UNASSIGNED: Rhabdomyosarcoma of the female genital tract often involves the vagina and cervix. It usually occurs in infants and children. Such tumors are uncommon in the uterus, especially in adults. Treatment options are based on studies of younger individuals.
UNASSIGNED: Rhabdomyosarcoma (RMS) is a malignant mesenchymal neoplasm with a tendency to differentiate into skeletal muscle cells. RMS is an aggressive tumor that tends to develop in children and younger patients. A vast majority of genital tract RMSs occur in the vagina and cervix. Such tumors rarely occur in adults. Usually, these tumors either occur as a component of a biphasic uterine tumor (carcinosarcoma or adenosarcoma) or can be a pure heterologous tumor. Pure uterine RMSs are extremely rare in adult patients and difficult to diagnose. Accurate diagnosis of these tumors depends on precise histopathological evaluation. The present report describes a rare case of embryonal RMS of the uterus in a postmenopausal female and explores the most recent literature. The aim is to strengthen the existing literature and aid clinicians in the management of similar cases. A 64-year-old postmenopausal female presented with a history of abdominal pain associated with abdominal distension, per vaginal bleeding, and foul-smelling discharge for 6 months. A transabdominal ultrasound revealed a bulky uterus with a well-circumscribed heterogeneous lesion. Histopathology confirmed the diagnosis of high-grade embryonal RMS within the corpus region of the uterus. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed, followed by adjuvant chemotherapy to prevent relapse of the disease. Six months after oncological care has passed, the patient remains symptoms-free without evidence of recurrence or metastasis.

There are a large number of gynaecological cancers with rare histologies, for which the available data are limited and usually retrospective. Because of their rarity and poor prognosis, the management of these cancers must be centralized in expert centres, for both histological diagnosis and treatment. With the exception of sarcomas, most endometrial or cervical cancers with rare histologies respond to the same radiation treatment modalities than cancers with more common histologies, although there are some specificities regarding treatments such as neuroendocrine carcinomas (chemotherapy with platinum and etoposide, major role of surgery). For localized or locally advanced ovarian cancer, external beam radiotherapy has a role in the management of hypercalcaemic small cell carcinoma of the ovary. This article summarizes the current role of external beam radiotherapy and brachytherapy in the management of cancers of the uterine cervix, uterine corpus and ovaries, with rare or very rare histologies, and with localized or locally advanced stages.

Endometrial cancer (EC) is one of the most pervasive malignancies in females worldwide. HOXA5 is a member of the homeobox (HOX) family and encodes the HOXA5 protein. HOXA5 is associated with various cancers; however, its association with EC remains unclear. This study aimed to determine the association between HOXA5 gene expression and the prognosis of endometrioid adenocarcinoma, a subtype of EC (EAEC). Microarray data of HOXA5 were collected from the Gene Expression Omnibus datasets, consisting of 79 samples from GSE17025 and 20 samples from GSE29981. RNA-sequencing, clinical, and survival data on EC were obtained from The Cancer Genome Atlas cohort. Survival analysis revealed that HOXA5 overexpression was associated with poor overall survival in patients with EAEC (p = 0.044, HR = 1.832, 95% CI = 1.006-3.334). Cox regression analysis revealed that HOXA5 was an independent risk factor for poor prognosis in EAEC. The overexpression of HOXA5 was associated with a higher histological grade of EAEC, and it was also associated with TP53 mutation or the high copy number of EC. Our findings suggest the potential of HOXA5 as a novel biomarker for predicting poor survival outcomes in patients with EAEC.

OBJECTIVE: Female genital alveolar soft part sarcoma (ASPS) is rare and has a favourable prognosis compared to ASPS from other sites. We reported our experience to manage a case with uterine corpus ASPS (UC ASPS) and conducted a literature review on prognosis of ASPS from different sites of female genital tract.
METHODS: This report represented a 33-year-old woman who had UC ASPS. She received tumor excision with uterine preservation and had the longest follow-up time (155 months) without recurrence in the literature.
CONCLUSIONS: UC ASPS has better prognosis than ASPS from the uterine cervix, the low uterine segment, vulvovaginal area and perineum. We recommended conservative treatment for young women with UC ASPS.

OBJECTIVE: Micropapillary pattern is a morphologically distinctive form of carcinoma composed of small, hollow, or morula-like clusters of cancer cells surrounded by clear stromal spaces. The neoplastic cells characteristically display a reverse polarity, also known as an \'\'inside-out\'\' growth pattern, that is linked to higher frequencies of lymphovascular invasion and lymph nodal metastasis. To the best of our knowledge, it has not been previously recognized in uterine corpus.
METHODS: We report 2 cases of endometrioid carcinoma of the uterine corpus with a micropapillary component. In these cases, histological examination identified an endometrioid carcinoma that had invaded the myometrial layer. The carcinoma cells that constructed the micropapillary components were immunohistochemically positive for EMA. They lined the stromal facing surface of the cell membrane, confirming the inside-out growth pattern, and D2-40 immunohistochemistry confirmed lymphovascular invasion of carcinoma cells.
CONCLUSIONS: We believe that the micropapillary pattern linked to higher frequencies of lymphovascular invasion and lymph nodal metastasis may be one of the most important invasive patterns in endometrioid carcinomas of the uterine corpus for predicting aggressive malignant potential, prognosis, and recurrence, although further, larger studies are required to evaluate its clinical significance.

