Separate Pathological Entity Research Articles

Papillary Craniopharyngioma: an integrative and comprehensive review.

Papillary craniopharyngioma (PCP) is a rare type of tumor, comprising ∼20% of all craniopharyngioma (CP) cases. It is now recognized as a separate pathological entity from the adamantinomatous type. PCPs are benign tumors, classified as WHO grade 1, characterized by non-keratinizing squamous epithelium. They typically grow as solid and round papillomatous masses or as unilocular cysts with a cauliflower-like excrescence. PCPs primarily occur in adults (95%), with increased frequency in males (60%) and predominantly affect the hypothalamus. Over 80% of these tumors are located in the third ventricle, expanding either above an anatomically intact infundibulum (strictly third ventricle tumors) or within the infundibulo-tuberal region of the third ventricle floor. Clinical manifestations commonly include visual deficits and a wide range of psychiatric disturbances (45% of patients), such as memory deficits and odd behavior. MRI can identify up to 50% of PCPs by the presence of a basal duct-like recess. Surgical management is challenging, requiring complex approaches to the third ventricle and posing significant risk of hypothalamic injury. The endoscopic endonasal approach allows radical tumor resection and yields more favorable patient outcomes. Of intriguing pathogenesis, over 90% of PCPs harbor the somatic BRAFV600E mutation, which activates the mitogen-activated protein kinase (MAPK/ERK) signaling pathway. A phase 2 clinical trial has demonstrated that PCPs respond well to BRAF/MEK inhibitors. This comprehensive review synthesizes information from a cohort of 560 well-described PCPs and 99 large CP series including PCP cases published from 1856-2023 and represents the most extensive collection of knowledge on PCPs to date.

A Rare Triploid Involving the Coexistence of Glioblastoma Multiforme, Arteriovenous Malformation and Intracranial Aneurysm: Illustrative Case and Literature Review

The coexistence of glioblastoma multiforme (GBM) and arteriovenous malformation (AVM) is rarely reported in the literature. According to the present literature, these GBM or glioma-related vascular malformations may present simultaneously in distinct regions of the brain or occur in the same area but at different times. So far, these distinct hypervascular glioblastomas have been described but are not classified as a separate pathological entities. Considering their heterogeneity and complexity, all the above mentioned cases remain challenging in diagnosis and therapeutic modality. Likewise, there is a paucity of data surrounding the simultaneous presentation of GBM with intracranial aneurysms. In the literature, the independent concurrence of these three intracranial lesions has never been reported. In this article, we present a case who suffered from intermittent headaches and dizziness initially and further radiographic examination revealed an internal carotid artery (ICA) aneurysm that occurred in the patient with coexisting GBM and AVM. Surgical intervention for tumor and AVM removal was performed smoothly. This patient underwent endovascular coiling for the ICA aneurysm 4 months postoperatively. In addition, we also review the current literature relating to this rare combination of medical conditions.

Cross-Communication Between Knee Osteoarthritis and Fibrosis: Molecular Pathways and Key Molecules.

Knee fibrosis is characterized by the presence of excessive connective tissue due to dysregulated fibroblast activation following local or systemic tissue damage. Knee fibrosis constitutes a major clinical problem in orthopaedics due to the severe limitation in the knee range of motion that leads to compromised function and patient disability. Knee osteoarthritis is an extremely common orthopedic condition that is associated with patient disability and major costs to the health-care systems worldwide. Although knee fibrosis and osteoarthritis (OA) have traditionally been perceived as two separate pathologic entities, recent research has shown common ground between the pathophysiologic processes that lead to the development of these two conditions. The purpose of this review was to identify the pathophysiologic pathways as well as key molecules that are implicated in the development of both knee OA and knee fibrosis in order to understand the relationship between the two diagnoses and potentially identify novel therapeutic targets.

