Metastatic Invasive Lobular Carcinoma of the Breast Presenting Peritoneal Metastasis with Bilateral Ureteral Obstruction.

The most common sites for recurrence of breast cancer are the lungs, liver, and bones. The frequency of peritoneal, gastrointestinal metastasis is significantly lower than those, and bilateral ureteral obstruction caused by peritoneal metastasis is relatively rare. A 66-year-old woman was referred to our hospital because of appetite loss and frequent urination. She was on adjuvant hormonal therapy for local recurrence of right breast cancer. She was diagnosed with bilateral ureteral obstruction due to extramural compression. Exploratory laparoscopy revealed omental cake and peritoneal nodules of which pathological examination showed peritoneal metastasis of invasive lobular carcinoma. Peritoneal metastases from breast cancer are unusual and consequently difficult to identify without non-invasive tools. Exploratory laparoscopy revealed that the cause of hydronephrosis in this case was peritoneal metastasis of invasive lobular carcinoma. Clinical history and histological study play a pivotal role in determining the correct diagnosis.

Importance of a Liver Biopsy in the Management of Wilson Disease.

A 37-year-old Wilson disease patient treated with D-penicillamine visited our hospital for the evaluation of his liver function. Laboratory data showed a low serum copper level and ceruloplasmin. The ratio of urinary copper to urinary creatinine in a spot urinary analysis after 4 days' cessation of D-penicillamine was under 0.1. We concluded that the copper chelation was excessive and changed D-penicillamine to zinc acetate. However, his liver function test results did not normalize. We performed a liver biopsy and discovered a high copper content. The liver dysfunction was improved after resuming chelating therapy. Accurate measurement of the hepatic copper content via a biopsy is important for the adequate management of this disease.

Idiopathic copper toxicosis: is abnormal copper metabolism a primary cause of this disease?

Idiopathic copper toxicosis (ICT) is characterized by marked copper deposition, Mallory-Denk body (MDB) formation and severe hepatic injury. Although the characteristics are apparently different from Wilson disease, large amounts of copper accumulate in the liver of the patients. We extensively treated a patient with ICT to reduce the body copper, however, the patient needed liver transplantation. Previous liver biopsy revealed high copper content. But extirpated liver contained an extremely small amount of copper, although MDBs and severe inflammation remained. These phenomena suggest abnormal copper metabolism is not the principle cause of ICT but some other abnormality must exist.

Lanthanum Deposition in the Gastroduodenal Mucosa of Dialysis Patients.

Lanthanum (La) carbonate (LC) is one of the most popular phosphate binders used in dialysis patients with end-stage renal disease. Only a small amount of LC is believed to be absorbed from the gastrointestinal (GI) tract because LC strongly binds to dietary phosphate and forms insoluble complexes. La deposition in the gastroduodenal mucosa has been recently identified. Endoscopically, La deposition is demonstrated as whitish lesions of varying sizes and shapes in the gastroduodenal mucosa. Microscopically, La deposition is characterized by histiocytic reaction or small foreign body granulomas containing gray or brown materials mainly in the lamina propria of the GI mucosa. Some histiocytes containing La can migrate into regional lymph nodes via the lymphatic flow. The amount of La deposition in the gastroduodenal mucosa is correlated with the total dose of LC administration, and La deposition is almost consistently observed in LC-treated dialysis patients. Although the detailed mechanism of La deposition in the GI tract is still unclear, several factors, such as gastric pH and metaplastic change of the mucosal epithelium, may be involved in the La deposition in the gastroduodenal mucosa. Here we present an overview of the feature of La deposition in the GI tract.

[A Case of Carcinoma Showing Thymus-Like Differentiation (CASTLE) of the Thyroid].

