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OBJECTIVE@#To investigate the value of using MDM2 amplification probe and DDIT3 dual-color, break-apart rearrangement probe fluorescence in situ hybridization (FISH) technique in the diagnosis of liposarcoma.@*METHODS@#In the study, 62 cases of liposarcoma diagnosed in Peking University First Hospital from January 2015 to December 2019 were analysed for clinicopathological information. Of these 62 cases of liposarcoma, all were analysed for MDM2 amplification and 48 cases were analysed for DDIT3 rearrangement using a FISH technique. Our study aimed to evaluate the status of MDM2 and DDIT3 by FISH in liposarcoma and correlate it with diagnosis of different subtypes of liposarcoma. The subtypes of liposarcoma were classified according to the FISH results, combined with the relevant clinicopathological features.@*RESULTS@#The patients aged 31-89 years (mean: 59 years) with a 1.75:1 male to female ratio. Histologically, there were 20 cases of atypical lipomatous tumour/well-differentiated liposarcoma (ALT/WDLPS), 26 cases of dedifferentiated liposarcoma (DDLPS), 13 myxoid liposarcoma (MLPS) and 3 pleomorphic liposarcoma (PLPS). Tumors with DDLPS (23/26) and WDLPS (8/20) were localized retroperitoneally, while both tumours of MLPS and PLPS were localized extra-retroperitoneally, and the difference of sites among the four subtypes of liposarcoma was statistically significant (P < 0.05). Histologically, varied mucoid matrix could be observed in the four subtypes of liposarcoma, and the difference was statistically significant (P < 0.05). MDM2 gene amplification was demonstrated in all cases of ALT/WDLPS and DDLPS (100%, 20/20 and 26/26 respectively); DDIT3 gene rearrangement was noted only in MLPS (100%, 13/13); most cases of DDLPS (96.2%, 25/26) and ALT/WDLPS (83.3%, 5/6, 6 cases selected for detection) demonstrated the picture of amplification of the DDIT3 telomeric tag. According to the instructions of DDIT3 break-apart rearrangement probe, the 5' telomere probe and 3' centromere probe spanned but did not cover the DDIT3 gene itself, on the contrary, the 5' telomere probe covered the CDK4 gene, while the DDIT3 and CDK4 gene were located adjacent to each other on chromosome, therefore, when the amplification signal appeared on the telomeric tag of the DDIT3 rearrangement probe, it indeed indicated the CDK4 gene amplification rather than the DDIT3 gene rearrangement. Then the 10 cases with DDIT3 telomeric tag amplification were selected for CDK4 and DDIT3 gene amplification probe FISH tests, and all the cases showed CDK4 gene amplification (100%, 10/10) and two of the 10 cases demonstrated co-amplification of CDK4 and DDIT3 (20%, 2/10); DDIT3 polysomy detected by DDIT3 gene rearrangement probe was found in 1 case of DDLPS and 2 cases of PLPS (66.7%, 2/3) with morphology of high-grade malignant tumour and poor prognosis.@*CONCLUSION@#Our results indicate that a diagnosis of different subtype liposarcoma could be confirmed based on the application of MDM2 and DDIT3 FISH, combined with clinicopathological findings. It is also noteworthy that atypical signals should be correctly interpreted to guide correct treatment of liposarcomas.
Subject(s)
Male , Female , Humans , In Situ Hybridization, Fluorescence/methods , Cyclin-Dependent Kinase 4/metabolism , Liposarcoma/pathology , Lipoma/pathology , Gene Amplification , Transcription Factor CHOP/genetics , Proto-Oncogene Proteins c-mdm2/metabolismABSTRACT
Introducción. La leucemia promielocítica aguda (LPA) es un subtipo poco frecuente de leucemia mieloide aguda (LMA), que se caracteriza por un comportamiento clínico particularmente agresivo, y en ausencia de tratamiento, su curso generalmente es fatal. El objetivo de este trabajo fue determinar las características clínicas y citogenéticas de una cohorte de pacientes con LPA, con la finalidad de evaluar su relación con las complicaciones, el pronóstico y el desenlace de estos pacientes. Metodología. Se realizó un estudio observacional, descriptivo, retrospectivo de los pacientes mayores de 15 años con diagnóstico de LPA, atendidos en el Hospital Universitario San Vicente Fundación, entre los años 2012 a 2020. Resultados. Un total de 32 pacientes fueron incluidos. La edad media del diagnóstico fue 37 años. El 84,4% de los pacientes tenía la traslocación (15;17) en el cariotipo, y el 93,75% tenían FISH positivo. El 12,5% de los casos tenían cariotipo complejo. La mortalidad en los primeros 30 días fue del 15,6%, siendo el sangrado la causa de muerte más frecuente. Todos los pacientes que sobrevivieron alcanzaron la remisión completa (84,3%). En un promedio de seguimiento de 24 meses, el 14,8% de los casos recayeron. En el análisis bivariado se encontró relación entre sexo masculino y tener cariotipo complejo (p=0,015). No se encontró relación entre cariotipo complejo y mortalidad temprana (p=0,358), tampoco entre cariotipo complejo y recaída (p=0,052). Conclusiones. Se presentan las características clínicas y citogenéticas de una cohorte de pacientes con LPA en Colombia. El sangrado en el sistema nervioso central fue la principal causa de mortalidad temprana, todos los pacientes que sobrevivieron alcanzaron la remisión completa con la terapia de inducción. Las tasas de mortalidad, remisión completa y recaída fueron similares a las reportadas por otras series latinoamericanas, pero inferiores a estudios provenientes de países europeos. Contrario a lo reportado en otros estudios, no se encontró relación entre el cariotipo complejo y la mortalidad temprana o recaída.
