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Accurate diagnosis of the localization of prostate cancer (PCa) on magnetic resonance imaging (MRI) remains a challenge. We aimed to assess discrepancy between the location of PCa pathologically diagnosed using surgical specimens and lesions indicated as possible PCa by the Prostate Imaging Reporting and Data System on MRI. The primary endpoint was the concordance rate between the site of probable clinically significant PCa (csPCa) identified using biparametric MRI (bpMRI) and location of PCa in the surgical specimen obtained using robot-assisted total prostatectomy. Among 85 lesions identified in 30 patients; 42 (49.4%) were identified as possible PCa on MRI. The 85 PCa lesions were divided into positive and negative groups based on the bpMRI results. None of the patients had missed csPCa. Although the diagnostic accuracy of bpMRI was relatively high for PCas located in the middle of the prostate (p = 0.029), it was relatively low for PCa located at the base of the prostate, all of which were csPCas. Although current modalities can accurately diagnose PCa, the possibility that PCa is present with multiple lesions in the prostate should be considered, even if MRI does not detect PCa.
Subject(s)
Magnetic Resonance Imaging , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/surgery , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged , Middle Aged , Magnetic Resonance Imaging/methods , Prostatectomy/methodsABSTRACT
Combined hepatocellular cholangiocarcinoma is a rare and challenging primary liver malignancy that lacks any established standard treatments for unresectable cases. We herein present the first known case of a 49-year-old woman diagnosed with unresectable combined hepatocellular-cholangiocarcinoma, who underwent novel chemotherapy involving durvalumab plus tremelimumab combination therapy. The treatment was temporarily discontinued owing to immune-related adverse events, such as rash, and the patient was subsequently managed with systemic steroid therapy; however, the disease progressed after two courses of this treatment. Further studies are needed to validate the efficacy and safety of immune checkpoint inhibitors such as durvalumab and tremelimumab for the treatment of unresectable combined hepatocellular cholangiocarcinoma.
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BACKGROUND: Meningioma is the second most common intradural extramedullary tumor, following schwannoma. Meningioma is primarily categorized as benign World Health Organization grade 1, but clear cell meningioma is grade 2 of the intermediate malignant category. Clear cell meningiomas are rare, accounting for less than 1% of all meningioma tumors. There is no previous report of multiple intraspinal clear cell meningiomas without dural attachment. CASE PRESENTATION: A 27-year-old Asian male patient presented with lower right extremity pain, and had undergone tumor resection for intracranial clear cell meningioma 7 years previously, with re-resection and radiotherapy for local tumor recurrence at our hospital's department of neurosurgery being carried out 4 years previously. No recurrence was observed since then. Preoperative lumbar magnetic resonance imaging showed two tumors at the L1 and L4 levels, both mimicking schwannoma with well-defined margins, no dural tail sign and homogeneous internal contrast. Intraoperative findings on tumor resection showed two tumors contiguous with the right L2 and L5 roots, which were not attached to the dura mater, similar to a schwannoma. After gross total resection, the postoperative pathology revealed no nuclear SMARCE1 antibody staining. The patient was diagnosed with clear cell meningioma. The patient's postoperative course went well, with no symptoms of nerve dropout and no recurrence 2 years after surgery. In this case, both lumbar lesions were well demarcated and spherical in shape, occurring with single roots. Tumor characteristics suggested a primary rather than a metastatic lesion. Clear cell meningioma is characterized by a SMARCE1 mutation and is different from other types of meningiomas. CONCLUSION: To the best of our knowledge, this is the first report of multiple intraspinal clear cell meningiomas without dural attachment at the lumbar spine after resection of intracranial clear cell meningioma. We speculate that the two tumors were de novo lesions on the basis of the features of the tumors, although they were detected 7 years after the resection of intracranial clear cell meningioma.
