The role of CD5 expression in thymic carcinoma: possible mechanism for interaction with CD5+ lymphoid stroma (microenvironment).

AIMS: Most thymic carcinomas express the lymphocyte marker CD5 aberrantly. This study was performed to examine the role of the self-reactive CD5 antigen in thymic carcinoma. METHODS AND RESULTS: We examined CD5 expression in thymic carcinoma in relation to the lymphoid stroma. All cases of thymic carcinoma examined expressed CD5. A number of CD5(+) lymphocytes were also present in the stroma of thymic carcinoma. The CD5(+) tumour areas were predominantly in contact with the lymphoid stroma, and the expression level was significantly lower in tumour cells than lymphocytes. Although p53 and Bcl-2 expression levels were significantly higher in thymic carcinoma than normal thymic epithelial cells (TECs), they did not differ between CD5(+) and CD5(-) areas. E-cadherin expression in thymic carcinoma was comparable with that of normal TECs, and it also did not differ between these areas. In contrast, both Ki-67 index and mitotic activity were significantly higher in thymic carcinoma than normal TECs, and they were significantly higher in CD5(+) than CD5(-) areas. CONCLUSIONS: CD5 may be induced by interaction with CD5(+) lymphoid stroma, and may be related to tumour proliferation. CD5 induction may also be a significant and/or specific effect of the tumour microenvironment of the thymus.

Pathological outcomes of Japanese men eligible for active surveillance after radical prostatectomy.

BACKGROUND: The aim of this study was to analyze the pathological features of prostatectomy specimens from patients with low-risk prostate cancer eligible for active surveillance (AS) and evaluate preoperative data suitable for predicting upstaged (≥pT3) or upgraded disease (Gleason score of ≥7), defined as 'reclassification'. METHODS: A retrospective analysis of 521 consecutive radical prostatectomy procedures (January 2005 through to December 2011) performed at our institution without neoadjuvant hormonal therapy was performed. Eighty-four patients fulfilled the following criteria-clinical T1 or T2 disease, prostate-specific antigen (PSA) level of ≤10 ng/ml, one or two positive biopsies, and Gleason score of <7. Clinicopathological features at diagnosis were compared between patients with and without reclassification after radical prostatectomy. RESULTS: Forty of 84 patients (47.6 %) had a Gleason score of ≥7, and 8 (9.5 %) had upstaged disease (≥pT3). Seven patients with upstaged disease also showed upgraded reclassification. Two patients with reclassification showed biochemical recurrence at 59 and 89 months after surgery, respectively. Preoperative parameters evaluated included age, PSA level, PSA density (PSAD), clinical T stage, and number and percentage of positive prostate cores. Among 82 patients with complete data, univariate analysis showed that PSAD (ng/ml(2)) was a significant parameter to discriminate patients with reclassified disease and those without reclassified disease (p < 0.001). Multivariate analysis revealed that PSAD was the only independent variable to predict disease with reclassification (p = 0.006). CONCLUSIONS: Preoperative PSAD may be a good indicator for selecting patients eligible for AS in the Japanese population.

Laparoscopic distal pancreatectomy for a pancreatic lymphoepithelial cyst: case report and review of literature.

CONTEXT: Lymphoepithelial cysts of the pancreas are a rare disease of true pancreatic cysts, the cause of which is unknown. The differential diagnosis is broad and includes many benign and malignant cystic lesions of the pancreas and surrounding organs. A combination of imaging modalities and fine needle aspiration might narrow the differential diagnosis. However, the final diagnosis can only be achieved with certainty after resection of the cyst. CASE REPORT: The present case report is a lymphoepithelial cyst of the pancreas that was resected laparoscopically. A 53-year-old man was incidentally found to have a cystic tumor in the tail of the pancreas after undergoing an abdominal ultrasound, which showed a 41x33 mm cystic mass in the pancreatic tail. He had no abdominal symptoms. Laparoscopic distal pancreatectomy and splenectomy were performed. Histologic examination revealed a lymphoepithelial cyst. CONCLUSION: Herein, we discuss the diagnostic difficulties and management decisions that face surgeons treating pancreatic cysts.

