Circulating Polyploid Giant Cancer Cells, a Potential Prognostic Marker in Patients with Carcinoma.

Polyploid Giant Cancer Cells (PGCCs) have been recognized as tumor cells that are resistant to anticancer therapies. However, it remains unclear whether their presence in the bloodstream can be consistently detected and utilized as a clinical marker to guide therapeutic anticancer regimens. To address these questions, we conducted a retrospective study involving 228 patients diagnosed with six different types of carcinomas (colon, gastric, NSCLC, breast, anal canal, kidney), with the majority of them (70%) being non-metastatic. Employing a highly sensitive liquid biopsy approach, ISET®, and cytopathological readout, we isolated and detected circulating PGCCs in the patients' blood samples. PGCCs were identified in 46 (20.18%) out of 228 patients, including in 14.47% of 152 non-metastatic and 29.85% of 67 metastatic cases. Patients were subsequently monitored for a mean follow up period of 44.74 months (95%CI: 33.39-55.79 months). Remarkably, the presence of circulating PGCCs emerged as a statistically significant indicator of poor overall survival. Our findings suggest that circulating PGCCs hold promise as a reliable prognostic indicator. They underscore the importance of further extensive investigations into the role of circulating PGCCs as a prognostic marker and the development of anti-PGCC therapeutic strategies to improve cancer management and patient survival.

Secretory carcinoma of the minor salivary gland: An in-depth case report.

A 56-year-old female was referred to our service for management of a malignant salivary gland neoplasm with compromised margins that had been biopsied previously at another service. The patient reported a twenty-year history of a lesion in the oral cavity with progressive and exuberant growth over the past two years, associated with local pain and dyspnea. Physical examination revealed an erythematous, ulcerated, and hemorrhagic lesion measuring approximately 3 cm on the left soft palate and tonsillar pillar. Computed tomography revealed an expansile lesion in the topography of the left soft palate, growing predominantly toward the lumen of the nasopharynx and partially invading the left wall of this region. The patient underwent surgery and histopathologic examination revealed an infiltrative and aggressive epithelial neoplasia with large vacuolated and eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. The neoplastic cells were arranged in a solid, microcystic, tubular, and follicular pattern with eosinophilic luminal secretion. Mitotic figures were frequent and all margins were affected by the neoplasia. Morphologic and immunohistochemical features supported the diagnosis of secretory carcinoma, and the patient is currently being followed for further therapeutic intervention.

Urothelial carcinoma in a mule.

Equine bladder neoplasms are rare. This report aimed to describe the clinical signs and treatment of urothelial carcinoma (UC) in a mule. Cystoscopy of a 20-year-old female mule with a one-week history of hematuria and anemia revealed vascular congestion in the mucosa and an intraluminal, pedunculated mass in the dorsal bladder region. Histopathological examination revealed UC. Initial therapy consisted of four weekly cystoscopic guided injections of fluorouracil. At the fourth chemotherapy session, a paler and more friable tumor mass was observed. Consequently, we opted to surgically remove it during cystoscopy. Following mass excision, patient comfort, gross appearance of urine, and the hematocrit returned to normal. Repeat cystoscopy examinations revealed no gross appearance of tumor recurrence 18 months after treatment. Bladder neoplasms clinically resemble urolithiasis and cystitis and should be considered a differential diagnosis in cases of anemia and hematuria.

Dendritic cell subpopulations in carcinoma ex-pleomorphic adenoma: A multicenter study.

OBJECTIVE: Carcinoma ex-pleomorphic adenoma (CEXPA) represents a malignant transformation from a recurrent or primary pleomorphic adenoma (PA), and the immune response may be essential in this process. Therefore, in this study, we aimed to identify and quantify subpopulations of dendritic cells (DCs) in CEXPA, residual PA in CEXPA (rPA), and PA. MATERIALS AND METHODS: A multicenter study was performed collecting salivary gland tumor (SGT) samples from three Oral and Maxillofacial Pathology Centers. A tissue microarray containing 41 samples of CEXPA and 22 samples of PA was included in this study and submitted to immunohistochemical reactions against CD1a, CD83, CD207, and Ki67 antibodies. RESULTS: Both PA and rPA showed a higher quantification of CD207+ and CD83+ cells when compared to CEXPA (p < 0.001 and p < 0.01, respectively). There was also a difference when comparing the cell proliferation index between PA/rPA and CEXPA using the Ki-67 marker (p = 0.043). However, there was no difference in the DC population regarding clinical parameters such as sex, anatomical location, size, and metastases (p > 0.06). CONCLUSIONS: Immunohistochemical profile of DC subpopulations and cell proliferation biomarkers in SGTs can contribute as an important tool in the differentiation of benign and malignant tumors or detection of initial areas with malignant transformation.