BACKGROUND: Although several studies have documented the histological features of uterine mesonephric-like adenocarcinoma (MLA), its cytological features have been rarely reported.
METHODS: We searched for histologically confirmed uterine MLA cases in the pathology archives of three institutions between 2010 and 2021. All available cytology slides were examined to identify the cytological features of uterine MLA.
RESULTS: We included 16 patients with uterine MLA and reviewed the slides obtained from 21 cytology samples. Samples were obtained from the cervicovagina (9/21, 42.9%), peritoneal washing (8/21, 38.1%), pleural effusion (2/21, 9.5%), and transbronchial needle aspiration of mediastinal lymph node (2/21, 9.5%). Preparation methods included ThinPrep (11/21, 52.4%), SurePath (8/21, 38.1%), and conventional smear (2/21, 9.5%). Regardless of the sampling site and preparation method, cytology samples displayed tight three-dimensional cellular clusters showing monotonous, small-to-medium-sized, round, hyperchromatic nuclei, indistinct nucleoli, scant cytoplasm, and high nuclear-to-cytoplasmic ratio. Approximately half of the samples (10/21, 47.6%) showed hyaline-like globules. Mitotic figures (7/21, 33.3%) and apoptotic bodies (13/21, 61.9%) were also observed. No tumor diathesis or nuclear feathering was identified.
CONCLUSIONS: Irrespective of sampling site and preparation method, the majority of uterine MLA cases showed the following cytological features: tight three-dimensional cellular clusters showing small-to-medium-sized, round, hyperchromatic nuclei with indistinct nucleoli and high nuclear-to-cytoplasm ratio. In case a cytology sample suspicious of a glandular lesion displays these cytological features, which are distinct from those of endocervical adenocarcinoma, uterine MLA should be included in the differential diagnosis.

Early-stage cervical cancer rarely extends to the uterine corpus and invades the serosal layer. Here, we present a case of cervical cancer extending to the uterine corpus and then penetrating the myometrium to invade the sigmoid colon. Transabdominal type C2 radical hysterectomy, bilateral salpingo-oopherectomy, pelvic lymphadenectomy, and sigmoid resection were performed. The patient then underwent chemotherapy as she was unable to tolerate chemoradiotherapy. She recovered well and was followed up for 14 months. Our report reveals that the uterine corpus can be a route of tumor metastasis in cervical cancer.

Rhabdomyosarcoma is a malignant neoplasm of mesenchymal origin with skeletal striated muscular differentiation. It is the most common sarcoma of childhood and has four subtypes: embryonal, alveolar, pleomorphic and spindle cell/sclerosing. Of all of them, the embryonal one is the most prevalent and presents a variant, botryoid, which usually involves hollow organs in the form of a multilobed polypoid mass. We present the case of a 27-year-old woman who consulted for vaginal bleeding and in whom colposcopy revealed a whitish polypoid lesion that was externalized through the external cervical os. Histological examination revealed cellular sectors alternated by lax, myxoid areas, together with typical isthmic-endometrial glands. The atypical spindle cell proliferation was arranged in nests, made up of ce lls with large eosinophilic cytoplasm with transverse cytoplasmic striations and eccentric nuclei with homogeneous chromatin. Areas of densely packed cells were exhibited immediately, but separated from, the intact epithelial lining by a thin layer of loose stroma (cambium layer). The immunostaining profile was positive for desmin, muscle-specific actin and myogenin, and negative for smooth muscle actin. A diagnosis of embryonal botryoid rhabdomyosarcoma of the uterine corpus was made.
El rabdomiosarcoma es una neoplasia maligna de origen mesenquimal con diferenciación muscular estriada esquelética. Es el sarcoma más común de la infancia y presenta cuatro subtipos: embrionario, alveolar, pleomórfico y de células ahusadas/esclerosante. De todos ellos el embrionario es el de mayor prevalencia y presenta una variante, botrioide, que suele comprometer órganos huecos en forma de una masa polipoide multilobulada. Presentamos el caso de una mujer de 27 años que consultó por sangrado vaginal y en quien se evidenció en la colposcopia, una lesión polipoide blanquecina que se exteriorizaba a través del orificio cervical externo. El estudio histológico reveló sectores celulares alternados por áreas laxas, mixoides, junto a glándulas ístmico-endometriales típicas. La proliferación fusocelular atípica, se disponía en nidos, constituidos por células de amplio citoplasma eosinófilo con estriaciones citoplasmáticas transversales y núcleos excéntricos con cromatina homogénea. Se exhibían áreas de células densamente condensadas inmediatas y próximas al revestimiento epitelial intacto, pero separadas de él, por una fina capa de estroma laxo (capa cambial). El perfil de inmunomarcación resultó positivo para desmina, actina músculo específico y miogenina, y negativo para actina músculo liso. Se realizó diagnóstico de rabdomiosarcoma embrionario botroide de cuerpo uterino.