Introduction. Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia (AML), characterized by a particularly aggressive clinical behavior, that in the absence of treatment is usually fatal. The objective of this work was to determine the clinical and cytogenetic characteristics of a cohort of patients with APL, in order to evaluate their relationship with the outcome and prognosis of these patients. Methodology. An observational, descriptive, retrospective study of patients older than 15 years with a diagnosis of APL treated at the Hospital Universitario San Vicente Fundación, between 2012 and 2020, was carried out. Results. A total of 32 patients were included. The mean age at diagnosis was 37 years, 84.4% of the patients had the t(15;17) in the karyotype, and 93.75% had positive FISH. 12.5% of cases had a complex karyotype. Mortality in the first 30 days was 15.6%, with bleeding being the most common cause of death. All patients who survived achieved complete remission (84.3%). In an average follow-up of 24 months, 14.8% of cases relapsed. In the bivariate analysis, a relationship was found between the male sex and having a complex karyotype (p<0.015). No relationship was found between complex karyotype and early mortality (p=0.358), nor between complex karyotype and relapse (p=0.052). Conclusions. We present the clinical and cytogenetic characteristics of a cohort of patients with APL in Colombia. Central nervous system bleeding was the main cause of early mortality, with all surviving patients achieving complete remission on induction therapy. Mortality, complete remission and relapse rates were similar to those reported by other Latin American series, but lower than studies from European countries. Contrary to what has been reported in other studies, no relationship was found between complex karyotype and early mortality or relapse
Subject(s)
Leukemia, Promyelocytic, Acute , Tretinoin , Idarubicin , In Situ Hybridization, Fluorescence , Karyotype , Arsenic TrioxideABSTRACT
Objective:To explore the characteristics of Siewert classification and microsatellite instability(MSI) and HER2 expression in adenocarcinoma of esophagogastric junction (AEG).Methods:The clinicopathological data of gastric adenocarcinoma from May 2019 to November 2020 were retrospectively analyzed. The patients were divided into two groups: AEG group and non AEG group. The composition ratio of Siewert type of AEG was counted, and the relationship between tumor size and Siewert type was analyzed. The MSI status and HER2 expression status of AEG and non AEG were statistically compared. The measurement data of normal distribution were expressed as mean ± standard deviation( Mean± SD), the comparison between groups were by t test, the comparison of count data between groups were by Chi-square test. Results:A total of 328 consecutive cases of gastric adenocarcinoma were collected, including 242 cases of AEG and 86 cases of non AEG. The Siewert classification of AEG was mainly type Ⅱ (151 cases, 62.40%), followed by type Ⅲ (86 cases, 35.54%) and type Ⅰ (5 cases, 2.07%). The analysis of the relationship between the size of the tumor length and the number of Siewert type showed that the number of Siewert type Ⅱ cases decreased and the number of Siewert type Ⅲ cases increased with the increase of the tumor size. MSI status was detected non selectively in 192 cases of gastric adenocarcinoma (140 cases of AEG and 52 cases of non AEG). There were 12 cases of MSI (6.25%), 2 cases of MSI-H (1.04%) and 10 cases of MSI-L (5.21%). There was no significant difference in MSI ratio between AEG group and non AEG group ( P>0.05). All MSI cases were negative or weakly positive for PMS2. The expression of HER2 was detected by immunohistochemistry in 313 cases of gastric adenocarcinoma, except 15 cases of PTIS/T1a. There were 30 cases (9.58%) with HER2 expression 3+ . Thirty-two cases (10.22%) expressed HER2 (2+ ), of which 7 cases were detected by fluorescence in situ hybridization (FISH), and 3 cases were positive. The proportion of HER2 (3+ ) in AEG was significantly higher than that in non AEG group ( P<0.05). Conclusions:The main type of AEG was Siewert type Ⅱ. AEG may mostly occur between 1 cm above the esophagogastric junction and 2 cm below the esophagogastric junction; For endoscopic screening of early AEG, more attention should be paid to this area of stomach. Siewert type Ⅲ may be derived from the development of Siewert type Ⅱ. The incidence of microsatellite instability in gastric cancer is low. Compared with other gastric adenocarcinoma, AEG has no specificity in MSI. The MSI of AEG was mainly the expression defect of PMS2. Compared with other gastric adenocarcinoma, there are more HER2 overexpression in AEG.
