Prevalence of anal high-risk human papillomavirus (HR-HPV) types in people living with HIV and a history of cancer.

This study aimed to describe the prevalence of high-risk human papillomavirus (HR-HPV) types in the anal canal in a cohort of people living with HIV (PLWHIV) with a history of malignancy. SETTING: Referral tertiary care hospital for adult patients with cancer. METHODS: We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high-resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed. RESULTS: A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32-47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non-Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR-HPV infection was 89% (n=138) (95% CI 83-93) with at least one HR-HPV infection, and 62% (96) had coinfection with at least two types; the median HR-HPV types of coinfection were 3 (IQR 2-4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8-49.3), HPV 18 was 74 (47.7%, 95% CI 39.9-55.7) and with both 35 (22.6%). Some 59 patients (38%) had high-grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low-grade squamous intraepithelial lesions (LSIL). The prevalence of HR-HPV and HSIL among patients aged ≤35 and >35 years was the same. CONCLUSIONS: In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR-HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy.

Metastatic solid tumours to the penis: a clinicopathologic evaluation of 109 cases from an international collaboration.

AIMS: To elucidate the spectrum of metastatic tumours to the penis and their clinicopathologic features. METHODS: The databases and files of 22 pathology departments from eight countries on three continents were queried to identify metastatic solid tumours of the penis and to characterize their clinical and pathologic features. RESULTS: We compiled a series of 109 cases of metastatic solid tumours that secondarily involved the penis. The mean patient age at diagnosis was 71 years (range, 7-94 years). Clinical presentation commonly included a penile nodule/mass (48/95; 51%) and localised pain (14/95; 15%). A prior history of malignancy was known in 92/104 (89%) patients. Diagnosis was made mainly on biopsy (82/109; 75%), or penectomy (21/109; 19%) specimens. The most common penile locations were the glans (45/98; 46%) and corpus cavernosum (39/98; 39%). The most frequent histologic type was adenocarcinoma (56%). Most primary carcinomas originated in the genitourinary (76/108; 70%) and gastrointestinal (20/108; 18%) tracts, including prostate (38/108; 35%), urinary bladder (27/108; 25%), and colon/rectum (18/108; 17%). Concurrent or prior extrapenile metastases were identified in 50/78 (64%) patients. Clinical follow-up (mean 22 months, range 0-171 months) was available for 87/109 (80%) patients, of whom 46 (53%) died of disease. CONCLUSION: This is the largest study to date of metastatic solid tumours secondarily involving the penis. The most frequent primaries originated from the genitourinary and gastrointestinal tracts. Metastatic penile tumours usually presented with penile nodules/masses and pain, and they often occurred in the setting of advanced metastatic disease, portending poor clinical outcomes.

Influence of luminal and basal subtype in prognosis of high-grade non muscle invasive urothelial carcinoma.

BACKGROUND: Recent studies have shown that the classification of high-grade urothelial carcinoma non-muscle invasive (HGBCNMI) based on molecular subtypes might be a valuable strategy to identify patients with a worse clinical prognosis. OBJECTIVE: Determine the effect of the luminal and basal molecular subtype determined by immunistochemical on prognosis in patients with HGBC in Mexican population. METHODS: Phenotypes were evaluated by immunohistochemical staining of luminal (GATA3, FOXA1) and basal (CK5/6, CK14) markers in paraffin-embedded tissue samples from 45 patients with a diagnosis of HGBCNMI treated at Instituto Nacional de Cancerología-México (INCan) between 2009 and 2019. The association with prognosis was evaluated using Kaplan-Meier curves and multivariable-adjusted Cox models. RESULTS: HGBCNMI patients showed mean age of 58.77 years (SD: ±12.08 years). We identified expression of the luminal molecular subtype in 35 cases (77.78 %), and 10 cases (22.22 %) with "combined" expression of the molecular subtype (basal and luminal expression). The combined phenotype was statistically more frequent in metastatic cases (p-value = 0.028). In Kaplan-Meier curves, combined expression of luminal and basal molecular markers was associated with disease progression (p-value = 0.002, log-rank test). Cox regression models confirmed this association, which was not influenced by age (p-value = 0.007) or gender (p-value = 0.007). No association of phenotypes with overall survival (p-value = 0.860) or relapse (p-value = 0.5) was observed. CONCLUSION: The combined expression of immunohistochemical markers of the luminal and basal subtype might be considered as predictor for disease progression in patients with HGBCNMI in Mexican population.

