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A 67-year-old man visited our hospital complaining of dark-colored urine and upper abdominal pain. Magnetic resonance cholangiopancreatography showed stricture of the distal bile duct, and contrast-enhanced computed tomography showed irregular thickening of the distal bile duct wall. However, no enlarged lymph nodes, pancreatic tumors, or other neoplastic lesions were apparent around the bile duct. Endoscopic ultrasonography and intraductal ultrasonography showed irregular thickening of the inner hypoechoic layer without the disappearance of the innermost thin hyperechoic layer. On the basis of these findings, we considered that the bile duct lesion was of non-epithelial origin. Thus, we repeatedly performed bile duct biopsies from the same site under fluoroscopy to obtain a sample of the submucosal tissue. The pathological diagnosis was diffuse large B-cell lymphoma, and the patient received systemic chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). After six courses of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, positron emission tomography-computed tomography showed the disappearance of 18-fluorodeoxyglucose uptake in the bile duct and endoscopic retrograde cholangiography showed improvement of the bile duct stricture. Endoscopic findings and repeated biopsies were useful in making the diagnosis of primary biliary diffuse large B-cell lymphoma.
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BACKGROUND: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer. CASE PRESENTATION: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor. CONCLUSIONS: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.
Sujet(s)
Tumeurs des voies biliaires , Voies biliaires , Carcinomes , Tumeurs de la vésicule biliaire , Anomalie de jonction biliopancréatique , Humains , Femelle , Sujet âgé , Hyperplasie/chirurgie , Hyperplasie/anatomopathologie , Conduits pancréatiques/anatomopathologie , Voies biliaires/anatomopathologie , Conduits biliaires/chirurgie , Conduits biliaires/anatomopathologie , Carcinomes/anatomopathologie , Tumeurs de la vésicule biliaire/chirurgie , Tumeurs de la vésicule biliaire/anatomopathologieRÉSUMÉ
Crystal-storing histiocytosis (CSH) is a rare disorder that shows infiltration of histiocytes with an aberrant cytoplasmic accumulation of crystalline structures and is often accompanied by lymphoproliferative-plasma cell disorders (LP-PCD) as background diseases. The diagnosis of CSH requires identification of crystalline structures that accumulate in the infiltrating histiocytes, which may be challenging by optical microscopy alone. In this case report, we describe an atypical course of systemic CSH with multifocal fibrosclerosis of an unknown background disease that was diagnosed by ultrastructural observation, including transmission electron microscopy (TEM) and scanning electron microscopy (SEM), in pathological autopsy. In addition, crystalline structures were successfully identified by scanning electron microscopic observations using formalin-fixed and paraffin-embedded (FFPE) tissue from biopsy specimens taken before death. Since CSH was identified by SEM in a tiny biopsy specimen, observation of histiocytic infiltrative lesions by SEM using FFPE tissue may lead to early detection of and initiation of treatment for CSH.
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Histiocytose , Humains , Microscopie électronique à balayage , Inclusion en paraffine , Histiocytes/métabolisme , Histiocytose/diagnostic , Histiocytose/complications , Histiocytose/métabolisme , Formaldéhyde/métabolismeRÉSUMÉ
Crystal-storing histiocytosis (CSH) is a rare disease associated with the accumulation of histiocytes containing crystalline matter within their cytoplasm. Herein, we present the case of a female patient who was diagnosed with Tolosa-Hunt syndrome at 45 years of age and idiopathic retroperitoneal fibrosis when she was 48 years. She developed portal hypertension (PH), but did not present with cirrhosis; as such, the cause of PH was not identified. Her PH gradually worsened when she was 54 years, and at the age of 60 years, she died from an acute subdural hematoma. Autopsy revealed retroperitoneal fibrosis with severe fibrosis extending around the hepatic veins and into the porta hepatis. Histologically, the retroperitoneal tissue showed a dense infiltrate of eosinophilic histiocytes with crystal structures in the cytoplasm, which was pathologically diagnosed as CSH. Nodular regenerative hyperplasia was observed in the liver parenchyma, whereas cirrhosis was not. In the present case, CSH caused fibrosis, which was believed to be the cause of PH. In addition, we considered that nodular regenerative hyperplasia caused by the altered hepatic blood flow due to treatment of gastric varices contributed to worsening PH. Hence, CSH should be considered as an underlying disease in noncirrhotic portal hypertension.
