International Journal of Gynecological Pathology最新文献

Upper female genital tract vascular proliferations are rare and generally not well characterized. We evaluated types, differences in distribution, and associations of such lesions. Fifty-five vascular lesions were identified: 42 benign (ovary 24; uterine corpus 11; para-adnexal 4; fallopian tube 1; ovaries, fallopian tubes, and corpus 1; ovary and fallopian tube 1) and 13 angiosarcomas. Patients with benign vascular lesions had a mean age of 55 (range: 13-82) yr. Twenty-six lesions were incidental findings, and 11 were associated with clinical manifestations. They had a mean size of 2.0 (range: <1-13) cm, and often were grossly cystic and hemorrhagic. Uterine benign vascular lesions included 6 arteriovenous malformations, 3 venous hemangiomas/malformations, 2 cavernous hemangiomas, and 1 mixed venous-cavernous hemangioma. In the ovary, there were 10 anastomosing hemangiomas, 8 arteriovenous malformations, 6 venous (2 in mature cystic teratomas, 1 bilateral in a patient with Klippel-Trenaunay syndrome), and 2 cavernous hemangiomas. Anastomosing hemangiomas were frequently associated with peripheral stromal luteinization/hilar cell hyperplasia; intravascular growth, extramedullary hematopoiesis, and one with adipocytic metaplasia. Venous hemangiomas/malformations were noted at a younger age in the ovary when compared to the uterine corpus. Patients with angiosarcomas had a mean age of 32 (range: 12-58) yr and a mean tumor size of 9.7 (range: 1.5-23) cm. Eight presented with a pelvic mass. Most angiosarcomas were grossly hemorrhagic and/or necrotic. Eleven arose in the ovary, 4 of them were associated with mature cystic teratoma, 1 with adenosarcoma with sarcomatous overgrowth, and 1 was part of a malignant mesenchymoma. Five were predominantly spindled, 3 epithelioid, 2 spindled and epithelioid, and one pleomorphic. Both uterine angiosarcomas were epithelioid. Follow-up was available for 8 patients: 7 died of disease between 6 and 43 mo, and 1 was alive and well at 106 mo. Vascular lesions in the upper female genital tract are uncommon, morphologically heterogeneous, and more frequent and clinically evident in the adnexa. Anastomosing hemangioma is the most common benign vascular lesion in the ovary and may be misdiagnosed as a steroid cell tumor due to associated stromal luteinization/hilar cell hyperplasia. Arteriovenous malformation is the most common benign vascular lesion in the uterine corpus. Angiosarcomas may be associated with another neoplasm, more commonly mature cystic teratoma, and have a poor prognosis.

Using immunohistochemistry, we examined a large cohort of 135 ovarian tumors, made up of 96 low-grade serous carcinomas (LGSCs) and 39 serous borderline tumors (micropapillary variant, mSBT), with the aim of exploring their HER2 status (overexpression). We followed with comprehensive genomic analyses on this sample set from our previous study, which revealed HER2 mutation in 5% (4/75) of LGSC and 10% (3/29) of mSBT. No cases were evaluated as HER2-positive, but 6 LGSCs and 1 mSBT were scored as HER2 1+, and 2 LGSCs and 1 mSBT showed the so-called HER2 "ultra-low" phenotype. This could be of clinical value as a potential therapeutical target concerning emerging therapeutic treatments (antibody conjugates). However, the clinical significance of this expression still needs to be established.

HER2 amplification in cervical cancer has been associated with worse clinical prognosis and a potential favorable response to HER2 inhibitors. Immunohistochemistry for the HER2 receptor is a universally accepted surrogate test for HER2 amplification, but no standardized scoring system currently exists for cervical carcinomas. In this study, we investigated HER2 overexpression in cervical squamous cell carcinoma and correlated it with HER2 amplification using fluorescence in situ hybridization (FISH) and molecular methods. Seventy-two cases of human papillomavirus-associated cervical cancer were retrospectively reviewed, and at least 2 representative tumor sections were stained for HER2. HER2 scoring was performed using the 2018 American Society of Clinical Oncology/College of American Pathologist breast cancer criteria, and cases with equivocal (2+) to positive (3+) expression were analyzed for HER2 amplification using FISH and next-generation sequencing. The average patient age was 50 yrs (range: 27-85 yr), with most patients being African American (73.6%) and diagnosed at FIGO stage I (65.3%). Nineteen (26.4%) had equivocal HER2 expression and 4 (5.5%) showed positive expression. Three of the 4 cases with positive expression had enough tumors for FISH, and all 3 were amplified. Three cases with equivocal expression showed HER2 polysomy on FISH, and none showed HER2 amplification. Late clinical stage, high tumor grade, and regional lymph node metastasis were significantly correlated with HER2 overexpression and HER2 amplification. Next-generation sequencing of the 3 HER2-amplified tumors showed amplification of various genes, including CD274, JAK2, BIRC3, and ERBB2, and a PIK3CA missense mutation. In summary, HER2 immunohistochemistry is a reliable predictive marker of HER2 amplification in cervical cancer.

