Mesenchymal-epithelial transition factor exon 14 skipping mutation-positive granulocyte colony-stimulating factor-producing lung adenocarcinoma mimicking lung abscess: A case report.

Granulocyte colony-stimulating factor (G-CSF)-producing lung tumours are rare, with their imaging features and effective treatments remaining elusive. Similarly, mesenchymal-epithelial transition (MET) exon 14 skipping mutations are also uncommon. Herein, we report a case of G-CSF-producing lung adenocarcinoma positive for a MET exon 14 skipping mutation, mimicking lung abscess. A 61-year-old man presented with cough and high fever. Contrast-enhanced chest computed tomography revealed a mass with a cavity and internal fluid accumulation. The patient initially underwent diagnostic treatment for a lung abscess but was ultimately diagnosed with lung adenocarcinoma positive for a MET exon 14 skipping mutation. Following tepotinib therapy, the primary lesion shrank, and serum G-CSF levels decreased, leading to a diagnosis of G-CSF-producing lung cancer. G-CSF-producing lung tumours can present imaging findings that mimic lung abscesses. Tepotinib therapy may be effective for patients with MET exon 14 skipping mutation, including those with G-CSF-producing lung cancer.

[A Case of Inflammatory Myofibroblastic Tumor of The Bladder Treated with Partial Cystectomy].

A 60-year-old woman with extensive hematuria visited our hospital. Cystoscopy revealed a tumor with an edematous surface on the left lateral wall of the urinary bladder. To diagnose the tumor, we performed a transurethral resection of the bladder tumor. Pathological examination suggested leiomyoma. Four weeks after the transurethral resection, magnetic resonance imaging revealed an increase in the bladder tumor. She received partial cystectomy. Pathological analysis revealed an inflammatory myofibroblastic tumor. No recurrence was observed 9 months after the initial operation.

Vasculitis mimicking immunoglobulin-G4-related disease with involvement of the submandibular and lacrimal glands and periaortitis: A case report.

INTRODUCTION: Vasculitis does not usually induce glandular tissue lesions. Herein, we present a case of vasculitis with a distribution similar to that of immunoglobulin-G4-related disease (IgG4-RD), including that of the submandibular and lacrimal glands, and periaortitis. CASE REPORT: A 70-year-old man presented with shortness of breath. Laboratory findings revealed an IgG4 level of 191 mg/dL, negative antineutrophil cytoplasmic antibody test, and C-reactive protein level of 8.33 mg/dL. Magnetic resonance imaging of the head and computed tomography of the neck revealed bilaterally enlarged submandibular and lacrimal glands. Neck-to-pelvis computed tomography revealed bilateral infiltrative shadows in the lower lobes of both lungs, mass shadows in both lungs, and periaortitis of the abdominal aorta extending to the common iliac artery. Thus, the patient was diagnosed with IgG4-related respiratory disease and periaortitis/periarteritis. Prednisolone was administered at a dose of 35 mg (0.6 mg/kg daily). The dose was gradually tapered while observing the effects of the treatment. Imaging findings indicated an improvement and the C-reactive protein and IgG4 levels decreased, indicating a successful treatment course. However, after reexamination of the pathological findings, the diagnosis changed from IgG4-RD to vasculitis. One year after treatment initiation, the patient symptoms have stabilized. CONCLUSION: Vasculitis can present with lesions and pathological findings similar to those of IgG4-RD.

Pseudo-Meigs' Syndrome in a Patient With Uterine Fibroids With Massive Pleural Effusion After Starting Gonadotropin-Releasing Hormone Agonist Therapy: A Case Report.

Pseudo-Meigs' syndrome is caused by uterine fibroids, which is often treated using gonadotropin-releasing hormone (GnRH) agonists. Here we report a case of pseudo-Meigs' syndrome that developed with massive pleural effusion after the initiation of GnRH agonist therapy for uterine fibroids. A 48-year-old woman presented with dyspnea. Her medical history included uterine fibroids and GnRH agonist therapy. Contrast-enhanced computed tomography revealed a massive pleural effusion, uterine fibroids, and ascites. A total laparoscopic hysterectomy was performed. The pathologic findings were consistent with those of uterine fibroids. The pleural effusion and ascites resolved completely. The patient was diagnosed with pseudo-Meigs' syndrome due to uterine fibroids.

