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Primary leptomeningeal medulloblastoma (PL-MB) in adults is a rare disease with a severe prognosis. A 35-year-old woman presented with headaches, diplopia, and gait ataxia, with triventricular hydrocephalus and descent of the cerebellar tonsils beyond the foramen magnum. Endoscopic third ventriculostomy was performed. Six months later, headaches recurred. Dilatation of the supratentorial ventricular system and massive cerebellar swelling without contrast-enhancing nodularities were reported. Occipitocervical decompression with duraplasty was performed. A bioptic diagnosis of PL-MB was made. Craniospinal irradiation and chemotherapy were administered. After 18 months, no recurrence was observed.Few cases of PL-MB have been reported: patients die before treatment or within a few days after surgery. Our long-term survival could be ascribable to a slow clinical presentation and an early diagnosis that allowed surgical treatment and the administration of a combined chemoradiotherapy protocol. Cerebellar swelling, even without associated enhancing lesions, with or without hydrocephalus, should be a neuroradiological alarm sign, and PL-MB should be considered.

The diagnosis and classification of primary Sjögren's syndrome (pSS) relies on labial biopsy, whereas the role of open parotid biopsy is mainly reserved to evaluate the lymphoproliferative complications. Recently ultrasound-guided core needle biopsy (US-guided CNB) appeared as a novel and safe technique useful in lymphoma assessment, however, its potential role in the diagnosis of pSS has never been assessed.The main aim of this study was to evaluate the diagnostic value of US-guided CNB of the parotid glands in patients affected by pSS.Patients affected by pSS who underwent US-guided CNB for a suspected glandular lymphoma were included. Adequacy of the samples and histopathological features related to pSS were analysed.US-guided CNB was performed on 29 parotid glands. The biopsied samples were adequate for diagnosis in 28/29 (96.5%) cases. Fifteen patients showed pathologic features of parotid lymphoma. Among the remaining patients, 9/13 presented focus score≥1; LELs were present in 8/13 patients, and GCs in 11/13. In 8 cases the histological features were coherent with MESA/LESA. Acinar atrophy, fibrosis and duct dilatation were also evaluated.This preliminary study suggests the possible usefulness of US-guided CNB for the diagnosis of pSS by enabling the collection of adequate salivary gland tissue to assess the FS, GCs, LELs, and other histopathologic features also useful in the management of pSS patients.

Thyroglossal duct (TGD) remnants in the form of cysts or fistulas usually present as midline neck masses and they are removed along with the central body of the hyoid bone (Sistrunk’s procedure). For other pathologies associated with the TGD tract, the latter operation might be not necessary. In the present report, a case of a TGD lipoma is presented and a systematic review of the pertinent literature was performed. We present the case of a 57-year-old woman with a pathologically confirmed TGD lipoma who underwent transcervical excision without resecting the hyoid bone. Recurrence was not observed after six months of follow-up. The literature search revealed only one other case of TGD lipoma and controversies are addressed. TGD lipoma is an exceedingly rare entity whose management might avoid hyoid bone excision.

Objective Persistent (≥2 months) major salivary gland enlargement in primary SS (pSS) patients is a well-known sign of possible involvement by B cell lymphoma. The study aimed to evaluate the diagnostic accuracy and safety of US-guided core needle biopsy (CNB) of major salivary glands compared with open surgical biopsy. Methods Prospective pSS patients (cases) with clinically persistent salivary gland enlargement underwent US-guided CNB and were compared with retrospective pSS patients (controls) submitted to open surgical biopsy. The features analysed were pre-biopsy clinical and laboratory findings, adequacy of the material for histology and diagnostic-rendered and biopsy-related complications (reported by the patient with a questionnaire and clinically verified). Results Thirteen cases underwent US-guided CNB: in nine, biopsy was performed on the parotid gland and in four it was performed on the submandibular gland. Sufficient material was obtained for pathological diagnosis in all samples. The final diagnoses were 5 (38.5%) B cell lymphoma, 1 (7.7%) lymphoepithelial sialadenitis, 4 (30.7%) other sialadenitis (granulomatous consistent with sarcoidosis, IgG4-related disease, chronic sclerosing, diffuse chronic) and 3/13 (23.1%) miscellaneous lesions. Thirteen controls underwent open surgical biopsy of the parotid. In one, inadequate material was obtained, while in 12 (92.3%) the pathologic diagnoses were 4 (33.3%) B cell lymphoma, 2 (16.7%) lymphoepithelial sialadenitis, 4 (33.3%) uncertain lymphoproliferative lesions and 2 (16.7%) miscellaneous lesions. Six cases (46.1%) reported six transient complications and 12/13 (92.3%) controls had 2 persistent and 14 transient complications. Conclusion US-guided CNB represents a novel, clinically relevant and safe approach for the management of pSS patients with parotid or submandibular persistent enlargement.

