Sonic hedgehog and androgen signaling in tumor and stromal compartments drives epithelial-mesenchymal transition in prostate cancer.

OBJECTIVE: Sonic hedgehog (Shh) signaling, androgens and epithelial-mesenchymal transition (EMT) are related to prostate cancer (PCa) progression. The aim of this study was to investigate how Shh and androgen [dihydrotestosterone (DHT)] signaling act in prostate epithelial and stromal compartments and whether this signaling pathway drives EMT and promotes PCa progression. MATERIAL AND METHODS: LNCaP, normal prostate fibroblast (NPF) and cancer-associated prostate fibroblast (CPF) cells were studied with DHT and/or the Shh signaling inhibitor cyclopamine. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the expressions of a potential Shh target gene, osteonectin (ON) and EMT-associated markers (E-cadherin, N-cadherin and vimentin). Immunohistochemical studies using PCa prostatectomy samples were performed to assess the expression levels of ON, Gli-1, androgen receptor, Shh, E-cadherin, N-cadherin and vimentin. RESULTS: While DHT enhanced cell proliferation in CPF more than LNCaP or NPF, cyclopamine inhibited cell proliferation enhanced by DHT in CPF. Real-time RT-PCR showed whereas both Shh and DHT induced N-cadherin and vimentin, DHT also induced the expression of osteonectin in LNCaP and cyclopamine blocked these expressions in osteonectin, N-cadherin and vimentin (p = 0.0084, 0.0002 and 0.0373, respectively). Immunohistochemistry showed that high expression of stromal, but, not epithelial, ON was significantly correlated with serum prostate-specific antigen (PSA) (p = 0.031), and high expression of Gli-1 and low expression of stromal ON with PSA recurrence (p = 0.0114 and p = 0.0005, respectively). CONCLUSIONS: Shh and androgen signaling in prostate tumor and stromal compartments drives EMT, and thus may play some role in PCa progression. Cyclopamine may be one therapeutic strategy for PCa.

Incidental detection of clinically unexpected breast lesions by computed tomography.

BACKGROUND: Increased use of computed tomography (CT) has resulted in greater detection of incidental breast lesions unrelated to the primary diagnostic inquiry. PURPOSE: To investigate the morphology and clinical significance of breast abnormalities detected incidentally by conventional CT. MATERIAL AND METHODS: A total of 2945 female patients underwent CT examinations of the body, including the chest, from May 2006 to April 2010. Two radiologists interpreted these CT scans independently and pointed out a mass or non-mass-like lesion as abnormalities in the breast. Patients who incidentally showed breast lesions on CT scans were identified by a computer-based search of the diagnostic reports and were enrolled in this study. The morphology and enhancement patterns of CT-detected breast lesions were evaluated according to BI-RADS-MRI. RESULTS: In total, 32 clinically unexpected abnormal breast lesions were found in 31 (1.1%) patients. Twenty-nine of the 32 lesions were detected by contrast-enhanced CT and three by unenhanced CT. Ten breast cancers were found in 10 patients (0.34%), which yielded the prevalence for malignancy of 31% (10/32). Invasive ductal carcinomas accounted for eight lesions, while two were ductal carcinomas in situ (DCIS). Nine lesions were depicted as a mass and one DCIS was a non-mass-like lesion. Good morphological predictors of breast cancers for a mass were an irregular shape, a lobulated shape, and an irregular margin. Benign lesions accounted for 22 lesions from 21 patients (0.71%). Of these, 13 lesions in 13 patients were depicted as a mass and nine lesions in nine patients as a non-mass-like lesion. CONCLUSION: Unexpected breast lesions can be identified as a mass or non-mass-like lesion on conventional chest CT scans. Among these, breast cancers that are not clinically apparent occur with considerable prevalence. We suggest that careful interpretation of the breast should be a routine part of CT examinations.

Nodular fasciitis of the hand in a young athlete. A case report.

