Utility of SATB2 and MOC-31 Immunostains to Distinguish Between Poorly Differentiated Rectal Adenocarcinoma and Anal Squamous Cell Carcinoma.

OBJECTIVES: Colorectal adenocarcinoma and squamous cell carcinoma (SCC) can arise in the anorectum and present a significant diagnostic challenge when poorly differentiated. Accurate diagnosis can significantly influence management, as the treatments for these conditions involve distinct neoadjuvant chemoradiotherapy regimens. MOC-31 and SATB2 have been utilized as specific markers of glandular differentiation and colorectal origin, respectively, but studies have shown that they may be positive in squamous cell carcinoma of other sites. This raises the concern that MOC-31 and SATB2 may be positive in squamous cell carcinoma of the anorectum, and overreliance on these stains may be a potential diagnostic pitfall in differentiating rectal poorly differentiated adenocarcinoma (PDA) from anal nonkeratinizing SCC. METHODS: We identified biopsies from 10 rectal PDA and 17 anorectal nonkeratinizing SCC cases and stained them for MOC-31 and SATB2. RESULTS: We found that MOC-31 was highly sensitive, being positive in 10/10 cases of rectal PDA, but not specific, as it was also positive in 11/17 SCC cases. In contrast, SATB2 was both sensitive, with positive staining in 10/10 rectal PDA cases, and specific, with negative staining in 17/17 SCC cases. This includes equivocal staining in 4 of these negative SCC cases. MOC-31 had a sensitivity of 100% and specificity of 35.3%, while SATB2 had a sensitivity of 100% and specificity of 100%. CONCLUSIONS: Unlike squamous mucosa of the head and neck, and esophagus, SCC of the anus does not frequently stain positively for SATB2. These data suggest that SATB2 is a reliable marker in distinguishing rectal PDA from anorectal nonkeratinizing SCC, whereas MOC-31 is commonly positive in SCC of the anus. It is also important to note that equivocal SATB2 staining may be seen in SCC.

[Anorectal melanoma: Clinical case]. / Melanoma anorrectal: un caso clínico.

Background: Anorectal melanoma (AM) is a rare and aggressive type of tumor, with varied and inconclusive scientific information. Its preoperative diagnosis is challenging due to its rarity and similarity to other anorectal conditions. It represents only 1.3% of melanomas and affects more women than men. Approximately 20-30% of AM cases are amelanotic, complicating endoscopic detection and leading to misdiagnoses. AM is often confused with hemorrhoids, polyps, and rectal cancer in two thirds of patients due to similar symptoms. The causes and risk factors of AM are not well understood, but they are suspected to differ from cutaneous and ocular melanomas. Diagnosis is performed through biopsy and immunohistochemical staining. Colonoscopy helps to characterize the lesions, and histological examination is crucial for definitive diagnosis. Clinical case: 50-year-old woman with rectal bleeding and proctalgia. AM was diagnosed through colonoscopy, and transanal resection with hemorrhoidectomy was performed. Conclusions: Management of AM is complicated by the lack of randomized trials. Resection surgery is the standard treatment, but there is no established protocol. Wide local excision may be an option for limited cases. Further research is needed to improve the management and treatment of AM. Early detection and complete surgical removal are crucial for enhancing survival in these patients.

Introducción: el melanoma anorrectal (MA) es un tipo raro y agresivo de tumor, cuya información científica es variada y poco concluyente. Su diagnóstico preoperatorio es un desafío debido a su rareza y a su similitud con otras afecciones anorrectales. Representa solo el 1.3% de los melanomas y afecta más a mujeres que a hombres. Aproximadamente el 20-30% de los casos de MA son amelanóticos, lo que complica su detección endoscópica y conduce a diagnósticos erróneos. El MA se confunde con hemorroides, pólipos y cáncer de recto en dos tercios de los pacientes debido a síntomas similares. Las causas y factores de riesgo del MA aún no se conocen bien, pero se sospecha que son diferentes de los melanomas cutáneos y oculares. El diagnóstico se realiza mediante biopsia y tinción inmunohistoquímica. La colonoscopía permite caracterizar las lesiones y el examen histológico es crucial para el diagnóstico definitivo. Caso clínico: mujer de 50 años con rectorragia y proctalgia. Se diagnosticó MA mediante colonoscopía y se realizó una resección transanal con hemorroidectomía. Conclusiones: el manejo del MA es complicado por la falta de ensayos aleatorizados. La cirugía de resección es el tratamiento habitual, pero no hay un protocolo establecido. La escisión local amplia puede ser una opción para casos limitados. Se necesita más investigación para mejorar el manejo y tratamiento del MA. La detección temprana y la extirpación quirúrgica completa son cruciales para mejorar la supervivencia en estos pacientes.

