Solitary fibrous tumor occurring in the colon as submucosal mesenchymal lesion: report of two cases and review of the literature.

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm most often arising from the pleura and rarely in extra-pleural locations, including the gastrointestinal tract. We describe two cases of a SFT presenting as submucosal colonic lesion and review the literature on this lesion. One submucosal lesion was localized in the cecum and was 10 mm in size. The second lesion presented as a 17 mm submucosal rectal lesion. Both lesions presented as well-circumscribed submucosal lesions arranged in short fascicles, blending with abundant collagenous stroma. In both cases, the spindle cells were positive for CD34, STAT6 and CD99, and molecular studies showed NAB2:STAT6 fusion supporting the diagnosis of SFT. Both patients are alive and well 10 and 5 years post-excision, respectively. In conclusion, SFT can occur in the colon as a submucosal lesion and should be included in the differential diagnosis of colonic mesenchymal lesions.

[Malignant solitary fibrous tumors: a clinicopathological and molecular genetic analysis].

Objective: To explore the clinicopathological features, immunophenotype and molecular genetic characteristics of malignant solitary fibrous tumor (MSFT). Methods: Seven cases of MSFT were collected from the First Affiliated Hospital of Zhengzhou University from July 2018 to December 2020. Immunohistochemistry, RNA-based NGS and DNA-based NGS were performed. Results Among the 7 patients, there were 5 males and 2 females with a median age of 53 years (37-69 years). Two tumors located at skull base, and one in the tentorium of cerebellum, parietal occipital region, occipital area, chest and buttock respectively. The maximum diameter of the tumor was 2.5-20.0 cm. Microscopically, typical hemangiopericomatoid structures were noted; the tumor was cellular, fusiform or oval, very pleomorphic, with necrosis and high mitotic figures (>4/10 HPF). In some cases, classical solitary fibrous tumor morphology and dedifferentiated region were observed. Immunohistochemically, the tumor was positive for CD34 (6/7), STAT6 (7/7), bcl-2 (7/7), but negative for S-100 (7/7); CKpan or EMA was positive to varying degrees; mutated p53 was noted (3/7); Ki-67 positive index was more than 10%. NAB2-STAT6 gene fusion was typically detected in all the 7 cases. In 4 cases, ZNF415-FGFR1, COPG1-MET, IPO11-LRRC70_ncRNA-PLAG1 and Clorf198-CD274 (PD-L1) gene fusions were also detected. NOTCH1 mutation was found in 7 cases and TP53 mutation in 4 cases. TERT promoter mutations were not detected in all the cases. Conclusions: MSFT is rare and needs to be differentiated from many other spindle cell tumors. Especially when tumors express epithelial markers, they are easily misdiagnosed as sarcomatoid carcinoma and synovial sarcoma, etc. Immunohistochemistry and molecular detection of NAB2-STAT6 gene fusion have important diagnostic values. NOTCH1 and TP53 mutations may be associated with the progression of MSFT. Some patients have FGFR1 gene fusion and MET gene fusion, which may be potential therapeutic targets.

Expression and prognostic analysis of STAT6(YE361) in Hodgkin lymphoma.

This study aimed to investigate the expression and prognostic significance of the signal transducer and activator of transcription protein 6 (STAT6YE361) and EB virus encoding a small molecule RNA (EBER) in Hodgkin lymphoma (HL), as well as their correlation with clinical parameters. The expression of STAT6YE361 and EBER was investigated in HL via immunohistochemistry and in situ hybridization. Patient clinical data were retrospectively collected from archival libraries, and statistical analysis was performed. Overall, the nuclear positive expression rate of STAT6YE361 was 46%, and the EBER positive expression rate was 57%. STAT6YE361 was specifically expressed on the nucleus in cHL tissues. EBER was overexpressed in HL and had correlations with several clinical data, including age, gender, ethnicity, and primary cancer site. Interestingly, nuclear STAT6YE361 expression was correlated with EBER expression. Based on survival analysis, the nuclear expression of STAT6YE361 and female patients were associated with poor prognosis and were independent prognostic factors for five-year OS. These findings suggest that STAT6YE361 is a potential valuable index in the differential diagnosis and prognosis of HL. The mechanism of STAT6YE361 is related to Epstein-Barr virus infection.

STAT6 and phosphorylated STAT6 are differentially expressed in lymphomas.