Endoscopic Management for Recurrent Hydrocephalus Associated with Neurosarcoidosis.

BACKGROUND: Recurrent hydrocephalus may occur as a complication of neurosarcoidosis with chronic inflammation. We present a case that required a combination of multistage endoscopic diversion of the cerebrospinal fluid pathway and shunt surgery. CASE DESCRIPTION: A 34-year-old man presented with progressive nausea and vomiting. Magnetic resonance imaging revealed hydrocephalus with leptomeningeal enhancement along the base of the fourth ventricle and the bilateral foramina of Luschka. Concurrent endoscopic third ventriculostomy and biopsy were performed. The diagnosis was neurosarcoidosis. Immediately after the procedure, the endoscopic third ventriculostomy stoma was occluded, and a right ventriculoperitoneal shunt was urgently performed. However, left unilateral hydrocephalus developed during the late phase of immunosuppressive therapy for neurosarcoidosis. Endoscopic septostomy with repositioning of the ventricular catheter was indicated. Intraoperative findings included a white pasty tissue with nodules that covered the ventricular wall close to the foramen of Monro and sealed the side holes of the catheter. Chemotherapy with a tumor necrosis factor-α inhibitor was initiated after the surgical procedure. The patient had an uneventful course without recurrence of hydrocephalus for >6 months. CONCLUSIONS: Endoscopic diversion of the cerebrospinal fluid pathway should be actively considered for treating hydrocephalus without a shunt and performing biopsy simultaneously. Even if a subsequent shunt is needed, complex hydrocephalus can be avoided with a combination of endoscopic techniques.

Epidural abscess caused by Schizophyllum commune: A rare case of rhinogenic cranial complication by a filamentous basidiomycete.

Central nervous system (CNS) infections due to filamentous basidiomycetes are extremely rare. We encountered a case of epidural abscess due to Schizophyllum commune that extended from sinusitis. A 53-year-old Japanese man presented at our hospital with a headache. Computed tomography (CT) of the cranium and sinuses showed ethmoid and sphenoid sinusitis with no intracranial abnormalities. The patient was diagnosed with acute sinusitis and underwent antibiotic treatment. However, the symptoms deteriorated, and the patient came to our hospital again with consciousness disturbance. CT scan of the cranium and sinuses showed no improvement of sinusitis after antibiotic therapy and an epidural abscess emerged in the middle cranial fossa. Therefore, emergency craniotomy and endoscopic sinus fenestration were performed. Filamentous fungal elements were observed in both rhinorrhoea and epidural abscess. The symptoms improved after the operation and administration of liposomal amphotericin B. The clinical isolate was identified as S. commune by a molecular-based method. To our knowledge, this is the first report of epidural abscess due to this fungus. Although rare, clinicians should be aware that S. commune could be a causative agent of CNS infections.

Ultrasound findings of diffuse metastasis of gastric signet-ring-cell carcinoma to the thyroid gland.

It has been shown that metastases to the thyroid from extrathyroidal malignancies occur as solitary or multiple nodules, or may involve the whole thyroid gland diffusely. However, diffuse metastasis of gastric cancer to the thyroid is extremely rare. Here, we report a case of a 74-year-old woman with diffuse infiltration of gastric adenocarcinoma (signet-ring-cell carcinoma/poorly differentiated adenocarcinoma) cells in the thyroid. The pathological diagnosis was made based on upper gastrointestinal endoscopy with biopsy and fine-needle aspiration cytology of the thyroid. An 18F-FDG PET/CT revealed multiple lesions with increased uptake, including the bilateral thyroid gland. On thyroid ultrasound examination, diffuse enlargement with internal heterogeneity and hypoechoic reticular lines was observed. On color Doppler imaging, a blood-flow signal was not detected in these hypoechoic lines. These findings were similar to those of diffuse metastases caused by other primary cancers, such as lung cancer, as reported earlier. Therefore, the presence of hypoechoic reticular lines without blood-flow signals is probably common to diffuse thyroid metastasis from any origin and an important diagnostic finding. This is the first report to show detailed ultrasound findings of diffuse gastric cancer metastasis to the thyroid gland using color Doppler.

Erratum: Carcinoma-like nonfunctional pheochromocytoma in the right adrenal gland: A case report.

[This corrects the article DOI: 10.3892/ol.2016.4776.].

