Mariana Costache

Carol Davila University of Medicine and Pharmacy

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Co-Authors

Adrian Dumitru

Carol Davila University of Medicine and Pharmacy

Maria Sajin

Carol Davila University of Medicine and Pharmacy

Olga Simionescu

Carol Davila University of Medicine and Pharmacy

Oana Maria Pătraşcu

Carol Davila University of Medicine and Pharmacy

Stefan G. Stanciu

Universitatea Națională de Știință și Tehnologie Politehnica București

Anca Mihaela Lăzăroiu

Clinical Emergency Hospital Bucharest

Radu Hristu

Universitatea Națională de Știință și Tehnologie Politehnica București

Monica Mihaela Cîrstoiu

Emergency University

Dana Antonia Țăpoi

Carol Davila University of Medicine and Pharmacy

A Oproiu

Carol Davila University of Medicine and Pharmacy

Cooperative Institutions

Carol Davila University of Medicine and Pharmacy

159

Clinical Emergency Hospital Bucharest

129

Emergency University

University of Bucharest

Amita Health St. Mary's Hospital

Universitatea Națională de Știință și Tehnologie Politehnica București

Bucharest Emergency University Hospital

Institutul de Pneumoftiziologie "Marius Nasta"

Institutul National Victor Babes

Institutul Clinic Fundeni

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Investigating and Assessing the Dermoepidermal Junction with Multiphoton Microscopy and Deep Learning

bioRxiv (Cold Spring Harbor Laboratory) (2019)

Mikko J. Huttunen Radu Hristu Adrian Dumitru Mariana Costache Stefan G. Stanciu

Abstract Histopathological image analysis performed by a trained expert is currently regarded as the gold-standard in the case of many pathologies, including cancers. However, such approaches are laborious, time consuming and contain a risk for bias or human error. There is thus a clear need for faster, less intrusive and more accurate diagnostic solutions, requiring also minimal human intervention. Multiphoton Microscopy (MPM) can alleviate some of the drawbacks specific to traditional histopathology by exploiting various endogenous optical signals to provide virtual biopsies that reflect the architecture and composition of tissues, both in-vivo or ex-vivo. Here we show that MPM imaging of the dermoepidermal junction (DEJ) in unstained tissues provides useful cues for a histopathologist to identify the onset of non-melanoma skin cancers. Furthermore, we show that MPM images collected on the DEJ, besides being easy to interpret by a trained specialist, can be automatically classified into healthy and dysplastic classes with high precision using a Deep Learning method and existing pre-trained Convolutional Neural Networks. Our results suggest that Deep Learning enhanced MPM for in-vivo skin cancer screening could facilitate timely diagnosis and intervention, enabling thus more optimal therapeutic approaches.

Dermoepidermal junction

Ex vivo

Gold standard (test)

Histopathology

10.1101/743054

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Citations (1)

Immunohistochemistry and Biochemistry Features of Interstitial Mesenchymal Cells in Ischemic Cardiac Diseases

Revista de Chimie (2020)

Zenaida Ceauşu Bogdan Socea Mihai Dimitriu D Gheorghiu Irina Pacu

In the cardiac remodelling game, the casting is represented by certain players in form of four mesenchymal cells: one main player, represented by the fibroblast /and three secondary players, represented by the endothelial cell, vascular smooth muscle cell and the cardiac stem cell. The fibroblast plays a role in recruiting inflammatory cells (PMN, macrophages) in the primary secretory phase and another role in extracellular matrix remodelling in the secondary proliferative phase. Myofibroblasts are mesenchymal cells that, due to their phenotype, are often described as a bridge between fibroblasts and smooth muscle. The endothelial cells and vascular smooth muscle cells are involved in vascular remodelling, while the cardiac stem cells are involved in cardiogenesis, but at a slow rate. Last, but not least, there are transient players, in the very first moments of the game, represented by the inflammatory cells (PMN, macrophages), which clean the injured (necrobiotic) area, paving the way for the myofibroblast to cardiac remodelling. Ischemic lesions, as well as cardiac tumours produce a large variety of symptoms and changes in extracellular matrix composition.

Myofibroblast

Cardiac muscle

Matrix (chemical analysis)

Cell type

10.37358/rc.20.7.8261

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Citations (1)

Cutaneous verrucous carcinoma - report of three cases with review of literature.

PubMed (2014)

Mariana Costache Laura Tatiana Desa L Mitrache Oana Maria Pătraşcu Adrian Dumitru

Verrucous carcinoma is a rare variant of squamous cell carcinoma. It is well differentiated and rarely metastases but can sometimes be very aggressive locally in depth. The paper presents three cases of cutaneous verrucous carcinoma with different localizations. The first patient shows a lesion in the sacrogluteal region, the second one presented a tumor localized on the auricle (external ear), and the third patient showed a tumor on the sole of the foot. All patients underwent tumor excision and the histopathological diagnosis was verrucous carcinoma. In the first two cases, the surgery was completely curative by excision of the tumors. In the last case, the patient had relapsed and due to the aggressive nature of the tumor, which infiltrated the deeper plans, the tumor had reached the bone. None of the patients showed any metastases.