Tumor histology is an independent prognostic factor in locally advanced cervical carcinoma: A retrospective study.

BACKGROUND: Even with different histologic origins, squamous cell carcinoma (SCC) and adenocarcinoma (AC) are considered a single entity, and the first-line treatment is the same. Locally advanced disease at the diagnosis of cervical cancer is the most important prognostic factor, the recurrence rate is high, making it necessary to evaluate prognostic factors other than clinical or radiological staging; histology could be one of them but continues to be controversial. The aim of this study was to evaluate tumor histology as a prognostic factor in terms of treatment outcomes, disease-free survival (DFS) and overall survival (OS) in a retrospective cohort of patients with Locally Advanced Cervical Carcinoma (LACC). METHODS: The records of 1291patients with LACC were reviewed, all of them were treated with 45-50 Gy of external beam radiotherapy with concurrent chemotherapy and brachytherapy. A descriptive and comparative analysis was conducted. Treatment response was analyzed by the chi-square test; DFS and OS were calculated for each histology with the Kaplan-Meier method and compared with the log-rank test; and the Cox model was applied for the multivariate analysis. RESULTS: We included 1291 patients with LACC treated from 2005 to 2014, of which 1154 (89·4%) had SCC and 137 (10·6%) had AC. Complete response to treatment was achieved in 933 (80·8%) patients with SCC and 113 (82·5%) patients with AC. Recurrence of the disease was reported in 29·9% of SCC patients and 31·9% of AC patients. Five-year DFS was 70% for SCC and 62·2% for AC. The five-year OS rates were 74·3% and 60% for SCC and AC, respectively. The mean DFS was 48·8 months for SCC vs 46·10 for AC (p = 0·043), the mean OS was 50·8 for SCC and 47·0 for AC (p = 0·002). CONCLUSION: Our findings support the hypothesis that SCC and AC are different clinical entities. TRIAL REGISTRATION: NCT04537273 .

Acantholytic squamous cell carcinomas of the cervix: A case series.

Squamous cell carcinoma of the uterine cervix is considered the most common histologic variant of cervical cancer, with well-established treatment protocols and prognosis. An infrequent histologic variant of cervical squamous cell carcinoma is the acantholytic variant (ASCC), which is characterized by discohesive cells that result in a pseudoglandular and/or angiomatoid pattern of growth. This variant of squamous cell carcinoma has been regarded as having a poor prognosis at certain anatomic sites such as the head and neck and vulva. In the uterine cervix, the importance of this variant has not been yet established. A ten-year retrospective review of squamous cell carcinoma of the uterine cervix was performed to identify this variant and correlate it with clinical characteristics to better define its prognostic implications. During the study period 19 cases were identified containing from 10 to 80% acantholytic component. Mean age at diagnosis was 49 years. Clinical stages were 1A2 (1 case), Ib1 (16), and IIA1 (2). Median follow-up was 92 months. When compared with controls, ASCC were larger in size (1.4 vs 3.5 cm), had deeper involvement of the cervical stroma (21 vs 47%), had more lymph node metastasis (8 vs 26%), more frequent recurrences (4 vs 15%) and a shorter disease-free survival; however, no statistical differences were identified in overall survival. ASCC is an infrequent variant of cervical cancer which seems to have an impact on disease-free survival but no in overall survival.

Histologic diversity in chromophobe renal cell carcinoma does not impact survival outcome: A comparative international multi-institutional study.