Carcinoma-like nonfunctional pheochromocytoma in the right adrenal gland: A case report.

Evaluation of the malignant potential of a pheochromocytoma (PCC) remains controversial. PCC is regarded as a neuroendocrine tumor (NET), and the classification of NETs has gradually been defined over the last decade, particularly for gastroenteropancreatic NET. The present study describes a case of locally advanced, carcinoma-like, nonfunctional PCC, which may be regarded as neuroendocrine carcinoma (NEC) rather than a malignant PCC. A 72-year-old man was referred to Saitama Red Cross Hospital (Saitama, Japan), presenting with a 2-month history of right flank pain. Computed tomography revealed a right adrenal gland tumor, which measured 6.0 cm in diameter, invading the hilum of the right kidney, liver and inferior vena cava (IVC). Radical surgery was performed with en bloc resection of the right kidney, and adjacent parts of the liver and IVC. Immunohistochemical examination demonstrated that all of the resected tissues were positive for cytokeratin AE1/AE3, chromogranin A, synaptophysin, cluster of differentiation 56 and Ki-67, and the specimen had a Ki-67 index of 80%. A diagnosis of carcinoma-like PCC or NEC of the adrenal gland was confirmed. Reports of NEC of the adrenal gland are extremely rare in the literature, and classification of PCC as a NET has not yet been fully discussed. The present case may therefore contribute to the classification of NETs in the adrenal gland.

Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma: the second report: relationship with tumor size and cell differentiation.

BACKGROUND: The purpose of this study is to investigate whether ordinary hepatocellular carcinomas (HCCs) show positivity of stem/progenitor cell markers and cholangiocyte markers during the process of tumor progression. METHODS: Ninety-four HCC lesions no larger than 8 cm from 94 patients were immuno-histochemically studied using two hepatocyte markers (Hep par 1 and α-fetoprotein), five cholangiocyte markers (cytokeratin CK7, CK19, Muc1, epithelial membrane antigen and carcinoembryonic antigen) and three hepatic stem/progenitor cell markers (CD56, c-Kit and EpCAM). The tumors were classified into three groups by tumor size: S1, < 2.0 cm; S2, 2.0-5.0 cm; S3, 5.0-8.0 cm. The tumors were also classified according to tumor differentiation: well, moderately and poorly differentiated. The relationship between the positive ratios of these markers, tumor size and tumor differentiation was examined. RESULTS: The positive ratios of cholangiocyte markers tended to be higher in larger sized and more poorly differentiated tumors (except for CK7). The positive ratios of stem/progenitor cell markers tended to be higher in larger sized and more poorly differentiated tumors (except for c-Kit). CONCLUSION: Ordinary HCC can acquire the characteristic of positivity of cholangiocyte and stem/progenitor cell markers during the process of tumor progression.

Is it possible to define early distal cholangiocarcinoma?

PURPOSE: The feasibility of defining early cholangiocarcinoma has not been adequately evaluated. The surgical outcomes of patients who had undergone pancreatoduodenectomy (PD) for pathological T1 (pT1) distal cholangiocarcinoma (DCC) were evaluated to determine whether it is possible to define early DCC. METHODS: The clinicopathological data of 18 patients with pT1 DCC who had undergone PD were reviewed retrospectively. Depth of fibromuscular (fm) layer invasion was divided into two categories: fm1 and fm2 (without adventitia fascia invasion and with adventitia fascia invasion). Comparative analyses were performed according to the depth of invasion. RESULTS: Disease-specific survival rates of patients with five mucosal tumors and 13 fm-invasive tumors were 80 and 61.9 % at 5 years and 80 and 41.2 % at 10 years, respectively. There was no significant difference in disease-specific survival rates between the two groups (P = 0.244). Disease-specific survival rates of patients with 7 fm1-invasive tumors and 6 fm2-invasive tumors were 85.7 and 40 % at 5 years and 85.7 and 0 % at 10 years. A significant difference in disease-specific survival rates was observed between mucosal tumors and fm2-invasive tumors (P = 0.043), and disease-specific survival rates of mucosal tumors and fm1-invasive tumors were similar (P = 0.968). CONCLUSIONS: Defining early DCC as carcinoma confined to the fm of the bile duct might be inappropriate; early DCC should be limited to the mucosal carcinoma.