Subject(s)
Brain Neoplasms , Meningeal Neoplasms , Meningioma , Neurilemmoma , Spinal Neoplasms , Humans , Male , Adult , Meningioma/diagnosis , Meningeal Neoplasms/diagnosis , Neurilemmoma/surgery , Neurosurgical Procedures , Brain Neoplasms/surgery , Spinal Neoplasms/surgery , Chromosomal Proteins, Non-Histone , DNA-Binding ProteinsABSTRACT
BACKGROUND: Left atrial myxoma is the most common benign tumor, with the growth rate remaining unknown because specific symptoms do not present until the tumor grows to a certain size. Early surgical management is performed in most cases once it is detected by physicians. Despite cardiac myxomas commonly being perceived as slow-growing tumors, rapid enlargement of myxomas has been reported. CASE PRESENTATION: A 64-year-old woman was referred to our hospital with a diagnosis of a left atrial tumor. The pointed tumor changed morphologically in a few hours, and her respiratory condition, which had been normal at admission, suddenly deteriorated. Emergent surgery was performed, and the diagnosis was myxoma with multiple intratumor massive hematomas. The patient recovered uneventfully and was discharged on postoperative day 12 without any complications. CONCLUSIONS: We report an extremely rare case of left atrial myxoma rapidly expanded due to acute multiple hemorrhages within itself. Massive internal hemorrhage alters the size, shape, and fragility of the tumor. We should recognize the potential risk of internal hemorrhage that may lead to acute deterioration of the so-called "slow-growing benign" tumors, such as myxomas.
Subject(s)
Heart Neoplasms , Myxoma , Humans , Female , Middle Aged , Heart Neoplasms/diagnosis , Heart Neoplasms/diagnostic imaging , Hemorrhage , Myxoma/complications , Myxoma/diagnosis , Myxoma/surgery , Heart Atria/surgery , Heart Atria/pathology , Hematoma/complicationsABSTRACT
OBJECTIVE: This study aimed to assess the usefulness of magnetic resonance imaging (MRI) findings for differentiating low-grade and high-grade malignant peripheral nerve sheath tumors (MPNSTs). METHODS: This study included 31 patients (onset age range, 19-83 years; mean onset age, 57 years; 9 men and 22 women) with 36 histopathologically proven MPNSTs (7 low-grade MPNSTs and 29 high-grade MPNSTs) who underwent preoperative MRI between December 2007 and October 2022. Quantitative and qualitative MRI findings were retrospectively evaluated and compared between the 2 subtypes. RESULTS: The maximum tumor diameter (106.1 ± 64.0 vs 54.9 ± 19.8 mm, P = 0.032) and tumor-to-muscle signal intensity ratio (SIR) of fat-suppressed gadolinium-enhanced T1-weighted images (2.69 ± 1.40 vs 1.62 ± 0.40, P = 0.005) were significantly higher in high-grade MPNSTs than in low-grade MPNSTs. The receiver operating characteristic analysis revealed that the tumor-to-muscle SIR of fat-suppressed gadolinium-enhanced T1-weighted images exhibited the highest area under the curve value (0.88), followed by the maximum tumor diameter (0.76). The sensitivity and specificity of the tumor-to-muscle SIR of fat-suppressed gadolinium-enhanced T1-weighted images for diagnosing high-grade MPNST at an optimal SIR threshold of greater than 1.73 were 90% and 83%, respectively. However, other MRI findings showed no significant differences between the 2 subtypes (P = 0.16-1.00). CONCLUSIONS: Although the MRI findings of low-grade and high-grade MPNST overlapped considerably, the maximum tumor diameter and degree of contrast enhancement can be used to differentiate low-grade MPNST from high-grade MPNST.
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This report describes CT and MRI findings of temporal bone metastasis from follicular thyroid carcinoma in two cases. Both of these had large, osteolytic, hypervascular masses of the temporal bone, accompanied by internal scattered bone fragments and extraosseous mass formation on unenhanced and contrast-enhanced CT images. In the first case, several dilated and tortuous vessels within the markedly hypervascular mass were observed on the arterial phase of dynamic contrast-enhanced CT images. Compared with the signal intensity of the cerebellum, temporal bone masses showed slightly hypo- to slightly hyperintense on T1-weighted images and slightly hypo- to moderately hyperintense on T2-weighted images. Both cases had flow voids in abnormally dilated vessels within the mass on T1- and T2-weighted images. Thyroid follicular carcinoma rarely metastasizes the temporal bone and presents with an osteolytic hypervascular mass with flow void sign.
