Pathological Series Research Articles

Diagnosis of mixed dementia by double dichotomy

AbstractBackgroundProper classification of patients with dementia is critical in clinical trials. Dual Alzheimer’s disease (AD) and vascular pathology (mixed dementia‐MX) is the most common form of dementia estimated to be as high as 70% in pathological series. However, separation clinically is difficult, which has led to use of biomarkers. A biological definition of AD based on biomarkers has been proposed for research studies with identification of amyloid and tau in CSF or PET. Including in the ATN formula, biomarkers for vascular disease (V), obtained from MRI, separates MX subjects, improving diagnosis of AD and vascular cognitive impairment (VCI).MethodsWe used vascular disease biomarkers from MRI and AD biomarkers from CSF with a double dichotomy statistical approach to more precisely define four major groups of patients in the UNM and Alzheimers's Disease Neuroimaging Initiative (ADNI) cohorts. We compared the UNM dataset (N=80) with subjects from ADNI (N=538). Diffusion tensor imaging (DTI) biomarkers (mean free water and PSMD) were combined with CSF amyloid (A) and tau (T) to identify MX patients. We formed a composite vascular disease score (cVDS) with DTI, and a composite AD score (cADS) with CSF amyloid and phosphoTau181.ResultsPlotting cVDS on the x‐axis and cADS on the y‐axis placed subjects in one of four biologically defined quadrants: bAD (biological AD) in the upper left, bSIVD (biological subcortical ischemic vascular disease) in the lower right, bMX (biological mixed dementia) in the upper right, and bCN (biological controls) in the lower left quadrant (Figure). We identified MX, using a double dichotomy statistical method. The UNM cohort had 25% MX, while in ADNI there were 11.5% (Table). The ADNI group had a higher percentage of bCN (43%) and bAD (35%) than the UNM cohort; this was because UNM was one of 7 sites in the MarkVCID consortium with enriched VCI subjects and ADNI excluded vascular disease subjects.ConclusionsOur results show that adding a vascular factor (V) to the ATN formula creates a MX group, improving classification of patients by creating a more homogeneous AD group, which permits AD clinical trials with fewer subjects

Primary cutaneous peripheral T-cell lymphomas with a T-follicular helper phenotype: an integrative clinical, pathological and molecular case series study.

Primary cutaneous peripheral T-cell lymphomas with a T-follicular helper phenotype (pcTFH-PTCL) are poorly characterized, and often compared to, but not corresponding with, mycosis fungoides (MF), Sézary syndrome, primary cutaneous CD4+ lymphoproliferative disorder, and skin manifestations of angioimmunoblastic T-cell lymphomas (AITL). We describe the clinicopathological features of pcTFH-PTCL in this original series of 23 patients, and also characterize these cases molecularly. Clinical and histopathological data of the selected patients were reviewed. Patient biopsy samples were also analysed by targeted next-generation sequencing. All patients (15 men, eight women; median age 66 years) presented with skin lesions, without systemic disease. Most were stage T3b, with nodular (n = 16), papular (n = 6) or plaque (atypical for MF, n = 1) lesions. Three (13%) developed systemic disease and died of lymphoma. Nine (39%) patients received more than one line of chemotherapy. Histologically, the lymphomas were CD4+ T-cell proliferations, usually dense and located in the deep dermis (n = 14, 61%), with the expression of at least two TFH markers (CD10, CXCL13, PD1, ICOS, BCL6), including three markers in 16 cases (70%). They were associated with a variable proportion of B cells. Eight patients were diagnosed with an associated B-cell lymphoproliferative disorder (LPD) on biopsy, including Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (n = 3), EBV+ LPD (n = 1) and monotypic plasma cell LPD (n = 4). Targeted sequencing showed four patients to have a mutated TET2-RHOAG17V association (as frequently seen in AITL) and another a TET2/DNMT3A/PLCG1/SETD2 mutational profile. The latter patient, one with a TET2-RHOA association, and one with no detected mutations, developed systemic disease and died. Five other patients showed isolated mutations in TET2 (n = 1), PLCG1 (n = 2), SETD2 (n = 1) or STAT5B (n = 1). Patients with pcTFH-PTCL have pathological and genetic features that overlap with those of systemic lymphoma of TFH derivation. Clinically, most remained confined to the skin, with only three patients showing systemic spread and death. Whether pcTFH-PTCL should be integrated as a new subgroup of TFH lymphomas in future classifications is still a matter of debate. What is already known about this topic? There is a group of cutaneous lymphomas that express T-follicular helper (TFH) markers that do not appear to correspond to existing World Health Organization diagnostic entities. These include mycosis fungoides, Sézary syndrome, or primary cutaneous CD4+ small/medium-sized T-cell lymphoproliferative disorder or cutaneous extensions of systemic peripheral T-cell lymphomas (PTCL) with TFH phenotype. What does this study add? This is the first large original series of patients with a diagnosis of primary cutaneous PTCL with a TFH phenotype (pcTFH-PTCL) to be molecularly characterized. pcTFH-PTCL may be a standalone group of cutaneous lymphomas with clinicopathological and molecular characteristics that overlap with those of systemic TFH lymphomas, such as angioimmunoblastic T-cell lymphoma, and does not belong to known diagnostic groups of cutaneous lymphoma. This has an impact on the treatment and follow-up of patients; the clinical behaviour needs to be better clarified in further studies to tailor patient management.

