Histological Prognostic Factors Research Articles

Histological predictors of the unfavorable outcome of anorectal melanoma

AIM: to find histological prognostic factors for survival in patients with anorectal melanoma.PATIENTS AND METHODS: single center retrospective study of histological specimens of patients with anorectal melanoma (2005-2023). A revision of histological specimens was carried out, using the following criteria: multifocal growth, maximum tumor size, maximum thickness by Breslow, ulceration, perineural and lymphovascular invasion, as well as depth of invasion. Statistical processing was carried out using the Cox regression.RESULTS: twenty-one patients were included in the study. In all patients, treatment started with surgery: 13 (61.9%) — abdominoperineal excision (APE); 8 (28.1%) — local excision). The sample contained patients with the following initial stages of the process: IB–IIB — 12 (57.1%); III — 9 (42.9%). Nine (42.9%) patients developed local recurrence, and 8 (38.1%) — distant metastases. On univariate analysis, DFS was significantly affected by ulceration RR 0.061 (CI 95.0%; 0.004–0.097, p = 0.048), there was a trend towards the role of neurotropism RR 3.654 (CI 95.0%; 0.934–14.297, p = 0.063) and pigmentation RR 2.485 (CI 95.0%; 0.832–7.424, p = 0.103). In multivariate analysis, none of the criteria had a significant effect on DFS. On OS in univariate analysis was a trend towards an effect of Breslow invasion depth of more than 2 cm HR 1.028 (CI 95.0%; 0.998–1.060, p = 0.070) and depth of tumor invasion HR 2.117 (CI 95.0%; 0.990–4.525, p = 0.053). In multivariate analysis, none of the criteria had a significant effect on OS.CONCLUSION: evaluation of the effectiveness by histological features of skin melanoma showed the potential use of neurotropism, Breslow invasion of more than 2 cm and depth of tumor invasion as factors of unfavorable impact on DFS and OS in ARM. More trials are needed.

Vascular Endothelial Growth Factor Expression by Immunohistochemistry as a Possible Indicator of Prognosis in Invasive Breast Carcinoma of No Special Type

Context: Angiogenesis, the formation of new blood vessels from preexisting vascular network, is essential for tumor growth and spread. Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor. Aims: To assess the expression of VEGF in invasive carcinoma of no special type and its correlation with all the known prognostic factors of breast carcinoma. Settings and Design: Descriptive. Materials and Methods: Mastectomy specimens were studied noting the clinical details. The formalin-fixed tissues were subjected to routine processing and hematoxylin and eosin sections and studied extensively for all the histological prognostic factors. Representative sections from each case with the tumor were subjected to immunohistochemistry (IHC) staining with VEGF, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) antibodies. Statistical Analysis Used: Descriptive statistics, Chi-square tests, contingency table analysis using SPSS for Windows. Results: One hundred and twelve cases of invasive carcinoma of special type were studied to evaluate various clinicopathological parameters. The association of VEGF with clinicopathological parameters and all the known prognostic factors was studied to note its significance. VEGF overexpression was observed in 69% of the cases. It was noted that larger tumor size, higher histological grade, lymphovascular invasion, nodal involvement, tumor necrosis, high microvessel density, ER negativity, PR negativity, and HER2/neu positivity had a significant statistical association with VEGF overexpression. Conclusions: We conclude that incorporating VEGF as a biomarker along with the known factors into a prognostic index will not only help predict clinical outcome more accurately, but also determines the patient who can be benefited with combinational therapy including anti-VEGF factors.

Comparative study between poorly differentiated thyroid cancer and anaplastic thyroid cancer: real-world pathological distribution, death attribution, and prognostic factor estimation.

