Long-term Histopathologic Follow-up of a Spherical Embolic Agent; Observation of the Transvascular Migration of HepaSphereTM.

Very few studies have been published on the long-term histopathologic follow-up of spherical embolic agents after their injection. To our knowledge, there are no reports in the literature regarding pathological analysis of the transvascular migration of HepaSphere particles. We here report a case of a patient with hepatocellular carcinoma (HCC) who underwent liver transplantation 12 months after drug eluting microsphere transcatheter arterial chemoembolization (DEM-TACE), and long-term histopathologic follow-up of the microspheres was performed. Furthermore, to our knowledge, this is the first report in which transvascular migration of a HepaSphere particle was confirmed histologically. A 60-year-old male with chronic hepatitis B was treated with entecavir and seroconversion was obtained. The patient had decompensated cirrhosis, and desired to undergo living donor liver transplantation (LDLT). However, 2 HCC tumors of 3 cm or less were detected in his liver. The transplantation surgeon proposed DEM-TACE as a bridge therapy. The HCCs were located in the right lobe and lateral segment of the liver. A 1.9 F preshaped microcatheter (ProgreatΣ, Terumo, Japan) was selectively inserted into the A3 and anterior segmental branch, 10 mg of epirubicin was injected into each artery, and the arteries were embolized with 7 mg and 13 mg of HepaSphere loaded with epirubicin, respectively. Two months later, contrast-enhanced CT displayed a complete response. At that time, lung metastasis was suspected, but after partial lung resection, the patient was diagnosed as having inflammatory granuloma. One year after DEM-TACE treatment, LDLT was performed. No cancerous cells were detected in the area where the tumor was present, but 22 HepaSphere particles were detected. All particles were present in the interstitium. Furthermore, the transvascular migration of a HepaSphere particle was histologically confirmed. The largest and smallest HepaSphere diameters were 241.6 ± 52.5 µm and 186.5 ± 41.4 µm, respectively, and deformity was 22.6% ± 13.0 %. All the HepaSpheres detected in the examined pathological specimen were noted to be extravascular.

Thyroid Carcinoma on the Side of the Absent Lobe in a Patient with Thyroid Hemiagenesis.

BACKGROUND: Thyroid carcinoma complicated by hemiagenesis is very rare, and previous reports have not described this cancer on the side of the absent lobe. METHODS AND RESULTS: We report the case of a 64-year-old woman in whom left thyroid hemiagenesis was discovered incidentally during investigations of abnormal sensation during swallowing. A tumorous 1.4 cm lesion was also found on the side of the absent lobe, left of the isthmus. Fine-needle aspiration biopsy revealed class V papillary carcinoma, but no lymph node metastases. Total thyroidectomy was performed for stage cT1bN0M0 carcinoma. Histopathology revealed normal thyroid tissues in the right lobe and isthmus, while the left lobe was absent. The mostly papillary carcinoma was adjacent to the truncated thyroid tissue, with a portion histologically consistent with poorly differentiated carcinoma. CONCLUSIONS: All previously reported cases of thyroid cancer complicated by hemiagenesis have represented carcinoma occurring within the present lobe. This case is extremely rare.

Salvage Embolization and Histologic Analysis of Gastric Cancer with Hemorrhagic Shock Using Spherical Embolic Material.

BACKGROUND: In a recent study, it was reported that transcatheter arterial embolization with spherical embolic material for life-threatening hemorrhages in various cancer patients was safe and effective. Calibrated microspheres are able to access distal regions of the target arteries, which results in the disappearance of tumor staining. However, there are few reports on the pathological behavior of EmboSpheres in gastric cancer specimens. In this case, we succeeded in salvage embolization for advanced gastric cancer with hemorrhagic shock using spherical embolic material. To our knowledge, this is the first report of a pathological evaluation of spherical embolic microspheres in a gastric cancer specimen. CASE REPORT: A 70-year-old man with scirrhous gastric cancer was admitted to our hospital for staging laparoscopy. Unfortunately, he had a sudden onset of hematemesis and melena leading to hemorrhagic shock due to bleeding from the gastric cancer. While undergoing a rapid blood transfusion, he underwent emergent embolization to achieve hemostasis. The left gastric and right gastroepiploic arteries were embolized with spherical embolic material, and the patient survived. Two days later, the patient was able to undergo gastrectomy. A large number of microspheres were observed in areas of hemorrhage. The range and median diameter of the minor axis were 177-1048 µm and 281 µm, respectively. CONCLUSIONS: Transcatheter arterial embolization using spherical embolic material could become one of safe and effective options, especially when there is no extravasation or pseudoaneurysm but only tumor staining from the clinical and pathological point of view.

A case of a gastrointestinal stromal tumor with skeinoid fibers of the sigmoid colon.

