International Journal of Gynecological Pathology最新文献

The simultaneous presence of distinct histologic types of ovarian cysts in a single patient, known as "collision tumors," presents a clinical challenge. In this study, we report 19 new cases of ovarian collision tumors involving both endometriomas and mature cystic teratomas (MCTs), and we review their characteristics alongside 30 previously reported cases. Among the total of 49 patients, the mean age was 32.28±8.07 yr, with 66.67% being nulliparous. The most common clinical symptom was abdominal pain (55.10%), while 12.24% were diagnosed incidentally. Primary infertility was identified in 14.28% of patients. Of the 44 cases with available surgical data, 32 underwent cystectomy and 12 underwent oophorectomy. In the 19 newly reported cases, 10 patients desired fertility preservation, yet only one achieved spontaneous pregnancy after surgery. Although both endometriomas and MCTs are benign ovarian lesions, their coexistence is rare. Tissue diagnosis is essential to exclude malignancy and guide follow-up, but preserving ovarian reserve is equally critical. Recognizing the presence of collision tumors can help physicians utilize radiologic methods more effectively and adopt a more proactive approach, safeguarding the future fertility and quality of life of these patients.

Lymphovascular space invasion (LVSI) is defined as tumor cells within blood vessels or lymphatic endothelial-lined spaces and, until recently, its prognostic significance in cervical cancer was somewhat controversial and less well studied than for some other tumor types in the female genital tract. Based on the available literature, there is now strong evidence that LVSI is not only a significant prognostic factor, especially in early-stage cervical cancers (squamous cell carcinomas and adenocarcinomas), but is also a predictive factor for lymph node metastases. Consequently, while LVSI does not impact FIGO or TNM staging, its presence should be recorded in the pathology report and considered in management decisions regarding adjuvant treatment, as suggested by various international guidelines. More recently, the extent of LVSI (substantial vs. focal vs. negative) has been demonstrated to predict survival in cervical cancer, although this is an area where more study is required both to determine whether substantial LVSI is of prognostic significance and to ascertain the optimal definition of substantial LVSI. LVSI can be diagnosed on routine microscopic examination without ancillary tests in most cases and thus can be reported even in low-resource settings. There are, however, various pathologic issues both in diagnosing and quantifying LVSI, with no universal recommendations. In this review, we examine the significance of LVSI in cervical cancer in terms of prognostication and in dictating the need for adjuvant treatment. We also discuss practical issues related to the pathologic reporting of LVSI.

Immunohistochemistry (IHC) for mismatch repair (MMR) proteins is routinely performed for endometrial cancer (EC). Loss of nuclear staining for MLH1/PMS2 triggers reflex testing for MLH1 promoter hypermethylation, while loss of MSH2/MSH6 or isolated loss of MSH6 and PMS2 prompts germline testing for Lynch syndrome. We observed an unusual nuclear membranous staining pattern of MLH1 (clone G168-15). The goal of the study was to determine its significance and highlight this IHC interpretation pitfall. A total of 52 EC cases with abnormal IHC staining patterns were identified in our database from 2017 to 2020. Of these, 41 were reported as MLH1/PMS2 deficient, and 11 as MSH2/MSH6 deficient. On review, 6/41 (14.6%) showed nuclear membranous expression of MLH1 (focal in 1 and diffuse in 5) with complete loss of PMS2 in the same foci. These foci demonstrated mucinous morphology or squamous/morular metaplasia in 3 cases. One additional consultation case showed nuclear membranous staining of MLH1 in the carcinoma and complete loss in the associated endometrial intraepithelial neoplasia, with PMS2 loss in both. Three of 7 cases were FIGO grade 1, and 4 were FIGO grade 2 to 3. MLH1 promoter hypermethylation was detected in 6/7 cases (not performed for one case). Repeat staining with ES05 clone showed complete loss of nuclear MLH1 expression in all 6 in-house cases. Nuclear membranous expression of MLH1 represents an aberrant staining pattern, observed with complete loss of PMS2 and frequently associated with MLH1 promoter hypermethylation. Failure to recognize this aberrant MLH1 expression pattern can lead to misinterpreting isolated PMS2 loss.

Endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (EAH/EIN) is the acknowledged precursor of most endometrial carcinomas. Our aim was to assess the molecular alterations and the 4 specific molecular subtypes in EAH/EIN diagnosed on endometrial biopsy. Forty EAH/EIN biopsies were stained for estrogen receptor (ER), mismatch repair (MMR) proteins (PMS2 and MSH6), and p53 and were subjected to genomic testing (NGS Panel, Canexia Health V5). Based on these results, cases were assigned to 1 of 4 molecular subtypes [ POLE mut, MMRd, p53abn, and no specific molecular profile (NSMP)]. Follow-up data was collected. There was 1 POLE mut case with a pathogenic POLE mutation (P286R), 5 were MMRd, 1 was p53abn, and the remaining 33 were NSMP. Thirty-nine of 40 cases harbored one or several mutations known to be associated with endometrial carcinoma pathogenesis ( PIK3CA, PTEN , and CTNNB1 ). On follow-up, there was carcinoma or EAH identified in a subsequent hysterectomy or biopsy in 6 of 6 patients with MMRd or p53abn EAH, compared with 19 of 34 with NSMP or POLE mut ( P =0.067). Most EAH/EIN (33/40, 81.5%) are of the NSMP molecular subtype. Molecular subtypes other than NSMP (eg, POLE mutation, MMR deficiency, and p53 mutant pattern staining) are present in EAH/EIN but are less common than in carcinoma. Mutations associated with EC pathogenesis were identified in 39/40 (97.5%) biopsies containing EAH/EIN, highlighting the neoplastic nature of this lesion and raising the possibility of using sequencing (NGS) as an adjuvant test to support a diagnosis of EAH/EIN.

Previous studies have evaluated the utility of estrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry (IHC) in differentiating uterine versus extrauterine leiomyosarcomas (LMS). At best, these studies have shown only modest sensitivity and specificity for these markers in this context. In our own practice, we have noticed that retroperitoneal LMS, such as those arising in the wall of the inferior vena cava, frequently exhibit a remarkable resemblance not to uterine LMS, but rather to uterine leiomyomas (LM) with bizarre nuclei, formerly known as symplastic LM. This includes areas with bland nuclear cytology, punctuated by the presence of cells with large bizarre nuclei but a paradoxically low mitotic index. We refer to these areas in retroperitoneal LMS as "symplastic-like." It has been our experience that these "symplastic-like" areas are frequently the predominant or exclusive component in small core biopsies of retroperitoneal LMS, even when the resection of these tumors reveals the presence of more conventional high-grade LMS morphology. In female patients, symplastic-like morphology in a smooth muscle tumor at an intra-abdominal site raises the possibility of iatrogenic dissemination of a uterine LM with bizarre nuclei from a prior myomectomy or morcellation procedure. We hypothesized that negative staining for ER and PR by IHC could effectively exclude a uterine origin, given the high sensitivity of these markers for all variants of uterine LM. After successfully using ER and PR IHC in our clinical practice on a few index cases, we decided to study a larger cohort of carefully selected cases to systematically determine the sensitivity and specificity of these markers in this very specific context. Confining our search to include only female patients, we identified 8 cases of retroperitoneal LMS that had been confirmed radiologically, intraoperatively and/or histologically to originate from a retroperitoneal source and 6 cases of uterine-based LM with bizarre nuclei, all diagnosed at our institution over an 8-year period. We tested only whole slides for ER and PR IHC. ER and PR were both completely negative in all 8 cases of retroperitoneal LMS and were both strongly expressed in all 6 cases of LM with bizarre nuclei. In conclusion, despite conflicting data in the literature regarding the utility of ER and PR in distinguishing uterine versus extrauterine smooth muscle tumors, we endorse the use of these markers for the specific distinction of retroperitoneal LMS with symplastic-like features from disseminated uterine LM with bizarre nuclei in female patients.