Pityriasis lichenoides: a clinical and pathological case series of 49 patients with an emphasis on follow-up.

The classification of pityriasis lichenoides (PL) into pityriasis lichenoides et varioliformis acuta (PLEVA), PL chronica (PLC) and febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is based on both clinical and chronological features. In this retrospective monocentric study, we aimed to investigate the relevance of the classification in routine practice. We enrolled 49 patients (25 female, 24 male; median age 41 years). The lesions were papular in 76% of patients, necrotic in 12% and mixed in 12%. We found three histological patterns: 'classic' (65%), 'lymphomatoid' (13%) and 'mild' (22%). The 'lymphomatoid' pattern was associated with necrotic presentation and the 'mild' pattern with papular lesions (P = 0.01). Among the 27 patients with follow-up, 18% had relapses and 44% had chronic disease. One patient had mycosis fungoides. Neither clinical nor histological findings were correlated with disease progression, and are a reflection of the intensity of epidermal injury rather than of the disease course. The term 'pityriasis lichenoides' should be preferred to the classic PLEVA/PLC/FUMHD classification.

A clinical, pathological and immunohistochemical series of 9 cases of primary cutaneous apocrine carcinomas of the head and neck.

Primary cutaneous apocrine carcinoma is a rare malignant adnexal skin tumour that can recur locally, spread to regional lymph nodes and metastatize to visceral organs. Wide dissemination and death from disease are much less common. The axilla is the most common site of presentation. It is infrequently reported in the head and neck region. All cases diagnosed as primary cutaneous apocrine carcinoma of the head and neck were retrospectively collected from the archives of the Division of Pathological Anatomy, University of Florence from 1996 to 2016. There was no history or clinical evidence of breast cancer. Clinical data and follow-up were collected by the clinicians. Nine cases were found, with a mean age of 76years, ranging in size between 0.3 and 3.5cm. Clinically, they were frequently mistaken for basal cell carcinomas. Histopathologically, all the tumours showed decapitation secretion, a tubular, solid or mixed (tubulo-papillary and solid-tubular) growth pattern and were predominantly classified as grade 2 tumours. GCDFP-15 and hormone receptors were variably expressed. HER2 and podoplanin were negative in all cases. In one case, spreading to regional lymph nodes was observed. No cases were associated with death due to the disease. As immunohistochemical analysis lacks specificity in distinguishing primary cutaneous apocrine carcinoma from a cutaneous metastasis of breast carcinoma, detailed clinical history, breast examination, adequate treatment and follow-up are necessary to confirm a diagnosis of primary cutaneous apocrine carcinoma.

Abnormal development of the paired and median fins in the hyperthyroidism case series of the zebrafish (Danio rerio)