Subject(s)
Adenocarcinoma, Follicular , Thyroid Neoplasms , Humans , Adenocarcinoma, Follicular/diagnostic imaging , Contrast Media , Magnetic Resonance Imaging/methods , Retrospective Studies , Temporal Bone/diagnostic imaging , Thyroid Neoplasms/diagnostic imaging , Female , Middle AgedABSTRACT
BACKGROUND: Decision-making and selection of treatment modalities for newly diagnosed prostate cancer (PCa) are often determined by risk stratification using grade group (GG), prostate-specific antigen (PSA), and clinical stage. The discrepancies between needle biopsy (NB) and radical prostatectomy (RP) specimens often occur because of the sampling errors in NB or multifocal features of PCa. Thus, we aimed to estimate the preoperative clinical factors for predicting GG upgrading after robot-assisted RP (RARP). METHODS: In this retrospective study, we reviewed the clinical and pathological records of patients who underwent RARP at Gifu University Hospital. We focused on patients with organ-confined PCa who had not received neoadjuvant therapy prior to RARP. The primary endpoint was identified as the predictive factor of GG upgrading for RARP specimens compared to those of NB specimens. RESULTS: Eighty-one patients were included in this study. The enrolled patients were divided into two groups: those who had GG upgrading for RARP specimens (the NB upgrade group) or those who did not have GG upgrading (the no upgrade group). The median age of all patients was 70 years, and the median body mass index (BMI) was 22.9 kg/m2. The median neutrophil count was 3720/µL, lymphocyte count was 1543/µL, and neutrophil-to-lymphocyte ratio (NLR) was 2.24. In univariate analysis, BMI, PSA, neutrophil count, and NLR were significantly associated with GG upgrading in RARP specimens compared to NB specimens. BMI and NLR were identified as strong predictive factors for GG upgrading in RARP specimens in the multivariate analysis. CONCLUSIONS: Although this study's small number of enrolled patients was a vital weakness, BMI and NLR might have been significantly correlated with GG upgrading for RP specimens compared with NB specimens. Therefore, BMI and NLR may have potential benefits for newly diagnosed patients with PCa in terms of decision-making and the selection of treatment modalities.
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Poorly differentiated chordoma (PDC) is a rare, aggressive subtype of chordoma. A two-year-old girl presented with cervical pain, limb paralysis and respiratory failure. Magnetic resonance imaging and positron emission tomography-computed tomography revealed a tumor compressing the pons at the clivus and osteoblastic metastatic lesions of the left upper arm and right iliac bone. Her tumors shrank substantially after treatment with chemotherapy and proton beam therapy. Our initial diagnosis was an atypical teratoma/rhabdoid tumor, but final diagnosis of PDC was made on the basis of the immunohistochemical expression of brachyury. In addition, the detection of SMARCB1/INI1 mutation confirmed the diagnosis of PDC.
Subject(s)
Chordoma , Neuroblastoma , Rhabdoid Tumor , Teratoma , Female , Child , Humans , Child, Preschool , Chordoma/genetics , Chordoma/diagnosis , SMARCB1 Protein/genetics , Rhabdoid Tumor/diagnosis , Cranial Fossa, Posterior/metabolism , Biomarkers, TumorABSTRACT
INTRODUCTION: Atraumatic splenic rupture is very rare and the case is often difficult to determine. We report a case of atraumatic splenic rupture in a patient with an infected aortic aneurysm. CASE PRESENTATION: A 40-year-old man under evaluation and treatment for renal dysfunction presented with the sudden onset of epigastric pain. The patient had a previous history of aortic arch replacement for Stanford type B aortic dissection. Contrast-enhanced computed tomography revealed intraabdominal hemorrhaging around the spleen and intrasplenic extravasation of contrast medium, and atraumatic splenic rupture was diagnosed. The patient slipped into hemorrhagic shock, and emergency splenectomy was scheduled. The histopathological diagnosis was splenic rupture with splenic infarction. The patient became febrile on postoperative day 10. Repeat contrast-enhanced computed tomography revealed enlargement of a cystic aortic aneurysm that was present prior to splenectomy. Infected aortic aneurysm was suspected, which was confirmed following thoracic endovascular aortic repair performed on postoperative day 12. DISCUSSION: We consider that splenic rupture occurred following infected of the kidney and spleen by an infected aortic aneurysm. CONCLUSION: Infection should be considered as a cause in patients with atraumatic splenic rupture.
