The "Forgotten" Subtypes of Breast Carcinoma: A Systematic Review of Selected Histological Variants Not Included or Not Recognized as Distinct Entities in the Current World Health Organization Classification of Breast Tumors.

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.

Nuck Canal Endometriosis Following IVF Attempts in a Young Patient-Report of a Case.

INTRODUCTION: Endometriosis is a common benign condition affecting 10-15% of women of reproductive age. An unusual site of endometriosis is the canal of Nuck, which is a physiologically obliterated space in women spanning the area from the deep inguinal ring to the labia majora. CASE PRESENTATION: A 37-year-old woman, with a past medical history of several in vitro fertilization attempts, presented with a right-sided painful inguinal mass. She was subsequently offered surgical exploration and excision of the lesion, which revealed the presence of endometrial glands and stroma. DISCUSSION: Despite being a relatively common and benign pelvic condition, endometriosis can rarely manifest in the inguinal region, within the canal of Nuck. The treating physician should be cognizant of Nuck canal endometriosis, especially in young female patients presenting with an irreducible mass in the inguinal region and associated cyclic pain or infertility. CONCLUSION: When clinically and radiologically suspected, surgical excision is indicated to establish the diagnosis, provide symptomatic relief and guide further decision making.

Standardised definitions and diagnostic criteria for extranodal extension detected on histopathological examination in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Detection of extranodal extension on histopathology in surgically treated head and neck squamous cell carcinoma indicates poor prognosis. However, there is no consensus on the diagnostic criteria, interpretation, and reporting of histology detected extranodal extension, which has contributed to conflicting evidence in the literature, and likely clinical inconsistency. The Head and Neck Cancer International Group conducted a three-round modified Delphi process with a group of 19 international pathology experts representing 15 national clinical research groups to generate consensus recommendations for histology detected extranodal extension diagnostic criteria. The expert panel strongly agreed on terminology and diagnostic features for histology detected extranodal extension and soft tissue metastasis. Moreover, the panel reached consensus on reporting of histology detected extranodal extension and on nodal sampling. These consensus recommendations, endorsed by 19 organisations representing 34 countries, are a crucial development towards standardised diagnosis and reporting of histology detected extranodal extension, and more accurate data collection and analysis.

Malignant Brenner Tumor of the Ovary: A Systematic Review of the Literature.

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.

Seasonal Variation in Sudden Cardiac Death: Insights from a Large United Kingdom Registry.

BACKGROUND: Sudden cardiac death (SCD) is relatively common and may occur in apparently healthy individuals. The role of seasonal variation as a risk factor for SCD is poorly understood. The aim of this study was to investigate whether SCD exhibits a predilection for specific seasons. METHODS: We reviewed a database of 4751 cases of SCD (mean age 38 ± 17 years) referred to our Center for Cardiac Pathology at St George's University of London between 2000 and 2018. Clinical information was obtained from referring coroners who were asked to complete a detailed questionnaire. All cases underwent macroscopic and histological evaluation of the heart, by expert cardiac pathologists. RESULTS: SCD was more common during winter (26%) and rarer during summer (24%), p = 0.161. Significant seasonal variation was not observed among cases of sudden arrhythmic death syndrome (SADS, 2910 cases) in which the heart is structurally normal. In contrast, a significant difference in seasonal distribution among decedents exhibiting cardiac structural abnormalities at the post-mortem examination (n = 1841) was observed. In this subgroup, SCDs occurred more frequently during winter (27 %) compared to summer (22%) (p = 0.007). In cases diagnosed with a myocardial disease (n = 1399), SCD was most common during the winter (27%) and least common during the summer (22%) (p = 0.027). CONCLUSIONS: While SADS occurs throughout the year with no seasonal variation, SCD due to structural heart disease appears to be more common during the winter. Bio-meteorological factors may be potential triggers of SCD in individuals with an underlying structural cardiac abnormality.

Diagnostic Challenges during Inflammation and Cancer: Current Biomarkers and Future Perspectives in Navigating through the Minefield of Reactive versus Dysplastic and Cancerous Lesions in the Digestive System.

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.

Cervical HPV Infections, Sexually Transmitted Bacterial Pathogens and Cytology Findings-A Molecular Epidemiology Study.