Predicting the clinical behavior and trajectory of chromophobe renal cell carcinoma (ChRCC) by histologic features has so far proven to be challenging. It is known that ChRCC represents a heterogeneous group of neoplasms demonstrating variable, yet distinctive morphologic and genetic profiles. In this international multi-institutional study, we aimed to assess the impact of histologic diversity in ChRCC (classic/eosinophilic versus rare subtypes) on survival outcome. This is an international multi-institutional matched case-control study including 14 institutions, examining the impact of histologic subtypes of ChRCC on survival outcome. The study group (cases) included 89 rare subtypes of ChRCC. The control group consisted of 70 cases of ChRCC including classic and eosinophilic features, age- and tumor size-matched. Most of the rare subtypes were adenomatoid cystic/pigmented ChRCC (66/89, 74.2%), followed by multicystic ChRCC (10/89, 11.2%), and papillary ChRCC (9/89, 10.1%). In the control group, there were 62 (88.6%) classic and 8 (11.4%) eosinophilic ChRCC. There were no statistically significant differences between the study and control groups for age at diagnosis, gender distribution, tumor size, presence of tumor necrosis, presence of sarcomatoid differentiation, and adverse outcomes. No statistically significant differences were found in clinical outcome between the rare subtypes and classic/eosinophilic groups by tumor size, necrosis, and sarcomatoid differentiation. Further, no statistically significant differences were found in clinical outcome between the two groups, stratified by tumor size, necrosis, and sarcomatoid differentiation. Our findings corroborated previous studies that both sarcomatoid differentiation and tumor necrosis were significantly associated with poor clinical outcome in classic/eosinophilic ChRCC, and this was proven to be true for ChRCC with rare histologic subtypes as well. This study suggests that rare morphologic patterns in ChRCC without other aggressive features play no role in determining the clinical behavior of the tumor.

Renal cell carcinomas with tubulopapillary architecture and oncocytic cells: Molecular analysis of 39 difficult tumors to classify.

So-called oncocytic papillary renal cell carcinoma (OPRCC) is a poorly defined variant of papillary renal cell carcinoma. Since its first description, several studies were published with conflicting results, and thus precise definition is lacking. A cohort of 39 PRCCs composed of oncocytic cells were analyzed. Cases were divided into 3 groups based on copy number variation (CNV) pattern. The first group consisted of 23 cases with CNV equal to renal oncocytoma. The second group consisted of 7 cases with polysomy of chromosomes 7 and 17 and the last group of 9 cases included those with variable CNV. Epidemiologic, morphologic and immunohistochemical features varied among the groups. There were not any particular histomorphologic features correlating with any of the genetic subgroups. Further, a combination of morphologic, immunohistochemical, and molecular-genetic features did not allow to precisely predict biologic behavior. Owing to variable CNV pattern in OPRCC, strict adherence to morphology and immunohistochemical profile is recommended, particularly in limited samples (i.e., core biopsy). Applying CNV pattern as a part of a diagnostic algorithm can be potentially misleading. OPRCC is a highly variable group of tumors, which might be misdiagnosed as renal oncocytoma. Using the term OPRCC as a distinct diagnostic entity is, thanks to its high heterogeneity, questionable.

Molecular Genetic Features of Primary Nonurachal Enteric-type Adenocarcinoma, Urachal Adenocarcinoma, Mucinous Adenocarcinoma, and Intestinal Metaplasia/Adenoma: Review of the Literature and Next-generation Sequencing Study.

The diagnosis of primary adenocarcinoma of the urinary bladder may be challenging in routine practice. These tumors may morphologically and immunohistochemically overlap with urachal adenocarcinoma and colorectal adenocarcinoma. Further, their genetic background is poorly understood. We systematically searched the PubMed database for results of complex genetic evaluation of primary bladder adenocarcinoma subtypes. Subsequently, we designed our own series of bladder lesions. We evaluated 36 cases: 16 primary enteric-type adenocarcinomas, 7 urachal enteric adenocarcinomas, 3 primary mucinous/colloid adenocarcinomas, and 10 intestinal-type metaplasia/villous adenoma. Detailed clinical data were collected, and all cases were examined using targeted next-generation sequencing. On the basis of the literature, the first mutated gene in these tumors was reported to be KRAS in 11.3% of cases, followed by TERT promoter mutations in 28.5%. In addition to KRAS and TERT, other genes were also found to be frequently mutated in primary bladder adenocarcinoma, including TP53, PIK3CA, CTNNB1, APC, FBXW7, IDH2, and RB1. In our series, the most frequent gene mutations in primary enteric-type adenocarcinomas were as follows: TP53 (56%); BRCA2, KMT2B (both 33%); NOTCH2, KDR, ARID1B, POLE, PTEN, KRAS (all 28%); in urachal enteric adenocarcinoma they were as follows: TP53 (86%); PTEN, NOTCH (both 43%); in primary mucinous/colloid adenocarcinomas they were as follows: KRAS, GRIN2A, AURKB (all 67%); and, in intestinal-type metaplasia/villous adenoma, they were as follows: APC, PRKDC (both 60%); ROS1, ATM, KMT2D (all 50%). No specific mutational pattern was identified using cluster analysis for any of the groups. Herein, we describe the pathologic features and immunohistochemical staining patterns traditionally used in the differential diagnoses of glandular lesions of the bladder in routine surgical pathology. We outline the mutational landscape of these lesions as an aggregate of published data with additional data from our cohort. Although diagnostically not discriminatory, we document that the most common genetic alterations shared between these glandular neoplasms include TP53, APC (in the Wnt pathway), and KRAS (in the MAPK pathway) mutations.

