Primary pulmonary hyalinizing clear cell carcinoma with fusions of both EWSR1::CREM and IRF2::NTRK3: report of a case with an aggressive behavior.

Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland-type tumor newly recognized in recent years, with approximately 21 cases reported to date in the English literature, which constitutes a challenge in pathology diagnosis, particularly in small biopsy specimens. Here, we present a case of pulmonary HCCC diagnosed by computed tomography-guided percutaneous lung biopsy in a 70-year-old man's right lower lung. Although the morphology and immunophenotype of the tumor suggested the diagnosis of mucoepidermoid carcinoma, fluorescence in situ hybridization failed to reveal the rearrangement of MAML2 gene, which is characteristic of mucoepidermoid carcinoma. Instead, further molecular genetic testing showed that the tumor harbored a rare EWSR1::CREM fusion combined with a previously unreported IRF2::NTRK3 fusion. Pulmonary HCCC is commonly regarded as a low-grade malignant tumor with an indolent course, but this case has a different biological behavior, presenting extensive dissemination and metastases at the time of diagnosis, which expands our understanding of the prognosis of this tumor. The patient has had five cycles of combination chemotherapy and has been alive with the tumor for eight months.

Perivascular Epithelioid Cell Tumor of Urinary Bladder.

OBJECTIVES: To review the clinicopathologic features of perivascular epithelioid cell tumor (PEComa) of the urinary bladder. METHODS: Seven cases of bladder PEComa were studied by light microscopy, immunohistochemistry, and fluorescence in situ hybridization (FISH). RESULTS: In our 7 cases, 5 patients were female and 2 were male, with ages between 26 and 78 years. Patients presented with hematuria and recurrent abdominal discomfort as the main clinical symptoms. Microscopically, the epithelioid and spindle-shaped tumor cells with clear to granular eosinophilic cytoplasm were arranged in fascicular, acinar, or nested patterns. The tumor cells were positive for HMB45, melan-A, and SMA, but no TFE3 gene rearrangement was detected in any of the 7 samples by FISH. The analysis of all 35 cases from the literature and ours showed a patient age range from 16 to 78 years (mean age, 39 years), a male-to-female ratio of 1:1.3, maximal tumor diameters from 0.6 to 18.8 cm (mean, 4.5 cm). With a mean follow-up of 27 months, the recurrence, metastasis, and mortality rates were 10.7%, 10.7%, and 7.1%, respectively. CONCLUSIONS: Bladder PEComa is extremely rare, remains a diagnostic challenge, and needs more attention. Strengthening the understanding of this tumor will improve diagnostic accuracy.

Nodal follicular dendritic cell sarcoma with four atypical histomorphologic features: an unusual case report.

BACKGROUND: Follicular dendritic cell sarcoma (FDCS) is a rare malignancy. In addition to the classical histopathologic features, it has also some special morphological variants that can present a challenge in the diagnosis of this disease. CASE PRESENTATION: A 45-year-old male who presented with a left supraclavicular mass was given a final diagnosis of FDCS after lymph node biopsy. The specimen obtained during radical resection revealed five different morphologies, including the classical histological appearance and atypical areas resembling desmoplastic infiltrative carcinoma, anaplastic large cell lymphoma (ALCL), hemangiopericytoma and classical Hodgkin's lymphoma (CHL). Immunohistochemistry was notable for positive CD21 and CD23 expression across all morphologies. Given the atypical appearance and location, the specimen was initially misdiagnosed as a metastatic carcinoma based on histology alone at an outside institution. The patient eventually underwent surgical resection followed by adjuvant chemotherapy and radiation. Despite treatment, the disease progressed, and the patient passed away 36 months after surgery. CONCLUSIONS: This unusual case of FDCS contains four types of atypical histomorphologies within a single tumor specimen, including those resembling ALCL and hemangiopericytoma which are described here for the first time. Our report further expands the histopathologic spectrum of FDCS and may help assist in the diagnosis of other such challenging cases.

Mediastinal follicular dendritic cell sarcoma: a rare, potentially under-recognized, and often misdiagnosed disease.