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Histiocytose , Hypertension portale , Humains , Femelle , Adulte d'âge moyen , Autopsie , Hyperplasie , Maladies rares/complications , Hypertension portale/étiologie , Cirrhose du foie/complications , Histiocytose/complications , Histiocytose/anatomopathologieRÉSUMÉ
Superficial CD34-positive fibroblastic tumor (SCPFT) is a fibroblastic/myofibroblastic soft tissue tumor of rarely metastasizing intermediate malignancy. Some recent studies have described a relationship between SCPFT and PRDM10-rearranged soft tissue tumor (PRT) based on SynCAM3 and PRDM10 expression on immunohistochemistry. We performed CD34, cytokeratin AE1/AE3, SynCAM3, and PRDM10 immunohistochemistry in SCPFT and its histological mimics, including myxoinflammatory fibroblastic sarcoma (MIFS), superficially localized myxofibrosarcoma (MFS), and undifferentiated pleomorphic sarcoma. We also examined cyclin D1 expression because it is expressed in MIFS and MFS. We conducted fluorescence in situ hybridization (FISH) of PRDM10 rearrangement in SCPFT cases. On immunohistochemistry, only SCPFT showed strong and diffuse SynCAM3 expression. SCPFT also exhibited strong nuclear and weak cytoplasmic cyclin D1 expression, which was similar to that observed in MIFS. Two of five SCPFT cases exhibited nuclear PRDM10 expression. FISH revealed PRDM10 split signals in 44% and 24% of tumor cells in two SCPFT cases showing nuclear PRDM10 expression on immunohistochemistry, respectively. A minority of non-SCPFT cases showed focal SynCAM3 expression, but a combination of SynCAM3 and cyclin D1 in addition to CD34 and cytokeratin AE1/AE3 may be useful for the differential diagnosis of SCPFT and its histological mimics.
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Fibrosarcome , Tumeurs cutanées , Tumeurs des tissus mous , Humains , Immunohistochimie , Cycline D1 , Hybridation fluorescente in situ , Tumeurs des tissus mous/diagnostic , Tumeurs des tissus mous/anatomopathologie , Fibrosarcome/anatomopathologie , Kératines , Marqueurs biologiques tumorauxRÉSUMÉ
BACKGROUND: Tenosynovial giant cell tumor (TSGCT) is a benign fibrohistiocytic tumor that affects the synovium of joints, bursa, and tendon sheaths and is categorized into localized TSGCT (LTSGCT) and diffuse TSGCT (DTSGCT). LTSGCT and DTSGCT are characterized by recurrent fusions involving the colony-stimulating factor 1 (CSF1) gene and its translocation partner collagen type VI alpha 3 chain. The fusion gene induces intratumoral overexpression of CSF1 mRNA and CSF1 protein. CSF1 expression is a characteristic finding of TSGCT and detection of CSF1 mRNA and CSF1 protein may be useful for the pathological diagnosis. Although there have been no effective anti-CSF1 antibodies to date, in situ hybridization (ISH) for CSF1 mRNA has been performed to detect CSF1 expression in TSGCT. We performed CSF1 immunohistochemistry (IHC) using anti-CSF1 antibody (clone 2D10) in cases of TSGCT, giant cell-rich tumor (GCRT), and GCRT-like lesion and verified its utility for the pathological diagnosis of TSGCT. METHODS: We performed CSF1 IHC in 110 cases including 44 LTSGCTs, 20 DTSGCTs, 1 malignant TSGCT (MTSGCT), 10 giant cell tumors of bone, 2 giant cell reparative granulomas, 3 aneurysmal bone cysts, 10 undifferentiated pleomorphic sarcomas, 10 leiomyosarcomas, and 10 myxofibrosarcomas. We performed fluorescence ISH (FISH) for CSF1 rearrangement to confirm CSF1 expression on IHC in TSGCTs. We considered the specimens to have CSF1 rearrangement if a split signal was observed in greater than 2% of the tumor cells. RESULTS: Overall, 50 of 65 TSGCT cases, including 35 of the 44 LTSGCTs and 15 of the 20 DTSGCTs, showed distinct scattered expression of CSF1 in the majority of mononuclear tumor cells. MTSGCT showed no CSF1 expression. Non-TSGCT cases were negative for CSF1. FISH revealed CSF1 rearrangement in 6 of 7 CSF1-positive cases on IHC. On the other hand, FISH detected no CSF1 rearrangement in all CSF1-negative cases on IHC. Thus, the results of IHC corresponded to those of FISH. CONCLUSION: We revealed characteristic CSF1 expression on IHC in cases of TSGCT, whereas the cases of non-TSGCT exhibited no CSF1 expression. CSF1 IHC may be useful for differentiating TSGCTs from histologically mimicking GCRTs and GCRT-like lesions.