UNASSIGNED: Mesonephric-like adenocarcinoma (MLA) is a recently characterized, rare, and aggressive neoplasm that mostly arises in the uterine corpus and ovary. MLA shows characteristic pathological features similar to mesonephric adenocarcinoma of the cervix. The origin of MLA is still controversial and recognition of it remains challenging for pathologists. The aim of this study was to enrich the clinicopathological features of MLA in the uterine corpus and explore its molecular alterations by targeted next-generation sequencing (NGS).
UNASSIGNED: Four cases of MLA were identified among a total of 398 endometrial carcinomas diagnosed in our institution between January 2014 and December 2021. Immunohistochemistry and targeted NGS spanning 437 cancer-relevant genes were performed.
UNASSIGNED: The most common symptom was abnormal vaginal bleeding, and the average age was 68 years. Histologically, the tumors showed a mixture of varied growth patterns including papillary, glandular, tubular, cribriform, solid, and slit-like architectures, which were lined by columnar to cuboidal cells with overlapping vesicular nuclei and sometimes nuclear grooves. Intraluminal eosinophilic colloid-like secretions were focally evident in three of the four cases. Immunohistochemically, the MLAs were positive for GATA3 (4/4), TTF-1 (3/3), luminal CD10 (3/3), calretinin (2/3), and patchy P16 (3/3) and were negative for ER (0/4) and PR (0/4). The expression of P53 was \"wild type\" (4/4). By targeted NGS, 3/4 (75%), 2/4 (50%), and 1/4 (25%) cases harbored PIK3CA, KRAS, and PTEN mutations, respectively. None of the tumors had mutations in DNA mismatch repair genes, ARID1A/B, POLE, CTNNB1, SMARCA4, or TP53. At the time of diagnosis, three were presented with FIGO IB stage and one with IIIC stage. Two patients received postoperative chemotherapy and radiotherapy and they were alive without evidence of disease at 8 and 56 months follow-up, respectively. One patient developed pulmonary metastasis 13 months after surgery and chemotherapy, and one was dead of the disease 24 months after the operation without adjuvant therapy.
UNASSIGNED: MLA is a rare and aggressive malignancy, representing approximately 1% of all endometrial carcinomas. It exhibits mixed architectures associated with distinctive immunophenotype and recurrent KRAS and PIK3CA mutations, supporting classified as of Müllerian origin with mesonephric differentiation.

OBJECTIVE: The pathological diagnosis of undifferentiated and de-differentiated endometrial carcinomas (UC/DCs) is prognostically important. However, undifferentiated components may be confused with other subtypes, particularly grade 3 endometrioid carcinomas (G3ECs). Zinc finger E-box binding homeobox 1 (ZEB1) has recently been identified as a promising marker because it is frequently expressed in the undifferentiated components of UC/DCs, but not in other carcinomas. Therefore, we herein evaluated the diagnostic utility of ZEB1 with an emphasis on distinguishing between UC/DCs and G3ECs using an expanded cohort of endometrial carcinomas and carcinosarcomas.
RESULTS: Immunostaining for ZEB1 was performed on whole-tissue sections of 19 UC/DCs, 194 non-UC/DC endometrial carcinomas and 29 carcinosarcomas. Staining was defined as negative (< 5%), focal (5-50%) and diffuse expression (> 50%). ZEB1 was expressed in 84% of the undifferentiated components of UC/DCs (diffuse in 14, focal in two). Focal expression was observed in eight non-UC/DC endometrial carcinomas and diffuse expression in seven, with the latter comprising G3ECs (four of 76), serous carcinoma (one of 37), clear cell carcinoma (one of 21) and neuroendocrine carcinoma (one of three). Epithelial differentiation was morphologically and immunohistochemically less evident in G3ECs and neuroendocrine carcinoma with diffuse ZEB1 expression. All carcinosarcomas showed diffuse ZEB1 expression in their sarcomatous components.
CONCLUSIONS: Immunostaining for ZEB1 was sufficiently sensitive to detect undifferentiated components. Diffuse ZEB1 expression showed high specificity for distinguishing between undifferentiated components and G3ECs; however, ZEB1 expression was not entirely specific to UC/DCs. The integration of ZEB1 into the diagnosis of UC/DCs requires careful examination to exclude other tumours, such as less differentiated G3ECs, neuroendocrine carcinomas and carcinosarcomas.