Verrucous carcinoma

Auricle

Surgical excision

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Citations (18)

Fibroblast involvement in cardiac remodeling and repair under ischemic conditions

Experimental and Therapeutic Medicine (2021)

Zenaida Ceauşu Bogdan Socea Mariana Costache Dragoş Predescu Dragoș Șerban

Cardiac fibroblasts play a main role in the physiological turnover of the extracellular matrix, as well as its pathological remodeling. A study was performed on a batch of 23 cases who died of various cardiac complications secondary to scarring myocardial infarctions. The aim of the study was to assess the fibroblast involvement in cardiac repair under ischemic conditions after myocardial infarction. Tissue myocardial samples from the left ventricle were taken from these cases for microscopy examination, in order to investigate the type and degree of fibrosis as well as the presence of cardiac interstitial fibroblasts. Multiple series of histological sections were also performed and examined, along with immunohistochemical analysis. The fibroblasts were diffusely distributed in the interstitium among the residual cardiomyocytes, showing variable expression of vimentin and smooth muscle actin. During cardiac remodeling, there was a successive interstitial deposition, first of reticulin fibers and then of collagen fibers, leading to interstitial fibrosis and myocardial replacement. There was a correlation between vimentin and smooth muscle actin expression and collagen deposition. Fibrosis with cardiac remodeling is based on maintaining proliferation capacity of the fibroblast and its capacity of protein synthesis in the extracellular matrix. Under hypoxic ischemic conditions, followed by myocardial infarction, the fibroblast switches phenotype and transdifferentiate into myofibroblast, contributing to the healing by secreting extracellular matrix proteins and collagen deposition, with subsequent cardiac remodeling and regulation of the micro‑environment metabolism.

Myofibroblast

Cardiac Fibrosis

Ventricular remodeling

Myocardial fibrosis

10.3892/etm.2021.9700

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Citations (6)

Cutaneous melanoma arising on pre-existing nevi - case reports.

PubMed (2019)

Ioana Mihaela Dogaru Natalia Dumitrescu A Oproiu Cristian Radu Jecan Mariana Costache

Skin cancer is a common healthcare issue that affects millions of people worldwide. Only a small part of that population is suffering from melanoma and an even smaller proportion has melanoma developed on a pre-existing nevus. This paper illustrates five such cases, diagnosed over an 18-month period, with their histological particular aspects. Among the total number of patients diagnosed and treated in the Department of Plastic and Reconstructive Surgery, University Emergency Hospital, Bucharest, Romania, over approximately one year, of which half for melanoma in general or for benign nevi, only a small fraction had developed melanoma on a common or dysplastic nevus. These patients, as well as those with de novo developed melanoma, are a reason for concern since most of the lesions were diagnosed in a locally advanced stage of the disease. Though efforts are being made to screen and diagnose early, there are still a lot to be done in order to lower the mortality and morbidity rates for this pathology.

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Histopathological diagnosis of cutaneous vascular sarcomas.

PubMed (2010)

Mariana Costache Ana Maria Ene Olga Simionescu Maria Sajin

Cutaneous sarcomas represent a heterogeneous group of mesenchymal lesions. This study investigates the histopathological and immunohistochemical features in different cases of angiosarcoma and Kaposi's sarcoma (cutaneous vascular sarcomas), which are representative for medical practice. The clinical-histopathological-immunohistochemical correlations render possible the differential diagnosis and a proper treatment can be applied to obtain a favorable prognosis.

Histopathological examination

Histopathology

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Citations (11)

Morphological and immunohistochemical diagnostic of extragastrointestinal stromal tumors – a 51 case series analysis

Romanian Journal of Morphology and Embryology (2022)

Valentin Tiberiu Moldovan Oana Maria Pătraşcu L. Ahmed Ali Mariana Costache Maria Sajin

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract, originating from structures differentiating towards Cajal cells. Due to their morphology and localization, the extragastrointestinal stromal tumors (EGISTs) can be a diagnostic challenge. We investigated a series of 51 EGISTs diagnosed in our institutions, aiming to explore the immunophenotypes and to analyze the process and the utility of the antibodies required for a positive diagnosis. Immunohistochemical examinations were done for pan-cytokeratin (pan-CK), Ki67, discovered on GIST1 (DOG1) protein and platelet-derived growth factor receptor alpha (PDGFRA), as necessary. The main tumor site was abdominal wall in 43 (84%) cases, most of the tumors showed spindle cell cellularity, followed by mixed and epithelioid type. Twenty-six cases revealed a full conventional immunohistochemical profile with DOG1 positivity. In 10 cases, c-KIT expression was absent but with the preservation of cluster of differentiation (CD)34 positivity, and eight cases were positive for PDGFRA. In our study, we found a subgroup of eight cases presenting in extra-abdominal settings (including one in lung and two in the head-and-neck area). We concluded EGISTs represent a histopathological and immunohistochemically challenging subgroup testing more often negative for c-KIT mutations and positive for PDGFRA compared to GIST. DOG1 remains the marker of choice regardless of tumor site, while CD34 and CD117 should be considered as adjuvants.