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Tumeur à cellules géantes de la gaine tendineuse , Tumeurs à cellules géantes , Humains , Adulte , Facteur de stimulation des colonies de macrophages/génétique , Facteur de stimulation des colonies de macrophages/métabolisme , Immunohistochimie , Tumeur à cellules géantes de la gaine tendineuse/diagnostic , Tumeur à cellules géantes de la gaine tendineuse/génétique , Tumeur à cellules géantes de la gaine tendineuse/anatomopathologie , Cellules géantes/anatomopathologie , ARN messagerRÉSUMÉ
Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a new entity of benign adipocytic tumor that spans a wide spectrum of histology from adipocytic to spindle cell/pleomorphic tumors. The latter non-adipocytic component rarely shows sarcomatous features although ASPLTs are not thought to dedifferentiate. A 78-year-old woman with ASPLT in the left thigh had a sarcomatous component with high mitotic activity and Ki-67 labeling index (LI) mimicking dedifferentiated liposarcoma. The adipocytic component consisted of various-sized adipocytic cells with few lipoblasts. The sarcomatous component consisted of a fascicular proliferation of atypical spindle cells with scattered large bizarre and multinucleated giant cells. Mitotic figures including atypical mitoses were frequently observed. Immunohistochemically, the tumor cells were positive for cluster of differentiation 34 but not mouse double minute 2 homolog (MDM2), cyclin-dependent kinase 4 (CDK4), or retinoblastoma (Rb) protein. Ki-67 LI in the sarcomatous component reached 40%. MDM2 and CDK4 genes were not amplified and 13q14 including the RB1 locus was deleted according to fluorescence in situ hybridization. The patient is alive with no evidence of local recurrence or distant metastasis 3.5 years after surgery. As ASPLT may exhibit morphological variation, it is important to rule out dedifferentiated liposarcoma with careful pathological examination.
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Lipome , Liposarcome , Femelle , Humains , Sujet âgé , Kinase-4 cycline-dépendante/génétique , Antigène KI-67/génétique , Hybridation fluorescente in situ , Marqueurs biologiques tumoraux/génétique , Liposarcome/diagnostic , Liposarcome/génétique , Liposarcome/anatomopathologie , Lipome/diagnostic , Lipome/génétique , Lipome/anatomopathologieRÉSUMÉ
OBJECTIVE: The aim of this study was to examine the clinical and histopathologic effects of neoadjuvant intra-arterial chemoradiotherapy (IACRT) using cisplatin in combination with oral S-1 (tegafur/gimeracil/oteracil potassium) on stage III and IV oral squamous cell carcinoma. STUDY DESIGN: Thirty patients received infusions of superselective intra-arterial cisplatin 60 mg/m2 by the Seldinger method and conventional external beam radiotherapy (total 40 Gy) combined with oral S-1 on the day of irradiation. Curative surgery and neck dissection were performed 4 to 6 weeks after IACRT. The clinical response of the primary lesion was evaluated approximately 4 weeks after IACRT. The surgically resected specimens were examined for histologic features according to the grading system for histologic evaluation and for residual tumor grade (RGrades). RESULTS: Histopathologic evaluation of the therapeutic effect was grade 2 in 10 patients and grade 3 in 16 patients. According to the distribution of RGrades, the remaining tumor cells were mostly in the central area of the primary lesion, as seen in 24 patients. CONCLUSIONS: These findings indicate that neoadjuvant IACRT with cisplatin and oral S-1 was an effective treatment, suggesting the possibility of reducing the extent of curative surgery based on RGrades.