Hypo‐ and hyperthyroidism are severe medical conditions frequently found in humans living all over the globe. These diseases are caused by the dysfunction of the thyroid gland and lead to the abnormal embryonic development, various neurological problems, and brain damage. In order to better understand these two conditions in humans, we used zebrafish (Danio rerio) as a model to study the variability of effects of thyroid hormones. We compared normal development of zebrafish fins with pathological series of fishes extensively treated with triiodothyronine (T3) hormone.Analysis of the fish hyperthyroidism case series revealed certain symptoms similar to those present in human patients. Namely, we observed malformations of the appendicular skeleton and fusion of bones, likely occurred due to the late ossification, as well as significant underdevelopment of the appendicular musculature. Surprisingly, T3 hormone treatment induced excessive myogenesis in the dorsal and anal fin folds where muscles do not normally develop. In addition to various anatomical defects, hyperthyroidism resulted into accelerated growth of fishes in general and led to heterochrony. Interestingly, defects found in our pathological series seem to be similar to defects caused in zebrafishes by stress of the environmental change. These similarities between defects caused by completely different conditions support Pere Alberch's idea of ‘logic of monsters', according to which evolution is so constrained that even when it goes ‘wrong’ ‐ e.g. in cases of severe defects ‐ the resulting phenotypes mirror those seen in other abnormal conditions as well as those seen in the natural variations and/or normal phenotype of other taxa.These results have crucial implications for both Evo‐Devo research and evolutionary developmental medicine, or ‘Evo‐Devo‐Path’. Specifically, because hyper‐ and hypothyroidism are two disorders frequently found in humans, and because such conditions are deeply connected with heterochrony and thus with micro‐ and macroevolution.Support or Funding InformationThis work was supported by Russian Foundation for Basic Research, project nos. 14‐04‐00590 and 17‐04‐01617. The research was done using equipment of the Core Centrum of Institute of Developmental Biology RAS.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hypertrophic Cardiomyopathy-Past, Present and Future.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy with a prevalence of 1 in 500 in the general population. Since the first pathological case series at post mortem in 1957, we have come a long way in its understanding, diagnosis and management. Here, we will describe the history of our understanding of HCM including the initial disease findings, diagnostic methods and treatment options. We will review the current guidelines for the diagnosis and management of HCM, current gaps in the evidence base and discuss the new and promising developments in this field.

Hashimoto’s Thyroiditis And Cancer: A Review

Background: No consensus exists on the association between Hashimoto’s thyroiditis (HT) and cancer. To resolve this controversy, this review aimed to evaluate the relationship between the two conditions.
 Methods: Using Pub-Med database, we searched studies relevant to the topic focusing on the association between HT and Papillary Thyroid Cancer (PTC), as well as the association between HT and Primary Thyroid Lymphoma (PTL).
 Findings: Both HT and PTC are common worldwide, and the two conditions may be closely related. However, the relationship remains controversial. Some studies found that PTC coexisted with HT 2.8-fold more frequently, with variable prevalence ranging from 0.5 to 30%. In contrast to surgical and pathological series that suggested a positive correlation between the two diseases and even a cause-and-effect relationship, the other studies evaluating fine-needle aspirate specimens did not find a statistically significant correlation. On the other hand, the relationship between PTL and HT appears well established.
 Conclusion: The existing data provide inconsistent evidence favoring a causal relationship between HT and PTC. Prospective studies are needed to further elucidate the relationship. However patients with HT are at risk for PTL. Therefore careful observation and follow-up of HT patients is recommended.

Polygenic risk score analysis of pathologically confirmed Alzheimer disease.

Previous estimates of the utility of polygenic risk score analysis for the prediction of Alzheimer disease have given area under the curve (AUC) estimates of <80%. However, these have been based on the genetic analysis of clinical case-control series. Here, we apply the same analytic approaches to a pathological case-control series and show a predictive AUC of 84%. We suggest that this analysis has clinical utility and that there is limited room for further improvement using genetic data. Ann Neurol 2017;82:311-314.

Contrast-enhanced shunt series ("shuntography") compare favorably to other shunt imaging modalities in detecting shunt occlusion.

