Cytokeratin-positive Malignant Tumor in the Abdomen With EWSR1/FUS-CREB Fusion: A Clinicopathologic Study of 8 Cases.

ATF1, CREB1, and CREM, which encode the CREB family of transcription factors, are fused with EWSR1 or FUS in human neoplasms, such as angiomatoid fibrous histiocytoma. EWSR1/FUS-CREB fusions have recently been reported in a group of malignant epithelioid tumors with a predilection to the peritoneal cavity and frequent cytokeratin expression. Here, we studied 8 cytokeratin-positive abdominal malignancies with these fusions for further characterization. The tumors affected males (15 to 76 y old) and presented as intra-abdominal masses with concurrent or subsequent peritoneal dissemination, ascites, and/or metastases to the liver or lymph nodes. Four patients died of the disease within 18 to 140 months. Cases 1 to 5 showed multinodular growth of monomorphic epithelioid cells with focal serous cysts. Lymphoplasmacytic infiltration was prominent and was associated with systemic inflammatory symptoms. Two patients suffered from membranous nephropathy with nephrosis. The tumors displayed partly overlapping phenotypes with malignant mesothelioma, including diffuse strong expression of AE1/AE3 and WT1 and membranous positivity of sialylated HEG1, although calretinin was negative. Case 6 showed similar histology to cases 1 to 5, but expressed smooth muscle actin diffusely, lacked WT1 and HEG1, and harbored prominent pseudoangiomatous spaces. Cases 7 and 8 displayed dense growth of small oval to short spindle cells, with occasional molding and minor swirling, superficially resembling small cell carcinoma. Lymphoplasmacytic infiltration was not observed. The tumors were positive for AE1/AE3 and CD34 (focal), whereas calretinin, WT1, and HEG1 were negative. The detected fusions were FUS-CREM (n=4), EWSR1-ATF1 (n=2), EWSR1-CREB1 (n=1), and EWSR1-CREM (n=1). We confirmed the prior observation that these tumors do not fit perfectly with known entities and provided additional novel clinicopathologic information. The tumors require wider recognition because of more aggressive behavior than angiomatoid fibrous histiocytoma despite similar genetics, and potential misdiagnosis as unrelated diseases, such as neuroendocrine neoplasms.

Solitary fibrous tumor of the anterior abdominal wall. A case report and review of the literature.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm affecting soft tissues with a not well defined biological behavior. SFT occurs mostly in the pleura and the thorax, while extra-thoracic localization is uncommon and abdominal localization is very rare. Histologically, SFT is a well defined mass with splindle-cell proliferation in collagenous matrix with staghorn vascular network and CD34 reactive. CASE REPORT: A 64 years-old man with a history of recurrent gastric cancer previously treated with total gastrectomy, was admitted with contrast enhanced CT-scan diagnosis of a well demarcated oval mass of 4.8 cm with microcysts, vascularized in the arterial phase and with wash out in the tardive phase, located in the peritoneal side of right rectus abdominis muscle, suspected for metastatic gastric tumor. The patient underwent minilaparotomy and en-bloc excision of the lesion. Histologically the tumor was characterized by a hemangiopericitoma like growth pattern and the immunostaining was positive to CD34, CD99, BCL-2 and Vimentin. The definitive diagnosis was SFT with a proliferation index (Ki-67/MIB-1) <3%. In our case, chemotherapy was not indicated. At the 6-month follow-up, the patient is in good clinical conditions with no recurrence or metastasis. CONCLUSIONS: We reported a rare case of primitive SFT located in peritoneal side of the of right rectus abdominis muscle treated surgically, in a patient previously affected by gastric adenocarcinoma. In this case, SFT showed a benign behaviour during a short term follow-up. Dimensional pattern, histopathological features and curative surgery remain the most important indicators of clinical outcome. KEY WORDS: Abdominal wall, Hemangiopericitoma, SFT, Solitary fibrous tumorSpindle cell.

"Pigmented Extramammary Paget Disease"-A Potential Mimicker of Malignant Melanoma and a Pitfall in Diagnosis: A Case Report and Review of the Literature.