BACKGROUND: The STAT6 pathway is implicated in the pathogenesis of various lymphomas; however, its immunohistochemical expression has not been fully investigated. Thus, the aim of this study was to investigate the immunohistochemical expression of the two forms of STAT6, phosphorylated or not, in a series of systemic lymphomas. MATERIALS AND METHODS: Immunohistochemical expression of two antibodies, STAT6 (clone YE361) and pSTAT6 (clone Y641), which recognise the phosphorylated form of the molecule was studied in 60 lymphomas. RESULTS: STAT6YE361 expression was cytoplasmic, with 23.3% of the cases showing high expression. pSTAT6Y641 expression was mostly nuclear and found in 45% of the cases. pSTAT6Y641 nuclear expression was associated with the lymphoma type (p < 0.0001), as it was seen mostly in follicular, Hodgkin and angioimmunoblastic T cell lymphomas. STAT6YE361 cytoplasmic expression was also associated with lymphoma type (p = 0.001), as it was mostly found in diffuse large B cell and marginal B cell lymphomas. No association with PD-L1 expression, other clinicopathological data or prognosis was found. CONCLUSION: The two STAT6 clones are differentially expressed between lymphoma types.

CD34-negative Solitary Fibrous Tumor: A Clinicopathologic Study of 25 Cases and Comparison With Their CD34-positive Counterparts.

CD34-negative solitary fibrous tumors (SFTs) are rare and have not been comprehensively studied. We retrospectively reviewed all cases of SFT confirmed with STAT6 immunohistochemistry and/or STAT6 gene fusion between 2013 and 2020 and collected pertinent clinicopathologic parameters. Of a total of 244 cases, 25 (10%) lacked CD34 expression by immunohistochemistry. Compared with CD34-positive SFT, CD34-negative SFT are more likely to arise in the head and neck area (32% vs. 24%, P=0.02) and present as metastatic disease (28% vs. 1%, P<0.0001). A significantly higher percentage of CD34-negative SFT exhibit high-grade cytologic atypia (hypercellularity, round cell or anaplastic morphology, nuclear pleomorphism, etc.) (48% vs. 22%, P=0.0073). There are no significant differences in the distributions of age, sex, tumor size, mitotic count, tumor necrosis, or risk stratification between CD34-negative and CD34-positive SFT. In addition, only 56% of CD34-negative SFT display a typical hemangiopericytoma-like vascular pattern. Special histologic features among CD34-negative SFT include prominent alternating hypercellular or fibrous and hypocellular myxoid areas with curvilinear vessels mimicking low-grade fibromyxoid sarcoma, pulmonary edema-like microcystic changes, and prominent amianthoid collagen fibers. In conclusion, compared with their CD34-positive counterparts, CD34-negative SFT is more likely to present as metastatic disease, show high-grade nuclear atypia, and lack the characteristic hemangiopericytoma-like vasculature, posing a unique diagnostic challenge. The use of STAT6 immunohistochemistry and/or molecular studies may be prudent in soft tissue tumors that appear CD34 negative and lack conventional SFT histopathologic characteristics.

Genetic variant of SRF-rearranged myofibroma with a misleading nuclear expression of STAT6 and STAT6 involvement as 3' fusion partner.

Pediatric neoplasms with a myofibroblastic differentiation are frequent in children, in particular myofibroma. Recently, a novel deep soft tissue myofibroblastic neoplasm has been described with high cellularity, a smooth muscle phenotype and SRF-RELA fusion. We report the case of a 15-year-old boy who presented with a tumor of the deep soft tissue of the arm, with overlapping histological features with the recently described SRF-RELA group of myofibromas but differing by the presence of calcifications, a novel SRF-STAT6 fusion transcript and nuclear expression of STAT6. No local recurrence nor distant metastasis was detected at the current follow-up of 29 months. The clinical relevance of this novel fusion requires further investigations.

Orbital solitary fibrous tumors: a multi-centered histopathological and immunohistochemical analysis with radiological description.