Obstruction is a common cause of ventriculo-peritoneal shunt failure. Head computed tomography and plain x-ray examinations of shunt tubing ("shunt series") are routinely used in patients readmitted for reemerging symptoms but are of limited value. The validity of shunt series can be improved by applying contrast agent into the system (contrast-enhanced shunt series, a.k.a. a "shuntogram" or "shuntography"). We hypothesized that contrast-enhanced shunt series have a high predictive value for shunt revision surgeries. We retrospectively re-evaluated 107 contrast-enhanced shunt series and reviewed the patient histories. We defined outcome parameters for calculating the utility of a pathological contrast-enhanced shunt series in predicting revision surgery. Of 107 contrast-enhanced shunt series, 41 examinations were positive for obstruction, mainly of the ventricular (36.5%) and the peritoneal catheter (48.8%). Within 30days, 35 successful revision surgeries and 3 revision surgeries without resolution of symptoms were performed. In two cases the shunt tubing was found to be patent. Sixty-six negative examinations resulted in two revision surgeries, in addition to ten surgeries not attempting to restore patency. After 30days, the specificity of contrast-enhanced shunt series for shunt failure identification was calculated at 92.8%, the sensitivity at 94.7%, the positive predictive value at 87.8%, and the negative predictive value at 97.0%. The contrast-enhanced shunt series method is a highly specific examination with a negative predictive value exceeding that of head computed tomography and plain shunt series. Compared to radionuclide marker studies, contrast-enhanced shunt series demonstrate better spatiotemporal resolution, enabling focused local surgical repair.

LRRK2 variation and dementia with Lewy bodies

IntroductionThe leucine-rich repeat kinase 2 (LRRK2) gene contains several variants that cause Parkinson's disease (PD) and others that modify PD risk. However, little is known about the role of LRRK2 in dementia with Lewy bodies (DLB). Aims of this study were to screen DLB patients for pathogenic LRRK2 variants and to evaluate associations between common LRRK2 variants and risk of DLB. Methods417 clinical DLB patients and 1790 controls were included in the primary analysis. Additionally, 355 Lewy body disease patients assessed as having a high likelihood of clinical DLB based on neuropathological findings were included in secondary analysis. Seven pathogenic LRRK2 variants were assessed in patients, while 17 common LRRK2 exonic variants and 1 GWAS-nominated common LRRK2 PD-risk variant were evaluated for association with DLB. ResultsWe identified carriers of 2 different pathogenic LRRK2 variants. One clinical DLB patient was a p.G2019S carrier, while in the pathological high likelihood DLB series there was one carrier of the p.R1441C mutation. However, examination of clinical records revealed the p.R1441C carrier to have PD with dementia. Evaluation of common variants did not reveal any associations with DLB risk after multiple testing adjustment. However, a non-significant trend similar to that previously reported for PD was observed for the protective p.N551K-R1398H-K1423K haplotype in the clinical DLB series (OR: 0.76, P = 0.061). ConclusionLRRK2 does not appear to play a major role in DLB, however further study of p.G2019S and the p.N551K-R1398H-K1423K haplotype is warranted to better understand their involvement in determining DLB risk.

Complexity quantification of cardiac variability time series using improved sample entropy (I-SampEn).

The sample entropy (SampEn) has been widely used to quantify the complexity of RR-interval time series. It is a fact that higher complexity, and hence, entropy is associated with the RR-interval time series of healthy subjects. But, SampEn suffers from the disadvantage that it assigns higher entropy to the randomized surrogate time series as well as to certain pathological time series, which is a misleading observation. This wrong estimation of the complexity of a time series may be due to the fact that the existing SampEn technique updates the threshold value as a function of long-term standard deviation (SD) of a time series. However, time series of certain pathologies exhibits substantial variability in beat-to-beat fluctuations. So the SD of the first order difference (short term SD) of the time series should be considered while updating threshold value, to account for period-to-period variations inherited in a time series. In the present work, improved sample entropy (I-SampEn), a new methodology has been proposed in which threshold value is updated by considering the period-to-period variations of a time series. The I-SampEn technique results in assigning higher entropy value to age-matched healthy subjects than patients suffering atrial fibrillation (AF) and diabetes mellitus (DM). Our results are in agreement with the theory of reduction in complexity of RR-interval time series in patients suffering from chronic cardiovascular and non-cardiovascular diseases.

Cardiac variability time-series analysis by sample entropy and multiscale entropy

Ever since the use of heart rate variability (HRV) as a tool for quantification of autonomic nervous system dynamics has become popular, the interest in exploring the hidden complexities of physiologic time series has increased immensely. The sample entropy (SampEn) has been in use for quite some time as a complexity measure. In the present work, the SampEn was evaluated for certain physiological and pathological time series. It is demonstrated that SampEn is small for higher values of tolerance r and is able to distinguish different physiologic time series with tolerance level r = 0.2 to 0.3 for data lengths of approximately three thousand RR interval samples. It was further observed that this traditional algorithm exhibits higher complexity for pathologic subjects than for healthy physiologic subjects, which is misleading observation. This may be due to the fact that SampEn do not account for multiple time scales inherent in the physiologic time series. The above considered physiologic and pathologic time series were also evaluated with multiscale entropy (MSE). The time–series were observed to be more effectively distinguished for patients with congestive heart failure (CHF), sudden cardiac death (SCD), atrial fibrillation (AF) and partial epilepsy.

