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In the setting of pronounced inflammation, changes in the epithelium may overlap with neoplasia, often rendering it impossible to establish a diagnosis with certainty in daily clinical practice. Here, we discuss the underlying molecular mechanisms driving tissue response during persistent inflammatory signaling along with the potential association with cancer in the gastrointestinal tract, pancreas, extrahepatic bile ducts, and liver. We highlight the histopathological challenges encountered in the diagnosis of chronic inflammation in routine practice and pinpoint tissue-based biomarkers that could complement morphology to differentiate reactive from dysplastic or cancerous lesions. We refer to the advantages and limitations of existing biomarkers employing immunohistochemistry and point to promising new markers, including the generation of novel antibodies targeting mutant proteins, miRNAs, and array assays. Advancements in experimental models, including mouse and 3D models, have improved our understanding of tissue response. The integration of digital pathology along with artificial intelligence may also complement routine visual inspections. Navigating through tissue responses in various chronic inflammatory contexts will help us develop novel and reliable biomarkers that will improve diagnostic decisions and ultimately patient treatment.
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Inteligência Artificial , Neoplasias , Humanos , Animais , Camundongos , Neoplasias/diagnóstico , Inflamação , Biomarcadores , Hiperplasia , Sistema DigestórioRESUMO
The interaction of programmed death-1 (PD-1) on T lymphocytes with its ligands Programmed Death Ligand 1 (PD-L1) and Programmed Death Ligand 2 (PD-L2) on tumor cells and/or tumor-associated macrophages results in inhibitory signals to the T-cell receptor pathway, consequently causing tumor immune escape. PD-L1/PD-L2 are currently used as predictive tissue biomarkers in clinical practice. Virtually PD-L1 levels expressed by tumor cells are associated with a good response to immune checkpoint blockade therapies targeting the PD-1/PD-L1 axis. These therapies restore T-cell antitumor immune response by releasing T-lymphocytes from the inhibitory effects of tumor cells. Immune checkpoint therapies have completely changed the management of patients with solid cancers. This therapeutic strategy is less used in hematological malignancies, although good results have been achieved in some settings, such as refractory/relapsed classic Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Variable results have been obtained in diffuse large B-cell lymphoma and T-cell lymphomas. Immunohistochemistry represents the main technique for assessing PD-L1 expression on tumor cells. This review aims to describe the current knowledge of PD-L1 expression in various types of lymphomas, focusing on the principal mechanisms underlying PD-L1 overexpression, its prognostic significance and practical issues concerning the evaluation of PD-L1 immunohistochemical results in lymphomas.
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Antígeno B7-H1 , Linfoma , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Linfoma/metabolismo , Linfoma/genética , Linfoma/patologia , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Inibidores de Checkpoint Imunológico/uso terapêuticoRESUMO
Breast carcinoma is the most common cancer in women. Nineteen different subtypes of breast carcinomas are recognized in the current WHO classification of breast tumors. Except for these subtypes, there are a number of carcinomas with special morphologic and immunohistochemical features that are not included in the 5th WHO classification, while others are considered special morphologic patterns of invasive breast carcinoma of no special type. In this manuscript, we systematically review the literature on four different subtypes of invasive breast carcinoma, namely lymphoepithelioma-like breast carcinoma, breast carcinoma with osteoclast-like giant cells, signet-ring breast carcinoma, and metaplastic breast carcinoma with melanocytic differentiation. We describe their clinicopathological characteristics, focusing on the differential diagnosis, treatment, and prognosis.
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Neoplasias da Mama , Organização Mundial da Saúde , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/classificação , Neoplasias da Mama/diagnóstico , Feminino , Prognóstico , Diagnóstico DiferencialRESUMO
Nasopharyngeal lymphoepithelioma is an undifferentiated carcinoma in a dominated lymphoplasma-histiocyte stroma. Lymphoepithelioma-like carcinoma of the breast is the mammary counterpart of the lymphoepithelioma of the nasopharynx and is characterised by proliferation of poorly differentiated malignant cells within a prominent lymphoid infiltrate. It is a very rare primary carcinoma of the breast first reported in 1994 by Kumar and Kumar. Fewer than 40 cases have been reported in the English literature. In this manuscript a case of lymphoepithelioma-like carcinoma of the breast in a 57-year-old patient is reported along with a literature review on this rare entity.
