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Chordoma is a rare primary central nervous system tumour of notochordal origin. Proper intraoperative or preoperative diagnosis of this entity is crucial for appropriate surgical management. The most common histopathological subtype is conventional chordoma. Cytological characteristics of this subtype are quite distinctive and the diagnosis can be easily made by cytology. There are two particularly important features that are observed in both squash smear and fine needle aspiration specimens: an abundant myxochondroid stroma and cells with large vacuoles, including physaliferous cells. The main differential diagnosis is conventional chondrosarcoma, but in problematic cases immunohistochemical studies are useful to establish the correct diagnosis.
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Cordoma , Humanos , Biópsia por Agulha Fina , Cordoma/diagnóstico , Cordoma/patologia , Vacúolos/patologia , Diagnóstico Diferencial , CitodiagnósticoRESUMO
Colorectal cancer (CRC) is a pressing global health challenge, with an estimated 1.9 million new cases in 2020. Ranking as the third most diagnosed cancer globally, CRC accounts for nearly 930,000 cancer-related deaths annually. Nectins, immunoglobulin-like adhesion molecules, are pivotal in intercellular adhesion formation and cellular function regulation. Altered nectin expression patterns have been identified in various cancers. However, the intricacies of their role in cancer development and progression remain underexplored. This study aimed to evaluate the expression of specific nectins in CRC tumors, explore their association with clinicopathological factors, and ascertain their potential as prognostic indicators for CRC patients post-resection. We retrospectively analyzed the medical records of 92 CRC patients who underwent surgical treatment between 2013 and 2014. Tumor specimens were re-evaluated to determine nectin expression using immunohistochemistry. The study identified heterogeneous expressions of nectin-2, -3, and -4 in 58%, 62.6%, and 87.9% of specimens, respectively. Elevated nectin-4 expression correlated with worse 5-year and overall survival rates, presenting a negative prognostic value (HR = 4, 95% CI: 2.4-6.8, p < 0.001). Conversely, reduced nectin-3 expression was linked to poorer CRC prognosis (HR = 0.54; 95% CI: 0.31-0.96; p = 0.036). Nectin-4 expression positively correlated with elevated carcinoembryonic antigen (CEA) levels and advanced disease stages. In contrast, nectin-3 expression negatively correlated with CEA levels, tumor size, presence of distant metastases, and disease stage. Notably, tumors in the right colon were statistically more likely to express nectin-2 compared to those in the left. This study underscores the potential prognostic significance of nectins in CRC. The high prevalence of nectin-4-expressing cells offers promising avenues for further evaluation in targeted therapeutic interventions with already available agents such as PADCEV.
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Antígeno Carcinoembrionário , Neoplasias Colorretais , Humanos , Nectinas/metabolismo , Prognóstico , Estudos Retrospectivos , Moléculas de Adesão Celular/metabolismo , Neoplasias Colorretais/patologiaRESUMO
Primary hyperparathyroidism (PHPT) secondary to parathyroid gland adenoma is mildly symptomatic and thus often incidentally diagnosed. In this report, we present a case of a 46-year-old man who was treated for hypertension and other nonspecific complaints. An elevated level of blood calcium led to the suspicion of parathyroid adenoma. Technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI) planar and single-photon emission computed tomographic scintigraphy (SPECT/CT) confirmed the presence of a 10-mm-wide adenoma behind the sternal handle in the anterior mediastinum. The tumor was excised by Kocher's cervical access along with the right and left upper horns of the thymus gland and was histologically confirmed as being of parathyroid nature. However, blood parathyroid hormone and calcium remained persistently elevated. Repeated scintigraphy imaging revealed the presence of another retrosternal tracer focus at the level of Ludwig's angle. The patient was reoperated with the longitudinal sternotomy access, and thymus remnants, parathymic nodule, and fragments of mediastinal fat and right parietal pleura were removed. On the second postoperative day, parathyroid hormone and calcium reverted to normal values, but the patient remained hypertensive. Despite the successful surgical treatment, the patient remained hypertensive suggesting that the underlying reason was a familial hypertensive disease rather than parathyroid adenoma. In conclusion, this report underscores the need for diagnostic vigilance in the case of persisting hypercalcemia with hypertension and diagnostic and surgical difficulties in the management of ectopic PHPT secondary to parathyroid gland adenomas.