The case presented herein was a 70-year-old woman who had no compliant, but had a mass in the lower part of the right lobe of the thyroid detected by ultrasound (US). The US image of the tumor, measuring 13 mm in diameter, showed a low and heterogeneous internal echo level with calcification and an irregular margin. The tumor appeared to extend to the adjacent sternothyroid muscle, and cervical lymph node swelling was detected in a computer tomography (CT) image, but no metastatic lesion was found by positron emission tomography (PET)-CT. In a fine needle aspiration cytology of the tumor, papillary thyroid carcinoma was suggested because of the atypical epithelial cells having some changes other than intranuclear inclusion bodies. A subtotal thyroidectomy and central neck lymph node dissection were performed. The excised tumor was histologically composed of irregular nests or sheets of atypical squamoid epithelial cells with some ductal structures that leached to the sternothyroid muscle and involved the right lower parathyroid gland. Carcinoma showing thymus-like differentiation (CASTLE) was diagnosed histopathologically and immunohistochemically with the following immunohistochemical results: Cluster of differentiation 5 (CD5) (+), tumor protein p63 (p63) (+), KIT proto-oncogene receptor tyrosine kinase (c-KIT(CD117)) (+), thyroglobulin (-), and thyroid transcription factor-1 (TTF-1) (-). CASTLE is a rare carcinoma of the thyroid that architecturally resembles thymic epithelial tumors. Many CASTLE patients have been misdiagnosed as other carcinomas, such as anaplastic carcinoma, poorly differentiated carcinoma or squamous cell carcinoma of the thyroid. Immunohistochemical examination, including CD5 played an important role in the final diagnosis of CASTLE, although the distinction from diagnosis as squamous cell carcinoma or mucoepidermoid carcinoma in Hematoxylin-Eosin staining was challenging in our case. Nodal metastasis and perithyroidal tumor extension of CASTLE can predict its worse prognosis. Thus, at least careful follow-up studies are mandatory in cases of CASTLE.

A unique case of a huge mixed squamous cell and glandular papilloma of non-endobronchial origin with a peripheral growth.

We report a case of a huge solitary non-endobronchial pulmonary tumor in a 76-year-old male smoker. The tumor measured 11 × 10 × 8 cm. It was ill-defined, and it was located periphery of the right lower lobe with the subpleural cystic spaces. He underwent right lower lobectomy with mediastinal lymph node dissection and is free from tumor 30 months after surgery. Microscopically, it was composed of a proliferation of squamous and ciliated columnar epithelial cells with a few mucous cells. These cells were arranged in a papillary growth fashion extending along the fibrously thickened alveolar septa together with metaplastic bronchiolar and squamous epithelia displaying an usual interstitial pneumonia-pattern. Although the histologic features of the tumor were that of a mixed squamous cell and glandular papilloma (MSCGP), it was peripherally located and showed a lepidic growth, and it was much larger than previously reported MSCGPs. It is possible that the tumor developed in association with bronchial metaplasia in the periphery of the lung, and then extended along the surface of the reconstructed air spaces, which resulted in its unique histologic appearance. Further investigations of respiratory papilloma are needed to clarify the pathogenesis of these lesions.

Lanthanum-Induced Mucosal Alterations in the Stomach (Lanthanum Gastropathy): a Comparative Study Using an Animal Model.

Lanthanum (La) carbonate (LC) is one of the most potent phosphate binders that prevents the elevation of serum phosphate levels in patients with end-stage renal diseases undergoing dialysis. LC binds strongly to dietary phosphate and forms insoluble complexes that pass through the gastrointestinal tract. La deposition in patients treated with LC is a recently documented finding particularly observed in gastric mucosa. We herein describe the detailed gastric mucosal lesions in 45 LC-treated patients and address the potential underlying pathologic mechanism using oral LC administration in rats. Microscopically, La deposition, as shown by subepithelial collections of plump eosinophilic histiocytes or small foreign body granulomas containing coarse granular or amorphous inclusion bodies, was found in the gastric mucosa of 44 (97.8%) of the 45 dialysis patients in the study cohort, which was most frequently associated with foveolar hyperplasia (37.8%). Using oral administration of rats with 1000 mg/day LC for 2 or more weeks, La deposition was consistently detectable in the gastric mucosa but not in other organs examined. In addition, various histologic alterations such as glandular atrophy, stromal fibrosis, proliferation of mucous neck cells, intestinal metaplasia, squamous cell papilloma, erosion, and ulcer were demonstrated in the rat model. Thus, orally administered LC can induce mucosal injury, designated here as La gastropathy, which may alter the local environment and result in La deposition in the gastric mucosa, thereby potentially inducing abnormal cell proliferation or neoplastic lesions.

Inhibition of WNT/ß-catenin signaling under serum starvation and hypoxia induces adipocytic transdifferentiation in human leiomyoma cells.

