Histological Components Research Articles

Histopathology of Autoimmune Hepatitis: An Update.

Autoimmune hepatitis (AIH) is a rare immune-mediated chronic liver disease that is diagnosed based on a combination of biochemical, immunologic, and histologic features and the exclusion of other causes of liver disease. According to the new consensus criteria of the International Autoimmune Hepatitis Pathology Group (IAIHPG), the likely histologic features include a chronic hepatitis pattern of injury with a lymphoplasmacytic portal infiltrate, interface activity, and portal-based fibrosis. More than mild lobular hepatitis with any of the above features can also be diagnosed as likely AIH in the absence of features of another liver disease. Centrilobular injury with prominent hepatocellular necrosis and mononuclear inflammation may represent an acute-onset disease and indicate possible AIH in the absence of concurrent liver disease. Kupffer cell hyaline bodies and portal lymphocyte apoptosis are significantly associated with AIH, whereas emperipolesis and hepatocellular rosette formation are nonspecific features indicative of disease severity. Liver histology is an integral part of the clinical diagnostic scoring system and is required to confirm or support AIH diagnosis. Substitution of the histologic component of the simplified AIH scoring system with the consensus IAIHPG criteria has been proposed to optimize clinical diagnosis. This review explores the significant role of histopathology in AIH by analyzing its main features and current histologic diagnostic criteria, different AIH presentations, differential diagnosis, assessment of concurrent liver disease, and identification of AIH variants with primary cholangiopathy.

Molecular characterization of early-stage lung adenocarcinoma presenting as subsolid nodules in a real-life European cohort

ObjectivesSubsolid nodules emerged as frequent radiological variants of lung adenocarcinoma. Radiological features including solid-component prevalence and larger tumour dimensions prompt tumoral invasiveness guiding prognosis and management. Thus, we aimed to clarify the molecular grounds that dictate these radiological appearances and clinical behaviour in a real-life European-cohort. Additionally, following the growing interest toward targeted-therapies in early-stage diseases, we aimed to present real-life epidemiological data of actionable mutations in these patients.MethodsIn this retrospective single-centre study, targeted next-generation sequencing was performed continuatively in all the resected subsolid lung adenocarcinomas in the period between May 2016 and December 2023. Clinico-radiological data were collected. The genetic landscape of our real-life European subsolid adenocarcinoma population is defined. Common and actionable mutations (frequency > 5%) relation to key clinico-radiological features are evaluated.ResultsOverall, 156 subsolid adenocarcinomas were analysed. KRAS-mutations, mostly KRAS p.G12C, were the most prevalent followed by EGFR, including 25% uncommon EGFR-mutations, TP53 and MET mutations. Amongst the clinico-radiological variables, KRAS-mutations and KRAS p.G12C-mutation were associated to smoking history (≥ 20 pack/years), aggressive histologic subtype and higher consolidation-to-tumor ratio (CTR). Moreover, KRAS-mutated nodules had faster tumour-doubling-time. Conversely, EGFR-mutations were associated to female sex and lower CTR. The latter not being confirmed in common EGFR-mutations. Additionally, in common EGFR-mutated nodules, aggressive histological components were rarer.ConclusionOur study presents the molecular profile of subsolid lung adenocarcinoma in a real-life European-cohort. KRAS-mutations were the most prevalent, and were related to smoking history, higher CTR and faster growth. Conversely, common EGFR-mutations were rarer than expected and unrelated to smoking history and radiological features.