Recurrent Hurthle cell thyroid carcinoma does not preclude long-term survival: a case report and review of the literature

BackgroundFollicular thyroid carcinoma is the second most common malignancy of the thyroid gland. In 2016, the so-called Hurthle cell thyroid carcinoma, formerly known as the oxyphilic variant of the follicular thyroid carcinoma, was reclassified by the World Health Organization as a separate pathological entity, which accounts for approximately 3% of all thyroid cancers. Although Hurthle cell thyroid carcinomas are known for their more aggressive tumor biology, metastases are observed in a minority of cases, and long-term survival can be expected. However, disseminated disease is often associated with poor outcome.Case presentationIn the presented case, a 63-year-old Caucasian female was incidentally diagnosed with Hurthle cell thyroid carcinoma after undergoing hemithyroidectomy for a nodular goiter. Following completion thyroidectomy, two courses of radioactive iodine therapy were administered. After 4 years of uneventful follow-up, the patient gradually developed metastases in five different organs, with the majority representing unusual sites, such as heart, kidney, and pancreas over a course of 14 years. The lesions were either treated with radioactive iodine therapy or removed surgically, depending on iodine avidity.ConclusionFollicular and Hurthle cell thyroid carcinoma are known to potentially spread hematogenously to typical sites, such as lung or bones, however; unusual metastatic sites as presented in our case can also be observed. A search of the literature revealed only scattered reports on patients with multiple metastases in unusual locations. Furthermore, the observed long-term survival of our patient is contradictory to the existing data. As demonstrated, recurrent disease may appear years after the initial diagnosis, emphasizing the importance of consistent aftercare. Radioactive iodine therapy, extracorporeal radiation therapy, and surgical metastasectomy are central therapeutic components. In summary, our case exemplifies that thorough aftercare and aggressive treatment enables long-term survival even in recurrent Hurthle cell thyroid carcinoma displaying unusual multisite metastases.

Fluid biomarkers of white matter hyperintensities in cerebrovascular disease and neurodegeneration: a systematic review protocol.

The goal of this systematic review is to evaluate the association between fluid biomarkers and white matter hyperintensities (WMH) in cerebrovascular disease and neurodegenerative disorders. While previous research has examined the etiology of WMH in specific diseases, we propose a comprehensive framework encompassing WMH of both vascular and non-vascular origin. Although WMH have been mostly described in aging populations with cerebrovascular disease, extensive lesions also occur in non-vascular diseases. Such lesions are traditionally treated as a separate pathological entity from vascular ones, but recent work has challenged the appropriateness of that framework when probing WMH etiology. Comparing biomarkers associated with WMH across various pathologies may improve our understanding of their etiology. The review will focus on cerebrovascular disease and neurodegenerative disorders and exclude infectious, metabolic, drug-induced, or radiation-induced white matter diseases. Original, peer-reviewed research on the relationship of WMH on magnetic resonance imaging with blood/cerebrospinal fluid biomarkers will be considered for inclusion. Postmortem studies will guide the selection of biomarkers of interest and the interpretation of our findings. Genomic markers will be excluded. The review will be conducted in accordance with PRISMA and JBI guidelines. English articles of interest published between 2000 and 2020 will be identified in MEDLINE and Embase. Two reviewers will perform abstract and full-text screening, standardized data extraction, and quality assessments of the selected studies. The relationship between each biomarker and WMH burden will be meta-analyzed, if possible, with subgroup or meta-regression analyses to assess differences between diseases. PROSPERO CRD42020218298.

HGG-50. TWO CASES OF H3 K27M-MUTANT DIFFUSE MIDLINE GLIOMA OF CERVICAL SPINAL CORD

BACKGROUND“Diffuse midline glioma, H3 K27M-mutant’ was newly categorized as a separate pathological entity in the 2016 WHO classification, based on recently discovered mutation. Spinal cord glioma with H3 K27M-mutant is rare, so we reported the clinical course of two cases. CASE 1: A 17-year-old male presented with posterior headache and right limbs paralysis. MRI showed cervical spinal cord with expansion, T2-weighted high intensity and a part of enhancement. The biopsy revealed a diffuse midline glioma, H3 K27M-mutant. He received bevacizumab plus radiotherapy-temozolomide. In a few months, he had quadriplegia and cranial nerve paralysis and needed respirator. There was not expansion of mass, but intracranial dissemination. CASE 2: A 16-year-old male presented with posterior neck pain and right limbs paralysis. On brain stem and cervical spine, MRI findings were same to case 1. The biopsy was undergone and revealed H3 K27M mutation. He received bevacizumab in addition to radiotherapy-temozolomide. Although he also had quadriplegia, the progression of tumor has stopped. He has received chemotherapy with respirator at home.DISCUSSIONIt was previously reported that the prognostic factors for diffuse midline glioma were tumor location, H3 K27M-mutation and age, but there are few relevant studies. The consensus on the treatment is also not clearly determined. Because the cervical spinal cord gliomas are rapidly advanced miserably, we added bevacizumab to standard radiotherapy-temozolomide for initial treatment. In addition, whole brain and spine radiation may be considered to avoid dissemination. Multicenter study is important to collect information and improve treatment of H3 K27M-mutant glioma.

