A case of unexpected diagnosis of fibronectin glomerulopathy with histological features of membranoproliferative glomerulonephritis.

Fibronectin (FN) glomerulopathy (FNG), a rare autosomal hereditary renal disease, is characterized by proteinuria resulting from the massive accumulation of FN in the glomeruli. It typically affects individuals aged 10-50 years. In this report, we describe the case of a 57-year-old man who was diagnosed with FNG through genetic analysis and histological examination that revealed membranoproliferative glomerulonephritis. Despite treatment with prednisolone, the therapeutic response was unsatisfactory. Prednisolone was subsequently tapered and discontinued because the patient had pulmonary thromboembolism. Subsequent comprehensive genetic testing, which was initially not conducted because the patient's parents did not have a history of kidney disease, identified a known disease-causing variant in the FN1 gene, indicating a de novo variant. FNG was further confirmed by positive staining of glomeruli with FN using an IST-4 antibody. Although corticosteroid therapy is commonly employed as the initial treatment for MPGN, its appropriateness depends on the underlying etiology. Thus, clinicians must be aware of potential rare genetic causes underlying MPGN.

[A Case of Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm of the Distal Bile Duct].

An 82-year-old male with jaundice was referred to our hospital for a detailed examination. The computed tomography (CT) examination detected an enhanced mass lesion of the distal bile duct. Endoscopic retrograde cholangiography showed a filling defect corresponding to the CT findings. Simultaneously, a forceps biopsy and an endoscopic retrograde biliary drainage were performed. We performed pancreatoduodenectomy, and adenocarcinoma was pathologically proven. The histopathological finding of the resected specimen was a mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) composed of large cell neuroendocrine carcinoma and well-differentiated adenocarcinoma. Although pathological R0 resection was achieved, liver metastasis was observed 6 months after the operation. Although neuroendocrine carcinoma (NEC) rarely develops in the bile duct, it manifests a higher degree of malignancy than other ordinary bile duct adenocarcinomas. Further investigation is needed to choose an appropriate treatment.

Homeobox transcription factor engrailed homeobox 1 is a possible diagnostic marker for adenoid cystic carcinoma and polymorphous adenocarcinoma.

Diagnostic utility of a homeobox transcription factor, engrailed homeobox 1 (En1) in the histopathology of salivary gland neoplasms was studied. The expression of En1 was immunohistochemically examined in 51 cases of adenoid cystic carcinoma (AdCC) and 143 cases of other salivary gland neoplasms. In all 51 AdCCs, En1 was expressed in 30-100% of tumor cells. In eight of nine polymorphous adenocarcinomas (PACs), En1 was expressed in 40-100% of tumor cells. Less than 5% of tumor cells expressed En1 in three of 12 epithelial-myoepithelial carcinomas, one of 17 basal cell adenomas (BCAs), and one of 34 pleomorphic adenomas (PAs). Among 55 other carcinoma cases, 1-30% of tumor cells expressed En1 in three salivary duct carcinomas (SDCs) ex PA. None of the myoepitheliomas and Warthin tumors expressed En1. When the cut-off value of the percentage of En1-expressing cells was set to 25%, all 51 AdCCs, eight of nine PACs and one SDC ex PA were En1-positive and the others were En1-negative. En1 is expressed consistently in AdCCs, frequently in PACs, but rarely in other salivary gland neoplasms. En1 is a possible diagnostic marker for AdCC and PAC in the histopathology of salivary gland neoplasms.

[A Case of Pulmonary Enteric Adenocarcinoma with Soleus Muscle Metastasis].