The clinic-pathological boundary between poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) is unclear due to a wide spectrum of histopathological features and the rarity of the disease. In addition to that, with the highest mortality rate and non-standard treatment modality, the PDTC/ATC population has not been subjected to comprehensive description and comparison with the extent of histological characteristics, therapeutic response, prognostic factors, and death attribution analysis. A total of 4,947 PDTC/ATC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival curve estimation and Cox proportional hazard regression were applied. Overall, the 5- and 10-year DSS for PDTC were 71.9% and 68.0%, respectively, whereas the 5- and 10-year OS are 59.3% and 51.2%, respectively. The median survival time for ATC patients was 3 months with 1-year OS being 26.9% and 1-year DSS being 31.2%. During the follow-up period, 68.1% of the PDTC/ATC cohort were dead, 51.6% of which were attributed to thyroid malignancies and 16.5% to non-thyroid causes. The top three common non-thyroid causes of death were miscellaneous cancers, lower respiratory system disease, and heart disease. The histological feature of papillary thyroid cancer (PTC) was the leading pathological category for PDTC patients (51.7%), whereas 76.7% of ATC patients' pathological feature was characterized as unidentifiable. Sarcoma histological characteristics found in ATC cases suffer the highest overall mortality (vs. PTC, HR = 2.61, 95% CI 1.68-4.06, P < 0.001). Older age unidentifiable histology feature, more advanced AJCC N1b, AJCC M1, and SEER stage, tumor size larger than 5cm, and more invasive tumor extension were independent bad outcome predictors. The populational analysis of the PDTC/ATC cohort has provided reliable support for better understanding of the difference between PDTC and ATC cases and the guidance of clinical practice and further studies.

Prognostic value of mitotic count in leiomyosarcoma: A comprehensive monocentric retrospective study

BackgroundLeiomyosarcomas (LMSs) include heterogeneous entities with different clinical courses not entirely predicted by known prognostic factors. In particular, the value of mitotic count as independent prognostic factor in LMS has been poorly investigated. MethodsWe retrospectively analyzed all patients with a diagnosis of LMS who accessed to our Institution from June 1999 to May 2022 for which mitotic count was numerically expressed within the pathology report. Univariate and multivariate analyses were conducted to explore the prognostic value of mitotic count along with other clinical and histological variables. ResultsWe identified 121 eligible patients, with a median follow-up of 91.03 months (range 0.62–275.2 months). Median progression-free survival (mPFS) was 16.7 months, and median overall survival (mOS) was 105.6 months. In univariate analysis, mitotic count showed a significant impact on PFS and OS, with an hazard ratio per mitotic unit of 1.03 (1.01–1.04, p < 0.001) and 1.03 (1.01–1.04, p = 0.007), respectively. Similar results were found for locally advanced and metastatic patients, separately. Other significant prognostic factors for PFS were stage at diagnosis, performance status, tumor size and Ki-67, while differentiation, necrosis, grade, stage at diagnosis, tumor size, performance status and age at diagnosis were identified for OS. In multivariate analysis, the only significant factors were mitotic count and the presence of metastases at diagnosis for PFS, whereas the same two factors plus age at diagnosis were identified for OS. ConclusionMitotic count represented the most important histological prognostic factor for OS and PFS in localized and metastatic LMS.

Wait and see: a case of EBV + cutaneous extranodal NK/T-type lymphoma with indolent behaviour.

Extranodal NK/T-cell lymphoma (ENKTL) is a rare lymphoma subtype associated with Epstein-Barr virus (EBV) infection, portending a poor prognosis despite systemic chemotherapy. We present the unusual case of an 85-year-old man receiving ibrutinib for mantle cell lymphoma, who developed a erythematous, subcutaneous nodule on the forehead, featuring a proliferation of pleomorphic CD8 + /CD56 - /EBV + cells. Given the negative staging and comorbidities, a watchful waiting strategy was performed, experiencing a benign course with self-resolution and complete remission over a 4-year follow-up. The literature on primary cutaneous ENKTL has been discussed, with particular attention to clinical and histological prognostic factors.

Surgical outcomes for cutaneous squamous cell carcinoma of the auricle.