Оценка пролиферативной активности и метаболизма глюкозы в клетках мукоэпидермоидной карциномы слюнных желез при различных системах градации

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary gland consisting of three main histological components: mucocytes, intermediate and epidermoid cells. Various grading systems (AFIP, Brandwein, modified Healy, MSKCC) are difficult to use. The Ki-67 and GLUT1 markers associated with tumor aggressiveness can improve MEC diagnosis and classification. The study aimed to assess the correlation of the cell proliferative activity and glucose metabolism with the MEC grading systems. Tumors of a total of 40 patients with MEC were analyzed and determined in accordance with the following grading systems: AFIP, Brandwein, modified Healy, and MSKCC. Immunohistochemistry (IHC) was used to estimate Ki-67 proliferation indices and GLUT1 expression intensity. IHC showed high Ki-67 indices and GLUT1 values in epidermoid and intermediate cells, while mucocytes showed low or no expression. There were significant differences in Ki-67 and GLUT1 expression between epidermoid (p < 0.005) and intermediate cells (p < 0.01). Comparison revealed the increase between grades 1 and 2, 1 and 3, but no differences between grades 2 and 3. Spearman’s rank correlation test revealed moderate positive correlations with tumor grades for GLUT1 and Ki-67, and the AFIP system showed the highest correlation (Ki-67: rs = 0.55; GLUT1: rs = 0.50). Thus, GLUT1 and Ki-67 are most intensely expressed in epidermoid and intermediate cells showing a strong correlation with the tumor grade and aggressiveness, especially in low-grade and intermediate-grade MEC. These markers can improve the diagnosis of MEC malignancy degree. The AFIP system most closely matches these markers in epidermoid and intermediate cells.

The Critical Role of Minor Histological Patterns in Prognosis Prediction in Early-Stage Lung Adenocarcinomas.

Lung adenocarcinomas often contain multiple histological components. This study discusses the role of minor components in the progression of the disease. A retrospective evaluation was conducted on 108 patients with lung adenocarcinoma who underwent surgery at our center between 2013 and 2018, with tumor sizes less than 3 cm. The patients were categorized into four groups based on the presence of lepidic (L) and micropapillary/solid (MP/S) patterns at a minimum threshold of 5% ("L+, MP/S-", "L+, MP/S+", "L-, MP/S-", "L-, MP/S+"). The groups were compared in terms of standard uptake value, pleural invasion, lymphovascular invasion, perineural invasion, spread through air spaces, N1-N2 station lymph node metastasis, recurrence, and survival. No tumors of perineural invasion, spread through air spaces, or lymph node metastasis was observed in the "L+, MP/S-" group, and lymphovascular invasion was found to be significantly lower compared to other groups (p = 0.040). The standard uptake value levels in groups containing the lepidic pattern were significantly lower than in other groups (p = 0.006). The time to recurrence in the "L+, MP/S-" group was 121.5 ± 10.9 months, with a median survival time of 110.9 ± 10.6 months, which was longer compared to the other groups (86.2 ± 5.9 and 77 ± 13.4 months). In lung adenocarcinomas, prognosis estimation should be based not only on the dominant component but also on the presence of histological components such as lepidic and micropapillary/solid, even if they are minor.

Stem cell therapy for bladder regeneration: A comprehensive systematic review.

Stem cell therapy for bladder regeneration: A comprehensive systematic review.

A six-year retrospective study of patient outcomes following involved or close margin basal cell carcinoma excision.

A six-year retrospective study of patient outcomes following involved or close margin basal cell carcinoma excision.

Breast Carcinomas Resembling Acinic Cell Carcinoma: Comprehensive Analysis of 14 Cases and Review of the Literature.

Acinic cell carcinoma (AciCC) of the breast is an exceptionally rare subtype of invasive breast carcinoma, often exhibiting a triple-negative phenotype and relatively indolent behavior. Since the first case reported by Roncaroli and colleagues in 1996, no more than 60 additional cases have been described in English medical journals, usually as case reports or small case series. In this study, we presented an in-depth analysis of 14 cases of AciCC of the breast, including 4 pure AciCCs and 10 AciCCs mixed with other histologic types. We reported the clinicopathologic characteristics, histologic components, treatment modalities including response to neoadjuvant treatment in 3 patients, and outcomes. In addition, we assessed the expression of nuclear transcription factor nuclear receptor subfamily 4 group A member 3 by immunohistochemistry and gene rearrangements by fluorescence in situ hybridization, which has been implicated in AciCC of the salivary gland. All 14 cases were negative for nuclear receptor subfamily 4 group A member 3 expression, and no gene rearrangements were detected. We also conducted a thorough review of the literature to highlight advancements in understanding this rare breast cancer subtype. This study aims to enhance clinical knowledge of AciCC of the breast and contributed to growing evidence that AciCC of the breast and AciCC of the salivary glands appear to be unrelated entities, despite sharing a similar histologic appearance.

