Relationship among clinical, pathological and bio-molecular features in low-grade epilepsy-associated neuroepithelial tumors

Abstract Purpose In addition to histology, genetic alteration is now required to classify many central nervous system (CNS) tumors according to the most recent World Health Organization CNS tumor classification scheme. Although that is still not the case for classifying pediatric low-grade neuroepithelial tumors (PLGNTs), genetic and molecular features are increasingly being used for making treatment decisions. This approach has become a standard clinical practice in many specialized pediatric cancer centers and will likely be more widely practiced in the near future. This paradigm shift in the management of PLGNTs necessitates better understanding of how genetic alterations influence histology and imaging characteristics of individual PLGNT phenotypes. Methods The complex association of genetic alterations with histology, clinical, and imaging of each phenotype of the extremely heterogeneous PLGNT family has been addressed in a holistic approach in this up-to-date review article. A new imaging stratification scheme has been proposed based on tumor morphology, location, histology, and genetics. Imaging characteristics of each PLGNT entity are also depicted in light of histology and genetics. Conclusion This article reviews the association of specific genetic alteration with location, histology, imaging, and prognosis of a specific tumor of the PLGNT family and how that information can be used for better imaging of these tumors.

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Low-grade serous epithelial ovarian cancer: a comprehensive review and update for radiologists

Insights into Imaging ◽

10.1186/s13244-021-01004-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Sofia Amante ◽

Filipa Santos ◽

Teresa Margarida Cunha

Keyword(s):

Ovarian Cancer ◽

Serous Carcinoma ◽

Low Grade ◽

Resonance Imaging ◽

Clinicopathologic Characteristics ◽

Borderline Tumour ◽

Molecular Features ◽

Serous Epithelial Ovarian Cancer ◽

The Difference

AbstractLow-grade serous carcinoma (LGSC) is an infrequent subtype of ovarian cancer, corresponding to 5% of epithelial neoplasms. This subtype of ovarian carcinoma characteristically has molecular features, pathogenesis, clinical behaviour, sensitivity to chemotherapy, and prognosis distinct to high-grade serous carcinoma (HGSC). Knowing the difference between LGSC and other ovarian serous tumours is vital to guide clinical management, which currently is only possible histologically. However, imaging can provide several clues that allow differentiating LGSC from other tumours and enable precise staging and follow-up of ovarian cancer treatment. Characteristically, LGSC appears as mixed lesions with variable papillary projections and solid components, usually in different proportions from those detected in serous borderline tumour and HGSC. Calcified extracellular bodies, known as psammoma bodies, are also a common feature of LGSC, frequently detectable within lymphadenopathies and metastases associated with this type of tumour. In addition, the characterisation of magnetic resonance imaging enhancement also plays an essential role in calculating the probability of malignancy of these lesions. As such, in this review, we discuss and update the distinct radiological modalities features and the clinicopathologic characteristics of LGSC to allow radiologists to be familiarised with them and to narrow the differential diagnosis when facing this type of tumour.

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O39: THE HISTOPATHOLOGICAL AND MOLECULAR FEATURES OF BREAST CARCINOMA WITH HIGH-GRADE TUMOUR BUDDING

British Journal of Surgery ◽

10.1093/bjs/znab117.039 ◽

2021 ◽

Vol 108 (Supplement_1) ◽

Author(s):

A Lloyd ◽

E Ryan ◽

M Boland ◽

S Medani ◽

Abd Elwahab ◽

...

Keyword(s):