Clinical and pathological differences between early- and late-onset colorectal cancer and determinants of one-year all-cause mortality among advanced-stage patients: a retrospective cohort study in Medellín, Colombia.

OBJECTIVE: To identify the differences between early- (EOCRC) and late-onset colorectal cancer (LOCRC), and to evaluate the determinants of one-year all-cause mortality among advanced-stage patients. METHODS: A retrospective cohort study was carried out. CRC patients ≥ 18 years old were included. Chi-Square test was applied to compare both groups. Uni- and multivariate regressions were performed to evaluate the determinants of one-year all-cause mortality in all advanced-stage patients regardless of age of onset. RESULTS: A total of 416 patients were enrolled; 53.1 % were female. Ninety cases (21.6 %) had EOCRC and 326 (78.4 %) had LOCRC. EOCRC cases were predominantly sporadic (88.9 %). Histology of carcinoma other than adenocarcinoma (p= 0.044) and rectum tumors (p= 0.039) were more prevalent in EOCRC. LOCRC patients were more likely to have smoking history (p < 0.001) and right colon tumors (p = 0.039). Alcohol consumption history (odds ratio [OR]: 3.375, 95 %CI: 1.022-11.150) and stage IV (OR: 12.632, 95 %CI: 3.506-45.513) were associated with higher one-year all-cause mortality among advanced-stage patients, the opposite was noted with left colon tumors (OR: 0.045, 95 %CI: 0.003-0.588). CONCLUSION: EOCRC was predominantly sporadic and had more cases of uncommon histological subtypes and rectal tumors. LOCRC was characterized by a higher prevalence of smoking history. Multivariate regression revealed an association between higher one-year all-cause mortality and alcohol consumption history and stage IV in advanced-stage patients. CRC exhibited differences based on age of onset. The evaluated factors associated with CRC mortality provide valuable insights for healthcare professionals, emphasizing the importance of adequate clinical assessment and early CRC diagnosis.

DNA content and clinicopathological features aid in distinguishing ameloblastic carcinoma from ameloblastoma.

BACKGROUND: Ameloblastoma and ameloblastic carcinoma are epithelial odontogenic tumors that can be morphologically similar. In the present study, we evaluated the DNA content and Ki-67 index in the two tumors. METHODS: The paraffin blocks of the tumors were selected to obtain sections for the immunohistochemical reactions and preparation of the cell suspension for acquisition in a flow cytometer. The Random Forest package of the R software was used to verify the contribution of each variable to classify lesions into ameloblastoma or ameloblastic carcinoma. RESULTS: Thirty-two ameloblastoma and five ameloblastic carcinoma were included in the study. In our sample, we did not find statistically significant differences in Ki-67 labeling rates. A higher fraction of cells in 2c (G1) was correlated with the diagnosis of ameloblastoma, whereas higher rates of 5c-exceeding rate (5cER) were correlated with ameloblastic carcinoma. The Random Forest model highlighted histopathological findings and parameters of DNA ploidy study as important features for distinguishing ameloblastoma from ameloblastic carcinoma. CONCLUSION: Our findings suggest that the parameters of the DNA ploidy study can be ancillary tools in the classification of ameloblastoma and ameloblastic carcinoma.

Bilateral intra-lymph node Warthin's tumor as a potential diagnostic pitfall mimicking metastatic carcinoma.