Cutaneous squamous cell carcinoma (CSCC) on the auricle is believed to carry a higher risk of metastatic spread. The rates of lymphatic metastasis reported in the literature have varied widely. There are no established prognostic criteria to determine which of these tumors are higher risk and warrant prophylactic treatment of the associated lymphatic basins. To retrospectively evaluate outcomes after surgical treatment of auricular CSCC in our department, examining excision completeness, tumor recurrence, and lymphatic metastasis. Secondarily, to identify factors associated with lymphatic metastasis. One hundred and thirty-eight consecutive cases of auricular SCC were excised from 126 patients in our department over a 7-year period (January 2012-December 2018). Data were retrospectively collected on patient characteristics, tumor histology, surgical procedures, and follow-up. Incomplete initial excision occurred in 17 cases (12.32%). Six patients (4.76%) had a local recurrence. Lymphatic metastasis occurred in eight patients (6.35%), on average within 10.25 months after primary excision. Six patients with metastasis died during follow-up, with a mean survival of 10.2 months. Older age was associated with lymphatic metastasis (P = 0.0267). Other factors, including tumor recurrence, size, grade, cartilage invasion, and positive margins, were evaluated and not significantly associated with metastasis. In this study, the metastatic rate of auricular SCC was 6.35%, which is within the previously reported ranges. No histological prognostic factors were identified in this study, which may be due to our limited sample size. In the absence of established prognostic criteria, decisions regarding prophylactic treatment should be made on an individual basis with multidisciplinary support.

Analysis of Histological Prognostic Factors in Colorectal Carcinoma and Relationship of VEGF and E-Cadherin Expression in Prognostic Assessment

Colorectal carcinomas (CRC) are associated with several histopathological and molecular factors of prognostic and hence therapeutic implications, including for epithelial mesenchymal transition (EMT) and angiogenesis. Downregulation of E-cadherin is a crucial step in EMT, directly related to tumor progression, invasion, and metastasis. Vascular endothelial growth factor (VEGF) induces angiogenesis and thereby tumour progression and metastases. Our objective was to analyse VEGF and E-cadherin expression in patients with CRC and to effectively assess the relationship of these with histopathological factors. 50 cases of CRC obtained over eighteen months duration, were included in the study. Haematoxylin and Eosin-stained sections were studied for histopathological factors. Immunohistochemistry with E-Cadherin and VEGF were performed on representative sections and evaluated. Histopathological features of importance noted were low grade tumour budding (55.5%), Infiltrative invasive front (83%), lympho-vascular invasion (50%). Preserved expression of E-Cadherin was seen in 66% of the cases, and 34% reduced expression, predominantly noted in patients above the age of 50, increased tumour size, mucinous variants, advanced TNM stage, lymph node involvement and high-grade tumour budding. VEGF staining was seen in 64% of the cases with varying intensity. Increased VEGF expression was noted in poorly differentiated tumours, advanced Duke’s stage and with lymph node metastasis. Colorectal carcinomas with high grade tumour budding were associated with lymph vascular invasion, infiltrative invasive front and significantly correlated with TNM stage. High grade tumours and adverse histopathological prognostic factors revealed a reduced E-cadherin expression and increased VEGF expression.

Fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease (25-30% of the global adult general population) with no approved treatment to-date, although its treatment is attractive for the researchers and the pharmaceutical industry. The cessation of ovarian function (natural or iatrogenic menopause, premature ovarian insufficiency) is associated with increased abdominal adipose tissue and changes in carbohydrate and lipid metabolism. These changes lead to a dysmetabolic milieu, characterized by unfavorable lipid profile and the development of NAFLD, which may contribute to the increase in cardiovascular risk observed after menopause. Not only the prevalence of NAFLD seems to be higher in postmenopausal compared with premenopausal women, but also the rates of advanced types of the disease, i.e., nonalcoholic steatohepatitis and hepatic fibrosis, the latter regarded as the main histological prognostic factor of advanced liver disease and a difficult-to-reverse target. These observations may render menopausal hormone therapy (MHT) an appealing way to retard or even restore NAFLD after menopause. Although there are some experimental data favoring this consideration, there are only a few interventional clinical studies evaluating the effect of MHT on NAFLD, which have provided conflicting results. Some of them showed encouraging effects of MHT on liver function tests and/or lower rates of NAFLD in women receiving as compared with those not receiving MHT. However, other studies showed that MHT may adversely affect NAFLD. Regarding the route of administration of MHT, there are currently not comparative data between per os and transdermal use on NAFLD. Until waiting for the publication of relevant studies, based on the favorable effect of transdermal MHT on triglyceride concentrations and the fact that high triglyceride and low high-density lipoprotein-cholesterol concentrations are associated with the severity of NAFLD, the use of transdermal MHT may be preferred in women with NAFLD after the cessation of ovarian function. Of course, MHT could not be recommended as standard treatment of NAFLD in women, because MHT may be used for a certain time frame in a woman’s life. However, given that NAFLD seems to be common after the pause of ovarian function, any potential effect of MHT on NAFLD may be considered before treatment initiation and during the follow-up of these women.