BACKGROUND: Solitary fibrous tumors (SFT), formerly called hemangiopericytoma, are rare tumors derived from mesenchymal cells originally described in the pleura, but these tumors may affect extraserosal tissues including the lacrimal gland and orbit. OBJECTIVE: Conduct a multi-centered clinical, radiological and histopathological analysis of 17 orbital SFT cases. DESIGN: A retrospective case series. SETTING: Three eye centers in two countries. PATIENTS AND METHODS: The data collected from the charts of 17 adult patients presenting with tissue diagnosis of orbital hemangiopericytoma or SFT from January 2003 to December 2018 included demographics, clinical imaging and histopathological information including immunohistochemical (IHC) characteristics. MAIN OUTCOME MEASURES: The demographic characteristics, clinical presentation, and histopathological patterns or variants of SFT were analyzed. SAMPLE SIZE: 17 adult patients. RESULTS: Mean age was 45 years (range 23-80 years). Male to female ratio was 3:1. The right eye was affected in 12 (70.5%) patients. Commonest presentation was proptosis in 13/17 (76% of patients). Other symptoms were impaired motility (29%) and ptosis (11%). Lesions mostly affected the medial orbit (35%), then orbital apex in 11%. The histopathological classic pattern-less variant was the commonest. One case with aggressive behavior, multiple recurrences and atypical features was encountered. Immunohistochemical (IHC) markers used included CD34 expression in all cases, Bcl-2 expression in 10/11, CD99 in 9/9 and Vimentin in 4/4. STAT6 was used in 2 cases. CONCLUSIONS: SFTs are rare tumors affecting the orbit in both genders equally in their mid-forties, but showed male predominance in our analysis with a predominant classic histopathological pattern. Tissue diagnosis is essential and requires IHC studies for confirmation. LIMITATIONS: Sample size is relatively small owing to the rarity of this tumor in the orbit. CONFLICT OF INTEREST: None.

The Importance of STAT6 in a Schwannoma-like Grade III Solitary Fibrous Tumor/Hemangiopericytoma Located in the Cerebellopontine Angle and Meckel's Cave.

BACKGROUND: Hemangiopericytoma (HPC) is a rare mesenchymal tumor of the brain that occurs in the central nervous system as a solitary fibrous tumor. Surgical treatment of HPC is known to be beneficial, but results on the role of complete resection and adjuvant radiation are conflicting. However, it is often difficult to detect a central nervous system solitary fibrous tumor/HPC before surgery. We describe a presumed left trigeminal schwannoma that was histopathologically shown to be an HPC. CASE DESCRIPTION: A 65-year-old man presented with paresthesia of the second and third branches of the left trigeminal nerve. Magnetic resonance imaging showed a tumoral lesion in the left cerebellopontine angle and Meckel's cave. We suspected a schwannoma and performed surgery, which resulted in only a partial resection because of tumor bleeding and unexpected intraoperative histologic findings. We could not achieve a definitive diagnosis. However, we observed local recurrence and disseminated lesions 5 and 6.5 years later, respectively. We performed a second surgery and were able to definitively diagnose the lesion as a grade III HPC based on the positive expression of STAT6 during immunostaining. CONCLUSIONS: As solitary fibrous tumor/HPC requires gross total resection for effective resolution, it is imperative to consider it in the differential diagnoses of similar tumors. If an unusual pathologic image is found, we recommend rapid immunostaining for STAT6 to reach a definitive conclusion regarding the tumor type. This case highlights the importance of considering HPC when screening or diagnosing central nervous system lesions, especially in this rare location.

Solitary fibrous tumors of the head and neck region revisited: a single-institution study of 20 cases and review of the literature.

A solitary fibrous tumor (SFT) is a rare, NAB2-STAT6 fusion gene-associated mesenchymal neoplasm. It most commonly arises in the pleural site, but it can occur at many other sites, and rarely also in the head and neck (H&N) region. STFs may show many growth patterns and therefore can be easily mistaken for other more common H&N spindle cell or epithelial lesions. In this study, we present our experience in the diagnosis of 20 cases of SFT in the H&N region and discuss their most notable mimickers. In all cases, STAT6 expression was found positive by immunohistochemistry, and the NAB2-STAT6 fusion was confirmed by next-generation sequencing. Three major fusion variants were detected: NAB2ex2-STAT6int1 (5/20, 25%), NAB2ex6-STAT6ex16 (4/20, 20%), and NAB2ex4-STAT6ex2 (3/20, 15%). Clinical follow-up was available for 16 patients (median follow-up time: 84 months). One patient with a morphologically malignant SFT experienced multiple local recurrences, followed by dissemination into the lungs and meninges. This malignant SFT also displayed an aberrant FLI1 expression, which was not previously reported in SFT cases. We also summarize findings from 200 cases of SFT of the H&N region, which included cases from our study, and from previous studies that reported on the fusion status of the STAT6 gene. The results suggest that metastatic disease developed only in cases with STAT6 variants that included the DNA-binding domain (STAT6-full variants), which contradicts expectations from previous reports and deserves further investigation.