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Carcinome épidermoïde , Tumeurs de la bouche , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Carcinome épidermoïde/anatomopathologie , Carcinome épidermoïde/thérapie , Chimioradiothérapie/effets indésirables , Chimioradiothérapie/méthodes , Cisplatine , Humains , Perfusions artérielles/méthodes , Tumeurs de la bouche/traitement médicamenteux , Tumeurs de la bouche/anatomopathologie , Traitement néoadjuvant , Stadification tumoraleRÉSUMÉ
A 77-year-old man was referred to our hospital because of a hepatic tumor. Blood biochemistry showed elevated serum alfa-fetoprotein, protein induced by vitamin K absence-II, and carbohydrate antigen 19-9 levels. Gd-EOB-DTPA-enhanced magnetic resonance imaging revealed a 95-mm-sized tumor in liver S7. The tumor showed heterogeneous hyperintensity in the arterial phase, slightly washed out from the portal vein phase, and hypointensity in the hepatocellular phase. Post-enlargement segmental resection was performed, and the pathological diagnosis was combined hepatocellular cholangiocarcinoma. Seven months after surgery, multiple liver tumors were found, and biopsy revealed combined hepatocellular-cholangiocarcinoma. Hepatic arterial infusion chemotherapy with cisplatin was initiated. However, the patient developed a pulmonary abscess, which was treated with antibiotics. He then underwent treatment with lenvatinib, 11 months after surgery. At 8 weeks follow-up, a complete response (according to the modified Response Evaluation Criteria in Solid Tumors [RECIST]) and a partial response (RECIST version 1.1) was noted. To the best of our knowledge, thus far, only a single case of lenvatinib treatment of unresectable mixed liver cancer has been reported. In that case, lenvatinib was used as a third-line treatment. The present report is the first to describe lenvatinib as a first-line therapy for unresectable combined hepatocellular-cholangiocarcinoma, which resulted in a meaningful response. This case provides useful insights into the choice of appropriate drug treatment in this disease in the absence of randomized controlled trials of drug treatment.
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Patients with coronavirus disease 2019 (COVID-19) primarily cause respiratory symptoms. However, gastrointestinal (GI) symptoms can also occur. The endoscopic characteristics of the GI tract in COVID-19 patients remain unclear. We herein report a 62-year-old male with severe COVID-19 who needed multidisciplinary treatment, including extracorporeal membrane oxygenation (ECMO). Despite the improvement in his respiratory status, GI bleeding developed. Capsule endoscopy and colonoscopy revealed extensive mucosal sloughing in the lower intestinal tract. Additionally, we performed a comprehensive analysis of the mRNA expression levels of various proinflammatory cytokines in the intestinal mucosal tissues. The results suggested a significant elevation of IL-6, which could be involved in the pathophysiology of the GI involvement in COVID-19. Further investigation with more clinical data, including endoscopic findings and molecular analyses, will contribute to a comprehensive understanding of COVID-19-associated GI injury.
