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Objective: To investigate the radiologic, pathologic, and molecular features of simple bone cysts (SBC), and their differential diagnoses. Methods: Fourteen cases of SBC were collected at the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from 2017 to 2022, and fluorescence in situ hybridization (FISH) was performed for retrospective analysis. Results: There were 14 patients, including 7 females and 7 males, with age range of 7 to 45 (median 29) years. The most common complaint was pain, including 4 cases with pathological fracture and 5 with history of previous trauma. The tumor size ranged from 3.4 to 13.5 (median 5.6) cm. The lesion involved the femur ( n= 4), humerus ( n= 5) and iliac bone ( n= 5). Radiologic diagnoses included SBC, aneurysmal bone cyst, and giant cell tumor of the bone or its combination with aneurysmal bone cyst-like region and fibrous dysplasia. Histologically, the cyst walls of the lesions were composed of fibrous tissue, fibrin-like collagen deposits, bone-like matrix and occasional woven bone. The lesional cells were spindled to ovoid, with scattered osteoclast-like giant cells, foamy histiocytes, hemosiderin deposits and cholesterol clefts. In 6 cases there were nodular fasciitis-like areas. Immunohistochemically, the spindled to ovoid cells were positive for SMA, EMA and SATB2 in varying degrees. FISH detection was performed in all 14 cases and EWSR1/FUS rearrangement were found in 9 cases. One case of FUS::NFATC2 fusion was detected by next-generation sequencing. Nine cases of SBC with the rearrangement were more cellular, and there were more mitotic figures in the recurrent FUS::NFATC2 fusion tumor. Clinical follow-up was obtained in all 14 cases with the time ranging from 5 to 105 (mean 46) months. Amongst them, the tumor with FUS::NFATC2 rearrangement had local recurrence twice after the first local excision, but had no more recurrence or metastasis 34 months after the subsequent segmental resection. The other 13 cases had no recurrence. Conclusions: EWSR1 or FUS rearrangement is most commonly identified in SBC, suggesting that SBC might be a neoplastic disease. In cases where the radiologic appearance and histomorphology are difficult to differentiate from aneurysmal bone cyst, FISH detection can aid in the definitive diagnosis.

Introduction: Solitary fibrous tumor (SFT) represents a fibroblastic neoplasm exhibiting NAB2::STAT6 gene rearrangement, displaying diverse clinical manifestations, spanning from benign to malignant. To predict prognosis, the modified (four-variable) Demicco (mDemicco) model was introduced. This investigation aims to authenticate the mDemicco risk model's precision in Asian patients while investigating the clinicopathological and molecular factors linked to the prognosis of extrameningeal SFTs., Methods: Clinicopathological data from 111 extrameningeal SFT cases in East China, covering the period from 2010 to 2020, were thoroughly analyzed. The tumors were classified using the mDemicco model. Immunohistochemical evaluation of P16 and P53, molecular detection of TP53 and TERT promoter mutation, and fluorescence in situ hybridization for CDKN2A gene alterations were performed. Statistical methods were utilized to assess the associations between clinicopathological or molecular factors and prognosis., Results: Histologically, only one parameter, the mitotic count, exhibited a statistical correlation with progression-free survival (PFS) and overall survival (OS). During the Kaplan-Meier analysis, the variation in PFS among the different risk groups exhibited a notable trend towards statistical significance. Nevertheless, 3 out of 74 patients classified as low-risk SFTs and 7 out of 21 patients classified as intermediate-risk exhibited disease progression. Among the 5 patients with TP53 mutations and/or mutant-type P53 immunophenotype, 3 experienced disease progression, including 2 intermediate-risk patients. Additionally, among the 4 patients with TERT promoter mutations who were followed up, 3 showed progression, including 2 intermediate-risk patients. Moreover, it was observed that hemizygous loss of CDKN2A was detected in more than 30% of one case, yet the patient exhibited a favorable survival outcome., Conclusion: The mDemicco risk model exhibits certain limitations when dealing with smaller tumor sizes, younger age groups, and occurrences of malignant and dedifferentiated SFTs. Furthermore, molecular factors, such as TP53 or TERT promoter mutations, may identify intermediate-risk SFTs with poorer prognoses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yao, Zhou, Li, Yang, Chen, Wei, Fan and Gong.)

Objective: To investigate the clinical manifestations, histomorphology, and differential diagnosis of primary hepatic angiosarcoma. Methods: Nine cases of primary hepatic angiosarcoma diagnosed in the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2021 were collected, including biopsy and surgical specimens. The histomorphology, clinical, and radiologic findings were analyzed. The relevant literature was also reviewed. Results: There were six males and three females, aged 30 to 73 years (mean 57 years). Grossly, the growth pattern of the tumor was classified as either mass formation or non-mass formation (sinusoidal). Microscopically, the mass-forming primary hepatic angiosarcoma were further subdivided into vasoformative or non-vasoformative growth patterns; and those non-vasoformative tumors had either epithelioid, spindled, or undifferentiated sarcomatoid features. Sinusoidal primary hepatic angiosarcoma on the other hand presented with markedly dilated and congested blood vessels of varying sizes, with mild to moderately atypical endothelial cells. Follow-up in all nine cases revealed 8 mortality ranging from 1 to 18 months (mean 5 months) from initial diagnosis. One patient was alive with disease within a period of 48 months. Conclusions: Primary hepatic angiosarcoma is a rare entity with a wide spectrum of histomorphology, and often misdiagnosed. It should be considered when there are dilated and congested sinusoids, with overt nuclear atypia. The overall biological behavior is aggressive, and the prognosis is worse.

