[A Case of Early Gastric Cancer with Esophageal Hiatal Hernia Treated by Laparoscopic Gastrectomy for Cancer and Repair of Hiatal Hernia].

We report a successful case of gastric cancer with esophageal hiatal hernia treated by laparoscopic surgery. The patient was a 75-year-old woman who was referred to our hospital with a diagnosis of early gastric cancer with esophageal hiatal hernia. Laparoscopic distal gastrectomy with lymph node dissection and esophageal hiatal hernia repair using primary suture method without mesh were performed simultaneously. She had a good postoperative course without the recurrence of both cancer and hernia.

[A Case of Synchronous Papillary Thyroid Cancer and Breast Ductal Cancer].

Occurrences of thyroid cancer and breast cancer metachronously or synchronously are common for women. Explanations for these associations include detection bias, shared hormonal risk factors, and genetic susceptibility, but the etiology behind specific associations is not elucidated well. The importance of the relationship between breast and thyroid cancer will continue to become evident and physicians should be aware of this association in caring for thyroid and breast cancer survivors. We report a case of synchronous papillary thyroid cancer and breast ductal cancer.

Complete response to combination therapy using nivolumab and ipilimumab for metastatic, sarcomatoid collecting duct carcinoma presenting with high expression of programmed death-ligand 1: a case report.

BACKGROUND: Collecting duct carcinoma and sarcomatoid renal cell carcinoma are tumors with poor prognosis. Immune checkpoint inhibitors have been established as the standard treatment for advanced renal cell carcinoma. Some cases of remission of collecting duct carcinoma and sarcomatoid renal cell carcinoma have been reported using immune checkpoint inhibitor interventions. Specifically, sarcomatoid renal cell carcinoma expresses high levels of programmed death-ligand 1, an immune checkpoint protein, and immune checkpoint inhibitors have been reported to be highly effective for treating sarcomatoid renal cell carcinoma. CASE PRESENTATION: We describe the case of a 70-year-old Japanese male who underwent radical right nephrectomy for a right renal mass identified on computed tomography. The pathological examination demonstrated that the renal mass was urothelial carcinoma and collecting duct carcinoma with sarcomatoid changes, and programmed death-ligand 1 was highly expressed with a tumor proportion score of more than 10%. There was no evident submucosal connective tissue invasion in the urothelial carcinoma component, and collecting duct carcinoma was diagnosed as primary cancer. The tumor-node-metastasis classification was pT3aN0, venous invasion 1, lymphovascular invasion 0, and Fuhrman nuclear grade 4. Two months after the nephrectomy, multiple metastases were observed in both lungs, the right hilar lymph node, and the S6 segment of the right liver lobe. We initiated first-line combination therapy with nivolumab (240 mg, fixed dose) and ipilimumab (1 mg/kg). One day after administration, the patient developed drug-induced interstitial pneumonia, thus we applied steroid injections. After one administration of immunotherapy, the metastatic lesion showed complete response within 6 months, which was maintained after 3 years. CONCLUSION: We report the first case of complete response to a single dose of combination therapy with nivolumab and ipilimumab for metastatic collecting duct carcinoma with sarcomatoid changes and high expression of programmed death-ligand 1. This case suggests high expectations for immune checkpoint inhibitors as treatment for sarcomatoid-transformed renal carcinoma tumors that express high levels of programmed death-ligand 1.

Immunostaining With Immunoglobulin G Subclass Antibody Cocktail for Diagnosis of Type 1 Autoimmune Pancreatitis.

BACKGROUND.: Immunoglobulin (Ig) G4-related diseases (RDs) are systemic diseases in which serum IgG4 levels are frequently elevated. They can cause diffuse or focal tumor formation, organ swelling, and tissue thickening in organs infiltrated by IgG4+ plasma cells. The diagnostic criteria for IgG4-RDs include an IgG4/IgG ratio >40%, but counting IgG+ cells can be difficult because of the weakness of IgG staining density. We hypothesized that an antibody cocktail of mixed IgG1, IgG2, IgG3, and IgG4 (AC-IgG) might give immunohistochemistry results comparable with those of IgG in IgG4-RD. METHODS.: We compared AC-IgG reactivity with IgG expression in type 1 autoimmune pancreatitis (AIP), a representative IgG4-RD. We compared immunohistochemistry results using AC-IgG and IgG-only in 10 cases of AIP. The coefficient of variation (Cv) was used to analyze differences between AC-IgG and IgG findings in AIP by 13 board-certified pathologists. RESULTS.: Although mean values for IgG+ cells did not significantly differ between AC-IgG (34.3; range = 27.4-37.1) and IgG (30.0; range = 23.0-45.6; P = .6254), Cv was lower for AC-IgG (33.4%) than for IgG (51.4%; regression equation; y[IgG] = 0.988x + 0.982; correlation coefficient = 0.907). The data showed that the results of both methods were largely consistent. CONCLUSION.: AC-IgG could replace IgG to count IgG+ cells because of its lower Cv.