Extramammary Paget disease (EMPD) is a rare intraepithelial carcinoma and an uncommon variant of Paget disease affecting areas of the apocrine-rich skin of the perineum, vulva, and less commonly, axilla. Women in their sixth to eighth decades are commonly affected. It is exceedingly rare for EMPD to present on the face, chest, abdomen, or other nonapocrine sites and even more unusual for EMPD to present as a pigmented lesion. The relationship between Paget cells in pigmented extramammary Paget disease (PEMPD) and reactive proliferation and colonization by melanocytes has been poorly explored. The relevance of this rare entity resides in its potential to be misdiagnosed clinically and histopathologically as malignant melanoma in situ. Therefore, application of a panel of immunostains and careful analysis and interpretation of these findings are essential to arrive at the correct diagnosis. We report a new case of PEMPD on a nonapocrine site. The specimen was examined by routine microscopy including hematoxylin and eosin stain as well as immunostains. Histologic examination revealed characteristic features of PEMPD confirmed with immunohistochemical stains.

Embryonal rhabdomyosarcoma within abdomen and pelvis in an adult.

Rhabdomyosarcoma arising in abdomen and pelvis is an uncommon but important type of soft tissue sarcoma, posing a great challenge for clinicians. Sporadic cases of intra-abdominal rhabdomyosarcoma were reported, but mostly in pediatrics. We demonstrated a rare case of primary abdominopelvic rhabdomyosarcoma in an elderly woman who presented with a notable increase in abdominal circumference and constipation. Abdominal magnetic resonance imaging showed a huge mass throughout the abdomen and pelvis. Cytoreductive surgery was performed by gynecologists due to the suspicious diagnosis of disseminated leiomyosarcoma. However, the final pathological analysis revealed embryonal rhabdomyosarcoma. Although adjuvant chemotherapy was administered, localized recurrence was identified 6 months after the initial operation. Gynecologists and radiologists should be aware of it so it can be listed in the differential diagnosis of masses that primarily arise in the abdomen and pelvis.

Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study.

IMPORTANCE: The data reported herein were accepted for assessment by the US Food and Drug Administration for Biologics License Application under priority review to establish the clinical benefit of durvalumab as second-line therapy for locally advanced or metastatic urothelial carcinoma (UC), resulting in its recent US approval. OBJECTIVE: To report a planned update of the safety and efficacy of durvalumab in patients with locally advanced/metastatic UC. DESIGN, SETTING, AND PARTICIPANTS: This is an ongoing phase 1/2 open-label study of 191 adult patients with histologically or cytologically confirmed locally advanced/metastatic UC whose disease had progressed on, were ineligible for, or refused prior chemotherapy from 60 sites in 9 countries as reported herein. INTERVENTION: Patients were administered durvalumab intravenous infusion, 10 mg/kg every 2 weeks, for up to 12 months or until progression, starting another anticancer therapy, or unacceptable toxic effects. MAIN OUTCOMES AND MEASURES: Primary end points were safety and confirmed objective response rate (ORR) per blinded independent central review (Response Evaluation Criteria In Solid Tumors [RECIST], version 1.1). RESULTS: A total of 191 patients with UC had received treatment. As of October 24, 2016 (90-day update), the median follow-up was 5.78 months (range, 0.4-25.9 months). The median age of patients was 67.0 years and most were male (136 [71.2%]) and white (123 [71.1%]). All patients had stage 4 disease, and 190 (99.5%) had prior anticancer therapy (182 [95.3%] postplatinum). The ORR was 17.8% (34 of 191; 95% CI, 12.7%-24.0%), including 7 complete responses. Responses were early (median time to response, 1.41 months), durable (median duration of response not reached), and observed regardless of programmed cell death ligand-1 (PD-L1) expression (ORR, 27.6% [n = 27; 95% CI, 19.0%-37.5%] and 5.1% [n = 4; 95% CI, 1.4%-12.5%] in patients with high and low or negative expression of PD-L1, respectively). Median progression-free survival and overall survival were 1.5 months (95% CI, 1.4-1.9 months) and 18.2 months (95% CI, 8.1 months to not estimable), respectively; the 1-year overall survival rate was 55% (95% CI, 44%-65%), as estimated by Kaplan-Meier method. Grade 3/4 treatment-related adverse events (AEs) occurred in 13 patients (6.8%); grade 3/4 immune-mediated AEs occurred in 4 patients (2.1%); and treatment-related AEs led to discontinuation of 3 patients (1.6%), 2 of whom had immune-mediated AEs that led to death (autoimmune hepatitis and pneumonitis). CONCLUSIONS AND RELEVANCE: Durvalumab, 10 mg/kg every 2 weeks, demonstrates favorable clinical activity and an encouraging and manageable safety profile in patients with locally advanced/metastatic UC. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01693562.

Primary undifferentiated small round cell sarcoma of the deep abdominal wall with a novel variant of t(10;19) CIC-DUX4 gene fusion.