Pulmonary enteric adenocarcinoma is a unique pulmonary adenocarcinoma subtype and has histopathological findings that are similar to those of colorectal adenocarcinoma. A man in his 50s visited our hospital because of discomfort in his right lower leg for the last 9 months. Imaging studies revealed a mass in his right soleus muscle, and needle biopsy was performed. Histological findings revealed adenocarcinoma, and immunohistochemical staining showed that the tumor cells were positive for CK20 and CDX-2. The tumor was first suspected to be metastasis of gastrointestinal malignant tumors. FDG-PET/CT showed increased FDG uptake in the right soleus muscle mass and presented with increased FDG uptake in a right upper lobe mass and right mediastinum lymphadenopathy. There were no findings in other organs. Scraping cytology of a transbronchial biopsy indicated adenocarcinoma. Upper and lower gastrointestinal endoscopy showed no findings of malignancy. He was finally diagnosed with pulmonary enteric adenocarcinoma(cT3N2M1b, Stage ⅣA). Treatment with cisplatin(CDDP), pemetrexed( PEM), and bevacizumab(BEV) was initiated. After 4 courses of the regimen, the tumor was partially reduced, and the patient showed stable disease(SD).

[Cerebrospinal fluid findings in chronic active Epstein-Barr virus infection with central nervous system involvement].

As chronic active Epstein-Barr virus (EBV) infection (CAEBV) progresses, EBV-infected tumor cells invade the central nervous system (CNS). To establish a diagnostic procedure for CNS invasion, we retrospectively analyzed cerebrospinal fluid (CSF) obtained from eight patients. Two patients presented with consciousness disturbance and were diagnosed with CNS invasion based on scan and autopsy results, respectively. The remaining six patients were diagnosed without CNS invasion by clinical findings and scans. In the two patients with CNS invasion, the number of mononuclear cells and the protein concentration were increased, whereas the CSF to serum glucose ratio and the adenosine deaminase concentration were raised. In one of the two patients, however, bacterial meningitis could not be excluded. Cytological examination of CSF demonstrated class 1-3. Notably, the CSF EBV-DNA load was positive in all patients, independent of CNS invasion diagnosis, and the CSF load correlated with that of the peripheral blood. Taken together, this indicates that CSF may lack the specific markers of CNS invasion in CAEBV patients. The CSF EBV-DNA load and the cytological analysis did not reflect CNS invasion; therefore, new biomarkers need to be established.

Cortical Actin Alteration at the Matrix-Side Cytoplasm in Lung Adenocarcinoma Cells and Its Significance in Invasion.

OBJECTIVES: Cortical actin is a thin layer of filamentous (F-)actin that lies beneath the plasma membrane, and its role in pathophysiology remains unclear. We investigated the subcellular localization of cortical actin by the histopathological and experimental studies of lung adenocarcinomas. MATERIALS AND METHODS: The subcellular localization of cortical actin was studied in surgically resected lung adenocarcinomas tissues and in 3-dimensionally cultured lung adenocarcinoma A549 cells. RESULTS: In normal type II alveolar cells and the bronchiolar epithelium, cortical actin was localized to the apical-side cytoplasm. In invasive adenocarcinoma cells, cortical actin was frequently localized to the matrix side. The degree of cortical actin localized to the matrix side was associated with the loss of basement membrane and a poor prognosis. In A549 cell spheroids cultured in a type I collagen and basement membrane extract Matrigel™ mixed gel, cortical F-actin was localized to the matrix side with phosphorylated myosin light chain. Super-resolution and electron microscopy results suggest that compact wrinkling of the plasma membrane by myosin-mediated F-actin contraction is an explanation for cortical actin accumulation at the matrix side. The myosin II inhibitor blebbistatin suppressed the 3-dimensional collective migration of A549 cells induced by constitutively active Cdc42 and MT1-MMP. CONCLUSION: Cortical actin accumulation at the matrix-side cytoplasm of cancer cells occurs in invasive lung adenocarcinomas and it possibly participates in the migration of cancer cells through myosin-mediated contraction.

A case of venous stasis colitis possibly caused by eplerenone.