Objective: To investigate the clinicopathological, immunophenotypic, and genetic features of malignant peripheral nerve sheath tumor (MPNST). Methods: Twenty-three cases of MPNST were diagnosed at the Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), China, between January 2012 and December 2022 and thus included in the study. EnVision immunostaining and next-generation sequencing (NGS) were used to examine their immunophenotypical characteristics and genomic aberrations, respectively. Results: There were 10 males and 13 females, with an age range of 11 to 79 years (median 36 years), including 14 cases of neurofibromatosis type I-associated MPNST and 9 cases of sporadic MPNST. The tumors were located in extremities (7 cases), trunk (4 cases), neck and shoulder (3 cases), chest cavity (3 cases), paraspinal area (2 cases), abdominal cavity (2 cases), retroperitoneum (1 case), and pelvic cavity (1 case). Morphologically, the tumors were composed of dense spindle cells arranged in fascicles. Periphery neurofibroma-like pattern was found in 73.9% (17/23) of the cases. Under low magnification, alternating hypercellular and hypocellular areas resembled marbled appearance. Under high power, the tumor cell nuclei were irregular, presenting with oval, conical, comma-like, bullet-like or wavy contour. In 7 cases, the tumor cells demonstrated marked cytological pleomorphism and rare giant tumor cells. The mitotic figures were commonly not less than 3/10 HPF, and geographic necrosis was often noted. Immunohistochemically, tumor cells were positive for S-100 (14/23, 60.9%) and SOX10 (11/23, 47.8%). The loss of the CD34-positive fibroblastic network encountered in neurofibromas was observed in 14/17 of the MPNST cases. The loss of H3K27me3 expression was observed in 82.6% (19/23) of the cases. Moreover, SDHA and SDHB losses were presented in one case. NGS revealed that NF1 gene loss of function (germline or somatic) were found in all 5 cases tested. Furthermore, four cases accompanied with somatic mutations of SUZ12 gene and half of them had somatic mutations of TP53 gene, while one case with germline mutation in SDHA gene and somatic mutations in FAT1, BRAF, and KRAS genes. Available clinical follow-up was obtained in 19 cases and ranged from 1 to 67 months. Four patients died of the disease, all of whom had the clinical history of neurofibromatosis type Ⅰ. Conclusions: MPNST is difficult to be differentiated from a variety of spindle cell tumors due to its wide spectrum of histological morphology and complex genetic changes. H3K27me3 is a useful diagnostic marker, while the loss of CD34 positive fibroblastic network can also be a diagnostic feature of MPNST. NF1 gene inactivation mutations and complete loss of PRC2 activity are the common molecular diagnostic features, but other less commonly recurred genomic aberrations might also contribute to the MPNST pathogenesis.

Objective: To investigate the histopathologic, immunohistochemical, molecular genetic characteristics of CIC-rearranged sarcoma (CRS) with rhabdoid features. Methods: The clinical and pathologic data of two cases of CRS diagnosed between 2019 and 2021 at the Department of Pathology, Jiangsu Province Hospital were analyzed. Immunohistochemical study and fluorescence in situ hybridization (FISH) were performed. The relevant literature was reviewed. Results: Both patients were female, one was 58 years old, with tumor located in left thigh; the other was 43 years old, with tumor located in left pelvic cavity. Microscopically, both tumors were composed of small to medium-sized round, oval cells, arranged in nodules or sheets. The tumor cells showed irregular nuclear outline, coarse chromatin with prominent nucleoli and brisk mitotic activity. Both cases showed rhabdoid phenotype with myxoid stromal changes. Immunohistochemically, both cases were positive for CD99 and c-myc. High WT1 reactivity was seen in classic area, with low reactivity in rhabdoid area. There was no INI1 lost in both cases. Both were negative for NKX2.2 and NKX3.1. By FISH both cases demonstrated convincing break-apart signals of CIC gene. One patient died of disease after 1 month, and the other died of disease after 3 months. Conclusions: CRS is a small round cell undifferentiated sarcoma of the bone and soft tissue defined by molecular genetic characteristics, and may show atypical morphologic and immunophenotypic characteristics such as rhabdoid features. A correct understanding of its rare morphologic and immunophenotypic characteristics, combined with molecular pathologic detection, is conducive to correct diagnosis.

Objective: To investigate the clinicopathological and molecular features, diagnosis and differential diagnosis of TFE3-rearranged epithelioid hemangioendothelioma (EHE). Methods Two cases of TFE3-rearranged EHE arising from soft tissues, diagnosed by the Pathology Department of the First Affiliated Hospital of Nanjing Medical University from 2013 to 2020 were observed. EnVision method was used for immunophenotyping, fluorescence in situ hybridization (FISH) was used to test TFE3 gene rearrangements and WWTR1-CAMTA1 fusion gene,and next-generation sequencing (NGS) was used to delineate the fusion transcripts. Results: Details of these two cases were as follows: case 1, male, 51 years old, with tumor in the right temporal region; case 2, female, 42 years old, with tumor in the right neck. The tumors showed progressive painless enlargement. Grossly, the tumor of case 1 was multinodular with unclear boundary and grayish red cut surface, while the tumor of case 2, originating from a vein, appeared as a firm, tan mass within vessel wall. Microscopically, both tumors showed moderate cellularity and were consisted of plump, epithelioid, or histiocytoid cells with eosinophilic cytoplasm and mild-to-moderate nuclear pleomorphism. Most of the tumor cells were arranged in solid or alveolar growth patterns, while some tumor cells showed intraluminal papillary growth pattern in case 1 and anastomosing vascular channels and extramedullary hematopoiesis in case 2. Immunohistochemically, the tumor cells showed diffuse positivity for CD31, CD34, ERG, and TFE3. FISH revealed TFE3 break-apart signals in two cases, but WWTR1-CAMTA1 gene fusion was not detected. NGS identified YAP1 (exon1)-TFE3 (exon6) fusion gene in case 2. Clinical follow-up information was available in both cases for a follow-up period of 15 and 59 months respectively. Patient 1 had a relapse 22 months after surgery, and was currently alive with the tumor. Patient 2 remained disease-free. Conclusions: TFE3-rearranged EHE is a rare molecular subtype of EHE, with accompanying characteristic morphologic features. However the morphologic spectrum remains under-recognized, and more experience is needed. Immunohistochemical and molecular examinations are helpful for the diagnosis and differential diagnosis of the disease.