Histological and immunohistochemical prognostic factors of primary angiosarcoma.

Angiosarcoma is a malignant vascular endothelial neoplasm with various histological patterns. Despite its highly malignant potential, histological prognostic prediction has not been adopted for angiosarcoma. This study aimed to establish a method of predicting the prognosis of primary angiosarcoma. Formalin-fixed, paraffin-embedded samples from 104 primary angiosarcomas were prepared. All the cases were reviewed based on histological examinations with H&E staining. Because the French Fédération Nationale des Centres de Lutte Contre Le Cancer system (FNCLCC) is not adopted for angiosarcoma, we experimentally established a modified version of FNCLCC. Immunohistochemical staining for ERG, CD31, CD34, D2-40, HHV-8, p16, C-MYC, and p53 was performed. Fluorescence in situ hybridization (FISH) was performed for 31 cases to assay c-MYC gene amplification. Multivariate analysis revealed that age (> 70years old) (p = 0.0011), non-cutaneous angiosarcoma (p = 0.0265), metastasis on diagnosis (p < 0.0001), size ≥ 5cm (p = 0.0388), no taxane chemotherapy (p = 0.0388), strong nuclear atypia (p = 0.0087), and the presence of luminal structure in ≥ 50% of the tumor volume (p = 0.0009) were independent poor prognostic factors. Among angiosarcomas with luminal formation, mFNCLCC scores were significantly correlated with a poorer prognosis. The overexpression of p16 was associated with less luminal formation (p = 0.0192). Immunohistochemical analysis of C-MYC showed a moderate level of concordance with FISH (Kappa value = 0.45). This study suggested that luminal formation and nuclear atypia may be poor histological prognostic factors of angiosarcoma and that mFNCLCC would be useful for predicting the prognosis of angiosarcoma with luminal formation.

Clinical, Histological, and Molecular Prognostic Factors in Childhood Medulloblastoma: Where Do We Stand?

Medulloblastomas, highly aggressive neoplasms of the central nervous system (CNS) that present significant heterogeneity in clinical presentation, disease course, and treatment outcomes, are common in childhood. Moreover, patients who survive may be diagnosed with subsequent malignancies during their life or could develop treatment-related medical conditions. Genetic and transcriptomic studies have classified MBs into four subgroups: wingless type (WNT), Sonic Hedgehog (SHH), Group 3, and Group 4, with distinct histological and molecular profiles. However, recent molecular findings resulted in the WHO updating their guidelines and stratifying medulloblastomas into further molecular subgroups, changing the clinical stratification and treatment management. In this review, we discuss most of the histological, clinical, and molecular prognostic factors, as well the feasibility of their application, for better characterization, prognostication, and treatment of medulloblastomas.

Comparison of CT- and MRI-Based Quantification of Tumor Heterogeneity and Vascularity for Correlations with Prognostic Biomarkers and Survival Outcomes: A Single-Center Prospective Cohort Study.