BACKGROUND: Mediastinal follicular dendritic cell sarcoma (FDCS) is extremely rare. Due to potential under-recognization of this disease, it happens to be misdiagnosed, especially on core needle biopsy. We report 3 cases of mediastinal FDCS and provide a literature review to improve better understanding of the tumor and to reduce misdiagnosis. METHODS: Three cases of mediastinal FDCS in our clinic practice were studied, including their core needle biopsy and resected specimens, and those cases reported previously in English literature were retrieved and analyzed. RESULTS: The core needle biopsy of case 1 showed a tumor reminiscent of classical Hodgkin's lymphoma (CHL), while the resected mass was finally diagnosed with FDCS combined with hyaline-vascular Castleman's disease. Both the biopsy and resected tissue of case 2 were constitutive of the clear epithelioid cells with marked atypia. In both cases, definitive diagnoses were not made on core needle biopsy. In case 3, there were some areas morphologically similar to CHL, and some areas contained ovoid to spindle-shaped tumor cells with fascicular pattern. The analysis of 43 cases of mediastinal FDCS showed the age of patients were from 16 to 76 years old, the male to female ratio was 1.5:1, the maximal tumor diameters were 3-17 cm. 18 cases were underwent preoperative biopsy, whereas 15 (83.3%) of which were misdiagnosed initially, often as lymphoma. 32 patients had available follow-up data, the rates of recurrence, metastasis, and mortality were 12.5, 18.8 and 28.1%, respectively. Current limited data suggested no statistical differences between adverse prognosis and gender, age, tumor size, necrosis, or different therapeutics, respectively. CONCLUSIONS: Mediastinal FDCS is a rare malignancy that has yet not been fully understood and been often misdiagnosed, particularly when making a diagnosis on core needle biopsy. Increased awareness of this enigmatic tumor is crucial to avoid diagnostic pitfalls.

Hepatic monotypic epithelioid angiomyolipoma with concomitant hepatocellular carcinoma.

Hepatic monotypic epithelioid angiomyolipoma (AML) is a rare lesion in which the predominant population of an epithelioid component can mimic hepatocellular carcinoma (HCC). The hepatic epithelioid AML with concomitant HCC is extremely uncommon. In this study, we present the clinical and pathologic features of a case of hepatic monotypic epithelioid AML with concomitant HCC in a 63-year-old man. Imaging examinations revealed two masses located in the liver, measuring 83×63 mm and 37×27 mm separately, which exhibited an early contrast enhancement and a rapid washout on enhanced computed tomography (CT), so that HCC with intrahepatic metastases was suspected. The small tumor was removed for intraoperative frozen section examination. Grossly, the tumor was solitary, well-circumscribed, and non-encapsulated. Microscopically, it was composed purely of a trabecular arrangement of epithelioid cells with a sinusoidal pattern. Immunohistochemically, it was positive for HMB45, Melan-A, and alpha smooth muscle actin (α-SMA). Interestingly, the large tumor has the histologic features similar to those of the small one. However, it was positive for epithelioid markers and negative for the melanocytic markers. It reminds us that there is a possibility of coexistence of HAML and HCC in the liver. We believe that this might be the first case report of a hepatic monotypic epithelioid AML with concomitant HCC. The patient gave up treatment and died in 6 months after the operation in the follow-up.

Perfusion Characteristics of Hepatocellular Carcinoma at Contrast-enhanced Ultrasound: Influence of the Cellular differentiation, the Tumor Size and the Underlying Hepatic Condition.

This study aimed to analyze the influence of the cellular differentiation, the tumor size and the underlying hepatic condition on the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). 276 patients with single lesion ≤ 5 cm who underwent CEUS exam and were pathologically confirmed as HCC were retrospectively enrolled. Enhancement patterns, washout patterns, wash-in time and washout time were observed and recorded. During the arterial phase, more poorly differentiated HCCs (42.5%) and lesions > 3 cm (35.2%) performed inhomogeneous enhancement (p < 0.05). More well differentiated HCCs (63.4%) performed late washout or no washout while compared with moderately (37.8%) or poorly (24.1%) differentiated HCCs (p < 0.05). Poorly differentiated HCCs showed the shortest washout time (83.0 ± 39.8 s), moderately differentiated HCCs showed the moderate washout time (100.4 ± 52.1 s), and well differentiated HCCs showed the longest washout time (132.3 ± 54.2 s) (p < 0.05). Lesions > 3 cm (97.2 ± 51.3 s) washed out more rapidly than lesions ≤ 3 cm (113.9 ± 53.5 s) (p < 0.05). The dynamic enhancement procedure of HCC was influenced by the cellular differentiation and the tumor size. While, hepatic background showed no influence on the dynamic enhancement of HCC.