A 50-year-old man was referred to our hospital for colitis with abdominal pain and diarrhea that had persisted for more than 8 months. 9 months earlier, he had been treated for fulminant eosinophilic myocarditis. During steroid therapy, ulceration appeared in the esophagus, stomach and large intestine. The biopsy results showed cytomegalovirus (CMV) inclusion bodies, and the patient was diagnosed with CMV gastrocolitis and treated with ganciclovir. Colonoscopy 7 months earlier revealed ischemia-like segmental colitis 10 cm in length in the hepatic flexure without evidence of CMV infection. Colonoscopy after 1 month and 3 months showed no improvement. We suspected drug-induced focal ischemic colitis, and discontinued eplerenone. Colonoscopy 2 months after withdrawal of eplerenone showed improvement in colitis, and colonoscopy 8 months later showed ulcer healing. Venous disorders are cautioned as a known side effect of eplerenone, but this is the first report of venous stasis colitis thought to be caused by eplerenone.

Pancreatic hamartoma: Possibility of a preoperative diagnosis via endoscopic ultrasound-guided fine-needle aspiration biopsy.

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is useful for preoperatively diagnosing various pancreatic tumors. Although there is a risk of complications, such as pancreatitis, this procedure achieves the crucial need of reducing unnecessary invasive surgery for benign lesions. Herein, we reported a surgically resected case of pancreatic hamartoma in the pancreatic head whose retrospective analysis revealed that the specimens obtained via EUS-FNAB contained hamartoma fragments. Pancreatic hamartoma is an extremely rare benign disease that is exceptionally difficult to diagnose before surgical resection owing to its rarity and lack of established imaging findings. To the best of our knowledge, the preoperative diagnosis of pancreatic hamartoma via EUS-FNAB specimens has not been reported to date. Herein, postoperative EUS-FNAB evaluation revealed a collection of pancreatic hamartoma lesions, although the initial diagnosis was pancreatic tissue with focal atrophy and fibrosis. Diagnosis using EUS-FNAB can be challenging owing to the very small sample size. If mature acini and ducts with fibrous stroma without islets are observed in the EUS-FNAB specimen, pancreatic hamartoma should be considered as a differential diagnosis. Thus, careful follow-up or reexamination of EUS-FNAB should be considered instead of surgery if a benign lesion is suspected preoperatively.

Synovial sarcoma of the stomach: a case report and a systematic review of literature.

Worldwide, 5-10% of soft tissue sarcoma cases in adults have been attributed to synovial sarcoma. It is often reported to occur near the joints of the arm, neck, and leg but rarely in the gastrointestinal tract. In this study, we report a case of synovial sarcoma arising in the stomach of a 59-year-old woman. Gastrointestinal endoscopy revealed an ulcerative and hemorrhagic tumor with marginal elevation in the fundus. Histological study showed that the tumor was composed of tightly packed spindle cells in bundles, and one of its component demonstrated significant mitotic activity (> 40/10 high-power fields) in several areas. The diagnosis was confirmed by the evidence of SS18 gene rearrangement, according to immunohistochemistry study, (including a novel SS18-SSX fusion-specific antibody), fluorescent in situ hybridization, and the identification of the SS18-SSX1 and SS18-SSX1/2/4 fusion transcripts using reverse-transcript polymerase chain reaction. No evidence of local recurrence or distant metastasis has been found in the more than 5 years since. Distinguishing synovial sarcoma in the digestive tract from other mesenchymal neoplasms, such as gastrointestinal stromal tumor, may be difficult, especially when spindle-shaped cell proliferation is predominant, as in our patient. Therefore, morphological, immunohistological, and molecular evaluations are important for a comprehensive diagnosis.

Substantial Epstein-Barr virus reactivation in a case of severe refractory ulcerative colitis: a possible role in exacerbation.

