Unraveling the Heterogeneity of Deficiency of Mismatch Repair Proteins in Endometrial Cancer: Predictive Biomarkers and Assessment Challenges.

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% of cases, approximately 30% of cases present with regional or distant spread, leading to nearly 20% mortality rates. Unlike many cancers, EC mortality rates are escalating, outpacing therapeutic advancements until recently. One of the reasons for this was the lack of effective therapeutic options for advanced disease until recently. The introduction of immunotherapy has marked a turning point in EC treatment, particularly benefiting patients with defects in mismatch repair proteins (dMMRs). However, dMMR status alone does not ensure a favorable response, underscoring the need for precise patient selection. This review explores the pivotal role of mismatch repair proteins in EC, emphasizing their heterogeneity, the challenges in their assessment, and their potential as predictive biomarkers.

Tumor-Infiltrating Lymphocytes and Tumor-Stroma Ratio on Early-Stage Cervix Carcinoma: Prognostic Value of Two Distinct Morphological Patterns of Microenvironment.

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. Their prognostic value could be demonstrated in different tumor tumor types, but they are poorly explored in cervical cancer. Methodology In this retrospective study, we analyzed the association of TILs, tumor-stroma ratio (TSR), and pattern of stromal fibroblasts with prognosis and classical clinicopathological variables. We studied 61 patients with early-stage cervical cancer. We reviewed histological type, tumor grade, Silva pattern of invasion for adenocarcinomas, tumor thickness, depth of stromal invasion, lymph vascular space invasion, and lymph node status. The median follow-up was 37.77 months (range 4.77 to 112.37 months). Results The TSR did not correlate with any clinicopathological features or disease-free and overall survival. On the other hand, the reactive pattern of stroma composed of larger fibroblasts and less collagenization was associated with the FIGO IB2 stage (p=0.04), larger tumor (p=0.03), and deeper infiltration (p=0.005). There were more recurrences in the group of reactive stroma (33.13% vs. 11.5%), although the difference did not reach statistical significance. Reactive stroma was associated with lower survival free of recurrence (p=0.05) and overall survival (p=0.009). High TILs were associated with squamous cell type (p=0.003), higher tumor grade (p=0.02), and more LVSI (p=0.02). Tumors with higher TILs presented higher free recurrence interval (p=0.06) and overall survival (p=0.03). No association was observed between stroma characteristics and TILs. Conclusions Our study suggested that although immune activation and stromal changes are important features of microenvironment remodeling during tumoral progression, they are independent, following distinct carcinogenetic pathways. Pathological assessment of stroma characteristics and TILs adds significant prognostic information and demonstrates how a simple routine laboratory assessment can generate a better understanding of biological phenomena.

Gemcitabine-Induced Radiation Recall Phenomenon in Cervical Cancer: A Case Report.

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, myositis, esophagitis, colitis, proctitis, and pneumonitis in areas within the irradiation field. Most patients respond to clinical treatment with corticosteroids. Here, we describe a 47-year-old patient with cervical carcinoma, FIGO stage IIB, submitted to external beam radiotherapy and concomitant chemotherapy with cisplatin (40 mg/m2 weekly), followed by intracavitary brachytherapy. One month after the end of radiotherapy and chemotherapy, the patient underwent laparoscopic completion hysterectomy plus bilateral salpingo-oophorectomy, followed by three cycles of cisplatin 50 mg/m2 D1 and gemcitabine 1,000 mg/m2 D1 and D8. Four months after the surgery, she presented with a suspicious mass in the vaginal dome that proved to be an exuberant inflammatory reaction that regressed after treatment with corticosteroids.

Role of systematic pelvic and para-aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy cycles for high-grade serous ovarian carcinoma.

