Wszystko co świeci w PET nie jest nowotworem złośliwym! Wychwyt 18F-deoksyglukozy a biologia nowotworu: incidentaloma przysadki mózgowej u chorego, który przebył dwie niezwiązane choroby nowotworowe

    Introduction: 18F-deoxy-glucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) is routinely used in the detection of malignant disease based on the property of malignant cells to fuel their growth and replication by increased glucose uptake. Malignant lesions are rare in the sellar region, while pituitary adenomas are the most common pathology. These are benign neoplasms with insidious onset and low proliferation activity, and therefore are only exceptionally detected by 18F-FDG PET/CT. Studies that compare the biology of pituitary adenomas and their radiological properties using PET/CT are still lacking. Case report: We investigate and discuss tumour biology in light of increased 18F-FDG avidity in a symptom-free, 70-year-old male patient, previously treated for two different malignancies (lung and rectal). Increased tracer accumulation in the sellar region was incidentally detected on a follow-up 18F-FDG PET/CT scan. Additional MRI disclosed pituitary adenoma. Normal hormonal status was found, consistent with the diagnosis of non-functioning pituitary adenoma. Analysis of tumour tissue after pituitary surgery confirmed a silent gonadotroph adenoma with low proliferation index. Low expression of oncogene-induced senescence markers did not support senescence as the explanation for the tumour’s low proliferative activity although it was in consonance with the hormonal activity. Conclusions: Pituitary adenomas can manifest as hypermetabolic foci on 18F-FDG PET/CT imaging with increased tracer uptake even in indolent, clinically silent pituitary adenomas with low mitotic activity. Special attention should be paid to evaluation of 18F-FDG avid pituitary adenomas in patients with multiple malignancies, bearing in mind that avidity does not always mirror its biological behaviour.Wstęp: Pozytonowa tomografia emisyjna sprzężona z tomografią komputerową przy użyciu 18F-deoksy-glukozy (18F-FDG PET/CT) to metoda stosowana rutynowo do wykrywania nowotworów złośliwych, opierająca się na właściwościach komórek nowotworowych, których wzrost i replikacja wiąże się ze zwiększeniem wychwytu glukozy. Zmiany złośliwe występują rzadko w okolicy siodła tureckiego, natomiast do najczęstszych patologii należą gruczolaki przysadki mózgowej. Są to łagodne nowotwory z podstępnym początkiem choroby i małą aktywnością proliferacyjną, dlatego też są wykrywane wyjątkowa rzadko za pomocą badania 18F-FDG PET/CT. Nie przeprowadzono dotychczas badania porównującego cechy biologiczne gruczolaków przysadki mózgowej i ich właściwości radiologiczne z zastosowaniem techniki PET/CT. Opis przypadku: Autorzy zbadali i omówili biologię nowotworu w aspekcie zwiększonego wychwytu 18F-FDG u 70-letniego chorego bez objawów, leczonego wcześniej z powodu dwóch różnych nowotworów (płuca i odbytnicy). Zwiększony wychwyt znacznika w okolicy siodła tureckiego wykryto przypadkowo podczas kontrolnego badania 18F-FDG PET/CT. Wykonane dodatkowo badanie MRI ujawniło gruczolaka przysadki mózgowej. Stężenia hormonów u chorego były w normie, co było zgodne z rozpoznaniem nieczynnego gruczolaka przysadki mózgowej. Badanie tkanki guza po resekcji chirurgicznej potwierdziło diagnozę niemego klinicznie gruczolaka gonadotropowego o niskim wskaźniku proliferacji. Niska ekspresja markerów starzenia się indukowanego onkogenami nie potwierdziła hipotezy, że starzenie się może tłumaczyć małą aktywność proliferacyjną nowotworu, natomiast była zgodna z aktywnością hormonalną. Wnioski: Gruczolaki przysadki mózgowej mogą być widoczne w badaniu 18F-FDG PET/CT jako ogniska hipermetaboliczne o zwiększonym wychwycie znacznika nawet w przypadku nieczynnych, niemych klinicznie guzów przysadki o małej aktywności mitotycznej. Należy zwrócić szczególną uwagę na ocenę 18F-FDG-awidnych gruczolaków przysadki u chorych z wieloma nowotworami, pamiętając, że intensywność wychwytu znacznika nie zawsze odzwierciedla biologię nowotworu

Significance of histopathological and molecular genetics investigations on the diagnosis and prognosis of astrocytic and oligodendroglial glioma

Histopathological evaluation should remain the chief support of brain tumor classification. Nevertheless, molecular genetic studies can play an important part in standardizing tumor categorization and resolving difficult diagnostic problems. These studies can be used to subdivide GBM into biologically distinct subsets and are currently being used to predict therapeutic response and survival in patients with anaplastic oligodendroglioma

Multiple cavernous hemangiomas of the orbit: Separate occurrence within a 24-year period

Background. Cavernous hemangioma is a frequent and the most common, primary, benign tumor of the orbit in adults. It is typically single and unilateral, considered not to recur after having been completely excised. Multiple orbital cavernous hemangiomas without signs of hemangiomatosis are rare. Multiple cavernous hemangiomas may recur after a complete excision and may exist with concurrent systemic tumors. Tumor recurrence is supposed to develop from vasculature that is present already in response to a proliferate stimulus. Case report. A 39-year old female with painless proptosis of the right orbit was found to have four orbital tumors. The first orbitotomy was performed in 1984 by excising four cavernous hemangiomas. Six years later, another, the fifth one cavernous hemangioma was totally excised from the same orbit. Nine years after the first operation, reorbitotomy was performed because of positive radiological and clinical signs of de novo tumor in the orbit. The operation did not confirm the tumorous tissue. The fourth orbitotomy was performed 24 years after the first operation and two cavernous hemangiomas were totally excised. Conclusion. This case show the possibility of cavernous hemangioma recurrence after a previously totally excised tumor, separated more than two decades. A very long follow-up of the patients operated for these benign tumor lesions is recommended