Epstein-Barr virus status drives morphological and molecular intra-tumour heterogeneity in gastric cancer: insights from a case report and literature review.

This case report describes a rare case of bi-phenotypic gastric cancer with two distinct, but clonally related, histological components. The first component, associated with Epstein-Barr virus (EBV) infection, exhibited the morphological features of gastric carcinoma with lymphoid stroma, suggesting that EBV, as an effective immunogenic factor, may trigger a prominent immune response within the tumour microenvironment. The second component, which was EBV-negative, displayed tubular/papillary morphology and features of increased biological aggressiveness, such as high-grade areas and lymphatic invasion. Immunohistochemical and molecular studies confirmed that, despite the differing morphologies and immunophenotypes, both components were clonally related, with the EBV-negative area showing more complex DNA aberrations, reminiscent of chromosomally instable (CIN) lesions. This case describes clonally related EBV-positive and -negative components within a single gastric cancer, contributing to a better understanding of EBV role in tumour heterogeneity and progression and highlights the impact of EBV loss on tumour behaviour.

Effect of chromium-methionine and zinc-methionine supplementation on histological changes of Awassi lamb testicles

This study was conducted in the sheep field of the Animal Production Department at the College of Agriculture / Tikrit University for the period 25 October 2021 to 1February 2022 (70 days) with the aim of measuring the effect of adding both Chromium- Methionine (Cr-M) and Zinc Methionine (Zn-M) on histological changes in the testicles of Awassi lambs. 24 lambs aged 4-5 months were distributed equally into four groups (group / 6 lambs), the initial weight was 25.35 ± 2.25 kg, the first group (T1) was not given only the basic feed (control), the second group added 1 gm Cr-M / 100 kg of live weight, the third group was given 0.33 gm of Zn-M / 100 live weight and the fourth group was given 1 gm Cr-M + 0.33 gm Zn-M /100 live weight. Tissue samples were taken from the testicles of lambs up on removal from the body, and the changes and histological components were studied using fixation and staining techniques to study the changes in the seminiferous tubules and interstitial cells including the thickness of the basement membrane. The results showed that treatment with T2 and T3 led to a significant improvement in the histological structures of the testicle, as well as an increase in the diameter of the seminiferous tubules and an increase in the thickness of the basement membrane. It was noted that there was an increase in the activity of sperm formation compared to the control group. Moreover, the T4 group was the most responsive to treatment, as the results showed a significant improvement in all histological parameters, as well as an increase in the density of sperm cells, and a decrease in amyloid deposition and necrosis. From this, we conclude that the addition of Cr-M and Zn-M, especially when added together, improves the health of the testicles and supports the production of sperm cells.

Metaplastic carcinoma of the breast containing three histological components: a case report

Metaplastic carcinoma of the breast containing three histological components: a case report