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-paclitaxel between 2008 and 2016. Patients were included only if they had FIGO IIIC-IVB high-grade serous carcinoma with clinically negative lymph nodes after six NACT cycles (carboplatin-paclitaxel) and underwent complete or near complete cytoreduction. Patients with partial lymphadenectomy or bulky nodes were excluded. Patients who underwent systematic pelvic and aortic lymphadenectomy and those who did not undergo lymph node dissection were compared. Progression-free and overall survivals were analyzed using the Kaplan-Meier method. RESULTS: Totally, 132 patients with FIGO IIIC-IVB epithelial ovarian carcinoma were surgically treated after NACT. Sixty patients were included (39 and 21 in the lymphadenectomy and nonlymphadenectomy group, respectively); 40% had suspicious lymph nodes before NACT. Patient characteristics, blood transfusion numbers, and complication incidence were similar between the groups. In the lymphadenectomy group, 12 patients (30.8%) had histologically positive lymph nodes and the surgical time was longer (229 vs. 164 min). The median overall survival in the lymphadenectomy and nonlymphadenectomy groups, respectively, was 56.7 (95% CI 43.4-70.1) and 61.2 (21.4-101.0) months (p = 0.934); the corresponding disease-free survival was 8.1 (6.2-10.1) and 8.3 (5.1-11.6) months (p = 0.878). Six patients exclusively presented with lymph node recurrence. CONCLUSIONS: Systematic lymphadenectomy after six NACT cycles may have no influence on survival.

Vulvar Paget disease secondary to high-grade urothelial carcinoma with underlying massive vascular embolization and cervical involvement: case report of unusual presentation.

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 Paget disease associated with massive dermal vascular embolization, cervicovaginal involvement and metastasis to inguinal and retroperitoneal lymph nodes. The intraepithelial vulvar lesion had a classical appearance and was accompanied by extensive component of dermal lymphovascular tumor emboli, similar to those observed in inflammatory breast carcinoma. Immunohistochemical analysis revealed that the lesion was secondary to high-grade urothelial cell carcinoma. The patient had a history of superficial low-grade papillary urothelial carcinoma of the bladder, which had appeared 2 years before the onset of vulvar symptoms. CONCLUSIONS: Eczematoid vulvar lesions merit careful clinical examination and biopsy, including vulva mapping and immunohistochemistry. The information obtained may help to define and classify a particular presentation of Paget disease. Noninvasive primary lesions do not require the same aggressive approaches required for the treatment of invasive and secondary disease.

Ovarian yolk sac tumor coexisting with epithelial ovarian cancer: An aggressive rare entity.

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 components. The recognition of this histological subtype is important not only for differential diagnosis but also for determining prognosis and treatment decisions. In this case report, we describe a 61-year-old woman with YST coexisting with epithelial carcinoma focusing on the efficacy of systemic therapies.

Expression of PGR, HBEGF, ITGAV, ITGB3 and SPP1 genes in eutopic endometrium of infertile women with endometriosis during the implantation window: a pilot study.

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 gene (PGR) and the genes related to endometrium-embryo interaction regulated by progesterone. This pilot study compared the expression of PGR, HBEGF, ITGAV, ITGB3, and SPP1 genes in eutopic endometrium during the implantation window (IW) in infertile women with endometriosis with that observed in the endometrium of fertile and infertile controls. METHODS: In this prospective case-control study, endometrial biopsies were performed during the IW in patients aged between 18 and 45 years old, with regular cycles and without endocrine/systemic dysfunctions, divided into endometriosis (END), infertile control (IC) and fertile control (FC) groups. Total RNA extraction, cDNA synthesis, and gene expression analysis by Real-Time PCR were performed. We assessed the size of the difference that our series was powered to detect. RESULTS: From the 687 patients who underwent diagnostic videolaparoscopy or tubal ligation at the University Hospital, 130 were eligible. Of these, 32 had endometrial samples collected, with 17 confirmed in the IW. Fifteen samples (5 END, 5 IC and 5 FC) were analyzed. There was no significant difference in the expression of any studied gene. Our sample size allowed us to identify or discard large differences (two standard deviations) among the groups. CONCLUSION: Endometriosis doesn't cause large changes in the endometrial expression of PGR, HBEGF, ITGAV, ITGB3 and SPP1 during the IW.

Ultrastructural Evaluation of Eutopic Endometrium of Infertile Women With and Without Endometriosis During the Window of Implantation: A Pilot Study.