Warthin's tumor (WT) is a benign and frequent salivary gland tumor primarily affecting the parotid gland. In some cases, this tumor can involve the extra parotid region and affect cervical lymph nodes. Fine-needle aspiration can be the first step in the diagnostic approach to lymphadenopathy; however, specimens from intra-nodal WT can present a potential pitfall, leading to a misdiagnosis of metastasis. Here, we report an unusual case of a patient with bilateral WT in parotid lymph nodes misdiagnosed as metastases. In addition, we highlight the cytopathological aspects of WT to alert cytopathologists about this challenging diagnosis.

Analysis of B7-H4 Expression Across Salivary Gland Carcinomas Reveals Adenoid Cystic Carcinoma-Specific Prognostic Relevance.

B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.

miR-186 regulates epithelial-mesenchymal transformation to promote nasopharyngeal carcinoma metastasis by targeting ZEB1.

OBJECTIVES: Nasopharyngeal carcinoma (NPC) is an aggressive epithelial cancer. The expression of miR-186 is decreased in a variety of malignancies and can promote the invasion and metastasis of cancer cells. This study aimed to explore the role and possible mechanism of miR-186 in the metastasis and epithelial-mesenchymal transformation (EMT) of NPC. METHODS: The expression of miR-186 in NPC tissues and cells was detected by RT-PCR. Then, miR-186 mimic was used to transfect NPC cell lines C666-1 and CNE-2, and cell activity, invasion and migration were detected by CCK8, transwell and scratch assay, respectively. The expression of EMT-related proteins was analyzed by western blotting analysis. The binding relationship between miR-186 and target gene Zinc Finger E-Box Binding Homeobox 1 (ZEB1) was confirmed by double luciferase assay. RESULTS: The expression of miR-186 in NPC was significantly decreased, and transfection of miR-186 mimic could significantly inhibit the cell activity, invasion, and migration, and regulate the protein expressions of E-cadherin, N-cadherin and vimentin in C666-1 and CNE-2 cells. Further experiments confirmed that miR-186 could directly target ZEB1 and negatively regulate its expression. In addition, ZEB1 has been confirmed to be highly expressed in NPC, and inhibition of ZEB1 could inhibit the activity, invasion, metastasis and EMT of NPC cells. And co-transfection of miR-186 mimic and si-ZEB1 could further inhibit the proliferation and metastasis of NPC. CONCLUSION: miR-186 may inhibit the proliferation, metastasis and EMT of NPC by targeting ZEB1, and the miR-186/ZEB1 axis plays an important role in NPC.

Extensive carcinoma cuniculatum of the maxilla: A rare variant of oral carcinoma

Carcinoma cuniculatum (CC), is a rare well-differentiated, low-grade variant of squamous cell carcinoma. However, diagnosis of oral CC has remained very difficult, because many pathologists and clinicians remain un acquainted with oral CC, because there are very few reported cases of this disease in the oral cavity. To our knowledge, no more than 60 head and neck cases have been reported since Flieger and Owinski first described a case involving the mandible in 1977, because there are very few published cases of this disease in the oral cavity, the aim of this report is to provide a detailed clinical and histopathologic description of carcinoma cuniculatum of the maxila, provide a brief review of the literature, and highlight the difficulties in arriving at the correct diagnosis.

Multivariate Prognostic Models for Patients with Stages I and Ii Colon Carcinoma: a Strobe-Compliant Retrospective Cohort Study.

Background: Colorectal cancer is the most frequent gastrointestinal malignancy worldwide. The value of adjuvant treatment is controversial in Stages I and II. Objective: The aim of this study was to construct post-operative prognostic models applicable to patients with stages I-II colon carcinoma (CC). Methods: This is a retrospective cohort study of patients with Stage I-II CC treated over a 25-year period. Exposure was defined as clinical, histopathological, and immunohistochemical factors (including CDX2 and MUC2 expression). Patients were randomly allocated to either a "modeling set" or a "validation set". Factors associated with recurrence, disease-free survival (DFS), and overall survival (OS) were defined in the "modeling set". Their performances were tested in the "validation set". Results: From a total of 556 recruited patients, 339 (61%) were allocated to the "modeling set" and 217 (39%) to the "validation set". Three models explaining recurrence, DFS, and OS were described. Tumor location in the left colon (Hazards ratio [HR] = 1.57; 95% Confidence interval [CI] 0.99-2.48), lymphocyte (HR = 0.46; 96% CI 0.27-0.88) and monocyte (HR = 0.99; 95% CI 0.99-1) counts, neutrophil/platelet ratio (HR = 1.3; 95% CI 0.74-2.3, and HR = 2.3; 95% CI 1.3-4.1; for second and third category, respectively), albumin/monocyte ratio (HR = 0.43; 95% CI 0.21-0.87), and microscopic residual disease after surgery (HR = 8.7; 95% CI 3.1-24) were independently associated with OS. T classification and expression of CDX2 and/or MUC2 were not independently associated with recurrence or prognosis. Conclusion: These models are simple and readily available, and distinguish the risk and prognosis in patients with CC stages I and II; these models require cheaper processes than the use of more sophisticated molecular biology techniques. They may guide either the need for adjuvant therapy versus post-operative surveillance only, as well as aid in the design of clinical trials.