[A case of ring melanoma found while treating traumatic glaucoma].

BACKGROUND: Ring melanoma, a malignant melanoma which infiltrates over 180 degrees degrees of the ciliary body is very rare in Japan. We report a case of ring melanoma found while treating treatment of traumatic glaucoma with an ultrasound biomicroscope (UBM). CASE: A 44-year old woman presented with high intraocular pressure after blunt trauma in her left eye. CLINICAL FINDINGS: Best-corrected visual acuity OS was 1.2, and intraocular pressure was 30 mmHg. Gonioscopy showed about 180 degrees of the angle recession. Intraocular pressure was difficult to control in spite of anti-glaucoma drug treatment. Rapid progression of iris elevation and 360 degrees thickening of the ciliary body were detected by UBM. We detected atypical cells with melanine granules in the aqueous fluid and positive findings in PET-CT, leading to a diagnosis of ciliary body malignant melanoma. Consequently we enucleated the left eye. The histopathological diagnosis was ring melanoma. CONCLUSION: Ring melanoma is an important element in the differential diagnosis for untreatable secondary glaucoma.

Utility of immunohistochemical analysis of KAI1, epithelial-specific antigen, and epithelial-related antigen for distinction of chromophobe renal cell carcinoma, an eosinophilic variant from renal oncocytoma.

Distinction of renal oncocytoma (RO) from chromophobe renal cell carcinoma (ChRCC) is important because their clinical behavior is different. As part of a search for the best available immunohistochemical markers to distinguish ChRCC from RO, we investigated the immunohistochemical profiles of these tumors. We selected 30 renal tumors consisting of ChRCC, typical variant (n = 14), ChRCC, eosinophilic variant (n = 6), and RO (n = 10). Their expression of cytokeratin (CK) 7, KAI1, epithelial-specific antigen (ESA), epithelial-related antigen (ERA), Claudin- 7, and Claudin-8 was studied using an autostainer. Immunoreactivity was assessed based on a combined score of the extent and intensity of staining. Compared to RO, a significantly higher percentage of the total ChRCCs stained positive for CK7 (85% vs. 10%, respectively), KAI1 (90% vs. 10%), ESA (95% vs. 10%), ERA (95% vs. 10%), and Claudin-7 (95% vs. 20%) (P < 0.001). Additionally, there was a significant difference between the percentage of ChRCC eosinophilic variant (ChRCC-E) and RO that stained positive for KAI1 (100% vs. 10%, respectively), ESA (83% vs. 10%), and ERA (83% vs. 10%) (P < 0.001). We recommend immunohistochemical analysis of KAI1, ESA, and ERA to distinguish ChRCC-E from RO.

Prostate cancer detection by prebiopsy 3.0-Tesla magnetic resonance imaging.

OBJECTIVES: The diagnostic value of 3.0-Tesla magnetic resonance imaging (MRI) for prostate cancer remains to be determined. The aim of the present study was to assess the features of prostate cancer detectable by prebiopsy 3.0-Tesla MRI. METHODS: From January 2007 through to December 2008, 116 patients who were examined by prebiopsy 3.0-Tesla MRI underwent radical prostatectomy for localized prostate cancer. Prostate specimens were examined to see whether the largest cancer area was the same as the area indicated on the MRI. Univariate and multivariate logistic regression analyses were conducted to identify variables predictive of agreement between MRI and histopathological findings. RESULTS: Sixty-six (56.9%) patients were suspected of having prostate cancer on the basis of MRI findings. In 49 of these patients (74.2%), it was considered that there was agreement between the abnormal area on the MRI and the index tumor. Univariate analysis revealed that there were significant differences in abnormal digital rectal examination, capsular penetration, the diameter of the index tumor of the radical prostatectomy specimen, and the Gleason scores of the biopsy and radical prostatectomy specimens. Multivariate analysis revealed that the Gleason score of the radical prostatectomy specimen was associated with the accurate detection of the prostate cancer by MRI (P = 0.0177). CONCLUSIONS: In conclusion, 3.0-Tesla MRI tends to accurately diagnose prostate cancer with high tumor burden and aggressiveness. Multimodal examination (T2-weighted imaging, dynamic contrast-enhanced imaging, and diffusion-weighted imaging) is recommended for the diagnosis of prostate cancer using 3.0-Tesla MRI.