Simultaneous bilateral testicular metastases from renal clear cell carcinoma: A case report and review of the literature.

Metastasis from renal cell carcinoma (RCC) to the testis is rare. This case report presented an extremely rare case of simultaneous bilateral testicular metastases from RCC in a 65-year-old man who had experienced indolent scrotal enlargement over a period of several months. Scrotal ultrasonography showed 4.0- and 2.0-cm-sized masses in the left and right testes, respectively. Contrast-enhanced computed tomography identified multiple tumors in the kidneys, the pancreas and the left adrenal gland. Left orchiectomy and pathological examination were performed and indicated testicular metastasis from clear cell RCC. The patient underwent complete surgical resection of all residual lesions. Postoperative follow-up examination without adjuvant therapy identified no recurrence over 11 months. This study also reviewed existing literature and determined that retrograde venous spread from the primary kidney tumor to the testis may be an important pathway for testicular metastasis from RCC. In conclusion, RCC can result in testicular metastases not only unilaterally, but also bilaterally, as was observed in the present case.

Tumor necrosis factor-α promotes bile ductular transdifferentiation of mature rat hepatocytes in vitro.

We previously showed that mature hepatocytes could transdifferentiate into bile ductular cells when placed in a collagen-rich microenvironment. To explore the mechanism of transdifferentiation, we examined whether inflammatory cytokines affected the phenotype of hepatocytes in a three-dimensional culture system. Spheroidal aggregates of rat hepatocytes were embedded within a type I collagen gel matrix and cultured in the presence of various cytokines. In the control, hepatocytes gradually lost expression of albumin, tyrosine aminotransferase, and hepatocyte nuclear factor (HNF)-4α, while aberrantly expressed bile ductular markers, including cytokeratin 19 (CK 19) and spermatogenic immunoglobulin superfamily (SgIGSF). Among the cytokines examined, tumor necrosis factor (TNF)-α inhibited expression of albumin and HNF-4α, both at mRNA and protein levels. After culturing for 2 weeks with TNF-α, hepatocytic spheroids were transformed into extensively branching tubular structures composed of CK 19- and SgIGSF-positive small cuboidal cells. These cells responded to secretin with an increase in secretion and expressed functional bile duct markers. TNF-α also induced the phosphorylation of Jun N-terminal kinase (JNK) and c-Jun, and the morphogenesis was inhibited by SP600125, a specific JNK inhibitor. Furthermore, in chronic rat liver injury induced by CCl(4) , ductular reaction in the centrilobular area demonstrated strong nuclear staining of phosphorylated c-Jun. Our results demonstrate that TNF-α promotes the ductular transdifferentiation of hepatocytes and suggest a role of TNF-α in the pathogenesis of ductular reaction.

Recovery of mature hepatocytic phenotype following bile ductular transdifferentiation of rat hepatocytes in vitro.

We previously demonstrated that mature rat hepatocytes transdifferentiate to bile ductular cells when cultured in a three-dimensional collagen-rich matrix. Here, we show that the phenotype of transdifferentiated hepatocytes can be reversed by modulating culture conditions. Spheroidal aggregates of hepatocytes were cultured within a collagen gel matrix in the presence of serum and tumor necrosis factor-α. Spheroids transformed into ductular structures composed of small cuboidal cells, lost the expression of hepatocytic markers, whereas aberrantly expressed bile ductular markers. The transdifferentiated cells were then retrieved from the gels, plated on surfaces coated with a basement membrane-like material, and cultured in serum-free media. Cells spontaneously formed spheroidal aggregates and recovered hepatocytic phenotype. Dexamethasone (Dex), which suppressed the phosphorylation of ERK and Jun N-terminal kinase, facilitated the recovery, and the combination with interleukin-6 or oncostatin M resulted in the recovery of hepatocyte nuclear factor 4 α protein expression and the typical hepatocytic morphology, and a decrease in the expression of bile ductular markers. A cDNA microarray analysis revealed that the hepatocyte-specific mRNA expression profile was recovered in these cells. Our results demonstrate that hepatocytes are able to recover their phenotypes following bile ductular transdifferentiation, suggesting that hepatocytic and bile ductular phenotypes may be mutually reversible.

Mast cell leukemia with rapidly progressing portal hypertension.

