Tumor-Infiltrating Lymphocyte Recognition in Primary Melanoma by Deep Learning Convolutional Neural Network.

The presence of tumor-infiltrating lymphocytes (TILs) is associated with a favorable prognosis of primary melanoma (PM). Recently, artificial intelligence (AI)-based approach in digital pathology was proposed for the standardized assessment of TILs on hematoxylin and eosin-stained whole slide images (WSIs). Herein, the study applied a new convolution neural network (CNN) analysis of PM WSIs to automatically assess the infiltration of TILs and extract a TIL score. A CNN was trained and validated in a retrospective cohort of 307 PMs including a training set (237 WSIs, 57,758 patches) and an independent testing set (70 WSIs, 29,533 patches). An AI-based TIL density index (AI-TIL) was identified after the classification of tumor patches by the presence or absence of TILs. The proposed CNN showed high performance in recognizing TILs in PM WSIs, showing 100% specificity and sensitivity on the testing set. The AI-based TIL index correlated with conventional TIL evaluation and clinical outcome. The AI-TIL index was an independent prognostic marker associated directly with a favorable prognosis. A fully automated and standardized AI-TIL appeared to be superior to conventional methods at differentiating the PM clinical outcome. Further studies are required to develop an easy-to-use tool to assist pathologists to assess TILs in the clinical evaluation of solid tumors.

Case report: Vitiligo-like toxicity due to ribociclib during first-line treatment of metastatic breast cancer: two cases of premature interruption of therapy and exceptional response.

Cancer treatment-related adverse events (AEs) are sometimes associated with outcomes for cancer patients, especially with the newest therapies such as target therapy and immunotherapy. A few years ago, the first-line therapy for hormone-receptor-positive metastatic breast cancer (mBC) patients has been deeply changed by the introduction of cyclin-dependent kinase (CDK) 4/6 inhibitors, and now, we are improving our knowledge about their AEs and significance in clinical practice. Here, we report our experience with two cases of vitiligo-like lesions that occur early during treatment with ribociclib. We tried to change the CDK4/6 inhibitor for one patient, but the skin reaction persisted. Both patients retained only the endocrine therapy alone and had an unexpected durable progression-free survival (PFS). Some data on skin toxicities, including vitiligo-like lesions by CDK4/6 inhibitors, have recently been reported in the literature, but for the first time, we highlight a possible correlation with improved survival outcomes of patients. Uncovering the etiology of this toxicity, verifying the involvement of the immune system, and demonstrating a possible positive impact in survival represent an intriguing research objective for the near future.

Melanocytic Lesions with Peripheral Globules: Proposal of an Integrated Management Algorithm.

INTRODUCTION: A peripheral rim of globules represents a marker of the horizontal growth phase in nevi and is a common feature in children and adolescents. The observation of melanocytic lesions with peripheral globules (MLPGs) in adulthood deserves more attention, since melanoma may exhibit this feature, albeit rarely. Risk-stratified management recommendations considering a global clinical approach are still missing. OBJECTIVES: To analyze current knowledge on MLPGs and propose an integrated management algorithm stratified for age groups. METHODS: We conducted a narrative review of current published data on MLPGs, analyzing clinical dermoscopic and confocal distinguishing features of melanoma from benign nevi. RESULTS: The risk of finding a melanoma when removing an MLPG increases with age, especially in people >55 years old, and is significantly higher in the extremities, head/neck and in case of a single asymmetrical lesion, ≥6 mm in diameter. Dermoscopic features associated with melanoma diagnosis include atypical peripheral globules, asymmetrical distribution, multiple rims as well as the reappearance of globules after prior loss. In addition, wide blue-grey regression areas, atypical networks, eccentric blotches, tan structureless peripheral areas and vascularization are atypical dermoscopic features. Confocal worrisome findings are represented by pagetoid cells within the epidermis, architectural disarrangement and atypical cells of the dermo-epidermal junction with irregular peripheral nests. CONCLUSION: We proposed a multi-step age-stratified management algorithm integrating clinical, dermoscopic and confocal findings that may increase the early recognition of melanoma and avoid surgical excision of benign nevi.