Objective: To investigate the clinicopathological diagnosis and differential diagnosis of inflammatory myofibroblastic tumor (IMT). Methods: Thirty-two cases of IMT collected at the People's Hospital of Jiangsu Province from May 2010 to May 2020 were evaluated for their clinical, histologic, immunohistochemical and genomic features, and relevant literature was reviewed. Results: There were 19 male and 13 female patients, with age ranging from 5 to 65 years (mean, 37 years). The tumors were located in the lung and mediastinum (10 cases), gastrointestinal tract and mesentery/omentum (12 cases), urinary bladder (5 cases), head and neck (3 cases), somatic soft tissue (1 case), and retroperitoneum (1 case). Four cases of epithelioid inflammatory myofibroblastic sarcoma (EIMS) were all located intra-abdominally. Histologically, the tumor cells were myofibroblasts and fibroblasts arranged in predominantly fusiform pattern, with variably edematous to myxoid background or sclerotic collagenized stroma, and variably mixed chronic or acute inflammatory cells infiltration. EIMS were composed mainly of epithelioid tumor cells, with myxoid stroma and numerous neutrophils. Immunohistochemically, the tumor cells expressed cytoplasmic ALK (25/32, 78%), whereas the four EIMS showed nuclear membrane ALK staining pattern. The tumor cells also expressed CKpan (8/19), SMA (24/32, 75%) and desmin (12/32, 38%); all four EIMS also showed strong positivity for desmin. Fluorescence in situ hybridization (FISH) for ALK gene rearrangement showed split apart signals in 12 of 15 cases, most commonly with atypical signals. Next-generation sequencing (NGS) was performed in three tumors and showed that one case of lower leg IMT harbored a novel CLIP2-ALK fusion, and two cases of EIMS harbored RANBP2-ALK fusion. Follow-up data were available in 29 patients. Twenty-two patients were alive with no evidence of tumor, four patients had tumor recurrences (three patients were treated with crizotinib and were alive with tumor), and three patients died of the disease (including two patients with EIMS). Conclusions: IMTs show a wide morphologic spectrum, and should be differentiated form a variety of benign or malignant tumors. Immunohistochemistry (ALKp80, ALKD5F3) and FISH (ALK break-apart probe) could assist the diagnosis of IMT, with NGS recommended for the atypical cases.

Objective: To study the clinicopathological significance of cyclin D1 expression in Rosai-Dorfman disease (RDD). Methods: Seventeen cases of RDD were evaluated by HE, immunohistochemical staining and molecular genetic analysis. Expression of cyclin D1 was compared between RDDs and control group that included 29 cases of reactive histiocytosis, 9 cases of IgG4-related disease, and 2 cases of Erdheim-Chester disease. Results: Cyclin D1 was expressed in RDDs (17/17), reactive histiocytosis (11/29), IgG4-related diseases (3/9), and Erdheim-Chester disease (2/2), respectively, with nuclear staining in the RDD cells or proliferative histiocytes. Chi-square test showed that expression of cyclin D1 was significantly higher in RDDs than in reactive histiocytosis and IgG4-related diseases ( P <0.01), but not in Erdheim-Chester diseases ( P >0.05). The expression threshold for recalculating the percentage of cyclin D1 positive cells was 27.5% (AUC=0.981 , P <0.01) by ROC curve. However, CCND1 gene had no rearrangement detected by fluorescence in situ hybridization, but with increased copies of gene in some RDD cells. ARMS-PCR analysis also did not detect KRAS, BRAF and NRAS gene mutations in any cases. Conclusions: Cyclin D1 may serve as an additional diagnostic marker for RDDs. Its high expression may be related to activation of MAPK pathway, but the pathogenetic significance of cyclin D1 in RDDs needs further study.

Objective: To study the clinicopathological features of large B-cell lymphoma (LBCL) with IRF4 rearrangement. Methods: Seven cases of LBCL with IRF4 rearrangement collected at the First Affiliated Hospital of Nanjing Medical University from November 2018 to October 2019 were evaluated by hematoxylin and eosin staining, immunohistochemistry and fluorescence in situ hybridization detection. The relevant literature was reviewed. Results: Four tumors were located in the tonsils, 2 tumors in the lymphoid nodes and one tumor in the adenoid.The patients were 3 males and 4 females patients with a median age of 24 years (range, 6 to 39 years).Microscopically, entirely follicular pattern was present in one case, entirely diffuse pattern in 2 cases, and follicular and diffuse pattern in other 4 cases. The tumor cells were medium to large in size and showed the morphology of centroblasts or blastoid cells with irregular nuclei, brisk mitotic activity in 3 cases and starry sky in 2 cases. All of the cases were positive for CD20, PAX-5, bcl-6, and MUM1 and had a Ki-67 index>80%, while CD10 and bcl-2 were positive in 3 cases. IRF4 gene rearrangement was identified in all cases and bcl-6 gene rearrangement in 2 cases. All patients presented with localized disease with clinical stage Ⅰ or Ⅱ, except one with stage Ⅳ at presentation and a new lesion in the mediastinum developed 8 months later. Conclusions: LBCL with IRF4 rearrangement is a clinicopathologically distinct entity. The observations reveal a broader spectrum of morphology and biological behaviors. The relationship between clinical stage and prognosis needs to be determined in more cases.