Tumor heterogeneity and vascularity can be noninvasively quantified using histogram and perfusion analyses on computed tomography (CT) and magnetic resonance imaging (MRI). We compared the association of histogram and perfusion features with histological prognostic factors and progression-free survival (PFS) in breast cancer patients on low-dose CT and MRI. This prospective study enrolled 147 women diagnosed with invasive breast cancer who simultaneously underwent contrast-enhanced MRI and CT before treatment. We extracted histogram and perfusion parameters from each tumor on MRI and CT, assessed associations between imaging features and histological biomarkers, and estimated PFS using the Kaplan-Meier analysis. Out of 54 histogram and perfusion parameters, entropy on T2- and postcontrast T1-weighted MRI and postcontrast CT, and perfusion (blood flow) on CT were significantly associated with the status of subtypes, hormone receptors, and human epidermal growth factor receptor 2 (p < 0.05). Patients with high entropy on postcontrast CT showed worse PFS than patients with low entropy (p = 0.053) and high entropy on postcontrast CT negatively affected PFS in the Ki67-positive group (p = 0.046). Low-dose CT histogram and perfusion analysis were comparable to MRI, and the entropy of postcontrast CT could be a feasible parameter to predict PFS in breast cancer patients.

Stage I Clear Cell and Serous Uterine Carcinoma: What Is the Right Adjuvant Therapy?

This single-center study aimed to retrospectively evaluate the survival outcomes of patients with FIGO stage I clear cell and serous uterine carcinoma according to the type of adjuvant treatment received. The data were collected between 2003 and 2020 and only patients with stage I clear cell or serous uterine carcinoma treated with primary surgery were included. These were classified into three groups: No treatment or brachytherapy only (G1), radiotherapy +/- brachytherapy (G2), chemotherapy +/- radiotherapy +/- brachytherapy (G3). In total, we included 52 patients: 18 patients in G1, 16 in G2, and 18 in G3. Patients in the G3 group presented with poorer prognostic factors: 83.3% had serous histology, 27.8% LVSI, and 27.8% were FIGO stage IB. Patients treated with adjuvant radiotherapy showed an improved 5-year overall survival (OS) (p = 0.02) and a trend towards an enhanced 5-year progression-free survival (PFS) (p = 0.056). In contrast, OS (p = 0.97) and PFS (p = 0.84) in the chemotherapy group with poorer prognostic factors, were similar with increased toxicity (83.3%). Radiotherapy is associated with improved 5-year OS and tends to improve 5-year PFS in women with stage I clear cell and serous uterine carcinoma. Additional chemotherapy should be cautiously considered in serous carcinoma cases presenting poor histological prognostic factors.

Pathological significance of GLUT-1 expression in breast cancer cells in diabetic and obese patients: The French Guiana study

The prevalence of obesity and type 2 diabetes is higher in French Guiana compared to mainland France. These metabolic disorders are associated with an increased risk of cancer. One of the factors involved is hyperinsulinemia that promotes the action of glucose transporter 1 (GLUT-1). The objective of this study is to characterize the expression of GLUT-1 in breast cancers cells in diabetic and obese patients compared to those who are not and to describe the clinical and histological prognostic factors of breast cancer in this population. We conducted a monocentric study between 2014 and 2020. Patients were classified into three groups: diabetes, obesity, and control group. The GLUT-1 expression was assessed by immunohistochemistry. In total, 199 patients were included in this study. The median age was 53.5 years, and the median tumor size was 2.8 cm. Luminal A was the most frequent molecular type (58.1%), followed by the triple-negative type (19.9%). The breast cancer in our population was characterized by a younger age at diagnosis, more aggressive molecular types, and larger tumor size. Thus, we suggest the advancement of the age of breast cancer screening in this territory. Overexpression of GLUT-1 was observed in 60.4% of cases and in all carcinoma in situ lesions. GLUT-1 overexpression was associated with more aggressive cancers. This overexpression is correlated with high histological grade, high proliferation index, and aggressive molecular types. Our study found no difference in GLUT-1 expression between the diabetic or obese patients and the control group.

Correlation between preoperative imaging biomarkers and histological prognostic factors in endometrial cancer: A prospective study.