Primary follicular dendritic cell sarcoma of the urinary bladder: the first case report and potential diagnostic pitfalls.

BACKGROUND: Extranodal follicular dendritic cell sarcoma (FDCS) is a very rare malignancy with a variable clinical course. It is often not considered and has the potential to result in a misdiagnosis of other common sarcomas or sarcomatoid carcinomas. This is particularly true with the preoperative biopsy specimen, in which the tissue sample is often small. CASE PRESENTATION: A case of FDCS in a 63-year-old woman, arising in the urinary bladder, a previously unreported site, is described. The patient presented with the typical clinical symptoms of a bladder cancer, and the morphology of the tumor was similar to a lymphoepithelioma-like carcinoma, ultimately resulting in it being misdiagnosed. The patient received radical cystectomy, without further radiotherapy or chemotherapy. Two years after operation, a metastatic tumor to the lung was found. The mass of the right main bronchus lumen was frozen and resected through bronchoscopy, and radiotherapy was performed. The patient has lived with the tumor since then. CONCLUSIONS: This paper presents the first FDCS occurring in the urinary bladder with metastasis to the lung and emphasizes potential diagnostic pitfalls.

Dynamic enhancement patterns of intrahepatic cholangiocarcinoma in cirrhosis on contrast-enhanced computed tomography: risk of misdiagnosis as hepatocellular carcinoma.

This study aimed to assess the features of intrahepatic cholangiocarcinoma (ICC) at computerized tomography (CT) and verify the risk of misdiagnosis of ICC as hepatocellular carcinoma (HCC) in cirrhosis. CT appearances of 98 histologically confirmed ICC nodules from 84 cirrhotic patients were retrospectively reviewed, taking into consideration the pattern and dynamic contrast uptake during the arterial, portal venous and delayed phases. During the arterial phase, 53 nodules (54.1%) showed peripheral rim-like enhancement, 35 (35.7%) hyperenhancement, 9 (9.2%) hypoenhancement and 1 (1.0%) isoenhancement. The ICC nodules showed heterogeneous dynamic contrast patterns, being progressive enhancement in 35 nodules (35.7%), stable enhancement in 28 nodules (28.6%), wash-in and wash-out pattern in 15 nodules (15.3%) and all other enhancement patterns in 20 nodules (20.4%). There were no significant differences in the dynamic vascular patterns of ICC according to nodule size (p > 0.05). ICC in cirrhosis has varied enhancement patterns at contrast-enhanced multiphase multidetector CT. Though the majority of ICC did not display typical radiological hallmarks of HCC, if dynamic CT scan was used as the sole modality for the non-invasive diagnosis of nodules in cirrhosis, the risk of misdiagnosis of ICC for HCC is not negligible.

Comparison of CT and contrast-enhanced ultrasound findings in hepatic angiomyolipoma with pathological correlations.

OBJECTIVE: To compare imaging findings of CT and contrast-enhanced US (CEUS) in hepatic angiomyolipoma (HAML) and investigate their pathological correlations. METHODS: Imaging findings and preoperative diagnosis of CT and CEUS were retrospectively compared head to head in 46 patients with 54 histologically proven HAMLs. Correlations between imaging features and preoperative diagnosis with pathological types of HAMLs were analyzed. RESULTS: Fat was detected in 100% of lipomatous type, 84.6% of mixed type, and 7.1% of myomatous type (p = 0.000) of HAML at unenhanced CT. Well-defined hyper-echogenicity was displayed in 100% of lipomatous type, 88.5% of mixed type, 50% of myomatous type, and 66.7% of angiomatous type of HAMLs at unenhanced US. More arterial hyper-enhancement was noted on CEUS (100%) than on CT (73.1%) in mixed type (p = 0.015) and in lipomatous type (90.9% vs. 9.1%, p = 0.000) of HAMLs. Washout was present in more HAMLs on CT than on CEUS (42.6% vs. 18.5%, p = 0.007). Correct preoperative diagnosis was suggested in more HAMLs of myomatous type on CEUS than on CT (42.9% vs. 0%, p = 0.016) but showed no difference in other types of HAMLs. CONCLUSION: There are considerable discrepancies between CT and CEUS findings of HAMLs, and the imaging appearance and preoperative diagnosis of HAMLs on CT and CEUS are significantly affected by pathological types of HAMLs.

Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is an uncommon primary liver malignancy and little known about the clinical and imaging characteristics of cHCC-CC. We aim to define the demographics, imaging features of cHCC-CC on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CT) in this study. METHODS: From January 2005 to December 2014, 45 patients with pathologically proven cHCC-CC who underwent preoperative CEUS and 43 patients who had additional CT scan in our institution were included. A retrospective review of the imaging studies and clinical data in these patients was conducted. RESULTS: In our series, cHCC-CC accounted for 1.6 % of all primary liver malignancy. Mean age of patient with cHCC-CC was 52.8 year (range: 28-74 year) and 88.9 % (40/45) of patients were male. Thirty of forty five patients (66.7 %) had cirrhosis and 20 % (9/45) of patients had chronic hepatitis B without cirrhosis. Alpha--fetoprotein (AFP) was elevated in 62.2 % (28/45) of patients and carbohydrate antigen 19-9 (CA19-9) elevated in 22.2 % (10/45) of patients). Both AFP and CA19-9 were simultaneously elevated in 15.6 % (7/45) of patients. Enhancement pattern resembling cholangiocarcinoma (CC) was noted in 53.3 % (24/45) of patients (on CEUS and in 30.2 % (13/43) of patients at CT. Enhancement pattern resembling hepatocellular carcinoma (HCC) was observed in 42.2 % (19/45) of patients on CEUS and in 58.1 % (25/43) of patients at CT. The percentage of tumors showing CC enhancement pattern (27.9 %, 12/43) was comparable with that of tumors showing HCC enhancement pattern (44.2 %, 19/43) on both CEUS and CT (p = 0.116). Simultaneous elevation of tumor markers (AFP and CA19-9) or tumor marker elevation (AFP or CA19-9) in discordance with enhancement pattern on CEUS was demonstrated in 51.1 % (23/45) of patients and on CT in 53.5 % (23/43) of patients, which was significantly more than simultaneous elevation of tumor markers (AFP and CA19-9) alone (p = 0.000). CONCLUSIONS: The clinical characteristics of cHCC-CC are similar to those of HCC. The cHCC-CC tumors display enhancement patterns resembling CC or HCC in comparable proportion on both CEUS and CT. Combination of simultaneous elevation of tumor makers (AFP and CA19-9) and tumor mark elevation (AFP or CA19-9) in discordance with presumptive imaging findings on CEUS or CT may lead significantly more patients to be suspicious of the diagnosis of cHCC-CC.

Diagnosis of Hepatic Angiomyolipoma by Combination of Baseline and Contrast-Enhanced Ultrasound--A Prospective Study in Non-Cirrhotic Patients.

OBJECTIVES: Hepatic angiomyolipoma (HAML) is a rare, benign mesenchymal tumor of the liver and its diagnosis has been considered challenging. The aim of this study was to investigate prospectively the diagnostic efficacy of the incorporation of both baseline ultrasound (US) and contrast-enhanced ultrasound (CEUS) features of HAML in patients without cirrhosis. MATERIALS AND METHODS: Consecutive 1748 non-cirrhotic patients with focal liver lesions (FLLs) were prospectively enrolled. Baseline US and CEUS were performed before resection or biopsy. Ultrasound imaging diagnosis of FLLs was compared with the pathological results. RESULTS: Final diagnoses were established in 41 patients with HAML (2.3%) with normal alpha fetal protein (AFP) level and in 1707 patients with FLL other than HAML. Diagnostic criteria for HAML was based on the combination of baseline US and CEUS appearance of the nodule: (1) Well-defined, marked hyper-echoic nodule without surrounding hypo-echoic halo on baseline US; (2) hyper-enhancement in the arterial phase (exclude initial peripheral nodular enhancement and spoke-wheel arteries) and remains hyper-enhancement or iso-enhancement in the late phase. The diagnostic criteria were fulfilled in 31 HAMLs, 1 hepatocellular adenoma and 1 hemangioma. Ten HAMLs were misdiagnosed as other liver tumors because they did not meet the diagnostic criteria mentioned above and consequently yielded a sensitivity, specificity, positive predictive values, negative predictive values and Youden index of 75.61%, 99.88%, 93.94%, 99.42%, and 0.75 respectively. CONCLUSION: The combination of baseline US and CEUS may lead to the correct diagnosis noninvasively in the majority of HAMLs in non-cirrhotic patients with normal AFP level.