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Hiperparatireoidismo Primário , Neoplasias das Paratireoides , Humanos , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/patologia , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
The cornea, while appearing to be simple tissue, is actually an extremely complex structure. In order for it to retain its biomechanical and optical properties, perfect organization of its cells is essential. Proper regeneration is especially important after injuries and in the course of various diseases. Eph receptors and ephrin are mainly responsible for the proper organization of tissues as well as cell migration and communication. In this review, we present the current state of knowledge on the role of Eph and ephrins in corneal physiology and diseases, in particular, we focused on the functions of the epithelium and endothelium. Since the role of Eph and ephrins in the angiogenesis process has been well established, we also analyzed their influence on conditions with corneal neovascularization.
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Córnea/fisiologia , Doenças da Córnea/etiologia , Efrinas/fisiologia , Receptores da Família Eph/fisiologia , Animais , Doenças da Córnea/tratamento farmacológico , Neovascularização da Córnea/etiologia , Endotélio Corneano/patologia , Endotélio Corneano/fisiologia , Epitélio Corneano/patologia , Epitélio Corneano/fisiologia , Humanos , Terapia de Alvo MolecularRESUMO
Retinal diseases are the leading cause of irreversible blindness. They affect people of all ages, from newborns in retinopathy of prematurity, through age-independent diabetic retinopathy and complications of retinal detachment, to age-related macular degeneration (AMD), which occurs mainly in the elderly. Generally speaking, the causes of all problems are disturbances in blood supply, hypoxia, the formation of abnormal blood vessels, and fibrosis. Although the detailed mechanisms underlying them are varied, the common point is the involvement of Eph receptors and ephrins in their pathogenesis. In our study, we briefly discussed the pathophysiology of the most common retinal diseases (diabetic retinopathy, retinopathy of prematurity, proliferative vitreoretinopathy, and choroidal neovascularization) and collected available research results on the role of Eph and ephrins. We also discussed the safety aspect of the use of drugs acting on Eph and ephrin for ophthalmic indications.
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Efrinas/metabolismo , Receptores da Família Eph/metabolismo , Doenças Retinianas/patologia , Neovascularização Retiniana/patologia , Animais , Humanos , Doenças Retinianas/metabolismo , Neovascularização Retiniana/metabolismoRESUMO
PURPOSE: The American College of Radiology (ACR) BI-RADS classification is the applicable for breast lesion assessment. BI-RADS categories 4 and 5 need to be followed by biopsy. The aim of our study was to evaluate the tissue biopsy-proven positive predictive value (PPV3) for BI-RADS 4 (and its subcategories) and for BI-RADS 5, and BI-RADS distribution, in comparison to ACR assumptions and literature. MATERIAL AND METHODS: We retrospectively analysed biopsies performed in our outpatient clinic in 2017. Our target group of patients consisted of 797 patients at the average age of 52 years. RESULTS: BI-RADS 5 constituted 12% of cases (95 cases), and BI-RADS 4 88% (698 cases). Within BI-RADS 4 subdivisions there were 359 cases in 4a (45.3%), 215 in 4b (27%), and 124 in 4c (15.6%). Overall PPV3 was 34.8%. BI-RADS 5 category PPV3 number was 97.89%. In category BI-RADS 4 the values of PPV3 equalled 26.22% without subdivision and 3.6%, 27.9%, and 88.7% for subcategories BI-RADS 4a, 4b, and 4c, respectively. CONCLUSIONS: BI-RADS categorisation by radiologists in the studied group matches the literature data according to achieved PPV and BI-RADS percentage distribution. The stratification of cancer risk among categories was proven with Mann-Whitney U test p value < 0.005. There was a statistically important unaccepted difference of PPV3 between core biopsy and vacuum-assisted biopsy, which needs further investigation.
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The nectin family comprises four proteins, nectin-1 to -4, which act as cell adhesion molecules. Nectins have various regulatory functions in the immune system and can be upregulated or decreased in different tumors. The literature research was conducted manually by the authors using the PubMed database by searching articles published before 2023 with the combination of several nectin-related keywords. A total of 43 studies were included in the main section of the review. Nectins-1-3 have different expressions in tumors. Both the loss of expression and overexpression could be negative prognostic factors. Nectin-4 is the best characterized and the most consistently overexpressed in various tumors, which generally correlates with a worse prognosis. New treatments based on targeting nectin-4 are currently being developed. Enfortumab vedotin is a potent antibody-drug conjugate approved for use in therapy against urothelial carcinoma. Few reports focus on hepatocellular carcinoma, which leaves room for further studies comparing the utility of nectins with commonly used markers.