"Skin rashes" and immunotherapy in melanoma: distinct dermatologic adverse events and implications for therapeutic management.

Immune checkpoint inhibitors have shown efficacy in the treatment of different cancers by stimulating the antitumoral activity of the patient's immune system, representing a major breakthrough in the field of cancer therapy. Monoclonal antibodies including anti-cytotoxic T-lymphocyte-associated protein 4, anti-programmed cell death protein 1 and its ligand inhibitors have been approved for advanced melanoma among other solid cancers. Although immunotherapy demonstrated a good safety profile, a new spectrum of multisystemic immune-related adverse events has been recently reported due to their use. Cutaneous reactions represent one of the leading adverse events, often reported in literature as "skin rash", and rarely further characterized in distinct dermatologic entities. Herein we describe the distinctive cutaneous rashes occurring during immunotherapies for advanced melanoma, discussing implications in the treatment management.

Inclusion of Synovial Tissue-Derived Characteristics in a Nomogram for the Prediction of Treatment Response in Treatment-Naive Rheumatoid Arthritis Patients.

OBJECTIVE: This study applied a synovitis score obtained during routine care from ultrasound (US)-guided biopsies of synovial tissue (ST) in patients with rheumatoid arthritis (RA) and patients with other inflammatory and noninflammatory joint diseases to identify pretreatment synovial biomarkers associated with disease characteristics, and to integrate the findings into a multiparameter nomogram for use in baseline prediction of diagnosis and treatment response in treatment-naive rheumatoid arthritis (RA) patients. METHODS: The study enrolled a total of 1,015 patients with various autoimmune diseases (545 patients with RA, 167 patients with psoriatic arthritis [PsA], 199 patients with undifferentiated peripheral inflammatory arthritis [UPIA], 18 patients with crystal-induced arthritis, 26 patients with connective tissue diseases, and 60 patients with osteoarthritis [OA] [as part of the SYNGem cohort]). All patients underwent a US-guided ST biopsy at baseline, and patients were then stratified according to disease phase. The KSS, along with disease characteristics and clinical outcomes, were incorporated into a nomogram for prediction of achievement of clinical remission in RA patients who were previously naive to treatment. In patients in whom a treat-to-target strategy was applied, remission was defined as change in the Disease Activity Score in 28 joints (DAS28) at 6 months after treatment initiation. RESULTS: The KSS significantly differed among RA patients, as well as PsA patients and UPIA patients, when compared to OA patients. In RA, the KSS directly correlated with the DAS28 and was related to autoantibody positivity in treatment-naive RA patients. Moreover, at baseline, treatment-naive RA patients achieving 6-month remission according to DAS28 had a lower KSS, shorter duration of symptoms (very early RA [VERA]), and lower disease activity than treatment-naive RA patients not achieving remission according to DAS28. Results of logistic regression analysis identified the following synergistic predictive factors of achievement of DAS28-based disease remission at 6 months: having a short disease duration (VERA), not having high disease activity, and having a KSS of <5 at baseline. A nomogram integrating these baseline clinical and histologic characteristics in treatment-naive RA patients yielded an up to 81.7% probability of achieving 6-month remission according to the DAS28. CONCLUSION: The KSS is a reliable tool for synovitis assessment on US-guided ST biopsy, contingent on the phase of the disease and the autoimmune profile of each patient. This tool could be integrated within a therapeutic response-predictive nomogram for the prediction of treatment response in RA patients who were previously naive to treatment.

Maxillo-facial reconstruction following cancer ablation during COVID-19 pandemic in southern Italy.

