[Grey zone lymphoma with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: clinicopathologic characterization of 16 cases showing different patterns].

OBJECTIVE: To profile the clinicopathologic features of a series of grey zone lymphoma (GZL) cases with hybrid features of diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (CHL), with a purpose to gain an in-depth understanding of the borderline B-cell neoplasm. METHODS: The clinical, morphologic and immunophenotyical characteristics of 16 cases were retrospectively analyzed. RESULTS: The patients were mostly male adults, with a male to female ratio of 1.7: 1.0 and a mean age of 40.2 years. Eight patients presented with peripheral nodal lesions and five cases with mediastinal involvement. Histologically and immunophenotypically, the 16 cases were classified into three sub-categories. In 4 cases, the morphologic features resembled CHL more closely, but the neoplastic cells showed uniform and intense positive staining of CD20 (pattern 1). Although the initial impression of the other 8 cases was that of DLBCL, the expression levels of CD20 and PAX5 were variable, and CD30 or CD15 was positive (pattern 2). A characteristic feature of pattern 3, observed in the remaining 4 cases, demonstrated a broad spectrum of morphology with hybrid features of both CHL and DLBCL. The neoplastic cells in pattern 3 were positive for CD20, CD30 and CD15. EBV-LMP1 was detected in 6 of the 11 tested cases. Clinically, most patients with GZL seemed insensitive to immuno-chemotherapy of the R-CHOP regimen. CONCLUSIONS: The diagnostic criteria for GZL with features intermediate between DLBCL and CHL is proposed by the three histologic patterns commonly seen in these lesions. Cases presented with peripheral lesions might differ from those with mediastinal presentation pathologically. At current time, there is no effective treatment for these borderline B-cell lymphomas and the prognosis is poor.

[Immunohistochemical classification and prognosis of diffuse large B-cell lymphoma in China].

OBJECTIVE: To study the immunohistochemical classification and prognosis of diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 148 cases of DLBCL were classified into germinal center B-cell-like (GCB) and non-GCB/activated B-cell-like (ABC) subtypes by Hans, Choi and Tally immunohistochemical stain algorithms. The clinical features and survival data of GCB and non-GCB/ABC subtypes were compared. Multivariate analysis about clinical features and results of immunohistochemical stain algorithms was carried out by using Cox regression, with overall survival as the outcome. RESULTS: The prevalence of GCB subtype was significantly lower than that of non-GCB/ABC subtype, as classified by whichever algorithms in the 148 DLBCL cases studied. The prevalence of GCB subtype by Tally algorithm was lowest. The prevalence of GCB subtype (19 cases, 16.7%) was also significantly lower than non-GCB/ABC subtype (95 cases, 83.3%; P = 0.000 1) in the 114 (77.0%) concordant cases by the three algorithms. There was no difference between GCB and non-GCB/ABC subtypes by the three algorithms in five-year overall survival rate and survival curve of the 80 DLBCL patients with follow-up data available (P > 0.05). Primary gastric DLBCL tended to show a higher prevalence of GCB subtype, a better five-year overall survival rate and survival curve than the other groups. Multivariate analysis showed that patient age (HR = 1.036, P = 0.001) and tumor stage (HR = 1.997, P = 0) were also significantly adverse predictors of overall survival. CONCLUSION: The Hans, Choi and Tally immunohistochemical stain algorithms cannot effectively classify Chinese DLBCL into different prognostic subtypes. Primary gastric DLBCL has different immunophenotype and outcome, as compared with DLCBL in other sites.

Two microRNA panels to discriminate three subtypes of lung carcinoma in bronchial brushing specimens.