Clinical Features of a Series of Non-Surgical Patients with Focal Cortical Dysplasia and Epilepsy

Most published series of patients with focal cortical dysplasia and epilepsy are surgical or pathological series of pediatric cases. Patients have a high frequency of seizure. The description of clinical features and the frequency patterns of non-surgical adult patients are less describe. We retrospectively reviewed the clinical records of adult patients (>18 years of age) that visited the Epilepsy Centre of the Ramos Mejía Hospital in the city of Buenos Aires between 2010 and 2012. We included all cases with confirmed diagnosis of epilepsy and MRI diagnosis of focal cortical dysplasia by standardized 1.5 T MRI. We analyzed the following variables: sex, age at seizure onset, seizure types, seizure frequency, presence of abnormal neurological exam, family history of epilepsy, existence of perinatal insults and electroencephalography or video-EEG with at least one ictal recording. We included 20 patients since 2010–2012. Mean age of our population was 25.9 years (9–46 years), 7 females, 13 males, they all had a negative family history of epilepsy, and only two patients had pathological neurological exam, both with mild contralateral paresis. Mean seizure onset age was 5.71 years (2 months–17 years) and the average frequency was 5.1 seizures per month (0–15). Two patients became seizure-free after adjusting antiepileptic drugs. Focal seizures were presented in the 100% of our population. The low frequency of seizure emphasizes the heterogeneity of these patients and the importance of the correct use of antiepileptic drugs schemes, as well as it can be dynamic over time. A proportion of medically resistant patients with cortical dysplasia are poor surgical candidates because the lesion cannot be completely identify or removed if it involves eloquent areas of the cortex. With the development of new drugs and the correct choice of treatment schedules is expected that more patients with focal cortical dysplasia would be treated successfully.

A comparative analysis of spectral exponent estimation techniques for 1/fβ processes with applications to the analysis of stride interval time series

BackgroundThe time evolution and complex interactions of many nonlinear systems, such as in the human body, result in fractal types of parameter outcomes that exhibit self similarity over long time scales by a power law in the frequency spectrum S(f)=1/fβ. The scaling exponent β is thus often interpreted as a “biomarker” of relative health and decline. New methodThis paper presents a thorough comparative numerical analysis of fractal characterization techniques with specific consideration given to experimentally measured gait stride interval time series. The ideal fractal signals generated in the numerical analysis are constrained under varying lengths and biases indicative of a range of physiologically conceivable fractal signals. This analysis is to complement previous investigations of fractal characteristics in healthy and pathological gait stride interval time series, with which this study is compared. ResultsThe results of our analysis showed that the averaged wavelet coefficient method consistently yielded the most accurate results. Comparison with existing methodsClass dependent methods proved to be unsuitable for physiological time series. Detrended fluctuation analysis as most prevailing method in the literature exhibited large estimation variances. ConclusionsThe comparative numerical analysis and experimental applications provide a thorough basis for determining an appropriate and robust method for measuring and comparing a physiologically meaningful biomarker, the spectral index β. In consideration of the constraints of application, we note the significant drawbacks of detrended fluctuation analysis and conclude that the averaged wavelet coefficient method can provide reasonable consistency and accuracy for characterizing these fractal time series.

Diffuse mesothelioma of the peritoneum: a pathological study of 64 tumours treated with cytoreductive therapy