Solitary fibrous tumor of the orbital region: report of a case with emphasis on the diagnostic utility of STAT-6.

Solitary fibrous tumor (SFT) is a relatively rare soft tissue neoplasm originally described in the pleura. Since its first description, several cases arising in extra-pleural superficial and deep soft tissues have been reported in the literature. SFT arising in the head and neck region is quite rare, representing about the 6% of all SFTs, and the sinonasal tract is the most common involved region, followed by the orbit, the oral cavity and the salivary glands. Herein, we report the clinico-pathologic features of a rare case of SFT of the orbital region, emphasizing the diagnostic role of the immunomarker STAT-6. A 52-year-old female presented to our hospital with a nodular mass in the left orbital region. Histological examination revealed a uniformly hypercellular tumor composed of pale to slightly eosinophilic bland-looking spindle cells arranged in intersecting short fascicles with interspersed stellate-shaped, keloid-type collagen fibers. Notable hypocellular areas, perivascular hyalinization and hemangiopericytoma-like branching vascular pattern were absent. Immunohistochemically, neoplastic cells were diffusely positive for vimentin, CD34 and STAT-6. The introduction of STAT-6 in daily diagnostic practice is helpful to confidentially render a diagnosis of SFT even in the presence of unusual morphology and site.

Solitary fibrous tumor with atypical features of the paravesical space: benign clinical course at the 10-years follow-up. Report of a case and review of the literature.

Extra-pleural solitary fibrous tumor (SFT) is a relatively rare soft tissue neoplasm, with only rare cases reported in the pelvic cavity. Most SFTs are histologically benign, with only a few malignant cases reported in the literature so far. We report a rare case of SFT arising in the paravesical space of a 79-year-old man. Histologically the tumor corresponds to an "intermediate risk tumor" according to a risk stratification scheme for metastatic potential, which incorporates patient age, tumor size, mitotic activity and necrosis. Notably tumor showed a benign clinical course without evidence of local recurrence after a 10-years follow-up. Tumor was composed of both spindle and epithelioid cells variably set in a fibro-myxoid stroma, with focal pleomorphic, necrotic and highly mitotic (> 4 mitoses/10HPF) areas. Immunohistochemistry, showing a diffuse CD34 and STAT6 immunoreactivity, supported the diagnosis of SFT. The present case emphasizes that the clinical course of the pelvic SFTs with atypical morphological features is unpredictable on the basis of morphology alone, and thus the term "SFT with atypical features, including the risk stratification class" should be preferred to "malignant SFT".

Diagnostic utility of STAT6YE361 expression in classical Hodgkin lymphoma and related entities.

Although the distinction of classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma using morphology and immunostains is straightforward in most instances, occasional cases pose diagnostic challenge. We sought to determine the utility of the novel YE361 STAT6 rabbit monoclonal antibody in Hodgkin lymphoma and diagnostically challenging B- and T-cell non-Hodgkin lymphoma entities with Hodgkin-like features. Cases from seven institutions included: 57 classical Hodgkin lymphomas (31% EBV+), 34 nodular lymphocyte predominant Hodgkin lymphomas, 34 mimicking B- and T-cell non-Hodgkin lymphomas, and 7 reactive lymphoproliferations. After review of histology, STAT6YE361 immunostaining was performed. The intensity and spatial localization of immunopositivity was assessed in neoplastic cells. Additional FISH for programmed death ligand-1 (PD-L1) was performed in one patient in paired treatment-naive and relapse biopsy tissues. Two STAT6YE361 immunopositive cases were examined by whole-exome sequencing after flow sorting to assess mutations in STAT6 pathway genes. Most classical Hodgkin lymphomas showed nuclear staining for STAT6YE361 [46/57 cases (80%)] on Hodgkin cells. Staining was exclusively nuclear in a minority [12/46 (26%)], while dual nuclear and cytoplasmic localization was more common [34/46 (74%)]. In contrast, all nodular lymphocyte predominant Hodgkin lymphomas [0/34 (0%)] were negative for nuclear STAT6YE361 staining on the lymphocyte predominant cells. Within B- and T-cell non-Hodgkin lymphomas, nuclear STAT6YE361 was seen in: B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, and in primary mediastinal large B-cell lymphoma. Strong PD-L1 gene amplification was noted in the paired cHL and relapse B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, although STAT6YE361 was negative in both biopsies. Whole-exome sequencing identified mutations in B2M, XPO1, and ITPKB as well CISHP213L (in the STAT pathway) in one classical Hodgkin lymphoma patient positive for nuclear STAT6YE361 although no underlying STAT6 mutations were observed in either sample examined. STAT6YE361 nuclear staining has 100% positive predictive value and 85.7% negative predictive value in confirming or excluding classical Hodgkin lymphoma diagnosis in the distinction from nodular lymphocyte predominant Hodgkin lymphoma and other benign and malignant entities.