Breast Carcinoma ◽

Epithelial To Mesenchymal Transition ◽

Lymph Node Involvement ◽

Low Grade ◽

High Grade ◽

Prognostic Variables ◽

Mesenchymal Transition ◽

Molecular Features ◽

Newcastle Ottawa Scale ◽

Tumour Budding

Abstract Background Tumour budding (TB) is an adverse histological feature in many cancers. It is thought to represent epithelial-to-mesenchymal transition, a key step in the metastatic process. The role of TB in breast carcinoma (BC) remains unclear. Aim To investigate the relationship between TB and other histological and molecular features of BC. Method A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Cochran–Mantel–Haenszel method. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale (NOS). Result Seven studies with a total of 1040 patients (high grade TB n=519, 49.9%; low grade TB n=521, 50.1%) were included. A moderate- to high-risk of bias was noted. The median NOS was 7 (range 6-8). High-grade TB was significantly associated with lymph node involvement (OR 2.28, 95% c.i. 1.74 to 2.98, P<0.001) and lymphovascular invasion (OR 3.08, 95% c.i. 2.13 to 4.47, P<0.001). Regarding molecular subtypes, there was an increased likelihood of high-grade TB in oestrogen- (OR 1.66, 95% c.i. 1.21 to 2.29, P=0.002) and progesterone-receptor positive (OR 1.68, 95% c.i. 1.10 to 2.59, P=0.02) tumours. In contrast triple negative breast cancer had a reduced incidence of high-grade TB (OR 0.46, 95% c.i. 0.30 to 0.72, P=0.0006). Conclusion High-grade TB is enriched in hormone-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic processes of luminal BC. Take-home message High-grade TB is enriched in hormone-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic processes of luminal BC.

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PATH-41. POLYMORPHOUS LOW-GRADE NEUROEPITHELIAL TUMOR OF THE YOUNG WITH FGFR3-TACC3 FUSION MIMICKING HIGH-GRADE GLIOMA: CASE REPORT AND SERIES OF HIGH-GRADE CORRELATES

Neuro-Oncology ◽

10.1093/neuonc/noab196.493 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi124-vi124

Author(s):

Danielle Golub ◽

Peter C Pan ◽

Benjamin Liechty ◽

Cheyanne Slocum ◽

Tejus Bale ◽

...

Keyword(s):

Progression Free Survival ◽

High Grade Glioma ◽

Proliferation Index ◽

Molecular Profile ◽

Low Grade ◽

High Grade ◽

Molecular Features ◽

Tert Promoter ◽

Tert Promoter Mutations ◽

Promoter Mutations

Abstract BACKGROUND Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently-described entity that can occasionally histologically and molecularly mimic high-grade glioma. The histologic and molecular features that predict aggressive behavior in FGFR3-TACC3 altered tumors are unclear. CASES We present a rare case of an indolent neuroepithelial neoplasm in a 59-year-old female with imaging initially suggestive of high-grade glioma and analyze common molecular features between this case and a series of high-grade gliomas. After total resection, pathology of the case patient revealed predominantly low-grade cytomorphology, abundant microcalcifications, unusual neovascularization, and a low proliferation index. The lesion was diffusely CD34 immunoreactive and harbored both an FGFR3-TACC3 fusion and a TERT promoter mutation. Based on the overall histologic and molecular profile, a diagnosis of PLNTY was favored. The patient was thereafter observed without adjuvant therapy with no evidence of progression at 15-month follow-up. In contrast, a series of eight adult patients with glioblastomas harboring FGFR3-TACC3 fusions and correspondingly aggressive clinical courses are also presented. Common molecular findings included IDH-wildtype status, absence of 1p19q codeletion, and CDKN2A loss. TERT promoter mutations and lack of MGMT promoter methylation were also frequently observed. These patients demonstrated a median 15-month overall survival and a 6-month progression-free survival. CONCLUSIONS PLNTY is a rare low-grade entity that can display characteristics of high-grade glioma, particularly in adults. The potential for a unique entity mimicking PLNTY which may act as a precursor lesion for a more malignant phenotype should be considered in cases with FGFR3-TACC3 fusions and other high-grade features.

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Small Lymphoid Proliferations in Extranodal Locations

Archives of Pathology & Laboratory Medicine ◽

10.5858/2007-131-383-slpiel ◽

2007 ◽

Vol 131 (3) ◽

pp. 383-396

Author(s):

Dinesh S. Rao ◽

Jonathan W. Said

Keyword(s):

B Cell ◽

Medical Center ◽

Correct Diagnosis ◽

Cell Types ◽

Correct Identification ◽

Low Grade ◽

Molecular Features ◽

Mantle Cell ◽

Ancillary Studies ◽

Widespread Dissemination

Abstract Context.—Low-grade non-Hodgkin lymphomas frequently involve extranodal sites including the gastrointestinal tract, skin, and lung, either selectively or as part of widespread dissemination. Differentiation from inflammatory or infectious conditions requires knowledge of specific histologic characteristics of the various entities as well as ancillary techniques. Objective.—To describe the key features and provide diagnostic clues to the identification of specific extranodal low-grade lymphomas of T-cell and B-cell types including small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, extranodal marginal zone B-cell lymphomas of mucosal-associated lymphoid tissue, and hairy cell leukemia. Histologic and cytologic features are highlighted, as well as appropriate integration of results of ancillary diagnostic studies including flow cytometry, immunohistochemistry, molecular features, and cytogenetics. Data Sources.—The published literature as well as personal experience from a specialized hematopathology practice at a large university medical center. Conclusions.—Correct identification of extranodal low-grade lymphomas and differentiation from hyperplastic and inflammatory or infectious processes require the ability to distinguish each of the specific entities discussed. Ancillary studies are often indispensable in reaching a correct diagnosis.