Diagnostic performance of intraoperative assessment in grade 2 endometrioid endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is the most common gynecologic malignancy in developed countries. Grade 2 carcinoma is associated with pelvic lymph-node metastasis, depending on selected risk factors. Intraoperative assessment (IOA) can identify patients at risk for lymph node metastasis who should undergo staging surgery. Our objective was to establish the diagnostic precision of IOA in determining the need for surgical staging in grade 2 endometrioid endometrial carcinoma. METHODS: Two hundred twenty-two patients underwent IOA. Results were compared to the final pathology report. The accuracy of the IOA parameters was calculated. Variables were evaluated in patients with positive versus negative IOA. Overall and disease-free survivals were calculated according to IOA, lymphadenectomy, and nodal metastasis. RESULTS: IOA was positive in 80 patients. It showed an accuracy of 76.13% when compared with the postoperative assessment. The best individual parameter was myometrial invasion. Nodal metastasis was observed in 16 patients in the positive IOA group and 7 patients in the negative group. Patients with lymph node metastasis had a 5-year overall survival rate of 80.9%, whereas patients without metastasis had a 5-year overall survival rate of 97.9%. CONCLUSIONS: IOA is an adequate tool to identify high-risk patients in grade 2 endometrial carcinoma. Myometrial invasion is the individual parameter that yields the highest diagnostic precision.

Expanding the morphologic spectrum of chromophobe renal cell carcinoma: A study of 8 cases with papillary architecture.

Although typically arranged in solid alveolar fashion, chromophobe renal cell carcinoma (RCC) may also show several other architectural growth patterns. We include in this series 8 chromophobe RCC cases with prominent papillary growth, a pattern very rarely reported or only mentioned as a feature of chromophobe RCC, which is lacking wider recognition The differential diagnosis of such cases significantly varies from the typical chromophobe RCC with its usual morphology, particularly its distinction from papillary RCC and other relevant and clinically important entities. Of 972 chromophobe RCCs in our files, we identified 8 chromophobe RCCs with papillary growth. We performed immunohistochemistry and array Comparative Genomic Hybridisation (aCGH) to investigate for possible chromosomal aberrations. Patients were 3 males and 5 females with age ranging from 30 to 84 years (mean 57.5, median 60 years). Tumor size was variable and ranged from 2 to 14 cm (mean 7.5, median 6.6 cm). Follow-up was available for 7 of 8 patients, ranging from 1 to 61 months (mean 20.1, median 12 months). Six patients were alive with no signs of aggressive behavior, and one died of the disease. Histologically, all cases were composed of dual cell population consisting of variable proportions of leaf-like cells with pale cytoplasm and eosinophilic cells. The extent of papillary component ranged from 15 to 100% of the tumor volume (mean 51%, median 50%). Sarcomatoid differentiation was identified only in the case with fatal outcome. Immunohistochemically, all tumors were positive for CK7, CD117 and Hale's Colloidal Iron. PAX8 was positive in 5 of 8 cases, TFE3 was focally positive 3 of 8 tumors, and Cathepsin K was focally positive in 2 of 8 tumors. All cases were negative for vimentin, AMACR and HMB45. Fumarate hydratase staining was retained in all tested cases. The proliferative activity was low (up to 1% in 7, up to 5% in one case). Three cases were successfully analyzed by aCGH and all showed a variable copy number variation profile with multiple chromosomal gains and losses. CONCLUSIONS: Chromophobe RCC demonstrating papillary architecture is an exceptionally rare carcinoma. The diagnosis can be challenging, although the cytologic features are consistent with the classic chromophobe RCC. Given the prognostic and therapeutic implications of accurately diagnosis other RCCs with papillary architecture (i.e., Xp11.2 translocation RCC, FH-deficient RCC), it is crucial to differentiate these cases from chromophobe RCC with papillary architecture. Based on this limited series, the presence of papillary architecture does not appear to have negative prognostic impact. However, its wider recognition may allow in depth studies on additional examples of this rare morphologic variant.