We compared transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) for detecting myometrial infiltration, cervical involvement, and for measuring tumor volume in endometrial cancer patients. We also correlated tumor volume to worse histological prognostic factors. We recruited women with a histological diagnosis of endometrial cancer between March 2019 and March 2021. Inclusion criteria were: age ≥ 18 years, written informed consent, biopsy-proven endometrial cancer, absence of previous neoadjuvant chemo- or radiotherapy treatment, patient suitable for primary surgery. Exclusion criteria were: advanced disease stage and other coexisting malignant tumors. TVUS and MRI were used, in the absence of any contraindication. We compared the preoperative imaging results with final histopathology. The accuracy of TVUS and MRI in evaluating myometrial infiltration, cervical invasion and tumor volume were comparable. A tumor volume ≥2 ml showed a positive correlation with worse histological prognostic factors, such as high tumor grade, diffuse lymphvascular space involvement (LVSI) and deep myometrial invasion (p < 0.05). TVUS should be used as first-line imaging modality, being more available, cost-effective, and more acceptable by patients. A careful local staging of endometrial cancer patients before surgery is fundamental in order to improve tailored treatment and minimize costs.

Prognostic of recurrence and survival in poorly differentiated thyroid cancer.

The prognosis of poorly differentiated thyroid carcinomas (PDTC) defined by the Turin criteria is variable. The aim of this study on 51 PDTC patients was to determine clinical, histological and molecular prognostic factors associated with recurrence in patients with localized disease at initial treatment and with overall survival in patients with distant metastases. Of 40 patients for whom next-generation sequencing (NGS) by ThyroSeq v3 was able to be performed on historical samples, we identified high-risk molecular signature (TERT, TP53 mutations) in 24 (60%) cases, intermediate risk signature in 9 (22.5%) cases and low-risk signature in 7 (17.5%) cases. Potentially actionable mutations were identified in 10% of cases. After a median follow-up of 57.5 months, recurrence occurred in 11 (39%) of the 28 patients with localized disease. The American Thyroid Association (ATA) high risk of relapse, high mitotic count, high molecular risk signature and CD163 expression were associated with recurrence (P = 0.009, 0.01, 0.049, 0.03 respectively). After a median follow-up of 49.5 months, thyroid cancer-related death occurred in 53% of the patients with distant metastases. There was no significant prognostic factor associated with death in univariate analysis. However, none of the patients with intermediate ATA risk of recurrence and none of the patients with low-risk molecular signature died from the disease. In addition, high molecular-risk signature was associated with the presence of synchronous or metachronous distant metastasis (P = 0.007) and with poor overall survival (P = 0.01). In conclusion, ATA risk of relapse and high mitotic count was associated with higher rate of recurrence in localized PDTC. High molecular-risk signature was associated with the presence of distant metastasis and poor overall survival. Further studies are needed to determine if molecular testing adds to ATA risk stratification or response to therapy in predicting outcomes.

Ferroptosis in Intrahepatic Cholangiocarcinoma: IDH1105GGT Single Nucleotide Polymorphism Is Associated With Its Activation and Better Prognosis.

ObjectivesIntrahepatic cholangiocarcinoma (ICC) has a dismal prognosis and often demonstrates an anti-apoptotic landscape, which is a key step to chemotherapy resistance. Isocitrate dehydrogenase 1 or 2 (IDH1-2)-mutated ICCs have been described and associated with better prognosis. Ferroptosis is a regulated iron-mediated cell death induced by glutathione peroxidase 4 (GPX4) inhibition, and may be triggered pharmacologically. GPX4 is overexpressed in aggressive cancers, while its expression is inhibited by IDH1R132C mutation in cell lines. We investigated tissue expression of ferroptosis activation markers in ICC and its correlation with clinical-pathological features and IDH1-2 status.Materials and MethodsWe enrolled 112 patients who underwent hepatic resection or diagnostic liver biopsy for ICC. Immunostaining for transferrin-receptor 1 and GPX4, and Pearls’ stain for iron deposits were performed to evaluate ferroptosis activation. Immunostaining for STAT3 was performed to study pro-inflammatory and anti-apoptotic landscape. Main IDH1-2 mutations were investigated in 90 cases by real-time polymerase chain reaction.ResultsGPX4 overexpression was seen in 79.5% of cases and related to poor histological prognostic factors (grading and perineural and vascular invasion; p < 0.005 for all) and worse prognosis (OS p = 0.03; DFS p = 0.01). STAT3 was expressed in 95.5% of cases, confirming the inflammation-related anti-apoptotic milieu in ICC, and directly related to GPX4 expression (p < 0.0001). A high STAT3 expression correlated to a worse prognosis (OS p = 0.02; DFS p = 0.001). Nearly 12% of cases showed IDH1105GGT single nucleotide polymorphism, which was never described in ICC up to now, and was related to lower tumor grade (p < 0.0001), longer overall survival (p = 0.04), and lower GPX4 levels (p = 0.001).ConclusionOur study demonstrates for the first time that in most inflammatory ICCs ferroptosis is not active, and its triggering is related to IDH1-2 status. This supports the possible therapeutic role of ferroptosis-inducer drugs in ICC patients, especially in drug-resistant cases.