RATIONALE: Effective treatment for lung cancer requires accuracy in subclassification of carcinoma subtypes. OBJECTIVES: To identify microRNAs in bronchial brushing specimens for discriminating small cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC) and for further differentiating squamous cell carcinoma (SQ) from adenocarcinoma (AC). METHODS: Microarrays were used to screen 723 microRNAs in laser-captured, microdissected cancer cells from 82 snap-frozen surgical lung specimens. Quantitative reverse-transcriptase polymerase chain reaction was performed on 153 macrodissected formalin-fixed, paraffin-embedded (FFPE) surgical lung specimens to evaluate seven microRNA candidates discovered from microarrays. Two microRNA panels were constructed on the basis of a training cohort (n = 85) and validated using an independent cohort (n = 68). The microRNA panels were applied as differentiators of SCLC from NSCLC and of SQ from AC in 207 bronchial brushing specimens. MEASUREMENTS AND MAIN RESULTS: Two microRNA panels yielded high diagnostic accuracy in discriminating SCLC from NSCLC (miR-29a and miR-375; area under the curve [AUC], 0.991 and 0.982 for training and validation data set, respectively) and in differentiating SQ from AC (miR-205 and miR-34a; AUC, 0.977 and 0.982 for training and validation data set, respectively) in FFPE surgical lung specimens. Moreover, the microRNA panels accurately differentiated SCLC from NSCLC (AUC, 0.947) and SQ from AC (AUC, 0.962) in bronchial brushing specimens. CONCLUSIONS: We found two microRNA panels that accurately discriminated between the three subtypes of lung carcinoma in bronchial brushing specimens. The identified microRNA panels may have considerable clinical value in differential diagnosis and optimizing treatment strategies based on lung cancer subtypes.

[Screening of differentially expressed microRNAs in borderline and malignant gastrointestinal stromal tumors].

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) have a broad spectrum of biological behaviors ranging from benign, borderline and malignant. This study aimed to screen differentially expressed microRNAs (miRNAs) between malignant and borderline GISTs and to investigate the potential role of miRNAs in the malignant transformation of GISTs. METHODS: Six GIST samples including borderline tumors (n = 3) and malignant tumors (n = 3) were collected based on the clinical and pathological characteristics. Total RNA was extracted, followed by miRNA microarray analysis to screen the differentially expressed miRNAs. The most significantly expressed 4 miRNAs were then chosen for further validation by real-time PCR in 22 additional GIST samples. RESULTS: Direct comparison of malignant group versus borderline group revealed 14 significantly and differentially expressed miRNAs (P < 0.05, with a fold change of < 0.5 or > 2). Five miRNAs were up-regulated and nine were down-regulated in the malignant group. Four miRNAs (miR-221, miR-135b, miR-675(*) and miR-218) were most significantly and differentially expressed between the two groups. The differential expression of 2 miRNAs (miR-221 and miR-675(*)) were subsequently confirmed with good concordance by real-time PCR. CONCLUSIONS: The differential miRNA expression profiles between two groups are revealed by miRNA microarray assay, and confirmed by real-time PCR. Among differentially expressed miRNAs, miR-221 and miR-675(*) might be related to the malignant transformation of GISTs, and have a potential value in predicting biological behavior of GISTs.

IRF4 rearrangement may predict favorable prognosis in children and young adults with primary head and neck large B-cell lymphoma.

PURPOSE: Large B-cell lymphoma with IRF4 rearrangement (LBCL, IRF4+) has been recently recognized as a specific entity that is frequently associated with young age and favorable prognosis. However, whether the good outcome of the disease is due to IRF4+ or other factors remains obscure. We thus analyzed 100 young patients with primary head and neck LBCL to see the clinicopathologic correlates of IRF4+. METHODS: The histopathology, immunophenotype, IRF4 status of the tumors, and clinical data were reviewed. RESULTS: Twenty-one tumors were diagnosed as LBCL, IRF4+, which were more frequently associated with a follicular growth pattern, medium-sized blastoid cytology, germinal center B-cell-like, and CD5+ phenotype, compared with IRF4- ones. While most of the patients received chemotherapy with or without radiation, eight IRF4+ patients received mere surgical resection of the tumor and exhibited excellent outcome. IRF4+ cases featured a significantly higher complete remission rate, and better survivals compared with IRF4- ones. Multivariate analysis confirmed IRF4+ correlates with a better survival. CONCLUSION: Our work confirmed the unique clinicopathologic features of LBCL, IRF4+, and disclosed for the first time the independent favorable prognostic impact of IRF4+. These findings may further unravel the heterogeneity of LBCL occurring in youth, and aid in risk stratification and tailoring the therapeutic strategy.

A20 inactivation in ocular adnexal MALT lymphoma.