Prevalent cervical HPV infection and high-risk HPV persistence consequences have been extensively investigated in the literature; nevertheless, any causative interrelations of other sexually transmitted bacterial infections (STIs) with cervical HPV infection have not yet been fully elucidated. This study aimed to investigate the possible association of STIs with cervical cytology aberrations and HPV genotyping results in a representative sample of predominantly young Greek women. Liquid-based cytology and molecular detection for bacterial STIs and HPV as well as extended HPV genotyping were simultaneously assessed in cervical samples from 2256 individuals visiting several urban outpatient Gynecology Departments for well-woman visits or cervical screening throughout a 20-month period. All specimens were centrally processed with validated molecular assays. The mean age of the studied women was 37.0 ± 11.7 years; 722 women (33.30%) tested positive for STI (mean age 34.23 ± 10.87 years). A higher mean age (38.34 ± 11.83 years (p < 0.05)) was associated with negative STI testing. Chlamydia trachomatis was detected in 59 individuals (8.2%), Mycoplasma hominis in 156 (21.6%), Mycoplasma genitalium in 14 (1.9%), and Ureaplasma spp. in 555 (76.9%); infections with two bacterial pathogens were identified in 73 samples (10.1%). Cervical HPV was detected in 357 out of 1385 samples with a valid HPV typing result (25.8%). The mean age of HPV-positive women was 32.0 ± 8.4 years; individuals testing HPV-negative were slightly older (N = 1028): 34.4 ± 9.2 (p < 0.05). Among the 1371 individuals with valid results both for bacterial STIs and cervical HPV detection, women with an HPV-positive sample were more likely to harbor an STI (OR: 2.69, 95% CI 2.10-3.46, p < 0.05). Interestingly, bacterial STI positivity illustrated significant heterogeneity between NILM and LSIL cases, with 28.88% of NILM and 46.33% of LSIL cases harboring an STI, respectively (p < 0.05). In brief, in a population with a high prevalence for STIs, especially Ureaplasma spp., an association was documented between bacterial pathogen detection and cervical HPV infection, as well as abnormal cytology; these findings merit further investigation.

Human Papillomavirus 16 DNA Methylation Patterns and Investigation of Integration Status in Head and Neck Cancer Cases.

Persistent high-risk human papillomavirus (HPV) infection is a pivotal factor in the progression of cervical cancer. In recent years, an increasing interest has emerged in comprehending the influence of HPV on head and neck squamous cell carcinoma (HNSCC). Notably, it is well established that HPV-associated HNSCC show cases with distinct molecular and clinical attributes compared to HPV-negative cases. The present study delves into the epigenetic landscape of HPV16, specifically its L1 gene and untranslated region (UTR), through pyrosequencing, while the HPV16 DNA physical status was evaluated using E2/E6 ratio analysis in HPV16-positive HNSCC FFPE biopsies. Our findings reveal substantial methylation across six sites within the HPV16 L1 gene and seven sites in the UTR. Specifically, methylation percentages of two L1 CpG sites (7136, 7145) exhibit significant associations with tumor histological grade (p < 0.01), while proving concurrent methylation across multiple sites. The HPV16 DNA physical status was not correlated with the methylation of viral genome or tumor characteristics. This is the first study that examines epigenetic modifications and the HPV16 DNA physical status in Greek HNSCC patients. Our findings suggest an orchestrated epigenetic modulation among specific sites, impacting viral gene expression and intricate virus-host interactions.

Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer.

Purpose: We conducted a phase II randomized noncomparative window of opportunity (WOO) trial to evaluate the inhibition of cellular proliferation and the modulation of immune microenvironment after treatment with olaparib alone or in combination with cisplatin or durvalumab in patients with operable head and neck squamous cell carcinoma (HNSCC). Experimental Design: Forty-one patients with HNSCC were randomized to cisplatin plus olaparib (arm A), olaparib alone (arm B), no treatment (arm C) or durvalumab plus olaparib (arm D). The primary endpoint was to evaluate the percentage of patients in each arm that achieved a reduction of at least 25% in Ki67. Secondary endpoints included objective response rate (ORR), safety, and pathologic complete response (pCR) rate. Paired baseline and resection tumor biopsies and blood samples were evaluated for prespecified biomarkers. Results: A decrease in Ki67 of at least 25% was observed in 44.8% of treated patients, as measured by quantitative immunofluorescence. The ORR among treated patients was 12.1%. pCR was observed in 2 patients. Two serious adverse events occurred in 2 patients.Programmed death ligand 1 (PD-L1) levels [combined positive score (CPS)] were significantly higher after treatment in arms A and D. Expression of CD163 and colony-stimulating factor 1 receptor (CSF1R) genes, markers of M2 macrophages, increased significantly posttreatment whereas the expression of CD80, a marker of M1 macrophages, decreased. Conclusion: Preoperative olaparib with cisplatin or alone or with durvalumab was safe in the preoperative setting and led to decrease in Ki67 of at least 25% in 44.8% of treated patients. Olaparib-based treatment modulates the tumor microenvironment leading to upregulation of PD-L1 and induction of protumor features of macrophages. Significance: HNSCC is characterized by defective DNA repair pathways and immunosuppressive tumor microenvironment. PARP inhibitors, which promote DNA damage and "reset" the inflammatory tumor microenvironment, can establish an effective antitumor response. This phase II WOO trial in HNSCC demonstrated the immunomodulatory effects of PARP inhibitor-induced DNA damage. In this chemo-naïve population, PARP inhibitor-based treatment, reduced tumor cell proliferation and modulated tumor microenvironment. After olaparib upregulation of PD-L1 and macrophages, suggests that combinatorial treatment might be beneficial. Synopsis: Our WOO study demonstrates that preoperative olaparib results in a reduction in Ki67, upregulation of PD-L1 CPS, and induction of protumor features of macrophages in HNSCC.