An 80-year-old man was diagnosed with rectal cancer and underwent Hartmann's procedure. Although no tumors were identified during the preoperative examination, gross examination of the resected specimen incidentally revealed a submucosal tumor that was 9 mm in diameter at the oral side and located in the proximal stump of the specimen from the sigmoid colon. We suspected a concurrent gastrointestinal stromal tumor (GIST) and performed a histopathological examination. An L-shaped nodular lesion measuring 9 × 6 mm was histologically composed of a patternless proliferation of spindle cells intermingled with eosinophilic globules. Cellular atypia, prominent mitotic figures and necrotic foci were not observed in the nodule. The spindle cells were positive for CD34, CD117 and vimentin, but negative for CD56, smooth muscle actin and S-100 protein. MIB-1 positivity was estimated to be as low as approximately 1-2%. Electron microscopy showed a bundle of wool-like fibers with a periodicity of approximately 40 nm. We therefore considered the lesion to be a low-risk GIST with skeinoid fibers in the large intestine. Although numerous previous reports have reported skeinoid fibers in the stomach and small intestines, there have been only 9 cases (including the present case) of skeinoid fibers in the large intestine.

Adenomatoid mesothelioma with intranuclear inclusion bodies: a case report with cytological and histological findings.

We report a very unusual cytologic feature, intranuclear inclusion bodies, in mesothelioma of a predominantly adenomatoid type. The patient, a 57-year-old woman, was presented with dyspnea and right pleural effusion. Pleural aspiration cytology revealed many cohesive ball-like clusters, with a tubular pattern, composed of small atypical cells displaying a high-nuclear-cytoplasmic ratio. They had a nuclear groove and irregular intranuclear inclusion bodies. Right lung partial resection with thoracoscopy revealed that a white tumor had proliferated along the pleural surface at S(8) . Histology revealed nodular tumor cells forming dilated structures mixed with small tubular or glandular structures similar to those seen in benign adenomatoid tumors. These tumor cells had invaded peripheral lung tissues. Such inclusion bodies have not been reported earlier in mesothelioma. On the basis of this observation, we propose that the adenomatoid type of malignant mesothelioma be added to the differential diagnosis of malignant effusions when tumor cells with nuclear grooves and intranuclear inclusions are found in pleural aspiration cytology.

[A case that showed an improved quality of life for rectal gastrointestinal stromal tumor patient treated with cytoreductive surgery].

A 49-year-old man was admitted to another hospital with the complaint of difficulty in defecating. He underwent laparotomy, and investigation of the biopsy revealed a huge intraperitoneal tumor. He began to take imatinib in April 2008 following a diagnosis of gastrointestinal stromal tumor (GIST), but the tumor increased in size. He was referred to our hospital for oral administration of sunitinib to reduce the tumor size. The tumor was 30 cm in diameter, and there were several peritoneal metastases around the liver. He began to take sunitinib in February 2009. The tumor increased in size from August 2010 but a partial remission was noted. We performed cytoreductive surgery in April 2011 as palliative care, but the tumor size increased again in October. We performed cytoreductive surgery again, but he died in December 2011. Although cytoreductive surgery for GIST is a potential treatment option, we suggest supportive care.

[A case of liver metastases from gastric cancer treated with stereotactic body radiation therapy].

A 69-year-old man underwent distal gastrectomy in September 2007 for type 2 gastric cancer with liver metastasis (S5) in LM area (p-T2N3aM1, Stage IV). After the operation, we performed chemotherapy. But the liver metastasis was enlarged, so we performed a partial hepatectomy in July 2008. After hepatectomy, liver metastases appeared on S6 and S7 in February 2009. So we performed the fifth-line chemotherapy with paclitaxel. The effect of paclitaxel was not so good. Therefore, SBRT was performed for the liver metastases (S6/7 and S7) in December 2009 and February 2010. After SBRT, he had no recurrent tumor. SBRT was one of the effective treatments for liver metastases from gastric cancer.

Hypoxia-inducible factor-1α expression and gemcitabine chemotherapy for pancreatic cancer.

The normal pancreas has an abundant blood flow, in contrast to pancreatic cancer, which is a hypovascular tumor. During hypoxia under a hypovascular environment, the transcription factor hypoxia-inducible factor-1α (HIF-1α) is activated. High HIF-1α expression reduces sensitivity to gemcitabine (GEM) which is used as a treatment for pancreatic cancer. The objective of this study was to clarify HIF-1α expression in pancreatic cancer and the association of its effects to GEM treatment. We used the human pancreatic ductal carcinoma cell lines AsPC-1 and BxPC-3 to evaluate cell proliferation, HIF-1α protein expression and sensitivity to GEM in a hypoxic environment of 1% O2 in 48 pancreatic cancer patients who received adjuvant GEM treatment after pancreatectomy. We divided the patients according to HIF-1α expression and the presence of single nucleotide polymorphisms, and we based our evaluation on the adverse events associated with GEM chemotherapy and patient outcome. The hypoxic environment promoted cell proliferation, induced HIF-1α expression and increased GEM resistance, especially in AsPC-1 cells, which included a mutant homozygote for HIF-1α(C1772T). There were no significant differences between the HIF-1α(-) and HIF-1α(+) groups in either adverse events or patient outcomes. HIF-1α enhanced neo-microvascularity in a hypoxic environment and increased drug resistance. The period until recurrence was shorter in the patients with a strong HIF-1α expression, than that in those with a weak HIF-1α expression.