Recent studies showed A20 inactivation by deletion, mutation and promoter methylation in ocular adnexal mucosa-associated lymphoid tissue lymphoma. However, the incidences of A20 abnormalities and their clinical impact remain for the most part unknown. It is also unknown whether ABIN-1 and ABIN-2, the components of the A20 NF-κB inhibitor complex, are inactivated by genetic changes in ocular adnexal mucosa-associated lymphoid tissue lymphoma. A total of 105 cases were investigated for A20 mutation/deletion, ABIN-1/2 mutation, MALT1 and IGH involved translocation. Somatic mutation was seen frequently in A20 (28.6%) but rarely in ABIN-1 (1%) and ABIN-2 (1%). A20 mutations were significantly associated with A20 heterozygous deletion, and both were mutually exclusive from the MALT1 or IGH involved translocations. A20 mutation/deletion was also significantly associated with increased expression of the NF-κB target genes CCR2, TLR6 and BCL2. The cases with A20 mutation/deletion required significantly higher radiation dosages to achieve complete remission than those without these abnormalities.

Myoepithelial carcinoma: first case reported in the trachea.

Myoepithelial carcinoma displaying exclusively myoepithelial differentiation mainly occurs in the salivary glands and breasts, and is considered extremely rare in the trachea. We present the first documented case of a primary myoepithelial carcinoma in the trachea. The patient was a 23-year-old man who presented with shortness of breath and cough for four months. Bronchoscopy and computed tomographic (CT) scan revealed an intraluminal mass in the trachea. A standard sleeve of trachea resection with end-to-end reconstruction was performed. The tumor was mainly composed of spindle cells and epithelioid cells which exhibited relatively uniform nuclei with finely distributed chromatin and inconspicuous nucleoli, suggesting that it may arise from benign myoepithelioma. Moreover, the tumor displayed marked cytologic atypia and an infiltrative tumor border in some areas, suggesting that it was a malignant tumor. Immunohistochemically, the tumor cells were diffusely positive for AE1/AE3, Vimentin and myoepithelial makers (Calponin, P63 and GFAP). The patient's postoperative course was uneventful with no evidence of recurrence at six months after surgery.

[Cytogenetic profiles of follicular lymphoma].

OBJECTIVE: To study the cytogenetic profiles of follicular lymphoma (FL) in Chinese patients. METHODS: Conventional karyotype in 57 FL patients from Shanghai area was analyzed. Fluorescence in-situ hybridization (FISH) for t(14;18) and Bcl-6 and IgH gene rearrangement was performed in these cases. RESULTS: The most frequent breakpoints (frequency > or = 10% ) of the 57 FL cases were at band 14q32 (68.4%), 18q21 (38.6%), 3q27 (21.1%), 1q10 (15.8%) and 1q21 (12.3%). Nineteen (33.3%) of the 57 cases had t(14;18). The breakpoint of 18q21 and t(14;18) were more frequent in FL grade 1-2 and less frequent in FL grade 3 (57.6% vs. 12.5%; 54.5% vs. 4.2%, P < 0.05), whereas the 3q27/Bcl-6 rearrangement was more frequent in FL grade 3 and less frequent in FL grade 1-2 (37.5% vs. 9.1% , P < 0.05). The cohort of FL was more frequent in gains of chromosomes X, 1q, 5, 6p, 7 and 12q and losses of chromosomes 1p, 6p and 14q32. Gain of 18q was more frequent in FL grade 1-2 than in FL grade 3 (P < 0.05). Loss of 14q32 was more frequent in t(14;18) negative FL than in t(14;18) positive FL (P < 0.05). CONCLUSIONS: Compared with the data of Western patients reported in the literature, Chinese FL cases had distinct cytogenetic profiles from Western FL cases that the t(14;18) is less frequent and the gain of 1q is more frequent in Chinese FL cases, which are more significant in high grade FL.

Chondroblastoma in the long bone diaphysis: a report of two cases with literature review.