Detailed analysis of temporal features on contrast enhanced ultrasound may help differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma in cirrhosis.

AIM: To verify if detailed analysis of temporal enhancement patterns on contrast enhanced ultrasound (CEUS) may help differentiate intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) in cirrhosis. METHODS: Thirty three ICC and fifty HCC in cirrhosis were enrolled in this study. The contrast kinetics of ICC and HCC was analyzed and compared. RESULTS: Statistical analysis did not reveal significant difference between ICC and HCC in the time of contrast first appearance and arterial peak maximum time. ICC displayed much earlier washout than that of HCC (47.93±26.45 seconds vs 90.86±31.26 seconds) in the portal phase, and most ICC (87.9%) showed washout before 60 seconds than HCC (16.0%). Much more ICC (78.8%) revealed marked washout than HCC (12.0%) while most HCC (88.0%) showed mild washout or no washout in late part of the portal phase (90-120 seconds). Twenty six out of thirty three ICC (78.8%) demonstrated both early washout(<60 seconds) and marked washout in late part of the portal phase, whereas, only six of fifty HCC (12.0%)showed these temporal enhancement features (p = 0.000).When both early washout and marked washout in the portal phase are taken as diagnostic criterion for ICC, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 78.8%,88.0%,81.3%,86.3%,and 84.3% respectively by CEUS. CONCLUSIONS: Analysis of detailed temporal enhancement features on CEUS is helpful differentiate ICC from HCC in cirrhosis.If a nodule in cirrhotic liver displays hyper-enhancement in the arterial phase followed by early and marked washout in the portal phase, the nodule is highly suspicious of ICC rather than HCC.

Dynamic enhancing vascular pattern of intrahepatic peripheral cholangiocarcinoma on contrast-enhanced ultrasound: the influence of chronic hepatitis and cirrhosis.

PURPOSE: To analyse the dynamic enhancing features by real-time contrast-enhanced ultrasound (CEUS) of intrahepatic peripheral cholangiocarcinoma (ICC) in patients with chronic hepatitis and cirrhosis. MATERIALS AND METHODS: CEUS was performed by using contrast pulse sequencing (CPS) imaging with mechanical index of <0.2 after injection of 2.4 mL of contrast agent. CEUS images of histologically confirmed ICC in 54 patents (15 patents with chronic hepatitis B, 16 patents with cirrhosis, and 23 patents with normal underlying liver) were analyzed. RESULTS: Heterogeneous hyperenhancement was more frequently identified in ICC with chronic hepatitis (9 of 15, 60.0%, p = 0.000) and cirrhosis (8 of 16, 50.0%, p = 0.010) than in patients with normal liver (6 of 23, 26.1%) during arterial phase. The majority of ICC in patients with normal liver displayed peripheral hyperenhancement (13 of 23, 56.5%), than in patients with chronic hepatitis (4 of 15, 26.7%, p = 0.000) and cirrhosis (5 of 16, 31.3%, p = 0.001). Intense contrast uptake during the arterial phase (heterogeneous hyperenhancement or global hyperenhancement) followed by washout in venous phases was more frequently displayed in ICC patients with chronic hepatitis (11 of 15, 73.3%, p = 0.000) and in patients with cirrhosis (11 of 16, 68.8%, p = 0.000) than in ICC patients with normal underlying liver (8 of 23, 34.8%). CONCLUSION: The enhancing vascular pattern of ICC on CEUS in patients with chronic hepatitis and cirrhosis is different from that in ICC without underlying liver disease. The enhancing vascular pattern is indistinguishable from HCC on CEUS in most ICC patients with chronic hepatitis or cirrhosis.

Multimodal therapy for adult Wilms' tumour: an experience from one centre.