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Low-grade glioneuronal tumour with novel molecular features associated with unusual partial epilepsy in a child

BMJ Case Reports ◽

10.1136/bcr-2020-237373 ◽

2020 ◽

Vol 13 (9) ◽

pp. e237373

Author(s):

Yan Yuen Lo ◽

Denise M Malicki ◽

Michael L Levy ◽

John Ross Crawford

Keyword(s):

Partial Epilepsy ◽

Low Grade ◽

Molecular Features

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Transcriptional Characterization of Stage I Epithelial Ovarian Cancer: A Multicentric Study

Cells ◽

10.3390/cells8121554 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1554

Author(s):

Enrica Calura ◽

Matteo Ciciani ◽

Andrea Sambugaro ◽

Lara Paracchini ◽

Giuseppe Benvenuto ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Stage I ◽

Molecular Heterogeneity ◽

Low Grade ◽

Multicentric Study ◽

Molecular Alterations ◽

Molecular Features ◽

Signaling Axis ◽

Tumor Biopsies

Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs. It is characterized by a complex histopathological and molecular heterogeneity, and it is composed of five main histological subtypes (mucinous, endometrioid, clear cell and high, and low grade serous), which have peculiar genetic, molecular, and clinical characteristics. As it occurs less frequently than advanced-stage EOC, its molecular features have not been thoroughly investigated. In this study, using in silico approaches and gene expression data, on a multicentric cohort composed of 208 snap-frozen tumor biopsies, we explored the subtype-specific molecular alterations that regulate tumor aggressiveness in stage I EOC. We found that single genes rather than pathways are responsible for histotype specificities and that a cAMP-PKA-CREB1 signaling axis seems to play a central role in histotype differentiation. Moreover, our results indicate that immune response seems to be, at least in part, involved in histotype differences, as a higher immune-reactive behavior of serous and mucinous samples was observed with respect to other histotypes.

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Localized- and advanced-stage follicular lymphomas differ in their gene expression profiles

Blood ◽

10.1182/blood.2019000560 ◽

2020 ◽

Vol 135 (3) ◽

pp. 181-190 ◽

Cited By ~ 3

Author(s):

Annette M. Staiger ◽

Eva Hoster ◽

Vindi Jurinovic ◽

Stefan Winter ◽

Ellen Leich ◽

...

Keyword(s):

Gene Expression ◽

Genetic Background ◽

Cox Regression ◽

Expression Profiles ◽

Low Grade ◽

Advanced Stage ◽

Free Survival ◽

Molecular Features ◽

Clinical Stages ◽

Follicular Lymphomas

Abstract The genetic background of follicular lymphomas (FLs) diagnosed in advanced clinical stages III/IV, and which are frequently characterized by t(14;18), has been substantially unraveled. Molecular features, as exemplified in the clinicogenetic risk model m7FLIPI, are important tools in risk stratification. In contrast, little information is available concerning localized-stage FL (clinical stages I/II), which accounts for ∼20% of newly diagnosed FL in which the detection rate of t(14;18) is only ∼50%. To investigate the genetic background of localized-stage FL, patient cohorts with advanced-stage FL or localized-stage FL, uniformly treated within phase 3 trials of the German Low-Grade Lymphoma Study Group, were comparatively analyzed. Targeted gene expression (GE) profiling of 184 genes using nCounter technology was performed in 110 localized-stage and 556 advanced-stage FL patients. By penalized Cox regression, a prognostic GE signature could not be identified in patients with advanced-stage FL, consistent with results from global tests and univariate regression. In contrast, it was possible to define robust GE signatures discriminating localized-stage and advanced-stage FL (area under the curve, 0.98) by penalized logistic regression. Of note, 3% of samples harboring an “advanced-stage signature” in the localized-stage cohort exhibited inferior failure-free survival (hazard ratio [HR], 7.1; P = .0003). Likewise, in the advanced-stage cohort, 7% of samples with a “localized-stage signature” had prolonged failure-free survival (HR, 2.3; P = .017) and overall survival (HR, 3.4; P = .072). These data support the concept of a biological difference between localized-stage and advanced-stage FL that might contribute to the superior outcome of localized FL.