To investigate the clinical characteristics of chondroblastoma with an emphasis on lesions located in the long bone diaphysis, we reviewed the clinical data of 7 patients with histologically proven chondroblastoma treated in Tianjin Medical University Cancer Hospital and Fudan University Cancer Hospital between January 1995 and May 2009. There were two rare cases of chondroblastoma in the long bone diaphysis. One patient with a lesion in the tibial diaphysis underwent intralesional curettage and bone grafting, and the postoperative bone function was measured as excellent according to the Enneking scoring system. The patient was still alive upon follow-up at 60 months. The other patient with a lesion in the humeral diaphysis underwent resection, and the postoperative bone function was excellent at 48 months, at which there was no evidence of recurrence or metastasis. Thus, except for the distinctive site of the long bone diaphysis, which made diagnosis difficult, the patients' ages, symptoms, X-ray and CT images, treatment, and prognosis were in accordance with typical lesions in the epiphysis and metaphysis. The diagnosis of chondroblastoma in the long bone diaphysis significantly depends on histopathologic characteristics.

[Study on clinicopathologic grading system and prognosis of primary hepatic neuroendocrine neoplasms].

OBJECTIVE: To study the clinicopathologic features, criteria for grading and prognostic factors of primary hepatic neuroendocrine neoplasms. METHODS: Thirty-five cases of primary hepatic neuroendocrine neoplasm were retrieved from the archival files over a period of 11 years (with 32 cases having integrated data). According to the 2010 WHO classification of tumors of the digestive system, the cases were categorized into three groups: neuroendocrine tumor grade 1 (NET G1), neuroendocrine tumor grade 2 (NET G2) and neuroendocrine carcinoma (NEC). Statistical correlation between various histologic parameters and survival data was analyzed. RESULTS: Statistical analysis showed significant difference between NET [G1 (1 case)/G2 (14 cases)] and NEC (17 cases) groups in terms of tumor differentiation, necrosis, nuclear atypia, mitotic count and Ki-67 proliferative index (P < 0.05). There was no statistically significant difference in tumor size, growth pattern and presence of vascular tumor emboli (P > 0.05). The survival rate of patients correlated with tumor differentiation, growth pattern, necrosis, nuclear atypia, mitotic count and proliferative index (P < 0.05). There was no statistically significant difference between patient survival and tumor size or presence of vascular tumor emboli (P > 0.05). CONCLUSIONS: The subdivision of primary hepatic neuroendocrine neoplasm according to the 2010 WHO classification of tumors of the digestive system helps to evaluate the malignant potential and prognosis of the tumors. Prognostically useful histologic parameters include tumor differentiation, growth pattern, necrosis, nuclear atypia, mitotic count and proliferative index.

[Staging and histologic grading of gastrointestinal stromal tumors].

OBJECTIVE: To investigate the clinical stage and histological grade of gastrointestinal stromal tumors. METHODS: Twelve clinical and pathological parameters were assessed in 613 patients with follow-up information. These parameters were classified into two gross spread parameters including liver metastasis and peritoneal dissemination, five microscopic spread parameters including lymph node metastasis, vascular, fat, nerve and mucosal infiltration, and five histological parameters including mitotic count ≥ 10 per 50 high-power fields, muscularis propria infiltration, coagulative necrosis, perivascular pattern and severe nuclear atypia. RESULTS: The accumulated 5-year disease-free survival (DFS) and overall survival (OS) of 293 patients without any of these predictive parameters of malignancy were 99.3% and 100.0%, respectively. They were regarded as nonmalignant and further evaluations on the stage and grade of these tumors were not performed. At least one and at most seven predictive parameters of malignancy were identified in 320 patients. For these patients, the accumulated 5-year DFS and OS rates were 43.9% (mean 6.7 years) and 59.7% (mean 9.3 years), respectively. The DFS showed significant difference between patients with and without gross spread (P < 0.01), with and without microscopic spread (P = 0.001). DFS and OS were associated with the number of predictive parameters of malignancy in patients without gross spread (P < 0.01 for both DFS and OS), but not in patients with gross spread (P = 0.882 and 0.441, respectively). CONCLUSIONS: Malignant GIST could be divided into clinical stages I and II based on the absence and presence of gross spread, respectively. The degree of malignancy of patients in clinical stage I could be graded according to the number of predictive parameters of malignancy. Patients in clinical stage II were of the highest degree of malignancy regardless of the number of parameters. The staging and grading of gastrointestinal stromal tumors in this study are strongly associated with prognosis.

[TMPRSS2-ERG gene fusion in metastatic prostate cancers: a study of fine needle aspiration specimens].