Fatty metamorphosis is an uncommon alteration in uterine leiomyoma (i.e., lipoleiomyoma), and the pathogenetic mechanisms underlying this phenomenon remain poorly understood. Because a conditional deletion of ß-catenin, a major transducer of the canonical Wingless/integrated (WNT) pathway, in the developing mouse uterus can induce adipogenesis in the myometrium, it is hypothesized that inhibition of the WNT/ß-catenin signaling may be also involved in the development of fat cells within uterine leiomyoma. In the current study, which was performed to address this point, intracytoplasmic lipid droplets were detectable in cultured human leiomyoma cells by treatment with a potent tankyrase inhibitor, XAV939, which antagonizes ß-catenin, in a serum-starved culture medium without additional adipogenesis-inducing agents or supplements, and showed increasing accumulation in a time-dependent manner. In addition, the induction of fat cells was greatly enhanced under hypoxic conditions (i.e., 2.5% O2)-recapitulating the local in vivo situation of uterine leiomyoma-in comparison to that under normoxic conditions (i.e., 21% O2). The marker genes of differentiated fat cells such as ADIPOQ and PLIN were highly expressed in leiomyoma cells that were treated with XAV939 under hypoxia and serum starvation, whereas the immunohistochemical expression of desmin-a cytoskeletal protein representing smooth muscle differentiation-was downregulated, which appears in line with the switch in differentiation. The results of our study suggest that the inhibition of canonical WNT/ß-catenin signaling under the stress due to hypoxia and serum starvation can initiate adipocytic transdifferentiation or metaplasia in human uterine leiomyoma cells, which is potentially related to the development of lipoleiomyoma.

Sclerosing Mucoepidermoid Carcinoma in the Parotid Gland With CRTC1-MAML2 Fusion: A Case Report.

In this article, we report a case of sclerosing mucoepidermoid carcinoma (MEC) arising in the parotid gland, with CRTC1-MAML2 gene fusion. A 73-year-old woman with a mass in the right parotid region was referred to our hospital. Radiological imaging tests revealed a well-defined mass, measuring 25 mm in diameter, with foci of calcification in the deep lobe of the parotid gland, extending to the parapharyngeal space. Microscopically, the tumor was composed of a proliferation of atypical glandular epithelial cells having intracytoplasmic mucin, squamoid cells, and intermediate cells arranged in nests embedded in a fibrosclerotic stroma, associated with a dense chronic inflammatory infiltrate containing immunoglobulin G4-immunoreactive plasma cells. Reverse transcription-polymerase chain reaction analysis using a formalin-fixed, paraffin-embedded tumor tissue specimen revealed the CRTC1-MAML2 fusion gene transcript. This is the first report of sclerosing MEC with the detection of the MEC-associated fusion gene, reinforcing a common genetic association between MEC and sclerosing MEC.

Bullous Pemphigoid Associated with the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin in a Patient with Liver Cirrhosis Complicated with Rapidly Progressive Hepatocellular Carcinoma.

A 78-year-old man presented with cutaneous blisters of the limbs and abdominal distension. He had been treated for various diseases, including liver cirrhosis. He had begun receiving sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, for diabetes mellitus three years before the hospitalization. A skin biopsy demonstrated bullous pemphigoid. Ultrasonography (US) revealed multiple liver tumors, although he had been receiving regular US studies. We stopped sitagliptin and started insulin and corticosteroids. However, his renal dysfunction progressed, and he died 14 days after the hospitalization. We should therefore be careful of various complications, including bullous pemphigoid and progression of tumors, when using DPP-4 inhibitors.

A Case of Matrix-Producing Carcinoma of the Breast.