Recently, a novel group of spindle cell tumors defined by S100 and CD34 co-expression harboring recurrent fusions involving RET, RAF1, BRAF, and NTRK1/2 gene has been identified. Morphologically, they are characterized by monomorphic neoplasm cells, "patternless" growth pattern, stromal, and perivascular hyalinization, lacked necrosis. We reported a 52-year-old Chinese female patient with a S100 and CD34 co-expression sarcoma presenting in the right proximal forearm. The forearm mass initially emerged 19 months ago when it was misdiagnosed as a solitary fibrous tumor and was surgically removed without further treatment. Microscopically, the primary and the recurred tumors share the same features, resembling the morphology of the recently characterized group. Nevertheless, some distinct features, such as predominantly epithelioid tumor cells and focally staghorn vessels, were also present in our case. Genomic profiling with clinical next-generation sequencing was performed and revealed CDC42SE2-BRAF gene fusion, MET amplification, and CDKN2A/B deletion. Both FISH and nested RT-PCR were performed to confirm the gene fusion. The patient was treated with crizotinib for two cycles but showed no obvious benefit. The presented case adds to the spectrum of the novel, characterized solid tumors, and provides suggestions for emerging therapeutic strategies for precision medicine involving targeted kinase inhibitors., (© 2020 Wiley Periodicals LLC.)

A 34-year-old Chinese woman found a lump in her left leg for more than 3 weeks without any discomfort. Grossly, the tumor was relatively well delineated with focal infiltration. Histopathologic evaluation showed a compact fascicular spindle cell proliferation with variable myxoid and collagenous stroma and scattered inflammatory infiltrate. Immunohistochemically, the tumor cells showed positive expression of ALKD5F3 and SMA and negative expression of CD34, desmin, and cytokeretin. Fluorescence in situ hybridization analysis of the ALK locus showed break-apart signals in 20% of tumor cells, and DNA sequencing discovered a novel CLIP2-ALK fusion gene. The lesion was diagnosed as an inflammatory myofibroblastic tumor (IMT). To the best of our knowledge, this is the first case with CLIP2-ALK gene fusion in the somatic soft tissue IMTs., (© 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Objective: To investigate the clinicopathological characteristics, genetic features, diagnosis and differential diagnosis of pulmonary artery intimal sarcoma (PAIS). Methods: Three cases of PAIS were collected from Jiangsu Province People's Hospital (from February 2016 to November 2019). The clinical data, imaging examination, morphology, immunostaining, and molecular changes were retrospectively analyzed. Results: There were 1 male and 2 females (age: 32, 50, 60 years), who had symptoms of cough, asthma or chest tightness. Imaging findings indicated low density filling defects which were suspected as thrombus, embolism or myxoma. Grossly, the main tumor was located in the elastic arteries and their lobar branches, also extended into the atrium and ventricle, with lung parenchymal infiltration focally. Microscopically, tumor cells were predominantly composed of abundant spindle cells with obvious atypia and myxoid background, resembling fibroblastic or myofibroblastic differentiation. Active mitotic figures and necrosis could be seen in some areas. Immunohistochemical staining of vimentin was strongly positive, while pan-cytokeratin, S-100, desmin, Fli-1, CD31, SMA and ERG etc were variably positive only in focal areas. FISH detection showed amplification of MDM2 gene in three cases and EGFR gene in two cases. Metastatic lesions were found in one case by 18, 32 and 42 months after surgery respectively. There was no recurrence or metastasis in the other two cases. Conclusions: PAIS is one of exceptionally poor differentiated mesenchymal tumor that arises from the arterial intima of elastic pulmonary arteries. There was no definite differention in morphology. Gene detection shows amplification of MDM2 and EGFR gene. This tumor often has poor prognosis with aggressive behavior. Complete resection is the only effective therapeutic option. There is disagreement as to whether chemotherapy and radiotherapy can improve survival.

Parkinson's disease (PD) is one of the most common diseases of the nervous system characterized by movement disorders arising from loss of midbrain dopaminergic neurons. The relationship between PD and autophagy has received considerable attention. This study aimed to investigate the involvement of the ATP13A2 gene in damage of dopaminergic neurons induced by abnormal autophagy in a MPTP-induced PD mouse model. MPTP was intraperitoneally injected into C57BL mice at 40 mg/kg for 7 days in experimental group. Saline was injected into mice in the control group. After the injection, the mice were tested at different time points for abnormal limb movement by a swimming test. The brain tissue was collected on day 1, 5, and 7 to measure concentration of intracellular calcium. The expression of ATP13A2 was evaluated by real-time PCR. The expression of α-synclein, LC3, LAMP-2, and CaMKK protein was detected by western blot. We found significant motor dysfunction on day 7 in the experimental group, and the expression of α-synclein in the substantia nigra of the midbrain was significantly increased while the expression of ATP13A2 gene was reduced significantly compared with the control group. The concentration of intracellular calcium in the experimental group was significantly higher than in the control group. Autophagy associated proteins LC3-II and LAMP-2 were downregulated and CaMKK protein was upregulated in midbrain tissues of the experimental group compared to control group. In conclusion, our findings suggest that decreased expression of ATP13A2 may lead to defective autophagy and damage to midbrain dopaminergic neurons., Competing Interests: None., (IJCEP Copyright © 2020.)