OBJECTIVE: To investigate diagnostic values of the detection of TMPRSS2-ERG gene fusion in metastatic prostate cancer. METHODS: A total of 32 fine needle aspiration (FNA) specimens of metastatic prostate carcinomas were retrieved from the pathology files at MD Anderson Cancer Center. The metastatic sites included the pelvic and remote lymph nodes, liver, bone, and thyroid gland. Immunohistochemical staining for PSA, PAP, synaptophysin, chromogranin A was performed. TMPRSS2-ERG gene fusion was evaluated on sections of cell blocks by fluorescence in situ hybridization (FISH) using ERG gene break-apart probes. RESULTS: The mean age of the patients was 67 years. Twenty-six patients had a previous history of prostatic adenocarcinoma, while 6 patients presented initially with metastasis. In 11 patients, the metastatic lesions showed characteristic features of small cell carcinoma (SCC) and were positive for synaptophysin (9/9), chromogranin A (7/8), but negative for prostatic specific antigen (7/7). FISH analysis demonstrated a rearrangement of ERG gene in 10 of 32 cases (31.3%), and the rearrangement was associated with deletion of the 5' ERG gene in 6 cases. In addition, the copy number of ERG rearrangement gene locus was increased in 8 cases. Among the 11 cases with SCC features, a rearrangement of ERG gene was present in 5 cases, of which a deletion of the 5' ERG gene and increased copy number were seen in 3 cases. CONCLUSIONS: TMPRSS2-ERG gene fusion can be evaluated in FNA specimens of metastatic prostate cancer. Metastatic prostate cancers have a high prevalence of TMPRSS2-ERG gene fusion along with a frequent copy number increase of ERG gene. TMPRSS2-ERG gene fusion persists in metastatic prostate cancers and even in those with poorly differentiated SCC features. Therefore, an identification of the TMPRSS2-ERG gene fusion may be used to establish the prostatic origin of metastasis.

[Follicular variant of peripheral T-cell lymphoma: a clinicopathologic and genetic study of 2 cases].

OBJECTIVE: To observe the clinicopathologic and genetic features of follicular variant of peripheral T-cell lymphoma (FV-PTCL), with particular attention to the relationship of this type of lymphoma with angioimmunoblastic T-cell lymphoma (AITL). METHODS: The clinical data, hematoxylin and eosin-stained sections of lymph node biopsies from 2 FV-PTCL cases were reviewed. Immunohistochemical phenotyping and detection of EBV-encoded RNAs (EBER) through in situ hybridization (ISH) were performed. The EnVision two-step method was used for all antibodies except CXCL13 (by using three-step streptavidin immunoperoxidase method). Analysis of clonality and ITK/SYK gene rearrangement was conducted using PCR and RT-PCR assays, respectively. RESULTS: Clinically, the two patients presented with superficial lymphadenopathy similarly. Histologically, case 1 showed a follicular/nodular lymphoid proliferation without marked germinal centers. The neoplastic cells comprised mainly medium sized cells with abundant, sometimes clear cytoplasms. Similar histologic findings were seen in case 2 in addition to a concurrent component mimicking typical AITL noticed. Of both cases, the neoplastic cells showed positive reactivity to CD3, CD4, CD10, PD1, and CXCL13. Positive hybridization signals for EBER were only seen in case 2, and double stains demonstrated that those EBV-positive cells were mostly the reactive transformed B-cells. Monoclonal T-cell proliferation was proved by the rearranged TCR gene detection in both cases. Neither of the current cases expressed ITK/SYK fusion transcripts. CONCLUSION: FV-PTCL shows the similar or overlapped morphological and immunophenotypic features to those of AITL, possibly suggesting the presence of a potential relationship between these two types of lymphomas.

[Urothelial hyperplastic lesion with endophytic growth pattern: a clinicopathologic study].