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Objective:To investigate the application values of bone marrow morphology, bone marrow immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH) and cytogenetic testing in newly diagnosed multiple myeloma.Methods:A total of 280 patients with multiple myeloma who were newly diagnosed in Tianjin KingMed Diagnosis Center from September 2018 to August 2019 were collected. The bone marrow biopsy was carried out according to the routine method, and bone marrow morphology, bone marrow immunohistochemistry, flow cytometry immunophenotyping, FISH and cytogenetic testing were performed. The detection results of each method were compared.Results:In 280 patients, the bone marrow immunohistochemistry results showed that the median ratio of plasma cells was higher than those of bone marrow morphology (20 cases, 0.675 vs. 0.300) and flow cytometry (47 cases, 0.650 vs. 0.147), and the differences were statistically significant ( Z = -3.883, P < 0.01; Z = -5.947, P < 0.01). Flow cytometry results showed that the positive rates of CD38, CD138, κ, λ, CD56 and CD19 were 100.0% (280/280), 100.0% (280/280), 57.5% (161/280), 42.5% (119/280), 62.1% (174/280) and 19.3% (54/280); bone marrow immunohistochemistry results showed that the positive rates of CD38, CD138, κ, λ and CD56 were 98.9% (277/280), 98.2% (275/280), 57.5% (161/280), 42.5% (119/280) and 62.1% (174/280); there was no statistical difference between the two detection methods in the detection coincidence rate of the same detection index (all P > 0.05). Among patients who underwent FISH detection, the detection rate of gene abnormalities was 69.9% (93/133); the detection rate of abnormalities by direct fluorescence in situ hybridization (D-FISH) was 42.9% (57/133); the detection rate of abnormalities by CD138 immunomagnetic sorting myeloma cells (MACS)-FISH was 82.7% (110/133). Among patients who underwent G-band karyotyping, the detection rate of abnormal karyotype was 38.5% (85/221). FSIH, especially MACS-FISH, had a higher detection rate of cytogenetic abnormalities than G-band karyotyping, and the difference was statistically significant ( χ2 = 65.697, P < 0.05). Conclusion:The comprehensive application of bone marrow morphology, bone marrow immunohistochemistry, flow cytometry, FISH (especially MACS-FISH), cytogenetic testing and other detection methods is more helpful for the diagnosis of multiple myeloma, and may be useful for prognostic judgment.
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OBJECTIVE@#To analyze the clinicopathological characteristics of mucosa associated lymphoid tissue (MALT) lymphoma secondary to Sjögren' s syndrome (SS) (SS-MALT lymphoma) in salivary gland and to explore the value of the combined application of histopathological morphology, protein expression and molecular phenotype in pathological diagnosis and prognostic evaluation of SS-MALT lymphoma.@*METHODS@#Sixteen patients with SS-MALT lymphoma were collected from 260 patients who were diagnosed with SS in Peking University School and Hospital of Stomatology from January 1997 to December 2016. Twelve patients with non-MALT lymphoma secondary to SS (non-SS-MALT lymphoma) in salivary gland were selected as controls. The clinical data of the patients were retrospectively reviewed and analyzed. All the patients were followed up until December 20, 2019. Hematoxylin-eosin staining, immunohistochemistry, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques were used to observe the histologic characteristics and to detect the manifestations of light chain restrictive expression, immunoglobulin (Ig) gene clonal rearrangement, chromosome translocation and gene abnormality, so as to evaluate their values in pathological diagnosis and prognostic evaluation.@*RESULTS@#The malignant transformation rate of SS to MALT lymphoma was about 6.15%, ranged from 3 to 240 months, during which 2 patients died due to high-level deterioration. Microscopically, the acini of the glandular tissue were atrophied and destroyed. The tumor cells dominated by central cell-like lymphocytes grew diffusely, destroying the epithelial islands. All SS-MALT lymphoma cases were positive in CD20 and Pax5. Half of them had the Ki-67 proliferation index of 10% or less, and half greater than 10%. 93.75% cases expressed AE1/AE3 protein, which showed the residual glandular epithelium. All the tumor cells were negative in CD3ε, and the plasma cells were detected by CD138 antigen. The light chain restrictive expression of κ and λ was 37.5% in SS-MALT lymphoma group. The positive detection rates of immunoglobulin heavy chain (IgH)-FR1, IgH-FR2, IgH-FR3, immunoglobulin kappa chain (IgK)-A, and IgK-B in SS-MALT lymphoma group were 33.3%, 53.3%, 33.3%, 20.0%, and 26.7%, respectively, and 93.3% when together used with IgH and IgK. The positive rates of the MALT1, IGH and BCL6 genes with dual color break-apart probes were 36.4%, 27.3% and 27.3%, and the detection rate of chromosome translocation and gene abnormality by applying the three probes was 72.7%.@*CONCLUSION@#There are no specific histological characteristics and protein phenotypes in the histologic diagnosis of SS-MALT lymphoma in salivary gland. The combined application of histopathological manifestations, immunohistochemistry, PCR and FISH techniques helps the accurate pathologic diagnosis of the disease. Although SS-MALT lymphoma is considered as an indolent lymphoma with a relatively favorable prognosis, the regular return visit and long-term follow-up should be conducted to detect the clues of recurrence and advanced deterioration.
Subject(s)
Humans , In Situ Hybridization, Fluorescence , Lymphoma, B-Cell, Marginal Zone/etiology , Neoplasm Recurrence, Local , Retrospective Studies , Salivary GlandsABSTRACT
Objective@#To investigate the histopathologic, immunohistochemical, molecular genetic characteristics of dedifferentiated liposarcomas with meningothelial-like whorls(DDLMW).@*Methods@#Six cases of DDLMW diagnosed at Jiangsu Province Hospital(the First Affiliated Hospital of Nanjing Medical University) from March 2012 to August 2018 were enrolled. The cases were analyzed by routine HE staining, immunohistochemistry(MDM2, CDK4 and p16) and fluorescent in-situ hybridization(FISH) on MDM2 gene. Related literatures were also reviewed.@*Results@#Three of the 6 patients were male.The patient ages ranged from 40 to 77 years (mean, 58 years). Four tumors occurred in the retroperitoneum and two in the mediastinum. Histologically, the tumors showed, in addition to foci of well-differentied liposarcoma, characteristic, scattered meningothelial-like concentrical whorls. The whorls were composed of tightly, concentrically arranged, spindle to ovoid cells with mild to mederate cytological atypia. Metaplastic bone was present within or in their immediate vicinity in four case. The tumors cell also showed strong and diffuse immunoreactivity to MDM2, CDK4 and p16, but no immunoreactivity to S-100 protein, SMA, SOX10, EMA, CD21, CD23 or CD35. The Ki-67 labeling indexes were low, while FISH showed high levels of MDM2 amplification in all cases.@*Conclusions@#DDLMW is a rare morphologic variant of dedifferentiated liposarcoma. The whorls in DDLMW do not represent perineurial or follicular dendritic differentiation. Recognition and familiarity with its existence, as well as combined application of immunohistochemical staining and MDM FISH, are important to avoid confusion with other lesions.