Immunohistochemical application of S100A1 in renal oncocytoma, oncocytic papillary renal cell carcinoma, and two variants of chromophobe renal cell carcinoma.

S100A1 is a calcium-binding protein and a member of the S100 family. Recently, S100A1 immunohistochemistry may be an available marker in the differential diagnosis between renal oncocytoma and chromophobe renal cell carcinoma (RCC). However, there are no reports on S100A1 expression in oncocytic papillary RCC that has been recently identified. In this article, we immunohistochemically examined the expression of S100A1 protein in 18 renal tumors including 4 renal oncocytoma, 10 chromophobe RCCs, and 4 oncocytic papillary RCCs. All the cases of renal oncocytoma and oncocytic papillary RCC showed a positive reaction for S100A1 with cytoplasmic pattern. In chromophobe RCC, 3 of 4 tumors with typical variant and 4 of 6 tumors in eosinophilic variant were completely negative for S100A1. Finally, S100A1 immunohistochemistry may be useful in distinguishing renal oncocytoma from chromophobe RCC, but it may be of no use in the differential diagnosis between renal oncocytoma and oncocytic papillary RCC.

Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B.

UNLABELLED: Hepatitis B virus X (HBx) protein is suspected to participate in oncogenesis during chronic hepatitis B progression. Transforming growth factor beta (TGF-beta) signaling involves both tumor suppression and oncogenesis. TGF-beta activates TGF-beta type I receptor (TbetaRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Reversible shifting of Smad3-mediated signaling between tumor suppression and oncogenesis in HBx-expressing hepatocytes indicated that TbetaRI-dependent pSmad3C transmitted a tumor-suppressive TGF-beta signal, while JNK-dependent pSmad3L promoted cell growth. We used immunostaining, immunoblotting, and in vitro kinase assay to compare pSmad3L- and pSmad3C-mediated signaling in biopsy specimens representing chronic hepatitis, cirrhosis, or hepatocellular carcinoma (HCC) from 90 patients chronically infected with hepatitis B virus (HBV) with signaling in liver specimens from HBx transgenic mice. In proportion to plasma HBV DNA levels, early chronic hepatitis B specimens showed prominence of pSmad3L in hepatocytic nuclei. HBx-activated JNK/pSmad3L/c-Myc oncogenic pathway was enhanced, while the TbetaRI/pSmad3C/p21(WAF1) tumor-suppressive pathway was impaired as human and mouse HBx-associated hepatocarcinogenesis progressed. Of 28 patients with chronic hepatitis B who showed strong oncogenic pSmad3L signaling, six developed HCC within 12 years; only one of 32 patients showing little pSmad3L developed HCC. In contrast, seven of 30 patients with little Smad3C phosphorylation developed HCC, while no patient who retained hepatocytic tumor-suppressive pSmad3C developed HCC within 12 years. CONCLUSION: HBx shifts hepatocytic TGF-beta signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway in early carcinogenic process. Hepatocytic pSmad3L and pSmad3C assessment in HBV-infected liver specimens should prove clinically useful for predicting risk of HCC.

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma: report of two cases.