Nuclear laminar or inner nuclear membrane proteins, including lamin A, B1, and B2 and emerin, are involved in maintaining nuclear morphology. However, their expression patterns vary among tumors and remain incompletely understood. Endometrioid carcinoma (EC) exhibits mild nuclear atypia, although the underlying reasons have not been thoroughly explored. In this study, we quantitatively analyzed emerin and lamin A, B1, and B2 expression levels in normal endometrium (NE), precancerous lesions, and EC using computer-assisted image analysis to assess the proteins' roles in nuclear morphologic change during tumorigenesis. From NE to EC, nuclear size remained unchanged, and lamin A and emerin were consistently expressed at low levels, whereas lamin B1 and B2 expression gradually decreased. Given the association between lamin A and emerin as well as their roles in nuclear morphology, these results indicate that their consistent low expression may underlie the preservation of nuclear size and shape in EC relative to NE. Conversely, lamin B1 and B2 are implicated in tumor progression rather than nuclear morphology maintenance. As lamin A and emerin are expressed in many organs and tumors, the consistently low expression of these proteins from NE to EC highlights a notable feature of the endometrium and endometrial carcinogenesis.

Definitive diagnosis of endometriosis is established by histologic confirmation in tissue from surgically visualized lesions; however, the diagnostic sensitivity of this approach varies widely. We hypothesized that incomplete tissue block sampling may contribute to false-negative diagnosis, particularly if the focus of endometriosis in the tissue section is scant. This study defined the diagnostic value of deeper level tissue sections in cases in which none of the specimen parts contained endometriosis on the initial tissue sections, using the World Health Organization essential criteria for diagnosis of endometriosis (presence of endometrial glands and endometrial stroma). Among 135 patients who underwent surgery for suspected endometriosis by a single surgeon at an academic institution from 2015 to 2019, the initial tissue sections resulted in a diagnosis of endometriosis in 73.3% (99/135), at an average diagnostic yield of 5.9 slides per diagnosis of endometriosis. An additional 9 patients were diagnosed with endometriosis by deeper level tissue sections, increasing the diagnostic rate to 80% (108/135). This 6.7% gain in the diagnostic rate came at an increase in resource utilization, with an overall overage diagnostic yield of 9.8 slides per diagnosis of endometriosis. Overall, 8.3% of patients had a false-negative diagnosis on the initial tissue sections. When extrapolated to a population level, the number of patients potentially affected by this source of false-negative diagnosis and the implications for patients merit consideration of the use of deeper level sections if none of the initial sections of any of the specimens contains endometriosis.

Cellular angiofibromas (CAFs) are benign mesenchymal neoplasms of the vulva and lower genitourinary tract. Although most cases are benign with excellent prognosis, data on CAFs with cytologic atypia (aCAF) and sarcomatous transformation (tCAF) is limited. We identified 13 vulvar CAFs comprising 4 aCAFs and 9 tCAFs. The median age at presentation was 49  yr (40-84). All tumors involved the subcutis with a median size of 4.75 cm (0.8-11.7). Vascular and stromal hyalinization was present in all cases. Fascicular growth pattern and chronic perivascular inflammation were seen in 10 cases, followed by wispy collagen in 11 and stromal inflammation in 12. Common features were fat entrapment (n=8), stromal edema (n=7), and hemangiopericytoma-like vessels (n=5), while myxoid change, necrosis (n=3 each), hemorrhage, collagen bundles (n=2 each), solitary fibrous tumor-like appearance, and large hyalinized vessels (n=1 each) were rare. The atypia ranged from isolated atypical cells to foci of multinucleated cells, with brisk mitoses in 1 case. The sarcomatous transformation involved 10% to 80% of total tumor volume and comprised features of well-differentiated liposarcoma, pleomorphic liposarcoma, leiomyosarcoma, and spindle and epithelioid cell sarcoma. Diffuse p16 expression was present in 2 tCAFs. Of 10 patients with available follow-up (median: 103.3 mo, 13.3-156.6), 2 (20%) recurred at 41 mo and 66 mo and remained disease-free at 157 and 99  mo post reexcision, respectively. The study provides a detailed clinicopathologic characterization of rare variants of CAF, aCAFs, and tCAFs, and reports rare recurrences, most likely due to incomplete surgical excision.

