Filomena M Carvalho

• M.D.,Ph.D
• Professor (Associate) at University of São Paulo

Context 17α-hydroxylase/17,20-lyase deficiency (17OHD) is a rare autosomal recessive condition. Women who have the complete form of 17OHD typically have a female phenotype, with an absence of secondary sexual characteristics, primary amenorrhea, and hypertension, which is usually detected in adolescence. Generally, 46,XY patients with a partial for...

Simple Summary Endometrial cancer is becoming more common globally, mainly due to factors such as aging populations and obesity. Despite the early detection in most cases, a significant number of patients still face advanced stages of the disease, leading to higher mortality rates compared to previous years. Recent advances in treatment, such as im...

Disclosure: M.M. Ferrari: None. M.Y. Nishi: None. A.A. Jorge: None. A.F. Benedetti,: None. R.L. Batista: None. E.S. Silva: None. A. Martinez: None. V. Mericq: None. F.M. Carvalho: None. B.B. Mendonca: None. S. Domenice: None. Introduction: Gonadal development in mammals is a dynamic and complex process, which requires the interaction of multiple fa...

Endometrial cancer (EC) poses a significant global health challenge, with increasing prevalence in 26 of 43 countries and over 13,000 deaths projected in the United States by 2024. This rise correlates with aging populations, the obesity epidemic, and changing reproductive patterns, including delayed childbearing. Despite the early diagnosis in 67%...

Introduction Precision medicine has revolutionized oncology, providing more personalized diagnosis, treatment, and monitoring for patients with cancer. In the context of female‐specific tumors, such as breast, ovarian, endometrial, and cervical cancer, proper tissue collection and handling are essential for obtaining tissue, immunohistochemical (IH...

Molecular characterization of endometrial cancer is allowing for increased understanding of the natural history of tumors and paving a more solid pathway for novel therapies. It is becoming increasingly apparent that molecular classification is superior to histological classification in terms of reproducibility and prognostic discrimination. In par...

Malignant mixed müllerian tumor (MMMT) is a rare neoplasm, consisting of carcinomatous (epithelial) and sarcomatous (mesenchymal) components that most commonly arise in the endometrium and more infrequently in the ovaries, fallopian tube, cervix, and vagina. Primary peritoneal carcinosarcoma (PPCS) is an extremely rare extragenital presentation of...

Triple-negative breast cancers (TNBCs) are more likely to occur in younger patients and have a poor prognosis. They are highly heterogeneous tumors consisting of different molecular subtypes. The only common characteristic among them is the absence of targets for endocrine therapy and human epidermal growth factor receptor 2 (HER2) blockade. In the...

Background Tumor progression is influenced by the complex network of different cellular elements that make up its microenvironment. Tumor-infiltrating lymphocytes (TILs) and stroma characteristics reflect two faces of the intricate mechanisms involved in the tumor-host interaction and can be easily evaluated by routine histological examination. The...

Cervical cancer is one of the most frequent gynecological malignancies in Brazil, and most of the patients require pelvic radiotherapy as part of oncological treatment. Pelvic radiotherapy induces ovarian premature insufficiency in pre-menopausal women. This condition impacts the life quality and increases the risk of osteoporosis, obesity, cardiov...

Isthmocele is a discontinuation of the myometrium at the uterine scar site in a patient with a previous cesarian section (CS). The cause of isthmocele appears to be multifactorial. Poor surgical technique, low incision location, uterine retroflection, obesity, smoking, inadequate healing of scars, and maternal age are possible related factors. Most...

DNA mismatch repair protein deficiency (MMRd) in endometrial carcinoma is associated with the risk of Lynch syndrome and response to immune checkpoint inhibitors. It is also related to microsatellite instability and corresponds to a molecular subtype of endometrial tumor with an unclear prognosis. Here, we evaluated the clinicopathological characte...

The radiation recall phenomenon is a rare, massive inflammatory reaction induced by some chemotherapeutic agents in previously irradiated areas. When it occurs in the pelvis it looks like a recurrence. Recognizing this phenomenon is paramount to avoiding unnecessary surgical intervention and complications. Symptoms manifest as dermatitis, mucositis...

Introduction: Radiation therapy (RT) plays an important role in the management of patients with ductal carcinoma in situ (DCIS) of the breast, treated by breast conserving surgery (BCS). RT reduces significantly the risk of local recurrences (LR). Efforts are being, currently, to de-escalate RT in this scenario with individualized decision-makings....

