International Journal of Gynecological Pathology最新文献

A subset of human papillomavirus (HPV)-associated endocervical adenocarcinoma (EA) displays exclusively exophytic growth, with or without a classic villoglandular appearance. Given that increased depth and extent of destructive stromal invasion are associated with poorer prognosis for HPV-associated EA, it is believed that exclusively exophytic tumors are associated with a relatively indolent clinical course. There is, however, a paucity of data regarding the behavior of these neoplasms. We assembled a cohort of 73 patients with entirely resected cervix-confined HPV-associated EA treated with primary operative therapy. The tumors were classified based on architecture and presence/extent of stromal invasion, and histopathologic parameters, including the International Federation of Gynecology and Obstetrics (FIGO) 2018 substage and lymphovascular invasion (LVI). Clinical outcomes including local recurrence, metastasis, and death were evaluated. Of 73 tumors, 4 (6%) demonstrated exclusively exophytic growth (0.4-2.2 cm in maximal dimension). All lacked LVI as well as nodal involvement. None of the 4 patients with exclusively exophytic tumors received adjuvant therapy. Two of the 4 (50%), however, experienced recurrence and both patients eventually died of causes related to EA. Of the remaining 69 cases with a component of nonexophytic growth, <6% of patients experienced tumor recurrence. Our study has found that, in at least a subset of cases, exclusively exophytic HPV-associated EA is associated with adverse outcomes. Additional studies are needed to substantiate these findings and to identify additional features (pathologic, molecular, etc.) that may aid in identifying those patients who could benefit from more aggressive treatment.

Female adnexal tumor of presumed Wolffian origin (FATWO) is a rare gynecologic neoplasm favored to arise from mesonephric (Wolffian) remnants. Although most tumors are benign, rare recurrences have been reported. Herein, we present a case of a 65-year-old female with incidental peritoneal lesions detected on routine ultrasound that morphologically and immunohistochemically were diagnostic of FATWO. Review of her medical history uncovered a remote history (>30 years) of a para-ovarian cystectomy, which was punctured intraoperatively. Slide review confirmed the diagnosis of FATWO, thereby suggesting iatrogenic dissemination from the original procedure. This report highlights the importance of a thorough review of the medical record when encountering a nonprototypical location for a distinctive tumor. In addition, the slow-growing nature of these lesions, as well as the absence of atypical histologic features, further contributes to the hypothesis that the majority of FATWOs are benign.

High-grade serous carcinomas (HGSCs) with homologous recombination deficiency (HRD) respond favorably to platinum therapy and poly ADP ribose polymerase (PARP) inhibitors. Mutations in BRCA1 and BRCA2 commonly cause HRD and have been associated with Solid, pseudoEndometrioid, and Transitional-like (SET-like) histology. Mutations in other homologous recombination repair (HRR) genes as well as epigenetic changes can also result in HRD; however, morphologic correlates have not been well-explored in these cases. We hypothesized that HGSCs with HRD, regardless of the etiology, are associated with specific morphologic features. Forty-three cases of HGSC with genomic profiling, which included HRR gene mutation analysis and HRD score, were evaluated. The morphologic patterns, degree of nuclear atypia, necrosis, mitotic index, and tumor-infiltrating lymphocytes (TILs) were determined. The results showed that HRD-high status was significantly associated with the presence of BRCA1/2 mutation, SET-like morphology, geographic necrosis, and severe nuclear atypia. Additional HRR pathway genes with oncogenic mutations identified included ATM, BRIP1, BLM, FANCC, CDK12, CHEK2, RAD51C, and RAD51D . Almost one-third of HRD-high tumors did not have mutations in any HRR pathway genes identified. In conclusion, HGSC with HRD, regardless of BRCA1/2- status, was associated with SET-like morphology and more severe nuclear atypia. Identifying and reporting these patterns of tumor morphology can prompt genomic profiling with prognostic, therapeutic, and genetic counseling implications.

Somatic malignancy arising from a mature ovarian teratoma is a rare phenomenon, occurring in 1% to 3.5% of cases. These somatic tumors are most commonly epidermal malignancies, but they can develop from any somatic component, including thyroid tissue. Increasing evidence suggests that in such cases, the pathogenesis is driven by the same mutational profile as seen in their conventional somatic counterparts. Here, we report the first case of an STRN::ALK fusion in a papillary thyroid carcinoma arising from the thyroid component of a mature ovarian teratoma. The patient presented with a 68 mm mass in the right ovary, which was histopathologically confirmed as a mature teratoma. Within the thyroid component, papillary thyroid carcinoma was identified. Next-generation sequencing revealed an STRN::ALK fusion, supported by positive ALK immunohistochemistry in the carcinoma. The identification of these genetic signatures not only aids in diagnosis but also provides potential therapeutic targets in the case of disease progression.