Cyclooxygenase-2 immunohistochemical expression is associated with worse prognosis in breast cancer: Retrospective study and literature review.

To assess the immunohistochemistry phenotype of cyclooxygenase-2 (COX-2) in breast cancer (BC) and to correlate it with histological and clinical prognostic factors. This retrospective study utilized COX-2 monoclonal antibody in an immunohistochemistry staining of tissue microarrays slides of 570 cases of previously diagnosed BC and with 52 of normal breast tissues from breast specimens resected for benign lesions or reconstruction (fibroadenoma and normal breast epithelium). This project was carried out in the Laboratory of pathology, King Abdulaziz University, Jeddah, Saudi Arabia, between September 2019 and September 2021. The present data showed an important connection between the COX-2 expression phenotype and BC compared to benign breast tissues (p=0.034). The expression pattern of COX-2 was allied significantly with some factors which distinguished aggressive subtypes of BC, such as stage, distant metastases, lymphovascular invasion, and poor survival. Cyclooxygenase-2 is a valuable marker that could facilitate BC diagnosis and prognosis.

MO054: Histological Findings in Drug-Induced Acute Interstitial Nephritis

Abstract BACKGROUND AND AIMS Acute interstitial nephritis (AIN) represents an important cause of acute kidney injury. The most common etiology of AIN is drug-induced disease. Definitive diagnosis of AIN requires renal biopsy. Despite this, there is a lack of consensus regarding precise histological diagnostic criteria, and the clinical significance of common histological findings is uncertain. The aim of this study was to explore the histological characteristics of drug-induced AIN and to evaluate their impact on the renal outcome. METHOD We conducted a retrospective study that included patients with biopsy proven drug-induced AIN, followed in the department of nephrology of Charles Nicolle hospital in Tunis during the period between 1990 and 2019. Histological diagnosis of AIN was based on the presence of an interstitial inflammatory cell infiltrate with or without fibrosis. RESULTS During the period of the study, we collected 69 cases of biopsy proven AIN. The diagnosis of drug-induced AIN was performed in 23 patients (33%), with a medium age of 35 years. In eight patients (35%), nonsteroidal anti-inflammatory drugs were the culprit, followed by antibiotics in six patients (26%) and other drugs in three cases (13%). In six patients (26%), no single drug could be identified as the culprit, and these were classified as multidrug causes. The presence of acute kidney disease was the main indication for the kidney biopsy. All cases were characterized by a prominent tubulointerstitial inflammatory cell infiltrate. Interstitial infiltration was mild in three cases (13%), moderate in five cases (17%) and severe in 15 cases (65%). The interstitial infiltrate consisted predominantly of lymphocytes. The presence of eosinophils has been noted in 10 cases (43%). Interstitial granulomas were noted in two patients (8%). Interstitial edema and tubulitis were observed in 13 (56%) and 6 cases (26%), respectively. In seven patients (30%) interstitial fibrosis was present, and four patients (17%) had mild-to-moderate tubular atrophy, whereas tubular necrosis was present in seven cases (30%). After a mean follow up of 24 months, eight patients (35%) progressed to chronic kidney disease. Histological factors associated with poor renal outcome, were interstitial fibrosis (P ˂ 0.001) and tubular atrophy (P = 0.01). Patients with interstitial edema (P ˂ 0.001) or tubulitis (P = 0.005) had a better renal prognosis. CONCLUSION Renal biopsy is required to establish a definitive diagnosis of drug-induced AIN. Nevertheless, it is not carried out in a systematic way. The composition of cells in the interstitial infiltrate may at times be helpful in determining the etiology of AIN. In particular, the presence of a considerable proportion of eosinophils favors a diagnosis of drug-induced AIN. Moreover, during drug-induced AIN, histological data have a great prognostic value. In our study, the main histological prognostic factors were interstitial fibrosis, tubular atrophy, interstitial edema and tubulits. Further studies are needed to validate these results and establish a score based on histological data in order to predict renal outcome during drug-induced AIN.