Nodular fasciitis is a rapidly growing mass, with high cellularity and mitotic activity, that can be both clinically and histologically misdiagnosed as a soft tissue sarcoma. Nodular fasciitis of the hand is an extremely rare condition. We report a 17-year-old male hand-ball player with nodular fasciitis in the dominant hand. The patient presented with a rapidly growing mass in his right hand and no history of major trauma. On physical examination, a painful mass measuring 2 cm in diameter was observed in the first web space. Magnetic resonance imaging (MRI) demonstrated a subcutaneous mass with isointensity on T1-weighted images and inhomogeneous high intensity on T2-weighted images. The lesion was inhomogeneously enhanced after intravenous administration of gadolinium. Moreover, thallium-201 scintigraphy showed high uptake at the early phase and no wash-out at the delayed phase. We performed an excisional biopsy. The mass was present subcutaneously and adhered to the interosseous muscle fascia. Although a pathological examination by frozen section during surgery showed a low-grade spindle cell sarcoma, the final histological diagnosis was nodular fasciitis. There was no evidence of local recurrence at the recent follow-up 2 years after the operation. We speculate that repeated small injuries as a result of sports activities played an important causative role in the nodular fasciitis.

CD56-positive diffuse large B-cell lymphoma: possible association with extranodal involvement and bcl-6 expression.

Among B-cell non-Hodgkin's lymphomas, neural cell adhesion molecule/CD56 expression is exceptional. In this study, seven cases of CD56-positive diffuse large B-cell lymphoma (DLBCL) are described. The frequency of CD56-positive DLBCL was 7% in our hospital. Four of seven (57.1%) cases expressed both CD10 and bcl-6 suggestive of a germinal center B-cell phenotype. Six of seven (85.7%) cases expressed bcl-6. Two cases expressed aberrant T cell-associated antigens, one each of CD7 and CD8. However, none of these seven cases showed CD5 expression. No significant difference was observed between CD56-positive and CD56-negative DLBCL in terms of the five international prognostic index risk factors. However, all seven cases had at least one extranodal involvement and showed a good response to initial treatment. The predominance of extranodal involvement in our series may be associated with the adhesion-related function of CD56. A high frequency of bcl-6 expression may be associated with a more favorable clinical course and prognosis.

Diagnostic performance of fluorodeoxyglucose-positron emission tomography/computed tomography of breast cancer in detecting axillary lymph node metastasis: comparison with ultrasonography and contrast-enhanced CT.

PURPOSE: The purpose of this retrospective study was to evaluate the diagnostic performance of positron emission tomography/computed tomography (PET/CT) with fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose (FDG) in comparison with that of ultrasonography and contrast-enhanced computed tomography (CT) in detecting axillary lymph node metastasis in patients with breast cancer. MATERIALS AND METHODS: Fifty patients with invasive breast cancer were recruited. They had received no neoadjuvant chemotherapy and underwent PET/CT, ultrasonography and contrast-enhanced CT before mastectomy. The clinical stage was I in 34 patients, II in 15 patients, and III in one patient. The images of these modalities were interpreted in usual practice before surgery and the diagnostic reports were reviewed for analysis. Sensitivity, specificity, positive predictive value, and negative predictive value of each modality were obtained taking histopathological results of axillary lymph node dissection or sentinel lymph node biopsy as the reference standard. RESULTS: Axillary lymph node metastasis was confirmed in 15 of 50 patients by histopathological studies. PET/CT identified lymph node metastasis in three of these 15 patients. The overall sensitivity and specificity, positive predictive value, and negative predictive value of PET/CT in the diagnosis of axillary lymph node metastasis were 20, 97, 75, and 74%, and those of ultrasonography were 33, 94, 71, and 77% and those of contrast-enhanced CT were 27, 97, 80, and 76%, respectively. CONCLUSIONS: PET/CT showed poor sensitivity and high specificity in the detection of axillary lymph node metastasis of breast cancer. Diagnostic performance of PET/CT was not superior to that of ultrasonography and contrast-enhanced CT.

Mucinous carcinoma of the breast: MRI features of pure and mixed forms with histopathologic correlation.

OBJECTIVE: The purpose of this study was to describe the MRI features of the pure and mixed forms of mucinous carcinoma of the breast and the histopathologic correlation. MATERIALS AND METHODS: Seventeen pure and three mixed mucinous tumors of the breast were examined with T2-weighted MRI and triple-phase dynamic MRI. MR images were reviewed for evaluation of the signal intensity and enhancement patterns of tumors and for correlation with the histopathologic findings. RESULTS: The presence of very high signal intensity on T2-weighted images was a common feature of pure and mixed mucinous tumors. Fourteen pure tumors and one mixed tumor had very high signal intensity, and three pure and two mixed tumors had very high signal intensity and isointensity on T2-weighted images. The enhancement pattern during the early phase varied with the cellularity of pure tumors and with the distribution of nonmucinous components in mixed tumors. Hypocellular pure mucinous tumors had a typical pattern of gradual enhancement. CONCLUSION: Hypercellular pure mucinous tumors exhibit strong early enhancement and may be difficult to differentiate from mixed mucinous tumors. The distinction between the pure and mixed forms of mucinous carcinoma is important because mixed mucinous carcinoma more frequently undergoes lymph node metastasis and has a poorer prognosis than does pure mucinous carcinoma.

t(14;18)(q32;q21)-bearing pleural MALT lymphoma with IgM paraproteinemia: value of detection of specific cytogenetic abnormalities in the differential diagnosis of MALT lymphoma and lymphoplasmacytic lymphoma.

