Cerebral Tumefactive Inflammatory Lesion Occurrence During Ixekizumab Treatment in a Patient With Active Psoriatic Arthritis.

INTRODUCTION: Ixekizumab is an anti-interleukin-17A (IL-17A) humanized monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis, active psoriatic arthritis, and ankylosing spondylitis. Central nervous system inflammatory manifestations are atypical during therapy with IL-17A inhibitors, with only one case of myelitis described to date. CASE REPORT: A 72-year-old man with a medical history of active psoriatic arthritis was admitted to our department owing to the acute onset of left face numbness 1 month after the first ixekizumab administration. Magnetic resonance imaging of the brain displayed a large T2-hyperintense infratentorial lesion involving the root of the fifth and seventh left cranial nerves. A thorough laboratoristic and instrumental work-up did not show elements suggestive of extracerebral neoplasms or infections. Therefore, neuronavigation-assisted brain biopsy was performed, and histologic analysis of the lesion revealed the presence of wide aggregates of foamy histiocytes diffusely infiltrating the brain parenchyma, in the absence of malignant tissue or histologic elements suggestive of central nervous system infections or primary histiocytoses. Steroid treatment (dexamethasone 8 mg/daily) was then administered with subsequent clinical amelioration. One month after hospital discharge, a brain magnetic resonance imaging showed a nearly complete resolution of the lesion. CONCLUSION: This is the first case of a cerebral inflammatory lesion occurring during treatment with ixekizumab. Although very rare, neurological complications may occur during anti-IL-17A therapies, thus leading to the need for careful monitoring of patients exposed to these drugs.

Barrett's esophagus and adenocarcinoma risk: the experience of the North-Eastern Italian Registry (EBRA).

OBJECTIVE: To establish the incidence and risk factors for progression to high-grade intraepithelial neoplasia (HG-IEN) or Barrett's esophageal adenocarcinoma (BAc) in a prospective cohort of patients with esophageal intestinal metaplasia [(BE)]. BACKGROUND: BE is associated with an increased risk of BAc unless cases are detected early by surveillance. No consistent data are available on the prevalence of BE-related cancer, the ideal surveillance schedule, or the risk factors for cancer. METHODS: In 2003, a regional registry of BE patients was created in north-east Italy, establishing the related diagnostic criteria (endoscopic landmarks, biopsy protocol, histological classification) and timing of follow-up (tailored to histology) and recording patient outcomes. Thirteen centers were involved and audited yearly. The probability of progression to HG-IEN/BAc was calculated using the Kaplan-Meier method; the Cox regression model was used to calculate the risk of progression. RESULTS: HG-IEN (10 cases) and EAc (7 cases) detected at the index endoscopy or in the first year of follow-up were considered to be cases of preexisting disease and excluded; 841 patients with at least 2 endoscopies {median, 3 [interquartile range (IQR): 2-4); median follow-up = 44.6 [IQR: 24.7-60.5] months; total 3083 patient-years} formed the study group [male/female = 646/195; median age, 60 (IQR: 51-68) years]. Twenty-two patients progressed to HG-IEN or BAc (incidence: 0.72 per 100 patient-years) after a median of 40.2 (26.9-50.4) months. At multivariate analysis, endoscopic abnormalities, that is, ulceration or nodularity (P = 0.0002; relative risk [RR] = 7.6; 95% confidence interval, 2.63-21.9), LG-IEN (P = 0.02, RR = 3.7; 95% confidence interval, 1.22-11.43), and BE length (P = 0.01; RR = 1.16; 95% confidence interval, 1.03-1.30) were associated with BE progression. Among the LG-IEN patients, the incidence of HG-IEN/EAc was 3.17 patient-years, that is, 6 times higher than in BE patients without LG-IEN. CONCLUSIONS: These results suggest that in the absence of intraepithelial neoplastic changes, BE carries a low risk of progression to HG-IEN/BAc, and strict surveillance (or ablative therapy) is advisable in cases with endoscopic abnormalities, LG-IEN or long BE segments.

Simultaneous occurrence of renal oncocytoma and B small cell lymphoma in the same kidney: report of two cases.

Two cases of simultaneous occurrence of oncocytoma (OC) associated with small B-cell lymphoma in the same kidney were investigated. Computed tomography, performed for staging purposes, incidentally revealed a small hypo- and hyperattenuating renal mass. Diagnosis of OC was performed on the specimen by morphology, immunohistochemistry and electron microscopy. The patients are in complete remission after a vaccinotherapy with follicular dendritic cells. The occurrence of OC and non-Hodgkin lymphoma in the same kidney has never been reported. These case reports outline that computerized tomography is a sensitive method in the staging of lymphoma. However, when some solid, small hyper- or hypoattenuating masses occur in the kidney, the diagnosis by computed tomography alone is always a challenge and other malignant neoplasms may be considered. Immunohistochemistry and electron microscopy allow a definitive diagnosis of OC.