Clinical and Histological Prognostic Factors of Recurrence and Malignant Transformation in a Large Series of Oral Potentially Malignant Disorders

BackgroundOral potentially malignant disorders (OPMDs) represent a heterogeneous set of different histological lesions, characterized by the capacity to transform in oral squamous cell carcinoma (OSCC). Despite optimal surgical treatment, approximately 20%–30% of OPMDs may evolve into OSCC. No clear clinical/histological factors are able to identify OPMDs at higher risk of malignant transformation.Materials and MethodsWe considered surgically treated patients with a diagnosis of OPMDs, enrolled from 1996 to 2019 at ASST Spedali Civili of Brescia without a diagnosis of OSCC within the previous 2 years. Clinical and histological characteristics were recorded. Outcomes of interest were recurrence-free survival (RFS), defined as the time from surgery for primary OPMD to any relapse of OPMD or malignant transformation, whichever occurred first, and carcinoma-free survival (CFS), defined as the time from surgery for OPMD to malignant transformation.ResultsWe retrospectively reviewed 106 OPMDs cases. Median age at first diagnosis was 64 years old (IQR = 18.75); female patients comprise 51.9% of the cases. During a median follow-up of 30.5 months (IQR = 44), in 23.5% of patients, malignant transformation occurred. RFS at 1, 5, and 10 years was 92.4%, 60.9%, and 43.2%, respectively. Female sex and history of previous OSCC were independent risk factors for RFS. CFS at 1, 5, and 10 years of follow-up was 97.1%, 75.9%, and 64.4%, respectively. Previous OSCC was an independent risk factor for CFS.ConclusionsIn this large series of OPMDs, only previous diagnosis of OSCC was a prognostic factor for further OSCC occurrence. Given the lack of additional clinical/pathological prognostic factors, we advocate further studies into molecular characterization of OPMDs to better stratify the risk of malignant transformation.

Histopathological factors versus margin size in single colorectal liver metastases: Does a 1-cm margin size matter?

The ideal margin width for surgical resection of colorectal liver metastases has been extensively studied, but not sufficiently in accordance with other pathological factors. The aim of this study was to assess for the first time the prognostic impact of margin widths according to different prognostic pathological factors in colorectal liver metastasis. We evaluated 101 patients with a single resected metastasis. Slides stained by HE were assessed for the presence of poorly differentiated clusters, peritumoral inflammatory infiltrate, tumor pseudocapsule, and tumor borders pattern. Overall survival, disease-free survival, and hepatic recurrence were evaluated. The pathologic factors prognostic impact was evaluated according to a (< or ⩾) 10-mm margin size. Factors independently associated with a shorter overall survival were absence of tumor pseudocapsule (p < 0.001) and infiltrative tumor border pattern (p = 0.019). The absence of tumor pseudocapsule was the only factor independently associated with shorter disease-free survival (p < 0.001). Hepatic recurrence was associated with infiltrative tumor border and absence of pseudocapsule. Margin width ⩾10 mm did not impact overall survival independently of the studied histological prognostic factors. In colorectal liver metastasis resection, the absence of tumor pseudocapsule was significantly associated with shorter overall survival and disease-free survival and hepatic recurrence. However, margins larger than 10 mm did not offer survival benefit when other pathologic negative prognostic factors were concomitantly analyzed, reinforcing the idea that biology, rather than margin size, is crucial for prognosis.