Cytokeratin AE1/AE3 mimicry in glioblastoma

Stoyanov, George S; Dzhenkov, Deyan; Ghenev, Peter

doi:10.14748/ssm.v49i1.2055

Cited by 5 publications

(7 citation statements)

References 9 publications

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“…The biggest innovations in the fi eld for this period were the commercial introduction of immunohistochemical (IHC) markers such as GFAP, S100, Vimentin and others which give a constant positive reaction and often help with the differential diagnosis of GBM and CNS metastatic diseases, while others give a varying IHC reaction. 17,18 With the introduction of modern molecular pathological and genetic test in oncopathology practices, however, the term multiforme has once again been popularized in the last fi fteen years of glioma research due to the multifomity of different genotypes bearing the same histomorphological and IHC picture. [17][18][19][20][21] As part of the research in this area and its relevance to therapeutic approaches, based on the presence of mutations, correlating with their biological potential and not the histomorphological and IHC hallmarks, some key mutations have been identifi ed in both pGBM and sGBM, giving a modern explanation to Scherers observations and estimations.…”

Section: Pheno-and Genotypisationmentioning

confidence: 99%

“…17,18 With the introduction of modern molecular pathological and genetic test in oncopathology practices, however, the term multiforme has once again been popularized in the last fi fteen years of glioma research due to the multifomity of different genotypes bearing the same histomorphological and IHC picture. [17][18][19][20][21] As part of the research in this area and its relevance to therapeutic approaches, based on the presence of mutations, correlating with their biological potential and not the histomorphological and IHC hallmarks, some key mutations have been identifi ed in both pGBM and sGBM, giving a modern explanation to Scherers observations and estimations. 1,3,6 The common presence of some mutations in different combinations has led to the discovery of a clinical correlation and even new therapeutic approaches to the diagnosis and treatment of GBM.…”

Section: Pheno-and Genotypisationmentioning

confidence: 99%

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On the Concepts and History of Glioblastoma Multiforme - Morphology, Genetics and Epigenetics

Stoyanov¹,

Dzhenkov²

2018

Folia Medica

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Glioblastoma multiforme (GBM) is a grade IV WHO malignant tumor with astrocytic differentiation. As one of the most common clinically diagnosed central nervous system (CNS) oncological entries, there have been a wide variety of historical reports of the description and evolution of ideas regarding these tumors. The first recorded reports of gliomas were given in British scientific reports, by Berns in 1800 and in 1804 by Abernety, with the first comprehensive histomorphological description being given in 1865 by Rudolf Virchow. In 1926 Percival Bailey and Harvey Cushing gave the base for the modern classification of gliomas. Between 1934 and 1941 the most prolific researcher in glioma research was Hans-Joachim Scherer, who postulated some of the clinico-morphological aspects of GBM. With the introduction of molecular and genetic tests the true multifomity of GBM has been established, with different genotypes bearing the same histomorphological and IHC picture, as well as some of the aspects of gliomagenesis. For a GBM to develop, a specific trigger mutation needs to occur in a GBM stem cell - primary GBM, or a slow aggregation of individual mutations, without a distinct trigger mutation - secondary GBM. Knowledge of GBM has been closely related to general medical knowledge of the CNS since these malignancies were first described more than 200 years ago. Several great leaps have been made in that time, in the footsteps of both CNS and advancements in general medical knowledge.

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Section: Pheno-and Genotypisationmentioning

confidence: 99%

Section: Pheno-and Genotypisationmentioning

confidence: 99%

On the Concepts and History of Glioblastoma Multiforme - Morphology, Genetics and Epigenetics

Stoyanov¹,

Dzhenkov²

2018

Folia Medica

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“…It is important to consider that around 2% of GBM lose their IHC reaction with GFAP, whilst preserving their vimentin reaction. Also key to note here is the already mentioned antigen mimicry reactions with EMA and CK AE1/AE3 [5]. Like all other glial tumors with astrocytic differentiation, GBM has a varying Ki-67 index, which cannot be used to determine the WHO grade alone.…”

Section: Cystic Lesionsmentioning

confidence: 99%

“…Despite morphology on hematoxylin and eosin (H&E) being highly suggestive in some cases, often IHC is also needed to distinguish between different entries, especially in cases of only small tumor fragments being sent for pathological investigation. Although IHC is a useful tool in the DD of any lesion, when regarding ICTs, it is especially important to avoid some common pitfalls due to antigen mimicry such as the glial fibrillary acidic protein (GFAP) mimicry with epithelial membrane antigen (EMA) and the pan-cytokeratin (CK AE1/AE3), where if all three reactions are positive, only the GFAP one should be considered valid [3][4][5][6].…”

Section: Reviewmentioning

confidence: 99%

A Practical Approach to the Differential Diagnosis of Intracranial Tumors: Gross, Histology, and Immunoprofile-based Algorithm