The immunohistochemical, DNA methylation, and chromosomal copy number profile of cauda equina paraganglioma is distinct from extra-spinal paraganglioma.

Paragangliomas are neuroendocrine tumors of the autonomic nervous system that are variably clinically functional and have a potential for metastasis. Up to 40% occur in the setting of a hereditary syndrome, most commonly due to germline mutations in succinate dehydrogenase (SDHx) genes. Immunohistochemically, paragangliomas are characteristically GATA3-positive and cytokeratin-negative, with loss of SDHB expression in most hereditary cases. In contrast, the rare paragangliomas arising in the cauda equina (CEP) or filum terminale region have been shown to be hormonally silent, clinically indolent, and have variable keratin expression, suggesting these tumors may represent a separate pathologic entity. We retrospectively evaluated 17 CEPs from 11 male and 6 female patients with a median age of 38years (range 21-82), none with a family history of neuroendocrine neoplasia. Six of the 17 tumors demonstrated prominent gangliocytic or ganglioneuromatous differentiation. By immunohistochemistry, none of the CEPs showed GATA3 positivity or loss of SDHB staining; all 17 CEPs were cytokeratin positive. Genome-wide DNA methylation profiling was performed on 12 of the tumors and compared with publicly available genome-wide DNA methylation data. Clustering analysis showed that CEPs form a distinct epigenetic group, separate from paragangliomas of extraspinal sites, pheochromocytomas, and other neuroendocrine neoplasms. Copy number analysis revealed diploid genomes in the vast majority of CEPs, whereas extraspinal paragangliomas were mostly aneuploid with recurrent trisomy 1q and monosomies of 1p, 3, and 11, none of which were present in the cohort of CEP. Together, these findings indicate that CEPs likely represent a distinct entity. Future genomic studies are needed to further elucidate the molecular pathogenesis of these tumors.

Do Myelin Oligodendrocyte Glycoprotein Antibodies Represent a Distinct Syndrome?

Do Myelin Oligodendrocyte Glycoprotein Antibodies Represent a Distinct Syndrome?

Non-specific colitis among patients with colitis: frequency and relation to inflammatory bowel disease, a prospective study

Background and study aimThe term non-specific colitis refers to an inflammatory condition of the colon that microscopically lacks the characteristic features of any specific form of colitis and is commonly seen in pathology reports of colonoscopy biopsies. In fact, it has been questioned whether it is a separate pathological entity or it is merely an intermediate stage in the course of inflammatory bowel disease. This study was conducted to estimate the prevalence of non-specific colitis among patients with colitis and characterize its natural history over a 6 months year period. Patients and methodsEighty adult patients presented for colonoscopy were enrolled. In the final analysis they were divided into Group A; the non-specific colitis Group and Group B; the inflammatory bowel disease Group. All patients were subjected to: full history taking, full clinical examination, laboratory investigations: which included stool analysis, CRP, ESR, complete colonoscopy and entire random colon biopsies for histopathological examination. ResultsGroup A included 67 patients (83.75%) while Group B included 13 (16.25%) patients. Patients with IBD had clinical and laboratory features of inflammation significantly higher than patients with non-specific colitis. Six patients (8.95%) of non-specific colitis group developed histologic features of florid inflammatory bowel disease after 6 months. There were no independent predictors of this conversion. ConclusionAmong our 80 patients with colonoscopy and biopsy 67 (83.75%) were diagnosed as non-specific colitis and out of them 6 patients (8.95%) were reexamined after 6 months and proved to have inflammtory bowel disese this change was not linked to predictive factors.