Primary renal well-differentiated neuroendocrine tumour (carcinoid): next-generation sequencing study of 11 cases.

AIMS: Primary renal well-differentiated neuroendocrine tumour (NET) (hereafter referred to as renal NET) is rare, with ~100 cases having been reported in the literature. There are also limited data on the molecular-genetic background of primary renal NETs. METHODS AND RESULTS: We analysed 11 renal NETs by using next-generation sequencing (NGS) to identify characteristic genetic aberrations. All tumours were positive for synaptophysin, and also expressed insulinoma-associated protein 1 (10/11), chromogranin-A (8/11), and CD56 (3/11). Cytoplasmic positivity of CD99 was present in eight of 11 cases, and strong nuclear expression of α-thalassaemia/mental retardation syndrome X-linked (ATRX) was retained in all 11 cases. Molecular-genetic analysis of aberration of VHL gave negative results in all cases. Loss of heterozygosity on chromosome 3p21 was found in three of nine analysable cases. NGS was successful in nine cases, showing a total of 56 variants being left after the updated filtering process, representing an average of five variants per sample. All analysable cases were negative for ATRX and DAXX (death-domain associated protein X) mutations. The most frequently mutated genes were CDH1 and TET2, with three mutations in two cases. Mutations in AKT3, ROS1, PIK3R2, BCR and MYC were found in two cases. The remaining 41 genes were found to be mutated only in individual cases. In four cases, the mutations affected a subset of genes related to angiogenesis. CONCLUSIONS: Overall, the mutation profile of primary renal NETs is variable, and none of the studied genes or affected pathways seems to be specific for renal NET.

Low-grade oncocytic tumour of kidney (CD117-negative, cytokeratin 7-positive): a distinct entity?

AIM: To describe a group of distinct low-grade oncocytic renal tumours that demonstrate CD117 negative/cytokeratin (CK) 7-positive immunoprofile. METHODS AND RESULTS: We identified 28 such tumours from four large renal tumour archives. We performed immunohistochemistry for: CK7, CD117, PAX8, CD10, AMACR, e-cadherin, CK20, CA9, AE1/AE3, vimentin, BerEP4, MOC31, CK5/6, p63, HMB45, melan A, CD15 and FH. In 14 cases we performed array CGH, with a successful result in nine cases. Median patient age was 66 years (range 49-78 years) with a male-to-female ratio of 1:1.8. Median tumour size was 3 cm (range 1.1-13.5 cm). All were single tumours, solid and tan-brown, without a syndromic association. On microscopy, all cases showed solid and compact nested growth. There were frequent areas of oedematous stroma with loosely arranged cells. The tumour cells had oncocytic cytoplasm with uniformly round to oval nuclei, but without significant irregularities, and showed only focal perinuclear halos. Negative CD117 and positive CK7 reactivity were present in all cases (in two cases there was focal and very weak CD117 reactivity). Uniform reactivity was found for PAX8, AE1/AE3, e-cadherin, BerEP4 and MOC31. Negative stains included CA9, CK20, vimentin, CK5/6, p63, HMB45, Melan A and CD15. CD10 and AMACR were either negative or focally positive; FH was retained. On array CGH, there were frequent deletions at 19p13.3 (seven of nine), 1p36.33 (five of nine) and 19q13.11 (four of nine); disomic status was found in two of nine cases. On follow-up (mean 31.8 months, range 1-118), all patients were alive with no disease progression. CONCLUSION: Low-grade oncocytic tumours that are CD117-negative/CK7-positive demonstrate consistent and readily recognisable morphology, immunoprofile and indolent behaviour.