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Neoplasias da Mama/patologia , Carcinoma/patologia , Linfócitos/patologia , Biomarcadores Tumorais/análise , Biópsia , Neoplasias da Mama/química , Neoplasias da Mama/cirurgia , Carcinoma/química , Carcinoma/cirurgia , Diferenciação Celular , Proliferação de Células , Feminino , Humanos , Imuno-Histoquímica , Linfócitos/química , Pessoa de Meia-IdadeRESUMO
PURPOSE: Inguinofemoral metastases are a major determinant of vulvar cancer relapse. Until today, the impact of micrometastases of inguinal nodes on local recurrence rates of patients with vulvar cancer remains unknown. The purpose of this retrospective study is to evaluate the rates of micrometastases in a series of patients with vulvar cancer treated with radical vulvectomy and inguinofemoral LND and to assess the probability of cancer relapse among this specific category. METHODS: We conducted a retrospective observational study on patients with vulvar cancer who attended the gynaecological department of Anticancer Hospital of St. Savvas between January 1989 and January 2007. Ultra-staging of lymph nodes for micrometastases was performed after cutting the remaining specimens with a microtome in multiple slices of 3 µm. Subsequently they were stained with traditional hematoxylin and eosin and CK AE1/AE3 antibodies for immunohistochemichal analysis. RESULTS: Ninety-two patients with primary vulvar malignancies were included in the present retrospective study. Ultrastaging of the lymph nodes revealed micrometastases in five patients (5.4%). Neither the duration of the procedure, nor the number of retrieved lymph nodes was directly associated with the presence of micrometastases. The patients were followed up for more than 5 years. Sixteen recurrences (17.4%) occurred during this period. The presence of micrometastases did not influence the recurrence rate (OR 3.57, 95% CI 0.55-23.36, p = 0.184). CONCLUSION: Ultrastaging of inguinal nodes does not seem to add any benefit in the prediction of local recurrence rates. Future multicenter studies are needed in the field to corroborate our findings.
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Micrometástase de Neoplasia , Neoplasias Vulvares/patologia , Idoso , Feminino , Virilha/patologia , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Malignant Brenner tumors are rare ovarian tumors, accounting for less than 1% of malignant ovarian neoplasms. The aim of this manuscript is to systematically review the current literature concerning malignant Brenner tumors. METHODS: We searched three medical databases (PubMed, Scopus, and Web of Science) for relevant articles published until 15 September 2023. RESULTS: After applying inclusion and exclusion criteria, 48 manuscripts describing 115 cases were included in this study from the English literature. CONCLUSIONS: We analyzed the demographic, clinical, pathological, and oncological characteristics of 115 patients with malignant Brenner tumors. The statistical analysis showed that recurrence was marginally statistically significantly related to tumor stage and was more common in patients with ascites and in women with abnormal CA-125 levels; patients that were treated with lymphadenectomy had better disease-specific survival.
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Myeloproliferative neoplasms (MPNs) are subdivided into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) and Ph-negative MPNs. BCR::ABL1 translocation is essential for the development and diagnosis of CML; on the other hand, the majority of Ph-negative MPNs are characterized by generally mutually exclusive mutations of Janus kinase 2 (JAK2), calreticulin (CALR), or thrombopoietin receptor/myeloproliferative leukemia (MPL). CALR mutations have been described essentially in JAK2 and MPL wild-type essential thrombocythemia and primary myelofibrosis. Rarely coexisting CALR and MPL mutations have been found in Ph-negative MPNs. BCR::ABL1 translocation and JAK2 mutations were initially considered mutually exclusive genomic events, but a discrete number of cases with the combination of these genetic alterations have been reported. The presence of BCR::ABL1 translocation with a coexisting CALR mutation is even more uncommon. Herein, starting from a routinely diagnosed case of CALR-mutated primary myelofibrosis subsequently acquiring BCR::ABL1 translocation, we performed a comprehensive review of the literature, discussing the clinicopathologic and molecular features, as well as the outcome and treatment of cases with BCR::ABL1 and CALR co-occurrence.