A 61-year-old woman was referred to our hospital because of a right breast mass. A 19 mm hard mass was palpable in the A area of the right breast. A contrast-enhanced MRI showed rim enhancement at the peripheral region of the tumor, which was thought to represent the carcinoma component mainly at the periphery and the matrix component inside the tumor. A low density mass with rim enhancement at the peripheral region was observed in a contrast-enhanced CT, the same as in the MRI. Neither axillary lymph node metastasis nor distant metastasis was observed. A core needle biopsy of the tumor lead to a diagnosis of matrix-producing carcinoma (MPC). A breast-conserving mastectomy with sentinel lymph nodes biopsy was performed on the right breast MPC (T1c, N0, M0 Stage I). Histopathologically, the tumor demonstrated overt carcinoma with direct transition to a cartilaginous or osseous matrix and lacked an intervening spindle cell component. Immunohistochemistry showed estrogen receptor (ER) (-), progesterone receptor (PgR) (-), human epidermal growth factor receptor 2 (HER2) (-), and Ki67 index of 50%, so-called triple negative breast cancer. The tumor was also positive for SRY-related HMG box-9 (SOX9), which is a useful marker of chondroid differentiation in normal and neoplastic tissues. The patient lived free from recurrence for 5 years, even though her adjuvant therapy was only radiation therapy without adjuvant chemotherapy. MPC is an uncommon and relatively rare variant of metaplastic carcinoma, and the prognosis for patients with MPC is poorer than that for patients with ordinary breast cancer. Here we report a case of MPC of the breast with characteristic rim enhancement in contrast-enhanced MRI and CT. The intrinsic subtype and prognosis of MPC is controversial, and then we may need more experience with MPC cases.

Retroperitoneal dedifferentiated liposarcoma with huge cystic degeneration: A case report.

Prominent cyst formation is an unusual feature of liposarcoma. We report here a case of dedifferentiated liposarcoma with huge cystic change without preoperative chemo- or radiation therapy. The lesion arose in the retroperitoneum juxtaposed to the right kidney of a 67-year-old woman. She underwent a surgical removal of the retroperitoneal cyst. The cystic tumor contained 1600 mL of old bloody fluid, and its wall was composed of edematous, inflamed or sclerosing fibrous tissue with fatty tissue containing abundant atypical stromal cells, which were immunohistochemically positive for MDM2 and CDK4, and demonstrated MDM2 gene amplification by fluorescence in situ hybridization. The wall was contiguous to an atypical lipomatous nodule located in the mesentery. The following surgical specimens of the right hemicolectomy and right nephrectomy revealed atypical cells infiltrating into the subserosa of the colon and the perirenal fat tissue or that in the renal sinus. This case indicates that well differentiated or dedifferentiated liposarcoma should be also considered as a differential diagnosis of perirenal cystic mass.

KIAA1199/CEMIP/HYBID overexpression predicts poor prognosis in pancreatic ductal adenocarcinoma.

BACKGROUND: KIAA1199 (also known as CEMIP or HYBID), a newly identified protein involved in hyaluronan degradation, has been suggested to play a critical role in cancer progression. The aim of this study was to investigate the expression and functional significance of KIAA1199 in pancreatic ductal adenocarcinoma (PDAC). METHODS: Using quantitative real-time RT-PCR, we analyzed KIAA1199 mRNA expression in 6 PDAC cell lines and frozen tissues from 14 patients with PDAC. We also used immunohistochemistry to analyze KIAA1199 protein expression in formalin-fixed, paraffin-embedded tissues from 98 patients with PDAC. The KIAA1199 expression pattern was then correlated with clinicopathological variables and patient outcome. The effect of KIAA1199 on migratory ability of PDAC cells was determined by KIAA1199 knockdown with small-interfering RNA (siRNA). RESULTS: The KIAA1199 mRNA expression was significantly higher in PDAC tissues than in the corresponding non-tumor tissues (P < 0.0001). Immunohistochemical analysis revealed high expression of KIAA1199 in 26 (26.5%) of 98 PDAC tissues. The overall survival was significantly shorter in patients with high KIAA1199 expression than in patients with low KIAA1199 expression (P = 0.0001). In multivariate analysis, high KIAA1199 expression (P = 0.003) and UICC stage (P = 0.003) were independent factors predicting poor prognosis. Furthermore, the KIAA1199 mRNA expression was higher in most PDAC cell lines and siRNA knockdown of KIAA1199 resulted in decreased migration. CONCLUSION: These findings suggest that overexpression of KIAA1199 may contribute to increased migration of PDAC cells and predict shorter survival after surgical resection.

Lanthanum deposition in the gastrointestinal mucosa and regional lymph nodes in dialysis patients: Analysis of surgically excised specimens and review of the literature.