Calreticulin Expression in Human Carcinomas: A Systematic Review and Meta-Analysis.

OBJECTIVE: The present study performed a systematic review and meta-analysis of observational studies on whether calreticulin levels could represent a prognostic factor in carcinoma patients. Calreticulin (CRT) is a multifunctional protein in the endoplasmic reticulum that can play distinct roles in different cancers. METHODS: The search was performed in PubMed, Scopus, the Cochrane Library, Web of Science, Lilacs, Science Direct, Embase, Bireme, and SciELO databases. After a full-text evaluation, only 14 articles remained. The RoBANS tool assessed the risk of bias. The meta-analysis was performed with R software, and the odds ratio (OR) was the effect measure. The random effects model was chosen, and the quality of evidence was evaluated according to GRADE. RESULT: The most frequent carcinomas were in the breasts and the colon. CRT expression varied according to carcinoma origin and type, but these diseases had a prevalence of high CRT levels, indicating tumor progression. The high CRT levels were associated with lymph node metastasis (OR = 3.06 [1.71; 5.48]/p = 0.0002/I2 = 0%). All included articles had a blinding bias. CONCLUSION: High CRT levels may represent a prognostic factor for metastatic lymph nodes in carcinoma patients.

Thrombotic microangiopathy and disseminated intravascular coagulation in a patient with carcinomatosis of the bone marrow due to gastric adenocarcinoma: Case report.

Carcinomatosis of the bone marrow is a rare clinical condition characterized by diffuse tumor infiltration of the bone marrow accompanied by hematological abnormalities, including thrombotic microangiopathy (TMA) and disseminated intravascular coagulation (DIC). In patients with gastric carcinoma, this association is infrequent. Below we present a case of a 19-year-old female patient with no known pathological history who presented with upper digestive tract bleeding. Upon examination, anemia and thrombocytopenia were documented, with schistocytes in the peripheral blood smear and prolonged coagulation times. Endoscopic studies indicated a lesion in the Borrmann IV gastric body, and the bone marrow biopsy showed the presence of signet ring cells. Because there was no possibility of systemic therapy, the patient died during hospitalization. This case contributes to the medical literature by describing an unusual presentation of a very frequent pathology.

Secretory carcinoma of the salivary gland is rich in lactoferrin: a possible lactational-like differentiation?

PURPOSE: It has been hypothesised that secretory carcinoma of the salivary gland (SCsg) might have a lactational-like differentiation. Therefore, we aimed to assess the immunoexpression of breast hormonal receptors and milk-related proteins in cases of SCsg and other salivary gland tumours with prominent secretory activity. METHODS: Immunohistochemistry against prolactin and growth hormone receptors, lactoferrin, human milk fat globule 1, MUC 1 and MUC4 was performed in twelve cases of SCsg and 47 other salivary gland tumours. RESULTS: Most cases of SCsg were negative for prolactin and growth hormone receptors. All cases of SCsg showed enhanced membranous-cytoplasmic staining for human milk fat globule 1, a pattern seen in other tumour groups. Only SCsg showed widespread strong staining for lactoferrin, concomitantly in the cell compartment and secretion. The other positive tumour types exhibited restricted staining. MUC1 and MUC4 showed no distinct pattern of expression. CONCLUSION: Although SCsg failed to demonstrate a complete lactational-like differentiation, lactoferrin showed a distinctive expression pattern in SCsg compared to other tumour types, which makes it a good marker to help in its differential diagnosis.