INTRODUCTION: Wilms' tumour (WT) is very rare in adults but very common in children. Treatment guidelines for adult patients with WT are still insufficient. Some study groups recommend that therapeutic protocols for adults with WT (AWT) should follow the guidelines that have been established for children. OBJECTIVE: To describe the clinical and pathological characteristics of AWT as well as the treatment protocols and outcomes for AWT at our treatment centre. MATERIAL AND METHODS: Seven patients (5 females and 2 males) were diagnosed with AWT in our hospital between 2002 and 2009. The tumours were staged and the patients were treated according to the paediatric regimen recommended by the National Wilms' Tumor Study Group. RESULTS: The median patient age at the time of diagnosis was 29 years (range, 16-37 years). Flank pain was the most common clinical presentation. One patient was in Stage I of disease development, two were in Stage II, two were in Stage III and two were in Stage IV. Anaplasia was present in 3 patients with Stage III or Stage IV disease. All of the patients but one underwent nephrectomy and 2 incomplete surgeries were performed. Seven patients received 2-drug or 3-drug chemotherapy (dactinomycin and vincristine and/or doxorubicin). Two patients with Stage III disease also received radiation therapy (a total dose of 3600 or 3960 cGy). Complete remission was achieved in 4 patients. Three patients (one with Stage III disease, 2 patients with Stage IV disease) died of their disease and those patients were all classified with an unfavourable histological type called anaplasia. With a median follow-up of 53.5 months (range, 40-102 months), the 3-year and 5-year overall survival rates were 57.1% (95% confidence interval, 20.4-93.8%). CONCLUSIONS: The results of this report suggest that histological anaplasia might be an adverse prognostic factor for AWT. Proper application of the diagnostic and therapeutic regimens established for children may improve the prognosis of adult patients with WT.

Endogenous axon guiding chemorepulsant semaphorin-3F inhibits the growth and metastasis of colorectal carcinoma.

PURPOSE: To elucidate the role of Semaphorin-3F (SEMA3F), originally described as an axon guiding chemorepulsant implicated in nerve development, in the progression of colorectal carcinoma. EXPERIMENTAL DESIGN: SEMA3F and its receptor NRP2 were examined in 72 cases of human colorectal carcinoma specimens and cell lines LoVo, SW480, and SW620 with immunohistochemistry and Western blotting. SEMA3F mRNA expression in the frozen tissue specimens and cell lines was examined with quantitative reverse transcriptase-PCR. Confocal laser scanning microscopy was used for detection of cellular localization of the proteins by immunofluorescent staining. MTT assay, flow cytometry, cell adhesion and migration, and xenografts were used to evaluate biological significance of SEMA3F. RESULTS: SEMA3F was significantly reduced in colorectal carcinoma tissues and cell lines. Overexpression of SEMA3F resulted in reduced proliferation, adhesion to fibronectin, and migratory capability as well as reduced S-phase population and integrin αvß3 expression of SW480 colon cancer cells. In addition, SEMA3F-overexpressing cells exhibited diminished tumorigenesis when transplanted orthotopically in nude mice and reduced liver metastases. Moreover, transfection of siRNA targeting SEMA3F in colon cancer cells increased their tumorigenicity in vivo. CONCLUSIONS: Endogenous SEMA3F acts as a suppressor of the growth and metastasis of human colorectal cancer cells.

Intraparenchymal myofibromatosis of the brain in an adult: report of an unusual case.

An unusual case of intraparenchymal myofibromatosis of the brain occurring in a 29-year-old woman is described. Preoperative CT and MRI examinations revealed two well-circumscribed nodular masses localized in the wall of the left lateral ventricle and right temporal lobe, respectively. Both masses were completely resected, and the patient remains disease-free 2 years post-surgery. Histopathologically, the lesions were characterized by stratification. From outer to inner, there was a reactive glial component, lamellated well-differentiated muscle-like cells, densely compact collagen fibers and cellular tumor with nodular and hemangiopericytoma-like patterns, respectively. The myofibroblastic nature of this tumor was verified by immunohistochemical staining and ultrastructural analysis. Intraparenchymal myofibromatosis may be confused with, and should be distinguished from, meningioma, myopericytoma, solitary fibrous tumor, leiomyoma and inflammatory myofibroblastic tumor for accurate diagnosis and optimal treatment.