Ulcerative colitis (UC) is an inflammatory bowel disease that causes chronic inflammation in the colon. 5-aminosalicylic acid and immunosuppressive medications such as corticosteroids, immunomodulators, and biologic agents are used to treat these patients. However, patients with UC who receive immunosuppressive medications may be at risk for certain opportunistic infections. Epstein-Barr virus (EBV) is one of those opportunistic infections, and its pathogenic role has been implicated in refractory UC, but its pathogenicity should be further investigated. Here, we report a surgical case of refractory UC that demonstrated a serologically post-infected pattern of EBV at admission but that later had a high load of EBV in both the peripheral blood and colonic mucosa. These findings suggest that EBV may have been reactivated in the colon, after which it damaged the colonic mucosa and aggravated inflammation in this patient with UC. Thus, EBV might lead to severity and a refractory response against corticosteroids and anti-TNFα agents, necessitating emergency surgery. Viral surveillance for EBV in patients with refractory UC may facilitate understanding of the patient's pathophysiology and predicting response to medications, and the development of antiviral intervention for those patients may improve their prognosis.

Feasibility of ultrafast dynamic magnetic resonance imaging for the diagnosis of axillary lymph node metastasis: A case report.

A 74 year old Japanese woman was diagnosed with invasive breast carcinoma. Her axillary lymph node was slightly swollen and had a short-axis diameter of 8 mm, but fine-needle aspiration did not lead to the diagnosis of metastasis. Subsequent 18F-fluorodeoxyglucose positron emission tomography/computed tomography showed no abnormal accumulation on the lymph node. Ultrafast dynamic magnetic resonance imaging yielded a very fast contrast enhancement like that of the primary lesion based on which we suspected lymph node metastasis. To our knowledge, this is the first report that shows that ultrafast imaging has contributed to the diagnosis of axillary lymph node metastasis.

Engrailed Homeobox 1 and Cytokeratin 19 Are Independent Diagnostic Markers of Eccrine Porocarcinoma and Distinguish It From Squamous Cell Carcinoma.

OBJECTIVES: The diagnostic utility of En1 in the histopathologic differentiation of eccrine porocarcinoma (EPC) from invasive squamous cell carcinoma (SCC) was investigated. METHODS: Expression of En1 and CK19 in 16 cases of EPC was immunohistochemically examined and compared with that in 32 cases of SCC. RESULTS: In all 16 EPCs, En1 was expressed in 3% to 100% of tumor cells. In 20 of the 32 SCCs, En1 was expressed in 3% to 90% of tumor cells. A total of 13 of the 16 EPCs and five of the 32 SCCs were judged as En1 positive, with a cutoff value of 25%. In addition, 11 of the 16 EPCs and four of the 32 SCCs were CK19 positive. The frequencies of En1- and CK19-positive cases were significantly higher in EPCs than in SCCs. In a logistic regression analysis for predicting EPC, En1 and CK19 were independent markers. When expression patterns of En1 and CK19 were combined, none of the 32 SCCs was both positive. In contrast, 15 of the 16 EPCs were positive for either En1 or CK19. CONCLUSIONS: A combination of En1 and CK19 expression can improve the accuracy of histologic diagnosis of EPC.

Myasthenia Gravis Complicated with Peripheral T-cell Lymphoma, Not Otherwise Specified (PTCL-NOS), Following Thymectomy and Longstanding Tacrolimus Therapy.

Myasthenia gravis (MG), a neuromuscular junction autoimmune disease, sometimes complicates second malignancies; however, T-cell lymphoproliferative disorders have rarely been reported. A 55-year-old man, who received oral tacrolimus and prednisolone for MG for 16 years after thymectomy, presented with left abdominal pain, lymphadenopathy, and splenomegaly. A lymph node biopsy revealed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). This is the first report of oral tacrolimus leading to a T-cell lymphoproliferative disorder in patient without a history of transplantation. Physicians should be aware of the possibility of rare T-cell lymphoproliferative disorders, such as PTCL-NOS, occurring as complications in MG patients on immunosuppressive regimens after thymectomy.