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is extremely rare; only four cases have been reported. Herein are presented the case reports of two Japanese male patients with thyroid-like LGNPPA. Macroscopically, these tumors were pedunculated polypoid masses on the roof of the nasopharynx. Microscopically, they were characterized by papillary and glandular epithelial proliferation. The papillae were complex and tightly packed with hyalinized fibrovascular cores and lined by columnar and pseudostratified cells with intervening spindle-shaped cells. Both cell types had round to oval vesicular nuclei with tiny nucleoli and mildly eosinophilic cytoplasm. Mitotic figures were not evident and necrosis was not observed. Psammoma bodies were seen focally in one of the patients. Transition from normal surface epithelium to tumor cells was identified in both cases. On immunohistochemistry the tumor cells were positive for cytokeratin (CK)7, CK19, thyroid transcription factor-1 (TTF-1) and vimentin. They were negative for CK5/6, CK20, thyroglobulin, S-100 protein and CD15. In situ hybridization for EBV was negative. Nasopharyngeal tumors with similar morphological appearance should be examined for TTF-1 immunoreactivity, and patients should be clinically followed to determine the course of this unusual disease and the significance of TTF-1 expression.

A case of splenic low-grade mucinous cystadenocarcinoma resulting in pseudomyxoma peritonei.

Primary splenic mucinous cystadenocarcinoma (MCCa) is extremely rare, and only six cases appear to have been reported previously. We present herein a case of primary splenic MCCa resulting in pseudomyxoma peritonei (PMP). A 66-year-old Japanese woman presented to a hospital with a chief complaint of upper abdominal pain and a 7-year history of splenic cyst. Cyst rupture was noted on computed tomography, and splenectomy was performed. The abdominal cavity was filled with a large amount of gelatinous ascites, with the appearance of PMP. On the cut surface, multiple cysts containing mucinous material were found within and outside the spleen. Microscopically, splenic parenchyma was occupied by large mucinous pools focally lined with mucinous epithelial cells and mesothelial cell-like cells, which were considered benign. Outside the spleen, a low-grade MCCa component was found. No ectopic pancreatic or intestinal tissue was identified. Although most PMP cases are known to be caused by low-grade mucinous appendiceal tumor, the present case represents the first report of a splenic MCCa resulting in PMP.

A case of high-grade mucinous tubular and spindle cell carcinoma.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare renal cell carcinoma that initially presents as low-grade renal cell carcinoma. However, cases of MTSCC with high-grade histology and poor prognosis have been reported. Here, we report a case of MTSCC with high-grade histological features and metastasis. A 77-year-old woman consulted a hospital following frequent and painful micturition. Computed tomography scan revealed a tumor of the left kidney. First, chemotherapy was performed, with no effects. Therefore, nephrectomy was subsequently performed. Histologically, the tumor showed the features of MTSCC with sarcomatoid component. Metastasis of the tumor into the lymph node was also observed. Although adjuvant chemotherapy was performed after nephrectomy, metastasis to the lungs and bone and local recurrence was observed. The patient is still alive 2 years after nephrectomy with metastasis and recurrence of the tumor. High-grade MTSCC shows a relatively poor prognosis, specifically MTSCC with metastasis upon nephrectomy.

Novel mutation (L157X) in the succinate dehydrogenase B gene (SDHB) in a Japanese family with abdominal paraganglioma following lung metastasis.

Recently, nuclear genes encoding two mitochondrial complex II subunit proteins, SDHD and SDHB, have been found to be associated with the development of familial pheochromocytomas and paragangliomas (hereditary pheochromocytoma/paraganglioma syndrome: HPPS). Growing evidence suggests that the mutation of SDHB is highly associated with abdominal paraganglioma and the following distant metastasis (malignant paraganglioma). In the present study, we report the case of a novel SDHB mutation (L157X) in a Japanese patient with abdominal paraganglioma following malignant lung metastasis. In addition, we identified an asymptomatic carrier of the SDHB mutation in this family.

[A rapidly progressed metastatic choroidal tumor from a hepatocellular carcinoma].