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In 2020, colorectal cancer was the third most common type of cancer worldwide with a clearly visible increase in the number of cases each year. With relatively high mortality rates and an uncertain prognosis, colorectal cancer is a serious health problem. There is an urgent need to investigate its specific mechanism of carcinogenesis and progression in order to develop new strategies of action against this cancer. Nectins and Nectin-like molecules are cell adhesion molecules that take part in a plethora of essential processes in healthy tissues as well as mediating substantial actions for tumor initiation and evolution. Our understanding of their role and a viable application of this in anti-cancer therapy has rapidly improved in recent years. This review summarizes the current data on the role nectins and Nectin-like molecules play in colorectal cancer.
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BACKGROUND: Undifferentiated round-cell sarcomas (URCSs) of soft tissue and bone are a group of clinically heterogeneous tumors. Diagnosis of these malignancies is based mainly on recurrent genetic alterations. The most common and the best known representative of this group is Ewing sarcoma (ES) which is characterized by gene fusions including EWSR1 or FUS and ETS transcription factors family. Other newly described entities are CIC-rearranged sarcoma, sarcoma with BCOR genetic alterations, and round-cell sarcoma with EWSR1-non-ETS fusions. All these novel tumors are known as Ewing-like sarcomas. SUMMARY: It is believed that morphologic features of ES and Ewing-like sarcomas vary only slightly or even that cytomorphology is not relevant. But differences are usually obvious, and some cytologic findings, such as spindle cells, connective tissue fragments, or myxoid stroma, are typical for Ewing-like sarcomas but not for ES. Each of these entities is also characterized by different immunoprofiles. The aim of this review was to summarize cytomorphologic and immunohistochemical features of URCS and compare them with other small round-cell tumors. KEY MESSAGES: Cytology can be successfully used in URCS diagnosis as a complementary tool for core-needle biopsy or even alone in selected cases, especially in recurrent and metastatic tumors. Knowing the morphologic and immunohistochemical differences between URCS is essential to provide appropriate ancillary studies and make a definitive diagnosis.
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Sarcoma de Ewing , Sarcoma , Neoplasias de Tecidos Moles , Biomarcadores Tumorais/genética , Técnicas Citológicas , Fusão Gênica , Humanos , Proteínas de Fusão Oncogênica/genética , Sarcoma/genética , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologiaRESUMO
Purpose: Full-field digital mammography (FFDM) is widely used in breast cancer screening. However, to improve cancer detection rates, new diagnostic tools have been introduced. Contrast enhanced mammography (CEM) and digital breast tomosynthesis (DBT) are used in the diagnostic setting, however their accuracies need to be compared.The aim of the study was to evaluate the diagnostic performance of CEM and DBT in women recalled from breast cancer screening program. Methods: The study included 402 consecutive patients recalled from breast cancer screening program, who were randomized into two groups, to undergo either CEM (202 patients) or DBT (200 patients). All visible lesions were evaluated and each suspicious lesion was histopathologically verified. Results: CEM detected 230 lesions; 119 were classified as benign and 111 as suspicious or malignant, whereas DBT identified 209 lesions; 105 were classified as benign and 104 as suspicious or malignant. In comparison to histopathology, CEM correctly detected cancer in 43 out of 44 cases, and DBT in all 33 cases, while FFDM identified 15 and 18 neoplastic lesions in two groups, respectively. CEM presented with 97% sensitivity, 63% specificity, 70% accuracy, 38% PPV and 99% NPV, while DBT showed 100% sensitivity, 60% specificity, 32%, PPV, 100% NPV and 66% accuracy. The CEM's AUC was 0.97 and DBT's 0.99. The ROC curve analysis proved a significant (p<0.000001) advantage of both CEM and DBT over FFDM, however, there was no significant difference between CEM and DBT diagnostic accuracies (p=0.23). Conclusions: In this randomized, prospective study CEM and DBT show similar diagnostic accuracy.
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Uveal melanomas (UMs) comprise the most common primary intraocular malignancies in adults, with the eye representing the second most common site for melanoma, following the skin. Prognosis remains poor, with approximately half of the cases presenting with metastatic disease at the time of diagnosis. Erythropoietin-producing human hepatocellular receptors (EPHs) comprise the largest known family of tyrosine receptors, in which, along with their ligands, ephrins, play an important role in a plethora of processes in human physiology, and are implicated in key steps of carcinogenesis. In the present study, EPHA2, EPHA4, and EPHA6 immunohistochemical expressions were investigated in UM tissues and further correlated to a multitude of clinicopathological parameters, including disease stage and patients' overall survival (OS). High levels of EPHA2 expression were significantly associated with increased tumor vertical thickness (p = 0.03) and the presence of intrascleral involvement (p = 0.05), whereas high EPHA6 nuclear expression was associated with older age at diagnosis (p = 0.03) and absence of retinal detachment (p = 0.05). In a multivariate survival analysis, increased EPHA4 expression was associated with shortened OS along with the presence of metastasis (p < 0.001) and monosomy 3 (p = 0.02). In a separate model, the concurrent overexpression of at least two of the investigated EPHs (HR = 14.7, p = 0.03) also proved to be an independent poor prognostic factor. In conclusion, our results implicate these specific members of the EPHA group as potential biomarkers for disease prognosis as well as possible targets for the development of novel therapeutic interventions.