Appropriate Slice for Microscopic of Hepar and Kidney Mice Fixed With BNF 10%

Background: Histological processing encompasses the steps of acquiring fresh tissue, preserving it through fixation to maintain its natural appearance, slicing it into thin sections, placing the sections on glass slides, and subsequently staining them. This enables the observation of various histological components within the tissue using a microscope. The objective of this study was to ascertain the microscopic characteristics of heparin preparations and the kidneys of mice (Mus musculus) through fixation using a formalin buffer solution.Method: This kind of research encompasses experimental research. The study employed a purposive sample methodology in its research design. This study concludes that preparations containing images provide a representative depic-tion of the cell nucleus, cytoplasm, and exhibit consistent coloration with different cutting thicknesses. The standard thickness for cutting the mice hepatic tissue using a microtome is 5 μm.Result: This thickness yields good microscopic results overall, with 25 field views from 5 preparations. The percentage of high-quality microscopic images obtained at this thickness is 100%. The statistical analysis revealed significant differences (p<0.05) between the 2 μm and 5 μm groups, as well as between the 5 μm and 8 μm groups. There was no statistically significant difference (p>0.05) observed between the 2 μm and 8 μm groups in terms of many aspects including structural, nucleolus, cytoplasm, color uniformity, and total structure scores.Conclusion: The optimum thickness in this research was 5 μm. Additional investigation is required to examine the microscopic characteristics of tissue samples by varying the duration of staining on the samples.

Clinicopathologic feature and treatment progress of high-grade ovarian neuroendocrine tumors.

High-grade Ovarian neuroendocrine tumors represent a rare subset of ovarian neoplasms characterized by aggressive behavior, poor prognosis, and early metastasis. Despite their clinical significance, the management of these tumors lacks consensus due to their low incidence. This comprehensive review encompasses literature spanning from 1991 to 2024, focusing on the clinical presentation, diagnostic criteria, differential diagnosis, prognostic indicators, treatment modalities, and recent advancements in the understanding of this condition. Notably, a substantial proportion of affected individuals present during the perimenopausal period with unilateral lesions displaying mixed histological components. Biomarkers such as CA125, CA199, and NSE hold promise for aiding in the diagnosis and screening of ovarian neuroendocrine tumors. Unfortunately, patients exhibit a dismal prognosis even diagnosed at an early stage. Primary treatment strategies predominantly involve surgical intervention coupled with etoposide-cisplatin combination chemotherapy. In cases of recurrence, second-line chemotherapeutic agents including paclitaxel, irinotecan, and doxorubicin are commonly employed alongside localized radiotherapy. While specific genetic mutations remain elusive, emerging evidence suggests potential therapeutic effect involving mTOR inhibitors, PD-1 monoclonal antibodies, and antiangiogenic agents based on isolated case reports. The exploration of representative set of mutations will help for precise targeted therapies and remains a focal point of our ongoing research efforts.

Neuroendocrine Tumors in Horseshoe Kidneys: A Review of the Literature With Report of a Novel Finding Expanding Their Morphologic Spectrum

Horseshoe kidney is a rare congenital anomaly with an unusually higher frequency of neuroendocrine tumors. Symptoms are rare, and, in most of the cases, are incidentally diagnosed. The clinical behavior of these tumors is heterogeneous and can be difficult to predict based on histology alone. Necrosis and percentage of Ki-67 may have a role in prognosis. Almost all tumors are carcinoids (well-differentiated neuroendocrine tumors) observed at an early age and with no sex dominance. It is not known the reason for the higher frequency of neuroendocrine tumors in horseshoe kidneys and the histogenesis is unknown. One of the hypotheses supports that renal carcinoid tumors may arise from neuroendocrine cells within foci of metaplastic or teratomatous epithelium within the kidney. With consonance with this hypothesis, there are reports of carcinoids in horseshoe kidneys associated with a cystic lesion lined by the intestinal epithelium, with mucinous differentiation and osseous metaplasia, arising in a mature teratoma of the kidney, arising within mature teratoma and clear cell renal cell carcinoma, with a mucinous cystadenoma element, and arising within mature cystic teratoma synchronous with primary adenocarcinoma. There is only one reported large cell neuroendocrine carcinoma of a horseshoe kidney in a 57-year-old Chinese woman. Herein, we report a patient that to the best of our knowledge is the first case of a combined well-differentiated neuroendocrine tumor and large-cell neuroendocrine carcinoma with rhabdoid features in horseshoe kidney. The histologic component of rhabdoid features expands the morphologic spectrum of neuroendocrine tumors in the horseshoe kidney. We provide a comprehensive review of the literature summarizing pertinent key clinical and pathologic aspects.