Extranodal follicular dendritic cell sarcoma of the pharyngeal region: a potential diagnostic pitfall, with literature review.

Extranodal follicular dendritic cell sarcoma (FDCS) of the pharyngeal region is a rare malignant tumor recognized in recent years, with approximately 37 cases so far reported in the literature. It is often not considered at the initial evaluation and may be misdiagnosed in a small biopsy specimen. We report 4 cases of extranodal FDCS, 2 cases in the nasopharynx that were diagnosed as undifferentiated carcinomas because they were characterized by syncytial epithelial cells with sheet or nest-like distribution and 2 cases in the tonsil and soft palate that were characterized by vaguely concentric whorls consisting of spindle to ovoid cells. The latter case was diagnosed as ectopic meningioma. The analysis of all cases from the literature and ours shows that 58% (21/36) of the cases are misdiagnosed initially, often as undifferentiated carcinoma or meningioma, which the differential diagnoses should be mostly focused on. With a median follow-up of 27 months, the recurrence, metastasis, and mortality rates are 23%, 21%, and 3%, respectively, suggesting that extranodal FDCS of the pharyngeal region remains a low-grade sarcoma. Radical surgery is recommended, whereas there is no evidence to support adjuvant therapy.

Isolation and enrichment of human genomic CpG islands by methylation-sensitive mirror orientation selection.

CpG islands (CGIs) in human genomic DNA are GC-rich fragments whose aberrant methylation is associated with human disease development. In the current study, methylation-sensitive mirror orientation selection (MS-MOS) was developed to efficiently isolate and enrich unmethylated CGIs from human genomic DNA. The unmethylated CGIs prepared by the MS-MOS procedure subsequently were used to construct a CGI library. Then the sequence characteristics of cloned inserts of the library were analyzed by bioinformatics tools, and the methylation status of CGI clones was analyzed by HpaII PCR. The results showed that the MS-MOS method could be used to isolate up to 0.001% of differentially existed unmethylated DNA fragments in two complex genomic DNA. In the CGI library, 34.1% of clones had insert sequences satisfying the minimal criteria for CGIs. Excluding duplicates, 22.0% of the 80,000 clones were unique CGI clones, representing 60% of all the predicted CGIs (about 29,000) in human genomic DNA, and most or all of the CGI clones were unmethylated in human normal cell DNA based on the HpaII PCR analysis results of randomly selected CGI clones. In conclusion, MS-MOS was an efficient way to isolate and enrich human genomic CGIs. The method has powerful potential application in the comprehensive identification of aberrantly methylated CGIs associated with human tumorigenesis to improve understanding of the epigenetic mechanisms involved.

[Characteristic and clinicopathologic significance of lymphangiogenesis in colorectal cancer].

OBJECTIVE: To investigate the distribution patterns and proliferative activity of lymphatic vessels in colorectal carcinomas (CRC) and their relationship with tumor metastasis and disease prognosis. METHODS: The microlymphatic density (MLD) and microvascular density in tumoral and non-tumoral areas of 96 cases of CRC were evaluated by immunohistochemistry, using monoclonal antibodies for podoplanin and CD34 respectively. The Ki-67 expression of the lymphatic and blood vessels was detected by double-labeling immunohistochemistry. The relationship between MLD and clinicopathologic features and prognosis was analyzed. RESULTS: The lymph vessels at central and superficia1 portions of CRC often had a reticular architecture with numerous tiny and ill-defined lumina, while those at the tumor borders had large and open lumina. The MLD at tumor borders (51.2 +/- 25.5) was significantly higher than that in normal colorectal mucosa (29.4 +/- 9.0) and other portions of CRC (P < 0.01). The Ki-67 labeling index of the lymphatic lining cells at tumor borders (0.23 +/- 0.17) was significantly higher than that in other portions of CRC (P < 0.05). The MLD significantly correlated with lymphatic involvement by tumor cells, regional lymph node metastasis and distant metastasis (P < 0.01). The 5-year survival rate was also significantly lower in patients with high MLD (P < 0.05). CONCLUSIONS: Neolymphatic vessels are commonly seen in CRC, especially at tumor borders. High MLD at tumor borders is associated with metastasis. The detection of MLD at tumor borders may thus be useful in predicting lymph node metastasis and prognosis in patients with CPC.