A 67-year-old woman presented with a pleural effusion and a tumor in the right pleural wall. Histological examination of thoracoscopic tumor and pleural biopsy specimens showed infiltration by medium sized cells, some of which showed plasmacytoid differentiation. In view of the presence of IgM paraproteinemia and bone marrow involvement by lymphoma cells, the patient was diagnosed tentatively as having lymphoplasmacytic lymphoma (LPL). However, chromosomal analysis of the cells in the pleural fluid detected t(14;18)(q32;q21), while fluorescence in situ hybridization was positive for 11% of the MALT1 split signal. Because of the presence of characteristic genetic abnormalities and notable extranodal involvement, the patient was diagnosed as having MALT lymphoma. She was treated with three courses of cladribine and rituximab, and achieved complete regression of the tumor. In this case the detection of t(14;18)(q32;q21) involving IGH and MALT1 was useful for the differential diagnosis of LPL and MALT lymphoma.

Genome-wide microsatellite analysis of focal nodular hyperplasia: a strong tool for the differential diagnosis of non-neoplastic liver nodule from hepatocellular carcinoma.

Allelic imbalance (AI), which represents certain chromosomal gains or losses, has been described in hepatocellular carcinoma (HCC), but the significance of AI analysis in focal nodular hyperplasia (FNH) has not been fully clarified. We hypothesized, therefore, that comprehensive allelotyping of FNH could be a useful tool for differentiating FNH from HCC. A 27-year-old man was admitted to the hospital because of general fatigue. A computed tomography (CT) scan disclosed a hepatic nodule 8 cm in diameter. No definite diagnosis was made after imaging or by biopsy before surgery. Macroscopically and microscopically, the surgical specimen showed typical features of FNH. Comprehensive microsatellite analysis was carried out with 382 microsatellite markers distributed throughout all chromosomes. To detect AI effectively, the cutoff value of the AI index was set at 0.70. Among the 382 microsatellite markers, 212 loci were informative, but no AI was detected. The absence of gross chromosomal alterations strongly suggested that the large nodule was FNH rather than HCC, in terms of its genetic background. The patient's subsequent clinical course revealed the nodule to be benign. The results suggest that this genome-wide microsatellite analysis is a useful tool for the differential diagnosis of non-neoplastic liver nodules from HCC.

Papillary renal cell carcinoma: a clinicopathological study of 35 cases.

AIM: The objective of the present study was to characterize the clinicopathological features of histologically defined papillary renal cell carcinoma (RCC). METHODS: The present study included a total of 35 patients who were treated by radical surgery and subsequently diagnosed as having papillary RCC between April 1995 and June 2004. Clinicopathological data of these patients were retrospectively reviewed according to the previously reported classification system (Mod. Pathol. 1997; 10: 537-44). RESULTS: Of these 35 patients, 23 (65.7%) and 12 (34.3%) were diagnosed as type 1 and type 2 papillary RCC, respectively. Despite the lack of significant differences in clinical parameters between these two groups, including age, gender, clinical stage and metastasis, the incidence of symptomatic disease in patients with type 2 papillary RCC was significantly higher than that in those with type 1 papillary RCC. Pathological examinations demonstrated that there were no significant differences between these two groups in pathological stage, tumor grade or vascular invasion. Furthermore, there was no significant difference between these two groups in overall or recurrence-free survival. CONCLUSIONS: Although the present study included a small number of patients with short follow-up period, the clinicopathological features including prognoses were almost similar between patients with type 1 and type 2 papillary RCC; therefore, careful postoperative follow-up should be considered for patients with papillary RCC irrespective of morphological subtype.

Histological and cytogenetic characterization of bone marrow in relation to prognosis and diagnosis of myelodysplastic syndromes.

