Dolores Caffarena, Julieta Cittadini, Carlos Miguel Lumi, Alejandro Gutierrez, Luciana La Rosa

INTRODUCTION 

High-grade intraepithelial squamous lesions (H-ASIL) are considered the precursor to squamous cell carcinoma. Although it is uncommon when compared to other gastrointestinal neoplasms, its incidence has doubled in the last 25 years with a current prevalence of 1.8/100,000 inhabitants. In 2019, the United States is expected to have an incidence of 8300 new cases and 1280 deaths from cancer.1,2 

There are multiple classifications, both histological and cytological to classify the different degrees of dysplasia. In 2012, the LAST (Lower Anogenital Squamous Terminology) classification was proposed, which unifies the different nomenclatures of the lesions caused by HPV in the anogenital tract. It subdivides them into low-grade (L-SIL) and high-grade (H-SIL) intraepithelial squamous lesions (SIL).3  

L-SILs are not premalignant lesions, but have the potential to progress to HSIL. H-SIL are premalignant lesions and are always recommended for treatment.4 

There are different risk factors: positive serology for human immunodeficiency virus (HIV), practice of anorective intercourse, smoking, multiplicity of sexual partners, history of human papillomavirus (HPV) infection, organ transplantation, and history of SIL or squamous carcinoma of the lower genital tract (TGI). In these groups, the prevalence of cancer increases considerably with respect to the general population, reaching up to 45/100000 in male patients who have sex with men (MSM) HIV positive.1

That is why different Societies recommend its screening and treatment in high-risk populations. 

The proposed method for the investigation consists of performing a proctologic examination, which should always include the performance of an anorectal touch and anal PAP, followed, if positive or having a risk factor, by a high-resolution anoscopy (AAR).7

OBJECTIVES 

To describe the population and manifestations of H-ASIL in the high-resolution anoscopy of our patients. 

Design: Retrospective, descriptive. 

MATERIAL AND METHOD 

We reviewed the medical histories and AAR images of patients diagnosed with H-ASIL between January 2016 and July 2017. As part of the H-ASIL screening, we performed anal cytology and AAR in patients at high risk for squamous cell carcinoma of the anus (SCA). We included in the MSM screening, patients with HIV infection, women with a history of HPV lesions of the lower genital tract (TGI) and immunosuppressed by iatrogenic cause. MSM patients and individuals with HIV predominate in our care population, most of them men. 

In all cases, anorectal examination, anal cytology and AAR were performed at the same time with the intention of increasing the sensitivity of the detection of lesions. 

The cytology is performed with a cytoobrush moistened with water. The brush is inserted into the anal canal approximately 4 cm, rotated repeatedly as it is removed, pressing against all faces to ensure a good sample and then the material obtained on a slide is spread and fixed with a paragliding lacquer or immersed in alcohol. To improve the return of the research, patients are asked to do so within 24 hours. prior to the study do not maintain receptive sex and do not place creams, gels, suppositories or enemas. 

In all cases, anorectal examination, anal cytology and AAR were performed at the same time with the intention of increasing the sensitivity of the detection of lesions. 

The cytology is performed with a cytoobrush moistened with water. The brush is inserted into the anal canal approximately 4 cm, rotated repeatedly as it is removed, pressing against all faces to ensure a good sample and then the material obtained on a slide is spread and fixed with a paragliding lacquer or immersed in alcohol. To improve the return of the research, patients are asked to do so within 24 hours. prior to the study do not maintain receptive sex and do not place creams, gels, suppositories or enemas. 

We perform the AAR with the patient in the left lateral position, without sedation and with local anesthesia with 2% lidocaine gel. We apply 5% acetic acid and, after 2 minutes, perform the magnified examination. We use a Newton brand colposcope with three magnifications (10x, 16x and 25x). We carefully observe the squamocolumnar junction, the distal anal duct and the perianal area, frequently moistening with 5% acetic acid. 

Aceto-white areas with a pointed and/or mosaic vascular pattern were considered suspicious of ASIL. Given these findings, to increase the degree of suspicion and delimit the injury, we used Lugol’s solution. We take biopsies for pathological anatomy in all cases. 

RESULTS 

Between January 2016 and July 2017, 184 ARAs were conducted. 143 lesions suspected of ASIL were biopsied. Twenty-six of them, present in 13 patients, were reported as H-ASIL. The rest were low-grade lesions (NSAID I or condyloma, according to the LAST classification).3 

Eleven of the H-ASIL patients were men; ten were MSM and had HIV infection. The remaining male was heterosexual, HIV negative, but had a history of peri- and endoanal condylomas. One of the women had a history of systemic lupus erythematosus of 20 years of evolution, kidney transplant treatment with sirulimus 4mg/day and stage 1b vulvar squamous cell carcinoma so she had been treated by vulvectomy. The other patient was detected a lesion in the anal duct during a videocolonoscopy for colon cancer investigation so she was referred for the performance of an AAR. He reported a history of cervical SIL. 