Perianal disease in inflammatory bowel disease: Broadening treatment and surveillance strategies for anal cancer.

The perianal disease affects up to one-third of individuals with Crohn's disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.

Cumulative Detection of Anal High-Grade Squamous Intraepithelial Lesions Over 2-Year Follow-up in Men Who Have Sex With Men Living With Human Immunodeficiency Virus in France.

We assessed cumulative detection and determinants of anal high-grade squamous intraepithelial lesions (HSILs) in men who have sex with men living with human immunodeficiency virus and who underwent 3 visits over 2 years, with cytology and high-resolution anoscopy, within the ANRS-EP57-APACHES study. The cumulative HSIL detection rate was 33% (134 of 410), of which 48% HSILs were detected at baseline. HSIL detection varied considerably by center (from 13% to 51%). The strongest HSIL determinants were baseline human papillomavirus 16 (adjusted odds ratio, 8.2; 95% confidence interval, 3.6-18.9) and p16/Ki67 (4.6 [2.3-9.1]). Repeated annual cytology and high-resolution anoscopy improved HSIL detection but did not fully compensate for between-center heterogeneity.

Gastroenterology healthcare in LGBTQ+ individuals.

Lesbian, gay, bisexual, transgender, queer, or questioning individuals, as well as those with another diverse identity (LGBTQ+), present specific nuances in healthcare that physicians must consider in clinical practice. Particularly, gastroenterologists are nowadays facing different issues in several fields regarding LGBTQ+ healthcare, such as endoscopy, inflammatory bowel disease, hepatology, and proctology. In this study, the authors provide a practice-oriented and up-to-date review reinforcing the importance of some of the most prevalent pathologies associated with sexuality that gastroenterologists may encounter in their clinical practice. In terms of endoscopy, authors describe the endoscopic findings related to human papillomavirus (HPV) infection: the esophageal squamous papilloma and cell carcinoma; also highlight the importance of retroflexion maneuver during a routine colonoscopy that allows detection of anal intraepithelial neoplasia lesions that can be anal cancer precursors. Regarding inflammatory bowel disease, some considerations are made about the differential diagnosis with infectious proctitis, and the topic of the risk of anal cancer due to HPV infection, in this specific population, is also addressed. Considering hepatology, the authors review the most important issues related to hepatotropic sexually transmitted infections. The authors also make some comments regarding the possibility of drug-induced liver injury in gender-affirming hormone therapy and pre-exposure prophylaxis for HIV prevention. Finally, considering the proctology field, an up-to-date review is performed regarding anal cancer screening, HPV infection and related diseases, and infectious proctitis management.

Anal intraepithelial neoplasia screening in women from the largest center for lower genital tract disease in China.

This study aimed to provide comprehensive clinical screening data for anal intraepithelial neoplasia (AIN). This study included 312 patients who underwent high-resolution anoscopy (HRA) examinations between January 1, 2020 and April 15, 2024. Clinical data, including demographic information, clinical history, cytology/high-risk human papilloma virus (hrHPV) results, and HRA records, were analyzed. The median age of all patients was 42 years (interquartile range: 33-52 years). Approximately 26.3% reported a history of VIN2/3+, 13.5% had a history of VaIN2/3+, 29.8% had a history of CIN2/3+, 44.6% had persistent cervical HPV16 infection, and 12.5% had immune suppression. Among the 312 patients, 14.4% were diagnosed with AIN2/3, 25.0% with AIN1 and 60.6% were normal. Anal cytological abnormalities were found in 41.3% of all patients, with a significantly higher rate in AIN2/3 patients than in ≤AIN1, 71.1% versus 36.3%, p < 0.001. The hrHPV positivity rate was 89.7%, with HPV16 being the most prevalent. The complete agreement rate for HRA impressions was 79.5%. Multi-variable analysis revealed immune suppression (odds ratio [OR]: 3.47, 95% confidence interval [CI]: 1.42-8.5) and VIN2/3+ (OR: 2.82, 95% CI: 1.27-6.28) were independent risk factors for AIN2/3. Abnormal cytology results (OR: 3.3, 95% CI: 1.52-7.17) and anal HPV16 infection (OR: 3.2, 95% CI: 1.26-8.12) demonstrated similar ORs for AIN2/3. Early screening for AIN2/3+ is crucial in Chinese women with lower genital tract precancerous and cancerous lesions, particularly in those with VIN2/3+ and immune suppression.

Accurate detection of copy number aberrations in FFPE samples using the mFAST-SeqS approach.