Idelalisib, a selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, is a newly approved second-line drug for patients with chronic lymphocytic leukemia. Recent clinical trials have suggested a possible association between idelalisib treatment and development of progressive multifocal leukoencephalopathy (PML) due to John Cunningham virus (JCV) reactivation. Nevertheless, clinical course and radiological and pathological features of idelalisib-induced PML still need to be clarified. We provide here the first clinicopathological description of idelalisib-associated PML in a patient who developed epilepsia partialis continua (EPC) as the first manifestation of the disease. Since EPC could present without electroencephalogram alterations, it is crucial to recognize the clinical features of this epileptic condition. EPC is characterized by the presence of repetitive, irregular, clonic jerking, often associated with hemiparesis and involvement of distal rather than proximal muscle groups. Moreover, we highlight the importance of brain biopsy in selected cases when there is a high clinical suspicion of PML, despite negative JCV testing in the cerebrospinal fluid. The pathological finding of prominent inflammatory infiltrate observed here was consistent with a diagnosis of immune reconstitution inflammatory syndrome (IRIS). IRIS is often associated with PML as a paradoxical worsening of clinical symptoms due to an overreacting immune response, in the context of previous immunosuppression. The unprecedented pathologic observation of IRIS in idelalisib-associated PML provides further insights into the pathogenesis of this rare neurological side effect.

Objective Persistent (≥2 months) major salivary gland (SG) enlargement in primary Sjögren's syndrome (pSS) patients is a well-known sign of possible involvement by B-cell lymphoma. The study aimed to evaluate the diagnostic accuracy and safety of ultrasound-guided core needle biopsy (US-guided CNB) of major SGs in comparison to open surgical biopsy. Methods Prospective pSS patients (cases) with clinically persistent SG enlargement underwent US-guided CNB, and were compared to retrospective pSS patients (controls) submitted to open surgical biopsy. The features analyzed were pre-biopsy clinical and laboratory findings, biopsy-related complications (reported by the patient with a questionnaire and clinically verified), adequacy of the material for histology and diagnosis rendered. Results Thirteen cases underwent US-guided CNB: in 9/13 biopsy was performed on the parotid and in 4/13 on the submandibular gland. Sufficient material was obtained for pathological diagnosis in all samples. The final diagnoses were: 5/13 (38.5%) B-cell lymphoma, 1/13 (7.7%) lympho-epithelial sialadenitis, 4/13 (30.7%) other sialadenitis (granulomatous consistent with sarcoidosis, IgG4-related disease, chronic sclerosing, diffuse chronic) and 3/13 (23.1%) miscellaneous lesions. Thirteen controls underwent open surgical biopsy of the parotid, in one inadequate material was obtained, in 12 (92.3%) the pathologic diagnoses were: 4/12 (33.3%) B-cell lymphoma, 2/12 (16.7%) lympho-epithelial sialadenitis, 4/12 (33.3%) uncertain lymphoproliferative lesions, 2/12 (16.7%) miscellaneous lesions. 6/13 (46.1%) cases reported 6 transient complications, and 12/13 (92.3%) controls 2 persistent and 14 transient complications. Conclusion US-guided CNB represents a novel, clinically relevant and safe approach to the management of pSS patients with parotid or submandibular persistent enlargement.