Objective: To study the clinicopathological features, diagnosis, and differential diagnosis of atypical epithelioid hemangioendothelioma (EHE). Methods: Eight cases of atypical EHEs were collected from Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University) between 2010 and 2018. EnVision method and fluorescence in situ hybridization (FISH) were used to detect immunophenotype, WWTR1-CAMTA1 and TFE3 gene rearrangement, respectively. Results: There were 4 males and 4 females, ranging from 42 to 59 years (median 47.5 years). The tumors located in soft tissue (3 cases), lung (3 cases), liver (1 case) and chest wall (1 case). One soft tissue EHE involved also adjacent fibula and pleural involvement was present in all three lung cases at the diagnosis. Regional lymph node metastases were present in two cases (one involving soft tissue tumor and one involving liver). Morphologically, the tumor cells were epithelioid with abundant eosinophilic cytoplasm, moderate to marked nuclear pleomorphism, irregular nuclear membrane, unevenly chromatin, and prominent nucleoli. The cells arranged in cords, small nests or solid pattern. The mitotic rate was 4.3 mitoses/2 mm(2) on average (ranging 2 to 9). Tumor necrosis was seen in every case. Among all 8 cases, blister cells were found upon careful observation. Myxohyaline stroma was present in 6 cases. Immunohistochemically, tumor cells expressed CD31 (8/8), CD34 (7/8), ERG (8/8), CKpan (2/7), and CAMTA1 (4/6). None of the tested cases stained for TFE3 (0/6). WWTR1-CAMTA1 fusion gene by FISH was found in all tested 6 cases and TFE3 gene rearrangement was not detected in any. Available clinical follow-up was obtained in 7 cases and the intervals range from 6 to 55 months (average 19.6 months). Six patients had metastasis and 3 patients died of disease. One patient was alive with no evidence of disease. Conclusions: Atypical EHE is a more aggressive tumor than classic EHE, with histological features including high nuclear grade, increased mitotic activity, the presence of solid growth pattern and tumor necrosis. The differential diagnoses include epithelioid angiosarcoma, carcinoma and epithelioid sarcoma.

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of dedifferentiated liposarcoma (DDLPS) with inflammatory myofibroblastic tumor (IMT)-like features. Methods: Five cases of DDLPS with IMT-like features were collected from the First Affiliated Hospital of Nanjing Medical University, the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine and the First People's Hospital of Qinzhou between 2013 and 2018. EnVision method and fluorescence in situ hybridization (FISH) were used to detect the immunophenotype of the tumor cells and the profile of MDM2 gene amplification respectively. Results: All five cases were male and the median age was 61 (range 53 to 65) years. The clinical symptoms were mainly related to the space-occupying lesions. The tumors were located in duodenal mesentery (two cases), intestinal wall (one case), retroperitoneum (one case), and spermatic cord (one case). Grossly, the tumors were not well encapsulated, ranging from 3 to 13 cm (median 6.7 cm) in diameter, with tan to gray and firm cut surface. Histologically, the dedifferentiated component closely resembled inflammatory myofibroblastic tumor (IMT), with spindle/polygonal/stellate-shaped cells arranged in storiform, sheet-like, or random pattern, with varying degrees of chronic inflammation and fibrosis. All three major patterns seen in IMT (myxoid, cellular and hypocellular fibrous) were observed, the hypocellular fibrous pattern was the most common. Well-differentiated liposarcomatous component was found in the peripheral areas of all the tumors. One case had high grade dedifferentiated component. Four cases were strongly positive for MDM2 and p16. Two cases were positive for SMA, and one case was focally positive for desmin and one for CD34. None of the cases stained for ALK-1. FISH demonstrated MDM2 gene amplification in all five cases. Clinical follow-ups were available in all five cases and the interval ranged from 3 to 66 months (median 23 months). Two patients developed recurrences and one patient had metastasis. The remaining two patients were alive with no evidence of tumor recurrence at 3 and 14 months after surgery respectively. Conclusions: DDLPS with IMT-like features is a more aggressive neoplasm than its histological mimic (IMT), and should not be misdiagnosed as other intermediate or low-grade malignant tumors, such as IMT, sclerosing liposarcoma, inflammatory liposarcoma, aggressive fibromatosis, solitary fibrous tumors, low-grade myofibroblastic sarcoma, and low-grade fibrosarcoma.

Objective: To study clinicopathologic features, diagnosis and differential diagnosis of myxoid variant of angiomatoid fibrous histiocytoma (AFH). Methods: Three cases of myxoid variant of AFHs were collected from First Affiliated Hospital of Nanjing Medical University during 2008 and 2017. EnVision method and fluorescence in situ hybridization(FISH) were used to detect immunophenotype and EWSR1 gene rearrangement, respectively. Results: There were 2 males and l female with age at 13, 31, and 42 years, respectively. The patients presented with a painless mass located superficially (subcutaneous or submucosal) in two cases or deep-seated (retroperitoneum) in one case. Grossly, the diameters of tumors were 1, 7, and 2 cm, respectively. The cut surface was solid and firm, tan to gray in colour. Histologically, the circumscribed tumor had fibrous pseudocapsule and peritumoal lymphoplasmacytic infiltrates. The tumor cells arranged in vaguely nodular growth pattern, with prominent myxoid stroma (present in 60% to 100% of the entire tumor). In hypocellular myxoid areas, the spindle to stellate tumor cells arranged in cords or reticular pattern, or in a haphazard manner. However, histiocytoid cells arranged in fascicular, sheet-like, or whorled growth pattern, as in classical AFH, were also identified in hypercelluar areas. Mild to moderate atypia was observed with low mitotic rate of (0-2)/10 HPF. Tumor necrosis was not seen. One case presented with slit-like hemorrhage and sclerosing collagen intermingled with myxoid matrix was identified in 1 case. Immunohistochemically, all cases were positive for CD68 and CD163. Two of three were positive for desmin, EMA, CD99 and one for Calponin, SMA. All cases were negative for S-100 protein, CD34, CD31, CD35, CD21 and CKpan. FISH detection was positive for EWSRl gene in all cases. Available clinical follow-up was obtained in 2 cases, revealing no evidence of disease in 6 and 89 months, respectively. Conclusions: Myxoid variant of AFH is a histological subtype of AFH, with clinical features, immunophenotypes, genomic profiles and biological behavior similar to typical AFH. Their unusual morphology is easily confused with a variety of other myxoid mesenchymal neoplasms, including myoepithelioma and nerve sheath tumors.