In COVID-19 pandemic era, one major concern is related to ensure optimal management to oncologic patients, even though a context of radical uncertainty. The aim of our effort is to guarantee high-quality and timely care, minimizing COVID-19 infection risk, according to our head and neck (HN) reconstructive mission, still more challenging because of the criticality of the period. Thus, our reconstructive decision algorithm is changed. Microvascular free flaps, reported to be the gold standard for surgical reconstruction, represent extremely specialized procedures necessitating an extended resource allocation not affordable in the adversities of the period. Therefore, we are obliged to define a paradigm shift in our approach, based on free-style reconstructive surgery principles of propeller flap concept. According to our experience, we believe that this viable and feasible surgical technique could represent a reconstructive landmark in this pandemic era, since any guideline is missing, besides HN reconstructive surgery is most likely heading towards a new reconstructive approach.

The Safety of Radiotherapy in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Multidisciplinary Systematic Review.

Primary cutaneous B-cell lymphomas (PCBCL) are rare types of extranodal non-Hodgkin's lymphoma. The choice of treatment usually depends on the variant of PCBCL, number, size, and location of the lesions, involved body surface area as well as patient's age and health condition. The efficacy of radiotherapy (RT) in the treatment of PCBCL has been widely reported conversely, data about the acute and late skin toxicity, patient's treatment satisfaction and quality of life are scarce. A systematic search using PubMed, Scopus, and Cochrane library was performed to identify full original articles analyzing the safety of RT in patients with PCBCL with the primary outcome to assess the acute and late skin toxicity. Secondary outcomes were complete remission, disease free survival, and overall survival. The literature search resulted in 276 articles including eight studies assessing the safety of RT for the treatment of PCBCL. Most patients (median 73%, range 11.9-99.9%) were recorded as having acute skin toxicity of grade 1-2, while acute grade 3-4 toxicity occurred in a median of 8% (range 4-23%) of patients. A median of 20% (range 4-54%) of patients had late skin toxicity of grade 1-2. No late grade 3-4 toxicity was reported. Only one study evaluated patient's satisfaction showing that the 97% of patients were satisfied with radiation therapy. This systematic review confirms the safety of RT in the treatment of PCBCL. Patients with a PCBCL should be managed in highly specialized centers in the context of a multidisciplinary team including dermatologist, hematologist, pathologist, and radiation oncologist.

Hyaluronic Acid Injections to Correct Lips Deformity Following Surgical Removal of Permanent Implant.

One of the most attractive areas of the face are the lips, they are crucial for emotion and communication, both during animation and at rest. Throughout the years, several techniques to obtain permanent lip enhancement have been introduced, such as the use of nonresorbable fillers. The main problem related to permanent fillers is that undesirable results could not always be repaired; although lip sequelae can be addressed surgically, some surgeons will not perform this type of procedure due to its complexity and the lack of guidelines.In this paper, the authors present a case of a labial incompetence developed after lips implant removal performed elsewhere; after clinical examination the patient was planned for surgery, although during preoperative instrumental examination (chest X-ray) a solitary pulmonary nodule was noted; further investigation performed with needle biopsy revealed a lung cancer. For this reason, the surgical procedure planned for lip restoration was not performed; however, the patient asked for a minimally invasive procedure, thus to improve, although temporarily, her lips appearance.For the aforementioned reasons, the patient was treated just with hyaluronic acid injections achieving a pleasant result, solving also the labial incompetence at rest.To the best of the author's knowledge, this paper represents the first one describing the use of hyaluronic acid injections to restore lip competence following surgical removal of permanent implant.

SKIN-COBRA (Consortium for Brachytherapy data Analysis) ontology: The first step towards interdisciplinary standardized data collection for personalized oncology in skin cancer.