Uterine collision tumor (PEComa and endometrioid carcinoma) in a tuberous sclerosis patient: a case report.

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.

Primary Adrenal Lymphomas with Cushing's Syndrome: Two Cases with Evidence of Endogeneous Cortisol Production by the Neoplastic Lymphoid Cells.

Primary adrenal lymphoma (PAL) is a rare entity that presents as unilateral or bilateral rapidly growing adrenal masses, with signs and symptoms most commonly related to adrenal insufficiency due to the mass effect on the surrounding tissues. Although steroeidogenesis has not been previously described in PAL, we herein report two cases of PAL presenting as adrenal incidentalomas (AIs) that demonstrated autonomous cortisol production. A 52-year-old woman presented with lumbar pain; a computed tomography (CT) scan demonstrated a left AI measuring 8.5 × 15 × 10 cm. Similarly, an 80-year-old woman presented with lumbar pain, demonstrating in a CT scan a bilateral AI (right: 9 × 6.5 cm, left: 3.6 × 3.2 cm). Both cases underwent a full hormonal evaluation according to the algorithm for the investigation of AIs, demonstrating increased 24-h cortisol excretion, suppressed fasting adrenocorticotropic hormone (ACTH) levels, and non-suppressed serum cortisol levels in both the overnight and the low-dose dexamethasone suppression tests, indicating autonomous cortisol secretion and Cushing's syndrome. In a relatively short time, both patients developed night sweats, and their clinical picture deteriorated, while the CT scans showed increased dimensions of the masses with radiological characteristics compatible to lymphoma. Both patients underwent ultrasound-guided biopsies (FNBs), revealing infiltration of the left adrenal by diffuse large B-cell lymphoma in the first case, whereas bilateral adrenal infiltration from the same histological type was noted in the second case. Subsequently, they were treated with immunochemotherapy, but the second patient died from an infection shortly after the initiation of the treatment. To our knowledge, this is the first report of PAL presenting with Cushing's syndrome due to autonomous cortisol production, indicating that neoplastic lymphoid cells in PAL might acquire the potential for steroidogenesis; therefore, more cases of PAL should be analyzed so as to further elucidate the complex pathogenesis and the natural course of this entity.

Multiple cerebral microinfarcts: an uncommon presentation of Cerebral Amyloid Angiopathy-related inflammation.

BACKGROUND: Cerebral Amyloid Angiopathy-related inflammation (CAA-ri) is a distinct but rare subset of CAA. The greater availability of high resolution Magnetic Resonance Imaging (MRI) has currently allowed the increasing recognition and diagnosis of this entity, without the risk of a brain biopsy. However, in rare cases with typical clinical characteristics but uncommon neuroimaging findings at presentation, the brain-biopsy is required for an early and reliable diagnosis. CASE DESCRIPTION: A 71-year-old man with arterial hypertension presented due to 1-week history of headache, vomiting, disorientation and impaired consciousness. Brain MRI revealed multiple acute cortical/subcortical microinfarcts, scarce microbleeds, extensive right parietooccipital and left frontotemporal leptomeningeal enhancement. After an extensive diagnostic work-up, excluding infectious, neoplastic and autoimmune etiologies, the patient underwent brain-biopsy. Histology disclosed amyloid deposition in an arteriolar wall and the patient fulfilled diagnostic criteria for probable CAA-ri with supporting pathology. He received intravenous methylprednisolone, followed by oral tapering with steroids showing clinical and radiological improvement with complete resolution of gadolinium enhancement. Follow-up MRI revealed an increase of cerebral microbleeds and the patient fulfilled CAA-ri neuroimaging criteria. CONCLUSIONS: This case highlights the importance of continuous vigilance from clinical neurologists to detect CAA-ri diagnosis and the diagnostic value of brain-biopsy in CAA-ri patients with atypical neuroimaging presentation, such as acute microinfarcts. The early diagnosis and the prompt treatment initiation can improve the prognosis and the evolution of this rare disorder.