We experienced a 38-year-old Japanese male with t(10;19) CIC-DUX4 -positive undifferentiated small round cell sarcoma in the deep abdominal wall. Three months before his first visit to our hospital, he noticed a mass in his right abdominal wall. Computed tomography on admission revealed a solid abdominal tumor 70×53mm in size and multiple small tumors in both lungs. The biopsy of the abdominal tumor revealed undifferentiated small round cell sarcoma, suggestive of Ewing sarcoma. Under the clinical diagnosis of Ewing-like sarcoma of the abdominal wall with multiple lung metastases, several cycles of ICE (ifosfamide, carboplatin and etoposide) therapy were performed. After the chemotherapy, the lung metastases disappeared, while the primary lesion rapidly grew. Additional VDC (vincristine, doxorubicin and cyclophosphamide) therapy was carried out without apparent effect. Although the surgical removal of the primary lesion was done, peritoneal dissemination and a huge metastatic liver tumor appeared thereafter. The patient died of disease progression two months after the surgery. The total clinical course was approximately one year, showing that the tumor was extremely aggressive. The tumor cells of the surgical specimen were positive for CD99, WT1, calretinin, INI1, ERG and Fli1 by immunohistochemistry. Fusion gene analyses using the frozen surgical material revealed negativity for EWSR1-Fli1, EWSR1-ERG and t(4;19) CIC-DUX4 fusions, but positivity for t(10;19) CIC-DUX4 fusion. Thus, we made a final pathological diagnosis of t(10;19) CIC-DUX4-positive undifferentiated small round cell sarcoma. To our knowledge, this is the 13th case of t(10;19) CIC-DUX4 undifferentiated small round cell sarcoma with precise clinicopathological information. Especially in our case, two types of t(10;19) CIC-DUX4 fusion transcripts were observed, both of which are in-frame and novel.

Collagenoma in an African Clawed Frog (Xenopus laevis).

A 3-y-old female Xenopus laevis was reported for a gray mass on the abdomen. The frog was used for egg collection and was otherwise experimentally naïve. On physical exam, the frog was bright and active and had a firm, gray, lobulated mass (1.5 cm × 0.5 cm × 0.5 cm) in the cutaneous tissue of the left lateral abdomen. An excisional biopsy was performed under anesthesia, and the entire mass was removed and processed for histopathology. Microscopically, the dermis was greatly expanded by connective tissue with a marked decrease in the number of glands, and occasional degenerative glands were present. When stained with Masson trichrome, the excessive connective tissue stained blue, indicating that it was composed of collagen. With Verhoeff-van Gieson staining, the connective tissue stained bright red with an absence of black-staining material, demonstrating the presence of collagen and ruling out elastic fibers. In light of the morphology of the mass and the results of the special stains, the mass was diagnosed as a collagenoma. To our knowledge, this report is the first description of a collagenoma in X. laevis.

Giant abdominal leiomyoma of male: a case report and literature reviews.

Abdominal leiomyomas are extremely rare intraabdominal tumors, especially in male patient. Here, we report a case of a 22 years-old male with a huge abdominal leiomyoma. The patient presented with a chief complaint of abdominal distension for three months, no others significant symptom were found. CT-scan showed a cystic-solid huge mass in the middle and lower abdominal peritoneal cavity with uneven density. An exploratory laparotomy was performed and the tumor was completely resected. Microscopically, Tumor cells have a spindled shape, eosinophilic cytoplasm, and cigar-like nuclei, arranged in bundles or intersecting fascicles. Immunohistochemistry, the tumor cells were SMA, desmin diffuse positive and CD117, S-100 negative, interestingly, ER, PR were positive. The characteristics of a few of the male abdominal leiomyoma reported in the literature were generalized.

Radiation-induced Sarcomas Occurring in Desmoid-type Fibromatosis Are Not Always Derived From the Primary Tumor.