STAT6 expression in spindle cell lesions of the breast: An immunohistochemical study of 48 cases.

The diagnosis of spindle cell lesions of the breast parenchyma is challenging. Some of these lesions share the expression of CD34, posing differential diagnostic problems, especially in core biopsies. Recently, antibodies against the STAT6 C-terminal, are being used in paraffin-embedded tissues as a surrogate for identifying the NAB2-STA6 fusion gene which is considered a specific molecular marker for solitary fibrous tumor. Accordingly, we investigated the expression of STAT6 in a large series of uncommon spindle cell tumor-like and tumor lesions occurring primarily in the breast parenchyma. We collected 10 classic-type myofibroblastomas, 9 desmoid-type fibromatosis, 6 spindle cell metaplastic carcinoma, 5 benign fibroblastic spindle cell tumors, 3 solitary fibrous tumors, 7 pseudoangiomatous stromal hyperplasias, 2 reactive spindle cell nodules, 1 leiomyoma, 1 spindle cell lipoma, 1 case of inflammatory pseudotumor, 1 nodular fasciitis, 1 myxoma and 1 dermatofibrosarcoma protuberans. A diffuse and strong nuclear STAT6 expression was restricted only to solitary fibrous tumors, while the other lesions were negative or showed only weak cytoplasmic expression. The present study confirms that the demonstration of a diffuse and strong STAT6 nuclear staining is very helpful in distinguishing solitary fibrous tumor from other spindle cell mimics arising in the breast.

[Clinicopathologic features of glomus tumor of the kidney].

Objective: To investigate the clinicopathologic and differential diagnostic features of glomus tumor of the kidney. Methods: Four cases of glomus tumor of the kidney were collected from the archives of Peking University Third Hospital, the Second Hospital of Tianjin Medical University, Ningbo Yinzhou Second Hospital and Zhejiang Provincial People's Hospital between January 2012 to June 2017; the clinical and radiologic features, histomorphology, immunohistochemistry, ultrastucture and prognosis were analyzed and the relevant literature was reviewed. Results: Patients consisted of 2 men and 2 women with ages ranging from 37 years to 66 years (mean 55 years). Three patients had history of hypertensive disease (grade Ⅱ, 3 to 10 years). The tumors measured in maximum diameter from 3.0 cm to 4.0 cm (mean 3.6 cm) and showed gray-white to yellow and tan on cut surface. Macroscopical examinations showed all tumors were circumscribed but non-encapsulated. Histologically, 1 tumor presented as glomus tumor with extensive myxoid change, 1 as cellular and solid pattern glomus tumor, 1 as glomangioma with focal myopericytoma-like pattern and 1 as symplastic glomus tumor with areas resembling myopericytoma. The tumor cells in two cases showed scant cytoplasm and uniform, bland-appearing nuclei without mitoses. In one case, the tumor cells were epithelioid with abundant eosinophilic cytoplasm and relatively well-defined cell borders. There was an increased mitosis of 4/50 HPF; however, no evidence of atypical mitosis or nuclear atypia was noted. In the symplastic glomus tumor the tumor cells showed frequently nuclear pleomorphism without mitoses. By immunohistochemistry, all tumors showed strong and diffuse reactivities to at least 3 of the 4 muscle-associated markers (SMA, h-Caldesmon, MSA and Calponin), 3 tumors strongly and diffusely expressed collagen Ⅳ, 2 expressed CD34 and 1 focally expressed desmin; whereas markers including epithelial, neuroendocrine, nephrogenic, melanoma-associated, STAT6, S-100 protein, CD117 and ß-catenin all were negative in all the 4 tumors. Ultrastuctural analysis was done in 2 cases and showed prominent cytoplasmic actin bundles and pericellular basement membrane, and lacking of rhomboid renin crystals in both tumors. The hypertension persisted after surgical resection for all the 3 patients with this medical history. Follow-up information (range: 6-64 months, mean: 44 months)showed that no evidence of local recurrence or distant metastasis was identified in all 4 patients. Conclusions: Glomus tumor rarely occurs in the kidney and usually has a good prognosis. Careful attention to its morphology with the judicious use of immunohistochemistry and ultrastuctural analysis can be helpful for its diagnosis and differential diagnosis.