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Objective@#To investigate the clinicopathological manifestations, molecular genetic, diagnostic histology and differential diagnosis of alveolar soft part sarcoma (ASPS) in children.@*Methods@#A total of 13 cases of ASPS diagnosed at Beijing Children′s Hospital from August 2009 to November 2018 were collected. HE staining, histochemical staining for PAS and D-PAS, immunohistochemical (IHC) staining for TFE3, INI1 and CD68 and florescence in situ hybridization (FISH) for TFE3 gene translocation were performed.@*Results@#There were four males and nine females, age ranged from 1 year and 2 months to 13 years and 8 months (mean 7.8 years); and four patients were under 5 years old. Histologically, the tumors showed a distinctive and characteristic nested or organoid growth pattern (11 cases) or solid, diffuse growth (2 cases). The tumor cells possessed abundant eosinophilic, or glycogen-rich and clear to vacuolated cytoplasm. The chromatin was relatively dispersed, with prominent and pleomorphic nucleoli; mitotic figures were rare. Vascular invasion was frequently seen. IHC staining showed specific nuclear TFE3 staining. The tumor cells were also positive for INI1,CD68 and vimentin; but were negative for MyoD1, Myogenin, CK and S-100 protein. Seven cases showed PAS and D-PAS staining, with fuchsia acicular or rod-shaped crystals in tumor cytoplasm. Nine cases showed TFE3 break-apart signals by FISH.@*Conclusions@#ASPS is a rare soft tissue sarcoma in children. Compared with ASPA in adults, it has both similarities and unique clinicopathologic characteristics. The diagnosis needs to be confirmed by combining clinical, pathologic, IHC and genetic testing.
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Objective@#To investigate the clinicopathological and radiological features of benign fibro-osseous lesion (BFOL).@*Methods@#Sixty-five cases of craniofacial BFOL, eight cases of peripheral ossifying fibroma (POF) and one case of low-grade central osteosarcoma diagnosed at Sichuan Provincial People′s Hospital between January 2010 and March 2019 were collected. The clinicopathologic features, hematoxylin-eosin and immunohistochemical (IHC) staining and radiographic features were analyzed. MDM2 gene amplification was detected by FISH in difficult borderline cases.@*Results@#This cohort of BFOLs included 50 cases of fibrous dysplasia (FD), 12 cases of ossifying fibroma (OF), and three cases of juvenile psammomatoid ossifying fibroma (JPOF). The average ages of patients with FD,OF and JPOF were 31.7, 39.2 and 26.0 years respectively. The male to female ratio was 1.0∶1.8.The average age of POF was 47.0 years, with male to female ratio of 1∶7. Patient of low-grade central osteosarcoma was a 48-year-old man. Twenty-seven cases of FD were located in the jaw, and 23 cases were in other craniofacial bones. Nine cases of OF were located in the jaw, and three cases were in the nasal cavity. Two cases of JPOF were in the nasal sinus, and one was in the jaw. All POF were located in the gingiva, and low-grade central osteosarcoma was located in the mandible. The imaging features of FD were luffa-like or ground-glass like signal shadows with poorly defined borders with expansion. OF had clear borders or sclerosing margins. Both JOF and low-grade central osteosarcoma were expansile intraosseously and with focally invasive nodular masses with ground-glass like signal shadows; and POF showed soft tissue mass with bone formation. Histological features of BFOLs showed mixed fibrous and irregular osteoid lesions. FD had no clear relationship with the host bone and no osteoblasts surrounded the bone trabeculae. Osteoblasts rimming was found in OF, and the boundaries of the host bone were clear. JPOF and low-grade central osteosarcoma infiltrated the host bone focally, and the latter showed mild cellular atypia. MDM2 amplification was detected in low-grade central osteosarcoma.@*Conclusions@#BFOLs are a group of fibro-osseous lesions with similar morphology in the head and neck and face, but their clinical features and prognosis are different; and their imaging and histological characteristics are also slightly different. Attentions should be given to the combination of clinical, imaging and pathologic features of BFOLs, especially the differential diagnosis between BFOLs and low-grade central osteosarcoma. Molecular detection could be used to assist the diagnosis in difficult cases.