[Prognostic significance of the Mandard TRG classification after induction therapy in carcinoma of the oesophagus and cardia]. / Significato prognostico della classificazione TRG di Mandard dopo terapia induttiva nel carcinoma di esofago e cardias.

Mandard's tumor regression grade (TRG) is widely used to evaluate the pathological response to induction therapy with concurrent chemoradiotherapy in cancer of the oesophagus or gastro-oesophageal junction. The aim of this study was to evaluate the prognostic significance and clinical applicability of TRG. From 2000 to 2007, 108 patients with squamous cell carcinoma of the oesophagus (57 cases) or Siewert type I and II adenocarcinoma of the cardia (51 cases) were treated with induction chemoradiotherapy followed by surgery in the 1st Division of General Surgery of the University of Verona. The treatment was identical for all patients and consisted of cisplatin, 5 FU and docetaxel together with 50 Gy of concurrent radiotherapy. The treatment-induced response was evaluated by TRG. Fifty-one, 24, 17, 9 and 7 patients were classified, respectively, as TRG1, 2, 3 4 and 5. Fifty-two patients died of the disease. Disease-related survival decreased with the increase in TRG class in node-negative patients (p < 0.001), while in N+ patients it was poor, irrespective of TRG class (p = 0.241). Mandard TRG is therefore useful for staging patients undergoing preoperative chemoradiotherapy, because it displays high prognostic significance. In our study, however, N was the main prognostic factor and for this reason it is mandatory to consider nodal status along with TRG. Moreover, among N negative patients, the prognosis of each different TRG class is statistically different and for this reason different TRG classes cannot be grouped together.

Low grade epithelial stromal tumour of the seminal vesicle.

BACKGROUND: The mixed epithelial stromal tumour is morphologically characterised by a mixture of solid and cystic areas consisting of a biphasic proliferation of glands admixed with solid areas of spindle cells with variable cellularity and growth patterns. In previous reports the seminal vesicle cystoadenoma was either considered a synonym of or misdiagnosed as mixed epithelial stromal tumour. The recent World Health Organisation Classification of Tumours considered the two lesions as two distinct neoplasms. This work is aimed to present the low-grade epithelial stromal tumour case and the review of the literature to the extent of establishing the true frequency of the neoplasm. CASE PRESENTATION: We describe a low-grade epithelial stromal tumour of the seminal vesicle in a 50-year-old man. Computed tomography showed a 9 x 4.5 cm pelvic mass in the side of the seminal vesicle displacing the prostate and the urinary bladder. Magnetic resonance was able to define tissue planes between the lesion and the adjacent structures and provided useful information for an accurate conservative laparotomic surgical approach. The histology revealed biphasic proliferation of benign glands admixed with stromal cellularity, with focal atypia. After 26 months after the excision the patient is still alive with no evidence of disease. CONCLUSION: Cystoadenoma and mixed epithelial stromal tumour of seminal vesicle are two distinct pathological entities with different histological features and clinical outcome. Due to the unavailability of accurate prognostic parameters, the prediction of the potential biological evolution of mixed epithelial stromal tumour is still difficult. In our case magnetic resonance imaging was able to avoid an exploratory laparotomy and to establish an accurate conservative surgical treatment of the tumour.

Microfluidic deletion/insertion analysis for rapid screening of KIT and PDGFRA mutations in CD117-positive gastrointestinal stromal tumors: diagnostic applications and report of a new KIT mutation.

Gastrointestinal stromal tumors (GISTs) frequently harbor mutations in the KIT and PDGFRA genes, the presence and type of which correlate with the response to the kinase inhibitor imatinib mesylate. Because most GIST mutations are deletions/insertions, we used a microfluidic apparatus to detect these size variations in polymerase chain reaction-amplified DNA. This approach, termed microfluidic deletion/insertion analysis (MIDIA), identified mutations in 30 of 50 DNA samples from paraffin-embedded CD117-positive GISTs (60%), comprising 25 deletions and five insertions. Sequencing of 14 MIDIA-positive samples confirmed the deletions/insertions, including two 3-bp alterations. Sequencing of all 20 MIDIA-negative samples also showed highly consistent results with MIDIA because 10 cases were wild type and eight displayed a single base substitution in which detection by MIDIA was not expected. Sequencing also revealed a 3-bp deletion undetected by MIDIA, thus establishing the resolution limit of MIDIA at deletions/insertions >or=3 bp. Denaturing high-pressure liquid chromatography analysis confirmed all mutations detected by MIDIA and sequencing. We pro-pose MIDIA as the first step in mutational screening of GIST because it allowed the detection of 75% of mutated cases (94% of deletions/insertions) in less than 30 minutes after polymerase chain reaction amplification and at a lower cost compared with denaturing high-pressure liquid chromatography and sequencing, which might then be used only for MIDIA-negative cases.

