial neoplasia (EIN), lack of benign hyperplasia (BH), less frequent squamous differentiation, and occasional aberrant p53 expression. In contrast, this condition in the young (<40 years) was characterised by frequent EIN, BH, and squamous differentiation. Univariate analysis revealed that elderly status (≥60 years), International Federation of Obstetrics and Gynecology (FIGO) 2009 stage and aberrant p53 expression were significantly associated with shorter progression-free survival, and multivariate analysis revealed that elderly status and FIGO 2009 stage were independently associated with a poor prognosis. CONCLUSIONS: G1 endometrioid carcinoma in the elderly is more aggressive than that in the young, and elderly status is an independent predictor of shorter progression-free survival in this condition. We propose that type 1 tumours can be subdivided into type 1a (young age at onset and indolent) and type 1b (old age at onset and relatively aggressive).

Prognostic implications of the coexisting precursor lesion types in invasive gallbladder cancer.

Invasive gallbladder carcinoma (GBC) is preceded by two main types of precursor lesions: intracholecystic papillary-tubular neoplasms (ICPNs) and biliary intraepithelial neoplasias (BilINs). Invasive GBCs with an ICPN component have more favorable prognoses than those without an ICPN component. Some BilINs show a relatively exophytic papillary pattern but do not meet the ICPN criteria; at our institution, we call these papillary neoplasias. To clarify the clinical significance of papillary neoplasia, we herein examined 80 invasive GBCs and classified them into three groups based on the type of preinvasive lesions: those with ICPN (ICPN group, n = 35), those with papillary neoplasia (pap-neoplasia group, n = 13), and those without ICPN/papillary neoplasia (group without ICPN/pap-neoplasia, n = 32). We then compared the prognostic differences and characterized the tumors of each group by determining the immunohistochemical expressions of various biomarkers. The overall survival periods of the ICPN and pap-neoplasia groups were significantly longer than that of the group without ICPN/pap-neoplasia (P < 0.0001, P = 0.0036, respectively). Multivariate analysis revealed that lacking ICPN/papillary neoplasia was independently associated with poor prognosis (P = 0.0007), as were poor differentiation (P = 0.0395), presence of preoperative symptoms (P = 0.0488), and advanced stage (P = 0.0234). Invasive components of the ICPN and pap-neoplasia groups were characterized by higher expressions of p16 and p53 compared with those of the group without ICPN/pap-neoplasia. The prognoses of the invasive GBCs with either papillary neoplasia or ICPN were thus more favorable than those of the invasive GBCs without ICPN/pap-neoplasia. Invasive GBCs with exophytic papillary preinvasive lesions (ICPN and papillary neoplasia) may be biologically different from those without such lesions.

A case of granulocyte colony-stimulating factor-producing intrahepatic sarcomatoid cholangiocarcinoma.

Here, we report a rare case of intrahepatic sarcomatoid cholangiocarcinoma that expressed granulocyte colony-stimulating factor (G-CSF). An 87-year-old man who presented with a continuous high-grade fever and cough over two weeks, and increased inflammatory response was admitted to our hospital. Laboratory tests revealed marked granulocytosis and high serum levels of G-CSF and interlukin-6. Imaging studies showed a huge liver mass in his right lobe and intrahepatic metastasis. He died of progressive disease. Pathological findings of the primary liver tumor at autopsy showed sarcomatous change; the specimen was positive for cytokeratins (AE1/AE3, cytokeratin-7, cytokeratin-19) and G-CSF. Few cases of G-CSF-producing intrahepatic sarcomatoid cholangiocarcinoma have been reported.

Breast metastasis from pelvic high-grade serous adenocarcinoma: a report of two cases.

BACKGROUND: Metastatic tumors to the breast reportedly account for 0.5% to 2.0% of all malignant breast diseases. Such metastatic tumors must be differentiated from primary breast cancer. Additionally, few reports have described metastases of gynecological cancers to the breast. We herein report two cases of metastasis of pelvic high-grade serous adenocarcinoma to the breast. CASE PRESENTATION: The first patient was a 57-year-old woman with a transverse colon obstruction. Colostomy was performed, but the cause of the obstruction was unknown. We found scattered white nodules disseminated throughout the abdominal cavity and intestinal surface. Follow-up contrast-enhanced computed tomography (CT) showed an enhanced nodule outside the right mammary gland. Core needle biopsy (CNB) of the right breast mass was conducted, and immunohistochemical staining of the mass suggested a high-grade serous carcinoma of female genital tract origin. We diagnosed the patient's condition as breast and lymph node metastasis of a high-grade serous carcinoma of the female genital tract. After chemotherapy for stage IVB peritoneal cancer, tumor reduction surgery was performed. The second patient was a 71-year-old woman with a medical history of low anterior resection for rectal cancer at age 49, partial right thyroidectomy for follicular thyroid cancer at age 53, and left lower lung metastasis at age 57. Periodic follow-up CT showed peritoneal dissemination, cancerous peritonitis, and pericardial effusion, and the patient was considered to have a cancer of unknown primary origin. Contrast-enhanced CT showed an enhanced nodule in the left mammary gland with many enhanced nodules and peritoneal thickening in the abdominal cavity. CNB of the left breast mass was conducted, and immunohistochemical staining of the mass suggested a high-grade serous carcinoma of female genital tract origin. After chemotherapy for stage IVB peritoneal cancer, tumor reduction surgery was performed. CONCLUSIONS: We experienced two rare cases of intramammary metastasis of high-grade serous carcinoma of female genital tract origin. CNB was useful for confirming the histological diagnosis of these cancers that had originated from other organs. A correct diagnosis of such breast tumors is important to ensure quick and appropriate treatment.

Chronic inflammatory changes and oxidative stress in the background of "pancreatic ductal adenocarcinoma concomitant with intraductal papillary mucinous neoplasm".

Cases of "pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm" (IPMN) have multiple PDAC lesions more frequently than cases of "PDAC without IPMN". However, the mechanism of carcinogenesis in this former disease category remains unknown. The main objective of this work was thus to investigate the effects of chronic inflammation on carcinogenesis in PDAC cases. We selected 31 "PDAC concomitant with IPMN" patients and 58 "PDAC without IPMN" patients and pathologically evaluated their background pancreatic parenchyma. Fibrosis and inflammation scores of background pancreas were higher in "PDAC concomitant with IPMN" than in "PDAC without IPMN" (P < 0.0001 and P < 0.0001, respectively), whereas the fatty infiltration score of background pancreas was high in "PDAC without IPMN" (P = 0.0024). Immunohistochemically, the expression of 8-hydroxy-2'-deoxyguanosine (8-OHDG), an oxidative stress marker, in the background pancreas was high in "PDAC concomitant with IPMN" compared with that in "PDAC without IPMN" (P < 0.0001). Chronic inflammation activates oxidative stress in tissue throughout the pancreas and probably confers susceptibility to tumorigenesis in "PDAC concomitant with IPMN".