OBJECTIVE: To study the clinicopathologic features of urothelial hyperplastic lesion with an endophytic growth pattern and the role of immunohistochemistry and multitargeted fluorescence in situ hybridization (FISH) in the differential diagnosis. METHODS: Forty-one cases of urothelial lesions exhibiting endophytic growth patterns were reviewed and reclassified as inverted papilloma, urothelial carcinoma with an endophytic growth pattern, and florid von Brunn nest. The gains of chromosomes 3, 7, and 17 and loss of 9p21 was detected by FISH, and performed immunohistochemical staining for CK20, p53, and Ki-67. Follow-up data of 12 cases were obtained. RESULTS: (1) Twelve inverted papillomas sized 1.2 cm in average, consisted of anastomosing cords and nests with uniform width distribution involving the lamina propria, the central portion contained streaming cells with squamous metaplasia, and the periphery showed palisading. No or rare atypia and mitosis were found. Focal exophytic papillary component lined by less than 6 layers of normal urothelium were observed in 4 cases. (2) Twenty-four urothelial carcinomas with an endophytic growth pattern sized 2.1 cm in average, demonstrated the similar architecture with inverted papilloma, but exhibited thick columns and variable thickness of the cords, irregular size and shape of large nests with transition into solids. Mild to moderate cytologic atypia was shown, and mitotic figures ranged 1 to 8 per 10 HPFs. Exophytic papillary component was not observed in 3 cases, but the superficial urothelium showed dysplasia, while coexisted exophytic component in other cases was associated with low malignant potential or low grade tumor. (3) Five florid von Brunn nests sized 0.9 cm in average, had normal or hyperplastic urothelium, variable nests with cysts compacted in lamina propria, no cytologic atypia and mitosis. Twenty-one of 24 (79.1%) urothelial carcinomas with an endophytic growth pattern displayed abnormally positive results by multitargeted FISH, whereas all inverted papillomas and florid von Brunn nests were negative. Immunohistochemically, CK20 was weakly positive in 2 cases of urothelial carcinoma with an endophytic growth pattern, and negative in all inverted papillomas and florid von Brunn nests. p53 weakly stained 5% to 50% nuclei of the tumor cells in 16 cases of urothelial carcinomas with an endophytic growth pattern and 1 inverted papilloma. 1%-5% tumor cells expressed Ki-67 in urothelial carcinoma with an endophytic growth pattern, and less than 1% in inverted papilloma and florid von Brunn nests. Follow-up study revealed that 2 cases of urothelial carcinoma with an endophytic growth pattern had developed invasive carcinoma, underwent cystectomy, and metastasized remotely. No recurrence occurred in cases of inverted papilloma. CONCLUSIONS: Benign and malignant urothelial lesions with an endophytic growth pattern present histologic overlapping. Urothelial carcinoma with an endophytic growth pattern displays unique characteristics in morphology and immunohistochemistry. Multitargeted FISH analysis is helpful in the differential diagnosis.

The clinicopathological relevance of uniform CD56 expression in anaplastic large cell lymphoma: a retrospective analysis of 18 cases.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) with uniform CD56 expression is a rare condition, that has been described in limited literature, and its clinicopathological features have not yet been well illustrated. The aim of our study was to fully investigate the clinical, histological, immunohistochemical and molecular features of CD56+ ALCL. METHODS: The clinical and histological characteristics of CD56+ ALCL cases were retrospectively evaluated. The immunohistochemical phenotype, status of Epstein-Barr virus (EBV) and T-cell receptor (TCR) gene rearrangement were examined. Overall survival was also analyzed. RESULTS: Eighteen (5.8%) cases with diffuse CD56 expression were identified out of 313 archived ALCL cases with CD56 test. CD56 expression was significantly higher in ALK+ systemic ALCLs (sALCLs) (13/64, 20.3%) than in ALK- sALCLs (3/101, 3.0%) (p < 0.001) as well as primary cutaneous ALCLs (2/148, 1.4%) (p < 0.001). Regarding the CD56+ ALK+ sALCLs, the median age was 20 years (range, 8-60 years) with a male-to-female ratio of 2.3:1, and these cases more frequently affected extranodal sites (11/38, 28.9%) rather than lymph nodes (2/26, 7.7%) (p = 0.038). Eleven (84.6%) cases presented with stage I-II diseases, which was significantly more than their CD56- ALK+ counterparts (45.5%) (p = 0.015). Histologically, 2 ALK+ cases were of small cell variant and all the others displayed characteristic morphology of classic ALCL. Regarding the immunophenotype, both CD30 and CD56 were diffusely positive in all cases. CD3, CD43, anaplastic lymphoma kinase-1 (ALK1), TIA-1, EMA expression was observed in 30.8% (4/13), 90.9% (10/11), 100% (13/13), 100% (9/9), and 80.0% (8/10) cases, respectively. EBV infection was consistently absent. Monoclonal TCR gene rearrangement was found in 100% (5/5) of investigated ALK+ cases. Chemotherapy with a CHOP regimen was most frequently employed. The 3-year overall survival (OS) rate for CD56+ ALK+ patients was 92.0%, compared with 73.0% for their CD56- counterparts, but there was no significant difference in OS between the two groups (p = 0.264). CONCLUSIONS: Uniform CD56 expression is an unexpected condition in ALCL. Of ALK+ ALCLs, CD56 expression correlated with a high frequency of early stage and an extranodal predominance. It is of great importance to raise awareness of this condition and familiarity with its characteristic features to avoid diagnostic and therapeutic pitfalls. Further investigations are warranted for a better understanding of this unusual phenotype and the significance of CD56 expression in ALCL.