PURPOSE: The primary objective of the SKIN-COBRA (Consortium for Brachytherapy data Analysis) ontology is to define a specific terminological system to standardize data collection for non-melanoma skin cancer patients treated with brachytherapy (BT, interventional radiotherapy). Through ontological characterization of information, it is possible to find, isolate, organize, and integrate its meaning. MATERIAL AND METHODS: SKIN-COBRA is a standardized data collection consortium for non-melanoma skin patients treated with BT, including 8 cancer centers. Its ontology was firstly defined by a multicentric and multidisciplinary working group and evaluated by the consortium, followed by a multi-professional technical commission involving a mathematician, an engineer, a physician with experience in data storage, a programmer, and a software expert. RESULTS: Two hundred and ninety variables were defined in 10 input forms. There are 3 levels, with each offering a specific type of analysis: 1. Registry level (epidemiology analysis); 2. Procedures level (standard oncology analysis); 3. Research level (radiomics analysis). The ontology was approved by the technical commission and consortium, and an ad-hoc software system was defined to be implemented in the SKIN-COBRA consortium. CONCLUSIONS: Large databases are natural extension of traditional statistical approaches, a valuable and increasingly necessary tool for modern healthcare system. Future analysis of the collected multinational and multicenter data will show whether the use of the system can produce high-quality evidence to support multidisciplinary management of non-melanoma skin cancer and utilizing this information for personalized treatment decisions.

Impact of Ascending Aorta Dilation on Mid-Term Outcome After Transcatheter Aortic Valve Implantation.

BACKGROUND: Severe aortic stenosis (AS) is often associated with ascending aorta dilation (AAD). AAD is amenable to surgical correction combined with aortic valve replacement. Transcatheter aortic valve implantation (TAVI) might represent a valid therapeutic option in these patients when AAD correction Is not indicated. The aim of the present study is to evaluate the impact of concomitant AAD on early and mid-term outcomes after TAVI for symptomatic severe AS. METHODS: This is a single-center observational study including patients undergoing transfemoral TAVI. All patients with previous surgery on the left ventricular outflow tract, aortic valve, or ascending aorta (except coronary artery bypass graft surgery) were excluded from the analysis. Patients undergoing TAVI for congenital aortic valve defects or subjects in whom a computed tomography (CT) scan was not available were excluded from the analysis. Ascending aortas were measured on CT scans using appropriate multiplanar reconstructions. Ascending aortas were qualified as dilated if the measurement was >40 mm. Study outcomes were death from any cause, significant paravalvular leaks (PVLs), and new permanent pacemaker (PPM) implant. RESULTS: The final population consisted of 680 subjects, 61% females, mean age 82 ± 7 years. One hundred subjects (15%) had AAD. No differences in terms of significant PVL or PPM implantation were found between subjects with or without AAD (P>.99 and P=.13, respectively). At a median follow-up of 498 ± 216 days, no significant difference in terms of mortality was found between subjects with or without AAD (P=.78). CONCLUSIONS: AAD does not appear to impact the mid-term outcomes in a cohort of subjects undergoing TAVI.

Differential synovial tissue biomarkers among psoriatic arthritis and rheumatoid factor/anti-citrulline antibody-negative rheumatoid arthritis.

BACKGROUND: Differential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Abneg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Abneg RA and test their predictive value of therapeutic response. METHODS: Thirty-four PsA patients [12 DMARD naive and 22 non-responder to methotrexate (MTX-IR)] with peripheral joint involvement and 55 Abneg RA (27 DMARD naive and 28 MTX-IR) underwent US-guided ST biopsy and immunohistochemistry (IHC) for CD68+, CD3+, CD20+, CD21+, CD117+, and CD138+ cells. After study entry, each DMARD-naive patient started MTX therapy and was followed in an outpatient setting for at least 6 months to define the achievement of Minimal Disease Activity (PsA) and DAS remission (Abneg RA) status respectively. Each IR-MTX patient was treated according to EULAR recommendations. RESULTS: At study entry, IHC analysis revealed that PsA patients had comparable levels of lining and sublining CD68+ and sublining CD21+, CD20+, and CD3+ cells than Abneg RA, despite the therapeutic regimen. Moreover, regardless of the therapeutic scheme, PsA patients showed higher IHC score of CD117+ cells (p = 0.0004 and p = 0.0005 for naive and MTX-IR patients respectively) compared to Abneg RA patients. Conversely, Abneg RA patients showed higher IHC score of CD138+ cells, irrespective to the therapeutic scheme (p = 0.04 and p = 0.002 for naive and MTX-IR patients respectively). Analyzing the response rate to the therapeutic scheme, naive PsA patients reaching MDA status at 6 months follow-up, showed, at the study entry, lower IHC score of CD3+ cells compared to PsA patients not reaching this outcome (p = 0.02); conversely, naive Abneg RA patients reaching DAS remission status at 6 months follow-up, showed, at the study entry, lower IHC score of sublining CD68+ cells compared to Abneg RA patients not reaching this outcome (p < 0.001). CONCLUSIONS: CD117+ and CD138+ cells are differentially distributed among PsA and Abneg RA. Histological analysis of ST may help to solve the clinical overlap between the two diseases and provides prognostic data about the therapy success.