BackgroundEnlargement of the major salivary glands (SGs) is a major risk factor for B-cell lymphoma among patients with primary Sjögren’s syndrome (pSS). Ultrasound-guided core needle biopsy (US-guided CNB) could be a novel technique to manage SG enlargement among patients with pSS.ObjectiveAccordingly, this study’s main aim was to evaluate the safety, patient tolerance and diagnostic accuracy of US-guided CNB procedure for patients with pSS with major SG enlargement.MethodsPatients with clinical diagnosis of pSS and a clinical indication for SG biopsy consecutively underwent US-guided CNB between September 2019 and June 2021. These patients were evaluated clinically 1, 2 and 12 weeks after US-guided CNB. Patients were asked to complete a questionnaire about postprocedural complications as well as periprocedural pain, using the Visual Analogue Scale. Complications were categorised as transient (persistent (≥12 weeks).ResultsUS-guided CNB was performed on 30 major salivary glands (22 parotid glands and 8 submandibular glands). The procedure was well tolerated. Transient complications—such as haematoma, swelling—were observed among 43% of patients, and mean periprocedural pain was low. However, no persistent complications were reported during the study’s follow-up period.ConclusionUS-guided CNB represents a novel approach for the management of patients with pSS with SG enlargement. The procedure showed remarkable patient safety and tolerance, allowing adequate glandular sampling and a definite diagnosis for almost all participating patients without long-term complications.

Refractory status epilepticus (RSE) is an increasingly recognized manifestation of autoimmune encephalitis, which can occur either as a paraneoplastic or non-paraneoplastic disorder. The effect of tumor removal in paraneoplastic status epilepticus has never been explored systematically, although early tumor treatment is usually recommended. In this study, we report clinical, pathological and EEG findings of a patient who developed RSE as one of multiple paraneoplastic manifestations of thymoma and the effect of thymectomy on seizure outcome. To our knowledge, this is the first report of successful treatment of RSE with tumor removal in paraneoplastic encephalitis.

Background:Persistent enlargement of major salivary glands (SGs) is one of the main risk factors for B-cell lymphoma in primary Sjögren’s syndrome (pSS). The Ultrasound-guided Core Needle Biopsy (US-guided CNB) could be a novel technique for the management of SGs enlargement in pSS (1).Objectives:To evaluate the procedure safety and the patient tolerance of US-guided CNB in pSS patients with major SGs enlargement.Methods:Consecutive patients, with either definite or clinically suspected pSS, and with clinical indication for SGs biopsy due to persistent glandular enlargement were screened for US-guided CNB from September 2019 to December 2020. All patients were evaluated clinically between 1 and 2 weeks and 12 weeks following US-guided CNB. All patients were asked to complete a questionnaire to report post-procedural complications (Figure 1, English version) and intra- and post-procedural pain Visual Analogue Scale (VAS). The complications were classified as transient (Results:US-guided CNB was performed in 21 glands (12 parotid and 9 submandibular glands) in 20 pSS patients. 16/20 (80%) patients fulfilled the ACR-EULAR classification criteria for pSS (2). The mean age at the time of biopsy was 62.1 (±11.7) years. US-guided CNB was well tolerated, no long-term complications were reported in the follow-up period (mean 9.5 ±5.7 months). Only transient complications were noticed in 11 patients (55%). In particular, two cases of local swelling at the biopsy site lasting no more than 6 days, one case of local bleeding and subsequently hematoma of the submandibular area, one case of transient facial paresis (lasting less than one hour), seven cases of post-procedural mild local pain, that resolved within 10 days without the need of analgesics (Table 1). The procedure was well tolerated, with a very low reported intra-operative pain (mean VAS 1.74 ±2.49) and a mean post-operative pain VAS of 1.39 (±2.33). The biopsy sampling was diagnostic in 19/20 patients (95%).Conclusion:US-guided CNB represents a novel approach for the management of pSS patients with SGs enlargement. This procedure shows a remarkable patient safety and tolerance, allowing an adequate glandular sampling and definite diagnosis in almost all the studied patients.References:[1]Zabotti A, Zandonella Callegher S, Lorenzon M, Pegolo E, Scott CA, Tel A, et al. Ultrasound-guided core needle biopsy compared with open biopsy: a new diagnostic approach to salivary gland enlargement in Sjögren’s syndrome? Rheumatology (Oxford) 2020.[2]Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, Rasmussen A, Scofield H, Vitali C, Bowman SJ, Mariette X; International Sjögren’s Syndrome Criteria Working Group. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren’s Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts. Arthritis Rheumatol. 2017 Jan;69(1):35-45. doi: 10.1002/art.39859. Epub 2016 Oct 26. PMID: 27785888; PMCID: PMC5650478.Table 1.Description of complicationsComplications of US-guided CNBPatients presenting complications, n/N (%)11/20 (55%)Description of transient complicationsSwelling at biopsy site, n2Bleeding, n1Hematoma, n1Local Pain, n7Local infection, n0Sialocele or fistula, n0Anaesthesia/paraesthesia, n0Transient facial palsy (< 1 hour), n1No persistent complications reportedAll the above specified complications were transient (< 12 weeks). No persistent complications were reported in the follow up.Figure 1.Post-biopsy complication QuestionnaireDisclosure of Interests:Alen Zabotti Speakers bureau: UCB, Novartis, Janssen, Paid instructor for: Amgen, Consultant of: Janssen, Ivan Giovannini: None declared, Sara Zandonella Callegher: None declared, Valeria Manfrè: None declared, Michele Lorenzon Consultant of: not relevant for this study, Enrico Pegolo: None declared, Cathryn Ann Scott: None declared, Alessandro Tel: None declared, Massimo Robiony Consultant of: not relevant for this study, Grant/research support from: not relevant for this study, Chiara Zuiani Consultant of: not relevant for this study, Grant/research support from: not relevant for this study, Salvatore De Vita Consultant of: GSK, Roche, Grant/research support from: not relevant for this study