Worsening cytology and lesion enlargement are useful indicators for malignant transformation of lobular endocervical glandular hyperplasia during follow-up: A case report.

•We report a case of MDA arising from clinical LEGH during 5 years of follow-up.•The first sign suggesting MDA was cellular atypia in endocervical cytology, and was followed by an increase in tumor size.•MDA lesion lacked in stromal reaction and MRI failed to detected MDA.•Worsening cytology and lesion enlargement are important signs for malignant change of LEGH during follow-up.

Sjögren syndrome-related plasma cell disorder and multifocal nodular AL amyloidosis: clinical picture and pathological findings.

Background: Localized nodular deposits of AL amyloid are seen in different tissues/organs; however, the pathogenesis of this form of amyloidosis remains unclear. Recently, Sjögren syndrome combined with localized nodular AL amyloidosis has been noted. Here, we report Sjögren syndrome cases showing multifocal nodular AL amyloidosis and the followed benign course. Materials and methods: We investigated the clinical pictures and histopathological findings of three cases with both presence of Sjögren syndrome and localized nodular AL amyloidosis, paying a special attention to the distribution of amyloidoma. Results: All three cases were middle-aged females. In two of three cases localized deposits of AL amyloid preceded Sjögren syndrome. Amyloidoma was detected in scalp, eyelid, cheek, larynx, trachea, lung and breast, and around these amyloid-deposited lesions infiltration of plasma cells was seen. Pulmonary amyloidosis was consistently accompanied with parenchymal cystic lesions, but this amyloidosis did not produce any significant respiratory symptoms. Some of large pulmonary amyloidomas showed cavity formation and subsequent shrinkage. In two cases amyloid deposition was found on gastric mucosa. Two cases received small doses of oral prednisone, with no further appearance of amyloidoma. Conclusion: Sjögren syndrome-related plasma cell disorder may be responsible for the formation of this unique multifocal nodular AL amyloidosis.

ACTH-producing thymic neuroendocrine tumor initially presenting as psychosis: A case report and literature review.

A 32-year-old woman was referred to our hospital because of severe psychosis and was found to have an ectopic ACTH-producing thymic neuroendocrine tumor. Laboratory data revealed an elevated serum cortisol and plasma ACTH level, hypokalemia, and metabolic alkalosis. Chest computed tomography (CT) revealed an anterior mediastinal mass and multiple pulmonary nodules. As the patient was unable to communicate because of her consciousness disturbance, she was managed with artificial ventilation and deep sedation. Metyrapone and potassium supplementation were administered, and steroid psychosis gradually improved. Thoracic surgery was performed and the histopathological diagnosis was thymic neuroendocrine tumor with positive anti-ACTH immunohistochemical staining. Here we present details of the case and review the literature.

A fulminant case of classical Hodgkin lymphoma: A diagnostic dilemma of Epstein-Barr virus-positive large B-cell neoplasms.

We report a fulminant case of classical Hodgkin lymphoma (CHL). The patient died only approximately 2 months after the onset of subjective symptoms. Autopsy specimens revealed atypical cells resembling Hodgkin and Reed-Sternberg (HRS) cells in a rich inflammatory background in various organs. There were marked, characteristic angiodestructive lesions from infiltrating HRS-like cells and numerous macrophages. The HRS-like cells were infected with Epstein-Barr virus (EBV), immunohistochemically positive for PAX5 and CD30, and negative for CD3, CD20, and ALK. Most B-cell markers other than PAX5 were negative, and the HRS-like cells also expressed cytotoxic molecules. Monoclonal rearrangement of immunoglobulin heavy chain was detected by PCR analysis. According to the 2016 WHO classification, we diagnosed mixed cellularity CHL. However, EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified and EBV-positive B-cell lymphoma, unclassifiable with features intermediate between DLBCL and CHL were considered as differential diagnoses because both tumors are aggressive EBV-positive large B-cell neoplasms with reactive inflammatory cells and sometimes contains HRS-like cells. The clinical condition of the current case was closer to these two entities than to CHL. A diagnosis of EBV-positive large B-cell neoplasms was difficult because of overlapping morphological and immunohistochemical characteristics, but should be considered for prognosis.

Initial clinical presentation of single soft tissue metastasis of medullary thyroid carcinoma without primary tumor in the thyroid gland.