Bone marrow (BM) histology of 102 myelodysplastic syndromes (MDS) patients was analyzed retrospectively. All the cases were reclassified according to the World Health Organization (WHO) classification. Karyotype study was conducted for all except one. Fifteen of the MDS cases were hypoplastic. The cellularity in bone marrow histology is sometimes ineffective in the differential diagnosis of MDS and aplastic anemia (AA). Nonetheless, a marked decrease in the number of megakaryocytes (average, 0.3/mm(2); range, 0-2/mm(2)) even in the hyperplastic foci of the marrow of AA was the most important histological feature differentiating AA from MDS, whereas the number of megakaryocytes increased in most MDS cases (44/mm(2); range, 1-240/mm(2)) and also in hypoplastic MDS (14/mm(2); range, 8-26/mm(2)). Hyperplastic marrow had a significantly high frequency of progress to acute myeloid leukemia (AML) and hypoplastic MDS had a lower rate of progress to AML. Severe myelofibrosis had a significantly poor prognosis. An increase in CD34-positive cells in MDS indicated a high rate of progress to AML. As for the patients with refractory cytopenia with multilineage dysplasia (RCMD; the new category under the WHO classification), the increased number of megakaryocytes was correlated with poor prognosis.

Photodynamic therapy for cervical intraepithelial neoplasia.

OBJECTIVES: Photodynamic therapy (PDT) is a minimally invasive treatment for cervical intraepithelial neoplasia (CIN). We report the effectiveness of PDT in 105 cases of CIN. METHODS: All patients received photofrin (PHE) 2 mg/kg intravenously and, 48-60 h later, phototherapy was performed using the Excimer dye laser or a YAG-OPO laser with an irradiation dose of 100 J/cm(2) using 630 nm wavelength. RESULTS: Mild photosensitivity occurred in 48% (50/105) of patients. The complete response (CR) rate was 90% (94/105) at 3 months following treatment. In the remaining 11 patients, 5 patients had CIN1, 2 patients had CIN2, and 4 patients had mild cytologic findings. However, in 9 of these 11 patients, CR was achieved 6 months after PDT. In 69 patients, human papilloma virus (HPV) typing was performed before and after PDT therapy. Pre-treatment, 64 of 69 patients (93%), were HPV-positive including 30 cases of high-risk HPV (43%). Testing performed 3, 6 and 12 months following PDT revealed no HPV-DNA in 75% (52/69), 74% (48/65) and 72% (41/57) of patients. At present, the median follow-up period is 636 days (90-2,232 days). In 3 patients, recurrence requiring surgical treatment was identified at 646, 717 and 895 days after PDT. CONCLUSIONS: PDT is an effective and minimally invasive treatment for CIN, which also appears to eradicate HPV infection.

High resolution CT findings of pulmonary epithelioid hemangioendothelioma: unusual manifestations in 2 cases.

Pulmonary epithelioid hemangioendotheliomas (PEH), also known as intravascular sclerosing bronchoalveolar tumor, is a rare vascular tumor of the lung common among young women. Primitive lumena lined by single cells is the characteristic pathologic feature. The endothelial nature of these cells is confirmed by positive staining with factor VIII and CD34. PEH usually presents as single or multiple pulmonary nodules. The present report describes high resolution CT (HRCT) findings of 2 cases with unusual manifestations of PEH. One case was a 54-year-old woman with multiple pulmonary nodules with irregular thickening of both the bronchovascular bundles and perilobular structures, representing intensive lymphangitic spread on HRCT. The other was an 18-year-old woman who had multiple minute peripheral nodules in the lungs bilaterally. These HRCT findings demonstrated the presence of tumor nodules in the lymphatic spaces, which is quite an unusual histologic presentation for this tumor. Both cases also showed hepatic lesions on abdominal CT; the former showing hypoattenuating masses with coarse calcifications and the latter showing multiple tiny calcifications in the hepatic parenchyma. Recognition of these features in the appropriate clinical setting may allow the clinician and the pathologist to consider this rare tumor.

Micropapillary variant of transitional cell carcinoma of the bladder.

A 77-year-old man visited the Kobe City General Hospital complaining of macroscopic hematuria. A computed tomography scan found a bladder tumor with left iliac and para-aortic lymph node metastasis. Two courses of cisplatin, cyclophosphamide and doxorubicin chemotherapy resulted in a minimal response. Radical cystectomy and a retroperitoneal lymph node dissection with bilateral ureterocutaneostomy reconstruction were then performed. A pathological examination revealed a micropapillary variant of transitional cell carcinoma (Grade 3, pT1pN2M1). The patient died of pelvic recurrence 7 months after the initiation of chemotherapy. Peritonitis carcinomatosa and lung metastases were observed at autopsy.