Introduction Complete Androgen Insensitivity Syndrome (CAIS) is characterized by a complete external genitalia appearance and testicular development in 46,XY individuals carrying inactivating mutations in the AR gene. Prophylactic gonadectomy versus saving gonads has been debatable in CAIS management, mainly due to the absence of an accurate biomar...

Timely and correct assessment of histopathological, immunohistochemical and molecular features of biopsy and surgical specimens is of paramount importance in the provision of care to patients with breast cancer, particularly in the current era of precision oncology. In order to ensure that tissue samples are obtained, processed, analyzed and report...

Introduction Due to scant literature and the absence of high-level evidence, the treatment of vulvar cancer is even more challenging in countries facing limited resources, where direct application of international guidelines is difficult. Recommendations from a panel of experts convened to address some of these challenges were developed. Methods T...

Introduction Nearly 85% of cervical cancer new cases are diagnosed in limited resources countries. Although several strategies have been proposed to reduce the disease burden, challenges remain to provide the best possible care. We report recommendations from an expert consensus meeting convened to address from prevention to management of cervical...

Objective: This study evaluated the frequency of GATA-binding protein 3 (GATA3) expression in early breast cancer and its relationship with histopathological and immunohistochemical parameters. Materials and methods: GATA3 was analysed by immunohistochemistry in histological sections of tumors from 105 female patients, with histological diagnosi...

Timely and correct assessment of histopathological, immunohistochemical and molecular features of biopsy and surgical specimens is of paramount importance in the provision of care to patients with breast cancer, particularly in the current era of precision oncology. In order to ensure that tissue samples are obtained, processed, analyzed and report...

Introduction: Radiation therapy (RT) plays an important role in the management of patients with ductal carcinoma in situ (DCIS) of the breast, treated by breast-conserving surgery (BCS). RT significantly reduces the risk of local recurrences (LRs) in unselected patients. Efforts are being made, currently, to de-escalate the RT in this scenario with...

Female adnexal tumor of probable Wolffian origin (FATWO) are a rare type of cancer that originates from Wolffian duct remnants. Due to its rarity, no standard systemic treatment is established for cases of recurrent or metastatic disease. Previous literature reported the use of platinum-based chemotherapy and c-Kit tyrosine kinase inhibitors for FA...

Introduction: We analyzed the role of systematic pelvic and para-aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy (NACT) cycles for advanced high-grade serous ovarian carcinoma. Materials and methods: We retrospectively reviewed patients with advanced ovarian carcinoma who underwent NACT with carboplatin-pac...

Background and objectives It is well established that tumor-free margin is an important factor for reducing local recurrence and reoperation rates. This systematic review with meta-analysis of frozen section intraoperative margin assessment aims to evaluate the accuracy, and reoperation and survival rates, and to establish its importance in breast-...

Introduction: GATA3 gene, at 10p14, a member of the GATA family with two GATA-type zinc-fingers, encodes the transcription factors GATA - binding protein 3 (GATA3), critical for the luminal breast epithelium development and maintenance. The GATA3 protein is a linear one, with more than 400 aminoacids, that can be recognized by immunohistochemical a...

Introduction: The broad acceptance of sentinel lymph node biopsy (SLNB) led to an analysis for finding out the anatomopathological characteristics that can help predict the involvement of other axillary lymph nodes (LN) in positive sentinel lymph node (SLN) cases. Currently, it is very appropriate to investigate the cases that enable the omission o...

Introduction: The expression of androgenic receptors (AR) is a new predictive marker of response and prognosis in invasive breast carcinoma (BC). It emerges as a potential therapeutic target. Objectives: To evaluate the frequency of AR positivity and its correlation with molecular and histopathological parameters in infiltrative BC. Methods: Retros...

The mortality rate of breast cancer (BC) in Brazil is increasing. Procedures that can improve the diagnosis and treatment of BC should be discussed by specialists to improve patient survival. Experts from five different specialties involved in the diagnosis and treatment of BC discussed possible problems and solutions in this context. The discussio...

Endometrial cancer is the only gynecological cancer that is rising in incidence and associated mortality worldwide. Although most cases are diagnosed as early stage disease, with chances of cure after primary surgical treatment, those with advanced or metastatic disease have a poor prognosis because of the quality of treatment options that are curr...

Background: Nipple-sparing mastectomy (NSM) is increasingly performed for breast cancer (BC) treatment. To ensure local control with this procedure, it is important to obtain clear surgical margins. Here, we aimed to estimate the confidence in intraoperative evaluation of the retroareolar margin (IERM) and the necessity of removing the intra-nippl...