Synovial Predictors of Differentiation to Definite Arthritis in Patients With Seronegative Undifferentiated Peripheral Inflammatory Arthritis: microRNA Signature, Histological, and Ultrasound Features.

Objectives: To examine synovial tissue (ST) predictors of clinical differentiation in patients with seronegative undifferentiated peripheral inflammatory arthritis (UPIA). Methods: Fourty-two patients with IgA/IgM-Rheumatoid Factor and anti-citrullinated peptide antibodies negative UPIA, naive to Disease-Modifying Anti-Rheumatic Drugs, underwent Gray Scale (GSUS) and power Doppler (PDUS) evaluation and Ultrasound (US) guided ST biopsy. CD68, CD3, CD21, CD20, and CD31 synovial expression was evaluated by immunohistochemistry. Whole ST microRNA expression was assessed using miScript miRNA PCR Array. Peripheral blood (PB) and synovial fluid (SF) IL-6, VEGF-A, and VEGF-D levels were measured by ELISA and ST TNF expression was assessed by RT-PCR. Each patient was prospectively monitored and classified at baseline and within 1 year as UPIA, Rheumatoid Arthritis (RA), Spondyloarthritis (SpA) or Psoriatic Arthritis (PsA), respectively. Results: At baseline, CD68+ cells were the most common cells within the lining layer (p < 0.001) in seronegative UPIA, directly correlating with GSUS (R = 0.36; p = 0.02) and PDUS (R = 0.55; p < 0.001). Synovial CD31+ vessels count directly correlated with GSUS (R = 0.41; p = 0.01) and PDUS (R = 0.52; p < 0.001). During the follow-up, 6 (14.3%) UPIA reached a definite diagnosis (2 RA, 2 SpA and 2 PsA, respectively). At baseline, UPIA who differentiated had higher GSUS (p = 0.01), PDUS scores (p = 0.02) and higher histological scores for CD68+ (p = 0.005 and p = 0.04 for lining and sublining respectively), sublining CD3+ cells (p = 0.002), CD31+ vessels count (p < 0.001) and higher IL-6 PB levels (p = 0.01) than patients who remained as UPIA. MiRNA PCR Array showed that among the 86 tested miRNA species, at baseline, miR-346 and miR-214 were significantly down-regulated (p = 0.02 for both) in ST of UPIA who differentiated than in patients who remained as UPIA, inversely correlating with the lining CD68+ cells IHC score (R = -0.641; p = 0.048) and CD31+ vessels count (R = -0.665; p = 0.036) and with higher baseline ST expression of TNF (p = 0.014). Finally, logistic regression analysis demonstrated that baseline GSUS and PDUS scores ≥1.5 [OR:22.93 (95%CI:0.98-534.30)] and CD31+ vessels count ≥24.3 [OR:23.66 (95%CI:1.50-373.02)] were independent factors associated with the development of definite arthritis. Conclusions: MiRNA signature, histological and US features of ST may help in the identification of seronegative UPIA with high likelihood of clinical differentiation toward definite seronegative arthritis.

Paradoxical arthritis occurring during anti-TNF in patients with inflammatory bowel disease: histological and immunological features of a complex synovitis.