Meningioma is one of the most common intracranial tumors. It is benign and slow growing in the majority of cases. Given the increase in life expectancy and the number of radiological tests performed, the incidence in the elderly population (&ge, 65 years) is continuously increasing. The surgical outcomes and prognostic factors in this age group are unclear. A retrospective analysis of all the patients treated for intracranial meningiomas in two different Italian institutions was performed. The clinical, radiological, surgical and follow-up data were retrospectively reviewed. Statistical analyses were performed to identify relationships between factors and outcomes. We also carried out an economic analysis. We analyzed 321 patients with intracranial meningioma. The mean age was 72.6 years (range, 65&ndash, 90), with a female predominance (F/M, 1.41). Pre-operative deficits, cognitive impairment and seizures (p &lt, 0.001) were associated with a worse post-operative Karnofsky performance scale (KPS) score (&lt, 80). A high pre-operative KPS score was associated with a good clinical and neurological outcome (p &lt, 0.001). Being aged between 65 and 74 years, low surgical timing and Simpson removal grades of I and II were associated with a good outcome (p &lt, 0.001). The length of hospitalization was significantly related to the outcome (p &lt, 0.001). The complication rate was 14.3%. At 6-month follow-up, the mortality rate was 2.5%. The average cost was higher in patients with a pre-operative KPS score lower than 80. The outcome of intracranial-meningioma resection in elderly individuals is favorable when the pre-operative KPS score is &gt, 80. Treatment should be patient-specific, and additional factors should be considered. Patients with poor pre-operative clinical conditions might benefit from a combined strategy with partial resection and radiosurgery in order to reduce surgical timing and the complication rate.

Despite recent discoveries in genetics and molecular fields, glioblastoma (GBM) prognosis still remains unfavorable with less than 10% of patients alive 5 years after diagnosis. Numerous studies have focused on the research of biological biomarkers to stratify GBM patients. We addressed this issue in our study by using clinical/molecular and image data, which is generally available to Neurosurgical Departments in order to create a prognostic score that can be useful to stratify GBM patients undergoing surgical resection. By using the random forest approach [CART analysis (classification and regression tree)] on Survival time data of 465 cases, we developed a new prediction score resulting in 10 groups based on extent of resection (EOR), age, tumor volumetric features, intraoperative protocols and tumor molecular classes. The resulting tree was trimmed according to similarities in the relative hazard ratios amongst groups, giving rise to a 5-group classification tree. These 5 groups were different in terms of overall survival (OS) (p &lt, 0.000). The score performance in predicting death was defined by a Harrell&rsquo, s c-index of 0.79 (95% confidence interval [0.76&ndash, 0.81]). The proposed score could be useful in a clinical setting to refine the prognosis of GBM patients after surgery and prior to postoperative treatment.