Variation in nuclear size and PD-L2 positivity correlate with aggressive chromophobe renal cell carcinoma.

Chromophobe renal cell carcinoma (CRCC) is not amenable to International Society for Urologic Pathology-endorsed nucleolar grading. Novel grading approaches were proposed, but the rarity of adverse pathology hampers their discriminatory value. We investigate simple linear micrometer measurements and a proposed immunostain in CRCCs. 32 patients' CRCCs were studied: 12 adverse cases (stage pT3, recurrence, or metastasis), 15 controls (stage ≤pT2, no recurrence or metastasis after >3 years), and 8 metastases (3 were paired with primary adverse cases). The ratio of greatest dimensions of largest and smallest nuclei, in each of 5 "worst" high-power fields, excluding those with degenerative features, was designated variation in nuclear size (VNS). Percent multinucleate cells (PMC) were also counted. Mouse anti PD-L2 monoclonal antibody immunostaining was performed. Mean VNS measured in adverse primary and control primary tumors were 3.7 ±â€¯0.5 and 2.4 ±â€¯0.4 respectively (P < .001), and 3.4 ±â€¯0.4 for metastases (P < .001). Optimal VNS cut-off was 2.5, with sensitivity and specificity 0.85 and 0.81, respectively. PMCs were 6.0 ±â€¯3.0 for adverse group, 5.7 ±â€¯2.7 for controls, and 4.1 ±â€¯1.6 for metastases (P = NS). PD-L2 could not discriminate adverse versus good primary tumors (χ21.6, P = .2), but was higher in metastases (χ2 6.9, P < .01), or metastases plus adverse primary tumors (χ2 4.8, P = .03), compared to good-pathology primary tumors. In conclusion, VNS is an easily obtained measurement that can predict adverse behavior of chromophobe RCC, and may impart value for needle biopsy reporting and the choice of active surveillance. PD-L2 was elevated in metastases but was less useful for primary tumors.

Histology as Prognostic Factor in Early-Stage Cervical Carcinoma. Experience in a Third-Level Institution.

BACKGROUND: Cervical carcinoma (CC) is one of the most frequent neoplasms, especially in developing countries. The most common histopathological type is squamous cell carcinoma (SCC), followed by adenocarcinoma (AC) and adenosquamous carcinoma (ASC). Prognosis according to histological type is controversial. OBJECTIVE: The objective of this study is to describe and compare the prognoses of the most common histologies of CC in the early stages. MATERIALS AND METHODS: We reviewed records of patients attended at the Instituto Nacional de Cancerología of Mexico with CC surgically treated Stages IA2-IB1 and IIA1, including the histological types SCC, AC, and ASC. Patients who had another malignant neoplasm, cervical cancer in situ, locally advanced neoplasm, and metastatic neoplasm were excluded from the study. A descriptive and comparative analysis was conducted. Overall survival (OS) and disease-free period were calculated for each histological type with the Kaplan-Meier method and were compared with the log-rank test. RESULTS: A total of 202 records were obtained, of which 131 (64.9%) had SCC, 57 (28.2%) AC, and 14 (6.9%) ASC. The 5-year DFS was 94.4% for SCC, 98.1% for AC, and 92.3% for ASC, without a statistically significant difference (p = 0.55). The 5-year OS for SCC was 97.9%, for AC was 97.8%, and for ASC was 100%, without a statistically significant difference (p = 0.702). CONCLUSIONS: DFS and OS did not differ between the most common histological types of CC at the early stages.

[Initial surgical management of squamous carcinoma of the vulva]. / Manejo quirúrgico inicial del carcinoma epidermoide vulvar.