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To investigate the clinicopathological and radiological features of benign fibro-osseous lesion (BFOL). Sixty-five cases of craniofacial BFOL, eight cases of peripheral ossifying fibroma (POF) and one case of low-grade central osteosarcoma diagnosed at Sichuan Provincial People's Hospital between January 2010 and March 2019 were collected. The clinicopathologic features, hematoxylin-eosin and immunohistochemical (IHC) staining and radiographic features were analyzed. MDM2 gene amplification was detected by FISH in difficult borderline cases. This cohort of BFOLs included 50 cases of fibrous dysplasia (FD), 12 cases of ossifying fibroma (OF), and three cases of juvenile psammomatoid ossifying fibroma (JPOF). The average ages of patients with FD,OF and JPOF were 31.7, 39.2 and 26.0 years respectively. The male to female ratio was 1.0∶1.8.The average age of POF was 47.0 years, with male to female ratio of 1∶7. Patient of low-grade central osteosarcoma was a 48-year-old man. Twenty-seven cases of FD were located in the jaw, and 23 cases were in other craniofacial bones. Nine cases of OF were located in the jaw, and three cases were in the nasal cavity. Two cases of JPOF were in the nasal sinus, and one was in the jaw. All POF were located in the gingiva, and low-grade central osteosarcoma was located in the mandible. The imaging features of FD were luffa-like or ground-glass like signal shadows with poorly defined borders with expansion. OF had clear borders or sclerosing margins. Both JOF and low-grade central osteosarcoma were expansile intraosseously and with focally invasive nodular masses with ground-glass like signal shadows; and POF showed soft tissue mass with bone formation. Histological features of BFOLs showed mixed fibrous and irregular osteoid lesions. FD had no clear relationship with the host bone and no osteoblasts surrounded the bone trabeculae. Osteoblasts rimming was found in OF, and the boundaries of the host bone were clear. JPOF and low-grade central osteosarcoma infiltrated the host bone focally, and the latter showed mild cellular atypia. MDM2 amplification was detected in low-grade central osteosarcoma. BFOLs are a group of fibro-osseous lesions with similar morphology in the head and neck and face, but their clinical features and prognosis are different; and their imaging and histological characteristics are also slightly different. Attentions should be given to the combination of clinical, imaging and pathologic features of BFOLs, especially the differential diagnosis between BFOLs and low-grade central osteosarcoma. Molecular detection could be used to assist the diagnosis in difficult cases.
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To investigate the clinicopathological manifestations, molecular genetic, diagnostic histology and differential diagnosis of alveolar soft part sarcoma (ASPS) in children. A total of 13 cases of ASPS diagnosed at Beijing Children's Hospital from August 2009 to November 2018 were collected. HE staining, histochemical staining for PAS and D-PAS, immunohistochemical (IHC) staining for TFE3, INI1 and CD68 and florescence in situ hybridization (FISH) for TFE3 gene translocation were performed. There were four males and nine females, age ranged from 1 year and 2 months to 13 years and 8 months (mean 7.8 years); and four patients were under 5 years old. Histologically, the tumors showed a distinctive and characteristic nested or organoid growth pattern (11 cases) or solid, diffuse growth (2 cases). The tumor cells possessed abundant eosinophilic, or glycogen-rich and clear to vacuolated cytoplasm. The chromatin was relatively dispersed, with prominent and pleomorphic nucleoli; mitotic figures were rare. Vascular invasion was frequently seen. IHC staining showed specific nuclear TFE3 staining. The tumor cells were also positive for INI1,CD68 and vimentin; but were negative for MyoD1, Myogenin, CK and S-100 protein. Seven cases showed PAS and D-PAS staining, with fuchsia acicular or rod-shaped crystals in tumor cytoplasm. Nine cases showed TFE3 break-apart signals by FISH. ASPS is a rare soft tissue sarcoma in children. Compared with ASPA in adults, it has both similarities and unique clinicopathologic characteristics. The diagnosis needs to be confirmed by combining clinical, pathologic, IHC and genetic testing.
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To investigate the histopathologic, immunohistochemical, molecular genetic characteristics of dedifferentiated liposarcomas with meningothelial-like whorls(DDLMW). Six cases of DDLMW diagnosed at Jiangsu Province Hospital(the First Affiliated Hospital of Nanjing Medical University) from March 2012 to August 2018 were enrolled. The cases were analyzed by routine HE staining, immunohistochemistry(MDM2, CDK4 and p16) and fluorescent in-situ hybridization(FISH) on MDM2 gene. Related literatures were also reviewed. Three of the 6 patients were male.The patient ages ranged from 40 to 77 years (mean, 58 years). Four tumors occurred in the retroperitoneum and two in the mediastinum. Histologically, the tumors showed, in addition to foci of well-differentied liposarcoma, characteristic, scattered meningothelial-like concentrical whorls. The whorls were composed of tightly, concentrically arranged, spindle to ovoid cells with mild to mederate cytological atypia. Metaplastic bone was present within or in their immediate vicinity in four case. The tumors cell also showed strong and diffuse immunoreactivity to MDM2, CDK4 and p16, but no immunoreactivity to S-100 protein, SMA, SOX10, EMA, CD21, CD23 or CD35. The Ki-67 labeling indexes were low, while FISH showed high levels of MDM2 amplification in all cases. DDLMW is a rare morphologic variant of dedifferentiated liposarcoma. The whorls in DDLMW do not represent perineurial or follicular dendritic differentiation. Recognition and familiarity with its existence, as well as combined application of immunohistochemical staining and MDM FISH, are important to avoid confusion with other lesions.