Background Incidentally discovered diffuse low-grade gliomas (iLGG) are poorly documented in the literature. They are diagnosed by chance during radiological examinations. Objective To review a cohort of patients with iLGG surgically treated in our institution, analyzing clinical, molecular, and surgical aspects. Methods Clinical, radiological, and treatment data of iLGG were retrieved and compared with those of symptomatic diffuse LGGs (sLGG). Histological and molecular review was carried out as well. The extent of resection was evaluated on preoperative and postoperative T2-weighted magnetic resonance imaging. Results Thirty-four iLGG cases were identified within a monoinstitutional cohort of 332 patients operated for low-grade gliomas from 2000 to 2017. Clinically, patients with iLGG had higher preoperative karnofsky performance scale (KPS) (P = .003), smaller tumor volume (P = .0001), lower frequency of eloquent areas involvement (P = .0001), and higher rate of complete resection (P = .0001) compared to those with sLGG. No differences in the molecular profile and O6-methylguanine-DNA-methyltransferase promoter methylation were detected between iLGG and sLGG. Importantly, patients with iLGG had longer overall survival than those with sLGG (P = .0001), even when a complete surgical resection was achieved (P = .001). Conclusion Although the therapeutic strategy of iLGG is still a matter of debate, our data support the safety and the effectiveness of early surgical resection. The favorable prognosis of iLGG may be due to the higher practicability of extensive resection, noneloquent tumor location, and smaller tumor volume.

Intraparenchymal meningiomas are very rare: only 26 cases have been diagnosed in patients younger than 20 years since 1954. They can lead to preoperative differential diagnosis mistakes due to their atypical neuroimaging appearance. A multimodal approach is thus necessary to plan a surgical procedure aiming to receive the best extent of resection while preserving the patient’s functional integrity. The authors report the case of a 7-year-old boy with a history of blurred vision, left eye deviation, and weakness on the left side of his body. Magnetic resonance imaging (MRI) revealed an intra-axial, cortical, right parietal lesion without dural attachment. MR spectroscopy and perfusion study were obtained. Since the patient was 100% left-handed, functional MRI, diffusion tensor imaging, and neuropsychological evaluation were performed before the surgical procedure. Histopathological analysis revealed the mass to be an atypical meningioma (WHO grade II). Postoperative MRI indicated complete macroscopic lesion removal. The postsurgical neuropsychological profile was not different from the profile before surgery. The boy was discharged 3 days after the surgical operation without any neurological deficits.

Mouse models can provide useful information to understand molecular mechanisms of human tumorigenesis. In this study, the conditional thyroid mutagenesis of Pten and Ras genes in the mouse, which induces very aggressive follicular carcinomas (FTCs), has been used to identify genes differentially expressed among human normal thyroid tissue (NT), follicular adenoma (FA), and FTC. Global gene expression of mouse FTC was compared with that of mouse normal thyroids: 911 genes were found deregulated ± 2-fold in FTC samples. Then the expression of 45 deregulated genes in mouse tumors was investigated by quantitative RT-PCR in a first cohort of human NT, FA, and FTC (discovery group). Five genes were found significantly down-regulated in FA and FTC compared with NT. However, 17 genes were found differentially expressed between FA and FTC: 5 and 12 genes were overexpressed and underexpressed in FTC vs FA, respectively. Finally, 7 gene products, selected from results obtained in the discovery group, were investigated in a second cohort of human tumors (validation group) by immunohistochemistry. Four proteins showed significant differences between FA and FTC (peroxisomal proliferator-activated receptor-γ, serum deprivation response protein, osteoglycin, and dipeptidase 1). Altogether our data indicate that the establishment of an enriched panel of molecular biomarkers using data coming from mouse thyroid tumors and validated in human specimens may help to set up a more valid platform to further improve diagnosis and prognosis of thyroid malignancies.