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 of implantation could affect the endometrial receptivity and be involved in the disease-related infertility. However, the data on pinopodes in these women are scarce and inconclusive. This pilot study aimed to evaluate the cell pattern, including the presence and developmental stage of pinopodes, in eutopic endometrium of infertile patients with and without endometriosis during the window of implantation, using scanning electron microscopy (SEM). Endometrial biopsies were performed using a Pipelle catheter, and 12 samples classified in the window of implantation (6 infertile women with endometriosis and 6 infertile controls) were analyzed by SEM. The frequencies of cell types (microvilli, ciliated, and pinopodes) and the developmental stage of pinopodes were compared between groups using Mann-Whitney U test. Although the study was limited by its sample size, no large differences were detected between the groups regarding the presence and developmental stage of pinopodes, suggesting the absence of large structural changes in the endometrium of infertile women with endometriosis during the window of implantation.

Uterine tumors resembling ovarian sex-cord tumor: A case-report and a review of literature.

•Uterine tumors with sex-cord elements are very rare.•UTROSCT can present with infiltration similar to endometrial stromal sarcomas.•Case report of a locally advanced UTROSCT.

Morphologic, molecular and microenvironment factors associated with stromal invasion in breast ductal carcinoma in situ: Role of myoepithelial cells.

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 ressection distributed in groups 1 (without invasion) and 2 (with invasive carcinoma). RESULTS: The risk of stromal invasion after a DCIS diagnosis in biopsy was associated to triple-negative profile and loss of CD10 expression by myoepithelial cells, and inversely associated with CK5/6 expression by neoplastic cells and high expression of Smooth Muscle Myosin Heavy Chain (SMMHC) by myoepithelial cells. CONCLUSIONS: A combination of characteristics of epithelial and myoepithelial cells in DCIS in biopsy specimens is related to the risk of stromal invasion.

Breast cancer in very young women: Clinicopathological study of 149 patients ≤25 years old.

BACKGROUND: 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). OBJECTIVES: The aim of the present study was to investigate the pathological characteristics of breast cancer in 149 Brazilian women who were ≤25 years old at the time of breast cancer diagnosis. MATERIALS AND METHODS: Tumor samples diagnosed between 2003 and 2009 were analyzed from the archives of the Bacchi Laboratory. RESULTS: In our series of 149 Brazilian women ≤25 years, 8.7% presented with in situ disease only. Of 136 invasive carcinomas, 91.9% were of the ductal type and 45.6% were of histological grade III. Overall, estrogen receptor (ER) was positive in 59.6% cases, and HER2 overexpression was detected in 32.8%. We also found a low prevalence of Luminal A cases and a high prevalence of Triple Negative cases. Statistical analysis showed that HER2 and basal-like groups had a lower overall survival expectation. Follow-up data showed high frequencies of regional lymph node metastasis, distant metastasis, and tumor-related deaths. CONCLUSION: The present study represents the largest series of breast cancer arising in women ≤25 years and establishes the main clinical, pathological, immunohistochemical and follow-up features of this population.

Clinical relevance of diagnostic hysteroscopy with concurrent endometrial biopsy in the accurate assessment of intrauterine alterations.

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 consecutive infertile patients who underwent diagnostic hysteroscopy followed by endometrial biopsy. Four-micrometer sections were stained with hematoxylin and eosin and examined microscopically. The data evaluated the frequency and characteristics of endometrial abnormalities found in the biopsies of patients with normal hysteroscopy outcome. Descriptive data are presented as percentages, and the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of hysteroscopy for diagnosis of endometrial alterations were calculated on the basis of pathologic reports. RESULTS: The hysteroscopy evaluation showed 50.0 % of patients with a normal uterine cavity, 40.5 % with endometrial polyps, 6.0 % with endometrial hyperemia, and 3.5 % with other endometrial abnormalities. Among the 42 patients with a normal uterine cavity at hysteroscopic examination, 60.0 % also had a normal biopsy outcome, but in other 40.0 % of patients at least one histopathological abnormal aspect was diagnosed at biopsy. The sensitivity (67.3 %), specificity (80.6 %), PPV (85.4 %) and NPV (59.5 %) of diagnostic hysteroscopy were calculated on the basis of histopathological findings. CONCLUSIONS: Our results show that diagnostic hysteroscopy demonstrated intrauterine alterations in half of infertile patients; histopathological endometrial alterations suggest high rate of false-negative outcomes. Therefore, diagnostic hysteroscopy and concurrent endometrial biopsy should be used as complementary diagnostic and therapeutic approach, especially for patients with previous IVF failures.