Highlights of This Issue

While trastuzumab-based chemotherapy has shown remarkable clinical benefits for HER2-positive breast cancer patients, a subset of patients (30%–40%) shows little or no effect. This highlights an important clinical need for biomarkers in addition to HER2 for better stratification of patients for therapy. In this multicenter retrospective study by Kang and colleagues, patients with HER2-positive breast cancer that also overexpress WBP2 had better pathologic complete response to trastuzumab-based neoadjuvant therapy. The potential to predict which patients would attain successful downstaging of their tumors from neoadjuvant therapy could help guide surgical decisions; for example, breast-conserving surgery versus mastectomy, consequently improving patients' outcome.Extending previous studies in more restricted populations, Nassar and colleagues examined 472 patients across the spectrum of urothelial carcinoma from nonmuscle-invasive bladder cancer (NMIBC) to upper-tract urothelial carcinoma (UTUC) for mutations in 237 cancer genes. Low-grade NMIBC has a distinct mutation spectrum from invasive disease, suggesting that it is truly a separate pathologic entity unrelated to invasive disease in most instances. Other key findings include enrichment of KDM6A mutations in women with low-grade NMIBC compared to men and identification of a subtype of high-grade UTUC with mutations in FGFR3, EP300, and PIK3CA associated with poorer survival.Drug-resistance is a major obstacle for the effective treatment of patients with high-grade serous ovarian cancer (HGSOC), often resulting in the selection of an ineffective treatment course. Using PET imaging with the radiotracer (4S)-4-(3-[18F]fluoropropyl)-L-glutamate ([18F]FSPG), Greenwood and colleagues showed decreased radiotracer uptake in chemotherapy-resistant A2780 tumors compared with parental drug-sensitive tumors, demonstrating the ability of [18F]FSPG to detect upregulated antioxidant pathways present in drug-resistant cancer. [18F]FSPG may, therefore, enable the identification of HGSOC patients who are refractory to standard-of-care, allowing the transferal of drug-resistant patients to alternative therapies and thereby improving outcomes in this disease.To understand the immunological nature of glioblastoma, Park and colleagues examined the expression of immune checkpoint inhibitory receptors in tumor-infiltrating CD8+ T cells from patients with primary glioblastoma and their differentiation status. In addition, they investigated the reinvigoration ability of tumor-infiltrating CD8+ T cells by ex vivo treatment with anti-PD-1 and anti-CTLA-4. They demonstrated that the differentiation status of tumor-infiltrating CD8+ T cells determines the reinvigoration ability. This study provides a rationale for developing optimal strategies for immune checkpoint inhibitor treatment in patients with glioblastoma.

Mechanisms Underlying Overactive Bladder and Interstitial Cystitis/Painful Bladder Syndrome.

The bladder is innervated by extrinsic afferents that project into the dorsal horn of the spinal cord, providing sensory input to the micturition centers within the central nervous system. Under normal conditions, the continuous activation of these neurons during bladder distension goes mostly unnoticed. However, for patients with chronic urological disorders such as overactive bladder syndrome (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS), exaggerated bladder sensation and altered bladder function are common debilitating symptoms. Whilst considered to be separate pathological entities, there is now significant clinical and pre-clinical evidence that both OAB and IC/PBS are related to structural, synaptic, or intrinsic changes in the complex signaling pathways that mediate bladder sensation. This review discusses how urothelial dysfunction, bladder permeability, inflammation, and cross-organ sensitisation between visceral organs can regulate this neuroplasticity. Furthermore, we discuss how the emotional affective component of pain processing, involving dysregulation of the HPA axis and maladaptation to stress, anxiety and depression, can exacerbate aberrant bladder sensation and urological dysfunction. This review reveals the complex nature of urological disorders, highlighting numerous interconnected mechanisms in their pathogenesis. To find appropriate therapeutic treatments for these disorders, it is first essential to understand the mechanisms responsible, incorporating research from every level of the sensory pathway, from bladder to brain.