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Objective@#To investigate clinicopathological, cytogenetic features and differential diagnoses of high grade endometrial stromal sarcoma (HGESS) with BCOR gene rearrangement.@*Methods@#Five cases of HGESS with BCOR rearrangement were collected from consultant files (2016-2018) at Fudan University Shanghai Cancer Center. Interphase FISH was performed using a dual color break-apart probe. The clinical data, histologic features and immunohistochemical findings were reviewed.@*Results@#All 5 cases occurred in adult women with a median age of 48 (range, 45-55) years. Abdominal pain and abnormal vaginal bleeding were the most common symptoms. Microscopically, the tumors showed mainly tongue-like and/or intersecting myometrial invasion. Stromal myxoid matrix and/or collagen plaques were prominent in all the cases. Most tumors consisted of uniform, haphazard fascicles of short spindle cells with mild to moderate nuclear atypia. Mitotic figures and necrosis were easily identified. Significant nuclear pleomorphism was not seen. Most tumors were rich in thick-walled small vessels. Prominent perivascular tumor cell whorling seen in conventional low-grade endometrial stromal sarcoma was not seen. All tumors expressed CD10 with only focal or absent desmin, SMA and/or h-caldesmon staining. ER or PR expression was seen in 4 tumors and 1 tumor showed both marker expression. Diffuse cyclin D1 was present in 2 tumors. BCOR immunoreactivity was present with strong staining in 3 cases and moderate staining in 1 case respectively. Ki-67 index ranged from 10% to 30%. Fluorescence in situ hybridization confirmed chromosomal aberration of BCOR gene in all tumors, that were previously diagnosed as myxoid leiomyosarcoma (2 cases), spindle cell uterine sarcoma (2 cases) and low-grade endometrial stromal sarcoma (1 case). Limited follow-up information revealed that 3/5 patients developed tumor recurrence, metastasis or death within one year.@*Conclusion@#BCOR rearranged HGESS has distinct morphological features and aggressive clinical behavior. In the presence of significant overlapping morphologic features between BCOR rearranged HGESS and other myxoid uterine mesenchymal tumors, especially myxoid leiomyosarcoma, molecular analysis is essential for accurate diagnoses.
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Objective@#To investigate the value of karyotype analysis, bacterial artificial chromosomes-on-beads (BoBs), chromosome microarray analysis (CMA) and fluorescence in situ hybridization (FISH) in the diagnosis of sex chromosome numerical and structural abnormalities.@*Methods@#Conventional G-banding staining technique was used to analyze the karyotypes of amniotic fluid cells and parental peripheral blood cells in two pregnancies with prenatal diagnosis indications. Sex chromosome numerical and structural abnormalities were analyzed based on the results of G-banding, BoBs, CMA and FISH.@*Results@#The results of G-banding karyotype analysis showed that there were mosaics in amniotic fluid cells collected from both cases. Karyotype of Case A was 45,X[25]/46,X,idic(Y)(q11.2?)[6], and Case B was 45,X[39]/46,X,psu idic(X)(q21.32?)[44]. Parental peripheral blood karyotypes of both families were normal. Prenatal BoBs indicated copy number abnormalities in sex chromosomes (Y chromosome in Case A and X chromosome in Case B). CMA results suggested a 20.1 Mb duplication in Yp11.32q11.222, and a 7.7 Mb deletion in Yq11.222q11.23 in fetus A with possible karyotype of 46,X,idic(Y)(q11.222); for fetus B, a 92.0 Mb duplication in Xp22.33q21.32, and a 63.0 Mb deletion in Xq21.32q28 were detected, and the karyotype might be 46,X,psu idic(X)(q21.32). The mid-term FISH test of amniotic fluid cells showed that 90% of the amniotic cells from Case A were 45,X, and 10% were 46,X,idic(Y)(q11.2); about 38% were 45,X, and 62% were 46,X,psu dic(X)(q21.3) from Case B.@*Conclusions@#Numerical and structural abnormalities of sex chromosomes could be accurately diagnosed by combination of several methods including G-banding karyotype analysis, prenatal BoBs, CMA and FISH, which would help to effectively reduce birth defects.
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Objective@#To investigate the clinical, histologic and immunophenotypic features, genetic alterations and prognosis of the rare Xp11 neoplasm with melanocytic differentiation.@*Methods@#Twenty-one cases were selected from the Department of Pathology, Jingling Hospital, Nanjing University School of Medicine from May 2008 to May 2018. The clinicopathologic, immunohistochemical, molecular analysis and follow-up details were collected.@*Results@#There were 7 males and 14 females, with their ages ranging from 4 to 57 years (mean 32.8 years). The tumors were located in kidney (11 cases), pelvis (three cases), and in pancreas, retroperitoneum, adrenal gland, small intestine, prostate, cervix and appendix (one case each). Microscopically, most tumors shared similar morphology such as purely nested or sheet-like architectures separated by a delicate vascular network, purely epithelioid cells with clear to granular eosinophilic cytoplasm, lacks of papillary structures, spindle cell or fat components, uniform round to oval nuclei with small visible nucleoli, and in most of them (16/21) melanin pigment. Immunohistochemically, all cases showed moderately (2+) or strongly (3+) positive staining for TFE3 and Cathepsin K. HMB45 and Melan A were focally expressed in three of 21 cases, while the remaining cases showed typically moderate(2+) or strong (3+) expression. None of the cases were immunoreactive for SMA, desmin, CKpan, S-100 and PAX8. All cases showed TFE3 rearrangement using fluorescence in-situ hybridization (FISH). Fusion FISH assays detected SFPQ-TFE3 gene fusion in 16 cases, NONO-TFE3 gene fusion in two, ASPL-TFE3 and MED15-TFE3 gene fusions in one case each. Polymerase chain reaction and direct sequencing detected SFPQ-TFE3 gene fusion in nine cases, NONO-TFE3 and MED15-TFE3 gene fusions in one case each. Clinical follow-up was available for 15 patients for 12 to 74 months. Six patients died of the disease; and three had recurrences and/or metastases. Six patients were alive with no evidence of disease after initial resection.@*Conclusions@#Xp11 neoplasm with melanocytic differentiation has unique morphologic, immunophenotypic and genetic characteristics. The tumor is aggressive, and should be differentiated from Xp11 translocation RCC and perivascular epithelioid cell tumor.