OBJECTIVE: Paradoxical arthritis under tumour necrosis factor inhibitor (TNF-i) for inflammatory bowel disease (IBD) has been described. This study aims to evaluate the histological features of paired synovial tissue (ST) and colonic mucosa (CM) tissue in patients with IBD developing paradoxical arthritis under TNF-i. METHODS: Patients with IBD without history of coexisting joint involvement who developed arthritis under TNF-i were enrolled. Each patient underwent ST biopsy and ileocolonoscopy with CM biopsies. ST and CM paired samples were stained through immunohistochemistry (IHC) for CD68, CD21, CD20, CD3 and CD117. Clinical and immunological parameters (anticitrullinated peptides antibodies (ACPA)-immunoglobulin (Ig)M/IgA rheumatoid factor (RF)) were collected. Psoriatic arthritis (PsA) and ACPA/IgM-RF/IgA-RF negative rheumatoid arthritis (RA) were enrolled as comparison. RESULTS: 10 patients with IBD (age 46.0±9.7 years, 13.2±9.9 years of disease duration, 2.5±1.6 years of TNF-i exposure, six with Crohn's disease and four with ulcerative colitis, respectively) were studied. At ST level, IHC revealed that patients with IBD with paradoxical arthritis showed more similar histological findings in terms of synovial CD68+, CD21+, CD20+, CD3+ and CD117+ cells compared with PsA than ACPA/IgM-RF/IgA-RF negative RA. Analysing the CM specimens, patients with IBD showed the presence of CD68+, CD3+, CD117+ and CD20+ cells in 100%, 70%, 60% and 50% of cases, respectively, despite endoscopic remission. Finally, addition of conventional disease-modifying antirheumatic drugs and switch to ustekinumab were more effective than swapping into different TNF-i in patients with IBD with paradoxical arthritis. CONCLUSION: Patients with IBD may develop histologically proven synovitis during TNF-i, comparable to PsA. The inhibition of inflammatory pathways alternative to TNF (IL12/1L23) may be an effective therapeutic option for severe paradoxical articular manifestations.

Debris of carbon-fibers originated from a CFRP (pEEK) wrist-plate triggered a destruent synovitis in human.

Application of carbon-fiber-reinforced-polymer (CFRP) artifacts in humans has been promoted in Orthopedic and Trauma Surgery. Literature documents the biocompatibility of materials used, namely carbon fibers (CF) and poly-ether thermoplastics, like poly-ether-ether-ketone (PEEK). A properly designed and accurately implanted composite artifact should not expose its fibers during or after surgery: however this may happen. A white Caucasian woman came to our attention 11 months after surgery for a wrist fracture. She had a severe impairment, being unable to flex the thumb; index finger and distal phalanx of third finger. We retrieved a correctly positioned plate and documented an aggressive erosive flexor tendons synovitis with eroded stumps of flexor tendons. The plate and soft tissues were analyzed by Visible Light and Scanning Electron Microscopy. Histopathology showed granulomatous fibrogenic process with CF engulfed inside multinucleated giant cells. Fibers were unmasked and disrupted inside the holes where screws were tightened and corrugation of the polymer coating led to further unmasking. The mechanism of foreign-body reaction to CF has not been studied in depth yet, particularly at the ultrastructural level and in Humans. This case documents a damage occurred in a clinical application and which was theoretically possible. Our opinion is that a proper way to promote the use of CRFP in the Clinic in the short term is to direct Research towards finding a better way to prevent CF debris to be exposed and released. In the longer term, the biological response to CF deserves a deeper understanding.

Prevention of postoperative recurrence with azathioprine or infliximab in patients with Crohn's disease: an open-label pilot study.