Diffuse peritoneal mesothelioma (DPM) forms a spectrum of indolent surface tumours to malignant invasive cancers. There are few pathological series that span well and poorly differentiated lesions that show diffuse peritoneal spread. Sixty-four DPM treated by initial cytoreductive therapy were retrospectively reviewed. Tumours were classified by surface and invasive growth pattern and correlated with risk factors, peritoneal cancer index (PCI) and completeness of cytoreduction (CCR). Degree of invasion was quantitated as absent (0), into stroma (I), into fat (II), and into adjacent structures (III) and was correlated with cytological features. Selected immunohistochemical stains were performed. There were three well differentiated papillary mesotheliomas (WDPM; type A), four multicystic mesothelioma (type B), 22 tubulopapillary epithelioid mesotheliomas (type C), and 35 poorly differentiated epithelioid mesotheliomas with solid or sarcomatoid growth (Type D). Seven type D tumours had prominent sarcomatoid areas, 12 deciduoid areas, and four lymphohistiocytoid features. Risk factors were present in all groups except type A, and included prior abdominal surgery (n=24), asbestos exposure (n=5) and radiation (n=2). Extra-pleural mesothelioma was present in all groups except type B (total n=7, 11%). Two type A and eight type C tumours lacked invasion; only type D showed level III invasion. The invasive portion of one type A tumour and two type B tumours showed adenomatoid features. PCI and CCR were greater in type D compared to the other groups (p=0.02), as well as mitotic rate, degree of necrosis, and nuclear pleomorphism (p<0.001). Degree of invasion was strongly correlated with CCR (p=0.007), necrosis (p<0.0001), nuclear grade (p<0.0001), and mitotic rate (p=0.001), but not PCI (p=0.1). Immunohistochemical results were similar across groups, with frequent positivity for CA125 (94%), EGFR (94%) and calretinin (93%), followed by p16 (85%), cytokeratin 5,6 (76%), D2-40 (71%) and WT-1 (47%). PAX-8 was negative in all tumours, except one type A tumour that showed diffuse nuclear positivity. Diffuse peritoneal mesotheliomas can be classified into four groups that reflect invasive potential, degree of adverse histological features, and amenability for CCR. Non-invasive tumours include both type A and type C tumours.

Contrast-Induced Acute Kidney Injury

The development of acute kidney injury is not an uncommon complication of invasive cardiovascular procedures requiring administration of radiocontrast, and it is associated with high acute and long-term morbidity and mortality.1–3 Recognized mechanism of acute kidney injury include embolization of atheroma (cholesterol embolism), which has been shown to occur in up to 1.4% of cases in clinical studies4 and in as high as 30% of cases in pathological series,5 and a direct toxic effect of contrast media on renal tubular cells (contrast-induced acute kidney injury). In the absence of cutaneous findings associated with cholesterol embolism, and in the absence of other symptoms and signs of distal embolization, it is difficult to determine the relative contribution of cholesterol embolism to the development of acute kidney injury when compared with contrast-induced acute kidney injury. The pathophysiology of contrast-induced acute kidney injury is complex and includes a direct toxic effect on tubular cells as well as the production of reactive oxygen species.6,7 Reactive oxygen species, by acting as scavengers of NO, lead to a reduction in Po2 and to increased vascular reactivity to various vasoconstrictors including angiotensin II, thromboxane, endothelin, adenosine, and norepinephrine. During the past 2 decades, we have made substantial progress in the identification of risk factors for the development of contrast-induced acute kidney injury2,8 and in the identification of interventions that can lead to a reduction of its incidence. As of today, minimization of the total amount of contrast by modification of procedure strategies and appropriate preprocedure hydration are mainstays in the prevention of contrast-induced acute kidney injury.9–11 In addition, the use of low-osmolar and iso-osmolar contrast media has been found to be beneficial when compared with high-osmolar contrast media.12 However, substantial differences …

Malignant struma ovarii: The west of Scotland experience and review of literature with focus on postoperative management

Malignant struma ovarii is an extremely rare ovarian tumour containing malignant thyroid carcinoma within differentiated thyroid tissue, as the predominant tissue type. Surgery for suspected ovarian tumour and incidental pathological diagnosis is the most common presentation. Evidence supporting any particular approach to the clinical management of this condition is limited, mainly consisting of case reports, small series or pathological case series. There is no randomised evidence for postoperative management in view of the rarity of this condition. The opinion is divided between conservative management versus total thyroidectomy and radio-iodine ablation. We carried out a retrospective review of our series with focus on postoperative management of this rare condition. A review of existing literature was also carried out. Six patients with a median age of 52 years presented with various symptoms of abdominal pain, pressure or menstrual problems. After the initial gynaecological resection and specialised pathology review, they were subsequently treated with total thyroidectomy and administration of radioactive iodine. All of these six patients are in remission at a median follow up of 60 months. We favour aggressive postoperative management with total thyroidectomy and radioactive iodine, and long-term follow up of these patients.