[Low-grade central osteosarcoma: a clinicopathologic analysis of nine cases].

OBJECTIVE: to study the clinicopathologic features and differential diagnosis of low-grade central osteosarcoma (LGCOS). METHODS: nine cases of LGCOS were retrieved from the archival consultation files. The clinical, radiologic and pathologic features were analyzed, with literature review. RESULTS: the mean age of the patients was 31 years. The male-to-female ratio was 3:6. All of the patients presented with painful mass and/or swelling. The sites of involvement included thigh (n = 4), tibia (n = 1), fibula (n = 1), cervical vertebra (n = 1), lumbar vertebra (n = 1) and maxilla (n = 1). Radiologic examination showed mixed lytic/blastic lesions with soft tissue shadow in 5 cases and associated periosteal reaction in 3 cases. The tumors were treated by surgical excision, with no adjuvant therapy given. The duration of follow up ranged from 2 to 43 months. Four cases had recurrence which occurred at 8 to 25 months after the operation. Gross examination showed that the tumors were fragmented on submission in 5 cases and en bloc in 4 cases. They had solid and firm cut surface, with various degree of grittiness. Histologically, LGCOS was characterized by the presence of hypocellular fibroblastic stroma associated with focal osteoid production. The spindly tumor cells showed mild degree of nuclear pleomorphism, with occasional mitotic figures demonstrated in all of the 9 cases. The newly formed neoplastic woven bone did not have any osteoblastic rimming. The bony trabeculae were slender and seam-like. Parallel arrays of woven bone were seen in 6 cases. Some of the bony trabeculae appeared irregularly branched and curved. The tumor cells permeated adjoining pre-existing bony trabeculae and bone marrow in all cases. Three cases also showed soft tissue involvement. CONCLUSIONS: LGCOS often posses important diagnostic pitfalls due to the relatively bland-looking tumor cell morphology and associated large woven or longitudinal seams of lamellar-like bone. Thorough understanding of the histologic features, when coupled with clinical and radiologic findings, are essential in arriving at a correct diagnosis.

[Angiomatoid fibrous histiocytoma: report of 5 cases with review of literature].

OBJECTIVE: To study the clinicopathologic features, immunophenotype and differential diagnosis of angiomatoid fibrous histiocytoma (AFH). METHODS: The clinicopathologic features of 5 cases of AFH were analyzed. Immunohistochemical study was carried out and the literature was reviewed. RESULTS: There were a total of 3 males and 2 females. The average age of patients was 21.4 years old. The average duration of symptoms was 13 months. The patients primarily presented with a slowly enlarging painless deep dermal or subcutaneous mass. The mass was located in the head and neck region in 3 cases, elbow in 1 case and foot in 1 case. The patients underwent complete resection of the tumor, with no adjuvant chemotherapy and/or radiotherapy given. During a period of follow up for 10 to 29 months, all of them had no recurrence or distant metastasis. Gross examination showed that the tumor was well-circumscribed and had a grey-colored cut surface, with focal hemorrhagic cystic changes. The average tumor dimension was 1.9 cm. Histologically, the tumor was composed of histiocytoid or spindly cells arranged in nodular pattern. Fibrillary neuropil-type intercellular material was identified in all cases and a fibrous pseudocapsule surrounded by lymphocytes and plasma cells was demonstrated in 3 cases. Immunohistochemical study showed that all of them were positive for vimentin and negative for S-100 protein, pan-cytokeratin, CD34 and CD31. Three of the cases expressed desmin and CD68. Two cases were epithelial membrane antigen and CD99-positive. CONCLUSIONS: AFH is a rare tumor of intermediate malignant potential. Definitive diagnosis requires thorough histologic examination and clinical correlation. Immunohistochemistry is also helpful for diagnosis and differential diagnosis. Wide local excision with post-operative follow up is the main modality of treatment.