The proliferative activity of breast cancer tissue can be estimated using the Ki67 biomarker. The percentage of positivity of such biomarker is correlated with proliferation and consequently with the prognosis of a breast tumor. Ki67 marked tissue samples are analyzed by an experienced pathologist who identifies the most active areas of tumor cell proliferation called hotspots, and estimates the positivity of each case. A method for the Automated Ki67 Hotspot Detection (AKHoD) is presented in this work. The main objective of the AKHoD method is to automatically and efficiently provide the pathologist with suggestions about Ki67 hotspot areas as a decision support. The input of AKHoD is a digital slide that is divided in tiles. For each tile, AKHoD provides a rough estimate of positivity and cellularity, summarized in very low resolution positivity and cellularity images. In a second step, an adaptive thresholding is applied to such positivity image to identify the most positive connected and convex areas, within cellularity limits set by current guidelines (that is, 500-2000). The method has been preliminarily validated on 50 digital slides for which three expert pathologists provided gold standard hotspots. 82% of the gold standard hotspots have been successfully recognized by the system, spending an average of 54s per slide. While further validation is needed taking into account also patients follow-up, this first experimentation suggests that the proposed method could be adequate for supporting the pathologist in hotspot detection.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a well-accepted procedure for the diagnosis and biological characterization of breast carcinoma. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status have a strong prognostic and predictive value in invasive breast carcinoma (IBC). ThinPrep (TP) cytology, which uses an alcohol-based fixative, is increasingly being used for immunocytochemistry. In this study, the authors compared the immunocytochemical evaluation of hormone receptors (HR) and HER2 on TP-processed FNAC with the immunohistochemical analysis performed on the corresponding formalin-fixed paraffin-embedded (FFPE) breast tumor specimens, which are considered the gold standard. METHODS: FNACs were performed on 116 primary IBCs at the time of diagnosis and subjected to immunocytochemical evaluation of HR and HER2 using the TP method. The same markers were immunohistochemical evaluated on the corresponding FFPE tissue specimens. HER2 fluorescent in situ hybridization analysis was performed only on the equivocal immunohistochemical results. RESULTS: The HR results of the TP cytology specimens showed a very good agreement with those of the corresponding FFPE tissue samples (Cohen kappa test = 0.92; concordance rate = 98%) for estrogen receptor, and a good agreement (kappa = 0.76; concordance rate = 90.9%) for progesterone receptor. A perfect agreement (kappa = 1) was observed between TP and FFPE tissue samples in evaluating HER2 status. CONCLUSIONS: Alcohol-based fixation seems not to affect the immunocytochemical evaluation of HR and HER2. Considering the high levels of agreement between the evaluation of HR and HER2, on both cytology specimens and on the corresponding FFPE tissue samples, the authors concluded that the TP technique can be routinely used for the biological characterization of IBC. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society.

Background: Malignant change in the scars of discoid lupus erythematosus (DLE) is a well-known event. In most cases, tumors are of epithelial origin, particularly squamous cell carcinomas and, less frequently, basal cell carcinomas and keratoacanthomas. The onset of soft tissue sarcomas in a DLE scar is a very rare event, however, because only one case of malignant fibrous histiocytoma has been described in the literature. Objective: We describe the first documented report of atypical fibroxanthoma (AFX) arising in an old scar of DLE. Results: Although we cannot exclude an accidental association between AFX and DLE, our case emphasizes that patients with DLE may develop AFX in the context of an old scar. Conclusion: Our finding further underlines the importance of strict and long-term surveillance of people with DLE to identify and remove eventual tumors at an early stage.