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BACKGROUND: A definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is challenging, especially in cases without neurofibromatosis 1 (NF1), because MPNST lacks specific markers on immunohistochemistry (IHC). METHODS: We performed IHC for histone 3 trimethylated on lysine 27 (H3K27me3) and evaluated the percentage of cells with H3K27me3 loss using measured values at 10% intervals, categorized as complete loss (100% of tumor cells lost staining), partial loss (10% to 90% of tumor cells lost staining), and intact (no tumor cells lost staining). We conducted fluorescence in situ hybridization (FISH) for NF1 and p16 deletions comparing 55 MPNSTs and 35 non-MPNSTs, consisting of 9 synovial sarcomas (SSs), 8 leiomyosarcomas (LMSs), 10 myxofibrosarcomas (MFSs), and 8 undifferentiated pleomorphic sarcomas (UPSs). We assessed the percentage of cells with homozygous and heterozygous deletions and defined "deletion" if the percentage of either the NF1 or p16 deletion signals was greater than 50% of tumor cells. RESULTS: Among the 55 MPNSTs, 23 (42%) showed complete H3K27me3 loss and 32 (58%) exhibited partial loss or intact. One each of the 9 SSs (11%), 8 LMSs (12%), and 8 UPSs (12%) showed complete H3K27me3 loss and many non-MPNSTs exhibited intact or partial H3K27me3 loss. Among the 55 MPNSTs, 33 (60%) and 44 (80%) showed NF1 or p16 deletion, respectively. Co-deletion of NF1 and p16 was observed in 29 (53%) MPNSTs. Among the 23 MPNTSs showing H3K27me3 complete loss, 18 (78%) and 20 (87%) exhibited NF1 or p16 deletion, respectively. Among the 32 MPNSTs with H3K27me3 partial loss or intact, 15 (47%) and 24 (75%) exhibited NF1 or p16 deletion, respectively. The frequency of NF1 and/or p16 deletion tended to be lower in non-MPNSTs than in MPNSTs. Approximately 90% of MPNSTs included cases with H3K27me3 complete loss and cases showing H3K27me3 partial loss or intact with NF1 and/or p16 deletion. Approximately 50% of MPNSTs showed co-deletion of NF1 and p16 regardless of H3K27me3 loss. CONCLUSIONS: FISH for NF1 and p16 deletions, frequently observed in high-grade MPNSTs, might be a useful ancillary diagnostic tool for differentiating MPNST from other mimicking spindle cell and pleomorphic sarcomas.
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Marqueurs biologiques tumoraux , Inhibiteur p16 de kinase cycline-dépendante/génétique , Délétion de gène , Histone/analyse , Immunohistochimie , Hybridation fluorescente in situ , Neurofibromine-1/génétique , Neurofibrosarcome/diagnostic , Marqueurs biologiques tumoraux/analyse , Marqueurs biologiques tumoraux/génétique , Diagnostic différentiel , Humains , Méthylation , Grading des tumeurs , Neurofibrosarcome/composition chimique , Neurofibrosarcome/génétique , Valeur prédictive des tests , Études rétrospectivesRÉSUMÉ
Background: Takayasu arteritis (TA) is a large vessel vasculitis of unknown etiology characterized by chronic inflammatory changes of the aorta and its major branches. Complications such as anastomotic aneurysm and valve detachment have been reported in active TA patients who received aortic valve replacement and graft replacement of aorta. Case Summary:A 61-year-old man with a history of emergency aortic valve replacement and patch closure of the noncoronary sinus of Valsalva due to acute heart failure induced by acute aortic regurgitation and ruptured sinus of Valsalva 4 years ago was referred for exertional dyspnea. Dilatation of the sinus of Valsalva together with protrusion of the right sinus of Valsalva and ostial stenosis of the left coronary artery were newly found by computed tomography (CT). A Bentall operation with concomitant coronary artery bypass grafting was successfully performed with a composite graft. Diagnosis of TA was made on the basis of histological analyses of the resected sinus of Valsalva, though other arterial manifestations were not detected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography. Three months later, a follow-up study revealed left coronary ostial pseudoaneurysm at the anastomotic site together with strong 18F-FDG uptake, leading to commencement of steroid therapy. Eight months later, disappearance of left coronary ostial pseudoaneurysm was found by a follow-up CT scan. Conclusion: This is a rare TA case in whom spontaneous resolution of coronary anastomotic aneurysm by steroid therapy was found without reconstructive surgery.