Epidemiology of Mucormycosis in Greece; Results from a Nationwide Prospective Survey and Published Case Reports.

Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We analysed the epidemiology of mucormycosis in Greece in a multicentre, nationwide prospective survey of patients of all ages, during 2005-2022. A total of 108 cases were recorded. The annual incidence declined after 2009 and appeared stable thereafter, at 0.54 cases/million population. The most common forms were rhinocerebral (51.8%), cutaneous (32.4%), and pulmonary (11.1%). Main underlying conditions were haematologic malignancy/neutropenia (29.9%), haematopoietic stem cell transplantation (4.7%), diabetes mellitus (DM) (15.9%), other immunodeficiencies (23.4%), while 22.4% of cases involved immunocompetent individuals with cutaneous/soft-tissue infections after motor vehicle accident, surgical/iatrogenic trauma, burns, and injuries associated with natural disasters. Additionally, DM or steroid-induced DM was reported as a comorbidity in 21.5% of cases with various main conditions. Rhizopus (mostly R. arrhizus) predominated (67.1%), followed by Lichtheimia (8.5%) and Mucor (6.1%). Antifungal treatment consisted mainly of liposomal amphotericin B (86.3%), median dose 7 mg/kg/day, range 3-10 mg/kg/day, with or without posaconazole. Crude mortality was 62.8% during 2005-2008 but decreased significantly after 2009, at 34.9% (p = 0.02), with four times fewer haematological cases, fewer iatrogenic infections, and fewer cases with advanced rhinocerebral form. The increased DM prevalence should alert clinicians for timely diagnosis of mucormycosis in this patient population.

Diffuse panniculitis in a teenage male with ZZ α1-antitrypsin deficiency.

Diffuse panniculitis is a rare manifestation of α1-ATD, albeit perhaps the most fulminant and life-threatening complication, associated usually with ZZ phenotype. Intravenous α1-AT treatment is lifesaving. https://bit.ly/3EDmCzT.

Next-generation sequencing (NGS) profiling of matched tumor and circulating tumor DNA (ctDNA) in head and neck squamous cell carcinoma (HNSCC).

OBJECTIVES: The aim of this pilot study was to evaluate the presence of somatic mutations in matched tumor and circulating DNA (ctDNA) samples from patients with primary head and neck squamous cell carcinoma (HNSCC) and assess the association of changes in ctDNA levels with survival. MATERIALS AND METHODS: Our study included 62 patients with stage I-IVB HNSCC treated with surgery or radical chemoradiotherapy with curative intent. Plasma samples were obtained at baseline, at the end of treatment (EOT), and at disease progression. Tumor DNA was extracted from plasma (ctDNA) and tumor tissue (tDNA). The Safe Sequencing System was used assess the presence of pathogenic variants in four genes (TP53, CDKN2A, HRAS and PI3KCA) in both ctDNA and tDNA. RESULTS: Forty-five patients had available tissue and plasma samples. Concordance of genotyping results between tDNA and ctDNA at baseline was 53.3%. TP53 mutations were most commonly identified at baseline in both ctDNA (32.6%) and tDNA (40%). The presence of mutations in this restricted set of 4 genes in tissue samples at baseline was associated with decreased overall survival (OS) [median 58.3 months for patients with mutations vs. 89 months for patients without mutations, p < 0.013]. Similarly, patients presenting with mutations in ctDNA had shorter OS [median 53.8 vs. 78.6 months, p < 0.037]. CtDNA clearance at EOT did not show any association with PFS or OS. CONCLUSIONS: Liquid biopsy enables real-time molecular characterization of HNSCC and might predict survival. Larger studies are needed to validate the utility of ctDNA as a biomarker in HNSCC.

Significance of MYB and NTRK Expression in Head and Neck Adenoid Cystic Carcinoma.

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.

Expression profile of miRNAs computationally predicted to target PDL-1 in cervical tissues of different histology groups.

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.