Insulin-like growth factor II mRNA binding protein 3 (IMP3) expression in cervical intraepithelial neoplasia and its relationship with HIV-infection status.

UNLABELLED: Background Cervical cancer is preventable through screening, and HIV treatment guidelines recommend that all HIV-infected women receive cervical cancer twice during the year after HIV diagnosis and annually thereafter. Different immunohistochemical markers have been studied to highlight cervical intraepithelial lesions of low and high grade, the most widely used being p16. Recent studies have shown that insulin-like growth factor mRNA binding protein 3 (IMP3) plays a role in the development of invasive squamous cell carcinoma from cervical dysplasia, both in histology and in liquid-based cytology. METHODS: We evaluated the clinical significance of the immunohistochemical expression of IMP3 and p16 in histological samples of cervical intraepithelial neoplasia from 56 samples of HIV-positive and 30 samples of HIV-negative patients. RESULTS: A significant difference was found in IMP3 and p16 protein expression between HIV-positive and HIV-negative specimens. All cases of HIV-positive low grade squamous intraepithelial neoplasia (L-SIL) with IMP3 expression progressed in high grade (H)-SIL. However, the HIV-positive patients with IMP3-negative L-SIL remained stable or had a negative follow up. The L-SIL of HIV-negative patients with IMP3 protein expression had an uneventful follow up. IMP3-positive H-SIL recurred with low- or high-grade dysplasia during follow up after conisation in both populations. All IMP3-negative L-SIL and H-SIL had negative pap tests at follow up. CONCLUSIONS: In HIV-positive cases, IMP3 showed a higher sensitivity than p16 in identifying patients at risk of progression and recurrence.

Borderline ovarian tumors and diagnostic dilemma of intraoperative diagnosis: could preoperative He4 assay and ROMA score assessment increase the frozen section accuracy? A multicenter case-control study.

The aim of our study was to assess the value of a preoperative He4-serum-assay and ROMA-score assessment in improving the accuracy of frozen section histology in the diagnosis of borderline ovarian tumors (BOT). 113 women presenting with a unilateral ovarian mass diagnosed as serous/mucinous BOT at frozen-section-histology (FS) and/or confirmed on final pathology were recruited. Pathologists were informed of the results of preoperative clinical/instrumental assessment of all patients. For Group_A patients, additional information regarding He4, CA125, and ROMA score was available (in Group_B only CA125 was known). The comparison between Group A and Group B in terms of FS accuracy, demonstrated a consensual diagnosis in 62.8% versus 58.6% (P: n.s.), underdiagnosis in 25.6% versus 41.4% (P<0.05), and overdiagnosis in 11.6% versus 0% (P<0.01). Low FS diagnostic accuracy was associated with menopausal status (OR: 2.13), laparoscopic approach (OR: 2.18), mucinous histotype (OR: 2.23), low grading (OR: 1.30), and FIGO stage I (OR: 2.53). Ultrasound detection of papillae (OR: 0.29), septa (OR: 0.39), atypical vascularization (OR: 0.34), serum He4 assay (OR: 0.39), and ROMA score assessment (OR: 0.44) decreased the probability of underdiagnosis. A combined preoperative assessment through serum markers and ultrasonographic features may potentially reduce the risk of underdiagnosis of BOTs on FS while likely increasing the concomitant incidence of false-positive events.

Middle ear metastasis from dormant breast cancer as the initial sign of disseminated disease 20 years after quadrantectomy.

We describe an unusual case of breast cancer metastatic to the middle ear in a 71-year-old woman. The metastasis was the initial sign of disseminated disease 20 years after the patient had undergone a quadrantectomy for her primary disease. Computed tomography (CT) demonstrated the presence of an intratympanic mass with a soft-tissue density that was suggestive of chronic inflammation. The patient underwent a canal-wall-down tympanoplasty. When a brownish mass was found around the ossicles, a mastoidectomy with posterior tympanotomy was carried out. However, exposure of the tumor was insufficient, and therefore the posterior wall of the ear canal had to be removed en bloc. Some tumor was left on the round window membrane so that we would not leave the patient with a total hearing loss. Our case highlights the limitations of CT and magnetic resonance imaging in differentiating inflammatory and neoplastic lesions.

A presacral solitary fibrous tumor with extramedullary hematopoiesis: radiologic and pathologic findings.

Solitary fibrous tumors (SFT) are rare, ubiquitous neoplasms of mesenchymal origin, with distinctive histopathological and immunohistochemical features. We herein report an unusual case of a presacral SFT diagnosed in an asymptomatic 40-year-old woman preoperatively investigated with computed tomography and magnetic resonance imaging. Post-operative pathology examination showed a SFT containing foci of extramedullary hematopoiesis. Revision of preoperative imaging did not evidenced any findings suggesting this unusual association. The patient was free from local recurrence and metastases one year after operation. Differential radiological and histological diagnoses of solid presacral masses is briefly discussed.