10.47162/rjme.62.4.13

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Metastatic Nodular Melanoma with Angiosarcomatous Transdifferentiation—A Case Report and Review of the Literature

Diagnostics (2024)

Adrian Dumitru Dana Antonia Țăpoi Mariana Costache Ana Maria Ciongariu Andreea-Iuliana Miron

Diagnosing cutaneous melanomas relies mainly on histopathological analysis, which, in selected cases, can be aided by immunohistochemical evaluation of conventional melanocytic markers. Nevertheless, these malignancies, particularly in metastatic settings, may display divergent differentiation with unusual histological and immunohistochemical features. In this context, we present the case of a 65-year-old male diagnosed with typical superficial spreading melanoma who developed recurrence and metastatic lesions featuring angiosarcomatous differentiation. The diagnosis of the initial tumour and the subsequently dedifferentiated lesions was confirmed by ample immunohistochemical analysis, which included several melanocytic markers, as well as mesenchymal and vascular markers. The recurrent tumour and lymph nodes metastases were completely negative for Melan-A and PRAME, and focally positive for SOX10. Additionally, they also displayed diffuse, intense positivity for CD10 and WT1 and focal positivity for CD99, ERB, and CD31. Thus, the diagnosis of primary cutaneous melanoma with recurrent and metastatic divergent angiosarcomatous differentiation was established. This occurrence is particularly rare and can pose important diagnostic challenges. Therefore, in addition to presenting this highly unusual case, we also performed a comprehensive review of the literature on divergent differentiation in melanomas.

CD31

CD99

Transdifferentiation

10.3390/diagnostics14131323

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Citations (4)

Parotid Gland Tumors: Molecular Diagnostic Approaches

International Journal of Molecular Sciences (2024)

Daniela Vrînceanu Mihai Dumitru Miruna Bratiloveanu Andreea Marinescu Crenguța Șerboiu

Parotid gland pathology represents a web of differential diagnoses. There are many complex cases that require extensive diagnostic tests for a complete and correct final pathology diagnosis. Currently the official classification of parotid gland tumors extends over more than 40 subtypes. We performed a query of the PubMed database regarding the use of molecular biology tests in performing a better characterization of the tumors in specific cases. By using fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR) or next-generation sequencing, the team managing complex cases can offer a personalized therapeutic solution. We review the molecular differential diagnosis according to published articles in the last 5 years for many types of parotid gland tumors ranging from benign to borderline malign tumors to malign aggressive tumors. Mucoepidermoid carcinoma is a distinct subtype of parotid malignancy that was the subject of a consistent number of articles. However, the molecular biology diagnosis techniques helped more in excluding the diagnosis of mucoepidermoid carcinoma, and probably retrospectively limiting the number of cases with this final diagnosis. In Romania, the molecular biology diagnosis is available only in limited research facilities and should receive more consistent funding that will make it available on a larger scale. The novelty of this scoping review is that we propose an algorithm for molecular differential diagnosis of the tumors that could be encountered in the parotid gland.

10.3390/ijms25137350

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The Impact of Clinical and Histopathological Factors on Disease Progression and Survival in Thick Cutaneous Melanomas

Biomedicines (2023)

Dana Antonia Țăpoi Diana Derewicz Ancuța-Augustina Gheorghișan-Gălățeanu Adrian Dumitru Ana Maria Ciongariu

Thick cutaneous melanomas (Breslow depth > 4 mm) are locally advanced tumors, generally associated with poor prognosis. Nevertheless, these tumors sometimes display unpredictable behavior. This study aims to analyze clinical and histopathological features that can influence the prognosis of thick melanomas. This is a retrospective study on 94 thick primary cutaneous melanomas diagnosed between 2012 and 2018 that were followed-up for at least five years to assess disease progression and survival. We evaluated the age, gender, tumor location, histological subtype, Breslow depth, Clark level, resection margins, mitotic index, the presence/absence of ulceration, necrosis, regression, microsatellites, neurotropism, lymphovascular invasion, and the pattern of tumor-infiltrating lymphocytes, and their association with disease progression and survival. By conducting univariate analysis, we found that progression-free survival (PFS) was significantly associated with female gender, the superficial spreading melanoma (SSM) subtype, mitotic index, necrosis, microsatellites, and perineural invasion. Overall survival (OS) was significantly associated with female gender, Breslow depth, SSM subtype, necrosis, microsatellites, and perineural invasion. Through multivariate Cox proportional hazards regression, we found that the only factors associated with PFS were Breslow depth, necrosis, microsatellites, and perineural invasion, while the factors associated with OS were Breslow depth, necrosis, microsatellites, and perineural invasion. Certain histopathological features such as Breslow depth, necrosis, microsatellites, and perineural invasion could explain differences in disease evolution. This is one of the first studies to demonstrate an association between necrosis and perineural invasion and outcomes in patients with thick melanomas. By identifying high-risk patients, personalized therapy can be provided for improved prognosis.

Breslow Thickness

Perineural invasion

Lymphovascular invasion

Mitotic index

10.3390/biomedicines11102616

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Citations (6)