Desmoid-type fibromatosis is a rare, highly infiltrative, locally destructive neoplasm that does not metastasize, but recurs often after primary surgery. Activation of the Wnt/ß-catenin pathway is the pathogenic mechanism, caused by an activating mutation in exon 3 of CTNNB1 (85% of the sporadic patients). Radiotherapy is a frequent treatment modality with a local control rate of approximately 80%. In very rare cases, this may result in the development of radiation-induced sarcoma. It is unclear whether these sarcomas develop from the primary tumor or arise de novo in normal tissue. In 4 tertiary referral centers for sarcoma, 6 cases of desmoid-type fibromatosis that subsequently developed sarcoma after radiotherapy were collected. The DNA sequence of CTNNB1 exon 3 in the desmoid-type fibromatosis and the subsequent postradiation sarcoma was determined. Sarcomas developed 5 to 21 years after the diagnosis of desmoid-type fibromatosis and included 2 osteosarcomas, 2 high-grade undifferentiated pleomorphic sarcomas, 1 fibrosarcoma, and 1 undifferentiated spindle cell sarcoma. Three patients showed a CTNNB1 hotspot mutation (T41A, S45F, or S45N) in both the desmoid-type fibromatosis and the radiation-induced sarcoma. The other 3 patients showed a CTNNB1 mutation in the original desmoid-type fibromatosis (2 with a T41A and 1 with an S45F mutation), which was absent in the sarcoma. In conclusion, postradiation sarcomas that occur in the treatment area of desmoid-type fibromatosis are extremely rare and can arise through malignant transformation of CTNNB1-mutated desmoid fibromatosis cells, but may also originate from CTNNB1 wild-type normal cells lying in the radiation field.

Epithelioid inflammatory myofibroblastic sarcoma with recurrence after extensive resection: significant clinicopathologic characteristics of a rare aggressive soft tissue neoplasm.

A case of epithelioid inflammatory myofibroblastic scarcoma (EIMS) developing in an 8-year-old boy who presented with a bulky intra-abdominal occupying lesion with recurrence undergoing a radical resection was reported. Histologically, the tumor cells arranged in cords, strands or sheets of round-to-epithelioid cells with a vesicular nuclear chromatin pattern, prominent nucleoli and weakly eosinophic or basophilic cytoplasm embedded in the abundant myxoid stroma with lymphocytes infiltration. They were positive for ALK, Desmin, SMA, CD30, but negative for AE1/AE3, LCA, CD2, CD3, CD5, CD7, S-100, CD34, CD31, EMA, MyoD1, and myogenin. An elevated proliferation index was demonstrated by Ki-67 comparing the first and the second lesion. Fluorescence in situ (FISH) showed the presence of chromosomal translocation involving ALK. This case show EIMS is a rare variant of inflammatory myofibroblatic tumor with aggressive biological behavior and unfavourable prognosis. To be familiar with its significant clinicopathologic characteristics could prompt us to take it into consideration when facing the relevant dieases.

Epithelioid inflammatory myofibroblastic sarcoma in abdominal cavity: a case report and review of literature.

In this study, we present a rare and difficult case of epithelioid inflammatory myofibroblastic sarcoma (EIMS) in abdominal cavity. A 47-year-old female presented as left upper abdominal pain for 6 months and abdominal distention for 1 month. CT examination showed a solid mass in the left upper intra-abdomen. Grossly, the tumor was found in the mesenterium of colon with the size of 7.5 × 6.5 × 3.5 cm, and was solid and gray-yellowish in the cut surface. Focal myxomatous appearance was observed. Microscopically, stromal myxoid change together with prominant infiltrated lymphocytes, neutrophils and eosinophils were found in the tumor, and the tumor cells were round, epithelioid with vesicular nuclei, large prominant nucleoli and high mitotic rate. Immunohistochemically, strong diffused positive for vimentin, desmin, ALK (nuclear membrane staining pattern) and AAT, focally positive for CD99 and CD30, were showed, Ki67 index was about 20%; Especially, WT-1 and D240 were focally expressed in this tumor. FISH analysis showed rearrangement of ALK, and reverse-transcription polymerase chain reaction (RT-PCR) analysis was used to detect the fusion location of the RANBP2 and ALK gene. The diagnosis of EMIS was made based on its location, typical morphology, the immunohistochemical features especially the nuclear membranous immunostaining of ALK and rearrangement of RANBP2-ALK. The tumor showed higher aggressive behaviors and a poor prognosis. The differential diagnosis and other treatments of EMIS are also discussed in the present study. This finding may increase the case information of EMIS.

Malignant metastasizing solitary fibrous tumors of the liver: a report of three cases.

Solitary fibrous tumors are rare neoplasms of mesenchymal origin that have been reported in various other extrathoracic sites, including the liver. We present a case series of three malignant solitary fibrous tumors of the liver, occurring in two women 74 and 80 years old and one 65-year-old man. No clinical features were predictive of malignancy except the large sizes and synchronous presence of lung metastases in two of the three cases. Histological examinations revealed the presence of high pleomorphic cellularity with nuclear atypia, necrosis and high mitotic ratios. All patients died of disease progression.

[Intra-abdominal soft tissue tumors. What needs to be known to reach the diagnosis with the help of immunohistochemistry, FISH and molecular biology]. / Tumeurs des tissus mous intra-abdominales. Ce qu'il faut savoir pour parvenir à un diagnostic en s'aidant de l'immunohistochimie, de la FISH, et de la biologie moléculaire.

