HPV nonrelated endocervical adenocarcinoma in hereditary cancer syndromes

Abstract

<jats:sec><jats:title>Introduction:</jats:title><jats:p> The relationship between endocervical cancer and cancer susceptibility syndromes is not yet fully understood. We present 2 cases of endocervical cancer: 1 arising in a patient carrier with a pathogenic BRCA1 variant and the second detected in a Lynch syndrome family carrying the MSH2 germline pathogenic variant. </jats:p></jats:sec><jats:sec><jats:title>Case description:</jats:title><jats:p> Somatic analyses including loss of heterozygosity and fluorescent in situ hybridization demonstrated that the second hit in patient 1 is BRCA1-related. Mismatch repair somatic analyses in the second family demonstrated that the endocervical cancers of patient 2 and of her sister are MSH2-related. These data confirm the relationship between the pathogenesis of endocervical cancer and the presence of germline BRCA1 and MSH2 mutations. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> Our study confirms that gynecologic cancers including rare entities such as non–human papillomavirus–related endocervical cancer (NHPVA) are sentinels for inherited cancer syndromes. Endocervical cancer NHPVAs might be considered for cancer genetic counseling in order to improve cancer prevention. For this reason, the role of pathologists is particularly important for the correct identification of the cervical tumor site. </jats:p></jats:sec>

Insufficient evidence of endocervical origin in germline BRCA1 and MSH2-associated tumors

“…Overall, the conclusion that primary adenocarcinomas of the endocervix (outside of gastric type endocervical adenocarcinoma) may be associated with an underlying hereditary cancer syndrome is not supported by the cases presented by Carnevali et al, 1 or elsewhere in the literature. It is critical to note that in cases of non-HPV-related adenocarcinomas involving the endocervix, diligent care must be taken to exclude tumors that may otherwise involve the cervix, particularly those of endometrial origin and drop metastases from the adnexa.…”

“…When the diagnosis is considered, it is mandatory to exclude mimics including HPV-associated adenocarcinoma, clear cell carcinoma, mesonephric carcinoma, and drop metastases from the adnexa or corpus. The latter possibility is particularly relevant in the case described by Carnevali et al, 1 as they report "p53 signatures" involving the right fimbria and immunohistochemical WT-1 positivity in the cervical tumor. Taken together, there is a lack of compelling evidence that the tumor is endocervical in origin.…”

“…We read with interest a recent article 1 in which two cases of apparent non-human papillomavirus (HPV)related endocervical adenocarcinomas associated with germline BRCA1 and MSH2 mutations, respectively, were described. Although germline and somatic analyses confirmed that the patients are carriers of BRCA1 and MSH2 germline mutations and that the tumors were pathogenetically underpinned by these respective abnormalities, there is a lack of evidence that the neoplasms are actually endocervical in origin.…”

“…The first case presented by Carnevali et al 1 is of a 63-year-old woman with germline BRCA1 mutation and apparent endocervical serous carcinoma. Although "papillary serous carcinomas" of the cervix have been described, modern studies have elucidated several important points regarding these neoplasms and have ultimately concluded that there is insufficient evidence that this entity truly exists.…”

Hereditary determinants of gynecological cancer and recommendations

“…(5) Gastric-type adenocarcinomas are related to Peutz-Jeghers syndrome. (6) Women with mutations in MMR genes (DNA repair genes) have an estimated 5.6 times greater risk for cervical cancer than the general population. (7) The definition of the site of origin of cervical adenocarcinoma in women with Lynch syndrome (LS) may be difficult, as this syndrome is also associated with endometrium carcinoma of the lower uterine segment.…”