Rare carcinoma of the ampulla of Vater with mixed histologies: A case report

The current case is about a 62-year-old female presented with persistent fever for 10 days and yellowing of the skin for 5 days at our outpatient clinic. Laboratory tests revealed elevated levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase. Abdominal computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography revealed a mass in the ampulla of Vater, as well as dilatation of the intra- and extra-hepatic bile and pancreatic ducts. The patient underwent pancreaticoduodenectomy under general anesthesia. Post-operative pathological and immunohistochemical results confirmed a tumor located in the ampulla, measuring 1.5 × 1 × 1 cm. The main component of the tumor was a moderately differentiated pancreaticobiliary adenocarcinoma (ADC), combined with squamous cell carcinoma (SCC) as well as small cell neuroendocrine carcinoma (SCNEC). The cancer tissue infiltrated the entire intestinal wall, with no invasion of microvessels, lymphatic vessels, or nerves observed. Until 46 months later, there was no tumor recurrence or distant metastasis. We present an uncommon case of ADC of the ampulla of Vater combined with SCC and SCNEC. Carcinoma of the ampulla of Vater may have mixed histological components; therefore, in cases of ampullary carcinoma, appropriate specimen collection is necessary, and further studies with more focus on histological origins are required.

Histopathological diagnosis of pulmonary sclerosing pneumocytoma in needle biopsy specimens

Objective: To investigate the diagnostic features of pulmonary sclerosing pneumocytoma (PSP) in needle biopsy specimens so as to improve the preoperative diagnostic accuracy and to prevent misdiagnoses. Methods: A total of 79 needle biopsy cases confirmed as PSP in surgical resection specimens were collected in the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from January 2015 to January 2023. A retrospective analysis was conducted to investigate the clinical, pathological, and immunohistochemical characteristics of PSP. Results: Among the 79 cases, there were 8 males and 71 females, with an age range of 14 to 67 years (median 47 years). Among the 79 needle biopsy cases of PSP, 5 cases were initially misdiagnosed as adenocarcinoma and 1 as carcinoid preoperatively, while the remaining 73 cases were correctly diagnosed. 84.8% (67/79) of the PSP presented with well-defined, homogeneous, solitary solid tumors on chest imaging. Morphologically, 26.6% (21/79) of the PSP mainly showed a single histological component, 67.1% (53/79) contained two histological components, and 6.3% (5/79) contained three histological components. There were no cases containing all four histological components simultaneously. The tumor was composed of cuboidal cells on the surface and round cells in the stroma and lacked significant cytological atypia and mitotic figures. Some cases exhibited variations in histology and cellular morphology, such as glandular spaces (58.2%, 46/79), sclerotic papillae (46.8%, 37/79), hypercellularity (16.5%, 13/79), and cytological atypia (24.1%, 19/79). Immunophenotyping indicated that both tumor cell types expressed TTF1, EMA and β-catenin, while surface cells expressed pan-cytokeratin and Napsin A, and stromal cells expressed vimentin. In some cases, ER and PR were also expressed. Conclusions: When diagnosing PSP in needle biopsy specimens, the key to avoiding misdiagnosis is recognizing the presence of dual-cell populations within the tumor. The useful clues include presence of cellular papillae, mild cellular atypia, morphological diversity, interstitial foam-like cell aggregates, and prominent background hemorrhage and sclerosis. The characteristic immunophenotype and middle-aged female predilection are also helpful for the diagnosis of PSP.