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We report a case of primary central nervous system vasculitis (PCNSV) with longitudinally extensive transverse myelitis. A 47-year-old woman presented with malaise, progressive cognitive impairment, and lower limb spasticity. Diffuse hyperintense areas in the deep cerebral white matter on the diffusion-weighted image and T2-weighted images were observed during brain magnetic resonance imaging. Gadolinium-enhanced T1-weighted images showed multiple linear enhancements. A sagittal T2-weighted image displayed a longitudinal extensive lesion of transverse myelitis in the spinal column from the upper cervical (C7) to the thoracic region (Th12). On brain biopsy, the patient was diagnosed as having granulomatous primary angiitis of the central nervous system (PCNSV). This case suggests that PCNSV could show longitudinally extensive transverse myelitis. (Received 14 January, 2021; Accepted 18 February, 2021; Published 1 August, 2021).
Subject(s)
Myelitis, Transverse , Vasculitis, Central Nervous System , Brain/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Myelitis, Transverse/diagnostic imaging , Myelitis, Transverse/etiology , Vasculitis, Central Nervous System/diagnostic imagingABSTRACT
PURPOSE: The purpose of this study was to evaluate computed tomography and magnetic resonance imaging of benign trichilemmal cysts and proliferating trichilemmal tumours. METHODS: Nineteen histologically confirmed cutaneous lesions with trichilemmal keratinisation (12 trichilemmal cysts and seven proliferating trichilemmal tumours) were enrolled. Among them, 10 lesions (six trichilemmal cysts and four proliferating trichilemmal tumours) were examined by computed tomography, while 13 lesions (eight trichilemmal cysts and five proliferating trichilemmal tumours) were examined by magnetic resonance imaging. Computed tomography and magnetic resonance imaging characteristics were retrospectively reviewed. RESULTS: Sixteen lesions (84%, 10 trichilemmal cysts and six proliferating trichilemmal tumours) occurred on the scalp. Lobulated margins were observed in five lesions (26%, three trichilemmal cysts and two proliferating trichilemmal tumours). With respect to computed tomography attenuation, calcification (>200 Hounsfield units) was observed in seven lesions (70%, five trichilemmal cysts and two proliferating trichilemmal tumours), hyperdense areas (≥80 and ≤200 Hounsfield units) in six (60%, three trichilemmal cysts and three proliferating trichilemmal tumours), and soft tissue density areas (<80 Hounsfield units) in nine (90%, five trichilemmal cysts and four proliferating trichilemmal tumours). On T1-weighted images, intratumoral hyperintensity was only observed in eight trichilemmal cysts but no proliferating trichilemmal tumours (100% vs. 0%, P<0.01). On T2-weighted images, hypointense rim and intratumoral hypointensity was observed in all 13 lesions (100%, eight trichilemmal cysts and five proliferating trichilemmal tumours), and linear or reticular hypointensity was observed in 10 (77%, six trichilemmal cysts and four proliferating trichilemmal tumours). CONCLUSION: Trichilemmal cysts and proliferating trichilemmal tumours predominantly occurred on the scalp with calcification, and usually exhibited linear or reticular T2 hypointensity. Intratumoral T1 hyperintensity may be a useful imaging feature for differentiating trichilemmal cysts from proliferating trichilemmal tumours.
Subject(s)
Epidermal Cyst , Skin Neoplasms , Epidermal Cyst/diagnostic imaging , Humans , Magnetic Resonance Imaging , Retrospective Studies , Scalp , Skin Neoplasms/diagnostic imagingABSTRACT
A 45-year-old Japanese man visited a community hospital with the chief complaint of asymptomatic macrohematuria. He was diagnosed with muscle-invasive bladder cancer (MIBC), and he received intra-arterial chemotherapy followed by radiation therapy at another institution. Twenty-eight months after chemoradiotherapy, magnetic resonance imaging (MRI) revealed MIBC recurrence. After neoadjuvant chemotherapy, robot-assisted radical cystectomy was performed. Pathological examination indicated high-grade urothelial carcinoma with lymphovascular invasion, a positive surgical margin, and skip lesions of cancer cells in the perivesical adipose tissue. Three months after surgery, he was brought to our hospital in an ambulance with the chief complaint of rotatory vertigo and was speaking inarticulately. Head and whole spine MRI revealed meningeal metastasis along both the vestibulocochlear nerves and cauda equina. Analysis of the cerebrospinal fluid revealed malignant cells. The patient was diagnosed with leptomeningeal carcinomatosis originating from the MIBC. He received whole-brain radiotherapy followed by the administration of pembrolizumab. Unfortunately, the patient's condition quickly deteriorated, and he died of cancer 4 months after surgery.