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Effective management of immune-related adverse events in patients receiving immunotherapy for cancer is problematic. In this report, we present the case of a 58-year-old man with advanced clear cell renal cell carcinoma who responded well to a combination of ipilimumab and nivolumab. However, after two courses of treatment, he developed fulminant hepatitis and died. An autopsy confirmed that the primary lesion in the left kidney was more than 99% necrotic with only six small residual tumor lesions. These lesions were infiltrated by large numbers of CD8-positive/TIA-1-positive lymphocytes. However, a metastatic lesion in the right kidney harbored few lymphocytes. Furthermore, the tumor cells in the metastatic lesion and one of the residual lesions showed decreased expression of HLA class I molecules, which are a prerequisite for cytotoxic T-lymphocyte-mediated immunotherapy in tumor cells. In this patient, more than 80% of hepatocytes were destroyed and the parenchyma was infiltrated with CD8-positive/TIA-1-positive lymphocytes. The patient had polyuria, which was attributed to neurohypophysitis caused by the infiltration of CD8-positive/TIA-1-positive lymphocytes. We believe that this is an instructive case for immuno-oncologists.
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Antinéoplasiques immunologiques/effets indésirables , Néphrocarcinome/traitement médicamenteux , Néphrocarcinome/anatomopathologie , Immunothérapie/effets indésirables , Ipilimumab/effets indésirables , Tumeurs du rein/traitement médicamenteux , Tumeurs du rein/anatomopathologie , Nécrose hépatique massive/induit chimiquement , Nivolumab/effets indésirables , Antinéoplasiques immunologiques/administration et posologie , Autopsie , Association de médicaments , Issue fatale , Hépatocytes/anatomopathologie , Humains , Ipilimumab/administration et posologie , Rein/anatomopathologie , Lymphocytes/anatomopathologie , Mâle , Nécrose hépatique massive/anatomopathologie , Adulte d'âge moyen , Nécrose , Nivolumab/administration et posologie , Résultat thérapeutiqueRÉSUMÉ
We report two cases of muscle-invasive bladder cancer (MIBC) with increasing multiple osteoblastic bone lesions but shrinking other lesions in response to chemotherapy. Case 1 had MIBC and received radical cystectomy followed by adjuvant gemcitabine plus cisplatin chemotherapy (GC). Three years after, follow computed tomography (CT) showed development of multiple lymph node metastasis, and then we performed GC as a first-line systemic chemotherapy. After two cycles of GC, CT showed de novo multiple osteoblastic lesions although metastatic lymph nodes were shrunk. Biopsy of the sternum revealed metastatic urothelial carcinoma. Case 2 had MIBC with multiple osteoblastic lesions on CT and bone scintigraphy, which was initially diagnosed as cT3bN0M1. After one cycle of GC, the number of osteoblastic lesions obviously increased although bladder tumor was regressed. Since the clinical course was unusual, biopsy of the clavicle was done. The histological diagnosis was benign osteoblastic bone disease, then the clinical diagnosis was revised to non-metastatic MIBC, and radical cystectomy was performed. Ten months after surgery, the patients complained worsening backache and CT showed increase in number of osteoblastic lesions. Eventually, ilium biopsy revealed bone metastasis of urothelial carcinoma. In case of atypical finding and unusual clinical course, biopsy of suspected metastatic lesion may be informative although adequate sampling should be secured.