Endometrioid carcinoma is a common malignant epithelial tumor of the uterus and ovary, exhibiting variable histomorphology and immunophenotype. Sex cord-like endometrioid carcinoma (SCLEC) is a rare histologic subtype with significant morphologic and immunohistochemical variability. Extra-ovarian, extra-uterine SCLEC arising from the broad ligament has been rarely reported. We report 2 cases of SCLEC arising from the broad ligament. The first patient, a 62-yr-old woman, presented with vague abdominal pain, and diagnostic imaging suggested a broad ligament fibroid. The second patient, a 47-yr-old woman, presented with a clinical history of abdominal pain and abnormal uterine bleeding. Diagnostic imaging suggested a subserosal fibroid. Histologic evaluation revealed a sex cord-like pattern with only rare foci of conventional endometrioid carcinoma. Immunohistochemical evaluation of both cases showed positivity for CK-7, EMA, ER, PR, CDX-2, CD-10, and nuclear β-catenin, while CK-20, PAX-8, GATA3, TTF-1, WT-1, napsin-A, p16, p53, inhibin, calretinin, chromogranin, and CEA were negative. The diagnosis of primary broad ligament SCLEC is extremely challenging. A thorough histologic and immunohistochemical evaluation is essential before excluding differential diagnoses.

Primary neuroendocrine carcinoma (NEC) of the fallopian tube is exceptionally rare, with only a small number of cases reported. We report an unusual case in a 77-yr-old woman where a fallopian tube was involved by serous tubal intraepithelial carcinoma (STIC), a small component of high-grade serous carcinoma (HGSC), and a predominant component of small cell neuroendocrine carcinoma (SCNEC). Molecular analysis of microdissected different elements supported a clonal origin, with both tumor components (STIC/HGSC and SCNEC) displaying homologous recombination deficiency and a shared TP53 mutation, while the neuroendocrine component uniquely exhibited 4q deletion and additional DNA repair gene mutations in PALB2 and CHEK2 .

This case report details the first known instance of an EML4::NTRK3 rearranged neoplasm in the ovary. The patient, a 32-yr-old woman, presented with prolonged abnormal uterine bleeding and was found to have a 5.0 cm right adnexal mass. Following surgical excision, histologic examination revealed neoplastic epithelioid to spindled cells with moderate cytologic atypia in a variably myxoid background, while immunohistochemistry confirmed positivity for inhibin, calretinin, and smooth muscle actin (SMA). Molecular analysis identified an EML4::NTRK3 fusion, establishing the diagnosis. This rare finding broadens the spectrum of NTRK fusion-related gynecologic tumors, typically observed in the uterus. Through this report and a literature review, we aim to enhance diagnostic recognition and underscore potential therapeutic strategies for NTRK fusion-positive ovarian tumors.

Cellular angiofibroma is a benign mesenchymal neoplasm which usually occurs in the vulvovaginal or inguinoscrotal areas. Although benign, cellular angiofibroma may rarely undergo sarcomatous transformation. We report a case of vulvar cellular angiofibroma with sarcomatous transformation in a 62-yr-old woman and a literature review of previously reported cases. By immunohistochemistry, our case was positive for vimentin and ER, mostly negative for smooth muscle markers, and showed patchy reactivity for CD10, Pan-TRK, and Rb1. The bland component was negative for p16 with wild-type p53 expression, while the sarcomatous area showed strong, diffuse p16 staining with p53 overexpression. Targeted DNA and RNA next-generation sequencing of the bland area showed chromosome 9p/9q copy number loss, while the sarcomatous area showed TP53 (p.G154V) mutation (90% allele frequency) and copy number loss of chromosome 17p (including TP53 ). Whole transcriptome sequencing was negative for tumor-associated gene fusions. As the lesion was completely encapsulated and excised, and with limited published data indicating an uneventful clinical course, the decision was made to follow the patient with no further therapeutic intervention. Four months following excision, the patient has no signs or symptoms of local recurrence.