The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors.

OBJECTIVE: 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. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2.

The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors

OBJECTIVE: 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. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2. .

Geographic differences in the distribution of molecular subtypes of breast cancer in Brazil.

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 by molecular subtype based on immunohistochemical expression of estrogen-receptor (ER), progesterone-receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 proliferation index. Cases were classified as luminal A (ER and/or PR positive and HER2 negative, Ki-67 < 14%), luminal B (ER and/or PR positive, HER2 negative, and Ki-67 > 14%), triple-positive (ER and/or PR positive and HER2 positive), HER2-enriched (ER and PR negative, and HER2- positive), and triple-negative (TN) (ER negative, PR negative, and HER2- negative). Comparisons of the ages of patients and molecular subtypes between different geographic regions were performed. RESULTS: South and Southeast regions with a higher percentage of European ancestry and higher socioeconomic status presented with the highest proportion of luminal tumors. The North region presented with more aggressive subtypes (HER2-enriched and triple-negative), while the Central-West region predominated triple-positive carcinomas. The Northeast--a region with a high African influence--presented intermediate frequency of the different molecular subtypes. The differences persisted in subgroups of patients under and over 50 years. CONCLUSIONS: The geographic regions differ according to the distribution of molecular subtypes of breast cancer. However, other differences, beside those related to African ancestry, such as socioeconomic, climatic, nutritional, and geographic, have to be considered to explain our results. The knowledge of the differences in breast cancer characteristics among the geographic regions may help to organize healthcare programs in large countries like Brazil with diverse economic and race composition among different geographic regions.

Basal cytokeratin as a potential marker of low risk of invasion in ductal carcinoma in situ.

OBJECTIVES: 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. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1) and 146 samples associated with invasive carcinoma (group 2). Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR) membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2) and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease.

Basal cytokeratin as a potential marker of low risk of invasion in ductal carcinoma in situ

OBJECTIVES: 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. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1) and 146 samples associated with invasive carcinoma (group 2). Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR) membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2) and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease. .

Immunohistochemistry applied to the differential diagnosis between ductal and lobular carcinoma of the breast.

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, categorization in one or another type can be a challenge. Several immunohistochemical markers, including epithelial cadherin, p120, ß-catenin, and low-molecular-weight and high-molecular-weight cytokeratins among others, have been introduced to help better discriminate between lobular neoplasia and ductal carcinoma. In this critical review of the literature, we comment about the usefulness and the limitations of these markers to improve the accuracy in the differential diagnosis of breast pathology.

Leiomyomatosis peritonealis disseminata associated with endometriosis and multiple uterus-like mass: report of two cases.

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 metaplasia, and some of the nodules with aspects of uterus-like mass. Laparoscopy, gross findings, and the pathological and immunohistochemical study of the surgical specimens were described. Our findings suggest an endometriotic origin for the LPD and indicate that the therapeutic approach might contemplate the surgical reduction of the nodules and endometriosis treatment.

Intratumoral lymphatic vessel density in vulvar squamous cell carcinomas: a possible association with favorable prognosis.

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 intratumoral lymphatic vessel density (LVD) in the behavior of vulvar carcinomas. The aim of this study was to analyze intratumoral LVD in relation to patient survival and well-characterized prognostic factors for cancer. Thirty-five patients with vulvar squamous cell carcinoma underwent vulvectomy and dissection of regional lymph nodes. Clinical records were reviewed, in addition to histological grade, peritumoral lymphatic invasion, and depth of infiltration for each case. Tissue microarray paraffin blocks were created, and lymphatic vessels were detected using immunohistochemical staining of podoplanin (D2-40 antibody). Intratumoral LVD was quantified by counting the number of stained vessels. Higher values for intratumoral LVD were associated with low-grade and low-stage tumors, and with tumors without lymphatic invasion and reduced stromal infiltration. In a univariate analysis, high intratumoral LVD was associated with a higher rate of overall survival and a lower rate of lymph node metastasis. Our results suggest that increased intratumoral LVD is associated with favorable prognosis in vulvar squamous carcinomas.