Fetal human leukocyte antigen-C and maternal killer-cell immunoglobulin-like receptors in cases of severe preeclampsia

IntroductionThe pathogenesis of preeclampsia may involve inadequate trophoblast invasion caused by excessive inhibition of uterine natural killer cells (uNK) by extravillous trophoblast cells (EVT). This may be the result of a combination of maternal killer-cell immunoglobin-like receptor (KIR) AA genotype and fetal human leukocyte antigen-C2 (HLA-C2) genotype. A few studies have reported a significantly increased frequency of the maternal KIR AA/fetal HLA-C2 combination in cases of preeclampsia compared to controls. MethodsStudy subjects were 259 cases of severe preeclampsia/eclampsia and 259 matched pregnant women without preeclampsia or eclampsia. All pregnancies were singleton pregnancies, and mothers were preferentially primigravidae. Blood samples from women and their newborns were obtained from the Danish National Birth Cohort (DNBC) and the Danish Neonatal Screening Biobank. Significant differences in the frequencies of KIR AA and HLA-C2 between cases and controls were investigated. ResultsNo significant difference was observed between cases and controls in the frequency of maternal KIR AA (OR = 0.86, 95%CI = 0.60–1.23, P = 0.41), neither when the fetus carried an HLA-C2 allele (OR = 0.85, 95%CI = 0.52–1.38, P = 0.51), nor when the fetus carried an HLA-C2 allele more than its mother (OR = 0.75, 95%CI = 0.34–1.64, P = 0.47). ConclusionThe Results show no influence of HLA-C/KIR genetic variation on the risk of severe preeclampsia, contrary to what some previous studies have observed. An explanation could be that severe preeclampsia represents a separate pathological entity compared to mild preeclampsia.

Vascular malformations of the maxillofacial skeleton — an overview of presentation and management

Background: Vascular disorders of the maxillofacial skeleton vary from benign localised lesions to aggressive, proliferative high-flow malformations that present enormous challenges for the clinician. Objectives: This presentation will describe the classification of vascular malformations within the maxillofacial complex, their characteristics and management. The distinction between arteriovenous malformations (AVM) and haemangiomas will also be highlighted to emphasise that these lesions are separate pathological entities. Methods: A retrospective review of patients (adults and paediatric patients) with a diagnosis of a vascular lesion of the facial skeleton was undertaken in an attempt to classify the main categories. The implications for elective and curative surgery were to be considered and treatment protocols outlined. Findings: Of 13 patients with AVM's, 6 were syndromic low-flow arteriovenous malformations, 4 were nonsyndromic low-flow lesions and 3 were high-flow malformations. Sturge-Weber syndrome is a phakomatosis due to an embryonal developmental anomaly (mutations in the GNAQ gene) with several subtypes. Nonsyndromic low-flow intraosseous lesions can be incidentally diagnosed on routine imaging and some may present with contour deformities or the displacement of teeth. However, high-flow lesions are rare and potentially life threatening. They may present with a pulsatile, expanding bony cortex, interdental bleeding or massive socket haemorrhage. For low-flow lesions, resection with a small margin may be sufficient for resolution of the lesion. However, high-flow lesions may require embolisation, sclerosing solutions, surgical resection or a combination of these interventions. A number of cases will be presented to illustrate the presentation of AVM's and the approach to management.

1422TiP - Phase II, singlearm, nonrandomized, and multicenter clinical trial of regorafenib (REG) as a single agent in the firstline setting for patients with metastatic and/or unresectable KIT/PDGFR wild-type GIST. A GEIS and ISG study