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Paraganglioma of the urinary bladder is an exceptionally rare tumor. It originates from chromaffin cells, which are responsible for producing catecholamines. We report a unique case of a 74-year-old woman diagnosed with nonfunctional bladder paraganglioma, who presented with macroscopic hematuria and right-sided renal colic but lacked the usual symptoms associated with catecholamine excess. This case highlights the diagnostic challenges of nonfunctional variants of paraganglioma due to their histological similarity to urothelial carcinomas. It underscores the importance of a thorough histological examination and the need for a multidisciplinary approach to establish a diagnosis and determine the optimal treatment strategy. Our case contributes to the sparse literature on this rare condition, and it aims to enhance clinicians' awareness and understanding of urinary bladder paragangliomas.
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Nasal chondromas and nasal atypical cartilaginous tumors (or chondrosarcoma grade 1) are very rare chondrogenic tumors. Approximately 150 cases of nasal chondroma and fewer than 50 cases of nasal atypical cartilaginous tumors have been described. We reported a case with nasal chondroma in the right ethmoid area and a case with a nasal atypical cartilaginous tumor of the anterior septum. No chondroma recurrence was noted for 17 years after endoscopic resection. Recurrence was noted for the nasal atypical cartilaginous tumor 36 months after wide surgical excision via midfacial degloving. Revision surgery was performed again via midfacial degloving. Recurrences of nasal chondroma and atypical cartilaginous tumors are extremely rare. The current data indicate adequate surgical excision, in some cases even radical, as the most important parameter to avoid recurrence. For inoperable recurrent cases of atypical cartilaginous tumors, observation may be followed.
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Neoplasias Ósseas , Condroma , Condrossarcoma , Humanos , Condroma/cirurgia , Condroma/patologia , Condrossarcoma/cirurgia , Condrossarcoma/patologiaRESUMO
Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss Syndrome, is a multisystem antineutrophil cytoplasmic antibody (ANCA) positive vasculitis, characterized by the presence of chronic rhinosinusitis, asthma and prominent peripheral blood eosinophilia. Although the most commonly involved organ is the lung, followed by the skin, EGPA can affect any organ system. Herein, we present the complicated case of an 18-year-old male patient with severe life-threatening EGPA, with central nervous system, cardiac and gasterointestinal involvement, which was resistant to initial treatment with glucocorticoids and cyclophosphamide. The patient responded well, achieving complete remission after the addition of rituximab and mepolizumab to glucocorticoids and cyclophosphamide.
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Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Masculino , Humanos , Adolescente , Rituximab/uso terapêutico , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/tratamento farmacológico , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Glucocorticoides , Ciclofosfamida/uso terapêutico , Anticorpos Anticitoplasma de NeutrófilosRESUMO
INTRODUCTION: Breast cancer affects almost 1.5 million women worldwide below the age of 45 years each year. Many of these women will be advised to undergo adjuvant chemotherapy to minimize the risk of death or recurrence of the tumor. For these patients, chemotherapy is a known cause of infertility, as it can damage primordial follicles, which can lead to early menopause or premature ovarian insufficiency. This systematic review aims to synthesize the current evidence of the most suitable treatments for fertility preservation. METHODOLOGY: This review was performed following the PRISMA guidelines. The authors conducted an extensive search from the last 15 years. Relevant studies were pursued in PubMed, Embase, and the Cochrane Library up until 31 July 2023. A total of seven eligible studies were identified. RESULTS: From the reviewed literature, ovarian suppression with gonadotropin-releasing hormone agonists showed promising results in preserving fertility for breast cancer patients undergoing chemotherapy. Additionally, oocyte and embryo cryopreservation demonstrated successful outcomes, with embryo cryopreservation being the most effective option. Notably, the slow-freezing and vitrification methods were both effective in preserving embryos, with vitrification showing superior results in clinical-assisted reproductive technologies. Ovarian tissue cryopreservation emerged as a viable option for prepubertal girls and those unable to undergo conventional ovarian stimulation. The potential of in vitro maturation (IVM) as an alternative method presents a promising avenue for future fertility preservation research. DISCUSSION: The most suitable treatments for fertility preservation in young patients is the temporary suppression with luteinizing hormone-releasing analogs, while the patient undergoes chemotherapy and cryopreservation. For cryopreservation, the physicians might deem it necessary to either cryopreserve ovarian tissue taken from the patient before any treatment or cryopreserve embryos/oocytes. Cryopreservation of oocytes and/or embryos is the most effective solution for fertility preservation in women of reproductive age, who have a sufficient ovarian reserve and are diagnosed with breast cancer, regardless of the histological type of the tumor. Because approximately 50% of young breast cancer patients are interested in becoming pregnant right after completion of therapy, the evolution and development of fertility preservation techniques promise to be very exciting.