[Prevalence of germinal center B-cell-like and non-germinal center B-cell-like types of diffuse large B-cell lymphoma in Shanghai, China].

OBJECTIVE: To study the prevalence of germinal center B-cell-like (GCB) and non-GCB-like types of diffuse large B-cell lymphoma (DLBCL) in Chinese patients. METHODS: Immunohistochemical study for CD10, bcl-6, MUM1, GCET1 and FOXP1 was performed on 124 cases of DLBCL from Shanghai, China. The Hans algorithm and Choi algorithm were applied to classify DLBCL into GCB and non-GCB-like types. Fluorescence in-situ hybridization (FISH) for t (14;18) and bcl-6 gene rearrangement was also carried out on 118 cases. RESULTS: Of the 124 DLBCL cases studied, 27 cases (22%) showed a GCB-like type and 97 cases (78%) showed a non-GCB-like type, when using Hans algorithm. On the other hand, 34 cases (27%) belonged to GCB-like type and 90 cases (73%) belonged to non-GCB-like type when applying Choi algorithm. The prevalence of GCB-like type was significantly lower than that of non-GCB-like type (P=0.0001). Only four cases (3%) were positive for t (14;18), and three of them were classified as GCB-like type. bcl-6 rearrangement was found in 46 cases (39%) and more frequently encountered in the GCB-like type. There is no relationship between bcl-6 gene rearrangement and bcl-6 protein expression. CONCLUSIONS: The GCB-like type of DLBCL is significantly less common than non-GCB-like type in Chinese population. This phenomenon is possibly related to the low frequency of t (14;18).

[Clinicopathologic study of giant cell angioblastoma].

OBJECTIVE: to study the clinicopathological features, imaging characteristics, immunophenotypes and differential diagnosis of giant cell angioblastoma (GCAB). METHODS: a case of GCAB in the left middle-upper tibia and fibula was studied by light microscopy, X-ray and CT imaging, immunohistochemistry. RESULTS: X-ray and CT imaging showed a clearer lesion in the left middle-upper tibia than in the ipsilateral fibula with enlarged ostealleosis and increased inhomogeneously medullary cavity density, irregular thickening of cortical bone, local cortical default at the inner edge, soft tissue swelling around the abnormal bone. Histologically, tumor tissue was located between the bone trabeculae by nodular, linear and plexiform aggregates of oval-to-spindle cells, large mononucleate cells and multinucleate giant cells with prominent nucleoli and abundant granular eosinophilic cytoplasm. Some aggregates had uncentain amount of discernible lumens, either empty or containing few erythrocytes. A concentric arrangement of oval-to-spindle Cells around small-caliber vascular structures together with collagen fiber contributed to a so-called 'onion-skin' arrangement. The background showed a loose mesenchymal stroma formed of some inconspicuous spindle-fibroblast-like cells, stellate-shape mesenchymal cells, a moderate mononuclear inflammatory cell infiltrate and scattered mast cells. Immunophenotype showed the tumor cells and giant cells strongly positive for vimentin. A good many oval-to-spindle cells stained markedly for CD31 and CD34, but weakly for FVIII, while the giant cells are highlighted instead by CD68, occasionally, very few giant cells showed positive focally for FVIII, a-SMA decorated notedly the cells surrounding the endothelium-like cells but weakly positive in some other tumor cells. CONCLUSION: GCAB is a rare, locally infiltrative but slow growing neoplastic angiogenesis with unique morphological characteristics during infancy, which may occur not only in the skin, mucosa, subcutis and deep soft tissue but also in the bone.