Approximately 10-15% of adults with GIST lack KIT or PDGFRA mutations. This KIT/PDGFRA wild-type (wt) GIST is considered a separate pathological entity and is highly clinically heterogeneous. Because most KIT/PDGFRA wt-GISTs do not respond to imatinib, new treatment approaches are needed. REG is an oral multikinase inhibitor that has been shown to improve progression-free survival (PFS) and disease control rate (DCR) vs placebo in patients with advanced GIST progressing after failure of imatinib and sunitinib (Demetri et al. Lancet 2013). This study was designed to assess the effectiveness of REG in patients with metastatic and/or unresectable KIT/PDGFR wt-GIST in the first-line setting. Trial design: Patients ≥18 years of age with histologically confirmed unresectable and/or metastatic KIT/PDGFR wt-GIST (lack of mutations in KIT exons 11,9,13,17 and PDGFR exons 12,18 confirmed by next-generation sequencing) are eligible. Other inclusion criteria include ≥1 measurable lesion (RECIST v1.1), ECOG PS 0-1, adequate bone marrow, liver, and renal function, not fulfilling any exclusion criteria, and written informed consent. FFPE-tumor blocks are to be provided. Collection of blood and fresh tumor samples for a translational substudy is optional. REG 160 mg will be administered once daily in a 3-weeks on, 1-week off schedule until disease progression, unacceptable toxicity, or investigator/patient decision to withdraw. Thirtythree patients (+ 20%) are to be recruited according to Simon Minmax 2stage Phase II design. Main endpoint is DCR relative to the historical control of imatinib in wt-GIST. Hypothesis 0: p0 = 73% (0% CR + 23% PR + 50% SD). Hypothesis 1: achieving a DCR of p1 = 90% with REG. Using error rates of a = 0.05 and b = 0.20, the first-stage sample size is 31 patients, with 26 patients as the upper limit for firststage drug rejection. Secondary outcomes include PFS, overall survival, response (CHOI criteria), correlation with translational research, early metabolic response by PETscan, and safety (CTCAE 4.03). Clinical trial identification: EudraCT Number: 2015-001048-12 Legal entity responsible for the study: Grupo Español de Investigación en Sarcomas (GEIS)

Reduced Tau protein expression is associated with frontotemporal degeneration with progranulin mutation.

Reduction of Tau protein expression was described in 2003 by Zhukareva et al. in a variant of frontotemporal lobar degeneration (FTLD) referred to as diagnosis of dementia lacking distinctive histopathology, then re-classified as FTLD with ubiquitin inclusions. However, the analysis of Tau expression in FTLD has not been reconsidered since then. Knowledge of the molecular basis of protein aggregates and genes that are mutated in the FTLD spectrum would enable to determine whether the “Tau-less” is a separate pathological entity or if it belongs to an existing subclass of FTLD. To address this question, we have analyzed Tau expression in the frontal brain areas from control, Alzheimer’s disease and FTLD cases, including FTLD- Tau (MAPT), FTLD-TDP (sporadic, FTLD-TDP-GRN, FTLD-TDP-C9ORF72) and sporadic FTLD-FUS, using western blot and 2D-DIGE (Two-Dimensional fluorescence Difference Gel Electrophoresis) approaches. Surprisingly, we found that most of the FTLD-TDP-GRN brains are characterized by a huge reduction of Tau protein expression without any decrease in Tau mRNA levels. Interestingly, only cases affected by point mutations, rather than cases with total deletion of one GRN allele, seem to be affected by this reduction of Tau protein expression. Moreover, proteomic analysis highlighted correlations between reduced Tau protein level, synaptic impairment and massive reactive astrogliosis in these FTLD-GRN cases. Consistent with a recent study, our data also bring new insights regarding the role of progranulin in neurodegeneration by suggesting its involvement in lysosome and synaptic regulation. Together, our results demonstrate a strong association between progranulin deficiency and reduction of Tau protein expression that could lead to severe neuronal and glial dysfunctions. Our study also indicates that this FTLD-TDP-GRN subgroup could be part as a distinct entity of FTLD classification.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0345-0) contains supplementary material, which is available to authorized users.

Desmoplastic small round cell tumor: A case report of a rare differential diagnosis of solid tumors of the pleura.

Desmoplastic small round cell tumor (DSRCT) presents as a rare separate clinical pathological entity, and pleural DSRCT is very rare. Following review of the English literatures it was revealed that, to date, <15 cases of primary DSRCT of the pleura have been reported worldwide. Among these, there are few computed tomography (CT) findings of pleural DSRCT which have previously been described in detail. The present study reports a pathologically proven case of pleural DSRCT, with varying contrast CT findings in a 72-year-old female, which appeared as a large (12.0×10.0×6.5 cm), smooth, oval mass in the left lower thorax with slight-moderate uniform enhancement on contrast-enhanced CT. To the best of our knowledge, the present report is the first to describe the large solid-tumor pattern and the patient is the eldest reported case of pleural DSRCT.