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Neurofibromatosis type 1 (NF1) is a genodermatosis caused by heterozygous germ line variations in the NF1 gene. A second-hit NF1 aberration results in the formation of café-au-lait macules, cutaneous neurofibroma and plexiform neurofibroma (PNF). Mosaic NF1 (mNF1), caused by a postzygotic NF1 mutation, is characterized by localized or generalized NF1-related manifestations. Although NF1 and mNF1 are associated with pigmentary skin lesions, clinically recognizable melanocytic nevi that developed over PNF have not been reported. Here, we report the first case of multiple melanocytic nevi that developed on a giant café-au-lait macule and PNF. The PNF had biallelic NF1 deletions, a whole deletion of NF1 and a novel intragenic deletion involving exons 25-30. The deletions were not detected in the blood, which resulted in the diagnosis of mNF1. Furthermore, the nevus cells had not only biallelic NF1 deletions but also NRAS Q61R, a common mutation found in congenital melanocytic nevi. These analyses revealed the coexistence of the two different mosaic diseases, mNF1 and congenital melanocytic nevi. For a diagnosis of cases with atypical NF1-like symptoms, genetic analyses using blood and lesional tissues are useful and aid in genetic counseling.
Sujet(s)
Taches café-au-lait/génétique , Mosaïcisme , Tumeurs primitives multiples/génétique , Neurofibrome plexiforme/génétique , Neurofibromatose de type 1/génétique , Naevus pigmentaire/génétique , Tumeurs cutanées/génétique , Taches café-au-lait/diagnostic , Taches café-au-lait/anatomopathologie , Enfant , Analyse de mutations d'ADN , Femelle , dGTPases/génétique , Dépistage génétique , Humains , Protéines membranaires/génétique , Tumeurs primitives multiples/diagnostic , Tumeurs primitives multiples/anatomopathologie , Neurofibrome plexiforme/diagnostic , Neurofibrome plexiforme/anatomopathologie , Neurofibromatose de type 1/complications , Neurofibromatose de type 1/diagnostic , Neurofibromatose de type 1/anatomopathologie , Neurofibromine-1/génétique , Naevus pigmentaire/diagnostic , Naevus pigmentaire/anatomopathologie , Peau/anatomopathologie , Tumeurs cutanées/diagnostic , Tumeurs cutanées/anatomopathologieRÉSUMÉ
A 70-year-old woman developed severe buttock pain that progressed to a walking disturbance. Radiographs and computed tomography scans revealed an osteolytic lesion with osteosclerosis extending from the body to the arch of the fifth lumbar vertebra. Magnetic resonance imaging showed multinodular masses in the fifth lumbar vertebral body extending into the spinous processes and right transverse process. The masses were hypointense to isointense on T1-weighted images and hypointense to hyperintense on T2-weighted images. Histologic examination of biopsy specimens showed destruction of the trabecula of the vertebral bone by a fascicular and solid proliferation of spindle tumor cells and scattered rhabdomyoblasts, in a fibrotic background. The tumor cells were immunoreactive for keratins, vimentin, desmin, MyoD1, myogenin, and anaplastic lymphoma kinase. Fluorescence in situ hybridization detected split signals for FUS and TFCP2 in 80% and 64% of the tumor cells, respectively, suggesting FUS-TFCP2 fusion. Reverse transcription-polymerase chain reaction revealed a FUS-TFCP2 fusion. The final diagnosis was spindle cell rhabdomyosarcoma of a lumbar vertebra with a FUS-TFCP2 fusion. A spindle cell rhabdomyosarcoma with a FUS-TFCP2 fusion in a vertebral bone is rare and should be differentiated from metastatic carcinoma, particularly in the elderly.