HPV-associated endocervical adenocarcinoma in situ (AIS) is typically ER-, vimentin-, and CEA+. By contrast, tubo-endometrioid metaplasia (TEM), a well-known mimicker of AIS, is typically ER+, vimentin+, and CEA-. Both AIS and TEM express p16, with block-positive expression in AIS and predominantly patchy expression in TEM; however, TEM may also exhibit p16 expression that is extensive enough that it borders on block-like expression. Here we share 2 cases of endocervical AIS that showed an endometrioid immunophenotype (ER+, vimentin+, and CEA-). The AIS in these cases also had a second population of pale p40- epithelioid cells resembling the ciliated cells of TEM; no true cilia were seen. High-risk human papillomavirus (HPV) in situ hybridization (HR-HPV ISH) testing was positive in both cases of AIS, establishing their HPV association. Despite the lack of true cilia, the morphology and immunophenotype of the AIS in these cases resulted in a very TEM-like picture. Given the aforementioned propensity of TEM to show a high degree of p16 expression, we share these cases as a reminder that an endometrioid-like immunophenotype by ER, CEA, and vimentin IHC does not unequivocally establish a benign diagnosis.

A well-differentiated endometrioid carcinoma at the site of extra-uterine/ovarian endometriosis complicates the differentiation between an uncommon metastatic pattern from a corpus cancer and a synchronous primary tumor originating from adjacent endometriosis. Herein, we present 2 cases of well-differentiated uterine endometrial carcinoma metastasizing to the intestinal tract and uterosacral ligament, which were adjacent to surrounding endometriosis. Case 1: a well-differentiated endometrioid carcinoma was identified in the uterus and the uterosacral ligament. Genetic analysis revealed shared driver gene mutations between the uterine corpus tumor and uterosacral ligament tumor, indicating a common clonal origin. Case 2: an endometrioid carcinoma was identified in the intestinal tract, with adjacent ectopic endometriosis. Furthermore, the patient had a history of treatment for early-stage uterine well-differentiated endometrial carcinoma 7 yr prior. Genetic analysis demonstrated shared genetic alterations between the uterine corpus tumor, treated 7 yr earlier, and the intestinal tumor, strongly supporting a shared clonal origin. Although clinical and pathologic findings suggested that these tumors could originate from endometriosis, detailed genetic analysis confirmed that they shared genetic alterations with the primary uterine endometrioid carcinoma, indicating a common clonal origin in both cases. When well-differentiated adenocarcinoma is identified at an extrauterine/ovarian site adjacent to endometriosis, the tumor can be considered to be derived from the surrounding endometriosis. However, if a uterine endometrial carcinoma is present concurrently or has a history of existing, metastasis from the uterine endometrial carcinoma should be considered first, even if its clinical malignant potential is not high.

Vulvar adenocarcinoma of the intestinal type (VAIt) is a rare subtype of primary vulvar carcinoma, with ∼30 cases documented in the English literature. This study presents 2 new cases of HPV-independent VAIt with lymph node metastasis and discusses their clinical presentation, histopathologic features, and whole exome sequencing (WES) analysis. Both cases exhibited histologic features consistent with VAIt, including tubular, papillary, and mucinous carcinoma components. Immunohistochemical analysis showed p16 patchy staining, CDX2, CK20, and SATB2 positivity, while being negative for ER, PAX8, and CK7. WES revealed pathogenic TP53 mutations in both cases, accompanied by distinct additional mutations ( GRIN2A and KDM6A in Case #1; CHD4 in Case #2). Common copy number alterations (CNAs) included TP53 loss of heterozygosity and CD274/PD-L1 amplification. However, other CNAs varied between the cases. Immunohistochemistry for p53 suggests the presence of both wild-type and mutant subclones, indicating that TP53 abnormalities may be acquired during tumor progression. Both tumors showed mutational signatures SBS1 and SBS5, associated with aging and DNA damage. Our findings deepen the understanding of the genetic events involved in the tumorigenesis of HPV-independent VAIt. Given the TP53 abnormalities and CD274/PD-L1 amplification, emerging p53-based therapies and immune checkpoint inhibitors may represent potential treatment targets. While these findings contribute to the understanding of VAIt tumorigenesis, further research is required to validate these observations in a larger cohort.

Tumor human papillomavirus (HPV) status is an important prognostic factor in vulvar cancer as indicated in the latest WHO classification of female genital tract tumors. Immunohistochemical detection of p16 is well established as a surrogate biomarker for tumor HPV association, including squamous cell carcinomas of the vulva. HPV-independent vulvar carcinomas are heterogeneous with 2 subcategories according to the TP53 mutation status. Therefore, the simultaneous use of p53 and p16 immunohistochemistry is recommended for accurate subclassification of vulvar squamous cell carcinomas. However, the role of molecular analytical tools, in particular RNA ISH and TP53 sequencing, is not so clear. This study aimed to investigate the performance of p53 and p16 immunohistochemistry for the diagnosis of vulvar carcinomas in comparison to TP53 mutation analysis and HPV RNA ISH. We analyzed 48 vulvar carcinomas in a tissue microarray format. Sensitivity and specificity for both methods, p16 (100% and 96%) and p53 (95% and 90%) immunohistochemistry for detection of HPV association as well as for TP53 mutations was high. Combining p16 and p53 immunohistochemistry we correctly classified all carcinomas in our series according to current WHO criteria. The sensitivity of HPV RNA ISH for the detection of HPV association was lower compared to p16 immunohistochemistry. Rare HPV-associated cases with TP53 mutation and HPV-independent tumors with p16 overexpression are discussed. In summary, the combined use of p16 and p53 immunohistochemistry for subclassification of vulvar carcinomas is justified in daily practice. Molecular tests should be restricted to rare cases with ambiguous clinicopathologic or immunohistochemical features.