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Uveal melanoma is the most common primary intraocular neoplasm in adults. As there are currently no effective methods of treating the disease in the metastatic stage, there is a need to search for new prognostic factors that would enable a reliable assessment of the patient's condition and constitute a possible therapeutic target. In this review, we have prepared the results of English-language studies on new prognostic factors determined with immunohistochemical methods. We found 64 articles in which the expression of various proteins was associated in a statistically significant manner with the histopathological and clinical prognostic factors identified by AJCC. The results of our work clearly show that the biology of uveal melanoma is extraordinarily complex. Numerous studies have shed new light on the complexity of the processes involved in the development of this cancer. Moreover, a careful analysis of the expression of individual proteins may allow the identification of homogeneous groups of patients requiring different treatment regimens.
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BACKGROUND: Uveal melanoma (UM) represents the most common primary intraocular malignancy in adults, exerting high metastatic potential and poor prognosis. Histone deacetylases (HDACs) play a key role in carcinogenesis, and HDAC inhibitors (HDACIs) are currently being explored as anti-cancer agents in clinical settings. The aim of this study was to evaluate the clinical significance of HDAC-1, -2, -4, and -6 expression in UM. METHODS: HDAC-1, -2, -4, and -6 expression was examined immunohistochemically in 75 UM tissue specimens and was correlated with tumors' clinicopathological characteristics, the presence of tumor-infiltrating lymphocytes (TILS), as well as with our patients' overall survival (OS). RESULTS: HDAC-2 was the most frequently expressed isoform (66%), whereas we confirmed in addition to the expected nuclear expression the presence of cytoplasmic expression of class I HDAC isoforms, namely HDAC-1 (33%) and HDAC-2 (9.5%). HDAC-4 and -6 expression was cytoplasmic. HDAC-1 nuclear expression was associated with increased tumor size (p = 0.03), HDAC-6 with higher mitotic index (p = 0.03), and nuclear HDAC-2 with epithelioid cell morphology (p = 0.03) and presence of tumor-infiltrating lymphocytes (p = 0.04). The association with the remaining parameters including Monosomy 3 was not significant. Moreover, the presence as well as the nuclear expression pattern of HDAC-2 were correlated with patients' improved OS and remained significant in multivariate survival analysis. CONCLUSIONS: These findings provide evidence for a potential role of HDACs and especially HDAC-2 in the biological mechanisms governing UM evolution and progression.
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BACKGROUND: Uveal melanoma is the most common primary intraocular malignancy in adults. In advanced cases, the prognosis is very poor. Thus far, no effective methods of pharmacotherapy of this cancer have been found. The aim of the study was to evaluate the expression of PARP-1, the best-known member of the family of poly(ADP-ribose) polymerases, in uveal melanoma and its associations with clinicopathological parameters, overall survival, and disease-free survival. METHODS: The study included 91 patients who underwent enucleation due to uveal melanoma. PARP-1 expression was assessed by immunohistochemistry. RESULTS: High PARP-1 expression was associated with more frequent chromosome 3 loss, higher histopathological grade, bigger tumor size, and absence of intrascleral extension. High PARP-1 expression was associated with shorter overall survival time and disease-free survival time. CONCLUSIONS: The above findings indicate that high expression of PARP-1 can be considered as an unfavorable prognostic factor in uveal melanoma.
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Imuno-Histoquímica/métodos , Melanoma/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias Uveais/tratamento farmacológico , Biomarcadores Tumorais , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Prognóstico , Neoplasias Uveais/patologiaRESUMO
OBJECTIVES: BCOR-CCNB3 sarcoma (BCS) is an undifferentiated tumor that has some clinical and morphologic similarity to classic Ewing sarcoma, but it is characterized by a distinct BCOR-CCNB3 gene fusion. There are no reports describing its cytomorphologic findings. METHODS: We describe cytologic findings of five molecularly proven BCS cases (four males and one female, aged 8.5-22 years). RESULTS: Smears showed mainly round cells, but some spindle cells and rhabdoid-like cells were also observed. Dispersed cells dominated in smears, but also distinct pseudopapillary structures with vascular cores were noted in four cases. Scant connective tissue fragments were found in four cases. There was no rosette formation in any case. CONCLUSIONS: BCS should be differentiated from other round cell tumors. Some cytologic features, especially rhabdoid-like cells, connective tissue fragments, and pseudopapillary formations, combined with immunohistochemical and molecular studies, may be helpful in making the appropriate diagnosis.