Connective tissue tumors located inside the abdomen are a rare heterogeneous group of tumors, except for gastro-intestinal stromal tumors. They may be benign, malignant, or intermediate in terms of biologic potential. Pathologists have to remember the list of all the lesions possibly involved, with their immunohistochemical characteristics, and to know which molecular analyses are needed, with which expected results, and by which team they can be performed. The main tumor types are discussed with diagnostic tools and treatment consequences.

Pre-operative 68Ga-DOTANOC somatostatin receptor PET/CT imaging demonstrating multiple synchronous lesions in a patient with head and neck paraganglioma.

Paragangliomas, or glomus tumors, are neoplasms arising from extra-adrenal chromaffin tissue. They frequently cause symptoms by over-production of catecholamines with known predilection to multicentricity. We describe the case of a patient with bilateral carotid body tumor who underwent a preoperative 68Gallium labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-Octreotide (68Ga-DOTANOC) positron emission tomography/computed tomography (PET/CT) imaging for staging. This is a unique case in which multiple paraganglioma and pheochromocytoma were demonstrated in a single patient using 68Ga-DOTANOC PET/CT.

Solitary fibrous tumors in abdomen and pelvis: imaging characteristics and radiologic-pathologic correlation.

AIM: To describe the imaging features of solitary fibrous tumors (SFTs) in the abdomen and pelvis, and the clinical and pathologic correlations. METHODS: Fifteen patients with pathologically confirmed SFTs in the abdomen and pelvis were retrospectively studied with imaging techniques by two radiologists in consensus. Patients underwent unenhanced and contrast-enhanced imaging, as follows: 3 with computed tomography (CT) and magnetic resonance imaging (MRI) examination, 8 with CT examination only, and 4 with MRI examination only. Image characteristics such as size, shape, margin, attenuation or intensity, and pattern of enhancement were analyzed and correlated with the microscopic findings identified from surgical specimens. In addition, patient demographics, presentation, and outcomes were recorded. RESULTS: Of the 15 patients evaluated, local symptoms related to the mass were found in 11 cases at admission. The size of the mass ranged from 3.4 to 25.1 cm (mean, 11.5 cm). Nine cases were round or oval, 6 were lobulated, and 10 displaced adjacent organs. Unenhanced CT revealed a heterogeneous isodense mass in 7 cases, homogeneous isodense mass in 3 cases, and punctuated calcification in one case. On MRI, most of the lesions (6/7) were heterogeneous isointense and heterogeneous hyperintense on T1-weighted images and T2-weighted images, respectively. All tumors showed moderate to marked enhancement. Heterogeneous enhancement was revealed in 11 lesions, and 7 of these had cysts, necrosis, or hemorrhage. Early nonuniform enhancement with a radial area that proved to be a fibrous component was observed in 4 lesions, which showed progressive enhancement in the venous and delayed phase. No statistical difference in the imaging findings was observed between the histologically benign and malignant lesions. Three patients had local recurrence or metastasis at follow-up. CONCLUSION: Abdominal and pelvic SFTs commonly appeared as large, solid, well-defined, hypervascular masses with variable degrees of necrosis or cystic change that often displaced adjacent structures.

Clinical and computed tomography features of adult abdominopelvic desmoplastic small round cell tumor.

To investigate the clinical and computed tomography (CT) features of desmoplastic small round cell tumor (DSRCT), we retrospectively analyzed the clinical presentations, treatment and outcome, as well as CT manifestations of four cases of DSRCT confirmed by surgery and pathology. The CT manifestations of DSRCT were as follows: (1) multiple soft-tissue masses or diffuse peritoneal thickening in the abdomen and pelvis, with the dominant mass usually located in the pelvic cavity; (2) masses without an apparent organ-based primary site; (3) mild to moderate homogeneous or heterogeneous enhancement in solid area on enhanced CT; and (4) secondary manifestations, such as ascites, hepatic metastases, lymphadenopathy, hydronephrosis and hydroureter. The prognosis and overall survival rates were generally poor. Commonly used treatment strategies including aggressive tumor resection, polychemotherapy, and radiotherapy, showed various therapeutic effects. CT of DSRCT shows characteristic features that are helpful in diagnosis. Early discovery and complete resection, coupled with postoperative adjuvant chemotherapy, are important for prognosis of DSRCT. Whole abdominopelvic rather than locoregional radiotherapy is more effective for unresectable DSRCT.