Aims L1 cell adhesion molecule (L1CAM) has been shown to be correlated with tumour progression, attributed to its possible association with epithelial-mesenchymal transition (EMT), characterised by the expression of vimentin and loss of e-cadherin. Herein, we investigate the associations between L1CAM and clinicopathological parameters, as well as...

Few reports have described the clinical and prognostic characteristics of endometrial cancer, which is increasing worldwide, in large patient series in Brazil. Our objective was to analyze the clinicopathological characteristics, prognostic factors, and outcomes of patients with endometrial cancer treated and followed at a tertiary Brazilian instit...

Introduction: The expression of androgenic receptors (AR) is a new predictive marker of response and prognosis in invasive breast carcinoma (BC). It emerges as a potential therapeutic target. Objective: To evaluate the frequency of AR positivity and its correlation with molecular and histopathological parameters in infiltrative BC. Method: Retrospe...

Introduction: Mammary adenectomy (MA) has been increasingly adopted to treat early-stage breast cancer (BC) for its cosmetic benefits and oncologic safety. In order to ensure the local control of the disease, the amount of remaining glandular tissue should be the least possible, and surgical margins must be free. Objective: To evaluate the predicti...

Introduction: The nipple-areola complex (NAC) has glandular tissue in intrapapillary ducts (IPDs). When the NAC is preserved during mammary adenectomies (MA) for the treatment of breast cancer (BC), this glandular tissue, which is a potential focus of tumor residues, remains. Objective: To estimate the frequency of neoplastic development in IPDs am...

Background: Vulvar extramammary Paget disease is a rare chronic condition, that presents with non-specific symptoms such as pruritus and eczematous lesions. Because most of these lesions are noninvasive, the distinction between primary and secondary Paget disease is crucial to management. Case presentation: We report an unusual case of vulvar Pa...

Percutaneous biopsies with histological sampling enabled the reduction of unnecessary surgeries in benign lesions and enhanced therapeutic planning in cases of malignant neoplasia. However, they require proper interpretation from the clinic, radiologic, and histologic context to minimize false-negative results. Therefore, the following are mandator...

Objectives The aim of this study was to assess the association between DNA mismatch repair protein MLH1 status and classical prognostic factors in patients with endometrioid endometrial carcinoma. Methods We studied 47 consecutive patients aged 37–88 (61.34±10.52) with confirmed diagnosis of endometrial carcinoma of endometrioid type. The tumors w...

Objectives To analyze the influence of histopathological response on clinicoradiological and survival of patients with high-grade serous ovarian carcinoma (HGSC) after neoadjuvant chemotherapy. Methods From 2008 to 2016, patients with advanced HGSC (FIGO IIIC-IVB) who underwent 6 cycles of NACHT (carboplatin-paclitaxel) followed by cytoreductive s...

Context: 46,XY gonadal dysgenesis (GD) is a heterogeneous group of disorders with a wide phenotypic spectrum, including embryonic testicular regression syndrome (ETRS). Objective: To report a novel gene for 46,XY GD etiology, especially for ETRS. Design: Screening of familial cases of 46,XY GD using WES and sporadic cases by target gene panel...

Phenotype of 46,XY gonadal dysgenesis patients with pathogenic allelic variant in DEAH-box helicase 37 gene, exome capture, sequencing, variant filtering and immunohistochemical expression analysis in human testis.

Context There are limited data regarding prevalence of metabolic risk factors in hyperandrogenic postmenopausal women. Also, the correlation between metabolic disorders and androgen excess is poorly understood in this scenario. Objectives We aimed to assess the prevalence of obesity, hypertension, diabetes (T2D), and dyslipidemia (DLP) in postmeno...

Leiomyomas are prevalent benign smooth muscle tumors in the uterus, displaying variable degrees of FDG uptake on PET/CT. The glucose metabolism intensity of those lesions relies on biologic features and markedly increased FDG accumulation is more typically related to malignant diseases, as in the case of leiomyosarcomas. Notwithstanding that uterin...

Background Risk stratification of endometrial carcinomas is primarily based on surgical staging that requires extensive retroperitoneal lymph node dissection. One of the most powerful predictor of lymph node involvement is the lymph vascular space invasion (LVSI). The objective of this study was to determine the potential of L1 Cell Adhesion Molecu...

46,XY gonadal dysgenesis is a heterogeneous disorder of sex development (DSD) that features abnormal gonadal development and varying degrees of undervirilization of the external genitalia, ranging from micropenis to female-like genitalia. Embryonic testicular regression syndrome (ETRS; MIM: 273250) is considered part of the clinical spectrum of 46,...