Stoyanov

Petkova

Dzhenkov

2019

Cureus

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Intracranial tumors are a diverse group of conditions, both benign and malignant, primary and metastatic and always require detailed medical information, radiological reports and deep knowledge of the histological hallmarks and immunohistochemical profile of different types of tumors and tumor-like processes. Despite it clinically often being possible to differentiate between primary and metastatic tumors, based on the tumor location and age of the patient, histological variants and rare tumor entries should always be considered in the histological differential diagnosis. A thorough diagnostic algorithm based on the location of the tumor and its histological features, together with some common pitfalls in immunohistochemical profiling, based on the 2016 revised World Health Organization (WHO) classification of tumors of the central nervous system should be implemented in all cases. Such an algorithm is especially valuable in cases where only small tumor fragments are sent for morphological evaluation, such as in deep parenchyma tumors. In these instances where only small fragments of the tumor are present for histology, some key features, corresponding to the WHO grade, may easily be missed or underreported. Furthermore, the histological verification of the tumor entry is the first, often overlooked, step in defining the presence or absence of WHO gradespecific mutations.

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“…While metastatic disease is often associated with an advanced age and some local tumors are generally reserved for younger individuals, both groups can be observed virtually in all age groups [ 13 , 19 - 20 ]. This can sometimes pose as a difficulty for both the clinical and pathological diagnosis, especially in the case of severely anaplastic tumors, even with the help of a wide range of immunohistochemical markers [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Demographics and Incidence of Histologically Confirmed Intracranial Tumors: A Five-year, Two-center Prospective Study

Stoyanov¹,

Dzhenkov²,

Kitanova³

et al. 2017

Cureus

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IntroductionIntracranial tumors (ICTs) are a diverse group of malignancies that pose an immediate threat to patients' lives, no matter their local or metastatic origin, benign or malignant nature. These lesions have severe clinical courses and need to be diagnosed and treated as soon as possible, with pathological verification being the pivotal moment in the process of determining curative modalities.AimThe aim of this study was to compare the incidence of histologically confirmed ICTs in Eastern Bulgaria, based on their type (primary, metastatic, and non-volume occupying lesions (NVOL)), their respective subtypes, and incidence in a descriptive manner.Materials and MethodsFor a period of five full calendar years (January 1st, 2012 – December 31st, 2016), all histologically confirmed cases of intracranial tumors were prospectively collected from two individual tertiary healthcare institutions. The cases were then statistically analyzed in a descriptive manner, and incidences of primary, metastatic, and NVOL were compared with regards to their specific origins, types, and subtypes. Metastatic tumors were further segregated relative to their intracranial metastatic location.ResultsThe total number of individual ICTs registered in the set timeframe was 822. Primary ICTs represented a total of 66.12% of the histologically confirmed cases, with the most common entries being tumors from a glial and meningeal origin, 30.90% were histologically confirmed as metastatic ICTs, from which the most common entries were of pulmonary origin, and the other 2.94% were NVOL. On behalf of their intracranial metastatic location, metastatic tumors were located predominantly in the supratentorial region, represented as a total of 87.80%, while the other 12.20% were located in the subtentorial region. Based on the descriptive analysis, the annual incidence per 100,000 capita of all ICTs is 9.12, comprised of 6.03 per 100,000 for primary ICTs, 2.82 per 100,000 for metastatic ICTs, and 0.27 per 100,000 for NVOL. The annual incidence of the most commonly diagnosed primary ICTs per 100,000 is 2.36 for meningioma, 2.03 for glioblastoma, and 0.48 for pituitary adenoma. The annual incidence of the most commonly diagnosed metastatic ICTs per 100,000 is 1.32 for lung cancer metastases, 0.28 for gastrointestinal tract (GIT) metastases, 0.22 for melanoma, and 0.17 for breast cancer metastases.ConclusionBased on our results, primary ICTs are operated and biopsied more than two times as much as metastatic ICTs and only a small fraction of neurosurgical interventions are undertaken due to NVOL. Metastatic ICTs are predominantly supratentorial with no evidence of a tumor predominantly metastasizing in the subtentorial region. The demographics reported in the study establish some aspects of age and gender preferences, as well as the annual incidence per 100,000 for the most commonly diagnosed types of ICTs in our population.

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Cytokeratin AE1/AE3 mimicry in glioblastoma

Abstract: INTRODUCTION:The diagnosis and treatment of intracranial tumors requires a multidisciplinary approach. A key moment in this process is the pathological verification of the tumor type. This process, although aided by immunohistochemistry (IHC), can often be difficult and misleading.

Cited by 5 publications

References 9 publications

On the Concepts and History of Glioblastoma Multiforme - Morphology, Genetics and Epigenetics

On the Concepts and History of Glioblastoma Multiforme - Morphology, Genetics and Epigenetics

A Practical Approach to the Differential Diagnosis of Intracranial Tumors: Gross, Histology, and Immunoprofile-based Algorithm

Demographics and Incidence of Histologically Confirmed Intracranial Tumors: A Five-year, Two-center Prospective Study

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