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Neoplasias Ósseas/patologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Adolescente , Biópsia por Agulha Fina , Neoplasias Ósseas/genética , Criança , Ciclina B/genética , Feminino , Humanos , Masculino , Fusão Oncogênica , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Sarcoma/genética , Neoplasias de Tecidos Moles/genética , Adulto JovemRESUMO
Uveal melanoma is the most common primary intraocular malignancy in adults. The development of distant metastases is associated with a poor prognosis. Ephrine receptors (Eph) are the largest subpopulation of tyrosine kinase receptors. They play an important role in processes related to the formation and progression of cancer. The aim of the study was to evaluate the expression of ephrin receptors EphA1, EphA5, and EphA7 in uveal melanoma and its associations with clinicopathological parameters, overall survival, and disease-free survival. The study included 94 previously untreated patients who underwent enucleation due to uveal melanoma. High expression of EphA1 was positively correlated with a smaller tumor size, less frequent extra-scleral extension, lower mitotic activity, and more frequent vitreous hemorrhage. High expression of EphA5 was associated with less frequent chromosome 3 loss, absence of distant metastases, and more frequent vitreous hemorrhage. High expression of EphA7 was associated with a more frequent primary tumor location in the posterior pole. High EphA5 expression was associated with longer overall survival time. The above findings indicate that high expression of EphA1 and EphA5 can be considered a beneficial prognostic factor in uveal melanoma.
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Ossifying fibromyxoid tumor (OFT) is a very rare soft tissue tumor which is characterized by incomplete peripheral mature bone shell. To date, cytological features of OFT have been poorly studied with only seven case reports. In this study, an additional case of OFT investigated by fine-needle aspiration is presented. A 75-year-old man with advanced nasopharyngeal carcinoma presented with peripherally calcified right breast mass. Smears were hypercellular and stroma-rich. Tumor cells were mainly dispersed, with epithelioid morphology and eccentrically located nuclei. In the background, there was abundant eosinophilic myxoid secretion. No necrosis, atypia, or mitotic activity was found. The tumor showed diffuse S-100, CD10, STAT6 expression and focal desmin, estrogen receptor (ER), and progesteron receptor (PgR) expression. Fluorescence in situ hybridization study revealed PHF1 rearrangement in 9% of cells. Cytological characteristic of OFT is quite distinctive and precise diagnosis can be made, especially when it is coupled with compatible radiological findings.
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Neoplasias da Mama Masculina/patologia , Fibroma/patologia , Ossificação Heterotópica/patologia , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biópsia por Agulha Fina , Neoplasias da Mama Masculina/metabolismo , Fibroma/metabolismo , Humanos , MasculinoRESUMO
BACKGROUND: Epithelioid sarcoma (ES) is a rare mesenchymal tumor that is divided into 2 types: classic and proximal. To the authors' knowledge, ES has been poorly studied in cytology, with fewer than 50 cases reported to date. The objective of the current study was to analyze the cytological and immunohistochemical information regarding 5 cases of ES. METHODS: Five cases of ES were analyzed: 4 of proximal type and 1 of classic type. The cases were taken from 4 female patients and 1 male patient. The patients ranged in age from 10 to 75 years. RESULTS: All smears obtained from the proximal type of ES were found to be hypercellular with a necrotic and inflammatory background. Smears from classic-type ES were hypocellular with a hemorrhagic background. Large, dispersed epithelioid cells and loosely cohesive groups of cells were most frequently noted in all cases. All cases of proximal-type ES demonstrated rhabdoid cells and marked nuclear atypia, but in only one case were rhabdoid cells found to be dominant. ES diagnoses were confirmed by immunohistochemistry in histological material. In 4 cases, epithelial marker expression was noted, whereas CD34 was found to be positive in only the classic type of ES. In 2 cases, total loss of SMARCB1/INI1 nuclear expression was observed. In the 2 SMARCB1/INI1-positive cases, loss of SMARCA2/BRM expression was observed in one case and partial loss was observed in the other case. CONCLUSIONS: The proximal type of ES differs from the classic type by the presence of rhabdoid cells and marked nuclear atypia. A specific immunohistochemical profile demonstrating loss of SMARCB1/INI1 or other proteins from the SWI/SNF complex also may be indicative of this diagnosis.