Mesonephric-like adenocarcinoma (MLA) of the uterus is a rare, aggressive malignancy of presumed Müllerian origin that was recently included in the 2020 World Health Organization (WHO) Classification of Female Genital Tumours. MLA is challenging to diagnose given its rarity and morphologic heterogeneity. The recently published first case report of MLA that underwent dedifferentiation via TP53 mutation expands the morphologic spectrum of dedifferentiated carcinoma. In here, we describe a second case of an endometrial MLA with dedifferentiation from a 41-yr-old woman who presented with bilateral ovarian masses, peritoneal carcinomatosis, and hypercalcemia. A diagnosis of small cell carcinoma of the ovary, hypercalcemic type, was initially rendered at an outside institution from an omental biopsy, which only showed the undifferentiated component. The subsequent endometrial curettings performed at our institution showed both the MLA and undifferentiated components, each of which demonstrated distinct immunophenotype with the immunoreactivity to epithelial markers, GATA3 and TTF1 limited to the MLA component and the aberrant nuclear expression of beta catenin, global loss of expression of SMARCA4 and loss of expression of SMARCA2 limited to the undifferentiated component. Molecular studies on the undifferentiated component from the omental biopsy identified not only a mutation in KRAS, gene mutation commonly seen in MLA, but also mutations in SMARCA4 and CTNNB1. In summary, we describe a second case of dedifferentiated MLA with dedifferentiation driven by various genetic alterations, including SMARCA4 and CTNNB1 gene mutations, novel gene alterations that have never been described in dedifferentiated MLA.

SOX17 has recently emerged as a novel immunohistochemical marker for cancers of endometrial and ovarian origin with improved specificity compared with the widely used Mullerian marker PAX8. However, evaluation of SOX17 in benign and malignant peritoneal mesothelial proliferations remains limited, and these may mimic gynecologic carcinomas, particularly on small biopsies. We evaluated SOX17 and PAX8 expression in 20 benign mesothelial lesions (5 adenomatoid tumors, 5 well-differentiated papillary mesothelial tumors, and 10 peritoneal inclusion cysts) and 16 epithelioid peritoneal mesotheliomas. The 17 female and 3 male patients with benign mesothelial lesions ranged from 20 to 80 yr (median: 56.5 yr), while the 9 females and 7 males with mesothelioma ranged from 47 to 85 yr (median: 57.5 yr). SOX17 was positive in 5 (25%) benign lesions (2 adenomatoid tumors, 3 peritoneal inclusion cysts) and 2 (13%) mesotheliomas, while PAX8 stained 8 (40%) benign lesions (1 adenomatoid tumor, 1 well-differentiated papillary mesothelial tumor, 6 peritoneal inclusion cysts), and 2 (13%) mesotheliomas. Results for the 2 stains showed incomplete concordance, with agreement in 15 (75%) benign proliferations and 14 (88%) mesotheliomas. Our findings suggest that SOX17 positivity alone is insufficient to confirm a diagnosis of gynecologic carcinoma over a mesothelial proliferation and pathologists should exercise caution when these entities are diagnostic considerations.

The International Society of the Study of Vulvovaginal Diseases (ISSVD) recently defined nonsclerotic lichen sclerosus (NSLS) as a scenario wherein the clinical findings are consistent with lichen sclerosus (LS), but no microscopic evidence of dermal sclerosis is found and recognized 4 histologic subcategories. Herein, we present an institutional experience with NSLS, with an emphasis on frequency, application of the ISSVD categories in routine practice, and clinicopathologic correlation. The authors reviewed clinical and pathologic findings for consecutive vulvar biopsies in which LS was a clinical and/or pathologic consideration. Cases were classified as classical/sclerotic LS (CLS), NSLS (per ISSVD criteria), and "unclassified," the latter of which were cases not classifiable as NSLS or CLS, despite a clinical impression or LS or LS being a significant clinical consideration (ie, "clinical LS"). In clinical LS cases, CLS and NSLS were diagnosed histologically in 61% (182/298) and 15% (44/298), respectively, whereas the remainder were histologically unclassified. The latter group was microscopically heterogeneous, devoid of a consistent pathologic profile, and generally showed absence, focality, minimality, ambiguity, or infrequency of features that would have allowed their categorization into one of the NSLS categories. Among the 4 categories for the categorizable NSLS cases, the "lichenoid dermatitis" pattern (61.4%) was the commonest, followed by dermal fibrosis with acanthosis (22.7%), dermal fibrosis without acanthosis (9.1%), and hypertrophic lichenoid dermatitis (6.8%). The clinical response rates to topical therapies for the NSLS and unclassified groups were 71% and 62%, respectively ( P =0.4). Our findings highlight the significance of clinicopathologic correlation in the diagnosis of NSLS. In the setting of clinical LS, some histologic evidence to support that impression is found in most cases when the ISSVD system for diagnosis and classification of biopsies is applied. However, a subset of clinical LS cases are not pathologically classifiable as either CLS or any of the NSLS categories; these display nonspecific histologic features and require future study.