The one-step nucleic acid amplification (OSNA) method is an increasingly used procedure for intraoperative analysis of sentinel lymph node (SLN) status in breast cancer patients. It measures cytokeratin19 (CK19) mRNA copy numbers in homogenized samples of SLN; CK19 has been chosen for identifying node metastasis because most breast cancers express this molecule. However, to avoid false-negative OSNA results, testing the preoperative needle core biopsy (NCB) of breast carcinomas for CK19 by immunohistochemistry (IHC) has been recommended. This procedure relies on the assumption that protein expression is strictly related to mRNA expression. We developed this study to evaluate if IHC gives similar result to the molecular assay. In a series of breast cancer patients with axillary metastasis, corresponding surgically resected tumor and metastatic lymph node specimens have been tested for CK19 protein by IHC and for CK19 mRNA by real-time PCR; furthermore, CK19 immunostaining has been performed in NCBs when available. Statistical analysis revealed that (1) the immunohistochemical evaluation of CK19 in NCB is a reliable test, reflecting protein expression in the whole tumor and in the metastatic lymph node; (2) there is no correlation between CK19 protein expression and CK19 RNA level neither within the primary breast cancer nor within the metastatic node; moreover, no correlation as well has been found between protein expression in NCB and mRNA level in metastatic lymph nodes. Thus, our results suggest that there is no evidence-based reason to stain every NCB for CK19 before performing OSNA in patients with breast cancer.

Background:Periostin is a secreted adhesion protein, normally expressed in mesenchime-derived cells. Aberrant expression of the periostin gene in epithelial tumours seems to play a role in angiogenesis and metastases.Aims:To investigate periostin expression in a consecutive series of breast carcinomas and correlate it with established biological and prognostic factors.Methods:A consecutive series of 206 breast carcinomas was investigated by immunohistochemistry with a specific antiperiostin antibody. Immunohistochemical expression of oestrogen and progesterone receptors, Ki-67 (MIB-1), HER-2/neu, VEGF-A, VEGFR-1 and VEGFR-2 was analysed. Periostin expression was also investigated in MCF-7 and MDA-468 cell lines by immunohistochemistry, western blot and quantitative RT-PCR. Localisation of periostin was investigated in MCF-7 cells by the green fluorescent protein (GFP) approach.Results:Periostin was highly expressed in carcinoma cells, but not in normal breast tissues. The pattern of expression was mainly cytoplasmic. However, in 12% of cases a nuclear reactivity was observed. Nuclear periostin significantly correlated with tumour size, and with expression of oestrogen receptor, progesterone receptor, VEGF-A, VEGFR-1 and VEGFR-2. A nuclear localisation of periostin was also observed in MCF-7 and MDA-468 cell lines. In MCF-7 cells the nuclear localisation of periostin was also shown by transfection of a vector expressing a GFP-periostin chimeric protein.Conclusions:Results indicate that the aberrant gene expression of periostin in breast cancer cells is associated with an abnormal nuclear localisation of the protein. The nuclear localisation of periostin in breast cancer may induce significant biological effects.