[More than 20 years of long-term survival case of intraabdominal GIST by combined therapies with frequent surgeries].

A jejunum partial resection was performed on a 49-year-old female for jejunum leiomyosarcoma of 7 cm in 1990. She was resected four times for recurrent tumors from 1993 to 2004. We started an internal use of imatinib in 2003, because we could get a diagnosis of GIST. After the surgery of 2004, she stopped taking the internal use of imatinib, but an intraabdominal recurrence occurred in 2006 and she restarted taking the internal use of imatinib.

[A case of posterior mediastinal mature teratoma].

The chest radiograph of a 57-year-old man, complaining of paroxysmal dyspnea, suggested the probably of a tumor. Chest CT showed a tumor containing calcification, behind the left crus of the diaphragm. Chest MRI suggested lipid components and a cystic lesion within the tumor. Their findings were clinically compatible with posterior mediastinal teratoma. The pathological diagnosis of the surgically resected tumor was mature teratoma with neither malignant components nor thymic tissue. Study of past case reports suggests that posterior mediastinal teratomas should have less malignant characteristics than anterior mediastainal teratomas. Our case is the fifteenth case report in the Japanese literature, and accumulation of more cases is required.

Intraductal approach to the detection of intraductal lesions of the breast.

Bloody nipple discharge is a clue in the detection of ductal carcinoma of the breast that do not display a mass. Since sensitivity of discharge cytology is not sufficiently high and mammary ductendoscopy (MS) contributes to the diagnosis of intraductal lesions. We set out to determine whether the intraductal approach is effective for detection of ductal carcinoma. We performed 445 MS procedure in 323 patients who had nipple discharge but no overt mass. The diagnostic accuracy rates of discharge cytology and intraductal breast biopsy (IDBB) were studied in detecting malignancy. The therapeutic value of IDBB for intraductal papillomas was studied in 73 patients. Out of 323 patients, 80 had breast cancer and 155 had intraductal papilloma. MS detected intraductal tumors in 47 cases (58.8%). IDBB was performed in 35 of these 47 cases. The sensitivity was 37.1% by touch cytology, 68.6% by IDBB, and 82.8% by directed ductal lavage cytology. Of the 73 intraductal papilloma patients who were followed for more than 3 years, the therapeutic effectiveness of IDBB was recognized in 57 (78.1%). Directed ductal lavage cytology was the most sensitive method in detecting malignancy. MS and IDBB were benefit in the treatment of intraductal papilloma.

[A case of splenic inflammatory pseudotumor].

A 74-year-old woman underwent abdominal echography at a local clinic and a splenic mass was found. She was hospitalized for detailed examinations and treatment. Splenectomy was performed to make a definite diagnosis and for treatment because a definitive diagnosis could not be made, despite various examinations. Histopathological examination revealed that the lesion was infiltrated by polyclonal lymphoid cells and contained proliferating spindle-shaped fibroblasts without any atypical cells, so the splenic mass was diagnosed as an inflammatory pseudotumor. Because some cases of inflammatory pseudotumor can be diagnosed from the clinical course and imaging findings, this possibility should also be considered in the differential diagnosis of a splenic mass.

Mucinous tubular and spindle cell carcinoma of the kidney: Report of a case with imprint cytologic features.

BACKGROUND: Mucinous tubular and spindle cell carcinoma of the kidney is a newly established subtype in the World Health Organization classification. The tumor has a good prognosis, and its diagnosis is clinically important. However, there are no reports of its cytologic features. Here we report the cytologic findings of this rare tumor. CASE: A 68-year-old female had left-sided abdominal pain, fatigue and hematuria. A large mass in the left kidney was removed. Histologically, the tumor was compatible with mucinous tubular and spindle cell carcinoma. Imprint cytologic examination revealed a large amount of tumor cells arranged in tubular, sheetlike and spindle structures. Some tumor cells showed clear cytoplasm. Nuclear atypia was mild, with occasional distinctive nucleoli. CONCLUSION: The cytologic features of mucinous tubular and spindle cell carcinoma have a varied appearance. It should be included in the differential diagnosis to avoid overtreatment.

Preoperative diagnosis and management of thick-walled gallbladder based on bile cytology obtained by endoscopic transpapillary gallbladder drainage tube.