Aim: CD30+ diffuse large B-cell lymphoma (DLBCL) has emerged as a new immunophenotypic variant of de novo DLBCLs. However, the prevalence of CD30 positivity is variable according to different studies, and the prognostic significance of CD30 is also controversial. This study aimed to investigate the positive expression rate and prognostic impact of CD30 in de novo DLBCLs and try to find the correlated influences., Methods: A total of 241 patients with de novo DLBCL in east China from 2008 to 2015 were included to investigate the prevalence, clinicopathological features and outcomes of CD30+ de novo DLBCLs. Immunohistochemical evaluation for CD10, CD30, BCL2, BCL6, MUM1/IRF4, MYC and Ki67, and fluorescence in situ hybridisation for MYC and BCL2 gene alterations were performed., Results: Using a >0% threshold, CD30 expression was detected in approximately 10% patient with de novo DLBCL. These predominately presented with centroblastic or anaplastic morphological patterns, less frequently showing immunoblastic morphology or 'starry sky' pattern, mutually exclusive with MYC gene rearrangement, and negatively associated with BCL2 protein expression. CD30 expression was associated with a favourable prognosis of patients' outcomes. However, the multivariate analysis revealed that it was not an independent prognostic factor in de novo DLBCLs. The impact of CD30 might be influenced by the international prognostic index and the expression of MYC and BCL2 proteins., Conclusion: CD30+ DLBCL may be a subset of de novo DLBCLs with characteristic clinicopathological features, but the prognostic role of CD30 is limited., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of pulmonary microcystic fibromyxoma. Methods: In March 2014, at the First Affiliated Hospital to Nanjing Medical University a 58-year-old female patient of pulmonary microcystic fibromyxoma was collected. The clinicopathologic, immunohistochemical and genetic profile of a case of pulmonary microcystic fibromyxoma were studied, and the relevant literature reviewed. Results: The patient was a 58-year-old female who presented with cough and sputum for 1 month. CT scan disclosed a 15 mm nodule in her right middle lobe of lung. The patient underwent a wedge resection with negative margin. Grossly, a well-demarcated peripheral lung nodule was detected, measuring 1.5 cm×1.5 cm×1.0 cm, with myxoid tan-white cut surface containing microcysts. Microscopically, the tumor was composed of bland spindled to stellate-shaped cells widely spaced within prominent fibromyxoid stroma with prominent cystic change. No mitosis or necrosis was present. There were inconspicuous slim curvilinear capillaries and occasional collection of stromal lymphocytes and plasma cells. Immunohistochemically, the tumor cells were positive for vimentin, but negative for CD34, SMA, desmin, S-100 protein, ALK, CKpan, EMA, calretinin and TTF1. Fluorescence in situ hybridization did not show chromosomal translocation involving EWSR1, DDIT3 or FUS genes. The patient was recurrence or metastasis free after follow-up for 38 months. Conclusion: Pulmonary microcystic fibromyxoma is a rare benign lesion that should be differentiated from other lung tumors with myxoid characteristics.

Objective: To study the clinicopathological features of primary hepatic extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) and hepatic pseudolymphoma, and to discuss their differential diagnosis, treatment and prognosis. Methods: Three primary hepatic MALT lymphomas and two hepatic pseudolymphomas collected from January 2012 to March 2017 in the First Affiliated Hospital of Nanjing Medical University were evaluated by HE and immunohistochemistry(IHC), in-situ hybridization and immunoglobulin (Ig) gene rearrangement detection, and the relevant literature reviewed. Results: In the three MALT lymphomas, tumor cells infiltrated the portal areas with nodular pattern, and invaded the surrounding normal liver with serpiginous configuration and formation of confluent sheets. A number of bile ducts were entrapped within the lesions, and showed lymphoepithelial lesion. Reactive lymphoid follicles were present and surrounded by tumor cells, consisting of predominantly centrocyte-like cells and monocytoid B cells. There were clusters of epithelioid histiocytes in one case. The tumor cells were positive for CD20, PAX5 and negative for CD5, CD23, CD10, bcl-6, and cyclin D1. In the two hepatic pseudolymphomas, the lesions presented as solitary nodules well-demarcated from the surrounding liver tissue; one case was partially encapsulated with fibrous tissue. Entrapped bile ducts were only found at the edge of the lesions without lymphoepithelial lesion. The lesions comprised of massive lymphoid proliferation consisting predominantly of reactive lymphoid follicles, but not monocytoid B-cells or atypical cells. By IHC, a mixture of B- and T-cell population was identified. A monoclonal rearrangement of the Ig gene was detected in all three MALT lymphomas but not in two pseudolymphomas. Interphase fluorescence in situ hybridiazation test for MALT1 break-apart gene was positive in two cases of MALT lymphomas and EBER was negative in all studied cases. Conclusions: Primary heptic MALT lymphoma and pseudolymphoma are both rare lymphoid proliferative lesions of liver. These two lesions have overlapping histological and IHC features and are top differential diagnosis to each other. A combination analysis of morphology, immunophenotype and Ig gene rearrangement is helpful to distinguish between them.