Vulvar cancer accounts for approximately 4% of gynecological malignancies. At the Instituto Nacional de Cancerologia in Mexico it occupies the fourth place. The purpose of this study is to assess the management of squamous carcinoma of the vulva with initial surgical treatment. It is a descriptive retrospective, observational study, from January 1, 2002 to December 31, 2012. Twenty-seven patients, clinical stages I, II, or III, initial surgical management, with at least one year of follow-up were included. In 51.85% a partial vulvectomy was performed and in 40.74% a wide excision; 66.66% underwent inguinofemoral dissection. Recurrence occurred in 25.91% of cases and the overall survival at 10 years was 63%. It is concluded that with invasion of up to 1 mm of lymph node, affection is 0%; with invasion of 1 mm and up to 5 mm this increases to 25%; an invasion of more than 5 mm implies up to 45%. Recurrence in our study was primarily distant, necessitating long-term monitoring with emphasis on symptoms to request imaging studies when suspected. Adjuvant therapy should be offered to patients with positive nodes, close or positive margins, and tumors larger than 4 cm.

Metaplastic breast cancer: a comparison between the most common histologies with poor immunohistochemistry factors.

BACKGROUND: Metaplastic carcinoma of the breast (MCB) is a rare histological type of breast cancer. This study aimed to determine whether MCB exhibits shorter overall survival (OS) and disease-free survival (DFS) compared with other histologies that are considered unfavorable. METHODS: We retrospectively analyzed 157 clinical file records of the Mexico City-based National Institute of Cancerology and compared the clinical characteristics and treatment of 24 patients with MCB, 37 patients with triple-negative invasive lobular carcinoma (TN-ILC), 48 patients with high-grade invasive ductal carcinoma (HG-IDC), and 48 patients with triple-negative invasive ductal carcinoma (TN-IDC), paired by clinical stage and age. We performed a comparative analysis and analyzed OS and DFS using a log-rank test. RESULTS: In patients with MCB, the 5-year DFS was 52.1% (mean, 48.52 months; 95%: 35.32-61.72), and the 5-year OS was 72.2% (mean, 59.77 months; 95% CI: 48.55-71.00). No differences were observed in the DFS of MCB compared with each of the other histologies (MCB vs. HG-IDC, p = 0.865; MCB vs. TN-IDC, p = 0.966, and MCB vs. TN-ILC, p = 0.132). Moreover, no differences were observed when comparing the OS of MCB with that of each of the other histologies (MCB vs. HG-IDC, p = 0.246; MCB vs. TN-IDC, p = 0.255, and MCB vs. TN-ILC, p = 0.387). CONCLUSIONS: Neither OS nor DFS differ between patients with MCB and those with other histologies with unfavorable immunohistochemical factors.

The value of SATB2 in the differential diagnosis of intestinal-type mucinous tumors of the ovary: primary vs metastatic.

Primary mucinous adenocarcinomas of the ovary are a diagnostic challenge because their histologic and immunohistochemical features usually overlap with metastatic tumors. SATB2 is a recently identified protein with restricted expression in the glandular cells lining the lower gastrointestinal tract. The aim of this study is to examine the differential expression of SATB2 in primary and metastatic tumors of the ovary. Mucinous ovarian tumors of intestinal type were retrieved from the pathology files of the Instituto Nacional de Cancerología de México. A double reading of the hematoxylin and eosin-stained slides was performed to confirm the diagnosis, and a detailed review of the clinical chart was performed to define the primary origin of the tumor (ovarian vs metastatic). Immunohistochemical staining for CK20, CDX2, and SATB2 was performed and evaluated by 2 gynecopathologists. A total of 106 mucinous tumors were identified, 26 of which were considered to be metastatic, and 80 of which were primary ovarian tumors. All of the primary tumors that were not associated with cystic teratomas were negative for SATB2, and the 4 that were associated with a teratoma were positive for SATB2. All 20 of the metastatic tumors of the colon and appendix were positive for CK20, and 4 were positive for CK7. In addition, all 20 of these tumors were positive for SATB2, and 19 were positive for CDX2. SATB2 appears to be a useful marker for the diagnosis of primary vs metastatic mucinous intestinal-type neoplasms and is highly sensitive in detecting lower gastrointestinal tract metastasis.