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Objective@#To study the clinicopathological characteristics of lung salivary gland-type tumors (SGT), and to compare with the corresponding primary SGT in salivary glands.@*Methods@#Twenty-three cases of lung SGT were retrieved from the files of Peking University First Hospital from January 2004 to September 2018. The morphology, immunophenotype, genotype and outcome of these cases were analyzed.@*Results@#The 23 patients included 13 males and 10 females, with age range of 13-79 years (median 54 years). There were 11 cases of adenoid cystic carcinoma, 10 cases of mucoepidermoid carcinoma (MEC), one case each of clear cell carcinoma and myoepithelioma. The morphology and immunophenotype of lung SGT were very similar to their counterparts in salivary gland. MYB rearrangement was detected in one of 11 adenoid cystic carcinomas. MAML2 rearrangement was detected in all the MECs. EWSR1 rearrangement was detected in the one case of clear cell carcinoma. Of patients with adenoid cystic carcinoma, the survival time was more than 60 months (three cases), 52 months (one case), and 12-36 months (three cases). There was no recurrence and death in seven cases of MEC with follow-up results. One case of clear cell carcinoma recurred after 52 months of follow-up.@*Conclusions@#Although the SGT of lung and their counterparts in salivary gland are very similar in their morphology, immunophenotype, genotype and prognosis, there are also some differences between each other. MYB rearrangement can be detected in most adenoid cystic carcinomas of salivary gland, but rarely in lung adenoid cystic carcinoma. The prognosis of patients with lung MEC is better than that of patients with salivary gland MEC, while the prognosis of patients with lung adenoid cystic carcinoma is worse than that of patients with salivary gland adenoid cystic carcinoma.
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Objective@#To correlate chromosomal translocations of DUSP22 or TP63 with clinical significance in ALK-negative anaplastic large cell lymphoma (ALK-ALCL).@*Methods@#Thirty-two patients with ALK-ALCL were selected from January 2004 to January 2014 at Fujian Provincial Hospital for the detection of chromosomal translocations of DUSP22 and TP63 by fluorescence in situ hybridization (FISH). The relationship between DUSP22 and TP63 chromosomal translocations and the clinicopathological parameters of ALK-ALCL was analyzed.@*Results@#Among the 32 ALK-ALCL patients, 7(21.8%) had DUSP22 gene rearrangement (DUSP22+ALK-ALCL). Three patients (9.4%) had TP63 gene rearrangement (TP63+ ALK-ALCL). There were 22 patients (68.8%) without rearrangement of either DUSP22 or TP63 (DUSP22-TP63-ALK-ALCL). The patients with DUSP22+ ALK-ALCL were among the younger, and the patients with TP63+ ALK-ALCL were among the elder. The mean age of patients with DUSP22-TP63-ALK- ALCL was between those of DUSP22+ALK-ALCL and TP63+ ALK-ALCL (P<0.05). Based on Ann Arbor staging, incidence of DUSP22 gene rearrangement decreased as the clinical stage of ALK-ALCL increased (P<0.05). Incidence of TP63 gene rearrangement cases increases in patients at more advanced clinical stage(P<0.05). The five-year survival rate and prognosis of patients with DUSP22+ALK-ALCL were the highest. Patients with TP63+ ALK-ALCL had the lower five-year survival and the worse prognosis (P<0.05).@*Conclusion@#Presences of DUSP22 and TP63 chromosomal translocations correlate with the clinical stages and prognosis of ALK-ALCL and may be used for the differential diagnosis, determination of tumor aggressiveness and prognostication of ALK-ALCL.
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Objective@#To investigate the clinicopathologic features, immunophenotype and prognosis of CIC-rearranged sarcoma (CRS).@*Methods@#The clinical and pathological data of 10 cases of CRS diagnosed between January 2017 and December 2018 at the Department of Pathology,Fudan University Shanghai Cancer Center were analyzed. Immunohistochemical study and fluorescence in situ hybridization (FISH) were performed. The literature was reviewed.@*Results@#There were five males and five females with a mean age of 28 years (range, 5 to 63 years). Eight tumors developed in the somatic soft tissues, including trunk (n=3),head and neck (n=3),and extremities (n=2). One case each arose in the small intestine and the occipital lobe. The average size was 4.9 cm (range,1.5-8.0 cm). Microscopically,all cases were composed of small to medium-sized round, oval to short spindled cells, showing nodular or lobular architecture, or were arranged in sheets. Compared with Ewing sarcoma, tumor cells of CRS usually showed irregular nuclear outline, coarse chromatin with prominent nucleoli and brisk mitotic activity. Necrosis was present in four cases with one showing geographic necrosis. Immunohistochemically, tumor cells usually showed focal or patch staining of CD99 (9/10),diffuse and strong nuclear expression of WT1 in half cases (2/4),and a high Ki-67 index (median 70%). By FISH, nine cases demonstrated convincing break-apart signal of CIC gene. Follow-up data available in seven cases (mean 12.1 months); of these two patients died of disease (2/7), whereas one patient was alive with unresectable recurrent tumor,the remaining four patients were alive with no evidence of disease. Five patients (5/7) experienced local recurrence and two patients (2/7) developed metastasis. The mean and median intervals to recurrence/metastasis were eight months and four months, respectively.@*Conclusions@#CRS is the most common type of EWSR1-negative small round cell sarcoma (SRCS). Although it has clinical and pathological overlapping features with Ewing sarcoma,the prognosis is comparatively poor. Focal or patch staining of CD99 but diffuse staining of WT1 in a case of small RCS should raise the possibility of CRS. FISH assay is required for the final diagnosis.