Reported herein is an autopsy case of mast cell leukemia, a rare form of systemic mastocytosis, complicated with portal hypertension. A 52-year-old woman presented with urticaria-like skin symptoms, anemia, and thrombocytopenia. Atypical mast cells (CD2+, CD25+, CD117+) with toluidine blue metachromasia were found in the peripheral blood and on bone marrow aspiration smears. Chemotherapy with cytosine arabinoside and idarubicin was ineffective and the patient died of multi-organ failure with rapidly progressing hepatosplenomegaly and large-volume ascites 3 months after admission. At autopsy the bone marrow, spleen, liver, and lymph nodes were extensively infiltrated by atypical tumor cells with occasional bi- or multi-lobated nuclei. They were positive for mast cell tryptase and possessed an activating mutation of the c-kitgene (D816V). Ascites (2200 mL) and non-ruptured esophageal varices with submucosal hemorrhage indicated the presence of severe portal hypertension. Although there was no evidence of liver cirrhosis, the hepatic sinusoids were clogged with tumor cells, with a tendency to be more severe in the perivenular areas, and the lumens of central veins were obliterated by tumor cell infiltration. The present case demonstrates that non-cirrhotic portal hypertension due to blocking of sinusoidal and venous flow could be a serious complication in mast cell leukemia.

Lansoprazole-associated collagenous colitis: diffuse mucosal cloudiness mimicking ulcerative colitis.

There have only been a few reports on lansoprazole-associated collagenous colitis. Colonic mucosa of collagenous colitis is known to be endoscopically normal. We present a case of collagenous colitis where the mucosa showed diffuse cloudiness mimicking ulcerative colitis. A 70-year-old woman developed watery diarrhea four to nine times a day. She had interstitial pneumonia at 67 and reflux esophagitis at 70 years. Lansoprazole 30 mg/d had been prescribed for reflux esophagitis for nearly 6 mo. Lansoprazole was withdrawn due to its possible side effect of diarrhea. Colonoscopy disclosed diffuse cloudiness of the mucosa which suggested ulcerative colitis. Consequently sulfasalazine 2 g/d was started. The patient's diarrhea dramatically disappeared on the following day. However, biopsy specimens showed subepithelial collagenous thickening and infiltration of inflammatory cells in the lamina propria, confirming the diagnosis of collagenous colitis. One month after sulfasalazine therapy was initiated, colonoscopic and histological abnormalities resolved completely. Five months later the diarrhea recurred. The findings on colonoscopy and histology were the same as before, confirming a diagnosis of collagenous colitis relapse. We found that the patient had begun to take lansoprazole again 3 mo ahead of the recent diarrhea. Withdrawal of lansoprazole promptly resolved the diarrhea. Endoscopic and histological abnormalities were also completely resolved, similar to the first episode. Retrospectively, the date of commencement of sulfasalazine and discontinuation of lansoprazole in the first episode was found to be the same. We conclude that this patient had lansoprazole-associated collagenous colitis.

Suppressive effect of orthovanadate on hepatic stellate cell activation and liver fibrosis in rats.

Orthovanadate (OV), an inhibitor of protein tyrosine phosphatases, affects various biological processes in a cell-type-specific manner. In this study, we investigated the effect of OV on hepatic stellate cells (HSCs). When primary rat HSCs were cultured in the presence of 10% serum, they spontaneously lost characteristic stellate morphology, proliferated, and were transformed into an activated state with the formation of abundant stress fibers and increased expression of both alpha-smooth muscle actin and collagen type I mRNA. OV treatment inhibited proliferation and activation of HSCs and partially reversed the phenotype of activated HSCs. Among the signaling molecules investigated, phosphorylation of the Src protein at tyrosine 416 was the most striking in OV-treated HSCs. Treatment of cells with Src family inhibitors partially abrogated the effects of OV. Furthermore, transfection of v-Src into activated HSCs induced a stellate morphology similar to that in the quiescent state. We then examined whether OV could effectively suppress HSC activation in vivo after liver injury induced by either carbon tetrachloride or dimethylnitrosamine. OV significantly reduced the appearance of alpha-smooth muscle actin-positive cells and decreased collagen deposition, concomitant with an improvement in liver function. Our study showed for the first time that OV was able to suppress the activation of HSCs, possibly through the modulation of Src activity, and attenuated fibrosis after chronic liver injury.