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Background: Human papilloma virus (HPV) is considered a successful pathogen as it has the ability to evade host immune responses and establish long-term persistent infection. It has been reported that programmed death ligand 1 (PDL-1) expression is correlated with HPV-positivity and is increased with lesion progression or tumor metastasis in cervical cancer. The expression of microRNAs (miRNAs) is often deregulated in cancer, and their potential targets are affected. Methods: RNA was extracted from formalin-fixed paraffin-embedded (FFPE) cervical samples of different histological types, previously typed for the presence of HPV. A specific quantitative polymerase chain reaction (qPCR) protocol with SYBR Green was used to check for the expression of four miRNAs that were computationally predicted to target PDL-1. Results and conclusion: hsa-miR-20a-5p and hsa-miR-106b-5p showed an expression increase with the severity of the lesions, while hsa-miR-125b-5p depicted a significant decrease in its expression in cancerous samples when compared to normal samples.
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Higher mammographic breast density in premenopausal and postmenopausal women is related to a higher breast cancer risk. In this review, we analyze the correlation between estrogen, progesterone, and mammographic density in postmenopausal women and clarify whether these findings are consistent across different types of mammographic breast density. We extracted data concerning mammographic density increases in the populations treated with estrogen-only hormone replacement therapy and those treated with estrogen and progestin hormone replacement therapy. Postmenopausal women treated with estrogen and progesterone regimens had a statistically significant lesser mammographic density increase than estrogen-only hormone replacement therapy regimens.
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BACKGROUND: Axillary lymph node metastasis is a rare stage IV ovarian carcinoma manifestation. This manuscript aims to systematically review the literature regarding axillary lymph node metastasis from ovarian carcinoma. METHODS: We searched three medical internet databases (PubMed, Scopus, and Web of Science) for relevant articles published until 22 July 2023. Cases describing supraclavicular or intramammary lymph node metastases and concurrent metastasis to the breast were excluded. RESULTS: After applying eligibility/inclusion and exclusion criteria, twenty-one manuscripts describing twenty-five cases were included from the English literature. Data were collected and analyzed regarding demographic, clinical, laboratory, radiological, histopathological, and oncological characteristics. CONCLUSIONS: We analyzed the clinical and oncological characteristics of patients with axillary lymph node metastasis from ovarian carcinoma, presented either as an initial diagnosis of the disease or as a recurrent disease. The analysis we performed showed a significant difference only in the serum CA-125 level (p = 0.004) between the two groups. There was no observed difference in womens' survival.
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Perivascular epithelioid cell tumors are very rare mesenchymal neoplasms arising in various locations, such as the female genital tract, kidney, lung, prostate, bladder, pancreas, soft tissues, and bone. They possess a unique immunophenotype, co-expressing myogenic and melanocytic markers; molecular findings include mutations of tuberous sclerosis complex and translocations of transcription factor E3, a member of the microphthalmia transcription factor gene family. We herewith report a uterine collision tumor consisting of a perivascular epithelioid cell tumor and a moderately differentiated endometrial endometrioid carcinoma in a patient with genetically proven tuberous sclerosis; two leiomyomas were also found in contact with the tumor. Although two such cases one with a benign and another with a malignant perivascular epithelioid cell tumor have previously been reported, ours is, to our knowledge, the first reported in a tuberous sclerosis patient.
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Ectopic or accessory breast tissue may occur in primitive embryonic milk lines or locations other than the milk line. The same pathology arising in breast tissue may occur less frequently in ectopic breast tissue. Fibroadenomas rarely occur in ectopic breast tissue, with less than 50 reported cases in the English literature, despite being the most common benign breast neoplasms. Diagnosing fibroadenoma in ectopic breast tissue can be challenging due to the lack of clinical suspicion and the atypical findings in imaging studies. Treatment consists of surgical excision. In this manuscript, we present a case of a 24-year-old patient with a fibroadenoma of the left axilla arising in bilateral axillary ectopic breast tissue, and we comprehensively review the literature.