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Tubular Carcinoma of the Breast: Further Evidence to Support Its Excellent Prognosis

Journal of Clinical Oncology ◽

10.1200/jco.2009.23.5051 ◽

2010 ◽

Vol 28 (1) ◽

pp. 99-104 ◽

Cited By ~ 103

Author(s):

Emad A. Rakha ◽

Andrew H.S. Lee ◽

Andrew J. Evans ◽

Sindhu Menon ◽

Nancy Y. Assad ◽

...

Keyword(s):

Ductal Carcinoma ◽

Disease Free Survival ◽

Distinct Type ◽

Second Primary ◽

Low Grade ◽

Breast Cancers ◽

Luminal A ◽

Cancer Specific Survival ◽

Tubular Carcinoma ◽

Molecular Features

Purpose Although tubular carcinoma (TC) is known to have a favorable prognosis, it is still unknown whether this subtype represents a distinct type of breast carcinoma or whether it behaves like other low-grade luminal A–type breast carcinomas. Methods In this study, we performed a retrospective analysis of a large well-characterized series of breast cancers (2,608 carcinomas) to assess the clinicopathologic and molecular features and prognostic value of TC compared with grade 1 ductal carcinomas of the breast. Results When compared with grade 1 ductal carcinoma (n = 212), TC (n = 102) was more likely to be detected on mammographic screening, had smaller median size, and less frequently showed lymphovascular invasion. Compared with grade 1 ductal carcinoma, TC was associated with longer disease-free survival (χ2 = 13.25, P < .001) and breast cancer–specific survival (χ2 = 8.8, P = .003). In this study, none of the patients with TC developed distant metastasis or died from the disease without an intervening recurrence as invasive carcinoma of different histologic type. Conclusion We conclude that the biologic behavior of TC is excellent and is more favorable than that of grade 1 ductal carcinoma. Patients with TC may be at risk of developing second primary carcinomas in the contralateral breast, which may be of higher grade and poorer potential prognostic outcome. In addition, patients with TC seem to have a close to normal life expectancy, and as a consequence, adjuvant systemic therapy may not be justified in their routine management.

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Pancreatic Solid Pseudopapillary Neoplasm: Key Pathologic and Genetic Features

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2019-0473-ra ◽

2020 ◽

Vol 144 (7) ◽

pp. 829-837 ◽

Cited By ~ 4

Author(s):

Stefano La Rosa ◽

Massimo Bongiovanni

Keyword(s):

Good Prognosis ◽

Low Grade ◽

Solid Pseudopapillary Neoplasm ◽

Prognostic Features ◽

Molecular Alterations ◽

Immunohistochemical Markers ◽

Molecular Features ◽

Pubmed Database ◽

Genetic Features ◽

Solid Pseudopapillary Neoplasms

Context.— Solid pseudopapillary neoplasm of the pancreas is a low-grade malignant tumor generally associated with a good prognosis. Solid pseudopapillary neoplasms show peculiar morphologic features, but sometimes the differential diagnosis with other pancreatic neoplasms (ie, pancreatic neuroendocrine tumors) can be a challenging task, especially in cytologic or biopsy specimens. In these cases immunohistochemistry is a useful tool, but the diagnostic utility of several proposed immunohistochemical markers is questionable. In recent years, despite several attempts to characterize the pathogenetic, molecular, and prognostic features of solid pseudopapillary neoplasms, they still remain unclear. Objective.— To give the reader a comprehensive update on this entity. Data Sources.— The PubMed database (US National Library of Medicine) was searched using the following string: pseudopapillary tumor [AND/OR] neoplasm [AND/OR] pancreas. All articles written in English were included. In addition, because a heterogeneous terminology has been used in the past to define solid pseudopapillary neoplasms, the reference lists of each paper selected in the PubMed database were also reviewed. Conclusions.— This review gives a comprehensive update on the pathologic, clinical, and molecular features of solid pseudopapillary neoplasms, particularly addressing issues and challenges related to diagnosis. In addition, we have tried to correlate the molecular alterations with the morphologic and clinical features.

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