Changes associated with dietary beetroot extract on diet-induced damage in the common carotid artery of the albino rat (<i>Rattus norvegicus</i>)

The high-fat high-fructose diet (HFHFr) has become widespread globally corresponding to a rise in obesity and cardiovascular diseases. Traditionally, these diseases were managed by multiple-drug regimens whose adherence was limited by side effects, hence leading to consideration of natural compounds. Recent studies have exploited the phytochemical properties of numerous plant extracts in ameliorating the histological changes seen in common carotid artery (CCA) damage, however, hardly any studies have investigated the effect of beetroot extract. The CCA were obtained from a biobank of a study that induced HFHFr in 45 male rats. Rats in the control group had received standard rat chow and water, and the positive control group received HFHFr. Those in the experimental group received HFHFr and 200mg/kg beetroot extract. These rats were randomly selected, euthanized and perfused on weeks 4,8,10 and 16. Their CCA were harvested, processed and stereological techniques applied to determine the densities of different histological components of the CCA.The HFHFr fed experimental animals revealed medial vascular thickening with a resultant increase in carotid intima-media thickness, increased vascular smooth muscle density, reduced elastic fiber density, and increased collagen fiber density compared to controls. Beetroot coadministration was protective against most of these structural changes. Dietary administration of beetroot extract has been found to be ameliorative to structural changes on the CCA following administration of HFHFr. Therefore, dietary beetroot extract may be indicated to mitigate harmful changes following long term exposure to a high fat high fructose diet.

Intratumoral heterogeneity of oncogenic drivers in mixed histology lung adenocarcinomas: How tissue selection impacts molecular testing?

Intratumoral heterogeneity of oncogenic drivers in mixed histology lung adenocarcinomas: How tissue selection impacts molecular testing?

MRI features of combined hepatocellular-cholangiocarcinoma.

Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare liver tumor which has a more aggressive behavior and worse survival outcome than hepatocellular carcinoma (HCC), with a prognosis similar to that of intrahepatic cholangiocarcinoma (iCCA). With limited literature on the appearance of this tumor on MRI, it remains a diagnostic challenge. In this review, we looked at the currently described MRI findings in this uncommon entity. Based on studies conducted to date, a mixed pattern at imaging has demonstrated the highest specificity, seen as a combination of areas showing progressive enhancement of the lesion, arterial enhancement with washout, and areas of arterial enhancement without washout and/or hypovascularity. Tumor markers may aid in identification, particularly in cases where the imaging appearance mimics that of isolated HCC or iCCA. Intratumoral heterogeneity leads to difficulties with pathologic diagnosis from sampling due to the possibility of an incorrect diagnosis if the biopsy specimen does not contain adequate tissue comprising both histologic components.

Distinctive Phenotypic and Microenvironmental Characteristics of Neuroendocrine Carcinoma and Adenocarcinoma Components in Gastric Mixed Adenoneuroendocrine Carcinoma

Distinctive Phenotypic and Microenvironmental Characteristics of Neuroendocrine Carcinoma and Adenocarcinoma Components in Gastric Mixed Adenoneuroendocrine Carcinoma

Clinical outcome predictors for metastatic renal cell carcinoma: a retrospective multicenter real-life case series

Over the last decades, the therapeutic armamentarium of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of tyrosin-kinase inhibitors (TKI), immune-checkpoint inhibitors (ICI), and immune-combinations. RCC is heterogeneous, and even the most used validated prognostic systems, fail to describe its evolution in real-life scenarios. Our aim is to identify potential easily-accessible clinical factors and design a disease course prediction system. Medical records of 453 patients with mRCC receiving sequential systemic therapy in two high-volume oncological centres were reviewed. The Kaplan-Meier method and Cox proportional hazard model were used to estimate and compare survival between groups. As first-line treatment 366 patients received TKI monotherapy and 64 patients received ICI, alone or in combination. The mean number of therapy lines was 2.5. A high Systemic Inflammation Index, a BMI under 25 Kg/m2, the presence of bone metastases before systemic therapy start, age over 65 years at the first diagnosis, non-clear-cell histology and sarcomatoid component were correlated with a worse OS. No significant OS difference was observed between patients receiving combination therapies and those receiving exclusively monotherapies in the treatment sequence. Our relapse prediction system based on pathological stage and histological grade was effective in predicting the time between nephrectomy and systemic treatment. Our multicentric retrospective analysis reveals additional potential prognostic factors for mRCC, not included in current validated prognostic systems, suggests a model for disease course prediction and describes the outcomes of the most common therapeutic strategies currently available.