BACKGROUND AND AIMS: Patients with Crohn's disease (CD) often require surgery over their clinical course. However, endoscopic and clinical recurrence of disease appear respectively in up to 80% and 30% of patients after one year. Thus, a prophylactic treatment is needed to reduce the possibility of recurrence. Both azathioprine and infliximab have been demonstrated to be effective, but head to head studies have not been performed so far. Aim of this open-label prospective study was to analyse endoscopic, histological and clinical recurrence after one year of treatment with azathioprine or infliximab as postoperative therapies in CD patients with "high risk" of recurrence. METHODS: Consecutive CD patients who underwent curative ileocolonic resection were randomized (1:1) to receive infliximab (standard induction and maintenance schedule) or azathioprine (2.5 mg/kg/day) for 1 year. Co-primary endpoints were endoscopic, histological and clinical recurrence after 12 months of therapy. RESULTS: Twenty-two consecutive CD patients (15 male; median age 32 years, IQR 22-38) were enrolled after curative ileocolonic resection. Eleven patients were treated with infliximab and 11 received azathioprine. Among patients treated with azathioprine, 4/10 (40%) had endoscopic recurrence compared to 1/11 (9%) in the infliximab group (p=0.14). Eight out of 10 (80%) among those who received azathioprine had severe histological activity, whereas 2/11 (18%) in the infliximab group presented histological recurrence (p=0.008). No significant clinical differences were found between the two groups. CONCLUSIONS: Infliximab was more effective than azathioprine in reducing histological, but not endoscopic and clinical recurrence after curative ileocolonic resection in "high risk" CD patients.

Lung adenocarcinoma presenting as a solitary gingival metastasis: a case report.

INTRODUCTION: Gingival metastases are very rare and generally occur in disseminated tumors. We report a case of solitary gingival metastasis of lung cancer. CASE PRESENTATION: We report the case of a 74-year-old asymptomatic Caucasian woman affected by a rapidly growing, painless gingival swelling. Histopathologic examination of the excisional biopsy showed metastasis of poorly differentiated thyroid transcription factor 1-positive adenocarcinoma. A total-body computed tomographic scan revealed a tumor of the right lung lower lobe with ipsilateral, mediastinal lymph node swelling. Moreover, bone scintigraphy revealed no bone metastases. No other metastases were found, so we planned a multi-modal therapeutic approach with a curative intent. However, the tumor proved to be intrinsically resistant and highly aggressive. CONCLUSION: The presentation of solitary gingival metastasis is exceptional. In view of its rapid clinical evolution, our case confirms that gingival metastasis is an important prognostic factor. This behavior raises the question whether the poor prognosis for patients with tumors with oral metastases depends on its diffuse spread or on its highly malignant nature.

Posterior spinal artery infarct due to patent foramen ovale: a case report.

STUDY DESIGN: Case report. OBJECTIVE: To report the first case of posterior spinal artery (PSA) infarct due to patent foramen ovale (PFO). SUMMARY OF BACKGROUND DATA: Infarct in the territories of PSA are very rare: till now 38 cases are reported in the literature. Moreover only 1 case of spinal cord infarction was attributed to paradoxical embolism through PFO, but in the anterior spinal artery territory. METHODS: A 60-year-old woman was hospitalized for sudden numbness of the right leg. Neurologic examination revealed right leg mild paresis and loss of proprioception and dysesthesia at T11. Spine-MRI showed T5-T7 posterolateral cord ischemia. Transesophageal echocardiography disclosed a PFO with severe right-left shunt confirmed by transcranial Doppler. RESULTS: During the hospitalization she was treated with oral-500 mg ticlopidine, because of a mild allergic reaction to acetylsalicylic acid. No steroids were administrated. Physiotherapy was performed daily. Motor and urinary symptoms disappeared in 20 days. At 1-month clinical follow-up only suspended dysesthesia on the right side was present. At 3 months follow-up spine-MRI showed no signal abnormalities within the spinal cord but the patient still complained of dysesthesia. The therapy was changed to oral 75 mg clopidogrel, cause of leucopoenia. At 1-year follow-up dysesthesia was still present, but less complaining and no recurrence and adverse effect due to clopidogrel therapy were reported. CONCLUSION: This report describe a case of acute nontraumatic myelopathy. At 4 days after onset, PSA infarct was diagnosed on the basis of neurologic findings and MR images. After extensive diagnostic work-up, we were able to identify only PFO, so it was the first case of PSA due to probable paradoxical embolism. The patient was treated with antiplatelet therapy with good recovery and no recurrence at 1-year follow-up.