All lesions were subclinical and were found at the endoanal level; they were entirely flat and olive-white. We searched for areas with pointing and/or mosaic suggestive of ASIL. The most frequently found vascular patterns were mosaic and thick lace. The use of Lugol allowed us to increase the degree of suspicion and delimit suspicious lesions. In all cases, the lack of staining (Lugol negative) of the suspicious area was evident. 

Biopsies were taken for pathological anatomy under direct vision (Figs. 1 to 6). 

Fig.1. Mosaico Acetoblanco
Fig.1. Mosaico Acetoblanco
Figura2. Lesión delimitada con Lugol
Fig. 2. Lesión delimitada con Lugol
Fig.3. Mosaico en hemiano anterior
Figura 4. Lesión Lugol negativa
Fig. 4. Lesión Lugol negativa
Figura 5. Puntillado fino y vasos en loop
Fig. 5. Puntillado fino y vasos en loop
Figura 6. Lesión delimitada con Lugol
Fig. 6. Lesión delimitada con Lugol

DISCUSSION 

Different risk groups for high-grade lesions or cancer have been described, with HIV-positive MSM being predominant in most international series.8 In our case studies, all patients were in at least one risk group. The majority of the population served in our Center’s STI clinic are MSM, mostly HIV positive. This is reflected in this study in which 10 of 13 H-SIL were found in patients with these characteristics. In other working groups, the distribution may vary, mainly due to the population served. For example, at the local level, reported that 14 of 20 patients screened were women, mostly with a history of HPV lesions in the TGI.9 Only two of our patients were female; both had a history of TGI (vulvar cancer and CIN) lesion and one of them was also immunosuppressed from a solid organ transplant. 

The main world reference of the AAR is Dr Palefsky. In 2012 he published an article in which he describes in detail the fundamentals of this technique and which, in his opinion, is the best technique to perform it. He concludes by saying that the learning curve of AAR is long, even for trained colposcopists and that the correlation between Cytology and histology should always be made.10 

In 2016, the International Guide of the International Society of Neoplasms (IANS) was published, which proposes a minimum of competences that must be met in order to carry out AAR in an efficient way.11 

In this study, all lesions were subclinical and required high-resolution anoscopy for detection and targeted treatment. 

In accordance with naomi Jay et al., all lesions were flat, with a dotted or mosaic pattern and Negative Lugol.12 

CONCLUSION 

Like other authors, we believe it is important for professionals to incorporate H-ASIL research in the at-risk population. Because there is no good correlation between PAP, AAR and histology, their combined use improves the likelihood of detection of preneoplastic lesions. 

BIBLIOGRAPHY 

  1. Roberts JR, Siekas LL, Kas AM, et al. Anal intraepithelial neoplasia: A review of diagnosis and management. World J Gastrointest Oncol. 2017; 15(2):50-61.
  2. Elorza G, Saralegui Y, Enríquez-Navascués JM, et al. Neoplasia intraepitelial anal: una revisión de conjunto. Rev Esp Enf Dig. 2016;108(1): 31-39.
  3. Darragh TM, Colgan TJ, Cox JT et al. The Lower Anogenital Squamous Terminology Standardization Project for HPVssociated Lesions: Background and Consensus Recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med. 2012; 136:1266-97.
  4. Danaire C, Reillo M, Martínez-Ezcoriza JC, et al. Anal study in immunocompetent women with human papillomavirus related lower genital tract pathology. European J Obst and Gyn. 2017; 211:15-20.
  5. Albuquerque A, High-resolution anoscopy: Unchartered territory for gastroenterologist. World J Gastrointest. 2015; 25(13):1083-7.
  6. Wang CJ, Sparano J, Palefky JM,et al. Human Immunodeficiency Virus/AIDS, Human Papillomavirus and Anal Cancer. Surg Oncol Clinic N Am. 2017; 26(1):17-31.
  7. Consenso argentino sobre virus de papiloma humano (HPV) y herpes simplex virus (HSV tipo 1 y 2). Sociedad argentina de dermatologia. 2016.
  8. Goldstone SE, Johnstone AA, Moshier EL, et al. Long term outcome of ablation of HG-AIN. Recurrence and incidence of cancer. Dis Colon Rectum. 2014; 57(3): 316-323.
  9. Presencia GJ, Pastore RLO, Svidler Lopez L, et al. Detección temprana de la displasia anal con Citologia (PAP) y anoscopia de alta resolucion (aar) en la población de riesgo: experiencia inicial. Rev Argent Coloproct. 2015; 26(1):1216.
  10. Palefsky JM. Practising high-resolution anoscopy. Sexual Health. 2012; 9: 580-586.
  11. Hillman RJ, Cuming T, Darragh T, et al. 2016 IANS International Guidelines for practica Standards in the detection of anal Cancer precursors. J Low Genit Tract Dis. 2016; 20:283-291.
  12. Jay N, Berry M, Miaskowski C, et al. Colposcopic characteristics and Lugol`s steining differentiate anal High-grade and los-grade squamous intraepithelial lesions during high resolution anoscopy. Papillomavirus Res. 2015; 1:101-108