BACKGROUND: Metastatic choroidal tumor stemming from a hepatocellular carcinoma (HCC) is very rare. We report a case of a metastatic choroidal tumor stemming from a hepatocellular carcinoma. CASE: A 50-year-old man became aware of a visual field defect in his left eye starting 1 month previously. He had undergone surgery for HCC nine years before, and had received radiation therapy for lung and brain metastasis of HCC. Funduscopic examination revealed a red choroidal mass with subretinal bleeding. One month later, light perception of the left eye disappeared with rapid growth of the tumor and high intraocular pressure. Because the ocular pain was uncontrollable, enucleation of the left eyeball was performed. In histopathological examination, the choroidal tumor consisted of tumor cells showing characteristics of HCC such as intracytoplasmic glycogen granules, fatty degeneration, and necrosis of the tumor cells. CONCLUSION: The clinical characteristics of metastatic choroidal tumors from an HCC are a red appearance and rapid growth with retinal detachment and subretinal hemorrhage.

Extra-gastrointestinal stromal tumor with a large cyst.

Gastrointestinal stromal tumors (GISTs) arising at sites other than the alimentary tract are rare, and they are called extra-GISTs (EGISTs). We report a case of a large EGIST forming a cyst, probably arising in the mesentery of the transverse colon. A 64-year-old Japanese man presented to a hospital with an abdominal tumor forming a large cyst. Intraoperatively, the tumor was neither present in nor in contact with the alimentary tract. It was present in the mesentery of the transverse colon and was attached to the greater omentum and peritoneum, immediately anterior to the body of the pancreas. The tumor was resected with the spleen and a part of the pancreas. Histological examination of the tumor revealed that it belonged to the high-risk category of cystic EGISTs.

Traumatic neuroma of the bile duct.

We present the CT and MRI findings of a traumatic neuroma of the bile duct, which is not a true neoplasm, but a reactive proliferation of pericholangial nerve tissue induced by cholecystectomy. Previous authors have shown a dilatation of the bile duct without a nodule. In our case, a nodule was present, and it was markedly enhanced.

Clinicopathologic study of small hepatocellular carcinoma with microscopic satellite nodules to determine the extent of tumor ablation by local therapy.

To determine the optimal treatment margin of local ablation therapy for small hepatocellular carcinoma (HCC), we investigated characteristics of microscopic satellite HCC nodules (msn) using resected livers, and the incidence of local recurrences in patients who underwent percutaneous microwave coagulation therapy (PMCT) according to whether or not an adequate treatment margin was achieved. We reviewed 117 single small HCCs (tumor size < or =3 cm ) resected with a > or =1-cm surgical margin. Among the surgically resected tumors, none of the msn were detected by preoperative imaging. When an msn was observed in the resected specimen, the maximum distance from the edge of the tumor to the msn was measured. Among the tumors sized < or =2 cm (n=66), the number having msn and the distance (mm) from the main tumor according to the degree of tumor differentiation were as follows: well (n=16), 1 (6.2%) and 1.4 mm; moderate (n=46), 5 (19.2%) and 5.8+/-1.2 mm; and poor (n=4), 1 (25.0%) and 4.8 mm. Among the tumors sized 2 to 3 cm (n=51), the corresponding results were: well (n=11), 3 (27.2%) and 3.5+/-2.2 mm; moderate (n=36), 6 (16.7%) and 5.4+/-1.4 mm; and poor (n=4), 1 (25.0%) and 4.9 mm. Of the 112 vascular tumors, 17 (15%) had msn. The 5 avascular tumors had no msn. Among the patients who underwent PMCT with a treatment margin measuring <5 mm, local recurrence occurred in 2 of 25 patients whose original tumor was < or =2 cm, and 3 of 25 (12%) patients of those with tumors of 2 to 3 cm. No patient with a tumor < or =3 cm and a > or =5-mm treatment margin suffered a local recurrence. The results of this study suggest that the incidence of local recurrence may be reduced by achieving a treatment margin of any width for avascular tumors and a margin of 1 cm for vascular tumors during local ablation therapy for small HCCs of < or =3 cm.

Amyloidosis of the gallbladder mimicking gallbladder cancer.