Value of the proliferative and hormonal markers in estimation of biological behaviour of meningioma

(Conclusion) Although the proliferative markers and hormonal (progesterone) receptor status of meningiomas seem to provide useful, convenient, and predictive criterions for the subsequent evolution of the tumor, they should be used only in combination with other established histopatological features of tumor malignancy (cellular density, nuclear pleomorphism, nucleolar prominence, mitosis and necrosis - especially multifocal micronecrosis). A simple, reproducible clear set of criteria for the tendency of a meningioma to recur is yet to be determined. In the last few years there are some new data concerning genetic characterization of meningiomas (9) and some cellular proteins (p53, p21, p27) (10) in meningioma cells which may be valuable in precisely discriminating atypical meningiomas from benign or anaplastic meningiomas, at least in histologically borderline cases

The impact of TP53 and RAS mutations on cerebellar glioblastomas

Cerebellar glioblastoma (cGBM) is a rare, inadequately characterized disease, without detailed information on its molecular basis. This is the first report analyzing both TP53 and RAS alterations in cGBM. TP53 mutations were detected in more than half of the samples from our cohort, mainly in hotspot codons. There were no activating mutations in hotspot codons 12/13 and 61 of KRAS and HRAS genes in cGBM samples but we detected alterations in other parts of exons2 and 3 of these genes, including premature induction of STOP codon. This mutation was present in 3 out of 5 patients. High incidence of RAS mutations, as well as significantly longer survival of cGBM patients compared to those with supratentorial GBM suggest that cGBM may have different mechanisms of occurrence. Our results suggest that inactivation of TP53 and MS may play an important role in the progression of cerebellar GBM. (C) 2014 Elsevier Inc. All rights reserved.Ministry of Education, Science, and Technical Development, Republic of Serbia {[}III41031

Leptomeningeal carcinomatosis can be presenting manifestation of breast carcinoma

Introduction. Leptomeningeal carcinomatosis (LC) is a serious complication occuring in solid cancer patients with rather poor prognosis. Case report. We presented a 47-yearold woman with the 6-month history of diffuse headache, nausea and visual obscuration. Initially, clinical status and brain magnetic resonance imaging (MRI) indicated syndrome of idiopathic intracranial hypertension. Due to clinical progression and high papillary stasis, cerebrospinal fluid (CSF) examination was performed only after ventriculoperitoneal shunt was implanted. This led to a significant although transient clinical improvement. Futher investigations led to the diagnosis of invasive lobular breast carcinoma and repeated CSF analysis revealed malignant breast carcinoma cells. In this case LC was an initial presentation of a malignant disease. Conclusion. In the presence of a high clinical suspicion of LC, in spite of initially negative findings, a clinician should persist in repeating relevant tests, such are MRI with larger amounts of gadolinium and high-volume cytological CSF analyses in order to make the diagnosis. [Projekat Ministarstva nauke Republike Srbije, br. 175022

Primary lymphoma of the brain in a young man whose brother died of hemophagocytic lymphohistiocytosis: Case report

Introduction. We represent the unique occurrence of primary central nervous system lymphoma (PCNSL) in a patient whose brother died of genetically confirmed hemophagocytic lymphohistiocytosis (HLH). Case Outline. We report a case of a 25-year-old male patient with primary aggressive diffuse large B-cell lymphoma affecting the brain and PCNSL. Despite one year of medical treatment outcome was lethal. However, our patient had a relatively longer survival compared to median survival time for PCNSL. Additionally, he had two older brothers who died at the age of about 11 years. One died of fulminate malignancy, shortly after pediatric admission, before the diagnosis could be established. The other one died from genetically confirmed (perforin mutation/PRF1) HLH. Our patient was heterozygous carrier of perforin mutation representing the genetic marker for HLH. Our patient’s father was the carrier of the same mutation but had no symptoms of any disease. Conclusion. This case points at the presence of HLH and diffuse large B-cell PCNSL in brothers. Extensive assessment of patients with probable PCNSL and familial HLH is necessary, including genetic analysis for HLH. [Projekat Ministarstva nauke Republike Srbije, br. 175090

Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients

Glioblastoma is the most frequent and malignant human brain tumor. High level of genomic instability detected in glioma cells implies that numerous genetic alterations accumulate during glioma pathogenesis. We investigated alterations in AP-PCR DNA profiles of 30 glioma patients, and detected specific changes in 11 genes not previously associated with this disease: LHFPL3, SGCG, HTR4, ITGB1, CPS1, PROS1, GP2, KCNG2, PDE4D, KIR3DL3, and INPP5A. Further correlations revealed that 8 genes might play important role in pathogenesis of glial tumors, while changes in GP2, KCNG2 and KIR3DL3 should be considered as passenger mutations, consequence of high level of genomic instability. Identified genes have a significant role in signal transduction or cell adhesion, which are important processes for cancer development and progression. According to our results, LHFPL3 might be characteristic of primary glioblastoma, SGCG, HTR4, ITGB1, CPS1, PROS1 and INPP5A were detected predominantly in anaplastic astrocytoma, suggesting their role in progression of secondary glioblastoma, while alterations of PDE4D seem to have important role in development of both glioblastoma subtypes. Some of the identified genes showed significant association with p53, p16, and EGFR, but there was no significant correlation between loss of PTEN and any of identified genes. In conclusion our study revealed genetic alterations that were not previously associated with glioma pathogenesis and could be potentially used as molecular markers of different glioblastoma subtypes.Ministry of Education, Science and Technological Development, Republic of Serbia [III41031