Objective: Alterations in endometrial receptivity may be involved in the etiopathogenesis of endometriosis-related infertility. The literature has suggested that patients with endometriosis present progestin resistance, which could affect embryo implantation. We question the presence of alterations in the expression of the progesterone receptor ge...

Yolk sac tumor (YST) is the second most common subtype of ovarian germ cell tumors. It usually occurs in the second and third decades of life and is rare in postmenopausal women. In postmenopausal women, YST is commonly an aggressive tumor and can present as a pure germ cell component or as a mixed component with other germ cell or epithelial compo...

Objective: To evaluate the contribution of clinical features, hormonal profiles and radiological studies to the differential diagnosis of VOT and OH. Design: A retrospective study. Setting: A tertiary center. Main outcome measures: Clinical data, hormonal status (T, E2, LH, and FSH), pelvic images (transvaginal sonography and MRI) and anatom...

Endometriosis is frequently associated with infertility and it is believed that the impairment of endometrial receptivity may be one of the mechanisms involved in this condition. Pinopodes are endometrial cycle-dependent structures that seem to participate in embryo implantation, and alterations in their presence and/or morphology during the window...

Objectives: Triple-negative breast carcinomas (TNBCs) correspond to a molecular heterogeneous disease defined by lack of estrogen and progesterone receptor expression, and the absence of overexpression and/or amplification of HER2. Recent data indicate that clinical outcome in TNBC is affected by tumor-infiltrating lymphocytes, suggesting that the...

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a T-cell lymphoproliferative disorder that has recently been recognized as an independent entity in the World Health Organization (WHO) classification of lymphomas. Despite the small number of reports to date, the number of cases is rapidly increasing. Of the few hundred cases t...

Robotic surgeries for cervical cancer have several advantages compared with laparotomic or laparoscopic surgeries. Robotic single-site surgery has many advantages compared with the multiport approach, but its safety and feasibility are not established in radical oncologic surgeries. We report a case of a Federation of Gynecology and Obstetrics (FIG...

Objective Triple-negative breast carcinomas (TNBCs) represent a heterogeneous group of neoplasias, even though they generally exhibit a clinically more aggressive phenotype, and are more prevalent in young women. To date, targeted therapies for this group of tumors have not been defined. The aim of this study was to evaluate the frequency of the ap...

17b-hydroxysteroid dehydrogenase 3 deficiency consists of a defect in the last phase of steroidogenesis, in which androstenedione is converted into testosterone and estrone into estradiol. External genitalia range from female-like to atypical genitalia and most affected males are raised as females. Virilization in subjects with 17b-HSD3 deficiency...

Fig. 1. Uterine tumor sections showing trabeculae and anastomosing cords of epithelioid cells (A) with areas of sertoliform (B) and retiform structures (C). Endovascular growth was evident (D) (hematoxylin–eosin).

Background: Ductal carcinoma in situ is the last step preceding invasive ductal carcinoma in breast carcinogenesis. Objective: We investigated the role of myoepithelial cells and epithelium characteristics as predictors of the risk of stromal invasion. Methods: We selected 236 cases with initial diagnosis of DCIS followed by surgical ressectio...

The aim of this study was to determine the lymph node status in a large cohort of women with endometrial cancer from the public health system who were referred to an oncology reference center in Brazil to identify candidates for the omission of lymphadenectomy based on clinicopathological parameters. We retrospectively analyzed a cohort of 310 wome...

Breast cancer in young women has different clinical and pathologic features and a more aggressive biological behavior when compared to breast cancers in older women. However, information is limited to the group of very young women (≤25 years). The aim of the present study was to investigate the pathological characteristics of breast cancer in 149 B...

Purpose: The aim of this retrospective observational study was to evaluate the reliability of diagnostic hysteroscopy, routinely performed along with endometrial biopsy, by analyzing and comparing both hysteroscopic and histopathological outcomes in asymptomatic infertile patients, previously to their IVF cycle. Methods: The study included 84 co...

Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. A total of 124 cases of mucino...

Background To compare the distribution of the intrinsic molecular subtypes of breast cancer based on immunohistochemical profile in the five major geographic regions of Brazil, a country of continental dimension, with a wide racial variation of people. Methods The study was retrospective observational. We classified 5,687 invasive breast cancers b...

PURPOSE: To examine the expression of AKT and PTEN in a series of HER2-positive primary invasive breast tumors using immunohistochemistry, and to associate these expression profiles with classic pathologic features such as tumor grade, hormone receptor expression, lymphatic vascular invasion, and proliferation. METHODS: A total of 104 HER2-positiv...