BACKGROUND: Single soft tissue metastasis of medullary thyroid carcinoma is extremely rare. In addition, several occult medullary thyroid carcinomas with distant metastasis were reported, but undetectable primary lesion at diagnosis was also extremely rare. CASE PRESENTATION: A 74-year-old man was admitted to our hospital because of a painful nodule in his left buttock for over 1 year. Needle biopsy was performed, and the histological findings revealed adenocarcinoma positive for thyroid transcription factor-1. No evidence of a primary tumor, including the lung and thyroid gland, could be found elsewhere despite detailed examinations, including thyroid echography, chest computed tomography, and fluorodeoxyglucose-positron emission tomography. The soft tissue tumor was resected with a wide margin. Immunohistochemical analysis showed the tumor cells to be positive for cytokeratin-AE1/3, cytokeratin 7, synaptophysin, chromogranin A, calcitonin, and carcinoembryonic antigen, but negative for cytokeratin 20, Napsin A, Pax8, and p40, resulting in a diagnosis of metastasis of medullary thyroid carcinoma. CONCLUSION: Initial presentation with a single metastasis to soft tissue and undetectable primary tumor in the thyroid gland is an extremely rare clinical manifestation in patients with medullary thyroid carcinoma.

A case of MUC5AC-positive intraductal neoplasm of the pancreas classified as an intraductal tubulopapillary neoplasm?

This report describes a unique case of intraductal tubulopapillary neoplasm (ITPN) of the pancreas in order to clarify its oncogenesis and more precisely classify pancreatic intraductal neoplasms. A 74-year-old man visited our institution for follow-up of acute pancreatitis. Imaging examinations revealed a hypovascular intraductal mass in the head of the pancreas with progressive dilation of the pancreatic duct, atrophy of the pancreatic parenchyma, and a non-mucinous appearance. A pancreatoduodenectomy was performed to identify this pancreatic intraductal neoplasm. Macroscopically, the tumor was a solid nodular mass with no visibly secreted mucin obstructing the dilated ducts. Histologically, it had a homogeneous appearance with nodules of back-to-back tubular glands and occasional papillary elements, and there were no apparent transitions to areas with less marked cytoarchitectural atypia. Although the intraductal neoplastic growth corresponded to an ITPN, immunohistochemical staining revealed partial positivity for MUC5AC, for which ITPNs are characteristically negative. Somatic mutations in KRAS, GNAS, BRAF, and PIK3CA were not detected. A loss of MUC5AC expression and mutations in KRAS and GNAS are key elements in the diagnosis of ITPN. Thus, it was difficult to distinguish the present case as a pancreatobiliary-type (PB-type) intraductal papillary mucinous neoplasm (IPMN) or a phenotypic variant of ITPN. As it is possible that some cases of PB-type IPMN and ITPN overlap, the precise classification of these rare lesions may require re-evaluation.

Helicobacter pylori-negative Differentiated Adenocarcinoma of the Stomach.

A 58-year-old Japanese man was diagnosed with differentiated adenocarcinoma of the stomach. Histological findings of the resected specimen revealed well- to moderately-differentiated tubular adenocarcinoma (tub1, tub2), 13 mm in diameter, which invaded into the submucosa (SM1, 300 µm) and lymphovascular lumen (ly1). Serum antibody against Helicobacter pylori (Hp) and the (13)C-urea breath test were negative, and there were no atrophic changes in the tumor-adjacent mucosa. The immunohistochemical analysis showed that gastric mucin (MUC5AC) was strongly positive and intestinal mucin (MUC2) was weakly and partially positive. According to these results, the final diagnosis of Hp-negative well-differentiated early gastric cancer was made.

Cornichon-like protein facilitates secretion of HB-EGF and regulates proper development of cranial nerves.

During their migration to the periphery, cranial neural crest cells (NCCs) are repulsed by an ErbB4-dependent cue(s) in the mesenchyme adjoining rhombomeres (r) 3 and 5, which are segmented hindbrain neuromeres. ErbB4 has many ligands, but which ligand functions in the above system has not yet been clearly determined. Here we found that a cornichon-like protein/cornichon homolog 2 (CNIL/CNIH2) gene was expressed in the developing chick r3 and r5. In a cell culture system, its product facilitated the secretion of heparin-binding epidermal growth factor-like growth factor (HB-EGF), one of the ligands of ErbB4. When CNIL function was perturbed in chick embryos by forced expression of a truncated form of CNIL, the distribution of NCCs was affected, which resulted in abnormal nerve fiber connections among the cranial sensory ganglia. Also, knockdown of CNIL or HB-EGF with siRNAs yielded a similar phenotype. This phenotype closely resembled that of ErbB4 knockout mouse embryos. Because HB-EGF was uniformly expressed in the embryonic hindbrain, CNIL seems to confine the site of HB-EGF action to r3 and r5 in concert with ErbB4.