BACKGROUND: It is often difficult to distinguish gallbladder cancers (GBC) from benign gallbladder diseases, which show thickened walls. OBJECTIVES: To evaluate the efficacy of bile cytology using endoscopic transpapillary gallbladder drainage (ETGD) and CT. DESIGN: Retrospective study. SETTING: Division of Gastroenterology, Tokyo Medical University, Tokyo, Japan. PATIENTS AND INTERVENTIONS: Eighty-five patients with gallbladder diseases, consisting of 27 GBC and 58 benign gallbladder diseases, were reviewed. A pigtail-type nasobilliary drainage tube was left indwelling in the gallbladder, and through this drainage tube washing cytology was performed with an ETGD tube. MAIN OUTCOME MEASUREMENTS: Diagnostic accuracy of CT and cytology. Complications and outcome were also evaluated. RESULTS: CT and cytology with the ETGD tube had 81% and 81% sensitivity, 91% and 83% specificity, and 88% and 82% accuracy, respectively (P > .05). Looking only at the 71 successful ETGD cases, CT and ETGD cytology had 82% and 100% sensitivity, 92% and 98% specificity, and 89% and 99% accuracy, respectively (P = .036 and .025, respectively). Four patients with GBC in whom CT showed benign findings underwent open cholecystectomy because ETGD cytology revealed malignant findings. In contrast, 4 patients with benign diseases in whom CT suggested malignant finding underwent LC because the findings of ETGD cytology suggested benign disease. CONCLUSIONS: Cytology using an ETGD tube is very useful in the diagnosis and management of gallbladder diseases.

Hypereosinophilia in a patient with invasive thymoma with clonal T-lymphocyte expansion expressing CD4, CD8, and CD25 antigens.

We report the case of a patient with hypereosinophilia and invasive thymoma harboring probable clonal proliferation of CD4+, CD8+, and CD25+ T-lymphocytes. A 64-year-old woman had eosinophilia (14.1 x 10(9)/L) and an anterior mediastinal tumor with elevated levels of serum immunoglobulin E (609.8 mg/dL) and interleukin 5 (239 pg/mL). Bone marrow aspirate showed marked infiltration by morphologically normal eosinophils with a normal karyotype but no FIP1L1-PDGFRA fusion gene. Flow cytometric analysis revealed an increasing number of CD3+/CD25+ lymphocytes in the peripheral blood, and the resected thymoma had infiltrated lymphocytes with CD4/CD8/CD25 antigens. Moreover, the thymoma had T-cell receptor rearrangements with a cytogenetically clonal nature, ie, t(2;4)(p22;q26). Although the number of patients with thymoma showing hypereosinophilia is small, this case suggests that a subset of patients with thymoma may have clonal expansion of T-lymphocytes with abnormal phenotypes that affect clinical manifestations, including hypereosinophilia.

Coexpression of actin-related protein 2 and Wiskott-Aldrich syndrome family verproline-homologous protein 2 in adenocarcinoma of the lung.

PURPOSE: Highly invasive and metastatic cancer cells, such as adenocarcinoma of the lung cells, form irregular protrusions by assembling a branched network of actin filaments. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2 (WAVE2). In this study, colocalization of Arp2 and WAVE2 in adenocarcinoma of the lung was investigated to elucidate its prognostic value. EXPERIMENTAL DESIGN: Immunohistochemical staining of Arp2 and WAVE2 was done on mirror sections of 115 adenocarcinomas of the lung from pathologic stage IA to IIIA classes. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of the coexpression of Arp2 and WAVE2. RESULTS: Immunoreactivity for both Arp2 and WAVE2 was detected in the same cancer cells in 78 (67.8%) of the 115 lung cancer specimens. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with lymph-node metastasis (P = 0.0046), and significantly lower in bronchioloalveolar carcinomas (P < 0.0001). The patients whose cancer cells coexpressed them had a shorter disease-free survival time (P < 0.0001) and overall survival time (P < 0.0001). Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent risk factor for tumor recurrence. CONCLUSIONS: Coexpression of Arp2 and WAVE2 is correlated with poorer patient outcome, and may be involved in the mechanism of cancer metastasis.

Chlamydia psittaci in ocular adnexal lymphoma: Japanese experience.

We searched for the Chlamydia psittaci DNA the touchdown enzyme time release PCR (TETR-PCR) in 23 specimens from 21 patients with ocular adnexal lymphoproliferative disorders, including 12 patients with MALT lymphoma to identify C. psittaci infection. Southern hybridization of the PCR product using the C. psittaci-specific probe failed to detect C. psittaci, although three samples appeared to be positive by ethidium bromide staining. This indicates that technical approach for detecting C. psittaci infection in ocular adnexal lymphoma might be an essential in disclosing this association.