We report a rare case of amyloidosis of the gallbladder in a 63-year-old woman with a history of primary amyloidosis. The patient was asymptomatic. Blood chemistry and hematologic laboratory levels, as well as values for tumor markers, were unremarkable. Ultrasonography (US) of the abdomen showed a focal echogenic lesion (22 x 15 mm) in the body of the gallbladder, and moderate enhancement was noted on contrast-enhanced US. Abdominal computed tomography revealed nodular wall thickening in the body of the gallbladder that was enhanced by contrast material. Although this patient was asymptomatic, the existence of gallbladder cancer could not be totally denied. Therefore, laparoscopic cholecystectomy was performed for total biopsy of the gallbladder. An intraoperative frozen-section examination revealed evidence of mild chronic cholecystitis with the appearance of hyalinal stroma. There was no malignant lesion. The final diagnosis, amyloidosis of the gallbladder, was obtained by alkaline alcoholic Congo red staining. Amyloid depositions were found in the walls of the vessels in the submucosa and the lamina propria mucosae, consistent with an elevated nodular lesion in the body of the gallbladder. To our knowledge, this is the first case of amyloidosis of the gallbladder mimicking gallbladder cancer that was diagnosed after laparoscopic cholecystectomy.

Pigmented villonodular synovitis originating from the lumbar facet joint: a case report.

The authors successfully treated a rare case of pigmented villonodular synovitis (PVNS) that originated from the lumbar facet joint (L4-5). A 43-year-old man presented with a complaint of left severe sciatica causing difficulty in walking. Magnetic resonance imaging (MRI) demonstrated an extradural mass on the left side at L4 and the mass compressed the dural tube and was continuous with the left L4-5 facet joint. A computed tomography myelogram revealed an extradural defect of contrast medium at the L4 level and an erosion of the L4 lamina. A total synovectomy with unilateral osteoplastic laminectomy was performed. The histological findings were a diagnosis of PVNS. The patient's symptoms resolved completely and the MRI at postoperative 3 years demonstrated no recurrence of PVNS. It is important to totally remove the synovium, which is the origin of PVNS in order to prevent the recurrence. We think that our procedure is reasonable and adequate for lumbar PVNS.

[Bellini duct carcinoma of the kidney: a case report].

We report a case of Bellini duct carcinoma. A 65-year-old man visited our hospital because of an asymptomatic right renal mass directed by ultrasonography and computed tomography in an other hospital. His urine cytology was negative. The tumor showed a minimal enhancement in computed tomography. Under the preoperative diagnosis of an atypical right renal tumor, laparoscopic right radical nephrectomy was performed. The tumor is 50 mm in diameter and the surface was grayish-white in color. The histopathological diagnosis was low-grade Bellini duct carcinoma. Immunohistostaining revealed positive staining for UA-1 and EMA in the tumor tissue. No evidence of recurrence or metastasis was noted 36 months after surgery without any adjuvant therapy.

[Small cell carcinoma of the prostate: a case report].

A 76-year-old man had been treated with maximum androgen blockade therapy for a poorly-differentiated prostate adenocarcinoma (T3cN1M0, prostate specific antigen (PSA) 65 ng/ml, Gleason Score 4+5=9) since September 2002. By August 2003, his serum PSA levels were undetectable and the lymph node swelling had vanished. However, in December 2004, his serum PSA levels started rising gradually up to 0.66 ng/ml. Radiation therapy on the prostate was then performed (66 Gy). At that time, no metastasis was detected by computed tomography and bone scintigraphy. In August 2005, multiple bone metastases were detected. Immunohistochemical examination of a biopsy specimen from the bone lesion revealed a small cell carcinoma/neuroendocrine cell carcinoma. He died with undetectable PSA levels (less than 0.008 ng/ml) in December 2005. The autopsy showed multiple organ metastases including bone, liver, lungs and others. The immunohistochemical examination revealed pure small cell carcinoma in all metastatic lesions. A precise histological examination of the lungs using a 1 cm serial section could not reveal any tumors compatible with primary lung cancer. We concluded from the clinical history and autopsy findings that his initial poorly-differentiated adenocarcinoma of the prostate dedifferentiated into a pure small cell carcinoma with neuroendocrine differentiation.