Lanthanum carbonate (LC) is one of the most potent phosphate binders currently used to reduce serum phosphate levels in dialysis patients with end-stage renal disease (ESRD). LC forms insoluble complexes with dietary phosphate that pass through the gastrointestinal (GI) tract with little absorption. GI lesions due to lanthanum deposition in biopsy specimens or those in endoscopic submucosal dissection (ESD) in dialysis patients have been recently identified. Here, we describe more detailed histopathological findings in the gastroduodenal mucosa and regional lymph nodes in three patients with gastric cancer. Three patients with ESRD, two elderly women and one man, underwent dialysis and were treated with LC for 3-36 months. The patients underwent laparoscopic distal gastrectomy and lymph node dissection due to gastric cancer. Many subepithelial histiocyte aggregates or small foreign body granulomas, which contained gray or brown pigments or crystal-like structures, were mostly present in non-neoplastic areas of the upper GI. Lanthanum accumulation was noted in the duodenal mucosa and the antral and body mucosae of the gastric lesser curvature. Lanthanum was also deposited in the regional lymph nodes of the three patients. Electron microscopy with energy dispersive X-ray spectroscopy confirmed lanthanum and phosphorus deposits in histiocytes. Long-term prognosis of patients and the excretion or the metabolic pathway of accumulated lanthanum remain unclear.

Preoperative factors predicting the need for additional ports during single-incision laparoscopic cholecystectomy.

INTRODUCTION: Single-incision laparoscopic cholecystectomy (SILC) is gaining popularity as a minimally invasive technique that provides some benefits in terms of improved cosmesis. However, the insertion of an additional port is required in a subset of cases. METHODS: We retrospectively analyzed 308 SILC procedures in patients with benign gallbladder diseases, except acute cholecystitis, to identify preoperative factors predicting the need for an additional port. RESULTS: SILC was completed with a single incision in 272 patients (88%); the insertion of at least one additional port was required in 36 patients (12%). The additional port requirement was associated with a longer operative time (P < 0.0001), greater intraoperative blood loss (P < 0.0001), and longer postoperative hospital stay (P = 0.0002). Multivariate analysis revealed male gender (odds ratio: 2.57, P = 0.0170), prior history of upper abdominal surgery (odds ratio: 5.53, P = 0.0132), and a higher preoperative white blood cell count (odds ratio: 3.62, P = 0.0244) to be independent factors associated with the requirement for an additional port. CONCLUSION: Our results suggest that gender, prior history of upper abdominal surgery, and white blood cell count can predict the likelihood of requiring an additional port in SILC.

Immunohistochemical and molecular detection of the expression of FGF23 in phosphaturic mesenchymal tumors including the non-phosphaturic variant.

BACKGROUND: Phosphaturic mesenchymal tumors (PMTs) are rare neoplasms that are often associated with tumor-induced osteomalacia (TIO) due to excessive serum levels of fibroblast growth factor 23 (FGF23). PMTs share overlapping histologic features with other types of tumors; thus, accurate pathological diagnosis may be challenging. We performed an immunohistochemical examination of FGF23 expression in PMTs and other types of tumors, together with pertinent molecular analyses. METHODS: Seven PMTs (5 with TIO and 2 without TIO) and 46 other types of bone and soft tissue tumors were retrieved, and immunohistochemistry was performed using a commercially available anti-FGF23 antibody. In addition, FGF23 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR), using RNA extracted from formalin-fixed, paraffin-embedded tissues. RESULTS: Immunohistochemical analysis of FGF23 expression showed distinct, punctate staining in the cytoplasm in 5 PMTs with TIO, whereas FGF23 expression was negative in the 2 PMTs without TIO and the other 46 tumors. FGF23 mRNA expression was detected in all 4 PMTs examined, as well as in 1 chondromyxoid fibroma and 1 myxoid liposarcoma. The real-time RT-PCR data showed that the relative expression levels of the FGF23 mRNA tended to be higher in PMTs with TIO than in PMTs without TIO, or in the chondromyxoid fibroma specimen. CONCLUSIONS: Our data suggested that the feasibility of immunohistochemical detection of FGF23 may depend on the level of secreted FGF23 from tumor cells. Thus, immunohistochemistry for FGF23 is an useful diagnostic adjunct for PMT, although its utility appears to be limited in cases without TIO.