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This study aimed to determine the predictive value of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) based on biparametric magnetic resonance imaging (bpMRI) with combined target biopsy (TBx) and systematic biopsy (SBx) in patients with suspicion of having clinically significant prostate cancer (csPCa). In this retrospective study, we reviewed the clinical and pathological records of 184 consecutive patients who underwent bpMRI before prostate biopsy. We focused on patients with PI-RADS v2 scores ≥ 3. MRI was performed using a 3-Tesla clinical scanner with a 32-channel phased-array receiver coil. PI-RADS v2 was used to describe bpMRI findings based on T2-weighted imaging and diffusion-weighted imaging scores. The primary endpoint was the diagnostic accuracy rate of PI-RADS v2 based on bpMRI for patients with prostate cancer (PCa) who underwent combined TBx and SBx. A total of 104 patients were enrolled in this study. Combined TBx and SBx was significantly superior to either method alone for PCa detection in patients with suspicious lesions according to PI-RADS v2. TBx and SBx detected concordant csPCa in only 24.1% of the patients. In addition, the rate of increase in the Gleason score was similar between SBx (41.5%) and TBx (34.1%). The diagnostic accuracy of bpMRI is comparable to that of standard multiparametric MRI for the detection of csPCa. Moreover, combined TBx and SBx may be optimal for the accurate determination of csPCa diagnosis, the International Society of Urological Pathology grade, and risk classification.
Subject(s)
Magnetic Resonance Imaging , Prostatic Neoplasms , Humans , Image-Guided Biopsy , Male , Prostatic Neoplasms/diagnostic imaging , Retrospective StudiesABSTRACT
PURPOSE: The purpose of this study was to determine the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of ovarian mature teratoma in patients with anti-N-methyl-d-aspartate receptor encephalitis (NMDAR-E). MATERIALS AND METHODS: A total of 125 women (mean age, 40.9±17.8 [SD] years; age range: 12-85 years) with 146 histopathologically or radiologically proven ovarian mature teratomas who underwent preoperative CT and MRI examinations were retrospectively included. Eight patients with 11 teratomas had NMDAR-E, whereas 117 patients with 135 teratomas did not have NMDAR-E. CT and MRI examinations were retrospectively reviewed and teratomas in patients with NMDAR-E were compared to those in patients without NMDAR-E. Comparisons were performed using Mann-Whitney U test or Fisher exact test. RESULTS: In patients with NMDAR-E, maximum diameter of teratomas (26.1±9.3 [SD] mm), prevalence of teeth/calcification (36%) and rate of occupation by fat components (26%) were lower than those in patients without NMDAR-E (67.0±37.6 [SD] mm [P<0.01]; 75% [P<0.05]; and 65%[P<0.01], respectively). More than 75% of space was occupied by fat components in 76/135 teratomas (56%) in patients without NMDAR-E, whereas this was not observed in any teratoma in patients without NMDAR-E. CONCLUSION: By comparison with teratomas in patients without NMDAR-E, teratomas in patients with NMDAR-E are smaller, have few teeth/calcification, and the amount of space occupied by fat components is smaller.
Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Ovarian Neoplasms , Teratoma , Adolescent , Adult , Aged , Aged, 80 and over , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnostic imaging , Child , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Ovarian Neoplasms/diagnostic imaging , Retrospective Studies , Teratoma/diagnostic imaging , Tomography, X-Ray Computed , Young AdultABSTRACT
PURPOSE: This study aimed to evaluate imaging findings of cutaneous angiosarcoma (cAS) of the scalp compared with those of cutaneous squamous cell carcinoma (cSCC). METHODS: This study included 15 patients with primary cAS and 10 with primary cSCC of the scalp. Seven patients with cAS and eight with cSCC underwent magnetic resonance imaging, and 11 patients with cAS and eight with cSCC underwent 18F-fluorodeoxyglucose-positron emission tomography/computed tomography imaging. Imaging findings for both pathologies were retrospectively reviewed and compared. RESULTS: All 15 cAS cases were elevated lesions with an obtuse angle, invading the subcutaneous fat tissue. Multiple lesions were observed in only five cAS cases (33%) and no cSCC cases. Maximum diameter-to-height ratio was significantly higher in cAS than in cSCC (3.3 ± 1.0 versus 2.3 ± 0.6; p < 0.01). On T2-weighted images, intratumoral hypointensity (86% versus 13%; p < 0.01) and mixed hyper- and hypointensity (71% versus 0%; p < 0.01) were observed more frequently in cAS than in cSCC. No significant differences were observed between cAS and cSCC regarding flow void (29% versus 25%; p = 0.656). Maximum standardized uptake values were marginally significantly lower in cAS than in cSCC (5.6 ± 3.1 versus 10.5 ± 6.6; p = 0.078). CONCLUSIONS: Cases of cAS of the scalp always exhibited flat elevated lesions with invasion of the subcutaneous fat tissue. Compared with cSCC, intratumoral hypointensity and mixed hyper- and hypointensity on T2-weighted images were more frequent in cAS. These findings will help with the differential diagnosis of cAS.
Subject(s)
Carcinoma, Squamous Cell , Hemangiosarcoma , Skin Neoplasms , Carcinoma, Squamous Cell/diagnostic imaging , Fluorodeoxyglucose F18 , Hemangiosarcoma/diagnostic imaging , Humans , Magnetic Resonance Imaging , Retrospective Studies , Scalp/diagnostic imaging , Skin Neoplasms/diagnostic imagingABSTRACT
BACKGROUND: Sarcomatoid renal cell carcinoma (SRCC) is associated with poor prognosis. Although there is no standard treatment for SRCC, recent studies have reported the effectiveness of immune checkpoint inhibitors. CASE: An 82-year-old Japanese man presented to our hospital with an incidental right renal tumor. Abdominal computed tomography (CT) showed an exophytic tumor in the right kidney with suspected right iliopsoas muscle invasion. Laparoscopic right radical nephrectomy was performed. Histopathological diagnosis revealed a clear cell RCC with a spindle cell carcinoma component. CT performed 3 months after surgery revealed multiple bilateral lung metastases and local recurrence. Although the patient received tyrosine-kinase inhibitors for treating multiple metastases, the lung metastases continued to gradually increase, and peritonitis carcinomatosis was observed. Thus, the patient was intravenously administered nivolumab once every 2 weeks. After nivolumab administration, lung metastases, local recurrence, and peritonitis carcinomatosis gradually reduced. After 20 months of nivolumab treatment, the patient achieved a complete response of multiple metastases on CT. CONCLUSION: Nivolumab may be used as a treatment option for sarcomatoid renal cell carcinoma with multiple metastases.
Subject(s)
Carcinoma, Renal Cell/therapy , Kidney Neoplasms/therapy , Lung Neoplasms/therapy , Nivolumab/therapeutic use , Peritoneal Neoplasms/therapy , Aged, 80 and over , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/secondary , Chemotherapy, Adjuvant/methods , Humans , Kidney/pathology , Kidney/surgery , Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/secondary , Male , Nephrectomy , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/secondary , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Evidence regarding intraductal papillary neoplasm of the bile duct (IPNB) as a type of precancerous lesion of cholangiocarcinoma is limited. Moreover, a reproducible in vivo model is lacking, and IPNB pathogenesis remains unclear. Here, we use a doxycycline-inducible tetracycline (Tet)-on mice model to control fibroblast growth factor 10 (FGF10) expression, which regulates branching and tubule formation. FGF10-induced IPNB mimics the multifocal and divergent human IPNB phenotypes via the FGF10-FGF receptor 2 (FGFR2)-RAS-extracellular-signal-regulated kinase (ERK) signaling pathway. A paracrine/autocrine growth factor is sufficient to initiate and maintain IPNB originating from the peribiliary glands, including biliary stem/progenitor cells. With KrasG12D, p53, or p16 mutations or both, Fgf10-induced IPNB shows stepwise carcinogenesis, causing associated invasive carcinoma. Fgf10-induced papillary changes and progression are suppressed by the inhibition of the FGF10-FGFR2-RAS-ERK signaling pathway, demonstrating that the signal is a therapeutic target for IPNB and associated carcinoma.