Using an immunohistochemistry (IHC) based method, diffuse large B-cell lymphoma (DLBCL) can be classified into germinal center B-cell (GCB) and non-GCB subtypes. However, the prognostic value of Hans algorithm was contradictory in the literature. Using IHC and fluorescence in situ hybridization, we analyzed the antibodies applied in Hans algorithm and other genetic factors in 601 DLBCL patients and prognostic value of Hans algorithm in 306 cases who were treated with chemoimmunotherapy. The results showed that patients with GCB subtype have better overall survival (OS) and progression-free survival (PFS) than non-GCB cases. However, to some extent, double positive (CD10(+)MUM1(+), DP) and triple negative (CD10(-)Bcl6(-)MUM(-), TN) showed different clinical characteristics and prognosis to others that were assigned to the same cell-of-origin group. The DP group showed similar OS (median OS: both not reached, P = 0.3650) and PFS (median PFS: 47.0 vs. 32.7 months, P = 0.0878) with the non-GCB group while the TN group showed similar OS (median OS: both not reached, P = 0.9278) and PFS (median PFS: both not reached, P = 0.9420) with the GCB group. In conclusion, Recognition of specific entities in Hans algorithm could help us to accurately predict outcome of the patients and choose the best clinical management for them.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease that great efforts had been made in to build up molecular and immunophenotypic subgroups that could relatively accurate indicate prognosis and give clue to therapy. Recently, CD30 was reported as a useful predictor with favorable clinical outcome. However, CD30 expression patterns and the clinicopathologic features of CD30 positive DLBCL are not well described thus far, especially in Asian patients. Here, we studied 232 cases of de novo DLBCL in East China to investigate the prevalence and clinicopathological features of CD30-positive DLBCL using a panel of immunohistochemical markers. Applying a >0% threshold, CD30 was expressed in approximately 12% patients with Epstein-Barr virus (EBV) negative DLBCL, affecting younger people and showing a lower frequency of BCL2 expression and MYC/BCL2 co-expression. Patients with CD30-positive DLBCLs showed better progression-free survival and overall survival compared with patients with CD30-negative DLBCLs, although the superior outcome of CD30 positivity had minimal effects on BCL2+ DLBCL or DLBCL with MYC/BCL2 co-expression. Moreover, CD30 could express in CD5+ DLBCL. We concluded that CD30 may be useful as a prognostic marker in rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treated DLBCLs, indicating favorable outcomes in a Chinese population. Further studies with larger samples should be performed to investigate the function of CD30 expression in BCL2+ DLBCLs, DLBCLs with MYC/BCL2 co-expression, and CD5+ DLBCLs, and to evaluate the feasibility of anti-CD30 targeted treatment in DLBCL therapy.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL). Patients with DLBCL harboring MYC aberrations concurrent with BCL2 or/and BCL6 aberrations constitute a specific group with extremely poor outcome. In this study, we retrospectively investigated the incidence and prognosis of MYC, BCL2, and BCL6 aberrations with DLBCL patients in Chinese population. We applied fluorescence in situ hybridization and immunohistochemical analysis in 246 DLBCL patients. The results showed that patients with MYC or BCL2 copy number aberration (CNA) had significantly worse overall survival (OS) and progression-free survival (PFS) than negative cases (P < 0.0001). Patients with both MYC and BCL2 CNA had similar outcomes to those with classic double hit lymphoma or protein double expression lymphoma (MYC and BCL2/BCL6 coexpression). By multivariate analysis, MYC CNA, BCL2 CNA and double CNA were the independent worse prognostic factors. In conclusions, patients with MYC or BCL2 CNA constituted a unique group with extremely poor outcome and may require more aggressive treatment regimens.

Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly is defined as patients older than 50 years alone. However, recent studies showed young patients with sound immune status could also be affected. In this study, we investigated the clinical features and outcomes of patients with EBV positive DLBCL in the different age groups using different EBER cut-off values. The prevalence of EBV positive DLBCL was 14.0% (35/250) and 10.4% (26/250) for EBER cut-off of 20% and 50%, respectively. With both EBER cut-off values, patients with EBV DLBCL shared many unfavorable prognostic characteristics, regardless of age. EBV positive patients, both in the elderly and young groups, showed significantly worse overall survival and progression-free survival than negative cases. Moreover, no significant differences of outcomes were identified between different age groups with EBV positive DLBCL. In conclusion, EBV positive DLBCL patients, regardless of age, shared similar poor prognostic features and showed worse outcome than negative cases. We suggest that the age criterion of EBV positive DLBCL of the elderly, and possibly the name itself, be modified in future.

Epstein-Barr virus (EBV) status was retrospectively analysed by the use of EBV-encoded small RNA (EBER) in situ hybridization (ISH) and EBV DNA analysis in whole blood with diffuse large B-cell lymphoma, to assess the clinical significance for diagnosis, prognostication, and monitoring of tumour burden. Three hundred and twenty-nine patients were retrospectively enrolled, with 232 patients being available for EBER ISH analysis, 189 patients for EBV DNA analysis, and 138 patients for both analyses. EBER was positive in 24 (10.3%) patients, and EBV DNA was positive in 18 (9.5%) patients; the two analyses had 92.8% concordance. Patients with pretreatment EBER positivity had worse overall survival (OS) than those without EBER positivity (p 0.03); the same pattern was observed for EBV DNA (p < 0.01). A significant p-value was also observed for OS when EBER and EBV DNA were combined (p < 0.01). On multivariate analysis, both EBV DNA (hazard ratio 3.71, 95% CI 1.78-7.74, p < 0.01) and EBER (hazard ratio 2.03, 95% CI 1.03-4.00, p 0.04) remained independent predictive factors for OS. Regarding the dynamic changes in copy number of elevated EBV DNA, the transformation from positive to negative after cycle 3 with chemotherapy may have the most capacity to distinguish a superior from an inferior outcome. These findings suggest that EBV DNA in whole blood has good concordance with EBER ISH, and that it may be a better prognostic and monitoring biomarker than EBER., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Gene expression profiling (GEP), which can divide DLBCL into three groups, is impractical to perform routinely. Although algorithms based on immunohistochemistry (IHC) have been proposed as a surrogate for GEP analysis, the power of them has diminished since rituximab added to the chemotherapy. We assessed the prognostic value of four conventional algorithms and the genes in each and out of algorithm by IHC and fluorescence in situ hybridization in DLBCL patients receiving immunochemotherapy. The results showed that neither single protein within algorithms nor the IHC algorithms themselves had strong prognostic power. Using MYC aberrations (MA) either on the genetic or protein levels, we established a new algorithm called MA that could divide patients into distinct prognostic groups. Patients of MA had much shorter overall survival (OS) and progression-free survival (PFS) than non-MA (2-year OS: 56.9% vs. 98.7%; 2-year PFS: 26.8% vs. 86.9%; P < 0.0001 for both). In conclusions, using additional prognostic markers not associated with cell of origin may accurately predict outcomes of DLBCL. Studies with larger samples should be performed to confirm our algorithm and optimize the prognostic system of DLBCL.

Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of epithelioid hemangioma., Methods: The morphologic features of 7 cases of epithelioid hemangioma of skin, bone and venous vessels were studied., Results: There were altogether 4 male and 3 female patients (median age = 34 years; age range from 14 to 54 years). The 3 skin cases presented as single or multiple erythematous to bluish nodules or papules, with or without itchiness. The 2 bone cases appeared as osteolytic expansile lesions on radiologic examination. The remaining 2 cases involved medium-sized venous structures and presented as small isolated nodules in soft tissue. Histologically, the lesions were characterized by the presence of exuberant endothelial proliferations with various degree of inflammatory reaction. The neoplastic endothelial cells were plump, eosinophilic and polygonal, forming vascular channels. Occasional solid sheet-like arrangement was demonstrated. Intracytoplasmic vacuoles were commonly identified, indicating formation of primary lumen. The surrounding stroma contained various number of eosinophils and lymphoplasmacytic cells. Immunohistochemical study showed that the tumor cells were positive for endothelial markers (CD31 and CD34) and negative for epithelial marker (cytokeratin). Follow-up information was available in 6 cases. The duration of follow-up ranged from 5 to 36 months (median = 14 months). There was no evidence of recurrence or distant metastasis., Conclusions: Epithelioid hemangioma is a rare benign curable lesion which can be multifocal, involving skin, soft tissue and bone. It needs to be distinguished from Kimura's disease and epithelioid hemangioendothelioma.

Objective: To improve the understanding of progressive transformation of lymph node germinal centers (PTGC) and to explore its clinical, histopathologic and immunohistochemical features and the differential diagnosis between the related disease of germinal center hyperplasia., Methods: The clinical manifestation, laboratory bindings, treatment and outcome of a patient with PTGC were presented., Results: The main manifestation of the patient was painless peripheral lymphadenopathy. Histopathologic examination of an axillary lymph node showed reactive follicular hyperplasia and the progressive transformation changes germinal centers. The borderline between the germinal center and the mantle layer was obscured. The cells in the progressive transforming germinal centers were positive for CD20(+), CD5(+), CDw75(+)., Conclusion: PTGC is a rare lymphoid disorder. Histopathology and immunohistochemistry are important basis of the diagnosis.

Objective: To study the pathological characteristics, diagnosis and differential diagnoses of hemangiopericytoma-solitary fibrous tumor with giant cells., Methods: Pathological characteristics of seven cases of orbital and extraorbital hemangiopericytoma-solitary fibrous tumors with giant cells were evaluated by HE and immunohistochemistry (EnVision method)., Results: Two cases were located in the orbit, one of which had recurred. Five cases were located in the extraorbital regions. Histologically, the tumors were well-circumscribed and composed of non-atypical, round to spindle cells with collagen deposition in the stroma. The tumors had prominent vasculatures and in areas, pseudovascular spaces lined by multinucleated giant cells lining which were also present in the stroma. Immunohistochemically, both neoplastic cells and multinucleate giant cells expressed CD34. Seven patients underwent tumor excision and were well and without tumor recurrence upon the clinical follow-up., Conclusions: Hemangiopericytoma-solitary fibrous tumor with giant cells is an intermediate soft tissue tumor. It typically involves the orbital or extraorbital regions. Histologically, the tumor should be distinguished from giant cell fibroblastoma, pleomorphic hyalinzing angiectatic tumor of soft part and angiomatoid fibrous histiocytoma.

Objective: To study the clinicopathologic features of inflammatory pseudotumor-like follicular dendritic cell tumor of spleen., Methods: One case of inflammatory pseudotumor-like follicular dendritic cell tumor of spleen was examined macroscopically and microscopically. Immunohistochemical study for CD21, CD23, CD35, clusterin, S-100 protein, vimentin, smooth muscle actin, CD1a, CD68, ALK protein, CD30, CD31, CD34, CD3 and CD20 was performed on formalin-fixed, paraffin-embedded sections by standard EnVision method. In-situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was also carried out., Results: Macroscopically, inflammatory pseudotumor-like follicular dendritic cell tumor was large in size, tan-colored, soft to rubbery in consistance and associated with central hemorrhage and necrosis. Histological examination showed scattered follicular dendritic cells admixed with abundant lymphocytes and plasma cells in the background, simulating inflammatory pseudotumor. On high-power magnification, the follicular dendritic cells possessed a moderate amount of pale to lightly eosinophilic cytoplasm, with indistinct cell borders. The nuclei were ovoid or spindly, with vesicular or stippled chromatin and small distinct, often centrally located, nucleoli. Some of the tumor cells showed nuclear pleomorphism and contained irregular foldings of nuclear membrane, coarse chromatin and prominent eosinophilic nucleoli. Mitotic figures were rarely identified. Immunohistochemical study showed that the tumor cells were positive for vimentin, clusterin, smooth muscle actin and CD68. They were weakly and focally positive for CD35 and S-100 protein, but negative for CD21, CD23, CD1a, ALK protein, CD30, CD31 and CD34. Most of the background lymphocytes were of T-lineage (CD3-positive) ,some were CD20 (B-cell marker)-positive. EBV RNA was demonstrated in the tumor cells by in-situ hybridization analysis., Conclusions: Inflammatory pseudotumor-like follicular dendritic cell tumor is a rarely encountered low-grade malignancy with distinctive morphologic pattern. It is associated with EBV infection.