Oncocytic sialolipoma of the submandibular gland with sebaceous differentiation: a new pathological entity.

CASE REPORT: We report the case of an oncocytic sialolipoma of the submandibular gland with sebaceous differentiation in a 73-year-old man. The initial symptom was a right submandibular painless mass. Ultrasonography showed a hypoechoic oval mass posterior to the submandibular gland. The tumorectomy was performed with preservation of the salivary gland. The tumor was composed of mature adipose tissue surrounded by a thin fibrous capsule, multiple nodules of oncocytes, normal ductal-acinar units with focal ductal sebaceous differentiation. DISCUSSION: We reviewed literature of the reported cases of mixed tumors of the salivary glands composed of mature adipose tissue with oncocytosis, salivary ducts, and acini with sebaceous differentiation. CONCLUSIONS: Sialolipoma and lipoadenoma with or without oncocytosis and/or sebaceous differentiation should be considered organ-specific tumors with a distinct histological appearance and specific terminology.

Clinical Outcome of High Risk Gastrointestinal Stromal Tumor in a Meckel's Diverticulum.

We describe a seven years follow-up of a high risk gastrointestinal stromal tumor in a Meckel's diverticulum in a 68-year-old man with abdominal pain and vomiting. The patient was operated in emergency for peritonitis due to perforation of small intestine and treated with imatinib mesylate. The metastatic progression of the disease demonstrated the value of prognostic indicators (mitotic rate >10/50 high power field, necrosis and 8 cm in maximum diameter) for assessing risk of aggressive behaviour. Computed tomography was a valuable procedure for detection of local recurrence, the distant metastases and for surveillance after surgery in the follow-up. The review of the literature shows that this case has the longest follow up and consents the comparisons of the same neoplasm in other sites most frequent and better described than Meckel's diverticulum.

Intestinal obstruction associated with chronic peritonitis caused by Sphingomonas paucimobilis.

We describe a very rare case of chronic peritonitis with secondary adhesive intestinal obstruction caused by Sphingomonas paucimobilis in a healthy 28-year-old Chinese man. This bacillus has not been described as a cause of spontaneous peritonitis in healthy people. It was an asymptomatic, generalized, and slow-growing peritonitis causing peritoneal adherens and at the end intestinal occlusion that needed surgical adhesiolysis.

Pathogenetic pathways in ovarian endometrioid adenocarcinoma: a molecular study of 29 cases.

It has been recently suggested that ovarian serous carcinoma follows a dualistic pathway with low-grade carcinomas arising from borderline tumors and high-grade carcinomas originating de novo. Similarly, our group has shown that based on their molecular profile endometrioid borderline tumors could predate low-grade endometrioid ovarian carcinomas (EOC). It is not clearly understood if low-grade EOC is in turn related to high-grade EOC, or if high-grade EOC may also arise de novo. The aim of our study was to compare the molecular profile of grade 1, 2, and 3 EOCs. Twenty-nine EOCs were selected including 10 grade 1 (G1), 11 grade 2 (G2), and 8 grade 3 (G3). Selected blocks were immunostained with beta-catenin and p53, and also microdissected, DNA extracted and amplified by polymerase chain reaction with primers for exon 3 of the beta-catenin gene, codons 12 and 13 of KRAS and codons 1 to 9 of PTEN. The length of BAT-26 and BAT-25 was analyzed to determine microsatellite instability (MSI). Patients with G1 EOC ranged from 21 to 71 (mean 52) years, those with G2 tumors ranged from 43 to 66 (mean 56) years, and patients with G3 EOC ranged from 41 to 67 (mean 57) years. Immunohistochemical analysis for beta-catenin showed nuclear staining in 14 cases (7 G1, 5 G2, and 2 G3 tumors), whereas the rest showed membranous staining. Beta-catenin mutations were found in only 3 G1 tumors. KRAS mutations were seen in 5 EOCs (2 G1 and 3 G2). MSI and mutations of PTEN were both detected in 1 G1 and 1 G2 tumor, respectively. There was no overlapping expression of MSI, beta-catenin, PTEN, or KRAS mutations. Finally, p53 overexpression was present in 6 EOCs (5 G3 and 1 G2), all G3 p53 positive tumors being negative for all other markers, whereas the G2 tumor also showed a KRAS mutation. In conclusion, beta-catenin and KRAS mutations, and MSI were strongly associated with low-grade EOC. In contrast, p53 overexpression characterized high-grade EOC, with no other molecular alterations present in the vast majority of these tumors. On the basis of these results, we suggest that there may also be a dual pathogenetic pathway for EOC.