Subject(s)
Bile Duct Neoplasms/enzymology , Carcinoma, Papillary/enzymology , Cholangiocarcinoma/enzymology , Extracellular Signal-Regulated MAP Kinases/metabolism , Fibroblast Growth Factor 10/metabolism , Neoplastic Stem Cells/enzymology , Precancerous Conditions/enzymology , Aged , Aged, 80 and over , Animals , Antineoplastic Agents/pharmacology , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/pathology , Carcinoma, Papillary/drug therapy , Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Cells, Cultured , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , Disease Progression , Female , Fibroblast Growth Factor 10/genetics , Gene Expression Regulation, Neoplastic , Genes, ras , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Nude , Mice, Transgenic , Middle Aged , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinase Kinases/metabolism , Mutation , Neoplastic Stem Cells/pathology , Phosphorylation , Precancerous Conditions/drug therapy , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Protein Kinase Inhibitors/pharmacology , Receptor, Fibroblast Growth Factor, Type 2/genetics , Receptor, Fibroblast Growth Factor, Type 2/metabolism , Signal TransductionABSTRACT
Giant cell glioblastoma (GCG) is a rare subtype of glioblastoma multiforme (GBM), and it often occurs in younger patients; however, its onset in children is extremely noticeable. A 7-year-old girl presented with a headache and restlessness. A giant tumor that was 7 cm in diameter was found by magnetic resonance imaging (MRI) in the left frontal lobe with intracranial dissemination. Because the tumor had extended to the lateral ventricles and occluded the foramen of Monro causing hydrocephalus, she underwent ventricular drainage and neuro-endoscopic biopsy from the left posterior horn of the lateral ventricle. The initial pathological diagnosis was an atypical teratoid/rhabdoid tumor (AT/RT). When the dissemination subsided after the first chemotherapy with vincristine, doxorubicin, and cyclophosphamide, she underwent the first tumor resection via a left frontal transcortical approach. After surgery, the second chemotherapy with ifosfamide, cisplatin, and etoposide was not effective for the residual tumor and intracranial dissemination. The second surgery via a transcallosal approach achieved nearly total resection leading to an improvement of the hydrocephalus. The definitive pathological diagnosis was GCG. Despite chemo-radiation therapy, the dissemination in the basal cistern reappeared and the hydrocephalus worsened. She was obliged to receive a ventriculo-peritoneal (VP) shunt and palliative care at home; however, her poor condition prevented her discharge. Ten months after admission, she died of tumor progression. The peritoneal dissemination was demonstrated by cytology of ascites. In conclusion, although unusual, pediatric GCG may be disseminated at diagnosis, in which case both tumor and hydrocephalus control need to be considered.
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OBJECTIVES: This study aimed to assess the efficacy of imaging findings when differentiating between human papillomavirus (HPV)-positive and -negative squamous cell carcinomas (SCCs) of the maxillary sinus. MATERIAL AND METHODS: This study included 37 patients with histopathologically and immunohistochemically confirmed SCCs of the maxillary sinus (three HPV positive and 34 HPV negative). Apparent diffusion coefficients (ADCs), MR signal intensities, CT findings, and maximum standardized uptake (SUVmax) were correlated with the two pathologies. RESULTS: The minimum ADC (ADCmin) was significantly lower in HPV-positive SCCs than in HPV-negative SCCs (0.50 ± 0.02 vs. 0.70 ± 0.13 × 10-3 mm2/s, P < 0.01). The mean ADC (ADCmean) was not significantly different between HPV-positive SCCs and HPV-negative SCCs (0.84 ± 0.07 vs. 0.97 ± 0.18 ×10-3 mm2/s, P = 0.18). The areas under the receiver operating characteristic curves for ADCmin and ADCmean were 0.986 (P < 0.01) and 0.754 (P < 0.05), respectively. The sensitivity and specificity, with a threshold of ADCmin (0.516 × 10-3 mm2/s) for a diagnosis of HPV-positive SCCs, were 100% and 96%, respectively. However, no significant differences were observed in MR signal intensities, CT findings, and SUVmax between HPV-positive and HPV-negative SCCs. CONCLUSION: ADCmin is a useful parameter for the differentiation of HPV-positive and HPV-negative SCCs of the maxillary sinus.