Correlation between computed tomographic findings, bronchioloalveolar carcinoma component, and biologic behavior of small-sized lung adenocarcinomas.

OBJECTIVE: Differentiation of bronchioloalveolar carcinoma from other subtypes of lung adenocarcinomas is important in the preoperative assessment of patients. We examined the biologic aggressiveness of small-sized adenocarcinomas according to the pathologically defined bronchioloalveolar carcinoma degree and its correlation with computed tomography findings. In addition, we attempted to predict which patients were suitable for a lesser resection. METHODS: Of 424 consecutive patients who underwent operation for primary lung cancer in the last 3 years, 114 with a histopathologically proven adenocarcinoma 3 cm or less in diameter underwent complete removal of the primary tumor. We examined the characteristics of patients classified into 3 groups based on the proportion of the bronchioloalveolar carcinoma component: 0% to 20% (n = 40), 21% to 50% (n = 38), and 51% to 100% (n = 36). We also investigated the correlation of the bronchioloalveolar carcinoma component with computed tomography findings such as ground-glass opacity (defined as a hazy increase on the lung window) and tumor shadow disappearance rate (defined as the ratio of the tumor area of the mediastinal window to that of the lung window). RESULTS: Male gender (P =.0001), advanced pathologic stage (P =.001), larger size of the tumor (P =.004), nodal involvement (P =.04), pleural invasion (P =.0003), lymphatic invasion (P =.002), and vascular invasion (P =.0002) were observed more often among patients with a smaller proportion of bronchioloalveolar carcinoma. A positive and significant correlation was found between the rate of bronchioloalveolar carcinoma component and ground-glass opacity (R(2) = 0.488, P <.0001) and tumor shadow disappearance rate (R(2) = 0.727, P <.0001). As an independent predictor of nodal status, tumor shadow disappearance rate (P =.015) and bronchioloalveolar carcinoma component (P =.015), as well as tumor size, were significantly valuable, although ground-glass opacity proportion (P =.086) was marginally informative. CONCLUSIONS: Small-sized adenocarcinomas with a greater ratio of bronchioloalveolar carcinoma component showed less aggressive behavior. Both tumor shadow disappearance rate and ground-glass opacity ratios, which are obtained preoperatively, were well associated with bronchioloalveolar carcinoma ratios, which are determined postoperatively. Furthermore, tumor shadow disappearance rate had a stronger impact as a predictor of bronchioloalveolar carcinoma component. Preoperative assessment of tumor shadow disappearance rate may be useful to identify patients requiring a less extensive pulmonary resection.

[Natural killer-cell lymphoma of the iris with a normal fundus].

BACKGROUND: Intraocular lymphoma is a relatively uncommon malignancy, rarely presenting with exclusively anterior segment findings in a normal fundus. CASE: A 38-year-old male, previously diagnosed with nasal lymphoma, currently in complete remission after chemotherapy and radiotherapy, presented with blurring of vision in his left eye, which initially responded to local steroid therapy. However, the patient developed resistance to steroid therapy and developed nodular masses in the left iris. Ultrasound biomicroscopy revealed diffuse thickenings leading to a complex and uneven shape of the left iris. An iris biopsy was done which led to the diagnosis of natural killer(NK)-cell lymphoma. Radiation therapy was instituted which led to rapid resolution of both the nodular masses and iritis. CONCLUSION: This is a case of malignant lymphoma presenting as metastasis to the iris without involvement of the chorioretinal tissues. When encountering a patient with iritis resistant to the steroid therapy, clinical ophthalmologists should consider metastatic malignancy in the differential diagnosis.

Association of intestinal malignant lymphoma and ulcerative colitis.

A 42-year-old woman with refractory ulcerative colitis (UC) developed ascites, pleural effusion, pretibial edema and severe anemia. Colonofiberscopic examination showed a bulky submucosal tumor in the sigmoid colon, which was histologically diagnosed as malignant lymphoma (diffuse large, B cell type). The lymphoma was resistant to chemotherapy. Autologous peripheral blood stem cell transplantation (PBSCT) was effective; however, she died of severe infection after the second PBSCT. Although the association of intestinal lymphoma with UC is rare, lymphoma should be taken into consideration when the clinical course of UC is atypical or when UC is refractory to therapy.