BACKGROUND: Shallow whole genome sequencing (Shallow-seq) is used to determine the copy number aberrations (CNA) in tissue samples and circulating tumor DNA. However, costs of NGS and challenges of small biopsies ask for an alternative to the untargeted NGS approaches. The mFAST-SeqS approach, relying on LINE-1 repeat amplification, showed a good correlation with Shallow-seq to detect CNA in blood samples. In the present study, we evaluated whether mFAST-SeqS is suitable to assess CNA in small formalin-fixed paraffin-embedded (FFPE) tissue specimens, using vulva and anal HPV-related lesions. METHODS: Seventy-two FFPE samples, including 36 control samples (19 vulva;17 anal) for threshold setting and 36 samples (24 vulva; 12 anal) for clinical evaluation, were analyzed by mFAST-SeqS. CNA in vulva and anal lesions were determined by calculating genome-wide and chromosome arm-specific z-scores in comparison with the respective control samples. Sixteen samples were also analyzed with the conventional Shallow-seq approach. RESULTS: Genome-wide z-scores increased with the severity of disease, with highest values being found in cancers. In vulva samples median and inter quartile ranges [IQR] were 1[0-2] in normal tissues (n = 4), 3[1-7] in premalignant lesions (n = 9) and 21[13-48] in cancers (n = 10). In anal samples, median [IQR] were 0[0-1] in normal tissues (n = 4), 14[6-38] in premalignant lesions (n = 4) and 18[9-31] in cancers (n = 4). At threshold 4, all controls were CNA negative, while 8/13 premalignant lesions and 12/14 cancers were CNA positive. CNA captured by mFAST-SeqS were mostly also found by Shallow-seq. CONCLUSION: mFAST-SeqS is easy to perform, requires less DNA and less sequencing reads reducing costs, thereby providing a good alternative for Shallow-seq to determine CNA in small FFPE samples.

Prognostic value of PD-L1 expression in patients with anal cancer: a meta-analysis.

Background: The present meta-analysis was performed to evaluate the prognostic and clinicopathological significance of PD-L1 in anal cancer (AC). Methods: Hazard ratios (HRs) and 95% CIs regarding overall survival (OS) and progression-free survival (PFS) were calculated based on PD-L1 levels. Results: According to the combined data, PD-L1 showed no significant relationship with OS (HR = 0.76; 95% CI = 0.35-1.67; p = 0.502) or PFS (HR = 0.88; 95% CI = 0.35-2.33; p = 0.789) in patients with AC. Based on subgroup analysis, PD-L1 overexpression significantly predicted prolonged OS (HR = 0.38; 95% CI = 0.17-0.84; p = 0.017) in tumor node metastasis stages I-III and inferior PFS (HR = 2.73; 95% CI = 1.32-5.65; p = 0.007) in patients with stage I-IV AC. Conclusion: PD-L1 level assessed by immunohistochemistry did not significantly predict survival outcomes in AC cases.

[Box: see text].

Prevalence of anal cytology screening among persons with HIV and lack of access to high-resolution anoscopy at HIV care facilities.

BACKGROUND: People with HIV at highest risk of anal cancer include gay, bisexual, and other men who have sex with men and transgender women aged 35 years or older as well as other people with HIV aged 45 years or older. Identifying and treating precancerous lesions can reduce anal cancer incidence in these groups. We assessed the prevalence of anal cytology and access to high-resolution anoscopy among people with HIV overall and in those individuals at highest risk. METHODS: Data were obtained from the Centers for Disease Control and Prevention's Medical Monitoring Project, a population-based survey of people with HIV aged 18 years and older, and a supplemental Medical Monitoring Project facility survey. We report weighted percentages of people with HIV receiving anal cytology during the past 12 months, access to high-resolution anoscopy, and characteristics of HIV care facilities by availability of high-resolution anoscopy. RESULTS: Overall, 4.8% (95% confidence interval [CI] = 3.4% to 6.1%) of people with HIV had undergone anal cytology in the prior 12 months. Only 7.7% (95% CI = 5.1% to 10.6%) of gay, bisexual, and other men who have sex with men as well as transgender women 35 years of age or older and 1.9% (95% CI = 0.9% to 2.9%) of all other people with HIV aged 45 years and older had anal cytology. Prevalence was statistically significantly low among people with HIV with the following characteristics: non-Hispanic or Latino, Black or African American, high school education or less, heterosexual orientation, and living in southern Medical Monitoring Project states. Among people with HIV, 32.8% (95% CI = 28.0% to 37.7%) had no access to high-resolution anoscopy on-site or through referral at their care facility; 22.2% (95% CI = 19.5% to 24.9%) had on-site access; 45.0% (95% CI = 41.5% to 48.5%) had high-resolution anoscopy available through referral. Most facilities that received Ryan White HIV/AIDS Program funding, cared for more than 1000 people with HIV, or provided on-site colposcopy also provided high-resolution anoscopy on-site or through referral. CONCLUSIONS: Rates of anal cytology and access to high-resolution anoscopy were low among people with HIV, including those individuals at highest risk of anal cancer. Our data may inform large-scale implementation of anal cancer prevention efforts.