Interleukin-4 protects from chemotherapy-induced peripheral neuropathy in mice modal via the stimulation of IL-4/STAT6 signaling.

PURPOSE: To investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. METHODS: The mouse model of vincristine-induced peripheral neuropathy and interleukin (IL)-4 knockout mice were utilized to investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Vincristine induced increased sensitivity to mechanical stimulation was measured by von Frey hair test 7 and 14 days after intraperitoneal administration of 0.1 mg/kg vincristine in mice. Relative expression levels of cytokines were detected by quantitative real-time PCR. STAT6 expression following vincristine treatment was assessed with western blotting. RESULTS: We discovered that IL-4/STAT6 signaling was down-regulated in vincristine-treated mice. Deletion of IL-4 in mice increased the sensitivity to mechanical allodynia. IL-4 knockout mice also produced more pro-inflammatory cytokines, including IL-1ß and TNF-α. Notably, co-administration of exogenous recombination IL-4 significantly prevented vincristine-induced mechanical allodynia. CONCLUSION: Anti-inflammatory cytokine IL-4 protects rodent model from vincristine-induced peripheral neuropathy via the stimulation of IL-4/STAT6 signaling and inhibition of the pro-inflammatory cytokines.

Utility of STAT6 and 13q14 deletion in the classification of the benign spindle cell stromal tumors of the breast.

The boundaries of the benign spindle cell stromal tumors of the breast are still confusing. This is the reason why different names are interchangeably used for the same tumor and vice versa the same name for different tumors. Therefore, we studied the immunoexpression of easily available markers, such as CD34, α-smooth muscle actin, and desmin, with the addition of STAT6, as well as the chromosome 13q14 region by fluorescence in situ hybridization analysis in a series of 19 cases of benign spindle cell stromal tumors of the breast. Based on the morphologic and immunohistochemical findings, the following histotypes were identified: (i) tumors (10/19 cases) with the characteristic morphology of myofibroblastoma and stained with vimentin, CD34, desmin, and α-smooth muscle actin; (ii) fibroblastic benign spindle cell tumors (5/19 cases) composed of fibroblast-like cells stained only with vimentin and CD34; (iii) tumors (2/19 cases) with the typical morphologic features of solitary fibrous tumor and stained with vimentin, CD34, and STAT6; (iv) 1 case of spindle cell lipoma stained with vimentin and CD34; and (v) 1 case of fibroma composed of a paucicellular, diffusely hyalinized stroma with expression of vimentin and CD34. Notably most of the tumors, with the exception of solitary fibrous tumor, showed monoallelic deletion of FOXO1. This finding supports that myofibroblastoma, fibroblastic benign spindle cell tumor, spindle cell lipoma, and fibroma of the breast are histogenetically related lesions which belong to the same tumor entity.

Interleukin-4 protects from chemotherapy-induced peripheral neuropathy in mice modal via the stimulation of IL-4/STAT6 signaling

Abstract Purpose: To investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Methods: The mouse model of vincristine-induced peripheral neuropathy and interleukin (IL)-4 knockout mice were utilized to investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Vincristine induced increased sensitivity to mechanical stimulation was measured by von Frey hair test 7 and 14 days after intraperitoneal administration of 0.1 mg/kg vincristine in mice. Relative expression levels of cytokines were detected by quantitative real-time PCR. STAT6 expression following vincristine treatment was assessed with western blotting. Results: We discovered that IL-4/STAT6 signaling was down-regulated in vincristine-treated mice. Deletion of IL-4 in mice increased the sensitivity to mechanical allodynia. IL-4 knockout mice also produced more pro-inflammatory cytokines, including IL-1β and TNF-α. Notably, co-administration of exogenous recombination IL-4 significantly prevented vincristine-induced mechanical allodynia. Conclusion: Anti-inflammatory cytokine IL-4 protects rodent model from vincristine-induced peripheral neuropathy via the stimulation of IL-4/STAT6 signaling and inhibition of the pro-inflammatory cytokines.