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Protéines de liaison à l'ADN/métabolisme , Protéine FUS de liaison à l'ARN/métabolisme , Rhabdomyosarcome/anatomopathologie , Tumeurs du rachis/anatomopathologie , Facteurs de transcription/métabolisme , Sujet âgé , Femelle , Humains , Rhabdomyosarcome/diagnostic , Rhabdomyosarcome embryonnaire/métabolisme , Tumeurs du rachis/diagnosticRÉSUMÉ
Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade spindle cell sarcoma that predominantly affects middle-aged women with multiple tumors in the sinonasal tract. BSNS shows biphenotypic expression of neural and myogenic markers on immunohistochemistry (IHC) with a specific chimeric PAX3-MAML3 fusion. The cytological features of BSNS have so far not been reported. Here, we describe a case of BSNS including findings of imprint cytology, histology, IHC, and genetic analysis. A 30-year-old woman presented with a nodular tumor that completely occupied the ethmoid sinus. The tumor was resected and submitted for imprint cytology, which revealed relatively bland spindle tumor cells that had mildly enlarged oval to spindle-shaped nuclei with fine nuclear chromatin and a thin nuclear rim in a clear background. Nucleoli were inconspicuous and there was no significant nuclear atypia and pleomorphism. These cytological findings were consistent with the histology of low-grade spindle cell sarcoma in BSNS. On IHC, the tumor cells were focally positive for S-100 protein and α-smooth muscle actin; nuclear ß-catenin expression was also seen. PAX3 split signals were detected in 52% of tumor cells by fluorescence in situ hybridization. Reverse transcriptase-polymerase chain reaction also identified a chimeric PAX3-MAML3 fusion gene. Based on these findings, we diagnosed the tumor as BSNS. Our findings revealed that a relatively bland spindle cell cytology with a clear background is a characteristic feature of BSNS. BSNS should therefore be differentiated from benign and bland-appearing malignant spindle cell tumors and the combination of cytology, histology, IHC, and genetic analysis facilitates the diagnosis of BSNS.
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Tumeurs des sinus de la face/anatomopathologie , Sarcomes/anatomopathologie , Adulte , Protéines de liaison à l'ADN/génétique , Femelle , Humains , Protéines nucléaires/génétique , Protéines de fusion oncogènes/génétique , Facteur de transcription PAX3/génétique , Tumeurs des sinus de la face/génétique , Phénotype , Sarcomes/génétique , Transactivateurs , Facteurs de transcription/génétiqueRÉSUMÉ
BACKGROUND: Clear cell sarcoma of soft tissue (CCSST) and clear cell sarcoma-like gastrointestinal tumor (CCSLGT) are malignant mesenchymal tumors that share some pathological features, but they also have several different characteristics. They are well known to express chimeric fusions of Ewing sarcoma breakpoint region 1 (EWSR1) and cAMP response element-binding protein (CREB) family members; namely, EWSR1-activating transcription factor 1 (ATF1) and EWSR1-CREB1. In addition, recent studies have suggested the presence of other fusions. METHODS: We used fluorescence in situ hybridization to detect specific rearrangements including EWSR1, ATF1, CREB1, and cAMP response element modulator (CREM) in 16 CCSST and 6 CCSLGT cases. We also used reverse transcription polymerase chain reaction (RT-PCR) to detect specific chimeric fusions of EWSR1-ATF1 and EWSR1-CREB1 using fresh tumor samples in available cases. RESULTS: A total of 15 of 16 CCSST cases (93.8%) had EWSR1 rearrangement, of which 11 (68.8%) also had ATF1 rearrangement, suggestive of the presence of EWSR1-ATF1 fusions. One CCSST case (6.3%) was found to have EWSR1 and CREM rearrangements, and 4 of 6 CCSLGT cases (66.7%) had EWSR1 rearrangement, of which 2 (33.3%) showed ATF1 rearrangement and the other 2 cases (33.3%) showed CREB1 rearrangement. These cases most likely had EWSR1-ATF1 and EWSR1-CREB1 fusions, respectively. RT-PCR was performed in 8 available cases, including 6 CCSSTs and 2 CCSLGTs. All CCSSTs showed EWSR1-ATF1 fusions. Among the 2 CCSLGT cases, one had EWSR1-ATF1 fusion and the other had EWSR1-CREB1 fusion. CONCLUSIONS: Rearrangements of EWSR1 and ATF1 or EWSR1-ATF1 fusion were predominantly found in CCSST, whereas those of EWSR1 and CREB1 or EWSR1-CREB1 tended to be detected in CCSLGT. A novel CREM fusion was also detected in a few cases of CCSST and CCSLGT. The cases in which EWSR1 rearrangement was detected without definitive partner genes should be considered for the presence of CREM rearrangement.