Comparative evaluation of Anyplex II HPV28 and Allplex HPV28 molecular assays for human papillomavirus detection and genotyping in anogenital cancer screening.

Persistent infection with high-risk human papillomavirus (HPV) is recognized as the main cause for the development of anogenital cancers. This study prospectively evaluated the diagnostic performance of the novel Allplex-HPV28 assay with the Anyplex-II-HPV28 to detect and genotype HPV in 234 consecutive swabs and 32 biopsies of the anogenital tract from 265 patients with atypical findings in cytomorphological screening. Agreement in HPV-DNA detection between the Anyplex-II and Allplex-HPV28 assays was 99%. There was a notable diversity in the HPV-virome, with the most prevalent high-risk HPV types being 16, 53, 66, and 68. The agreement rates for detecting these genotypes exceeded 93% between the Anyplex-II and Allplex-HPV28 assays. Discrepancies in test results were solely noted for Anyplex-II-HPV28 results with a low signal intensity of "+", and for Allplex-HPV28 results with cycle thresholds of ≥36. The semi-quantitative analysis of HPV-DNA loads showed significant agreement between the Anyplex-II-HPV28 and Allplex-HPV28 assays (p < 0.001). Furthermore, HPV-DNA detection rates and mean HPV-DNA loads significantly correlated with the grade of abnormal changes identified in cytopathological assessment, being highest in cases of HSIL, condyloma accuminatum, and squamous cell carcinoma. Overall agreement rates for detecting specific HPV-types among the Anyplex-II and Allplex-HPV28 assays exceeded 99.5% in cases of atypical squamous cells, condyloma accuminatum, and squamous cell carcinoma. The novel Allplex-HPV28 assay shows good diagnostic performance in detecting and genotyping HPV commonly associated with anogenital cancers. Consequently, this assay could offer substantial potential for incorporation into future molecular screening programs for anogenital cancers in clinical settings.

[Anal canal cancer : epidemiology, work-up, treatment and perspective]. / Le cancer du canal anal : épidémiologie, bilan, traitement et futur.

Although rare, around 2 % of digestive tumours, anal canal tumours remain a pathology that should not be neglected. These are frequently underdiagnosed due to the affected region and the symptoms that can be confused with more common and benign pathologies such as haemorrhoids or anal fissures. The treatment of these tumours is mainly based on radio-chemotherapy to avoid heavy surgical treatment which remains the salvage option. This article aims to review the epidemiology, diagnosis, management, monitoring and future developments for these cancers.

Bien que rares (environ 2 % des tumeurs digestives), les tumeurs du canal anal restent une pathologie à ne pas négliger. Elles sont souvent sous-diagnostiquées en raison de la région touchée et de la symptomatologie non spécifique, et confondues avec des pathologies plus fréquentes et bénignes comme des hémorroïdes ou des fissures anales. Le traitement de ces tumeurs repose principalement sur la radio-chimiothérapie, afin d'éviter une prise en charge chirurgicale lourde qui reste l'option de sauvetage. Cet article a pour but de passer en revue l'épidémiologie, le diagnostic, la prise en charge, le suivi et les futurs développements pour ces cancers.

Multiple carcinomas in a woman with HIV infection: a case report and literature review.

Non-acquired immunodeficiency syndrome-defining cancers (NADCs) are malignancies in persons living with human immunodeficiency virus (PLWHIV) and are not primarily due to the host's immunodeficiency. There is renewed clinical interest in long-term morbidities in PLWHIV as well as malignancies that occur in this population. We herein describe a 36-year-old woman with a 2-year history of an anal wound and right breast mass. She had been diagnosed with HIV infection prior to the development of these lesions. Clinical and laboratory evaluations led to diagnoses of breast and anal cancers. Chemotherapy and antiretroviral therapy were begun, but the patient discontinued these treatments early and was lost to follow-up. NADCs will continue to be a major clinical issue as the global population ages. This presentation of two NADCs (breast and anal cancers) in a PLWHIV further highlights the burden of multiple malignancies on the depleted health of HIV-infected patients. Early identification and treatment of HIV upon patients' presentation to cancer care sites and screening for NADCs at HIV/AIDS care sites are recommended for improved outcomes.