Prevalence of Small Intestinal Bacterial Overgrowth Syndrome in Patients with Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis: A Cross-Sectional Study.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial, wide-spectrum liver disorder. Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the number and/or type of colonic bacteria in the upper gastrointestinal tract. SIBO, through energy salvage and induction of inflammation, may be a pathophysiological factor for NAFLD development and progression. AIM/METHODS: Consecutive patients with histological, biochemical, or radiological diagnosis of any stage of NAFLD (non-alcoholic fatty liver [NAFL], non-alcoholic steatohepatitis [NASH], cirrhosis) underwent upper gastrointestinal endoscopy. Duodenal fluid (2cc) was aspirated from the 3rd-4th part of duodenum into sterile containers. SIBO was defined as ≥103 aerobic colony-forming units (CFU)/mL of duodenal aspirate and/or the presence of colonic-type bacteria. Patients without any liver disease undergoing gastroscopy due to gastroesophageal reflux disease (GERD) comprised the healthy control (HC) group. Concentrations (pg/mL) of tumor necrosis factor alpha (TNFα), interleukin (IL)-1ß, and IL-6 were also measured in the duodenal fluid. The primary endpoint was to evaluate the prevalence of SIBO in NAFLD patients, while the comparison of SIBO prevalence among NAFLD patients and healthy controls was a secondary endpoint. RESULTS: We enrolled 125 patients (51 NAFL, 27 NASH, 17 cirrhosis, and 30 HC) aged 54 ± 11.9 years and with a weight of 88.3 ± 19.6 kg (NAFLD vs. HC 90.7 ± 19.1 vs. 80.8 ± 19.6 kg, p = 0.02). Overall, SIBO was diagnosed in 23/125 (18.4%) patients, with Gram-negative bacteria being the predominant species (19/23; 82.6%). SIBO prevalence was higher in the NAFLD cohort compared to HC (22/95; 23.2% vs. 1/30; 3.3%, p = 0.014). Patients with NASH had higher SIBO prevalence (6/27; 22.2%) compared to NAFL individuals (8/51; 15.7%), but this difference did not reach statistical significance (p = 0.11). Patients with NASH-associated cirrhosis had a higher SIBO prevalence compared to patients with NAFL (8/17; 47.1% vs. 8/51; 15.7%, p = 0.02), while SIBO prevalence between patients with NASH-associated cirrhosis and NASH was not statistically different (8/17; 47.1% vs. 6/27; 22.2%, p = 0.11). Mean concentration of TNF-α, IL-1ß, and IL-6 did not differ among the different groups. CONCLUSION: The prevalence of SIBO is significantly higher in a cohort of patients with NAFLD compared to healthy controls. Moreover, SIBO is more prevalent in patients with NASH-associated cirrhosis compared to patients with NAFL.

Evidence That Cigarette Smoking Alters Alveolar Type I Cell Nuclear Fractal Dimension.

A large number of alveolar type I and II cells from the lungs of both smokers and non-smokers was collected using 40x magnification histological images from our digital archive. These images underwent a transformation into binary images of nuclear contours, followed by the application of the box-counting method. Statistical analysis revealed a significant difference in the mean box-counting dimension values between type I cells of smokers and non-smokers. However, no significant difference was observed in the mean fractal dimensions of alveolar type II cells. This study provides preliminary evidence of the impact of cigarette smoking on the nuclear shape of alveolar type I cells. Given the high toxicity of cigarette smoke to lung cells and the interconnection between morphology and function, further study is needed to understand its impact on the nuclear shape of these cells. Future research should also explore the effects of second-hand smoke on cell shape.

Diagnostically Challenging Subtypes of Invasive Lobular Carcinomas: How to Avoid Potential Diagnostic Pitfalls.

Invasive lobular carcinoma is the most common special breast carcinoma subtype, with unique morphological (discohesive cells, single-cell files, targetoid pattern) and immunohistochemical (loss of E-cadherin and ß-catenin staining) features. Moreover, ILC displays a poor response to neoadjuvant therapy, a different metastatic pattern compared to invasive breast carcinoma of no special type, as well as unique molecular characteristics. In addition to the classic variant of invasive lobular carcinoma, several other well-recognized variants exist, including classic, alveolar, tubulolobular, solid, pleomorphic, signet-ring, and mixed. Furthermore, three novel variants of invasive lobular carcinoma, i.e., with extracellular mucin production, papillary features, and tubular elements, have been described during the last decade. We herewith focus on the unique morphological and immunohistochemical characteristics of these novel varieties of invasive lobular carcinoma, as well as differential diagnostic considerations and potential diagnostic pitfalls, especially when dealing with biopsy specimens.