Symptomatic Spinal Metastases from Intracranial High-grade Glioma – Report of Four Cases and Review of the Literature

Intraspinal (leptomeningeal or intramedullary) metastases from primary intracranial gliomas have been well documented in several clinical and pathological series; however, symptomatic intraspinal metastases remain rare. We conducted a retrospective search of cases of intraspinal metastases treated at our centre and report four cases of symptomatic intraspinal leptomeningeal and intramedullary metastases from an intracranial glioma. The mean age of the four cases was 43 years (range 28–55 years). The intraspinal metastases were detected after a median time of 18.5 months after onset of the disease and the median survival time of the four patients from detection of spinal metastases was one month. Median overall survival of the four patients was 19 months. One patient was treated with surgery and all received radiotherapy treatment. Radiotherapy provided good initial palliation of pain but improvement in neurological deficits was limited.Overall, prognosis in cases of leptomeningeal and intramedullary metastases from primary intracranial glioma is very poor; however, this diagnosis should be considered in patients with malignant glioma presenting with new back pain and/or associated spinal neurological signs or symptoms. Radiotherapy provided relief of pain and some improvement in neurological function but no survival advantage. Clinical awareness and recognition of this entity will become increasingly important as local control of primary malignant glioma improves and corresponding improvements in outcome and prognosis of this disease are observed.

Infundibulo-tuberal or not strictly intraventricular craniopharyngioma: evidence for a major topographical category

This study investigates retrospectively the clinical, neuroradiological, pathological and surgical evidence verifying the infundibulo-tuberal topography for craniopharyngiomas (CPs). Infundibulo-tuberal CPs represent a surgical challenge due to their close anatomical relationships with the hypothalamus. An accurate definition of this topographical category is essential in order to prevent any undue injury to vital diencephalic centres. A systematic review of all scientific reports involving pathological, neuroradiological or surgical descriptions of either well-described individual cases or large series of CPs published in official journals and text books from 1892 to 2011 was carried out. A total of 1,232 documents providing pathological, surgical and/or neuroradiological evidence for the infundibulo-tuberal or hypothalamic location of CPs were finally analysed in this study. For a total of 3,571 CPs included in 67 pathological, surgical or neuroradiological series, 1,494 CPs (42%) were classified as infundibulo-tuberal lesions. This topography was proved in the autopsy of 122 non-operated cases. The crucial morphological finding characterizing the tubero-infundibular topography was the replacement of the third ventricle floor by a lesion with a predominant intraventricular growth. This type of CP usually presents a circumferential band of tight adherence to the third ventricle floor remnants, formed by a functionless layer of rective gliosis of a variable thickness. After complete surgical removal of an infundibulo-tuberal CP, a wide defect or breach at the floor of the third ventricle is regularly observed both in the surgical field and on postoperative magnetic resonance imaging studies. Infundibulo-tuberal CPs represent a major topographical category of lesions with a primary subpial development at the floor of the third ventricle. These lesions expand within the hypothalamus itself and subsequently occupy the third ventricle; consequently, they can be classified as not strictly intraventricular CPs. A tight attachment to the hypothalamus and remnants of the third ventricle floor is the pathological landmark of infundibulo-tuberal CPs.

Primary breast sarcoma: prevalence, clinical signs, and radiological features

Primary breast sarcoma is very rare. Most reports regarding sarcoma of the breast are clinical observations or pathological series and provide either no or inconstant radiological information. Radiological publications consist predominantly of isolated case reports or small series. To determine the prevalence, clinical signs, and radiological features of primary breast sarcoma. This is a retrospective review of 21 patients with breast sarcoma. All patients were female and their median age was 66 years (range 27-86). In all patients the diagnosis was confirmed histopathologically. The prevalence of breast sarcoma was 0.1% of all identified cases with breast malignancies. Clinically, all patients presented with solitary painless breast lumps. There was no uni- or bilateral axillary lymphadenopathy. On mammography (n = 19), two mammographic patterns could be identified: breast masses (68%), and architectural distortion (32%). On ultrasound (n = 8), most lesions were homogeneously hypoechoic, lobular or oval in shape with microlobulated or indistinct margins. On magnetic resonance imaging (n = 3), marked inhomogeneous contrast enhancement was seen in all investigated cases. The imaging findings of primary breast sarcoma are not pathognomonic. However, they should be taken into consideration in the differential diagnosis of breast lesions.