Chromophobe renal cell carcinoma with neuroendocrine and neuroendocrine-like features. Morphologic, immunohistochemical, ultrastructural, and array comparative genomic hybridization analysis of 18 cases and review of the literature.

Chromophobe renal cell carcinoma (CRCC) with neuroendocrine differentiation (CRCCND) has only recently been described. Eighteen cases of CRCC with morphologic features suggestive of neuroendocrine differentiation were selected from among 624 CRCCs in our registry. The tissues were fixed in neutral formalin, embedded in paraffin, cut into 4- to 5-µm-thick sections, and stained with hematoxylin and eosin. As CRCC with neuroendocrine features, tumors with following morphology were suggested: (1) trabecular/palisading/ribbon-like, gyriform, insular, glandular, and solid pattern; (2) uniform polygonal cells formed in small islets; and (3) cribriform pattern in combination with palisading. Selected cases were further analyzed using immunohistochemistry, electron microscopy, array comparative genomic hybridization, and fluorescence in situ hybridization. Cases were classified as CRCCND or CRCC with neuroendocrine-like features (CRCCND-L) based on the immunohistochemical expression of neuroendocrine markers: CRCCND, 4 cases, age range 49 to 79 years, size ranged from 2.2 to 22 cm, and CRCCND-L, 14 cases, age range 34 to 74 years, size range 3.8 to 16.5 cm. Follow-up information was available for 11 of 18 patients aged 0.5 to 12 years. Two of 4 CRCCNDs showed aggressive clinical course with metastatic spreading. Chromophobe renal cell carcinomas with neuroendocrine differentiation were focally positive for CD56 (4/4), synaptophysin (4/4), chromogranin A (1/4), and neuron-specific enolase (3/4). All 14 CRCCND-Ls were mostly negative or very weakly focally positive for some of the aforementioned markers. All 18 tumors were positive for cytokeratin 7 and CD117. Ultrastructural analysis showed poorly preserved neuroendocrine granules only in 2 of 4 analyzed CRCCNDs. Losses of chromosomes 1, 2, 6, and 10 were found in all analyzable CRCCNDs, whereas multiple losses (chromosomes 1, 2, 6, 10, 13, 17, and 21) and gains (chromosomes 4, 11, 12, 14, 15, 16, 19, and 20) were found in CRCCND-L.

Paracrine stimulation of P2X7 receptor by ATP activates a proliferative pathway in ovarian carcinoma cells.

P2X7 is a purinergic receptor-channel; its activation by ATP elicits a broad set of cellular actions, from apoptosis to signals for survival. Here, P2X7 expression and function was studied in human ovarian carcinoma (OCA) cells, and biopsies from non-cancerous and cancer patients were analyzed by immunohistochemistry. Ovarian surface epithelium in healthy tissue expressed P2X7 at a high level that was maintained throughout the cancer. The cell lines SKOV-3 and CAOV-3 were used to investigate P2X7 functions in OCA. In SKOV-3 cells, selective stimulation of P2X7 by 2'(3')-O-(4-benzoylbenzoyl) adenosine-5'-triphosphate (BzATP) induced a dose-dependent increase of intracellular Ca(2+) concentration ([Ca(2+)](i)) but not cell death. Instead, BzATP increased the levels of phosphorylated ERK and AKT (pERK and pAKT), with an EC(50) of 44 ± 2 and 1.27 ± 0.5 µM, respectively; 10 µM BzATP evoked a maximum effect within 15 min that lasted for 120 min. Interestingly, basal levels of pERK and pAKT were decreased in the presence of apyrase in the medium, strongly suggesting an endogenous, ATP-mediated phenomenon. Accordingly: (i) mechanically stimulated cells generated a [Ca(2+)](i) increase that was abolished by apyrase; (ii) apyrase induced a decrease in culture viability, as measured by the MTS assay for mitochondrial activity; and (iii) incubation with 10 µM AZ10606120, a specific P2X7 antagonist and transfection with the dominant negative P2X7 mutant E496A, both reduced cell viability to 70.1 ± 8.9% and to 76.5 ± 5%, respectively, of control cultures. These observations suggested that P2X7 activity was auto-induced through ATP efflux; this increased pERK and pAKT levels that generated a positive feedback on cell viability.