CAMTA1 is a useful immunohistochemical marker for diagnosing epithelioid haemangioendothelioma.

AIMS: The diagnosis of epithelioid haemangioendothelioma (EHE) is usually straightforward, based on characteristic histological features. However, it is sometimes difficult to differentiate EHE from a variety of other tumours with epithelioid morphology. The WW domain-containing transcription regulator 1-calmodulin-binding transcription activator 1 (WWTR1-CAMTA1) fusion gene, resulting in the overexpression of CAMTA1, is demonstrated in approximately 90% of EHEs, and the yes-associated protein 1-transcription factor E3 (YAP1-TFE3) fusion gene, associated with the strong and diffuse nuclear expression of TFE3, is present in another small subset of EHEs. The aim of our study was to examine CAMTA1 expression in EHEs and a variety of other tumours to evaluate its diagnostic utility, and to analyse TFE3 expression status in EHEs. METHODS AND RESULTS: Immunohistochemistry was performed on 16 EHEs, including five cases with CAMTA1 rearrangement and 276 non-EHE tumours. Fourteen of 16 EHEs and only one case of ductal carcinoma of the breast were positive for CAMTA1 and its expression was focal and weak in the latter (sensitivity 87.5%, specificity 99.6%). TFE3 expression was expressed focally and weakly in three (19%) EHEs (two with the CAMTA1 rearrangement). CONCLUSIONS: Nuclear CAMTA1 expression is sensitive and highly specific for EHE and can be applied to diagnostic immunohistochemistry in epithelioid tumours.

Risk factors for a prolonged operative time in a single-incision laparoscopic cholecystectomy.

BACKGROUND: A prolonged operative time is associated with adverse post-operative outcomes in laparoscopic surgery. Although a single-incision laparoscopic cholecystectomy (SILC) requires a longer operative time as compared with a conventional laparoscopic cholecystectomy, risk factors for a prolonged operative time in SILC remain unknown. METHODS: A total of 20 clinical variables were retrospectively reviewed to identify factors for a prolonged operative time (longer than 3 h) in a total of 220 consecutive patients undergoing SILC. RESULTS: The median operative time was 145 min (range, 55-435) and a prolonged operative time was required in 62 patients (28%). Independent factors that predict a prolonged operative time as identified through multivariate analysis were body mass index (BMI) (P = 0.009), acute cholecystitis (P < 0.001) and operator (resident or staff surgeon) (P < 0.001). Furthermore, a prolonged operative time was significantly associated with an increased amount of intra-operative blood loss (P < 0.001) and a prolonged stay after surgery (P < 0.001). CONCLUSIONS: These findings suggest that a higher BMI, acute cholecystitis and a resident as an operator significantly increase the duration of SILC procedures.

Stapled gastro/duodenojejunostomy shortens reconstruction time during pylorus-preserving pancreaticoduodenectomy.

AIM: To investigate whether a stapled technique is superior to the conventional hand-sewn technique for gastro/duodenojejunostomy during pylorus-preserving pancreaticoduodenectomy (PpPD). METHODS: In October 2010, we introduced a mechanical anastomotic technique of gastro- or duodenojejunostomy using staplers during PpPD. We compared clinical outcomes between 19 patients who underwent PpPD with a stapled gastro/duodenojejunostomy (stapled anastomosis group) and 19 patients who underwent PpPD with a conventional hand-sewn duodenojejunostomy (hand-sewn anastomosis group). RESULTS: The time required for reconstruction was significantly shorter in the stapled anastomosis group than in the hand-sewn anastomosis group (186.0 ± 29.4 min vs 219.7 ± 50.0 min, P = 0.02). In addition, intraoperative blood loss was significantly less (391.0 ± 212.0 mL vs 647.1 ± 482.1 mL, P = 0.03) and the time to oral intake was significantly shorter (5.4 ± 1.7 d vs 11.3 ± 7.9 d, P = 0.002) in the stapled anastomosis group than in the hand-sewn anastomosis group. There were no differences in the incidences of delayed gastric emptying and other postoperative complications between the groups. CONCLUSION: These results suggest that stapled gastro/duodenojejunostomy shortens reconstruction time during PpPD without affecting the incidence of delayed gastric emptying.