HISTOPATOLOGIA DAS NEOPLASIAS INTRAEPITELIAIS CERVICAIS ASSOCIADAS AO PAPILOMAVÍRUS HUMANO

Introdução: Neoplasias intraepiteliais cervicais (NICs) são lesões precursoras do carcinoma de células escamosas no colo uterino, categorizadas segundo a proporção epitelial afetada: baixo grau (NIC I), grau moderado (NIC II) e alto grau (NIC III), a última correspondendo ao carcinoma in situ. Infecções persistentes de subtipos oncogênicos de alto risco do papilomavírus humano (HPV) podem levar ao desenvolvimento das NICs, com potencial de progressão para câncer invasivo entre 10 e 20 anos. Objetivos: Descrever a histologia cervical, relacionada ao surgimento das NICs decorrentes da infecção pelo HPV. Material e Métodos: Pesquisa bibliográfica nas bases Pubmed e Scielo, utilizando descritores: “cervical cancer”, “cervical intraepithelial neoplasms” e “human papilloma virus”. Foram utilizados Robbins Patologia Básica 9ª Ed.; Junqueira e Carneiro Histologia Básica 12ª Ed. Resultados: A histologia do colo do útero apresenta poucas artérias espiraladas e grandes glândulas ramificadas, não sofre alterações significativas de espessura durante ciclos menstruais e possui três componentes. A ectocérvix se projeta para a vagina e possui epitélio estratificado pavimentoso não queratinizado. A endocérvix é revestida por tecido epitelial glandular colunar simples. Entre as duas regiões está a junção escamocolunar (JEC), ponto de mudança abrupta entre os epitélios. Após ectrópio, a JEC sofre metaplasia escamosa devido à irritação causada pela acidez vaginal, gerando a zona de transformação (ZT). Células-tronco de reserva sustentam a JEC, conduzem a metaplasia e são mais suscetíveis à infecção pelo HPV. A patogênese pelo HPV abrange infecção inicial na JEC que, se persistente, possibilita integração do genoma viral ao do hospedeiro. A expressão das oncoproteínas virais E6 e E7, somada à desregulação do ciclo celular, promove o desenvolvimento de displasia. A invasão do epitélio por subtipos de alto risco do HPV (16 e 18) é o principal fator no desenvolvimento das NICs e cânceres cervicais, seja escamoso ou adenocarcinoma. Ainda, condições genéticas, alimentares e ambientais são fatores de risco para desenvolvimento das NICs. A prevalência de HPV nos carcinomas cervicais pode alcançar 99,7%. Conclusão: As características morfológicas encontradas no colo uterino explicam sua relação com a infecção pelo HPV. Assim, destaca-se a importância do estudo desta histologia, possibilitando a compreensão da fisiopatogenia da doença.

Mixed Intraepithelial Neoplasia—Well-Differentiated Neuroendocrine Tumor of the Gallbladder: A Hitherto Unreported Combination

Adenocarcinomas and noninvasive intraepithelial neoplasms (either polypoid or flat) are the most common gallbladder tumors; however, neuroendocrine neoplasms (NENs) can also occur. The majority of NENs are represented by neuroendocrine carcinomas (NECs), while neuroendocrine tumors (NETs) are extremely rare in this location. Occasionally, NEN may present as a part of a mixed neoplasm, with a coexisting non-neuroendocrine component. The latest World Health Organization classification denotes these lesions as mixed neuroendocrine–non-NENs (MiNENs). A novel type of MiNEN, the mixed adenoma well-differentiated NET (MANET), has been increasingly recognized and reported. In such lesions, a dysplastic noninvasive neoplasm and a NET represent the exocrine and endocrine component, respectively. MANETs have mostly been identified in the colon, small intestines, and stomach. In this article, we report, we believe, the first case of mixed gallbladder neoplasm with both biliary intraepithelial neoplasia (BilIN) and NET components, which may be regarded as a variant of MANET. Given the expectably favorable prognoses of MANETs, it is imperative not to misdiagnose the infiltrative yet indolent neuroendocrine component as an invasive adenocarcinoma or a NEC.

An unusual presentation of corneal intraepithelial neoplasia

Introduction: Conjunctival/corneal intraepithelial neoplasms are premalignant lesions usually showing conjunctival or limbal involvement. We report the rare case of an isolated corneal intraepithelial lesion.Clinical case: An 80-year-old woman with an elevated, avascular, well-demarcated grey corneal plaque. After epitheliectomy and alcohol, the excised lesion was identified as a high-grade epithelial neoplasia. Treatment was topical interferon α-2b for 1 month without recurrences.Conclusions: A well-defined greyish corneal opacity should always raise suspicion of an intraepithelial neoplasia. In the present case, epitheliectomy and topical recombinant interferon proved successful.

Survival Outcomes of Pancreatic Intraepithelial Neoplasm (PanIN) versus Intraductal Papillary Mucinous Neoplasm (IPMN) Associated Pancreatic Adenocarcinoma

Pancreatic intraepithelial neoplasms (PanINs) and intraductal papillary mucinous neoplasms (IPMNs) are common pancreatic adenocarcinoma precursor lesions. However, data regarding their respective associations with survival rate and prognosis are lacking. We retrospectively evaluated 72 pancreatic adenocarcinoma tumor resection patients at the University of Kansas Hospital between August 2009 and March 2019. Patients were divided into one of two groups, PanIN or IPMN, based on the results of the surgical pathology report. We compared baseline characteristics, overall survival (OS), and progression free survival (PFS) between the two groups, as well as OS and PFS based on local or distant tumor recurrence for both groups combined. 52 patients had PanINs and 20 patients had IPMNs. Patients who had an IPMN precursor lesion had better median PFS and OS when compared to patients with PanIN precursor lesions. However, the location of tumor recurrence (local or distant) did not show a statistically significant difference in OS.

p16 Expression Correlates with Invasive Ocular Surface Squamous Neoplasms in HIV-Infected Mozambicans

Background: p16 immunohistochemistry is widely used to diagnose human papillomavirus (HPV)-related squamous neoplasms of cervix, anogenital, head, and neck tissues. The incidence of these HPV-related squamous neoplasms is markedly increased in the HIV-infected population. Ocular surface squamous neoplasia (OSSN) is also more common in HIV-infected patients. However, the expression pattern of p16 in OSSN among HIV-infected patients is unclear. Here, we examined the expression of p16 in OSSN surgical excisions collected from a large HIV-infected cohort from ­Mozambique. Methods: OSSN surgical tissue specimens were collected from 75 Mozambican patients. Formalin-fixed, paraffin-embedded tissue blocks from these OSSNs were sectioned, stained with hematoxylin and eosin (H&E), and p16 expression by immunohistochemistry. H&E slides were reviewed to determine if OSSNs were noninvasive conjunctival intraepithelial neoplasms or invasive squamous cell carcinomas (SCC). Cases were classified as p16 positive or negative based on diffuse nuclear and cytoplasmic expression of p16 in neoplastic cells. Results: p16 positivity was found in a minority of OSSN cases (14/75). p16 positivity was significantly associated with the invasive SCC type of OSSN in HIV-infected patients (p value of 0.026). Conclusions: The majority of OSSNs in our HIV-infected cohort do not express p16. However, those cases that are p16-positive are significantly more likely to be the invasive SCC form of OSSN. We propose that p16 expression may identify more aggressive OSSNs in HIV-infected populations.