To explore the relationship between morphological characteristics and histologic localization of metastasis within sentinel lymph nodes (SLN) and axillary spread in women with breast cancer. We selected 119 patients with positive SLN submitted to complete axillary lymph node dissection from July 2002 to March 2007. We retrieved the age of patients...

17β-hydroxysteroid dehydrogenase 3 deficiency (17β-HSD3) consists of a defect in the last phase of steroidogenesis, in which androstenedione is converted into testosterone and estrone into estradiol. Patients present female-like or with ambiguous genitalia at birth and most affected males are raised as females. Virilization in subjects with 17β-HSD...

Objective: Functional polyps and chronic endometritis are among the most common abnormalities seen in the endometrium of patients with implantation failures and recurrent miscarriages. In this study we describe morphological vascular changes in endometrial samples from asymptomatic infertile patients and their association with chronic endometritis...

The knowledge of the microscopic morphology of normal skin helps to better understand the clinical presentation of dermatologic diseases involving the male genital area.

Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. We constructed tissue microarrays using 236 ductal carcinoma in situ...

To compare the prognostic and predictive features between in situ and invasive components of ductal breast carcinomas. We selected 146 consecutive breast samples with ductal carcinoma in situ (DCIS) associated with adjacent invasive breast carcinoma (IBC). We evaluated nuclear grade and immunohistochemical expression of estrogen receptor (ER), prog...

Leiomyomatosis peritonealis disseminate (LPD) is a rare benign disease of unknown etiology of women in reproductive age. A few reported cases of association with endometriosis have been described suggesting a possible origin from submesothelial multipotential cells. We present two cases of LPD associated with endometriosis expressing smooth muscle...

The distinction between classic lobular and ductal carcinoma, both in situ and invasive, has important therapeutic and management implications. Most ductal and lobular carcinomas are distinguished readily on hematoxylin-eosin-stained sections because of distinct histomorphologic features. In cases with ambiguous morphologic features, however, categ...

Differentiation between benign and malignant ovarian neoplasms is essential for creating a system for patient referrals. Therefore, the contributions of the tumor markers CA125 and human epididymis protein 4 (HE4) as well as the risk ovarian malignancy algorithm (ROMA) and risk malignancy index (RMI) values were considered individually and in combi...

The epithelial cells of the breast are under the influence of a range of hormones and growth factors. The HER2, a member of the family of growth factor receptors with tyrosine kinase activity, is amplified in approximately 15-20% of breast tumors, defining a highly aggressive subgroup. The breast cancers that overexpress HER2 inaugurated the era of...

Synchronous endometrial and cervical cancer is a very rare condition. This report describes a case of a 46-year-old woman who presented with a cervical mass that measured 5.6 cm along its longest diameter, whose biopsy analysis revealed an endocervical mucinous adenocarcinoma. She was classified as having an IB2 cervical carcinoma and treated with...

Fanconi Anemia (FA) is an autosomal recessive disease characterized by chromosome instability, cellular hypersensitivity to DNA cross-linking agents, and increased predisposition to malignancies. We describe here a 28 year-old female with FA and vaginal squamous cell carcinoma treated by radiation therapy alone. The patient developed arm phlebitis,...

Human epidermal growth factor receptor 2 (HER2)-positive breast cancers are aggressive neoplasms associated with a variable response to systemic therapies. Therefore, the identification of biomarkers to better characterise this heterogeneity would improve treatment efficacy. The aim of this study was to evaluate the influence of androgen receptor (...

Lymphatic vessels serve as major routes for regional dissemination, and therefore, lymph node status is a key indicator of prognosis. To predict lymph node metastasis, tumor lymphatic density and lymphangiogenesis-related molecules have been studied in various tumor types. To our knowledge, no previous studies have evaluated the role of intratumora...

WT1 mutations have been described in a variety of syndromes, including Denys-Drash syndrome (DDS), which is characterized by predisposition to Wilms' tumor, genital abnormalities and development of early nephropathy. The most frequent WT1 defects in DDS are missense mutations located in exons 8-9. Our aim is to report a novel WT1 mutation in a 46,X...

Breast cancer accounts for approximately one quarter of all cancers in females. Estrogen and progesterone receptor testing has become an essential part of the clinical evaluation of breast carcinoma patients, and accurate results are critical in identifying patients who may benefit from hormone therapy. The present study had the aim of investigatin...

Vulvar Paget's disease is very rare malignancy originating in vulvar apocrine-gland-bearing skin cells or as a manifestation of adjacent primary anal, rectal or bladder adenocarcinoma.1 It is also called extramammary Paget's disease and affects both sexes, in the vulvar, perineal or scrotal areas. Vulvar Paget's disease is most commonly seen in pos...