Immunostaining of stromal CD56 cells in ovarian malignancies.

OBJECTIVES: The aim of this study was to evaluate CD56 immunostaining in the stroma of benign and malignant ovarian epithelial neoplasms and associate the CD56 immunostaining with prognostic factors and survival in ovarian cancer. METHODS: Patients with ovarian epithelial neoplasia (n=77) were studied with a prospective cohort. The CD56 immunostaining was evaluated in the peritumoral stroma. Two groups were evaluated: benign ovarian neoplasms (n=40) and malignant ovarian neoplasms (n=37). Data were recorded for histological type and grade, International Federation of Gynecology and Obstetrics staging, molecular subtype, and lymph node metastases. Fisher's exact test and Kaplan-Meier survival curves were used, with a significance level of ≤0.05. RESULTS: We found greater CD56 stromal immunostaining in malignant neoplasms when compared to the group of benign neoplasms (p=0.00001). There was no significant difference in relation to the prognostic factors and survival. CONCLUSION: Malignant ovarian neoplasms showed higher stromal CD56 immunostaining. As the prognostic value of natural killer in ovarian cancer is controversial, knowing the specific function of each cell present both in the tumor tissue and systemically may help guide successful immunotherapies in the near future.

Impact of Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography on the Therapeutic Decision of Prostate Carcinoma Primary Staging: A Retrospective Analysis at the Brazilian National Public Health System.

BACKGROUND: Prostate cancer (PCa) is the most common malignant tumor in males and conventional imaging does not provide accurate primary staging. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) presents superior performance and strongly affects therapeutic choice. OBJECTIVE: The aim of this study was to evaluate the impact of PSMA PET, compared with conventional imaging methods, on the therapeutic approach in primary staging scenarios in patients with PCa treated at the Brazilian National Public Health System. METHODS: Overall, 35 patients diagnosed with PCa were evaluated using PSMA after conventional staging imaging with multiparametric magnetic resonance (MMR) and/or total abdominal computed tomography (CT) scan and bone scintigraphy (BS). The PCa extension identified by PET was compared with conventional imaging; staging changes and the management impact were then determined. PET comparison with conventional imaging, staging, and decision-making changes was analyzed using descriptive statistics. RESULTS: PET revealed local disease (LD) in 15 (42.9%) patients, seminal vesicle invasion (SVI) in 5 (14.3%) patients, pelvic nodal impairment (PNI) in 7 (20%) patients, pelvic and distant nodes in 3 (8.6%) patients, pelvic nodes and bone metastasis in 4 (11.4%) patients, and pelvic and distant nodes and bone metastasis in 1 (2.8%) patient. Staging changes were observed in 60% of patients, with downstaging predominance (76.2%). Volume increase was identified in 11 (31.4%) patients (only 4 related to upstaging, 36.4%). The board changed management decisions for 60% of the patients. The main limitations of this study were the sample size and its retrospective nature. CONCLUSIONS: PSMA findings changed the management decisions in more than half of the patients, which made the majority eligible for locoregional treatment and avoided unnecessary procedures in the systemic disease scenario.

Prostate cancer tissue classification by multiphoton imaging, automated image analysis and machine learning.

Prostate carcinoma, a slow-growing and often indolent tumour, is the second most commonly diagnosed cancer among men worldwide. The prognosis is mainly based on the Gleason system through prostate biopsy analysis. However, new treatment and monitoring strategies depend on a more precise diagnosis. Here, we present results by multiphoton imaging for prostate tumour samples from 120 patients that allow to obtain quantitative parameters leading to specific tumour aggressiveness signatures. An automated image analysis was developed to recognise and quantify stromal fibre and neoplastic cell regions in each image. The set of metrics was able to distinguish between non-neoplastic tissue and carcinoma areas by linear discriminant analysis and random forest with accuracy of 89% ± 3%, but between Gleason groups of only 46% ± 6%. The reactive stroma analysis improved the accuracy to 65% ± 5%, clearly demonstrating that stromal parameters should be considered as additional criteria for a more accurate diagnosis.