[Clinicopathologic features of atypical spindle cell lipomatous tumor].

Objective: To investigate the clinicopathologic characteristics, immunophenotype, differential and diagnostic features of atypical spindle cell lipomatous tumor (ASLT). Methods: Three cases of ASLT were collected from January 2010 to March 2017 at Zhejiang Provincial People's Hospital. The clinical and imaging features, histomorphology, immunophenotype and prognosis were analyzed. Fluorescence in situ hybridization (FISH) was used to detect MDM2 gene amplification, and relevant literature was reviewed. Results: All three patients were adult males, aged 38, 43 and 54 years, respectively. One tumor originated in the subcutaneous soft tissue in the head and neck, one was located in the left primary bronchus and one in the latissimus dorsi muscle. Grossly, all three tumors were circumscribed and ranged from 4.0 to 5.8 cm in size. Microscopically, all showed a focally infiltrative front. These tumors were composed of variable proportions of spindle-shaped and adipocytic cells in a background of variable fibrous and edematous matrix. Scattered lipoblasts were easily seen. One tumor was composed predominately of spindle tumor cells, one of adipocytic cells, and one of equally mixed cell populations. The spindle tumor cells were generally bland-appearing with focal nuclear enlargement and hyperchromasia noted in one case. Mitosis was not seen in neither the spindle cells nor the adipocytic cells. By immunohistochemistry, diffuse and strong reactivity to CD34 of the spindle cells was noted in all cases, definite loss of Rb expression was noted in one of three cases, and S-100 protein was expressed only in the adipocytic cells. INI-1 was intact and Ki-67 index was 1% to 3%. All other markers including CDK4, MDM2, STAT6, SOX10, CD99, bcl-2, ß-catenin, CD117, GFAP, CK, EMA, SMA and desmin were negative. FISH of MDM2 was done in two cases, and both showed no amplification. The ASLT in the head and neck had two recurrences during 17 months of follow-up, whereas the tumor in the latissimus dorsi was free of disease during 33 months of follow-up. Conclusions: ASLT is a rare subtype of low-grade adipocytic neoplasm and is distinctive from atypical lipomatous tumor/well-differentiated liposarcoma. The histomorpholgy of ASLT has significant heterogeneity and forms a continuous spectrum. ASLT needs to be distinguished from a series of benign and malignant soft tissue tumors.

Multifocal Cytokeratin Expression in a Dedifferentiated Solitary Fibrous Tumor With Heterologous Rhabdomyosarcomatous Differentiation: A Challenging Diagnosis!

We report the case of a dedifferentiated solitary fibrous tumor with heterologous rhabdomyosarcomatous differentiation in a 74-year-old male presenting with a rapidly growing, large soft tissue tumoral mass in the gluteal muscles of the right hip. Dedifferentiation in solitary fibrous tumor had not been recognized until very recently and is an extremely rare phenomenon in this tumor type. In the present case, the diagnosis of dedifferentiated solitary fibrous tumor was difficult because of the absence of areas of conventional solitary fibrous tumor with a predominantly poorly differentiated, anaplastic tumor component in the incision biopsy composed of heterogeneous areas with small blue round cell (Ewing sarcoma-like), rhabdoid, epithelioid, and pleomorphic morphology. Moreover, the "unforeseen" strong patchy to multifocal positivity for cytokeratin AE1/AE3 and desmin made the diagnosis of a dedifferentiated solitary fibrous tumor even more challenging in this case. The morphology (presence of branching thin-walled, hemangiopericytoma-like blood vessels) and the immunohistochemical profile (including STAT6 and GRIA2 positivity) were very useful to differentiate this very challenging case of a cytokeratin-positive dedifferentiated solitary fibrous tumor with heterologous rhabdomyosarcomatous differentiation from a broad list of differential diagnoses.