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Objective@#To detect the expression of New York esophageal squamous cell carcinoma antigen 1 (NY-ESO-1) in common types of mesenchymal myxoid tumors, and to investigate its significance in the diagnosis and differential diagnosis of myxoid liposarcoma.@*Methods@#A total of 43 formalin-fixed paraffin-embedded samples of mesenchymal myxoid tumors from the Affiliated Hospital of Qingdao University and Qingdao Municipal Hospital ranging between 2010 and 2017 were selected. NY-ESO-1 expression was detected by immunohistochemical staining. DDIT3 gene status was detected by fluorescence in situ hybridization (FISH). NY-ESO-1 mRNA was detected by reverse transcription-PCR (RT-PCR).@*Results@#Histopathology and FISH results confirmed that there were 11 cases of myxoid liposarcoma and 32 other types (including 7 cases of well-differentiated liposarcoma, 1 dedifferentiated liposarcoma, 3 lipomas, 2 lipoblastomas and 19 non-adipocytic tumors). Immunohistochemical staining showed that the positive expression propotion of NY-ESO-1 in myxoid liposarcoma was 11/11, and the positive location was the cytoplasm and nucleus of lipoblast cells. The expression intensity is higher in regions with round cell differentiation. Among the 32 cases of other mesenchymal myxoid tumors, only one well-differentiated liposarcoma showed positive immunoreactivity for NY-ESO-1. RT-PCR confirmed that 7 cases of myxoid liposarcoma (7/11) and one well-differentiated liposarcoma (1/7) had NY-ESO-1 mRNA expression.@*Conclusions@#NY-ESO-1 is positively expressed in myxoid liposarcoma. It can be served as a useful marker for the diagnosis and differential diagnosis of myxoid liposarcoma.
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Objective@#To investigate the clinicopathologic features and prognosis of ALK-positive Spitz tumors.@*Methods@#Thirteen patients with ALK-positive Spitz tumors diagnosed at Shanghai Cancer Center, Fudan University from October 2016 to December 2017 were collected. All cases were routinely evaluated histopathological features in HE staining and detected ALK protein expression by immunohistochemistry. The ALK fusions of 7 cases were confirmed by fluorescence in situ hybridization (FISH).Follow-up data was collected.@*Results@#The age of patients including 2 males and 11 females ranged from 4 to 47 years (mean 25 years). 12 patients were diagnosed with atypical Spitz tumors and 1 patient was diagnosed with Spitz nevus. Clinically, most lesions presented as papules or nodules, while a few lesions presented as plaques. Histologically, most tumors were exophytic (9/13). More than half of the tumors were amelanotic and the junctional component was mainly composed of melanocytic nests. Kamino bodies were not found. The bases of the tumors were mainly wedge-shaped (5/13) and flat (7/13). Eight tumors displayed mixed cell types, while 5 tumors were composed of only spindle cells. All the tumors showed a plexiform and/or intersecting fascicular growth pattern, and perineural extension was observed in 3 tumors. ALK immunohistochemistry showed diffuse and intense cytoplasmic staining in 13 cases, and 7 of them were detected by FISH to confirm the presence of ALK fusions. All patients were followed up for 7 to 21 months (median=12), with no recurrence or lymph node dissemination.@*Conclusions@#Spitz tumors with ALK fusions have their special histopathologic features.ALK fusions mainly occur in Spitz nevi and atypical Spitz tumors. The follow-up data of the existing literatures and our research indicates that the prognosis of ALK-positive Spitz tumors may be good.
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Objective@#To investigate the impact of ultrasonic assisted rapid processing technique combined with the environment friendly reagent (which can be utilized in fixing,dehydrating and clearing) on processing tumor biopsy specimens and the subsequent target detection.@*Methods@#Postoperative tissue samples of 56 cases of breast cancer, colorectal cancer, lung cancer, stomach cancer, liver mass, bladder mass, uterus mass were obtained at the National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences from February to April, 2017. Three specimens ranging in size from 1 to 3 mm were collected from each sample, and were separated into control group (traditional tissue-processing method); experiment group 1 (3.7% neutral buffered formaldehyde fixation, composite environment friendly reagent and ultrasonic assisted rapid processing) and experimental group 2 (composite environment friendly reagent direct fixation, higher temperature and longer time for tissue processing). Two pathologists blinded to the experimental groups scored totally the nuclear, cytoplasmic, and membrane staining of 43 cases of immunohistochemistry (IHC), four HER2 fluorescence in situ hybridization (FISH), 20 extracted DNA quality and four EGFR gene mutation detection in lung adenocarcinoma; the results were compared with the control group.@*Results@#There was no difference in the IHC staining, HER2 FISH, the DNA quality, and EGFR genetic results between experimental group 1 and control group. For experiment group 2, comparing results of IHC staining, HER2 FISH and the quality of DNA, there was no obvious difference from control group and experiment group 1, but might show an increase in the background of IHC staining. The difference between the treatment temperature and time in the experimental group 2 did not affect the results of the gene mutation detection.@*Conclusions@#Environment freindly reagent and ultrasonic assisted rapid processing equipment could be used for rapid processing and diagnosis for tumor biopsies. Using complex environment-friendly reagents supplement fixation, higher treatment temperature and longer treatment time do not significantly affect the IHC, FISH and molecular detection accuracy.