Dear Editor: Kaposi's sarcoma (KS) is a vascular neoplasm associated with human herpesvirus-8 (HHV-8) infection that is primarily categorized into 4 different types: endemic (African), iatrogenic (associated with immuno-suppressive therapy), AIDS-associated (rapidly progressive form in HIV-infected patients), and classic. The classic type is frequently observed in elderly male patients of Mediterranean origin and Ashkenazi Jews, presenting as an indolent disease with bluish-red (hematoma-like) cutaneous macules that tend to progress only slowly both horizontally and vertically and develop into firm angiomatous plaques and nodules. The most frequently affected sites are the lower limbs and feet; extracutaneous involvement is uncommon1. The lesions of KS are rarely localized exclusively in unusual mucocutaneous areas, thus leading to frequent diagnostic errors2. To our knowledge, there are no reports of KS confined to female external genitalia not associated with HIV infection. Here, we report the first case of classic KS restricted to the vulva in an HIV-negative patient. An 85-year-old Caucasian woman presented to our clinic for evaluation of asymptomatic vulvar lesions that appeared over the last year and progressed. Physical examination showed several brownish-violaceous angiomatous nodules and slightly raised plaques on both labia majora and minora (Fig. 1). No other significant mucocutaneous lesions were observed, and there was no evidence of inguinal lymphadenopathy. Furthermore, no other signs or symptoms suggestive of HIV infection or immunosuppression were present. The patient denied other health problems and drug use. Skin biopsy from a lesion on the right labia majora was performed for histological examination. The clinical diagnosis of KS was confirmed on the basis of revealing dermal proliferation of spindle cells, slit-like vascular spaces, and extravasated red blood cells (Fig. 2A). Immunohistochemical investigation also demonstrated positivity for D2-40, CD34, and CD31 (Fig. 2B). Moreover, polymerase chain reaction assay revealed HHV-8 DNA sequences in the lesional skin tissue; positive and negative controls were also tested and yielded the expected results. HHV-8 in the lesional tissue was also detected by in situ hybridization. Serological test for HIV was negative; chest x-ray as well as abdominal and pelvic computed tomography showed no visceral lesions. The patient refused all proposed treatments for the vulvar lesions, including intralesional therapy with bleomycin, cryotherapy, and laser photocoagulation. The 6-month follow-up did not show any disease progression. Fig. 1 (A) Several brownish-violaceous angiomatous nodules and slightly raised plaques on both the labia majora and minora, (B) magnified image of the lesions on the right labia majora. Fig. 2 (A) Dermal proliferation of spindle cells, slit-like vascular spaces, and extravasated red blood cells (H&E, ×200), (B) immunohistochemical positivity for vascular marker CD31 (×100). Overall, KS restricted to the external genitalia is a very rare finding that is more frequent in men, particularly on the penis; approximately 50 cases have been reported in the English-language literature3. Meanwhile, it is very uncommon in women, with only 9 reported cases, all of which involved the vulva2,4. Most cases of KS of the external genitalia are related to HIV infection. In fact, to our knowledge, only 15 well-documented cases of primary penile KS in HIV-negative patients have been reported5, while there are no instances of KS confined to female external genitalia not associated with HIV infection. All previous cases of vulvar KS were monolesional forms, clinically presenting as a non-specific mass, nodule, papilloma, or abscess; none were initially suspected to be KS2. The present case of classic KS restricted to the vulva is of particular interest because of its more typical clinical appearance than previous cases, with multiple lesions showing an angiomatous aspect as well as onset in an HIV-negative patient; the latter finding emphasizes the need to include KS in the differential diagnosis of vulvar disorders in immunocompetent women, especially elderly women.

21090 Background: Mesenchyme-specific genes are highly expressed by various types of human cancers. Recent lines of evidence suggest that periostin, a myoepithelial/basal gene, may play a role in the biology of breast cancer. Periostin is involved in metastatic process by taking part in mechanisms of adhesion and migration of epithelial cells. Furthermore, periostin seems to have a role in tumor angiogenesis through the up-regulation of vascular endothelial growth factor receptors in endothelial cells. We aimed at investigating the immunohistochemical expression of periostin in breast cancer and its correlation with established biological and prognostic factors. Methods: We performed immunohistochemical analysis of periostin in a consecutive series of 206 tumor samples from 200 patients with early breast carcinoma. To this aim, we used a specific antiperiostin antibody (Biovendor Laboratory Medicine, Inc., Palackeho 56, 612 00 Brno, Czech Republic). The intensity of immunoreactivity was scored as 0, 1, 2 or 3 denoting negative, weak, moderate and strong staining, respectively. Therefore, for statistical analysis, the periostin expression level for each case was putatively defined as positive if the predominant intensity was =1. We also analyzed immunohistochemical expression of Ki-67 (MIB-1), HER-2/neu, VEGF, VEGFR-1 and VEGFR- 2. Results: Periostin was found to be highly expressed by carcinoma cells, whereas it was absent in normal breast tissues. The pattern of expression was mainly cytoplasmic, although in some cases (11%) a nuclear reactivity was observed. A cytoplasmic expression was found in 108 out of 189 (57%) evaluable cases. Interestingly, a significant correlation was found between periostin expression and VEGF and VEGFR-1 (Spearman's rank test rho =0.37, p No significant financial relationships to disclose.