Wild-type GIST: a comprehensive review

34 Wild-type GIST: a comprehensive review 1 3 Abstract Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The vast majority demonstrates mutually exclusive KIT or PDGFRA gain-of-function mutations. KIT or PDGFRA mutation is an early event in GIST pathogenesis and development, and has led to the introduction of KIT and PDGFRA kinase inhibitors in GIST, which has tremendously changed survival of patients suffering from this disease. Approximately 85 % of pediatric GISTs and 10–15 % of adult GISTs are devoid of mutations in the KIT and PDGFRA genes and are referred to as wild-type GISTs (WT-GIST). Over the past years, it has been shown that WT-GISTs are profoundly different from mutant GIST with regard to their clinical behavior as well as their molecular profile, and are now considered a separate pathological entity. Based on their significant molecular and clinical heterogeneity, WT-GISTs should be considered a group of diseases rather than a single disease entity. The following short review will exclusively focus on WT-GISTs, a group of tumors traditionally divided into a syndromic and a nonsyndromic (sporadic) subgroup. In addition, immunohistochemical expression of succinate dehydrogenase B (SDHB) has recently been introduced to subtype WT-GISTs into an SDHB-positive (proficient) from SDHB-negative (deficient) group.

Calcifying Cystic Odontogenic Tumor with Compound Odontoma

ABSTRACTCalcifying cystic odontogenic tumor (CCOT) previously known as calcifying odontogenic cyst (COC) is a relatively rare lesion. It was first reported as a separate pathologic entity by Gorlin et al in 1962 as a likely analog of the cutaneous calcifying epithelioma of Malherbe or pilomatricoma. Because of the diverse clinicohistologic features and the various neoplastic potential, there have been disagreements on the terminology as well as whether to classify CCOTs as a cyst or a neoplasm. CCOT is frequently associated with other lesions, such as odontoma, ameloblastoma and ameloblastic fibroma, and the most common of these is the CCOT-associated odontoma (CCOTaO). CCOTaO tends to occur in the anterior portion of upper jaw and occurs in younger age group as compared to other types. We present a case of CCOTaO in the posterior mandible of a 23-year-old male.How to cite this articleSidana S, Poonja K, Galinde J, Poonja LS. Calcifying Cystic Odontogenic Tumor with Compound Odontoma. J Contemp Dent 2013;3(1):36-39.

Exstrophy Polyp is a Unique Pathology Entity

Classic bladder exstrophy is a rare congenital malformation occurring with an incidence of about 1 in 50 000 live births. Polypoid lesions frequently arise in the exstrophic bladder template; this has been well described in the pediatric urological literature. These lesions, however, are not as familiar to pathologists and oftentimes constitute diagnostic challenges. Careful observation revealed that these polyps are unique in their histopathologic appearance, with deep penetrating nests of urothelium or cysts and surrounding concentric fibrosis. Combining the unique clinical setting, a separate pathologic and diagnostic entity should be initiated for this type of polyp; we propose the term 'bladder exstrophy polyp' or simply an 'exstrophy polyp.'

Inflammatory Vascular Disease: A Unifying Hypothesis

Research scientists and physicians alike describe many different forms of inflammatory vascular disease, reporting each separate pathological entity in terms of individual causes, symptoms, signs, and physical findings Atherosclerotic plaque, recurrent plaque growth after angioplasty and stent implant, transplant rejection, arthritic disorders, and the inflammatory vasculitic syndromes such as giant cell arteritis or Takayasu’s disease, are all associated with increased inflammatory cell activation and severe arterial disease. Viewing these vasculitic disorders autonomously, as separate entities, leads to a risk of misdiagnosis, longer treatment, increased mortality, and in short limits treatment options. This has significant implications for morbidity and mortality. The very classifications on which we rely prevent us from seeing that inflammatory arterial disorders actually represent a continuum. We propose here that these separate classifications of vascular disease are artificial, that these vascular diseases represent a continuum of inflammatory arterial disorders, rather than separate pathological entities. We postulate that the underlying central cause for a wide spectrum of occlusive arterial diseases is an up-regulation of innate immune responses that drive ongoing arterial damage.