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Teratomas are a type of germ cell tumor that may contain several different types of tissue. Neurofibroma is a benign peripheral nerve sheath tumor with the plexiform type being pathognomonic for neurofibromatosis type 1. We report a case of a 33-year-old woman with a background of Neurofibromatosis type 1 who presented with left-sided chest pain and shortness of breath. She was diagnosed with a large mediastinal mass which was confirmed from a CT-guided biopsy as neurofibroma. Following a multidisciplinary team discussion, she underwent mediastinal mass resection and the final histopathology report revealed mediastinal mature teratoma.
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Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like adenocarcinoma (SRCC) is a very rare PA subtype, with around 200 cases reported in the English literature. Histologically, the tumor cells show a vacuole compressing the nucleus to the periphery. Pagetoid spread in acini and ducts is usually related to metastases from urothelial or colorectal carcinomas, less commonly associated with intraductal carcinoma (IC); histologically, the tumor cells grow between the acinar secretory and basal cell layers. To our knowledge, we report the first prostatic SRCC (Gleason score 10, stage pT3b) associated with IC and pagetoid spread to prostatic acini and seminal vesicles. To our systematic literature review (PRISMA guidelines), it is the first tested case for both PD-L1 (<1% of positive tumor cells, clone 22C3) and mismatch repair system proteins (MMR) (MLH1+/MSH2+/PMS2+/MSH6+). We found no SRCC previously tested for MMR, while only four previous cases showed high expression of another PD-L1 clone (28-8). Finally, we discussed the differential diagnoses of prostatic SRCC.
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Hematological neoplasms sharing a blastic morphology may involve the skin. The skin may be either the primary site of occurrence of hematological malignancies with blastic features or cutaneous lesions are the first manifestation of an underlying systemic malignancy. The assessment of skin biopsies of hematological neoplasms with blastic features poses diagnostic problems and requires expert hematopathologists considering a wide range of differential diagnoses. The precise diagnosis of diseases sharing blastic features but with different outcomes and requiring distinct therapies is essential for patient management. The present paper mainly focuses on cutaneous involvement of the blastoid variant of mantle cell lymphoma and lymphoblastic lymphoma of B-cell or T-cell origin. The relevant literature has been reviewed and the clinical aspects, pathological features, prognosis, and therapy of both blastoid mantle cell lymphoma and lymphoblastic lymphoma involving the skin are discussed. A focus on other hematological entities with blastic features, which may involve the skin, to be taken into consideration in differential diagnosis is also given.
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BACKGROUND/AIM: Adenoid cystic carcinoma (ACC) is an aggressive neoplasm even though it has low-grade histological appearance and slow growth. The aim of this study was to identify the immunohistochemical and molecular characteristics of ACC, as well as their correlation with the clinical course of patients. PATIENTS AND METHODS: This is a retrospective multicenter analysis. We included 50 patients diagnosed with ACC in the head and neck between 2000 and 2021. The expression of MYB proto-oncogene transcription factor (MYB), neurotrophic tyrosine kinase receptor (NTRK), human epidermal receptor-2 (HER-2), and Ki-67 was examined through immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). We also performed a clinical follow-up of the patients. RESULTS: The median age of the patients was 58.5 years; moreover, 54% of the patients were male. Compared with female patients, male patients were at a higher risk of both recurrence and death. No HER-2-positive cases were revealed. MYB expression was positive in 28 (56%) cases. However, MYB expression did not significantly affect survival. NTRK expression was positive in eight (16%) cases. NTRK-positive patients had worse overall survival (OS) than NTRK-negative patients (p=0.0246). Additionally, the percentage of NTRK-stained cells was negatively correlated with disease-free survival (p=0.0016) and OS (p=0.0027). CONCLUSION: There was no correlation between MYB positivity and survival. Contrarily, NTRK-positive patients had worse survival, indicating that NTRK is a negative prognostic factor. Tropomyosin receptor kinase inhibitors can be used to treat these patients. Furthermore, MYB-targeted inhibitors are promising therapeutic agents.